Ras p21 protein levels in human plasma from patients with chronic obstructive pulmonary disease (COPD) compared with lung cancer patients and healthy controls

To explore the value of an increase in ras p21 proteins in plasma as a biomarker for the carcinogenic process or for the general disease state, we have directly analysed for ras p21 proteins, plasma samples from Polish human patients with chronic obstructive pulmonary disease (COPD). They were compared with appropriate controls and also with the Polish lung cancer patients previously examined before treatment [D. Anderson, J.A. Hughes, A. Cebulska-Wasilewska, E. Nizankowska, B. Graca, Ras oncoproteins in human plasma from lung cancer patients and healthy controls, Mutat. Res. 349 (1996) 121-126]. An elevated level of ras p21 proteins was considered to be greater than 2 standard deviations (SD) above the mean negative control values. Nine out of 20 COPD patients (mean age = 65.9 years) had increased ras p21 protein levels when compared with 20 age-matched (mean age = 62.4 years) controls of the present study with a mean + 2 SD of 0.70. Eighteen out of 40 lung cancer patients (mean age = 60.1 years) had increased ras p21 protein levels compared with their concurrent controls (mean age = 40.2 years) with a mean + 2 SD of 2.53. However when compared with the age-matched controls of this present study, there were 35 out of 40 (87.5%) with increased levels. When the COPD patients and lung cancer patients were compared with 101 historical controls (age range 25-76 years, of those whose age was recorded) from unexposed healthy populations from Poland, Estonia and Spain with a mean + 2 SD of 1.83, then 4 out of 20 (20%) COPD patients and 30 out of 40 (75%) lung cancer patients had increased levels. Whether using concurrent controls, age-matched controls or historical controls, the data would suggest that an increase in ras p21 protein levels in plasma from lung cancer patients could be a possible prognostic marker or biomarker for lung cancer. COPD patients when compared with historical controls or age-matched controls had lower ras p21 protein values than cancer patients. Their ras p21 protein values might also be a biomarker for cancer. It is possible that some of these COPD patients were in the process of developing cancer or perhaps would die from COPD before cancer develops. It cannot be ruled out that the increases could be a biomarker of exposure since many of the lung cancer patients and most of the COPD patients were smokers.     

Lipoxygenase products induce ultraweak light emission from human erythroleukemia cells

Several lipoxygenase products were able to enhance ultraweak light emission and membrane permeability of human erythroleukemia K562 cells. In particular, 13-hydroperoxyoctadecadienoic acid (13-HPOD) was more effective than hydrophilic hydroperoxides, like H2O2 and tert-butyl hydroperoxide. The enhancement of luminescence induced by 13-HPOD was inhibited by superoxide and hydroxyl radical scavengers. The effect of 13-HPOD was inhibited by superoxide and hydroxyl radical scavengers. The effect of 13-HPOD was potentiated by the calcium ionophore A23187 and inhibited by the calcium chelator EDTA, and was observed also in liposomes containing unsaturated lipids. Cholesterol enrichment, which decreases the membrane fluidity, did not modify the effect of 13-HPOD on K562 cells.     

Fibronectin in tissues and saliva of patients with oral lichen planus

BACKGROUND: Whilst gastrin has been found to be trophic for some colorectal cancer cell lines, and gastrin receptor antagonists are able to block this phenomenon, their potency has been modest. METHODS: The effect of a new, potent and selective CCK B receptor antagonist, CI-988 on the growth of LoVo, a human colon cancer cell line both in vitro and in vivo was instigated. RESULTS: Basal growth of LoVo in vitro was inhibited by up to 58.93 +/- 7.30% with concentrations of CI-988 as low as 1 X 10(-11) mol/L whereas the addition of gastrin (G17) at 0.5 nmol/L had no effect. LoVo was also grown in vivo for 10 days in nude mice subsequently treated with CI-988 at 10 mg/kg per day orally for 20 days. CI-988 inhibited the growth of xenografts by 53%. CONCLUSION: This was the first study in cancer with this potent gastrin receptor antagonist, CI-988. The results suggest that CI-988 may be of use in inhibiting the growth of colorectal cancer.     

