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Biomedical subjects

D Mitchell

Publications and source records attributed to D Mitchell.

At least 181 records · Page 10Linked to original sources
PubMed1990

Memory factors in age-related differences in simple reasoning.

Adults in their 50s were compared with adults in their late teens or 20s in the accuracy of relatively simple reasoning decisions involving varying amounts of information. Because the magnitude of the age differences in decision accuracy was independent of the amount of information relevant to the decision, it was suggested that adults in their 20s and 50s do not differ in the effectiveness of integrating information across multiple premises. However, the 2 groups differed in the accuracy of trials involving only a single relevant premise, and thus it was inferred that 1 factor contributing to reasoning differences within the age range from 20 to 60 may be a failure to encode, or retain, relevant information.

Adult↗
PubMed1990

Lymphotoxin and tumor necrosis factor-alpha production by myelin basic protein-specific T cell clones correlates with encephalitogenicity.

Lymphokine activity in seven myelin basic protein (MBP)-specific T cell clones was examined. All of the clones recognize MBP peptide 1-9 in the context of I-Au. A strong positive correlation was found between levels of lymphotoxin (LT) and tumor necrosis factor alpha (TNF-alpha) mRNA and biological activity on L929 cells and their capacity to induce paralysis, the clinical hallmark of experimental allergic encephalomyelitis (EAE). No correlation was found between interleukin-2 or gamma interferon production and encephalitogenicity. LT and/or TNF-alpha may play a central role in the pathogenesis of EAE.

Animals↗
PubMed1990

Observations on the morphology of pronuclei and nucleoli in human zygotes and implications for cryopreservation.

The effects of cryopreservation on human zygotes at various stages between the appearance of pronuclei and their close association were investigated. Pronuclear zygotes (n = 233) from 101 patients were frozen using propanediol 21-35 h following egg collection. The incidence of implantation of thawed pronuclear zygotes frozen 29-35 h following oocyte collection was significantly higher than that of younger pronuclear zygotes (28 versus 10%, respectively). Zygote age did not affect cell survival following cryostorage. The diameter and association of pronuclei and the number and distribution of nucleoli were determined from video tape recordings of 140 fresh zygotes. Pronuclear migration continued after pronuclear enlargement. The number of nucleoli remained constant during pronuclear migration, but their random distribution within the pronucleus diminished. Strongly adhered pronuclei had significantly more aligned nucleoli on adjacent sides than pronuclei which were still visually separated by ooplasm. This equatorial distribution of nucleoli was noted in the majority of zygotes older than 26 h. The findings suggest that zygote cryopreservation should be initiated when pronuclear migration is completed. This moment can be determined accurately by studying pronuclear association and nucleolar alignment.

Cell Nucleolus↗
PubMed1990

Detection of HIV-1 in human lung macrophages using the polymerase chain reaction.

We have used the polymerase chain reaction to investigate HIV-1 infection of lung macrophages from 44 AIDS patients with pneumonia. Proviral HIV-1 DNA was detected in the lung macrophages of 47% (21 of 44) of patients tested; 32% (seven of 21) of the patients had Pneumocystis carinii pneumonia (PCP), and 56% (11 of 21) had pneumonia caused by other aetiological agents. Matched peripheral blood specimens were obtained from 22 patients in this study, and HIV-1-specific DNA was detected in 100% (22 out of 22) of non-adherent white cell preparations tested. HIV was detected in blood monocytes of 11 out of 22 patients (50%), and a virus signal was also found in the lung macrophages of eight of these patients. Our results indicate that PCP does not predispose lung macrophages to HIV-1, nor does HIV-1 infection of lung macrophages increase the probability of contracting PCP.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Serum type III procollagen peptide, dynamic liver function tests and hepatic fibrosis in psoriatic patients receiving methotrexate.

