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Biomedical subjects

D J Anderson

Publications and source records attributed to D J Anderson.

At least 343 records · Page 19Linked to original sources

Basic FGF induces neuronal differentiation, cell division, and NGF dependence in chromaffin cells: a sequence of events in sympathetic development.

To define further the molecules that control sympathoadrenal differentiation, we have investigated the effects of FGF, NGF, and glucocorticoid on cultured neonatal rat adrenal chromaffin cells. Basic FGF (bFGF), like NGF, induces cell division and neurite outgrowth from these cells. Dexamethasone inhibits neuronal differentiation but not proliferation induced by bFGF. Unlike NGF, bFGF will not support the survival of chromaffin cell-derived sympathetic neurons. However, bFGF induces a dependence on NGF. The overlapping but distinct responses to NGF and bFGF may underlie a sequence of events in sympathetic differentiation. bFGF (or another factor) may act locally in developing ganglia to stimulate mitotic expansion and initial axon outgrowth. Subsequent survival and maturation are then controlled by NGF, which is provided by peripheral targets of innervation. In the adrenal gland, glucocorticoids may permit bFGF to amplify the chromaffin population, while preventing neuronal differentiation.

Adrenal Medulla↗

The senior radiology clerkship. Disparate goals of students and faculty.

A survey of medical students taking our radiology elective over the past five years revealed that 51% were chiefly interested in learning "to read x-rays." Other motivations for taking the elective, such as learning "radiographic workups" were relatively low-priority goals. On the other hand, a survey of our staff revealed a low priority placed on teaching medical students to interpret radiographic images and a high value placed on imparting an understanding of the role of radiology in clinical diagnosis and management. This disparity between the goals of the students and teachers delineates one of the major challenges in designing a radiology curriculum for medical schools.

Clinical Clerkship↗

Student analysis of imaging studies. A radiology clerkship exercise.

Senior radiology clerkships often must cope with medical students whose overly optimistic course goals are quite different from the objectives of the radiology faculty. Conference formats that satisfy both the clerks and the teachers are therefore difficult to design. We use a conference based on student assessments of radiology examinations that attracts student interest while accomplishing staff objectives. This learning session relies on student-prepared analyses of radiologic examinations. The five-year experience with this teaching method has been quite positive from the perspectives of students and the staff.

Clinical Clerkship↗

Cell-mediated immunity in infertility.

A role of cell-mediated immunity in immunologic infertility is indicated by a number of animal immunization studies and by reported clinical associations between cellular immune responses and infertility. Furthermore, recent technical advances in the field of cellular immunology have enabled advanced studies on the cellular and soluble mediators of cell-mediated immune responses and their interactions with reproductive processes. In this article we review some of the recent technical and conceptual advances in cellular immunology, the classic literature on cellular immune responses in infertility, and recent evidence that certain products of activated lymphocytes and macrophages significantly affect reproductive functions.

Biological Factors↗

Temporal and geographical distributions of epilithic sodium dodecyl sulfate-degrading bacteria in a polluted South Wales river.

Epilithic bacteria were isolated nonselectively from riverbed stones and examined by gel zymography for their ability to produce alkylsulfatase (AS) enzymes and thus to metabolize alkyl sulfate surfactants such as sodium dodecyl sulfate. The percentages of AS+ isolates from stone epilithon at five sites from the source to the river mouth were measured on five sampling days spread over 1 year. The results showed that (i) the prevalence of epilithic AS+ strains (as a percentage of all isolates) was much higher at polluted sites than at the source; (ii) when averaged over the whole river, percentages of AS+ strains were significantly higher at the end of summer compared with either the preceding or the following winter; (iii) analysis of site-sampling time interactions indicated that water quality factors (e.g., biochemical oxygen demand and dissolved oxygen concentration) rather than climatic factors determined the distributions of epilithic AS+ isolates; (iv) constitutive strains were the most prevalent (7.2% of all isolates), with smaller numbers of isolates with inducible (4.5%) and repressible (1.7%) enzymes.

Analysis of Variance↗

The moxFG region encodes four polypeptides in the methanol-oxidizing bacterium Methylobacterium sp. strain AM1.

The polypeptides encoded by a putative methanol oxidation (mox) operon of Methylobacterium sp. strain AM1 were expressed in Escherichia coli, using a coupled in vivo T7 RNA polymerase/promoter gene expression system. Two mox genes had been previously mapped to this region: moxF, the gene encoding the methanol dehydrogenase (MeDH) polypeptide; and moxG, a gene believed to encode a soluble type c cytochrome, cytochrome cL. In this study, four polypeptides of Mr 60,000, 30,000, 20,000, and 12,000 were found to be encoded by the moxFG region and were tentatively designated moxF, -J, -G, and -I, respectively. The arrangement of the genes (5' to 3') was found to be moxFJGI. The identities of three of the four polypeptides were determined by protein immunoblot analysis. The product of moxF, the Mr-60,000 polypeptide, was confirmed to be the MeDH polypeptide. The product of moxG, the Mr-20,000 polypeptide, was identified as mature cytochrome cL, and the product of moxI, the Mr-12,000 polypeptide, was identified as a MeDH-associated polypeptide that copurifies with the holoenzyme. The identity of the Mr-30,000 polypeptide (the moxJ gene product) could not be determined. The function of the Mr-12,000 MeDH-associated polypeptide is not yet clear. However, it is not present in mutants that lack the Mr-60,000 MeDH subunit, and it appears that the stability of the MeDH-associated polypeptide is dependent on the presence of the Mr-60,000 MeDH polypeptide. Our data suggest that both the Mr-30,000 and -12,000 polypeptides are involved in methanol oxidation, which would bring to 12 the number of mox genes in Methylobacterium sp. strain AM1.