Heat rate responses in patients with sinus node disease compared to controls: physiological implications and diagnostic possibilities

The autonomic regulation of heart rate was examined in 30 patients with symptoms of sinus node disease (SND) and 18 control subjects. Heart rate, expressed as sinus cycle length, was determined after injection of isoprenaline (0.1 microgram/kg), propranolol (0.1 mg/kg), and atropine (0.02 mg/kg); heart rate was also determined at maximal exercise and during carotid sinus stimulation. In addition, heart rate responses, expressed as the absolute change in sinus cycle length, were calculated. Mean heart rates after the applied maneuvers were all significantly different in the patient group, but so was the mean spontaneous heart rate. None of the induced changes differed significantly between the groups. Thus, although all these patients had impaired sinus node automaticity no uniform decrease in responsiveness to adrenergic or cholinergic stimulation or to inhibition of autonomic influences could be detected. The response patterns were heterogeneous, indicating diversity of the underlying mechanisms. No single heart rate reaction provided a satisfying diagnostic capacity for SND. However, the combined sensitivity of the three tests--isoprenaline stimulation, carotid sinus pressure, and autonomic inhibition--was 97% with a specificity of 50%. Clinically, normal findings in all these three tests, i.e., with resulting heart rates greater than 100, 55, and 70 beats/min, respectively, strongly suggest absence of SND.     

Lipoxygenase products and expression of 5-lipoxygenase and 5-lipoxygenase-activating protein in human cultured synovial cells

Limb regeneration is a phenomenon occurring only in some urodeles. The process seems to be initiated by the dedifferentiation of the terminally differentiated cells. These cells differentiate, subsequently, to the tissues that comprise the limb, thus reconstructing the pattern of the missing limb part. In this paper we review and present evidence that certain cell types of the limb have the capacity to differentiate to different cell types than their original one by cellular metaplasia. This switch is called transdifferentiation. The focus of this review is the process of dedifferentiation which is the necessary prerequisite for differentiation, and the possible mechanisms involved.     

p53 antibodies in the saliva of patients with squamous cell carcinoma of the oral cavity

A significant age dependence of the risk of complete heart block complicating radiofrequency ablation of the AV nodal slow pathway was noticed, with no patients <45 years of age experiencing this complication.     

In-flight electrocorticograms compared to ground controls in behaving monkeys: differences in attentional states?

Electrocorticographic recordings were taken from the posterior parietal cortical area in monkeys performing a variety of tasks on ground and in space flight. The question addressed here was whether ECoG analysis would be a reliable index of attention to the learned task. It is shown that measuring the instantaneous frequency, rather than instrumentally evaluating the spectral content of the ECoG, may provide useful information on the attentional states of the animals. Investigations on Rhesus performed in Paris provided a useful database to evaluate the more complex results obtained in the Russian experiments with space flights, during which, according to the ECoG marker, some attentional disorders occurred. It is not unreasonable to envisage using similar evaluation in the scalp EEG in human flights in the future.     

Chewing gum and saliva in oral health

The crucial role played by many properties of saliva in preventing dental caries, maintaining the plaque pH and controlling the equilibrium between enamel de- and remineralization has been demonstrated. This has been documented by the effects of salivary dysfunction on caries incidence and by the distribution of sites of caries predilection in areas where saliva presence is restricted. The use of sugar-free chewing gum has been increasingly accepted as one adjunct to oral hygiene procedures. It has become part of an anti-caries prevention program, especially in patients suffering from xerostomia. Chewing gum not only acts as a salivary stimulant but may also be a useful vehicle for some agents such as fluoride, chlorhexidine and calcium phosphate. Moreover, in some countries gum containing nicotine has been used to substitute the nicotine from cigarettes to reduce the effects of nicotine withdrawal reaction from people attempting to stop smoking.     

Volumetric MRI measurements in bipolars compared with schizophrenics and healthy controls

Twenty-six patients with RDC bipolar disorder were compared with a previously reported group of 48 RDC schizophrenics and 34 healthy controls, using volumetric MRI measurements of cerebral, cortical and sulcal volumes. The bipolar group appeared no different from the controls, and both of these groups had significantly larger cerebral and cortical volumes than the schizophrenics. Our previous report of a significantly reduced cortical volume in the schizophrenic group, with a corresponding increase in the volume of sulcal fluid is, therefore, not a generalized feature of psychotic illness but may be more specific to schizophrenia.     

Prophylactic mupirocin could reduce orthopedic wound infections. 1,044 patients treated with mupirocin compared with 1,260 historical controls

We analyzed the effect of perioperative elimination of nasal carriage of Staphylococcus aureus using mupirocin nasal ointment on the reduction of the postoperative wound infection rate in orthopedics. In an unblinded intervention trial, we compared 1,044 patients treated with mupirocin (intervention group) with 1,260 historical controls (control group). From each group a random sample of 50 patients was taken. Risk factors were analyzed in these random samples and we found it unlikely that different distributions of risk factors might have influenced the results. The wound infection rates were 14/1,044 in the intervention group and 34/1,260 in the control group (p = 0.02). The rates of wound infections caused by S. aureus were subsequently 7/1,044 and 14/1,260 (p = 0.3). On checking the data we found that prophylaxis had unintentionally not been given to 172 patients in the intervention group. Correction of the data gave a comparable total infection rate, but a further reduced infection rate by S. aureus. Our findings suggest that prophylactic treatment with mupirocin in orthopedic surgery can reduce the infection rate.     

