Biomedical subjects
Publications and source records attributed to C Cohen.
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Members of the spectrin superfamily of proteins contain different numbers of homologous repeats arranged in tandem. Each of these consists of a three-alpha-helix motif, comprising two similarly and one oppositely directed alpha-helical segment joined by nonhelical linkers of characteristic length. The right-handed alpha-helices each display a heptad repeat in their amino acid sequences indicative of left-handed coiled-coil-like packing. We have calculated the potential number of inter-helix ionic interactions that specify the spatial arrangement of the helices in the motif in terms of both the handedness of helix connectivity (left or right) and the relative axial stagger between the three alpha-helices. All of the models examined were constrained to have optimal coiled-coil packing. For alpha-spectrin and alpha-actinin the results provide strong support for a left-handed connectivity of the three helices and axial repeat lengths of 5.05 and 6.24 nm, respectively. Furthermore, the axial staggers between homologous segments in the preferred models are identical. The insights provided into the topography of this widespread tertiary fold may prove of value to those concerned with the problem of de novo protein design.
OBJECTIVE: To develop a reliable and valid test of cognitive function suitable for patients with severe cognitive impairment. DESIGN: Administration of a test; test-retest reliability; comparison to traditional test. SETTING: Chronic long-term-care facility. PATIENTS OR OTHER PARTICIPANTS: The participants were 40 elderly residents with severe cognitive impairment. MAIN OUTCOME MEASURES: Results of the Test for Severe Impairment (TSI) and its subsections (language, memory, executive function, and motor performance); correlation of test and retest scores; correlation of TSI with Mini-Mental State Exam. RESULTS: The TSI was significantly correlated with the Mini-Mental State Exam (r = 0.83, P less than or equal to 0.0001). Test-retest reliability was high (r = 0.96, P less than 0.0001). The internal reliability of the test was also good (alpha = 0.90). Preliminary result of a factor-analysis suggests that factor scores may be derived that relate to memory, language production, and knowledge of body parts. CONCLUSIONS: The TSI is a valid and reliable test of cognitive function in patients with severe cognitive impairment. It is appropriate to use it as a unified scale.
Cellular proliferation has been implicated as an important predictor of biologic behavior in breast cancer. Cellular proliferation of 95 breast carcinomas was evaluated by comparing Ki-67 immunoreactivity in frozen sections quantitated by image analysis with S-phase and S + G2/M phase fraction determined by flow cytometry on nuclei extracted from fixed, paraffin-embedded sections (modified Hedley's technique). These parameters were correlated with traditional morphologic features of histologic grade, including mitotic count. Ki-67 immunoreactivity correlated with S-phase fraction determined by flow cytometry (r = .41, P = .001) and with S + G2/M phase fraction determined by flow cytometry (r = .29, P = .008). There was also a correlation between histologic grade and Ki-67 immunoreactivity (r = .30, P = .004) and between histologic grade and S-phase fraction (r = .42, P = .0001). Mitotic count correlated with Ki-67 immunoreactivity (r = .25, P = .015) and with S-phase fraction (r = .35, P = .001). Image and flow cytometric analysis systems provide comparable measurements of cellular proliferation; their measurements correlate with histologic grade and mitotic count in breast cancer.
A twice-yearly audit of a sample of medical records from each department of a general hospital was initiated by a quality assurance committee and pursued for 8 years. Missing entries that were considered obligatory for good medical performance of each service were identified, and the results (expressed as percent of missing entries of the total) were communicated in graphic form to the specific departments and the senior staff of the hospital. This approach led to an improvement in the medical records (decrease of missing entries), which may reflect a higher quality of medical care. Thus, a sequential audit of medical records by a quality assurance committee may constitute a simple and effective method of monitoring and improving physicians' knowledge and performance.
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Sixteen ear malignant melanomas (MM) were studied for ploidy and cell cycle analysis by flow and image cytometry. The results were compared with clinical (age, sex, stage), histologic (depth of invasion, level, type) and prognostic (recurrence, death) parameters. Single nuclear suspensions were obtained from fixed, paraffin-embedded tumor and adjacent normal tissue processed separately according to Hedley's technique. These, a "spiked" specimen of normal tissue and tumor, and a spleen diploid control were analyzed on a FACScan flow cytometer (Becton Dickinson, Mountain View, California, U.S.A.). Feulgen-stained Cytocentrifuge preparations of nuclear suspensions of normal, MM and diploid spleen were analyzed with the CAS 200 Image Analyzer (Cell Analysis Systems, Inc., Elmhurst, Illinois, U.S.A.) against commercial calibration rat hepatocytes defined as diploid. Six (37.5%) MM were diploid, and 10 (62.5%) were aneuploid; 8 (90%) were hypodiploid, for a high frequency. There were no statistically significant correlations between clinical, pathologic, prognostic or cell cycle analysis parameters and ploidy, although poor prognostic features tended to be in aneuploid lesions.
