The effects of preoperative therapy with angiotensin-converting enzyme inhibitors on clinical outcome after cardiovascular surgery

PURPOSE: Quality of life of breast cancer survivors 8 years after diagnosis was compared with that among similarly aged women who had never confronted cancer (controls). METHODS: Survivors of a consecutive series of 227 breast cancer patients first treated in 1984 were approached for this study. Random-digit dialing was used to identify controls with the same age and residential distribution as the survivors. Quality of life was assessed in terms of physical health, functional status, psychologic distress, and social functioning. RESULTS: Participation was obtained from 96% (n = 124) of 129 eligible survivors and 61% (n = 262) of 427 potentially eligible controls. Consistently smaller proportions of survivors reported positive quality-of-life outcomes compared with controls, but these differences were generally small and nonsignificant statistically. When limited to women who remained free of disease over the entire follow-up period (n = 98), survivors' quality of life was similar to that among controls, with the exception of arm problems and sexual satisfaction for those women who lived with a partner. In contrast, survivors who developed recurrence or new primary breast cancer (n = 26) experienced a worse quality of life in all domains except social functioning. CONCLUSION: In most domains and for women without further disease events after diagnosis, quality of life does not seem to be permanently and globally impaired by breast cancer. Consequently, breast cancer survivors who remain free of disease probably do not need organized late psychosocial follow-up to improve quality of life. However, arm problems and sexuality are two areas in which additional effort may be still needed to improve quality of life of long-term survivors.     

Making vitamin C lipophilic enhances its protective effect against free radical induced peroxidation of low density lipoprotein

Human sera contain anti-5-hydroxymethyl-2'-deoxyuridine (HMdU; an oxidized thymidine) autoantibodies (aAbs), which are significantly higher in chronic inflammatory diseases. The intent of this study was to establish whether anti-HMdU aAbs can serve as predictors of breast and colorectal cancer risk. Sera of 169 women were analyzed by ELISA. Women healthy at blood donation but who were diagnosed 0.5-6 years later with breast or colorectal cancer exhibited significantly increased anti-HMdU aAbs over the age-matched controls (P = 0.028 and P < 0.001, respectively). Subjects diagnosed with rectal cancer had the highest levels of anti-HMdU aAbs (44.80 +/- 11.50; n = 6) in comparison to colon (29.03 +/- 2.49; n = 33) and breast (35.86 +/- 8.55; n = 9) cancers. Individuals with benign breast disease also had elevated anti-HMdU aAb (35.12 +/- 8.77; n = 10), with a borderline statistical significance (P = 0.095), whereas those with benign gastrointestinal tract diseases had those titers (30.95 +/- 3.64; n = 8) significantly increased (P < 0.02). Anti-HMdU aAb levels in subjects with a family history of any cancer (23.57 +/- 2.86; n = 55) did not significantly differ from those of the controls (19.41 +/- 2.90; n = 48), but women with a family history of breast cancer (two primary relatives or one with a bilateral disease) showed increased levels (34.48 +/- 8.16; n = 8; P = 0.024). Ps for linear trend of age-adjusted odds ratios were 0.049 for breast and < 0.001 for colorectal cancers. Anti-HMdU aAb titers showed a remarkable stability over a period of 6 years, with a low (14%) intraindividual variance. Thus, elevated anti-HMdU aAb titers may be an early signal of cancer risk, because they were significantly increased in otherwise healthy women who had a family history of breast cancer; in those who had benign breast disease or benign gastrointestinal tract diseases; and, most importantly, in those who at 0.5-6 years after the initial blood donation developed breast or colorectal cancer.     