Bacterial Proteins↗

Ultrasound lumbar canal measurement in hospital employees with back pain.

The oblique parasagittal diameter of the lumbar spinal canal at the L5-S1 level was measured in 49 employees of the Wm Jennings Bryan Dorn Veterans' Hospital using real time ultrasound in a case-control study. Individuals with a canal diameter of less than 14 mm represented the lowest 10th percentile in this population and being in the narrowest 10th percentile constituted a risk factor for time missed from work because of low back pain (odds ratio 10.7). Whereas numbers in this pilot study are small, results are consistent with earlier ultrasound studies done in the United Kingdom and with other research showing increased morbidity from low back pain in individuals with small lumbar canals. Ultrasound has advantages over other modalities for measuring the size of the lumbar canal and may be useful as a preplacement screening examination in industry.

Adult↗

Pulmonary vascular permeability during the adult respiratory distress syndrome: a positron emission tomographic study.

The natural history of change in pulmonary vascular permeability (PVP) during the adult respiratory distress syndrome (ARDS) is unknown. Therefore, we evaluated PVP by measuring the pulmonary transcapillary escape rate (PTCER) for transferrin with positron emission tomography (PET) in 15 ARDS patients, including 5 patients studied within 4 days of onset and 13 patients studied at least 7 days after onset. In 3 patients, studies were performed at both early and late stages. These results were compared to 12 non-smoking adult volunteers. Regional PTCER and extravascular lung density (EVD) were determined from a 1-h PET scan after intravenous injection of gallium-68 citrate, which binds rapidly to native transferrin. Oxygenation, radiologic score, as well as outcome were recorded for each patient. Mean PTCER was highest during the early phase of ARDS (560 +/- 275 x 10(-4) min-1) although PTCER in the late ARDS patients was also significantly higher than in normals (319 +/- 187 vs 58 +/- 33 x 10(-4) min-1; p less than .01). EVD was similar in both early and late ARDS groups (.39 +/- .08 and .37 +/- .13 g/ml lung, respectively) and markedly higher than in normals (.22 +/- .05 g/ml lung, p less than 0.01). PTCER decreased in each of the 3 serial studies. The correlation between PTCER and EVD was poor, as were correlations for either PTCER or EVD versus changes in oxygenation, radiologic score, survival, or duration of ventilator dependency. In the late ARDS patients, PTCER was usually elevated even if EVD had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Characterization of leukocyte subpopulations in the peritoneal fluid of women with endometriosis.

Monoclonal antibodies identifying leukocytes subpopulations were applied to smears of laparoscopically collected peritoneal fluid leukocytes and parallel samples of peripheral blood leukocytes from women with endometriosis (n = 33), those with unexplained infertility (n = 9), and fertile controls (n = 8). Peripheral blood leukocyte profiles in all groups were indistinguishable from reported normal values. Peritoneal fluid leukocyte profiles were observed to be different between groups. The most significant elevations in total leukocytes, macrophages, helper T lymphocytes and natural-killer cells were observed in women with stage I and II endometriosis. Significantly elevated levels of total leukocytes, macrophages, and T lymphocytes were also observed in peritoneal fluid from women with unexplained infertility. The results from this study indicate that the peritoneal environment is immunologically dynamic and suggest that cellular immune mechanisms may contribute to reproductive failure in women with endometriosis and unexplained infertility.

Antibodies, Monoclonal↗

Immunohistologic characterization and quantitation of leukocyte subpopulations in human semen.

Various major leukocyte subpopulations (granulocytes, monocytes/macrophages, B lymphocytes, helper and suppressor/cytotoxic T lymphocytes) were detectable in human semen by applying monoclonal antibodies (MAbs) specific for pan-leukocyte and leukocyte subpopulation markers. MAb-labeled cells in smears of washed human semen were visualized by a standard streptavidin-biotin immunoperoxidase method. This approach was validated by testing the MAb panel against sections of human testis and epididymis to rule out cross-reactivity with immature germ cells or other reproductive tract cells, and against peripheral blood leukocytes that had been incubated in human semen to ascertain leukocyte marker stability in seminal plasma. When the immunoperoxidase technique was applied to semen smears from 17 proven fertile men and 51 randomly selected infertility patients, the authors found highly varying total leukocyte numbers, ranging from 8970 to 20,520,000 per ejaculate among fertile men (median, 170,000), and from 43,120 to 104,580,000 among infertility patients (median, 1,035,000). Higher means and medians of granulocytes, monocytes/macrophages, and lymphocyte subsets were seen in the infertility group. These results warrant further investigation on the diagnostic utility of semen leukocyte profiles and the possible role of seminal leukocytes in male infertility.

