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Biomedical subjects

C Jennings

Publications and source records attributed to C Jennings.

At least 55 records · Page 3Linked to original sources

A phenotypic study of CD8+ lymphocyte subsets in infants using three-color flow cytometry.

Flow cytometry is a powerful tool for the multiparametric evaluation of cell surface phenotype in patients with HIV disease. Many cell surface molecules can be evaluated by three-color flow cytometry and the markers correlated with functional activity. It has recently been recognized in adults that the CD8 cell is an important lymphocyte subset in HIV disease that correlates with disease outcome, but there is little information about CD8 subsets in infants. Therefore, we studied infants born to HIV-infected mothers and those born to uninfected mothers. No significant differences were seen in phenotypic markers of activation (CD38, HLA-DR), maturation (CD45RO, CD45RA), and function (CD28) between uninfected infants born to HIV infected or uninfected mothers. In HIV-infected infants, a substantial increase in CD8+ CD38+ HLA-DR+ expression was seen. In addition, we found that there was a significant increase in the CD8+ CD45RO+ CD45RA- subset which is characteristic of the memory phenotype. Finally, evaluation of CD28 (costimulatory molecule involved in T cell activation), which is expressed on almost all CD8 cells at birth, showed that this population was significantly reduced in infected infants. These studies suggest that three-color flow cytometry is a powerful tool for evaluating phenotypic changes in lymphocyte subsets and enhancing our understanding of the pathobiology of HIV disease.

CD8 Antigens↗

Whole blood method for simultaneous detection of surface and cytoplasmic antigens by flow cytometry.

Dual parameter analysis of surface antigens in flow cytometry has become a standard method for detection of cell subsets. However, few methods have been described for the extension of multiparameter analyses to include cytoplasmic or intracellular antigens. Here we describe a simple and reproducible method for simultaneous detection of surface and intracellular antigens by flow cytometry in lysed whole blood samples. This method employs the use of digitonin, a mild glycoside detergent, and formaldehyde for permeabilization and fixation. Red blood cells are lysed with 2% acetic acid. Preparation of samples in this manner resulted in altered light scatter characteristics relative to unpermeabilized samples; however, gating issues were overcome using a combination of scatter vs. fluorescence gating. Quantitation of CD3+/CD4+ and CD3+/CD8+ cells using this method was equivalent to counts obtained with the reference method using a commercially available lysis procedure and fluorescence vs. scatter gating. The effectiveness of the permeabilization process was assessed using a monoclonal antibody designated TIA-1, which is specific for a cytoplasmic antigen associated with cytotoxic granules predominantly found in CD8+ cells. The method effectively quantitated TIA-1 positive cells and demonstrated the specificity of the reagent for a subpopulation of CD8+ lymphocytes. Using this simplified procedure for simultaneous identification of surface and cytoplasmic antigens could help in studies of cell activation, proliferation, and other functional characteristics of the immune system.

Antibodies, Monoclonal↗

Caffeine and nicotine improve visual tracking by rats: a comparison with amphetamine, cocaine and apomorphine.

Psychomotor stimulant drugs such as caffeine, nicotine, amphetamine and cocaine, have been shown to improve vigilance in man under conditions of fatigue. Nicotine has also been shown to improve performance in some cognitive tests in patients with Alzheimer's disease. In rodents these drugs increase activity which may confound "performance enhancing effects" in rodent models. However, improvements have been found in a number of tests that do not seem to be directly dependent upon an enhancement of locomotor activation. In one example, Evenden and Robbins (1985) reported consistent improvements in a visual tracking test following amphetamine. The present study was undertaken to determine whether these performance enhancing effects of amphetamine could also be obtained with cocaine and apomorphine, which both have psychomotor stimulant effects through their actions as, respectively, indirect and direct dopamine agonists, and by caffeine and nicotine, which do not have a direct dopaminergic mechanism of action. The results of the study indicate that all five drugs improved tracking performance at one or more doses. The most consistent effects were obtained with amphetamine which, like cocaine and nicotine, improved tracking at a dose which did not produce other changes in behaviour. Taking into account previous studies (Evenden and Robbins 1983, 1985), these results were interpreted as indicating that psychomotor stimulant drugs produce a general activation of behaviour. At all but the highest doses of such drugs, the form of behaviour that is observed depends upon the environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

Spatial organization of repetitive DNA sequences in the bovine sperm nucleus.