Young children''s understanding of pretense expressions of independent agency

Data from the Cancer Registry of Slovenia were used in a cohort study to determine whether the incidence of second primary cancers in patients with first primary breast cancer differs from the incidence expected in the general population. Special interest was given to long-term survivors. The expected numbers of second primary cancers were calculated by multiplying the number of appropriate person-years at risk by the corresponding age- and calendar-period-specific cancer incidence rates for women in Slovenia. The risk of a second primary cancer was expressed as the standardized incidence ratio (SIR). Of the 8,917 patients newly diagnosed in the period 1961-85 and followed-up to the end of 1994, 547 (6.2 percent) developed second primary cancers, whereas 410 (4.7 percent) were expected (SIR = 1.3, 95 percent confidence interval [CI] = 1.2-1.4). The risk was higher among younger patients. In long-term survivors, the risk was increased significantly for second primary cancer of the breast (SIR = 1.4, CI = 1.1-1.7), lung cancer (SIR = 1.6, CI = 1.1-2.3), melanoma (SIR = 2.7, CI = 1.5-4.4) and non-melanoma skin cancers(SIR = 2.0, CI = 1.6-2.4), corpus uteri cancer(SIR = 1.6, CI = 1.2-2.1), ovarian cancer(SIR = 2.3, CI = 1.7-3.0), and thyroid cancer (SIR = 2.5, CI = 1.2-4.6). Our results confirm the findings of several cohort studies carried out in Europe, the United States, and Japan, indicating that breast cancer patients should be monitored carefully for the occurrence of second primary cancers.     

Structural changes in the oligosaccharide moiety of human IgG with aging

In order to elucidate the relationship between glycosylation of IgG and aging, oligosaccharide structures of human IgG purified from sera of men and women aged 18 to 73 years were investigated. Oligosaccharides were liberated quantitatively from IgG by hydrazinolysis followed by N-acetylation and were tagged with p-aminobenzoic acid ethyl ester. The oligosaccharide structures were then analyzed by HPLC in conjunction with sequential exoglycosidase digestion. All IgG samples were shown to contain a series of biantennary complex type oligosaccharides which consisted of +/-Galbeta1-4GlcNAcbeta1-2Manalpha1-6(+/-GlcNAcbeta 1-4)(+/-Galbeta1-4GlcNAcbeta1-2Man(alpha)1-3)Man(beta)1-+ ++4GlcNAcbeta1-4(+/- Fucalpha1-6)GlcNAc and their mono- and disialo glycoforms in different ratios. In female IgG samples only, the incidence of non-galactosylated oligosaccharides with non-reducing terminal GlcNAc residues increased with aging (r>0.8), whereas that of digalactosylated oligosaccharides decreased (r<-0.8). A weaker correlation was observed between aging and the incidence of neutral and monosialo oligosaccharides in female IgG (r=0.461 and r= -0.538, respectively) and between aging and the incidence of oligosaccharides with a bisecting GlcNAc in both male and female IgG samples (r=0.566 and r=0.440, respectively). In addition, a significant change with aging in the galactosylation of IgG oligosaccharides was observed in females in their thirties, fifties, and sixties (p<0.02, p<0.01, and p<0.04, respectively). These findings may contribute to our understanding of autoimmune diseases such as rheumatoid arthritis in which glycosylation is involved.     

Multiple primary cancers in families with Li-Fraumeni syndrome

BACKGROUND: Li-Fraumeni syndrome is a dominantly inherited disorder characterized by early-onset breast cancer, sarcomas, and other cancers in children and young adults. Members of families with this syndrome also develop multiple primary cancers, but the frequency is unknown. To approach this issue, we quantified the incidence of second and third primary cancers in individuals from 24 Li-Fraumeni kindreds originally diagnosed with cancer during the period from 1968 through 1986. METHODS: The relative risk (RR) of subsequent cancers and 95% confidence intervals (CIs) were calculated by use of population-based incidence data from the Connecticut Cancer Registry. Kaplan-Meier analysis was used to determine the cumulative probability (+/- standard error) of subsequent cancers. RESULTS: Among 200 Li-Fraumeni syndrome family members diagnosed with cancer, 30 (15%) developed a second cancer. Eight individuals (4%) had a third cancer, while four (2%) eventually developed a fourth cancer. Overall, the RR of occurrence of a second cancer was 5.3 (95% CI = 2.8-7.8), with a cumulative probability of second cancer occurrence of 57% (+/- 10%) at 30 years after diagnosis of a first cancer. RRs of second cancers occurring in families with this syndrome were 83.0 (95% CI = 36.9-187.6), 9.7 (95% CI = 4.9-19.2), and 1.5 (95% CI = 0.5-4.2) for individuals with a first cancer at ages 0-19 years, 20-44 years, and 45 years or more, respectively. Thirty (71%) of 42 subsequent cancers in this group were component cancers of Li-Fraumeni syndrome. CONCLUSIONS: Compared with the general population, members of Li-Fraumeni syndrome families have an exceptionally high risk of developing multiple primary cancers. The excess risk of additional primary cancers is mainly for cancers that are characteristic of Li-Fraumeni syndrome, with the highest risk observed for survivors of childhood cancers. Cancer survivors in these families should be closely monitored for early manifestations of new cancers.     