One important role for the primary care provider is to be familiar with all available treatment options for HIV disease. Because only a few treatments are approved, unapproved therapy becomes important for many patients. As a result, clinicians have had systems developed that create access to promising investigational drugs. In addition, because of the urgent need to increase the number of proven treatments, some clinicians have chosen to become more directly involved in the evaluation of new treatments for HIV disease by becoming community based "clinician-researchers."
Electron microscope images of frozen-hydrated crystals of a proteolytically modified fibrinogen show excellent preservation of the structure. An electron density map of the key centric projection of the crystal at 18 A resolution has been obtained by combining the phases derived from cryo-electron microscopy with X-ray amplitudes. Simulation methods developed in earlier studies have been used to interpret the map. In contrast to the earlier images, the map allows us to visualize the coiled-coil region of the molecule and possible substructure in the beta domains. The map also shows that there is a marked difference in density in the two regions corresponding to the molecular ends where the gamma domains interact. A possible interpretation of this finding is provided by assuming substructure in the gamma domains and the breaking of molecular symmetry where these domains interact. Some additional constraints useful for the determination of the three-dimensional structure were obtained from cryo-electron micrographs of a perpendicular view at 25 A resolution. Implications of this working model for the molecular length and contacts in the filaments in both the crystal and fibrin are described. The data used here will be valuable as a starting point for obtaining the three-dimensional structure.
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Two arguments underlie a widespread unwillingness to consider patients with alcoholic cirrhosis of the liver as candidates for transplantation. First, alcoholics are morally blameworthy, their condition the result of their own misconduct; such blameworthiness disqualifies alcoholics in unavoidable competition for organs with others who are equally sick but blameless. Second, because of their habits, alcoholics will not exhibit satisfactory rates of survival after transplantation; good stewardship of a scarce lifesaving resource therefore requires that alcoholics not be considered for liver transplantation. These arguments are carefully analyzed and shown to be defective. There is not good moral or medical reason for categorically precluding alcoholics as candidates for liver transplantation. It would, in addition, be unjust to implement such a preclusion simply because others might respond negatively if we do not.
Memory for temporal order information was examined in patients with chronic schizophrenia using the recency discrimination task. In this task, subjects were shown a pair of previously studied words and were asked to choose which one of the two words they had seen more recently. In addition, subjects performed the Wisconsin Card Sorting Test (WCST). The results showed that schizophrenic patients differed from normal control subjects in their performance on the recency discrimination task. In addition, for schizophrenic patients, performance on the recency discrimination task was inversely related to the number of perseverative errors on the WCST. These results provide further evidence of prefrontal-type cognitive deficits in schizophrenia.
The ability to perceive affect was examined in 19 patients with Alzheimer's disease and in 19 control subjects. Nine tasks were given. All participants were asked to recognize facial emotion, to provide verbal labels of facial emotion, and to identify emotion portrayed in drawings or in verbal descriptions of emotional situations. The results indicate that there are significant differences between patients with Alzheimer's disease and control subjects on all of the tasks. However, when test scores were adjusted for the cognitive abilities of the subjects, few of the tests continue to differentiate the groups. These results suggest that the deficits of patients with Alzheimer's disease on perception of affect tasks are likely to be the result of their cognitive defects and not the result of a primary impairment in the perception of emotion.
The interactive effect of caffeine and nicotine on spontaneous locomotor activity in a tunnel maze was determined in nicotine-naive and nicotine-tolerant rats. Rats were daily injected subcutaneously for 12 days with nicotine (0.4 mg/kg) to induce nicotine tolerance. Nicotine-naive rats were injected with saline. During the next two days, they were exposed to a tunnel maze for two 6-min trials. On the third day, locomotor activity was measured (30-min trial) in the tunnel maze 15 minutes after subcutaneous injection of saline, nicotine (0.2 mg/kg), caffeine (8 mg/kg), or nicotine (0.2 mg/kg) and caffeine (8 mg/kg) in combination. Acute exposure to nicotine decreased locomotor activity in nicotine-naive rats. This decrease was antagonized by simultaneous injection of caffeine. Chronic nicotine exposure induced the development of tolerance to the acute behavioral depressive effects of nicotine. In nicotine-tolerant rats, caffeine and nicotine in combination significantly increased locomotor activity above saline level, whereas given alone they had no significant stimulant effect. Neither chronic nicotine treatment nor acute drug treatments affected exploratory efficiency of rats.