During spermatogenesis, DNA in the sperm head becomes more tightly condensed as histones are replaced by protamine-like molecules. In this article, the question is asked whether, during the production of this highly differentiated cell, controls are imposed on the spatial organization of DNA within the nucleus. Heads from bull spermatozoa were isolated by a technique that removed the plasma membrane and acrosomal contents, and the DNA was induced to decondense by addition of 2-mercaptoethanol and trypsin. Under these conditions, decondensation was induced in all regions of the head. To determine whether there was any spatial restraint on packaging of the genome, three DNA probes were used (pl.709-512, containing an interspersed repetitive sequence; pCSIH, containing a copy of the major bovine centromeric statellite sequence; p18 s and p28 s, containing the 18 S and 28 S ribosomal genes) that might be expected to hybridize to different regions. Results showed that the interspersed repetitive probe hybridized to all regions of the head, whereas the ribosomal and centromeric probes hybridized to sequences that were largely confined to the equatorial region of the sperm. We conclude that organization of the genome in the bovine sperm nucleus is not random.

Animals↗

A quality assurance model for multidivision clinical departments.

Structuring a workable quality assurance (QA) program for multidivision and multispecialty clinical departments presents a considerable challenge. The Medical Center of the University of California, San Francisco (UCSF) found that QA activities in such departments were best handled by a committee of department physicians assisted by a QA staff person. This article provides examples of how two departments at the UCSF medical center structured QA committees to fit their departments' individual needs and explains how these committees fit in the medical center's overall QA program.

Hospital Bed Capacity, 500 and over↗

Ulnar nerve compression at the wrist.

Two cases of compression of the ulnar nerve by ganglions in the distal ulnar tunnel are reported. The type of neurologic deficit (motor, sensory, or both) was helpful in predicting both the zone of nerve compression and the nature of the compressing lesion.

Aged↗

Von Hippel-Lindau disease in a large British family: clinicopathological features and recommendations for screening and follow-up.

We describe the clinical and pathological features in nine members of a large British family with von Hippel-Lindau disease. Twenty living family members underwent detailed assessment for features of the disease, including retinal examination and computed tomography of the head and abdomen. The hospital records of three deceased family members were reviewed and detailed information about a fourth was obtained from members of the family. As a result of this study, three asymptomatic family members were found to have features of the disease and all three living affected family members were found to have additional features. Lesions discovered included retinal angiomas requiring treatment in four family members, one asymptomatic renal cell carcinoma and one asymptomatic pancreatic endocrine tumour. We also report the occurrence of a spermatic cord mesenchymal hamartoma in von Hippel-Lindau disease.

Adolescent↗

A glial high-affinity binding site with specificity for angiotensin II not angiotensin III: a possible N-terminal-specific converting enzyme.

Anomalous binding properties of angiotensin II to fetal rat brain primary cultures suggested a possible contribution from contaminating glia. To investigate this possibility, cultures of C6 glioma, a clonal rat cell line, were examined for the presence of angiotensin II receptors. A specific high-affinity site for [125I]angiotensin II was measured both by traditional methodology using whole cells and by autoradiography. This site shared properties similar to that found with the brain cells, namely low ligand internalization and markedly decreased affinity for N-terminal sarcosine or arginine-angiotensin analogs. The competition rank order was angiotensin II much greater than (Sar1,Ile8)angiotensin II greater than or equal to des(Asp1,Arg2)angiotensin II. Angiotensin III did not compete for binding to the site. High-pressure liquid chromatography analysis indicated that the ligand either in the incubation or bound to the site was stable at 15 degrees C, but there was very rapid and extensive degradation by the C6 glioma cells at 37 degrees C. It is concluded that the site exhibits unusual N-terminal specificity for angiotensin with nanomolar affinity for angiotensin II. If angiotensin III is an active ligand in the brain, the site may have a converting enzyme function. Alternatively, it may form the des-Asp derivatives of angiotensin for subsequent degradation by other enzymatic pathways. Either way, it is proposed that the site may modulate the brain-angiotensin system.

