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Biomedical subjects

C Herman

Publications and source records attributed to C Herman.

At least 37 records · Page 2Linked to original sources

Incidental white matter hyperintensities on magnetic resonance imaging in HIV-1 infection. Multicenter AIDS Cohort Study.

Magnetic resonance (MR) scans were performed as part of a prospective neuropsychological study within the Multicenter AIDS Cohort Study. Fifty HIV-1-seronegative men, 85 HIV-1-seropositive men without constitutional symptoms, and 14 with symptomatic HIV disease underwent MR imaging using a uniform protocol. Scans were rated by neuroradiologists blinded to all clinical details except age. The majority of MR scans were normal in all of the clinical groups and no covert mass lesions or diffuse white matter abnormalities were identified. Focal hyperintensities in the white matter were observed in 24% of the HIV-1 seronegatives, 26% of HIV-1 asymptomatic seropositives (CDC II/III), and 17% of those with ARC/AIDS. No significant associations were noted between the white matter hyperintensities and HIV-1 serostatus, neurological abnormalities, CD4 count, alcohol or drug use, hypertension, or smoking. In one individual classified with early HIV-1 dementia, MR demonstrated several hyperintensities in the deep parietal white matter, but at autopsy no microscopic abnormalities corresponding to the MR findings were identified. Our studies imply that focal white matter hyperintensities identified on MR are not specific for HIV-1 infection and are probably incidental and of no clinical significance.

AIDS-Related Complex

The public cost of motorcycle trauma.

Despite the effectiveness of motorcycle helmet legislation, many states have repealed these laws during the last decade. Aspects often neglected by policymakers are who pays for the care of these victims and how much of this cost is subsidized by public funds. To determine the extent of this subsidy, we studied the cost of care of 105 motorcyclists hospitalized at a major trauma center during a 12-month period. Total direct costs for these 105 patients, followed up for a mean of 20 months, were more than $2.7 million, with an average of $25,764 per patient. Only 60% of the direct costs were accounted for by the initial hospital care; 23% of costs were for rehabilitation care or readmission for treatment of acute problems. The majority (63.4%) of care was paid for by public funds, with Medicaid accounting for more than half of all charges.

Adult

The medical and social impact of nonaccidental injury.

To determine the medical and economic impact of nonaccidental trauma at a regional trauma and emergency care facility, a prospective patient database was used to follow up all victims of intentional injury admitted during one year. Specific patient data were combined with financial data to determine the medical outcome, expenditure, and hospital reimbursement. We found that 17% of the 2451 trauma patients admitted to our facility were victims of nonaccidental injury. The majority of these patients were severely injured, with an average hospital stay of six days. Hospital charges averaged $13,000 per patient. Three fourths of these individuals required governmental funding for medical care. Six months after completion of the review, only two thirds of all expenditures had been reimbursed. These patients represent a high medical services use group and consume a disproportionately high percentage of medical resources.

Alcohol Drinking

Morphometric analysis of epithelial cells of frog urinary bladder. I. Effect of antidiuretic hormone, calcium ionophore (A23187) and PGE2.

Changes in epithelial cell morphology, especially at the apical plasma membrane, are frequently cited as initial evidence for antidiuretic hormone (ADH)-induced increase in membrane permeability. The effects of ADH and agents that alter and modify calcium and prostaglandin concentrations on the morphology and cytology of the epithelial cells of frog (Rana pipiens) urinary bladder are presented using the techniques of transmission and scanning electron microscopy. It was found that, like ADH, calcium ionophore, A23187, produce intense microvilli formation, microfilament mobilization and an increase in the density of granules and membrane associated vesicles, suggesting a prominent role of calcium in these processes. Moreover, our results suggest that these membrane and cytosolic transformations may be mediated in part through prostaglandin formation, as exogenous PGE2 mimicked these effects, and indomethacin, a prostaglandin synthesis inhibitor, attenuated ionophore's effect on luminal cytomorphology. However, unlike ADH, prostaglandins and ionophore inhibit hormonal-induced increase in transepithelial water flow. These results suggest that other components more distal to the luminal membrane, perhaps the basolateral membrane, may be rate-limiting for transepithelial water flow and possibly are regulated by either changes in calcium concentrations or prostaglandins.

Actin Cytoskeleton

Antibodies to cytokeratin and vimentin in testicular tumour diagnosis.

Thirteen primary and metastatic testicular germ cell tumours, including classical and anaplastic seminomas, and non-seminomatous testicular tumours were examined for their intermediate filament protein (IFP) types. The seminomas were shown to react with a monoclonal and a polyclonal antibody to bovine lens vimentin, while non-seminomatous germ cell tumours were strongly positive for a polyclonal and a monoclonal antibody to cytokeratin. In one case of seminoma with elevated serum levels of beta HCG and alpha FP, cytokeratin positive tumour cells were found. In the case of teratocarcinoma, several components of the tumour could be distinguished using a combination of antisera in double-label immunofluorescence microscopy. The glandular component of this tumour was positive with the polyclonal antikeratin, but also with the monoclonal cytokeratin antibody specific for glandular epithelia (RGE 53). However, the squamous component was negative with this latter antibody. Strikingly, the spindle cell component showed focal positivity for vimentin, with coexpression of cytokeratin and vimentin in some cells. Our data show that antibodies to cytokeratin and vimentin can be helpful in the diagnosis of testicular germ cell tumours, especially in the differentiation between seminomas and non-seminomatous tumours.

Antibodies, Monoclonal

Cytokeratin expression during neoplastic progression of human transitional cell carcinomas as detected by a monoclonal and a polyclonal antibody.

