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Biomedical subjects

D Mann

Publications and source records attributed to D Mann.

At least 109 records · Page 6Linked to original sources
PubMed1989

Interleukin-1 alpha gene intron containing variable repeat region coding for the SP1 transcription factor recognition sequence is polymorphic.

Interleukin-1 alpha (IL-1 alpha) is a cytokine produced by a number of cell types including macrophages, fibroblasts, keratinocytes, and mesangial cells. We were interested in identifying a DNA restriction fragment length polymorphism (RFLP) for the IL-1 alpha gene for use in studies of genetic alteration in various human cancers. Human genomic DNA from 32 unrelated individuals was digested with various restriction enzymes, alone and in combination, and subjected to Southern blot analysis. Hybridization to 32P-labeled IL-1 alpha cDNA revealed an insertion-deletion-type polymorphic pattern. After digestion with RsaI, insertion-deletion-type polymorphic bands with sizes of 3.4 kb, 3.1 kb, and 2.8 kb and one invariant band of 0.8 kb were observed. These three alleles, designated A1, A2, and A3, had relative frequencies of 0.18, 0.06, and 0.78 with heterozygosity observed in 38% of the unrelated individuals studied. Evaluation of nine related individuals for this RsaI polymorphism was consistent with a Mendelian inheritance. Comparison of restriction patterns following Southern analysis of DNA digested with several different enzymes showed that the polymorphic region resides within the sixth intron. Furthermore, this RFLP results from a variable length region containing multiple copies of a recognition sequence for SP1, an imperfect copy of viral enhancer elements, and an inverse and complementary sequence of the glucocorticoid receptor binding site. The identified polymorphism may be of value in analyses of chromosome 2 and may help to elucidate mechanisms by which IL-1 alpha transcription is regulated.

Binding Sites↗
PubMed1989

A case of fluoxetine-induced serum sickness.

After 3-4 weeks of taking fluoxetine for depression, a 27-year-old man developed fever, skin eruptions, arthralgia, and lymphadenopathy. His clinical symptoms and results of laboratory assessment were consistent with a diagnosis of serum sickness reaction to the fluoxetine.

Adult↗
PubMed1989

Slipped capital femoral epiphysis. Results of treatment with a single cannulated screw.

Thirty patients with 36 slipped capital femoral epiphysis underwent pinning with a single cannulated screw. All patients were pinned in situ, allowed immediate weight bearing as tolerated, discontinued crutches at 6 weeks, and had a minimum of 1 year follow up (average 21 months). One patient had avascular necrosis, one patient had bilateral chondrolysis, and two patients required repinning.

Adolescent↗
PubMed1988

Recognition by cytotoxic T lymphocytes of Qa-2 antigens. Sensitivity of Qa-2 molecules to phosphatidylinositol-specific phospholipase C.

Con A splenic lymphoblasts were incubated with phosphatidyl-inositol specific phospholipase C (PIPLC) derived from Bacillus thuringiensis and subsequently analyzed for Qa-2 Ag with the Qa-2 reactive mAb Qa-m2. This treatment completely removed Qa-2 detectable Ag on lymphoblasts from H-2d animals, indicating that these molecules are likely anchored to the cell membrane through phosphatidyl inositol (PI). Although exposure of lymphoblasts from H-2b mice to PIPLC greatly reduced Qa-2 expression, a subpopulation of cells retained a limited quantity of the Ag. Bulk cultured anti-Qa-2 CTL generated against the Qa-2 region from H-2b haplotype mice lysed Qa-2+ targets from B6.K2 (H-2b) and BALB/cJ (H-2d) animals. Pretreatment of these lymphoblast targets with PIPLC completely abolished lysis of the BALB/cJ target cells, whereas lysis of B6 targets was reduced only slightly. Anti-Qa-2 CTL clones tested against PIPLC-treated B6 target cells revealed two patterns of reactivity. One group of clones was unaffected in its ability to lyse PIPLC-pretreated targets and cross-reacted on Q6d/Ld molecules expressed on transfected L cells. A second group was unable to lyse PIPLC-pretreated lymphoblasts and cross-reacted on Q7d/Ld targets. These data suggest that H-2b-derived lymphoblasts express two different types of Qa-2 molecules with respect to PIPLC sensitivity; one type is sensitive to PIPLC and cross-reactive with Q7d, the other type is resistant to PIPLC and cross-reactive with Q6d. In contrast, H-2d lymphoblasts express only the PIPLC-sensitive type of molecules. It was also noted that bulk cultured anti-Qa-2 CTL more readily lysed H-2b target cells expressing a smaller quantity of PIPLC-resistant Ag than H-2d targets expressing a larger amount of PIPLC-sensitive Ag. Further, anti-Qa-2 CTL clones readily lysed PIPLC-treated target cells expressing very low levels of serologically detectable Qa-2. This suggests that recognition of class I molecules anchored to the membrane via a PIPLC-resistant linkage may more readily activate CTL for expression of lytic activity than molecules anchored through PI.