Cholecystokinin, beta-endorphin and vasoactive intestinal peptide in peripheral blood mononuclear cells of drug-naive schizophrenic patients treated with haloperidol compared to healthy controls

The site and sequence specificity of protein kinases, as well as the role of the secondary structure and surface accessibility of the phosphorylation sites on substrate proteins, was statistically analyzed. The experimental data were collected from the literature and are available on the World Wide Web at http://www.cbs.dtu.dk/databases/PhosphoBase/. The set of data involved 1008 phosphorylatable sites in 406 proteins, which were phosphorylated by 58 protein kinases. It was found that there exists almost absolute Ser/Thr or Tyr specificity, with rare exceptions. The sequence specificity determinants were less strict and were located between positions -4 and +4 relative to the phosphorylation site. Secondary structure and surface accessibility predictions revealed that most of the phosphorylation sites were located on the surface of the target proteins.     

Performance status and comorbidity in elderly cancer patients compared with young patients with neoplasia and elderly patients without neoplastic conditions

MARCKS, the major protein kinase C substrate in various cells and tissues, binds to calmodulin, acidic membrane phospholipids, and actin filaments, and these interactions are regulated by protein phosphorylation. We have previously analyzed MARCKS purified from bovine brain using capillary liquid chromatography/electrospray mass spectrometry and found that the protein structure differed significantly from that deduced from cDNA sequences [Taniguchi, H., Manenti, S., Suzuki, M., and Titani, K. (1994) J. Biol. Chem. 269, 18299-18302]. Moreover, the alignment of the protein from various species showed a lack of any conserved sequences in the C-terminal half of the molecule. This prompted us to reexamine the C-terminal amino-acid sequence of bovine MARCKS. The purified protein was digested with lysyl endoprotease, and the obtained C-terminal peptide was further digested with either Staphylococcus V8 protease or NTCB. The small peptides thus obtained were analyzed by liquid chromatography/electrospray/tandem mass spectrometry. This combined with gas-phase Edman sequencing allowed us to determine the C-terminal primary structure. The sequence obtained differed significantly from that reported previously, and the comparison with other species revealed the presence of a novel conserved domain in the C-terminal region of MARCKS.     

Surgical variables affecting speech in treated patients with oral and oropharyngeal cancer

A well-characterized collagen-glycosaminoglycan matrix (CGM) that has been shown to function as a dermal analog was seeded with freshly disaggregated autologous keratinocytes and applied to full-thickness wounds in a porcine model. CGM were impregnated with 50,000 keratinocytes per cm2, a seeding density that produces a confluent epidermis within 19 d post-grafting and affords a 60-fold surface expansion of the donor epidermis. In this study, the temporal sequence of events in epidermal and neodermal formation was analyzed histopathologically and immunohistochemically from 4 to 35 d post-grafting. The epidermis was observed to form from clonal growth of individual keratinocytes into epithelial cords and islands that gradually enlarged, coalesced, differentiated to form large horn cysts, and finally reorganized at the graft surface to form a fully differentiated, normally oriented epidermis with rete ridges. Simultaneously, a neodermis formed from migration of endothelial cells, fibroblasts, and macrophages into the CGM from the underlying wound bed, resulting in formation of blood vessels, the production of abundant extracellular matrix, and the degradation of the CGM fibers, respectively. Gradually, the stromal cellularity of the CGM decreased and collagen deposition and remodeling increased to form a neodermal connective tissue matrix beneath the newly formed epidermis. Complete dissolution of the CGM occurred, partly as a result of degradation by an ongoing foreign-body giant cell reaction that peaked at 8-12 d post-grafting, but neither acute inflammation nor evidence of immune stimulation were observed. Within 1 mo, many structural components of normal skin were reconstituted.     

Protein diffusion patterns in human saliva

BACKGROUND: There are two modes of saliva protein diffusion on a cellulose flat matrix. The monophasic mode of diffusion consists in a homogeneous distribution of salivary protein components on the matrix. On the contrary, in the biphasic mode, an area occupied by nondiffusible proteins is surrounded by an area occupied by diffusible proteins. AIM: To study protein diffusion patterns of saliva obtained from normal human volunteers. MATERIAL AND METHODS: Saliva was obtained from 33 subjects aged 67.5 +/- 12 years old (29 female). Forty microliters of saliva were deposited in the center of cellulose disks for protein diffusion assays. RESULTS: Thirty three whole saliva samples and 31 submandibular/sublingual samples showed a biphasic diffusion pattern. On the contrary, 62 out of 66 samples of parotid saliva displayed a monophasic diffusion pattern. In one parotid saliva samples and 2 submandibular/sublingual samples, the diffusion pattern could not be established. Patterns of salivary protein diffusion were highly consistent within the same individual. Eighty percent of subjects had an unequivocal pattern of saliva protein diffusion. CONCLUSIONS: The monophasic mode of saliva protein diffusion is a feature of parotid saliva, whereas the biphasic mode is characteristic of submandibular/sublingual and whole saliva.     