Cancer incidence among active female workers at Electricité de France-Gaz de France

Our aim was to draw up a first general view of cancer pathology among the EDF-GDF women thanks to the cancer register among active employees created by the social security department of the French national electric and gas company EDF-GDF. Between 1978 and 1992, 764 cases of cancer were diagnosed. Breast cancer was the most common (52.4%), followed by gynaecological cancers: uterus (8.6%) and ovary (6.2%), and colon and rectum cancers (5.4%). The age-standardized breast cancer incidence using the 1978-1982 period as a basis increased over time. A higher incidence for breast cancer and a lower incidence for uterus cancer were observed among the EDF-GDF women during the 1978-1982 and 1983-1987 periods, compared to French women of same age. The study of the relationship between breast cancer risk and socioeconomic status, by means of indirect standardization, showed that the breast cancer risk increased with increasing socioeconomic status. Thus manual workers had a lower breast cancer risk than the EDF-GDF woman cohort (SIR = 0.72), foremen had the same risk (SIR = 1.05) and managers had a significantly higher risk (SIR = 1.64). Moreover a case-control study showed that the change in socioeconomic status between the beginning (20 years old) and the middle of a career (35 years old) was important but it was essentially the socioeconomic status at the beginning which determined the breast cancer risk. The results support the hypothesis of a "social class" effect through risk factors during the first part of the life.     

Metastases to the pancreas and their surgical extirpation

BACKGROUND: The pancreas is an unusual but occasionally favored site for metastases, notably from carcinomas of the kidney and lung. The pancreas may be the only identified locus of spread, and therefore may provide an opportunity for significant palliation or even cure using pancreatectomy. OBJECTIVE: To report the treatment and outcome of patients presenting with metastases to the pancreas. DESIGN: Five-year survey. SETTING: Tertiary referral center. PATIENTS: Ten patients with apparently isolated metastases to the pancreas were identified from January 1, 1991, to December 31, 1995. All patients were followed up until death or to September 1997. RESULTS: The patients had been treated previously for carcinoma of the lung (n=4), renal cell carcinoma (n=2), sarcoma (n=2), breast carcinoma (n=1), and endometrial carcinoma (n=1). The interval between primary treatment and presentation of the metastases averaged 70 months (14-24 months for lung cancer, 10 and 22 years for renal cell carcinoma, 4 and 6 years for sarcoma, 8 years for breast cancer, and 36 months for endometrial carcinoma). Metastases were initially misdiagnosed as primary pancreatic cancers in 7 patients. In 4 patients (those with renal cell cancer and sarcomas), the tumor was completely resected using total pancreatectomy (n=3) or Whipple resection (n=1). Survival after diagnosis averaged 22 months. Two of the 4 patients undergoing pancreatic resection remain alive and well 20 and 25 months after pancreatectomy. CONCLUSIONS: The pancreas may be the presenting and perhaps sole locus for metastasis, typically years after treatment for certain extrapancreatic malignant neoplasms. Recognition and surgical treatment can provide worthwhile palliation and long-term survival.     

