Unusual chromosomal organization of telomeric sequences and expeditious karyotypic differentiation in the recently evolved Mus terricolor complex

The Mus terricolor complex displays a stable homozygous arrangement of autosomal heterochromatin variations in the form of accretion of definitive autosomal short arms among three nonoverlapping populations, in concert with an expeditious evolutionary differentiation into three chromosomal species: M. terricolor I, II, and III. In contrast to the highly conservative M. musculus-like chromosomes in the coexisting sibling species, M. booduga, reshuffling and differentiation of centric heterochromatin has occurred in harmony with a revision of centric configurations, resulting in acrocentric and submetacentric autosomes. The chromosomal distribution of the prevalent vertebrate telomeric sequence (TTAGGG)n was examined by fluorescence in situ hybridization to metaphase cells of M. terricolor I, II, and III. An unusual centric organization of internal telomeric sequences was detected in all the submetacentric and acrocentric autosomes. An auxiliary role of these presumably fragile, recombinogenic telomeric sequences in the evolutionary revision of centric configurations in the terricolor complex is hypothesized.     

Interstitial methotrexate kinetics in primary breast cancer lesions

The transfer of cytotoxic agents across the tumor endothelium into the interstitial tumor space is considered a critical step in clinical resistance of solid tumors to antineoplastic chemotherapy. However, experimental data on drug transfer from the blood into the interstitium of solid tumors are scarce. Therefore, in this study, we used an innovative technique, in vivo microdialysis, for measuring interstitial tumor pharmacokinetics and plasma-to-tumor transfer rates of methotrexate (MTX) in breast cancer patients. Microdialysis probes were inserted into the primary tumor and the periumbilical s.c. adipose layer of nine previously chemotherapy-naive breast cancer patients to monitor interstitial concentrations following i.v. administration of MTX (40 mg/m2) during a three-drug treatment regimen. Mean interstitial MTX load in breast tumors, expressed as area under curve (AUC), was 60 +/- 20% (mean +/- SE; coefficient of variation = 100%) of mean plasma MTX load. There was no correlation between plasma AUC and the AUC in the interstitial space of tumor tissue (P = 0.93). Not one of the parameters plasma, interstitial tumor load, and transfer rate of MTX to the interstitial space was associated with favorable clinical response. In conclusion, plasma levels of MTX are not predictive of intratumor levels. There is a high interindividual variability in transendothelial MTX transfer. Under the present conditions, access of MTX to the interstitial space is not a rate-limiting step for clinical response to chemotherapy.     

The role of human papillomavirus DNAs in cervical carcinoma and risk of lymph node metastasis: association with 72-kilodalton metalloproteinase immunostaining

BACKGROUND: The role of human papillomavirus (HPV) as a prognostic factor in cervical carcinoma is not understood completely and little is known regarding the intrinsic mechanisms involved in the metastatic process of HPV positive carcinoma. The authors evaluated HPV status with respect to clinical features in early stage cervical carcinoma, with special emphasis on lymph node spread. The authors also analyzed the relation between HPV, lymph node involvement, and 72-kilodalton (kDa) metalloproteinase immunostaining, an enzyme that cleaves Type IV collagen and may play a role in tumor metastasis. METHODS: Thirty-two patients with International Federation of Gynecology and Obstetrics Stage I and IIA squamous cell cervical carcinoma treated by primary radical surgery were reviewed. Histologic grade of differentiation, tumor size, fractional depth of invasion, and lymph node spread were evaluated with respect to HPV status and 72-kDa metalloproteinase immunostaining. HPV DNA was detected by polymerase chain reaction and the primers potentially recognized at least the following HPV subtypes: 6, 11, 16, 18, 31, 33, 34, 35, 42, 51, 56, and 58. Immunohistochemical staining was performed using the avidin-biotin complex technique. Affinity-purified rabbit anti-72-kDa metalloproteinase antibody was used. RESULTS: HPV DNA was detected in a total of 69% of cases, and HPV-16 was the most frequent type detected. HPV positive carcinomas showed a significantly higher rate of lymph node metastases than HPV negative carcinomas (45% vs. 10%; P = 0.03); similarly, 72-kDa metalloproteinase index was significantly higher (P = 0.001). CONCLUSIONS: These findings suggest a relation between HPV and risk of lymph node metastasis, which may be mediated by an increased production of 72-kDa metalloproteinase.     

