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Biomedical subjects

M E Cohen

Publications and source records attributed to M E Cohen.

At least 19 recordsLinked to original sources

CFTR protein expression in primary and cultured epithelia.

The gene responsible for the lethal disorder cystic fibrosis encodes a 1480-amino acid glycoprotein, CFTR. Using polyclonal antibodies directed against separate phosphorylation sites in the pre-nucleotide-binding fold (exon 9) and the R domain (exon 13), we have identified a 165-kDa protein in Xenopus laevis oocytes injected with recombinant CFTR cRNA transcribed from the full-length CFTR plasmid pBQ4.7. A protein of the same mobility was also detected with Western blotting techniques in whole cell extracts of cells that express CFTR mRNA (T84, FHTE, HT-29), including biopsied human nasal and bronchial tissue. Immunodetectable 165-kDa protein was concentrated in the apical membrane fraction of ileal villus tissue. We also report that the 165-kDa protein levels can be modulated pharmacologically, and these levels are appropriately correlated with second-messenger-regulated Cl- efflux. Thus, native or recombinant CFTR can be recognized by these anti-CFTR peptide polyclonal antibodies.

Animals

Patterns of breast calcification in patients on renal dialysis.

Patients on renal dialysis are prone to form areas of metastatic calcification in soft tissues. In this study we have analysed the mammograms of 16 women on renal dialysis and compared them with a control group of 32 women attending for routine mammographic screening. We found a significant increase in vascular and parenchymal calcifications in the women on renal dialysis. Ductal calcifications were no more prevalent in the patients on dialysis, and in no case did the calcification simulate malignancy.

Breast Diseases

Changes in the approach to central nervous system tumors in childhood.

Current approaches to children with brain tumors are in a state of evolution. Currently, 50% of children with all types of brain tumors may be expected to survive 5 years. Therefore, the goals of neuro-oncology have broadened to include improved survival and improved quality of life. This article reviews changes in therapy that have altered survival as well as changes in therapy as a consequence of increasing recognition of complications and toxicity of treatment.

Brain

Motor power differences within the first two weeks post-SCI in cervical spinal cord-injured quadriplegic subjects.

The purpose of this study was to confirm the clinical impression that motor power significantly changed within the first 2 weeks after a spinal cord injury (SCI) and to determine the time for motor power assessment within the first 2 weeks post injury that best correlated with motor power determined 6 months post-SCI. Our hypothesis was that within the first 2 weeks postinjury, the manual muscle test (MMT) scores would change significantly from the < or = 24 h examination and that the post-24 h evaluations of strength would have a higher correlation with the 6 month measure of motor outcome than the evaluation of strength performed < or = 24 h after SCI. The biceps, extensor carpi radialis, triceps, flexor digitorum profundus, and interosseous muscle strength was measured in 40 subjects using the MMT (muscles graded 0/5 to 5/5) at < or = 24 h, 72 h, 1 week, 2 weeks, 3 months, and 6 months post-SCI. Upper extremity motor index scores (MIS) obtained at the four testing periods within 2 weeks of injury were analyzed using a Friedman analysis of variance with Duncan's post-hoc tests to identify significant differences. Separate analyses were performed on subgroupings of the total sample based on the strength of the most rostral key muscle having less than antigravity strength. There were three groups evaluated: initial MMT 0/5 (n = 22), initial MMT 1-1.5/5 (n = 17), and initial MMT 2-2.5/5 (n = 13).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The role of computerized information systems in quality assurance in hospital social work departments.

Computerized information systems can be valuable tools in the total quality assurance program of hospital social work departments. This paper presents a matrix of potential roles for the information system at various levels of assessment-structural, process, and outcome. It then illustrates these roles, based on examples from a country-wide information system developed for hospital social work departments in Israel.

Data Interpretation, Statistical

Treponema denticola and Porphyromonas gingivalis as prognostic markers following periodontal treatment.