Risk of second primary cancer in two-year survivors of small cell lung cancer]

A total of 498 patients with small cell lung cancer received chemotherapy with or without chest irradiation at Osaka Prefectural Habikino Hospital from October 1977 through December 1991. Sixty-one who survived for more than two years were evaluated to determine the incidence and anatomic patterns of redevelopment of small cell lung cancer and development of second primary cancers. The numbers of expected cancers were estimated by cumulating person years of observation from 2 years after the start of treatment for small cell lung cancer to the date of death. Second primary cancers were observed in seven patients (four cases of non-small cell lung cancer, two of gastric cancer, and one of prostate cancer). The risk of a second primary cancer was 3.2 times greater than in the general population (95% Cl: 1.3-6.6). the relations between occurrence of a second primary cancer and family history of cancer, smoking history, smoking cessation after treatment of small cell lung cancer, and thoracic irradiation were studied. Occurrence of a second primary cancer correlated with family history (relative risk 7.5, 95% Cl: 1.5-22) and smoking cessation (relative risk 3.2, 95% Cl: 1.2-6.9). Long-term survivors were more likely to have a second primary cancer than a relapse of small cell lung cancer. Therefore, long-term survivors should be closely monitored for second primary cancers. Meta-analyses of studies done at several institutions may provide more detailed information on the occurrence of second primary cancers after small cell lung cancer.     

Differential activity of nitric oxide synthase in human nasal mucosa and polyps

A quantification method suitable for determination of individual oligosaccharide compounds from human milk has been established. The crude milk oligosaccharide fraction was separated into acidic oligosaccharides, neutral oligosaccharides, and lactose by gel permeation chromatography. After this separation step neutral and acidic oligosaccharides were analyzed separately by high-pH anion-exchange chromatography with pulsed amperometric detection. The concentrations of 14 neutral oligosaccharides, of 6 acidic oligosaccharides, and of N-acetylneuraminic acid were determined on the internal standards stachyose and galacturonic acid, respectively. Thus, previously applied quantification methods for milk oligosaccharides based on gel permeation chromatography have been decisively improved.     

Profiling glycoprotein n-linked oligosaccharide by capillary electrophoresis

A method for analysis of N-linked oligosaccharides derived from glycoproteins including sialic acid-containing species is presented. It is based on the combination of specific chemical and enzymatic conversions coupled with capillary electrophoretic (CE) separation and laser-induced fluorescence (LIF) detection. Glycoproteins were heat-denatured in the presence of a reducing agent and the N-linked oligosaccharides were released by peptide N-glycosidase (PNGase F; EC3.5.1.52)-catalyzed hydrolysis. The released N-linked oligosaccharides were derivatized with 8-aminopyrene-1,3,6-trisulfonate (APTS) under mild reductive amination conditions in which desialylation and loss of fucose residues are minimized. A model N-linked oligosaccharide, desialylated, galactosylated biantennary, core-substituted with fucose (A2F) was tested for APTS-based derivatization chemistry with excellent recovery of the adduct without losing fucose and neuraminic acid residues. The profiles of heavily sialylated N-linked oligosaccharides derived from fetuin, recombinant human erythropoietin and kallikrein are reported and the data show that the present method produces a high resolution of the N-linked oligosaccharide profile for fingerprinting glycans derived from glycoproteins.     

Screening women aged less than 50 years with a family history of breast cancer

Family history is an important breast cancer risk factor and is a common reason for referral to specialist breast clinics for consideration of breast screening. The aims of this study were to determine cancer detection rates and prognostic features of breast cancers identified in women aged less than 50 years at increased risk of breast cancer who attend a Family History Breast Screening Clinic (FHC). Between January 1988 and December 1995, 1371 asymptomatic women aged less than 50 years underwent annual clinical breast examination and biennial mammography due to a family history of breast cancer. A total of 29 cancers (23 invasive and 6 in situ) were detected or presented as interval cancer during a mean follow-up of 22 months (range 0-96 months). This gave a relative risk for invasive breast cancer in this high-risk group of 5 when compared with an age-matched female population in the U.K. The cancer screening detection rates were similar to those of women aged 50 years or over undergoing population screening in the NHS Breast Screening Programme (NHSBSP)--FHC prevalent screen 8 per 1000 screening visits versus NHSBSP 6.5 per 1000, FHC incident screen 3.3 per 1000 screening visits versus NHSBSP 3.8 per 1000. A higher proportion of in situ cancers were detected in the FHC screened group compared with cancers identified in symptomatic patients from an age-matched risk group (21% versus 4%). No differences were demonstrated for invasive tumour size, grade or lymph node stage between symptomatic and screened women. The early results of this study suggests that young women at risk of breast cancer due to a family history may benefit from regular breast screening due to the early detection of in situ lesions.     