Two regimens were tested, CHAP I and CHAP II, the latter, a hexamethylmelamine dosage-intensive regimen, first as second line (salvage) therapy and then as primary therapy. Both produced the most successful results achieved in the Mount Sinai series up to the time of their introduction, when compared to their predecessor regimens: CAP, AP and P. In an overall interim comparison, CHAP II was significantly superior to historical AP and CAP as primary therapy, as was CHAP I vs. AP in several important subgroups compared as part of a randomized trial. CHAP II overall progression-free survival was improved in spite of added new sensitive test methods. Salvage therapy also improved markedly with the addition of intensive hexamethylmelamine. Several biological and treatment characteristics strongly influenced outcome, especially young age and adding hexamethylmelamine. Other possible factors included: poor tumor grade, poor performance status, and extent of surgical debulking, even to intermediate residual, 2-6 cm size [CHAP II only]; extensive (optimum) surgery [CHAP I only]. The hexamethylmelamine-containing regimens interact favorably with some of these factors, better than did the preceding regimens. Five-year follow-up analyses weakened slightly for extensive surgery, intermediate size and poorly differentiated tumors. It confirmed and strengthened several findings favoring CHAP I & II, the hexamethylmelamine-containing regimens.
A comparison has been made between cryoelectron microscope images and the x-ray structure of one projection of the Bailey tropomyosin crystal. The computed transforms of the electron micrographs extend to a resolution of approximately 18 A compared with the reflections from x-ray crystallography which extend to 15 A. After correction of the images for lattice distortions and the contrast transfer function, the structure factors were constrained to the plane group (pmg) symmetry of this projection. Amplitude and phase data for five images were compared with the corresponding view from the three-dimensional x-ray diffraction data (Phillips, G.N., Jr., J.P. Fillers, and C. Cohen. 1986. J. Mol. Biol. 192: 111-131). The average R factor between the electron microscopy and x-ray amplitudes was 15%, with an amplitude-weighted mean phase difference of 4.8 degrees. The density maps derived from cryoelectron microscopy contain structural features similar to those from x-ray diffraction: these include the width and run of the filaments and their woven appearance at the crossover regions. Preliminary images obtained from frozen-hydrated tropomyosin/troponin cocrystals suggest that this approach may provide structural details not readily obtainable from x-ray diffraction studies.
The mediating role of social support in the mental health and behaviours of persons coping with life-threatening chronic illness is of potentially great importance in determining the quality of life of persons with HIV infection (PWHs). As part of a biracial pilot study of the ways black and white men manage the stresses of sexually acquired HIV infection, we have examined the relationship between social support and mental health and behaviours. Forty homosexual/bisexual men (20 white and 20 black) attending a Detroit hospital-based HIV outpatient clinic were recruited for the study and underwent physical and mental health (HSCL-59 and NIMH DIS interview), behavioural and psychosocial evaluations, and a neuropsychologic screening test battery. The black and white men did not differ in terms of age, education, sexual behaviours, physical or mental health status. However, the black men were less likely to be open about their sexuality to their primary social support network, and to report that their social support was less affirmative than did the white men. When correlations between the six-dimensional social support measures (Wortman & O'Brien, 1987) and HSC-L distress scores were examined, both availability of material social support and affirmation were correlated negatively with distress among the white men but positively among the black men. Similarly, the previously observed positive relationship between perceived adequacy of social support and adoption of safer sexual practices was observed among white but not black participants.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors immunohistochemically assessed the presence of estrogen receptor (ER) in formalin-fixed, paraffin-embedded tissue sections of 68 breast carcinomas by an automated method using Pronase (CalBiochem, La Jolla, CA) predigestion and alkaline phosphatase detection (Method 1). These results were compared with those obtained by an automated peroxidase-antiperoxidase method with DNAse pretreatment of fixed embedded sections (Method 2), with ER immunostain on frozen sections (Method 3), and with biochemical results (dextran-coated charcoal cytosolic [DCC] assay). Compared with the DCC assay, Methods 1, 2, and 3 gave sensitivities of 54%, 25%, and 89%, respectively. The sensitivity for Method 1 was increased to 74% in those cases with DCC results showing greater than 50 fmol/mg protein. These findings indicate that ER immunohistochemical studies on formalin-fixed paraffin-embedded tissues (as assayed by Method 1) provide useful clinical information when the results are positive. A negative result, especially if surrounding normal elements are not positive, may indicate no receptors, receptor levels less than 50 fmol/mg protein, or improper tissue preservation. In the absence of fresh tissue for ER assay by DCC assay or of frozen sections for immunostaining, and with an understanding of its limitations, this method may be useful.