Subgingival plaque samples were collected from individuals with advanced periodontitis before and 3 to 11 weeks after scaling and root planing periodontal treatment. The plaque levels of Treponema denticola and Porphyromonas gingivalis antigens were measured before and after treatment by a quantitative immunoassay procedure using monoclonal antibodies specific for these oral bacteria. A decrease in mean levels of T. denticola (P less than .05) and P. gingivalis antigens (P less than .09) were observed following periodontal therapy. Improved health, as measured by a decrease in probing depth, was associated with a decrease in T. denticola antigen (P less than .05). These results suggest that the T. denticola levels of successfully treated sites decreased, while non-responding sites had levels of this microbial marker which were equal to or greater than the pre-treatment levels. These results provide additional evidence that T. denticola is associated with human adult severe periodontal disease, and can serve as a prognostic marker for disease recurrence.

Adult

Risk indicators for periodontitis in a military treatment population.

The association between the periodontal diagnosis and a variety of subject characteristics was studied in a group of 1,783 patients examined at a large military dental clinic. In order of importance, age greater than 30, smoking, male sex, and Filipino racial background were all found to be statistically significant risk indicators for the presence of moderate or advanced periodontitis. A logistic regression equation serving as a predictive model employing these four variables was presented. The strong association found between smoking and advanced periodontitis is consistent with the hypothesis that smoking has cumulative detrimental effects on periodontal health. While these and other risk indicators are neither causative, diagnostic, nor prognostic, they may be helpful in alerting the clinician to more carefully evaluate other clinical signs or laboratory findings of disease.

Adolescent

Relationship between two measures of upper extremity strength: manual muscle test compared to hand-held myometry.

One hundred and twenty-two individuals with spinal cord injuries at levels C4-6, Frankel classifications A through D, were evaluated to determine the relationship between the manual muscle test (MMT) and hand-held myometry as accurate methods for measuring muscular strength. More specifically, this study attempted to define a range of myometry scores that could be correlated with discrete MMT grades. It also investigated which of the two modalities (MMT or hand-held myometry) is the best reflection of improvement in muscle strength over time. Sequential motor strength examinations using both modalities were performed at 72 hours, one week, and two weeks post SCI and then one, two, three, four, six, 12, 18, and 24 months post injury. The data analyses included calculations of Spearman ranked correlations, analyses of variance, and linear regressions. Results showed that 22 of 24 correlations between MMT and myometry were significant at p values less than .001. The range of myometry measurements for a particular MMT grade appears to be most specific for MMT scores less than 4 (ie, poor-plus to good), and less specific for MMT scores greater than or equal to 4. The results of this study also indicate that myometry measurements detect increases in strength over time, which are not reflected by changes in MMT scores.

Adolescent

Hyperfractionated radiation therapy in brain stem tumors. Results of treatment at the 7020 cGy dose level of Pediatric Oncology Group study #8495.

Between May 1986 and February 1988, 57 patients were accrued to the second dose level of a Phase I/II Pediatric Oncology Group (POG) study exploring the use of hyperfractionated radiation therapy (HRT) in children with high-risk brain stem tumors. Local fields were treated with fraction sizes of 117 cGy given twice daily, with a minimum interfraction interval of 6 hours, to a total dose of 7020 cGy in 60 fractions over 6 weeks. Information regarding clinical status during HRT was available for 55 patients (44 [80%] improved, 6 remained stable, and 5 deteriorated). Results of initial and follow-up computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were available for review for 52 patients. One patient had a complete response (CR) to treatment, 3 had a partial response (PR) (more than 50% response), and 40 remained stable, for a total response rate (CR + PR + stable) of 77%. Median time to disease progression was 6 months. Median survival time was 10 months. Survival rate was 39.6% (standard error [SE] = 6.6%) at 1 year and 23% (SE = 5.8%) at 2 years. Complications of treatment included an enhanced skin reaction in six patients and otitis media and/or externa in nine. One patient bled into tumor shortly after completion of HRT, and three had intralesional necrosis. Five patients continued taking steroids for protracted periods in the face of improved clinical and/or radiologic findings. Complications related to the use of steroids included opportunistic infections, impaired glucose tolerance, hypertension, osteoporosis, and significant mood changes. In no patient was there evidence of any late injury attributable to HRT. When compared with results of treatment with HRT at a lower dose level (6600 cGy), there appears to be a trend toward improved survival at 7020 cGy despite a less favorable patient population at the higher dose level. A second dose escalation to 7560 cGy in 60 fractions over 6 weeks has been implemented as planned.