The impact of cancer on daily living: A comparison with cardiac patients and healthy controls.

Examined the psychosocial and physical problems of 32 Ss with cancer by comparing them to Ss with cardiac disease with a similar functional performance status and to Ss without any illnesses. All Ss completed a cancer inventory of problem situations. Ss with cancer were found to have a larger number of problems and more severe problems than Ss with cardiac disease. Some of the problem subscales that were particularly notable for cancer patients were Functional Health Status, Body Image, Weight Maintenance, Worry, Sexual Dysfunction, Problems Associated with Treatment, and Job-Related. Ss with cancer and cardiac disease did not differ greatly from one another or from the healthy controls in subscales associated with the medical setting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relation between depression and circulating immune products in patients with advanced colorectal cancer

We have previously suggested that colorectal liver metastases might produce 'toxins' that reduce both quality of life (QoL) and survival. In this study we assessed whether QoL in patients with such metastases was related to immune activation, as determined by increased serum levels of interleukin 6 (IL6), soluble tumour necrosis factor receptor 1 (sTNFr1), soluble interleukin 2 receptor alpha (sIL2r alpha) or the interferon-gamma marker neopterin. Serum IL6, sTNFr1, sIL2r alpha, neopterin, alkaline phosphatase and carcinoembryonic antigen levels, liver metastasis volume, and QoL (Hospital Anxiety and Depression [HAD] scale, Rotterdam Symptom Checklist [RSC], and Sickness Impact Profile [SIP]) were measured in 43 patients. There were significant positive correlations between serum sIL2r alpha and HAD depression score (r = 0.66, P = 0.0001), RSC physical symptom score (r = 0.46, P < 0.01), and SIP score (r = 0.47, P = 0.009). Multiple regression analysis suggested that serum sIL2r alpha level was a significant independent predictor of HAD depression score. Although survival was shorter (logrank test P < 0.05) where sIL2r alpha, sTNFr1 and IL6 levels were higher, the ability of sIL2r alpha to predict HAD depression score was independent of survival.     

Quantitative MRI volume changes in late onset schizophrenia and Alzheimer's disease compared to normal controls

Volumes of medial and lateral temporal lobe structures were assessed using magnetic resonance imaging (MRI) in 11 patients with late-life onset schizophrenia (LOS), 18 normal elderly controls and 12 patients with moderate cognitive impairment due to Alzheimer's disease (AD) who had no non-cognitive symptoms. While both patient groups had smaller volumes of several medial temporal regions (e.g. entorhinal cortex, left hippocampus), schizophrenics had significantly smaller anterior superior temporal gyri (STG) than normal controls, but AD patients did not. We have previously demonstrated anterior STG volume to be reduced in early life onset schizophrenia.     

Combination hepatic intra-arterial 5-fluorouracil and CDDP administration with oral regimen in patients with colorectal cancer metastasis to the liver

We investigated therapeutic effectiveness and side effects of a combination weekly high-dose 5-FU plus one shot CDDP HAI (WHF + CDDP method) with oral regimen in patients with colorectal cancer metastasis to the liver. All 24 patients enrolled in this study showed 54% efficacy whereas patients combined HAI with oral regimen over one week obtained 83% efficacy for multiple liver metastasis. They showed good quality of the life during combination chemotherapy without any symptoms of metastatic lesions. The WHF + CDDP method combined with oral regimen is a promising treatment for colorectal cancer metastasis to the liver as well as extrahepatic distant organs, and this protocol may be satisfactorily accepted by most colorectal cancer laden patients because of negligible side effects.     

Origin of esterases in human whole saliva

Whole saliva of 59 healthy persons was used for determination of esterase activity. The pattern of esterase was studied by means of isoelectrofocusing on thin-layer acrylamide gels. The esterases found in whole saliva are suggested to be derived from the cells of the tissue in the oral cavity. This origin is indicated (e.g.) by comparison between isolectrophoretic esterase patterns of whole saliva, submandibular saliva, gingival biopsy and fibroblast culture. Antisera against partially purified saliva esterases were produced in rabbits. These sera, used in immunoelectro-osmophoresis, gave esterase-active immunoprecipitate against whole saliva, the water-soluble materials of disrupted gingival biopsy and fibroblast culture, but not against the material of the bacteria, Streptococcus sanguis, Strptococcus mutans, Streptococcus mitis, Actinomyces viscosus and Lactobacillus fermentum.