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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 397 records · Page 22Linked to original sources

Application of numerical systematics to the phenotypic differentiation of legionellae.

A total of 163 strains, including 106 strains of Legionella pneumophila, 28 strains of Tatlockia micdadei, and 29 strains of other legionellae (including members of the proposed genus Fluoribacter), were studied. Ten tests which together could distinguish the genera previously proposed were identified. These tests included catalase-peroxidase, gelatinase, hippurate hydrolysis, starch hydrolysis, medium browning, acetoin production, oxidase, medium fluorescence, colony fluorescence, and the bromcresol purple spot test. T. micdadei strains were strongly catalase positive and bromcresol purple spot test positive and produced acetoin but otherwise were usually inert in the other tests. L. pneumophila and Fluoribacter species could usually be distinguished by strength of catalase activity, blue-white colony fluorescence (if present), and differences in frequency of hippurate hydrolysis, starch hydrolysis, yellow-green medium fluorescence, and, to a lesser extent, oxidase activity. With a simple algorithm and computer program, the overall accuracy was 98.8%.

Algorithms↗

Concurrent incidence of depression and physical symptoms among hostile young women.

Analyses of questionnaire responses from 166 young women on the Cook-Medley Hostility scale of the MMPI, Beck Depression Inventory, and Wahler Physical Symptoms Inventory indicated significant differences between hostile and nonhostile women on depression scores, ranging from mild mood disturbance to borderline clinical depression. Hostile women also endorsed more items which indicated pervasive somatic complaints such as nausea, fatigue, respiratory, gastrointestinal, and cardiovascular distress. These results are discussed in the context of negative emotion and degenerative disease.

Adolescent↗

Peritoneal barrier to the spread of Semliki forest virus in mice.

The LD50 for encephalitis caused by Semliki forest virus in 6- to 8-week-old mice is 1 plaque-forming unit (PFU) in C3H/Ten strain of mice when injected intracerebrally, iv, or in the footpad; however, the LD50 by the ip route is 4 x 10(3) PFU. In the ICR strain of mice at the same age, the LD50 for the intracerebral route is 1 PFU, 10(3) PFU for the iv and footpad routes, and 4 x 10(3) PFU for the ip route. A number of in vivo and in vitro experiments were done to explain the relative resistance to Semliki forest virus injection by the ip route. The results suggest that the viruses are adsorbed to and enter adherent cells of the peritoneal cavity but do not replicate and release progeny virus. After inoculation with the virus, viral antigens could only be observed in methanol-treated cells as a halo by immunofluorescence at or just below the plasma membrane of only a small fraction (less than 0.5%) of peritoneal adherent cells. Naturally occurring interferon-alpha/beta (less than 1 unit/ml) was found to probably play a marginal role, if any, in the resistance.

Animals↗

Assessment of canine intestinal permeability, using 51Cr-labeled ethylenediaminetetraacetate.

The 51Cr-labeled EDTA was validated as a suitable permeability probe in dogs for measurement of passive, unmediated diffusion across intestinal mucosa via intercellular pathways. The 51Cr-labeled EDTA was stable in aqueous solution and did not bind to biologic tissue and fluids. After incubation of 51Cr-labeled EDTA in isolated jejunal loops, analytic subcellular fractionation of jejunal mucosa on reorientating sucrose-density gradients was performed, and no association of 51Cr-labeled EDTA with particulate intracellular organelles was detected. Intravenously administered 51Cr-labeled EDTA was rapidly and completely excreted in urine. Intestinal permeability to 51Cr-labeled EDTA after oral administration was assessed in healthy dogs. The percentage of the administered dose of 51Cr-labeled EDTA excreted in the urine in 24 hours ranged from 2.3 to 17.6% (median, 13%).

Animals↗

Immunocytochemical and lectin histochemical studies of plaques and tangles in Down's syndrome patients at different ages.