Optimistic Personality and Psychosocial Well-Being During Treatment Predict Psychosocial Well-Being Among Long-Term Survivors of Breast Cancer.

In considering well-being among survivors of life-threatening illnesses such as breast cancer, 2 important questions are whether there is continuity between initial adjustment and longer term adjustment and what role personality plays in long-term adjustment. In this research, a sample of 163 early stage breast cancer patients whose psychosocial adjustment was first assessed during the year after surgery completed the same measures 5-13 years after surgery. Initial reports of well-being were relatively strong predictors of follow-up well-being on the same measures. Initial optimism and marital status also predicted follow-up adjustment, even controlling for earlier adjustment, which exerted a substantial unique effect in multivariate analyses. In contrast, initial medical variables played virtually no predictive role. There is substantial continuity of subjective well-being across many years among survivors of breast cancer, rooted partly in personality and social connection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cutaneous gangrene secondary to metastatic calcification in end stage renal failure--a case report

The belief that oestrogens are involved in the pathogenesis both of testicular cancer in young men and of cancers of the endometrium and female breast has become widespread. In a search for possible hormonal links between these cancers, we investigated the cancer pattern in a cohort of women who had given birth to sons who developed testicular cancer. Particular focus, was given to oestrogen-related cancers. The present retrospective population-based cohort study is based on data from the Danish Cancer Registry. Mothers of 2,204 testicular-cancer patients were followed for the occurrence of cancer over a total of 70,063 person years. The ratio of observed cancers in the cohort over the expected numbers based on cancer incidence in the underlying female population served as measure of the relative risk (RR). The RR of developing breast cancer among mothers of testicular-cancer patients was 0.8 (95% confidence interval 0.6-1.1), the relative risk of endometrial cancer 0.6 (0.3-1.0) and of ovarian cancer 1.0 (0.6-1.6). Mothers of testicular-cancer patients are not at increased risk of developing oestrogen-related cancers.     

Comparative incidence of de novo nonlymphoid malignancies after liver transplantation under tacrolimus using surveillance epidemiologic end result data

BACKGROUND: An increased incidence of de novo nonlymphoid malignancies has been shown in immunocompromised patients. However, the true risk over time compared to the general population has not been determined. METHODS: One thousand consecutive patients were carefully followed for an average of 77.8+/-11.1 (range, 56.3-96.3) months after primary liver transplantation at a single center. All de novo nonlymphoid malignancies were recorded. Each malignancy was compared with a standard Occupational Cohort Mortality Analysis Program population matched for age, sex, and length of follow-up using modified life table technique and surveillance epidemiology end result (SEER) data. RESULTS: Fifty-seven patients accounted for de novo malignancies and contributed 4795.3 total person years, a mean+/-SD of 36+/-21 (median, 36; range, 6-74) months after liver transplantation. Twenty-two of these malignancies were skin malignancies including two melanomas. Oropharyngeal cancers (n=7) were found to be 7.6 times higher (P<0.05) and respiratory malignancies (n=8) were 1.7 times higher (P>0.05) compared to the SEER incidence rate. Female reproductive system malignancies including breast cancer (n=3) were 1.9 times lower (P>0.05) and genitourinary malignancies were (n=5) 1.5 times lower (P>0.05) than their matched cohorts. No differences was observed in gastrointestinal malignancies (n=5). There was a significant difference in survival of the patients after diagnosis of malignancy depending on the type of cancer. There were two Kaposi's sarcomas, two metastatic unknown primaries, one thyroid, one brain, and one ophthalmic malignancies in the series. Mortality for Kaposi's and metastatic disease of unknown primary was 100% within 5 months, while the 1-year mortality for oropharyngeal cancer was 57.1% and that for lung cancers was 62.5%. Long-term survival for skin cancer was highest: 86.4% at 3 years (P=0.015 by log-rank test). CONCLUSION: An increased incidence of de novo cancers in the chronically immunocompromised patient demands careful long-term screening protocols which will help to facilitate the diagnosis at an early stage of the disease. This is particularly true for oropharyngeal cancers where the risk is more than 7 times higher compared to SEER incidence data matched for age, sex, and length of follow-up.     