Animals↗
PubMed1988

Molecular epidemiology of HTLV-I-associated non-Hodgkin's lymphomas in Jamaica.

As part of epidemiologic studies of human T-lymphotropic virus (HTLV)-I-associated malignancies in Jamaica, the authors evaluated 26 patients with non-Hodgkin's lymphoma for the presence of integrated HTLV-I provirus in their malignant cells. Fifteen of 26 patients had integrated provirus. All 15 also were HTLV-I antibody positive. Eleven patients did not have integrated provirus, and all 11 were antibody negative. All of the antibody-positive cases had onset of their disease in adulthood (age range, 21-57 years) as opposed to the broad age range of negative cases (4-66 years). Clinical features which were more common in provirus positive than negative patients included leukemic phase, skin involvement, and hypercalcemia, which are all features frequently seen in HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL). The presence of skin involvement, circulating malignant cells, abnormal liver function tests, or the presence of two or more of these four features were statistically significantly different between virus-positive and virus-negative cases. Although the survival of positive cases (6 months) was shorter than that of negative cases (9 months), this was not statistically significant. The only significant determinant of survival was hypercalcemia, with those who developed hypercalcemia at some point in their disease course, independent of their HTLV-I status, surviving a mean of 5 months as compared to a mean of 17.5 months in those who never became hypercalcemic. The six HTLV-I-positive lymphomas that underwent cell typing were all primarily OKT4 positive, whereas two HTLV-I antibody-negative cases that were typed were B-cell lymphomas.

Antibodies, Viral↗
PubMed1988

The application of immunoassays and fluorometry to the detection of polycyclic hydrocarbon-macromolecular adducts and anti-adduct antibodies in humans.

The metabolic activation of polycyclic aromatic hydrocarbons (PAH) to chemical species that form covalent adducts with cellular macromolecules (DNA and protein) is central to theories of carcinogenesis. Assays are currently being developed that will accurately reflect human macromolecular exposure to these carcinogens. Immunoassays are capable of detecting low levels of PAH-DNA adducts and antibodies directed against these adducts in humans and HPLC/spectrophotofluorimetry allows the detection of carcinogen-DNA or carcinogen-protein adducts in human peripheral blood. Both types of method have inherent advantages and disadvantages, and the use of more than one type of corroborative assay is a feature in our work. Simplified but highly specific synchronous fluorescence spectra have been obtained for BP-tetrols after mild acid hydrolysis and HPLC of sample materials. When using a wavelength difference of 34 nm to drive the excitation and emission monochromators simultaneously, the pyrene fluorophore, when present, has a signature peak at 345 nm (excitation). The results of immunoassays demonstrate human exposure to PAH as a class of carcinogen, since serological cross-reactivity of antibodies does not limit detection in this system to a single chemical compound. In addition the formation in humans of anti-PAH-DNA antibodies has been shown, presumably in response to both past and present exposure to the parent compounds. In summary the results of each assay can indicate human exposure to PAH and have the potential for molecular dosimetry of this exposure.

Antibodies↗
PubMed1988

Location of lesions in Korsakoff's syndrome: neuropsychological and neuropathological data on two patients.

Psychometric and neuropathological findings on two Korsakoff amnesics are described. Both patients showed anterograde and retrograde amnesia, poor performance on the Peterson short-term memory task, on the Wisconsin card sort test and on certain visuo-spatial tasks. Patient J.W. performed consistently worse on tests of anterograde, but not retrograde amnesia, whereas patient B.C. showed more perseverative difficulties and, unlike J.W., his measured intelligence seemed to have declined from its premorbid level. Both patients showed marked neuronal loss from the medial mammillary bodies and a narrow band of gliosis in the medial thalamus, adjacent to the wall of the third ventricle, a region known as the paratenial nucleus. Only B.C. showed visible signs of cortical atrophy. Morphometric measures did, however, reveal reduced nucleolar volumes in layers III and V of the frontal cortex, with B.C. also showing more marked neuronal loss from these layers. B.C. also showed neuronal loss from the CA1 region of the hippocampus and reduced nucleolar volumes in the septum. Significantly, both patients had normal neuronal numbers and nucleolar volumes in the nucleus basalis of Meynert. J.W. only showed greater dysfunction than B.C. in one region: the locus caeruleus. This finding was related to his more severe amnesia.