The presence of numerous senile plaques (SP) and neurofibrillary tangles (NFT) within association areas of the neocortex and within the hippocampus and amygdala, is generally regarded as providing the histopathological hallmarks of Alzheimer's disease (AD) (Mann, 1985). Similar pathological changes, to those of AD, are seen in the brains of nearly all persons with Down's syndrome (DS) who live beyond 40 years of age, though such features are only rarely seen before 20 years of age (Mann, 1988). Because of this similarity between AD and DS at middle age, DS has been considered (Mann, 1988) to provide a useful model for the pathological process of AD. Hence a study of DS patients at different ages (and in all of whom the pathological changes typical of AD would have been expected had they lived long enough) can provide important data concerning the time course of the acquisition and the morphological and biochemical genesis of SP and NFT in DS, with obvious implications as to the changes of AD itself. In this study, the brains of 24 patients dying, between the ages of 13 and 65 years, with DS have been examined for the presence and the morphological appearance of SP and NFT using various markers for structural or biochemical components known, from previous work on AD (Ihara, 1988; Ihara et al., 1986; Davies et al., 1988; Mann et al., 1988) to be associated with SP and NFT.

Adolescent↗

Rapid haemodynamic response to adrenocorticotrophin and the role of peripheral resistance in adrenocorticotrophin-induced hypertension in conscious sheep.

The haemodynamic effects associated with the onset of hypertension induced by infusion of adrenocorticotrophin (ACTH) were investigated in sheep. Analysis of haemodynamic data collected over 24 h by a computer-based monitoring system revealed that mean arterial pressure (MAP) was significantly increased after 4 h. Cardiac output was significantly raised after 1 h. The increased cardiac output was initially offset by a fall in calculated total peripheral resistance (CTPR) and MAP did not begin to rise until CTPR had returned to control values. This suggested that the return of CTPR to control values was essential for the development of hypertension. The development of ACTH-induced hypertension was prevented by both nisoldipine, a calcium channel blocker, and minoxidil, a vascular smooth muscle relaxant. Nisoldipine administration was also found to reverse established ACTH hypertension. A greater fall in MAP and CTPR occurred in the onset and established phase of ACTH hypertension sheep compared with normotensive controls. These results indicate that constriction of the peripheral vasculature is essential for the onset and maintenance of ACTH-induced hypertension in the sheep, and that the vasoconstriction does not involve a specific Ca21+-dependent mechanism because minoxidil was as effective as nisoldipine in abolishing the pressor response to ACTH. The onset of ACTH-induced hypertension in sheep is characterized by very rapid haemodynamic changes with an increase in cardiac output and a relative increase in CTPR after an initial peripheral vasodilatation.

Adrenocorticotropic Hormone↗

Involvement of cytoplasmic membranes in the non-lytic infection of K-562 cells by Semliki Forest virus.

An analysis of the human leukemia cell line, K-562, infected with Semliki Forest virus, has been made with transmission electron microscopy. In contrast to the usual surface budding of the enveloped virus on the plasma membrane of vertebrate cells leading to cytolysis within 20 h, K-562 cells do not show surface budding, and the cells remain intact for periods of several months. Several unusual features of the infection include: 1) the rough endoplasmic reticulum arranges early into continuous perinuclear chains; 2) during the time of virus replication and release, the nucleocapsids aggregate on the cytoplasmic side of internal vesicles in the region of the cell where the Golgi complex is normally located; and 3) during this same time period, the vesicles are seen to contain enveloped virions and rod-like formations, a result suggesting that budding has occurred into these vesicles. Viruses are presumably released from the cell as these vesicles fuse with the plasma membrane. By 12 days post-infection and thereafter, the intact cells show electron-dense aggregates of chromatin, large vacuoles and lipid inclusions throughout the cytoplasm, and only a few virion-containing vesicles.

Cell Line↗

AIDS and chastity.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

The effect of ultraviolet B radiation treatments on calcium excretion and vitamin D metabolites in kidney stone formers.