Rationale and design of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study that evaluates atorvastatin in unstable angina pectoris and in non-Q-wave acute myocardial infarction

Pediococcus sp. is a nonpathogenic heat-resistant spoilage organism that has been used as a test organism in milk pasteurization studies. These characteristics make this bacterium an attractive test organism to study the mode of bacterial thermal inactivation in a food pilot plant. We report here the effect of growth medium on the thermal D value of this organism in skim milk, whole liquid egg, 10% glucose solution, pineapple juice, apple juice, tomato juice, and water at 60 degrees C. Thermal inactivation was done in a submerged coil; D values were calculated from the linear portion of the survival curves by linear regression analysis. The range of D values of stationary-phase cells grown at 28 degrees C in tryptone glucose yeast extract (TGY) or tryptic soy broth (TSB) was 0.14 to 12.05 min in all heating menstrua tested. The TSB-grown cells exhibited the highest thermal resistance with skim milk and 10% glucose solution as the heating menstrua. Survival curves of the TGY-grown cells indicated the presence of a cell population heterogeneous in thermal resistance. The TSB-grown cells exhibited a cell population uniform in thermal resistance and with a lag time for thermal inactivation. When compared to TGY-grown cells, Pediococcus sp. grown in TSB showed a significant (P < 0.05) increase in D values by up to eightfold in all heating menstrua. Results from this study suggested that thermal inactivation of Pediococcus sp. was dependent on the growth medium and on the heating menstruum with respect to both pH and composition.     

Tracheobronchiomegaly (Mounier-Kuhn syndrome)

Tracheobronchiomegaly is a rare congenital disorder due to defective development of elastic and muscle tissues in the upper airways. The characteristic radiologic features shown by bronchography include marked dilatation of the tracheobronchial system and diffuse saccular bronchiectasis. These findings and recurrent episodes of pneumonia lead to a progressive loss of pulmonary function. Even with vigorous medical therapy the prognosis is poor and severe respiratory failure eventually develops.     

Nuclear magnetic resonance measurement of skeletal muscle: anisotrophy of the diffusion coefficient of the intracellular water

Four cases of chiasmal syndrome resulting from chromophobe adenoma with normal-sized sella turcica are reported. The predominantly suprasellar growth of these tumors was probably the result of a well-pneumatized sphenoid sinus and/or a congenitally deficient diaphragma sellae. In patients with chiasmal syndrome, a high suspicion of a surgically treatable lesion must be maintained in spite of radiographs showing a normal-sized sella. In spite of the difficulties presented by normal variations, subtle findings should be searched for on the plain films and given additional weight in the patient with a chiasmal syndrome. An aggressive diagnostic work-up, including pneumoencephalography with thin-section tomography, should be pursued in all such patients before accepting some alternate explanation, such as demyelinating disease, for visual impairment.     

The association of gonorrhoea and syphilis with premature birth and low birthweight

The indications and results of single and double lung transplantation are described on the basis of 66 operations performed by the authors and on the background of the world literature. Lung transplantation is considered a new and promising therapeutic mode for treating patients with end-stage pulmonary failure related to fibrosis, emphysema, infective conditions, and pulmonary hypertension yielding satisfactory early results. The long-term prognosis of patients undergoing lung transplantation, like that of any other organ transfer, remains guarded.     

Interobserver variation in the assessment of the sampling quality of cervical smears

The present study was carried out to investigate the biochemical and morphological changes in the liver after ligation of the hepatic artery (HA) in the presence and in the absence of extrahepatic cholestasis (EHC). The study was conducted on 100 rats divided into four groups of 25 animals each: group 1, sham operation; group 2, hepatic artery ligation (HAL); group 3, bile duct ligation (BDL); and group 4, HAL plus BDL. All animals were sacrificed 7 days after surgery when total bilirubin and fractions, alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in serum and on the inner hepatocyte mitochondrial membrane (IHMM); the incidence of necrosis and the volume fractions of vessels, bile ducts and hepatocytes in the liver were also determined. HAL reduces the relative volumes of bile ducts, with no changes in levels of bilirubin and fractions, AP, ALT, AST and IHMM, but HAL associated with EHC reduces duct proliferation and the liver becomes more vulnerable to necrosis. In conclusion, the normal liver depends on HA flow and this dependence is more evident in the presence of EHC.     

HIV seroprevalence in sexually transmitted disease clients in a low-prevalence southern state. Evidence of endemic sexual transmission

Seventy male Fischer 344 (F-344) rats were treated with s.c. injection of (-)deprenyl (0.5 mg/kg, n = 35) or physiological saline (n = 35) 3 times a week from the age of 18 months until the time of their natural death. The fifty percent survival time was 28 months in control animals and 30 months in the deprenyl treated group. The mean survival time after the start of treatment (18 months) and after 24 months were 378.3 +/- 97.4 days (mean +/- SD) and 196.3 +/- 97.4 days, respectively, in deprenyl treated rats and 328.7 +/- 108.8 days and 146.7 +/- 108.7 days in control rats. The increases in average life expectancies caused by deprenyl treatment (15% from 18 months and 34% from 24 months) were both statistically significant (P < 0.05, two-tailed t-test). The average body weights were comparable for both groups but the variation of body weight was greater in control groups, thus excluding the possibility that the life prolonging effect of deprenyl results from reduced dietary intake. The results confirm those of two previous studies (1,2) which reported a significant life prolonging effect of deprenyl in aged rats and lend added support to the results of a study on male F-344 rats where the effect was only marginally significant (16% increase after 24 months, P = 0.048 by one-tailed t test) (2).