Immunological characterisation of the acrosomal filament in the marine shrimp Sicyonia ingentis

Human alpha-galactosidase A (alpha-Gal A) is the lysosomal glycohydrolase that cleaves the terminal alpha-galactosyl moieties of various glycoconjugates. Overexpression of the enzyme in Chinese hamster ovary (CHO) cells results in high intracellular enzyme accumulation and the selective secretion of active enzyme. Structural analysis of the N -linked oligosaccharides of the intracellular and secreted glycoforms revealed that the secreted enzyme's oligosaccharides were remarkably heterogeneous, having high mannose (63%), complex (30%), and hybrid (5%) structures. The major high mannose oligosaccharides were Man5-7GlcNAc2 species. Approximately 40% of the high mannose and 30% of the hybrid oligosaccharides had phosphate monoester groups. The complex oligosaccharides were mono-, bi-, 2,4-tri-, 2,6-tri- and tetraantennary with or without core-region fucose, many of which had incomplete outer chains. Approximately 30% of the complex oligosaccharides were mono- or disialylated. Sialic acids were mostly N -acetylneuraminic acid and occurred exclusively in alpha2, 3-linkage. In contrast, the intracellular enzyme had only small amounts of complex chains (7.7%) and had predominantly high mannose oligosaccharides (92%), mostly Man5GlcNAc2 and smaller species, of which only 3% were phosphorylated. The complex oligosaccharides were fucosylated and had the same antennary structures as the secreted enzyme. Although most had mature outer chains, none were sialylated. Thus, the overexpression of human alpha-Gal A in CHO cells resulted in different oligosaccharide structures on the secreted and intracellular glycoforms, the highly heterogeneous secreted forms presumably due to the high level expression and impaired glycosylation in the trans- Golgi network, and the predominately Man5-7GlcNAc2 cellular glycoforms resulting from carbohydrate trimming in the lysosome.     

Different O-glycosylation of respiratory mucin glycopeptides from a patient with cystic fibrosis

The O-linked oligosaccharides from three fractions of highly glycosylated mucin glycopeptides obtained from sputum of a patient with cystic fibrosis were characterized and compared regarding size, composition, sequence and when possible linkage positions. Neutral and sialic acid-containing glycans were permethylated and analyzed by high-temperature GC-MS and MALDI-MS, showing more than 60 different oligosaccharides with a size of up to 15 monosaccharide units. Some of the observed oligosaccharides are novel for respiratory secretions, one being a trifucosylated heptasaccharide with the proposed structure: Fuc-Gal-4(Fuc-3)GlcNAc-(Fuc-)Gal-3GalNAcol. The glycosylation of two of the glycopeptide fractions was similar with regard to the neutral and sialylated oligosaccharides despite their different origins from the sol or gel phase. Analysis of the sulfated oligosaccharides by FAB-MS/MS indicated that the gel fraction contained C-6 linked sulfate groups while the two sol fractions also contained C-3 linked sulfate. The results suggest the presence of different glycosylated mucin domains, probably originating from different mucin glycoforms and/or apoproteins in the airway of cystic fibrosis patients.     

Increased mortality after successful treatment for Hodgkin's disease

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.     

Alkaline degradation of oligosaccharides coupled with matrix-assisted laser desorption/ionization Fourier transform mass spectrometry: a method for sequencing oligosaccharides

A new technique for determining sequence and linkage information of underivatized oligosaccharides is developed using alkaline degradation and matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS). Alkaline degradation (also known as the "peeling" reaction) is a chemical degradation technique that only cleaves the glycosidic bond at the reducing end by beta-elimination to yield a new reducing end. The reaction products are sampled directly with minimal cleanup and monitored by MALDI-FTMS to elucidate the oligosaccharide sequence. Linkage information is provided by cross-ring cleavage fragmentation of the new reducing ends, created by either MALDI source fragmentation or sustained off-resonance irradiation collision-induced dissociation. This method is illustrated by the successful sequence and linkage determination of neutral, branched, fucosylated, and sialylated oligosaccharides. Experiments on differently linked disaccharides are also performed to determine the specificity of the cross-ring cleavage reactions. The power of this technique is enhanced by the Fourier transform mass analyzer, which provides high-resolution, exact mass, and facile tandem mass spectrometry experiments of MALDI-produced ions.     