Angiotensin II↗

Intussusception: influence of age on reducibility.

Our experience of hydrostatic reduction of intussusception by barium enema over the last 7 years is reviewed. There were 115 attempted hydrostatic reductions out of a total of 129 patients diagnosed as having intussusception on barium enema or at surgery. Age at presentation varied from one month to nine years, 81% of patients presenting before one year of age. Of 115 attempted reductions, 63 were successful giving an overall success rate of 55%. Looking at the different age groups, it was found that hydrostatic reduction was much less successful in infants aged 3 months and younger; success rate 20% compared to a 60% success rate in the remainder. Conscious of recent reports in the literature of bowel perforation during attempted hydrostatic reduction in young infants, we suggest that there should be a reappraisal of the role of hydrostatic reduction in the three months and younger age group.

Age Factors↗

The uptake of swainsonine, a specific inhibitor of alpha-D-mannosidase, into normal human fibroblasts in culture.

Swainsonine, an indolizidine alkaloid, found in plants of the genus Swainsona, has been shown to be a strong inhibitor in vitro of the alpha-D-mannosidase activity in normal human fibroblasts. Therefore, inhibition of alpha-D-mannosidase activity in extracts of harvested cells grown with swainsonine in the medium has been used to follow the association of the alkaloid with normal human fibroblasts in culture. Swainsonine that could not be removed by extensive washing became associated with the cells within 1 min, and it is concluded that the alkaloid is internalized rapidly by the cells. The amount of swainsonine taken up into the cells depended on the length of time in contact and the concentration of swainsonine in the medium, but at 37 degrees C a plateau of internalized swainsonine occurred after 2 hr with extracellular concentrations of swainsonine of 100 microM or greater. At lower concentrations of swainsonine the rate of uptake was found to be temperature-dependent, increasing greatly at 20 degrees C. The rapidity and temperature sensitivity of the uptake, together with the observation that mannose or mannose-6-phosphate did not prevent the association, suggest that swainsonine enters the cells by permeation rather than by endocytosis. When swainsonine is withdrawn from the culture medium, there is a decrease with time of cell-associated swainsonine. The kinetics of uptake and release of swainsonine and its slightly basic nature make it likely that swainsonine is concentrated initially in the lysosomes. This rapid, but reversible, concentration of swainsonine in lysosomes would be consistent with the observed effects of the toxin in vivo.

Alkaloids↗

Ultrasonic evaluation of simple and ectopic ureteroceles.

Ureteroceles appear as transonic intravesical lesions on ultrasonic demonstration of the bladder, producing a 'cyst within a cyst' appearance. Four patients, three with simple ureteroceles and one with an ectopic ureterocele were investigated by intravenous urography (IVU), ultrasound (US) and cystoscopy. Two patients had bilateral simple ureteroceles with non-dilated ureters and two had unilateral ureteroceles, one simple, and one ectopic with a hydroureter. Previously ultrasonography of the fluid-filled bladder has demonstrated only large ureteroceles. The present study was successful in demonstrating both large and small ureteroceles.

Adult↗

Legal and administrative influences on the English suicide rate since 1900.

We examined the hypothesis that changes in the suicide rate of England and Wales since 1900 are an artefact of changes in the process of classifying violent deaths. Four potential sources of artefact were considered: (1) the reliability of the procedure for investigating suspected suicides; (2) coding by the Office of Population Censuses and Surveys; (3) changes in the law; (4) High Court decisions on suicide. None of these can explain the large observed fluctuations in the suicide rate.

Accidents↗

Have the Samaritans lowered the suicide rate? A controlled study.

Suicide rates in towns with a Samaritan branch were compared with rates in matched control towns without a branch. Four methods of choosing controls are described, all of which have advantages over those used by Bagley (1968). No statistically significant differences between Samaritan and control towns were found. The scientific case for the effectiveness of the Samaritans in reducing the suicide rate is therefore seriously weakened.

Crisis Intervention↗