Several factors could explain the effect of warm, sunny weather on kidney stone formation. To determine the role of sun exposure, we used a light box to administer artificial ultraviolet B radiation during the winter months in New York City. Eleven male stone formers and 7 age- and sex-matched controls received 10 UVB light exposures over a two-week period while maintaining a 400 mg calcium diet. 25-OH vitamin D levels increased significantly (p less than 0.001) in both patients (25.9 +/- 9.8 to 51.6 +/- 14.1 ng/ml) and controls (21.3 +/- 7.1 to 49.6 +/- 3.1 ng/ml). However, 1,25 dihydroxyvitamin D levels rose in the patients (50.8 +/- 14.8 to 55.9 +/- 13.1 pg/ml) but fell (60.1 +/- 6.5 to 49.4 +/- 3.1 pg/ml) in the controls. Only 2 of the 11 patients but all of the controls demonstrated this down regulation of 1,25 dihydroxyvitamin D levels (p less than 0.002). 24,25 dihydroxyvitamin D levels tended to rise in both groups but parathyroid hormone levels were unchanged. There was a trend, which did not reach statistical significance, for parameters of calcium excretion to increase after UVB radiation. 24-hour urinary calcium excretion rose 24% from 140 to 173 mg in the patients and 31% from 113 to 148 mg in the controls. The ratio of calcium/creatinine following a one gram calcium load showed a small increase after UVB radiation from 0.17 to 0.20 in patients and 0.118 to 0.124 in the controls. However, no correlation could be discerned between changes in vitamin D metabolite concentrations and changes in urinary calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Multiple ligninase-related genes from Phanerochaete chrysosporium.

We have investigated four distinct sequences in genomic DNA of Phanerochaete chrysosporium that show strong homology to a lignin peroxidase cDNA sequence [Tien and Tu: Nature 236 (1987) 520-523, and 328 (1987) 742]. The complete nucleotide sequence of one of these genes is presented here. Comparison of the sequenced gene, LIG1, with the published cDNA sequence reveals the presence of eight short intervening sequences. The open reading frame encodes a polypeptide of 372 amino acids (aa), which includes a 28-aa residue hydrophobic leader sequence. The predicted Mr of the mature protein product is 37,000. Partial sequencing of the other three genes reveals substantial nucleotide and amino acid homology.

Agaricales↗

A transgene containing lacZ inserted into the dystonia locus is expressed in neural tube.

The site of integration of transgenes in the host genome can affect levels of expression and occasionally confer ectopic patterns of expression on otherwise tissue-specific genes. We describe here a line of mice in which an hsp68-lacZ transgene is expressed in unstressed developing neural tissue and where the transgene insertion has caused a mutation of a neural tissue-specific gene, dystonia musculorum (dt). This coincidence suggests that expression of the hsp68-lacZ construct may be controlled directly by cis-acting regulatory sequences that normally control the developmental expression of the dt gene. Such constructs may serve as useful tools for identifying new tissue-specific enhancers and their associated genes.

Animals↗

Mortality of employees of the Atomic Weapons Establishment, 1951-82.