Stable expression of the Golgi form and secretory variants of human fucosyltransferase III from BHK-21 cells. Purification and characterization of an engineered truncated form from the culture medium

Stable BHK-21 cell lines were constructed expressing the Golgi membrane-bound form and two secretory forms of the human alpha1, 3/4-fucosyltransferase (amino acids 35-361 and 46-361). It was found that 40% of the enzyme activity synthesized by cells transfected with the Golgi form of the fucosyltransferase was constitutively secreted into the medium. The corresponding enzyme detected by Western blot had an apparent molecular mass similar to those of the truncated secretory forms. The secretory variant (amino acids 46-361) was purified by a single affinity-chromatography step on GDP-Fractogel resin with a 20% final recovery. The purified enzyme had a unique NH2 terminus and contained N-linked endo H sensitive carbohydrate chains at its two glycosylation sites. The fucosyltransferase transferred fucose to the O-4 position of GlcNAc in small oligosaccharides, glycolipids, glycopeptides, and glycoproteins containing the type I Galbeta1-3GlcNAc motif. The acceptor oligosaccharide in bovine asialofetuin was identified as the Man-3 branched triantennary isomer with one Galbeta1-3GlcNAc. The type II motif Galbeta1-4GlcNAc in bi-, tri-, or tetraantennary neutral or alpha2-3/alpha2-6 sialylated oligosaccharides with or without N-acetyllactosamine repeats and in native glycoproteins were not modified. The soluble forms of fucosyltransferase III secreted by stably transfected cells may be used for in vitro synthesis of the Lewisa determinant on carbohydrates and glycoproteins, whereas Lewisx and sialyl-Lewisx structures cannot be synthesized.     

Angiogenin expression and prognosis in primary breast carcinoma

Angiogenin is a protein originally isolated as an inducer of new blood vessel growth, and it has been reported to be an effective substrate for tumor cell adhesion. To understand the role of angiogenin in cancer progression, we evaluated the expression of angiogenin in 459 cases with primary breast carcinoma and in 40 benign breast specimens using an immunoassay. Higher angiogenin concentrations were observed in carcinomas in comparison with fibrocystic disease (mean, 17.3 versus 10.9 ng/mg; P = 0.008), but not with fibroadenomas. We selected 5 ng/mg cytosol protein of angiogenin as the normal cutoff for primary breast carcinoma. Eighty-eight percent of carcinomas expressed elevated angiogenin levels and 12% had low levels. We observed an association between elevated levels of angiogenin and low/ moderate histological grade (P = 0.001) and small tumor size (P = 0.026), but not with age, menopausal status, lymph node status, stage of disease, or hormonal receptor status. With a median follow-up of 31 months, breast cancer patients with elevated angiogenin levels had significantly longer disease-free survival (DFS) than patients with low angiogenin (log-rank, P = 0.003). This effect was equally observed in node-negative and node-positive cases. In a multivariate analysis of DFS, only angiogenin, tumor size, and histological grade showed statistical significance. A multivariate analysis of overall survival showed that angiogenin and tumor size were the only significant variables. Serum samples from the breast cancer patients at the time of surgery were available in 194 cases. We evaluated the levels of circulating angiogenin using the same immunoassay as in tumor tissue. Serum angiogenin levels were higher in cancer patients than in 40 healthy controls (mean, 401.2 versus 206.0 ng/ml; P < 0.0001). In breast cancer patients, we observed no correlation between the serum concentrations and the tissue levels of angiogenin (r = 0.115; P = 0.110). In addition, serum levels of angiogenin did not have a prognostic impact on the DFS of breast cancer patients (log-rank, P = 0.581). Our results indicate that elevated levels of tissue angiogenin, but not of circulating angiogenin, are a favorable prognostic factor in primary breast carcinoma, which is consistent with a role of angiogenin as a cancer cell substrate.