Aged↗
PubMed1988

Human class I MHC-restricted cytotoxic T-lymphocytes specific for human immunodeficiency virus envelope antigens.

Vaccines incorporating HIV envelope antigens are being developed for the prevention of AIDS. To determine whether HIV envelope antigens are recognized by human cytotoxic T-lymphocytes (CTL), we assessed class I MHC-restricted, HIV envelope antigen-specific cytotoxic activity of peripheral blood mononuclear cells (PBMC) from HIV-infected individuals, following in vitro stimulation. The target cells were human skin fibroblasts of known tissue type, infected with recombinant vaccinia viruses, either containing or lacking the whole HIV envelope gene. Ten out of 17 (59%) asymptomatic HIV-seropositive individuals demonstrated HIV envelope antigen-specific cytotoxicity at levels that were above those seen in HIV-seronegative controls. MHC restriction of cytotoxicity was evident in that 13 out of 19 (68%) of the targets matched for the tissue type of the donor at one or more class I MHC loci were lysed, but only two out of 18 (11%) mismatched targets (P = 0.0004). Both partial purification of effector cells and evidence of MHC restriction indicated that T-lymphocytes were responsible for the observed cytotoxicity. HIV envelope antigen-specific CTL can be detected following in vitro stimulation of the PBMC in many asymptomatic HIV-seropositive individuals. HIV envelope antigens are recognized by human CTL and are, therefore, potentially relevant immunogens for induction of HIV-specific CTL responses.

Antigens, Viral↗
PubMed1987

[Results of the complex evaluation of scintigraphy of the intracardiac space in patients with coronary disease].

With the help of the comparison of the results of 95 patients with coronary heart disease who were examined by means of the intracardiac space scintigraphy for the purpose of the subjective subdivision according to the NYHA-classification there is no close correlation between the nuclear-medically obtained functional sizes (EF, maximum ejection and filling rate) and the clinical degree of severity of the disease. Only at the degree of severity 3 and 4 a discrimination is possible. In 64 patients laevocardiographic and coronarographic, respectively, findings were present. The trend to the deterioration of the functional parameters and to the increase of the nuclear-medically recognizable disturbances of the kinetics, respectively, with a more intensive expression of the vascular stenoses is distinctly readable. From the examination in rest in the individual case no statement is possible concerning the findings which are to be expected in the invasive diagnostics. When there are discrepancies between the result of the intracardiac space scintigraphy and the clinical and electrocardiographic preliminary investigations in many cases a clarification becomes possible by the immediately following study under submaximal exercise. On the assumption of a close cooperation with experienced cardiologists the relatively little expensive intracardiac space scintigraphy which does not stress the patient provides an essential evidence for the prognosis and estimation of the functional capacity of the patients with coronary heart disease.

Coronary Disease↗
PubMed1987

Adrenaline stimulation of phospholipid metabolism in adipocyte ghosts.

The incorporation of long-chain fatty acids into phospholipids has been detected in adipocyte ghosts that were incubated with [1-14 C] stearic, [1-14 C] linoleic or [1-14 C] arachidonic acid. Adrenaline and adenosine activated this incorporation within 15 s of exposure of the ghosts to the hormones and the response was dose dependent. Maximum incorporation of labelled linoleic acid occurred at 10(-5) M adrenaline and 10(-7) M adenosine. The alpha-agonist phenylephrine and the beta-agonist isoproterenol were also shown to stimulate the incorporation of fatty acid in a dose dependent manner. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were each labelled preferentially with linoleic or arachidonic acid. p-Bromophenacylbromide, quinacrine and centrophenoxine inhibited the adrenaline-stimulated incorporation of fatty acids into ghost membrane phospholipids, and p-bromophenacylbromide also reduced the activation of adenylate cyclase by adrenaline. NaF, an activator of adenylate cyclase, like adrenaline, stimulated the incorporation of linoleic acid into ghost membrane phospholipids.

Acetophenones↗
PubMed1987

Spontaneous free perforation and perforated abscess in 30 patients with Crohn's disease.