A total of 22,552 workers employed by the Atomic Weapons Establishment between 1951 and 1982 were followed up for an average of 18.6 years. Of the 3115 who died, 865 (28%) died of cancer. Mortality was 23% lower than the national average for all causes of death and 18% lower for cancer. These low rates were consistent with the findings in other workforces in the nuclear industry and reflect, at least in part, the selection of healthy people to work in the industry and the disproportionate recruitment of people from the higher social classes. At some time during their employment 9389 (42%) of the workers were monitored for exposure to radiation, the average cumulative whole body exposure to external radiation being 7.8 mSv. Their mortality was generally similar to that of other employees, even when exposures were lagged by 10 years. The rate ratio after a 10 year lag in workers with a radiation record compared with other workers was 1.01 (95% confidence interval 0.92 to 1.10) for all causes of death and 1.06 (0.89 to 1.27) for all malignant neoplasms. The only significant differences were for prostatic cancer (rate ratio 2.23; 95% confidence interval 1.13 to 4.40) and for cancers of ill defined and secondary sites (rate ratio 2.37; 1.23 to 4.56). Cancers of lymphatic and haemopoietic tissues were notable for their low occurrence in the study population, with only four deaths from leukaemia and two from multiple myeloma in workers with a radiation record, 9.16 and 3.55 deaths respectively being expected on the basis of national rates. Among workers who had a radiation record 3742 (40%) were also monitored for possible internal exposure to plutonium, 3044 (32%) to uranium, 1562 (17%) to tritium, 638 (7%) to polonium, and 281 (3%) to actinium. In these workers mortality from malignant neoplasms as a whole was not increased, but after a 10 year lag death rates from prostatic and renal cancers were generally more than twice the national average, these excesses arising in a small group of workers monitored for exposure to multiple radionuclides. Though mortality from lung cancer in workers monitored for exposure to plutonium was below the national average, it was some two thirds higher than in other radiation workers, the excess being of borderline statistical significance. Mortality from malignant neoplasms as a whole showed a weak and non-significant increasing trend with increasing level of cumulative whole body exposure to external radiation. When the exposures were lagged by 10 years the trend became stronger and significant, the estimated increase in relative risk per 10 mSv being 7.6% (95% confidence interval 0.4% to 15.3%). This trend was confined almost entirely to workers who were also monitored for exposure to radionuclides (p<0.001), the main contributions coming from lung cancer and prostatic cancer. Exposures of the lung and prostate from internal sources of radiation were not quantified, except for the contribution from tritium. It was therefore not possible to assess the extent to which the associations were due to internally deposited radionuclides rather than external exposure. The finding for prostatic cancer taken in conjunction with the results of other studies suggest a specific occupational hazard in a small group of workers in the nuclear industry who had comparatively high exposures to external radiation and who were also monitored for internal exposure to multiple radionuclides. Research is needed to discover whether any of the radionuclides and other substances concerned are concentrated in the prostate. The occurrence of lung cancer in this workforce requires further investigation taking into account smoking habits and tissue doses from inhaled radionuclides.

Cardiovascular Diseases↗

Evaluation of ricin A chain-containing immunotoxins directed against CD19 and CD22 antigens on normal and malignant human B-cells as potential reagents for in vivo therapy.

Ricin A chain-containing immunotoxins (IT-As) specific for the human B-cell antigens, CD22 and CD19, were constructed using the monoclonal antibodies, HD6 and HD37, respectively. IT-As were prepared by coupling intact antibodies, F(ab')2, or Fab' fragments to native or chemically deglycosylated ricin A chain. The IT-As were then evaluated for cytotoxicity to normal and neoplastic human B-cells in vitro with the major objective of appraising their suitability for in vivo therapy of human B-cell tumors. The IT-As prepared with both the HD6 and HD37 antibodies were specifically toxic to normal B-cells and to most of the neoplastic B-cell lines tested. However, the IT-As prepared from HD6 were generally more potent than those prepared from HD37. On Daudi cells, to which the two antibodies bound in similar numbers and with similar affinities, IT-As prepared with intact HD6 antibody or its Fab' fragment were 10-fold and 1.5- to 4-fold more potent, respectively, than the corresponding HD37 IT-As. The IT-As constructed from intact HD6 antibody and native or deglycosylated A chain reduced protein synthesis in Daudi cells by 50% at a concentration of 1.2 X 10(-11) M indicating that they were only 5-fold less toxic to the cells than ricin itself. Intact HD37 IT-As produced equivalent inhibition of protein synthesis at 1.5 X 10(-10) M. With both antibodies, IT-As constructed from the Fab' fragments were 10- to 20-fold less potent than their intact antibody counterparts. Different neoplastic B-cell lines varied in sensitivity to the IT-As. In most cases, their sensitivity correlated with the levels of CD19 and CD22 antigens expressed. Neither HD6 nor HD37 IT-As affected the ability of normal human bone marrow cells to form granulocyte-macrophage colony-forming units in soft agar, suggesting that both antigens are absent from these progenitor cells. Examination of sections of frozen human tissues using immunoperoxidase staining procedures indicated that the antibodies did not bind to a panel of normal tissues lacking B-lymphocytes. These results suggest that HD6 and HD37 IT-As are candidates for in vivo therapy in humans with certain B-cell tumors. However, HD6 IT-As are more potent, reduce protein synthesis more completely, and hence appear to be the ITs of choice for treating tumors expressing the CD22 antigen.

Antigens, CD↗