Antibodies to intermediate filament proteins were used to study different cell layers in normal human transitional epithelium, 16 human transitional cell carcinomas, and two cell lines derived from human bladder carcinomas. Conventional rabbit antisera to human skin keratins stained all layers of the transitional epithelium from bladder, ureter, and kidney. A slightly higher staining intensity was found in the basal and superficial layers as compared with the intermediate cell layers. A monoclonal antibody to cytokeratin 18 (RGE 53), however, stained only the superficial cell layer of transitional epithelium, the so-called umbrella cells. In well-differentiated (grade I) transitional cell carcinomas, RGE 53 stained only the superficial cells of papillary structures. In higher grade papillary tumors, RGE 53 also stained cells within the basal and intermediate layers, whereas in high-grade, invasive tumors almost all tumor cells were RGE 53 positive. These results show that monoclonal antibodies to cytokeratins can provide both an indication of processes involved in neoplastic progression of bladder tumors and a means of studying the molecular relationship of the tumor cells to normal cells.

Animals

Continuous measurement and analysis of staining kinetics by flow cytometry.

The measurement of color development with time in cells following the start of a staining reaction is of interest in a number of biological systems. These include the subsets of peripheral white blood cells after acridine orange staining, the uptake by cells and nuclei of fluorescent agents, especially antitumor drugs, and measurement of intracellular enzyme kinetics using fluorogenic or absorbing substrates. The present work describes a simple computer program for analyzing flow cytometric (FCM) data versus time, including both the population kinetics of color development and the variability of staining speed within one population of cells. A single-channel absorption measurement in flow (Technicon Hemalog D) was used to record peroxidase kinetics in peripheral blood cells. Every 5 s, a 64-channel absorption histogram was recorded, up to a maximum of 64 histograms. The data were then analyzed by a computer program which searched for the peak channel of each histogram. A least-squares fit was computed for these maxima. The asymmetries of the 64 absorption histograms were compared to see if there was more than one population present with different time constants. Although developed for enzyme kinetic measurements, this program may have wider usefulness in any measurements of time-dependent phenomena by FCM.

Computers

Monoclonal antibody to keratin filaments, specific for glandular epithelia and their tumors. Use in surgical pathology.

A monoclonal antibody (RGE 53) against keratin intermediate filaments was prepared by fusing myeloma cells with splenic lymphocytes from mice immunized with a HeLa cell cytoskeleton preparation and human callus keratins. The antibody, selected for fibrillar staining in HeLa cells and a negative reaction on human skin, was tested on frozen sections from normal and malignant human tissues. RGE 53 specifically recognizes glandular epithelial cells from female breast, digestive, respiratory, and urogenital tracts, endocrine and exocrine tissues, and mesothelial cells. No reaction is found in stratified squamous epithelia or nonepithelial tissues. Furthermore, RGE 53 can distinguish adenocarcinomas and mesotheliomas, which stain positively in the indirect immunofluorescence technique from squamous cell carcinomas and nonepithelial tumors, which are negative for this antibody. RGE 53 may, therefore, be a useful tool for differential diagnosis in surgical pathology, especially in those cases in which anaplastic carcinomas have to be characterized.

Adenocarcinoma

Quantitative analysis of flow microfluorometric data for screening gynecologic cytology specimens.

Gynecologic cytology specimens that included the entire spectrum of cervical cytology classification were stained with a combination of propidium iodide and fluorescein isothiocyanate, then analyzed using a flow microfluorometer to measure nucleic acid and protein content, respectively. Numerous descriptors of the resulting two parameter distribution (nucleic acid versus protein) were defined. These descriptors included assessment of the presence or absence of abnormal cells. They also included measures of the staining intensity and dispersion of the normal squamous cell population and the intensity of inflammatory response in the cell population. Relative percentages of inflammatory and epithelial cells were demonstrated to effect the screening performance of this system only in borderline lesions. Decision tree algorithms allowed optimization of the selected parameters for screening logic of normal-abnormal decisions on a specimen-by-specimen basis. In addition, quantitative definitions of specimen adequacy were determined. Appropriate controls for batch staining of specimens were evaluated. These results of applying pattern recognition techniques to flow microfluorometer multiparameter data demonstrate that considerably more information about cell populations and subpopulations can be extracted than heretofore possible.

Adolescent

Measurement of cellular DNA mass by flow microfluorometry with use of a biological internal standard.

Use of a biological standard (chicken erythrocytes) mixed with experimental cell populations allows control of all variables in flow microfluorometric determination of DNA content. These variables include both staining and instrument procedures. In addition, the use of a biological standard allows determination of cellular DNA mass in unperturbed cell populations. DNA mass measured by FMF technique correlates closely with values reported in the literature that used biochemical techniques.

DNA

Drug-induced changes in DNA fluorescence intensity detected by flow microfluorometry and their implications for analysis of DNA content distributions.

Chicken erythrocytes, which contain less DNA than mammalian diploid cells, were used as an internal standard to control instrumental and staining variables during flow microfluorometric analysis. With the DNA stain, mithramycin, and with an EPICS II flow microfluorometer, ratios between the modal G1 fluorescence of experimental cells and that of chicken erythrocytes were determined. The results indicate that unperturbed cell populations of L1210 and HeLa cells in vitro and L1210 ascites cells in vivo have relatively stable fluorescence ratios, although there is a significant difference between the ratios of one L1210 cell line in vitro and another in vivo. In contrast, L1210 ascites treated in vivo with different schedules of cyclophosphamide and Adriamycin showed wide fluctuations in the fluorescence intensity ratios for 96 hr after treatment. Also, differences in the fluorescence ratios were observed between less advanced and more advanced L1210 ascites after treatment with the same schedule. These effects indicate an alteration in DNA staining with mithramycin, brought about by drug treatment that could seriously affect the interpretation of DNA histogram data. Nevertheless, changes in mithramycin staining may prove to be a very important probe to detect persistent drug effects.

Animals