Adult↗

Evaluation of granulocyte elastase as a seminal plasma marker for leukocytospermia.

To evaluate the relationship between concentrations of the granulocytic enzyme polymorphonuclear (PMN) elastase in seminal plasma and the presence of high numbers of white blood cells (WBC) in semen, specimens from 118 infertility patients were analyzed for each variable. PMN-elastase levels were determined by an enzyme-linked immunosorbent assay and WBC numbers by a recently described immunohistologic technique. PMN-elastase levels in seminal plasma correlated well with WBC numbers in semen (r = +0.755). A three-step grading system of PMN-elastase values as low/normal (less than 250 ng/ml), intermediate (250 to 1000 ng/ml) and high/pathologic (greater than 1000 ng/ml) showed a highly significant relationship to a similar WBC number grading system: low/normal, less than 10(5) WBC/ml, intermediate, 10(5) to 10(6) WBC/ml, and high/leukocytospermic, greater than 10(6) WBC/ml semen. Incubation of semen at 37 degrees C resulted in a slight continuous decrease of immunoreactive PMN-elastase at a rate of approximately 10% per 3 hours. As all 18 samples with more than 1000 ng PMN-elastase per ml seminal plasma showed more than 10(6) WBC/ml semen, PMN-elastase levels above 1000 ng/ml were diagnostic for leukocytospermia.

Humans↗

Products of activated lymphocytes and macrophages inhibit mouse embryo development in vitro.

The effects of activated leukocyte products on embryonic development were assessed by adding mouse and human leukocyte culture supernatants and purified murine and human lymphokines and monokines to mouse embryos in tissue culture. Supernatants from mitogen-stimulated and mixed lymphocyte cultures arrested embryonic development at the two-cell to morula stage. Of a panel of six individual lymphokines and monokines tested for effects in this system, both murine and human forms of the lymphokines colony-stimulating factor, interferon-gamma, and human B cell growth factor significantly arrested embryonic development over a wide concentration range. The monokines, interleukin 1 and tumor necrosis factor, also had significant effects but only at high doses. These results indicate that products of activated lymphocytes and macrophages can have detrimental effects on preimplantation embryos. Early abortion could result from local (intrauterine) production of such embryotoxic factors by activated lymphocytes and macrophages in response to stimulation by microorganisms or reproductive tissue antigens.

Animals↗

Differences in immunogenicity indicating polymorphism of sperm antigens from mice of different inbred strains.

Polymorphism of mouse sperm was investigated by analysis of immune sera generated in BALB/c female mice against sperm from 6 inbred strains. The immune sera were analyzed by immunofluorescence and Western blot techniques against sperm antigens from the 6 immunizing strains. Immunofluorescence revealed no differences in reactivity patterns or titers. However, several different reaction patterns were detected by Western blot technique which indicated that both the sperm extracts and the antisperm immune sera contained different components. Syngeneic (anti-BALB/c sperm) antisera showed far fewer reactive antibody species than allogeneic immune sera. The anti-BALB/c sera recognized an antigen of 23 kDa in sperm extracts from DBA/2J and C57BL/6 mice, and failed to react with an antigen of the same molecular weight when applied to sperm from A/J and 129/J mice, indicating antigenic differences between sperm from these inbred strains. Anti-C57BL/6 sera contained a unique antibody which reacted with an antigen of 80 kDa in all of the 6 sperm extracts, whereas others antisera did not detect this antigen. These findings indicate antigenic and immunogenic polymorphism in sperm from different inbred strains of mice.

Animals↗

Monoclonal antibodies to human trophoblast and sperm antigens: report of two WHO-sponsored workshops, June 30, 1986--Toronto, Canada.

Two WHO-sponsored workshops were recently held to obtain a consensus view from researchers active in the field of reproductive immunology on the current status of the application of monoclonal antibodies to studies of molecular events underlying reproduction and to determine the feasibility of using this approach to identify trophoblast- or sperm-specific antigens that might represent suitable candidates for the development of antifertility vaccines. A total of 66 mouse monoclonal antibodies reacting with human sperm and 45 monoclonal antibodies reacting with human trophoblast membrane components were submitted by 29 laboratories. These were evaluated in coded form by 42 laboratories with the appropriate expertise in biochemistry, immunohistology and tests of reproductive cell function. The majority of both anti-sperm and anti-trophoblast monoclonal antibodies cross-reacted with cellular elements in non-reproductive tissues. However, at least five monoclonal antibodies (two anti-trophoblast and three anti-sperm) appeared to demonstrate sufficient specificity to warrant further investigation as reagents for the identification of antifertility vaccine candidates.

Antibodies, Monoclonal↗