Adolescent

Comparison of reflex modification procedures and auditory brainstem response in high-risk neonates.

This study compared the results of reflex modification (RM)--an objective technique for assessing brainstem sensorineural processing--with those of auditory brainstem response (ABR) for a group of high-risk infants at comparable postconceptional ages. For the RM procedure, an eyeblink-eliciting tap to the glabella was presented either alone or accompanied by a brief 90dB SPL tone. 37 high-risk infants were tested with both RM and ABR at a mean postconceptional age of 37.3 weeks. Seven had an increased brainstem conduction time ('failed ABR') and eight did not exhibit significant reflex augmentation ('failed RM'), seven of whom also failed the ABR. These data provide evidence that sensory stimuli which affect the neural mechanisms responsible for the organization of the startle response and auditory processing share essential neural components.

Auditory Pathways

Randomization analysis of dental data characterized by skew and variance heterogeneity.

Many distributions of dental variables exhibit positive skew and variance heterogeneity. Although the use of parametric tests on data with these disturbances usually does not pose a problem with respect to alpha error level, transformation of data sometimes increases power. Occasionally one or both of these expectations do not hold and it becomes problematic as to whether data should be transformed and which analyses should be considered valid. Simulated dental trials were conducted on independent samples (n = 25 per group) drawn from exponential distributions with the same or different population means, t-tests on raw, log, and square root transformed data; the Mann-Whitney-Wilcoxon ranking test; and a randomization test, all exhibited satisfactory levels of alpha error but the randomization test exhibited the greatest power followed closely by the t-test on raw scores. The present results demonstrate that the log transformation does not increase power for all forms of positively skewed data. Randomization tests, not being subject to normality and variance homogeneity assumptions, may yield greater confidence in validity in these cases. Some implications for analytical strategy are discussed.

Analysis of Variance

Carbachol- and elevated Ca(2+)-induced translocation of functionally active protein kinase C to the brush border of rabbit ileal Na+ absorbing cells.

Protein kinase C is involved in mediating the effects of elevated Ca2+ in ileal villus Na+ absorbing cells to inhibit NaCl absorption. The present studies were undertaken to understand the mechanism by which this occurs. The effects of carbachol and the calcium ionophore A23187, agents which elevate intracellular Ca2+ and inhibit NaCl absorption in ileal villus cells, were studied. Carbachol treatment of villus cells caused a rapid decrease in protein kinase C activity in cytosol, with an accompanying increase in microvillus membrane C kinase. Exposure of the villus cells to calcium ionophore also caused a quantitatively similar decrease in cytosol C kinase and increase in C kinase activity in the microvillus membrane. This increase caused by carbachol and Ca2+ ionophore was specific for the microvillus membrane. In fact, 30 s and 10 min after exposure of the cells to carbachol, basolateral membrane protein kinase C decreased, in a time-dependent manner; whereas 10 min of Ca2+ ionophore exposure did not alter basolateral C kinase. Exposure of villus cells to Ca2+ ionophore or carbachol caused similar increases in microvillus membrane diacylglycerol content. As judged by the ability to inhibit Na+/H+ exchange measured in ileal villus cell brush border membrane vesicles, the protein kinase C which translocated to the microvillus membrane was functionally significant. Inhibition of Na+/H+ exchange required ATP and was reversed by the protein kinase C antagonist H-7. In conclusion, the effect of carbachol and Ca2+ ionophore in regulation of ileal NaCl absorption is associated with an increase in microvillus membrane diacylglycerol content and functionally active protein kinase C. The effects of both carbachol and Ca2+ ionophore are different on brush border and basolateral membrane distribution of protein kinase C.