Spontaneous free perforation is an uncommon event in the natural history of Crohn's disease. It occurred in 21 of 1415 patients (1.5%) admitted with Crohn's disease to The Mount Sinai Hospital between 1960 and 1983. The mean duration from onset of Crohn's disease to occurrence of perforation was 3.3 years. Ten patients had small bowel perforation, ten patients had large bowel perforation, and one patient had simultaneous perforation of both ileum and cecum. The incidence of perforation in disease segments of small bowel was 1.0% (jejunum 6.0%, ileum 0.7%), and in the colon, 1.3%. Besides the 21 patients with spontaneous free perforation, an additional nine patients had spontaneous free rupture of an abscess into the peritoneal cavity. The mean duration from onset of Crohn's disease to rupture of abscess was 8.5 years. All 30 patients had surgery within 24 hours of perforation or rupture. All 21 patients with spontaneous free perforations survived, as did all but one of the nine patients with perforated abscess. The cornerstone of the treatment of ileocolonic lesions perforating into the general peritoneal cavity is proximal diversion with delayed reconstruction of intestinal continuity whenever possible. With perforation of the small bowel, primary reanastomosis is possible in selected patients.

Abscess↗
PubMed1986

Distinct types of hip disorder in Mseleni joint disease.

Painful arthropathy of the hips is common in the black population around Mseleni in northern Kwazulu. Despite considerable variability in clinical and radiographic appearance, the disorder has always been regarded as a single entity. This study addressed the possibility that 'Mseleni joint disease' embraces more than one condition. In a survey of 1659 people in the Manguzi Health Ward, 60 km north of Mseleni, 126 were reported to have hip pain and/or impaired walking ability; 92 of these subjects were examined radiographically. Osteo-arthritis (OA) of the hips was found in 33 cases, the prevalence increasing with age to over 16% in those aged over 60 years. In most cases the OA was associated with two distinct abnormalities: protrusio acetabuli, which affects mainly females and increases in frequency with age, and hip dysplasia, which has a constant frequency with age. The protrusio disorder is fairly common among women of other black populations and is attributed to environmental factors. The hip dysplasia is unique to the population around Manguzi; it is part of a generalized condition indistinguishable from multiple epiphyseal dysplasia, which is a known genetic disorder.

Acetabulum↗
PubMed1986

In vivo mechanical behavior of canine pericardium.

We examined the in vivo mechanical behavior of the pericardium by measuring simultaneous atrial and intrapericardial pressures and mutually orthogonal, circumferential, and longitudinally oriented pericardial segment lengths (ultrasonic gauges) in 10 open-chest dogs. Venous return was varied by a combination of caval occlusion followed by volume loading. Up to a mean left atrial pressure of 25 mmHg, the pericardium lengthened virtually exclusively in the circumferential direction (n = 9). Thus, at an intrapericardial pressure of 6.0 +/- 1.0 (+/- SD) mmHg, circumferential strain (normalized to length at pericardial pressure 0 mmHg) was 0.30 +/- 0.28, whereas longitudinal strain was 0.02 +/- 0.06 (P less than 0.05). In five of these dogs, alteration of external pericardial loading by severing the pericardial diaphragmatic attachments did not change the difference between circumferential and longitudinal strain, and in two the same directional strain difference was observed during production of cardia tamponade. In three additional dogs the square of the circumferential segment length was closely correlated with the directly measured intrapericardial volume when saline was infused into the pericardial space in an in situ, arrested heart preparation. Our results indicate that there is marked directional variability in lengthening of the pericardium when the volume of its contents is altered in vivo. This phenomenon is probably the result of complex interactions between the properties of the pericardial tissue and the influence of its internal and external loads.

Animals↗
PubMed1986

Finger extension game.

The finger extension game was designed in response to a learning exercise by two students on preclinical assignment. It is an activity designed to facilitate the rehabilitation process of the finger extensors on a subcortical level. Occupational therapy literature emphasizes exercise techniques rather than incorporating activities with exercise. This game allows the occupational therapist to provide activities that direct the patient's concentration away from the exercise itself. This article includes a description and a detailed plan for constructing the finger extension game.

Equipment Design↗
PubMed1986

Measurement of aflatoxin B1, its metabolites, and DNA adducts by synchronous fluorescence spectrophotometry.

Sensitive and specific methods are needed for measuring human exposure to carcinogens. Synchronous fluorescence spectrophotometry can be used to measure fmol of aflatoxins, their metabolites, and DNA adducts. Computer-assisted analysis of spectra of these agents obtained by synchronous fluorescence spectrophotometry can be displayed as contour maps which are highly specific for each agent. Individual agents in mixtures, e.g. aflatoxins B1 and M1, can be identified by fourth derivative spectral analysis. This physical method should complement immunological and other methods to measure aflatoxin B1, its metabolites, and nucleic acid adducts.

Aflatoxin B1↗