Absorption

Neural network approach to detection of metastatic melanoma from chromatographic analysis of urine.

Chromatographic analysis of sera or urine is important in medicine for the evaluation of patients whose clinical status is associated with the presence of specific biochemical markers. Malignant melanoma has been a model for such studies due to the elaboration of melanin precursors and pigment as the tumor metastasizes. Computer-assisted methods for categorizing chromatographic data and clinical status are imperative due to the large number of detectable compounds and possible correlations. In addition, computer-based analysis of the data can readily extract patterns that are not obvious by visual inspection. In this paper, we present a neural network analysis of melanoma chromatographic and clinical data that categorizes subjects into normals, NED patients (No Evidence of Disease), and metastatic patients. The set of marker compounds for metastatic disease represents a significant advance over the correlations derived by visual inspection.

Algorithms

Optic pathway tumors.

Overall, the majority of patients with optic pathway tumors will have stable disease regardless if they are radiated or receive chemotherapy. This is a very indolent tumor system and, for the most part, not a threat to life. Because of this, issues regarding appropriate therapeutic approaches have yet to be resolved. Most agree that in patients with progressive visual loss and tumor limited to the orbit, surgery can be associated with a cure. The downside is the loss of vision associated with surgical extirpation. Radiation rather than surgery has been the mainstay of treatment for intracranial tumors of the optic pathway. To eliminate side effects associated with radiotherapy in the young child, chemotherapy may be the more considered choice. However, on escape of control, i.e., conversion of stable disease to progressive disease, radiotherapy should be considered.

Child

The long-term effects of central nervous system therapy on children with brain tumors.

Survivals of children with brain tumors have increased over the past 20 years owing to advances in surgery, radiation, and, most recently, chemotherapy. Unfortunately, central nervous system therapy, particularly radiation, may be associated with the development of dementia and learning disabilities, leukoencephalopathy, endocrinopathies, and oncogenesis. Recognition of these long-term effects of therapy is important as some are amenable to treatment and others may be prevented by modification of current treatment regimens.

Brain

Rabbit ileal villus cell brush border Na+/H+ exchange is regulated by Ca2+/calmodulin-dependent protein kinase II, a brush border membrane protein.

Ileal brush border membranes contain an endogenous Ca2+/calmodulin (CaM)-dependent protein kinase activity that modulates the activity of the apical membrane Na+/H+ exchanger. To further characterize this kinase, synapsin I, a substrate for Ca2+/CaM-dependent protein kinases, was added to preparations of ileal brush border membranes. In the presence of Ca2+/CaM, synapsin I was phosphorylated. Phosphopeptide mapping demonstrated that the addition of Ca2+/CaM to brush border membranes stimulated the phosphorylation of sites in synapsin I specific for Ca2+/CaM-dependent protein kinase II. Immunoblots containing brush border and microvillus membrane proteins were probed with an antibody that recognizes the 50-kDa subunit of rat brain Ca2+/CaM-dependent protein kinase II. This antibody labeled major and minor species of 50 and 53 kDa, respectively, with more labeling of the brush border than the microvillus membranes. Right-side-out ileal villus cell brush border vesicles were prepared containing CaM, ATP, and 350 nM free Ca2+. Na+/H+ exchange was inhibited by the presence of Ca2+/CaM/ATP within the vesicles. A 21-amino acid peptide inhibitor of CaM kinase II was enclosed within some vesicle preparations by freeze-thaw. The effect on Na+/H+ exchange of Ca2+/CaM/ATP was partially reversed by the inhibitor peptide. These studies demonstrate the presence of Ca2+/CaM-dependent protein kinase II in rabbit ileal villus cell brush border membranes. Based on the effect of a specific inhibitor peptide of Ca2+/CaM kinase II, it is concluded that this kinase inhibits brush border Na+/H+ exchange, which participates in the regulation of ileal Na+ absorption.

Animals