The serum level of the aminoterminal peptide of type III procollagen (P3NP) was measured in 51 psoriatic patients on long-term, once weekly, low-dose methotrexate and in a control group of patients with extensive psoriasis who had never had systemic treatment. Serum P3NP levels were normal in all control patients, but were elevated in the majority of methotrexate-treated patients, even those with normal or non-specific liver histology. Although the highest P3NP values were found in the groups of patients with fibrosis and cirrhosis, isolated P3NP measurements did not discriminate between individuals with and without significant liver pathology. Neither standard nor dynamic liver function tests were able to identify patients with significant liver damage and in most cases results were in the normal range.

Adult↗
PubMed1990

Identification of genes affecting production of the adhesion organelle of Caulobacter crescentus CB2.

Transposon (Tn5) mutagenesis was used to identify regions in the genome involved with production, regulation, or attachment to the cell surface of the adhesive holdfast of the freshwater bacterium Caulobacter crescentus CB2. A total of 12,000 independently selected transposon insertion mutants were screened for defects in adhesion to cellulose acetate; 77 mutants were detected and examined by Southern blot hybridization mapping methods and pulsed-field gel electrophoresis. Ten unique sites of Tn5 insertion affecting holdfast function were identified that were clustered in four regions of the genome. Representative mutants of the 10 Tn5 insertion sites were examined by a variety of methods for differences in their phenotype leading to the loss of adhesiveness. Four phenotypes were identified: no holdfast production, production of a smaller or an altered holdfast, production of a holdfast that was unable to remain attached to the cell, and a fourth category in which a possible alteration of the stalk was related to impaired adhesion of the cell. With the possible exception of the last class, no pleiotropic mutants (those with multiple defects in the polar region of the cell) were detected among the adhesion-defective mutants. This was unexpected, since holdfast deficiency is often a characteristic of pleiotropic mutants obtained when selecting for loss of other polar structures. Overall, the evidence suggests that we have identified regions containing structural genes for the holdfast, genes involved with proper attachment or positioning on the caulobacter surface, and possibly regions that regulate the levels of holdfast production.

Bacterial Adhesion↗
PubMed1990

Historical and contemporary issues in nursing home reform.

Historical developments leading to the enactment of nursing home reform legislation (P.L. 100-203) were discussed. The results of the nursing home component of a nationwide University of Illinois at Chicago study of public mental retardation/developmental disabilities spending were also presented. Approximately 51,000 individuals with mental retardation and related conditions resided in nursing homes in 1989. The cost of their care was approximately $900 million annually. Within the first 12 months of the enactment of P.L. 100-203, 46 states had requested an extension to the original mandated services deadline imposed under that legislation. Under P.L. 100-203 guidelines, state agencies estimated that nearly 40% of all nursing home residents with mental retardation might need to be relocated to alternative settings. Implementation issues were also discussed.

Eligibility Determination↗
PubMed1990

Sezary cell-like leukemia: a distinct type of mature T cell malignancy.

We describe the clinical, ultrastructural, and immunophenotypical characteristics of four cases of an unusual type of T cell leukemia. Clinical features included high WBC, ranging from 26-148 x 10(9)/liter, bone marrow infiltration, splenomegaly, and lymphadenopathy. Skin involvement was not documented at presentation, but it was seen as a terminal event in one patient with a pattern of dermal lymphocytic infiltration different from that usually seen in Sezary syndrome. By ultrastructural analysis, the circulating lymphoid cells were indistinguishable from small Sezary cells in two cases, resembled large Sezary cells in one case, and consisted of a mixture of small Sezary cells and prolymphocytes in the remaining case. The cells from all cases had a mature T cell phenotype, TdT-, CD1a-, CD2+/-, CD3+, CD5+. In addition, the cells were either CD8+, CD4- or CD8+, CD4+ or CD4-, CD8-; and, in only one case, the findings were similar to those of Sezary syndrome cells: CD4+, CD8-, CD7-, BE-2+. In the latter case, serological and immunological assays were positive for HTLV-I while these were negative in two other patients investigated. The features of these patients suggest that Sezary cell leukemia is a distinct clinico-pathological entity although the alternative diagnosis of adult T cell leukemia/lymphoma could not be excluded in the HTLV-I+ case. Sezary cell leukemia appears to be resistant to current chemotherapy regimens and is associated with an aggressive clinical course and short survival.

Adult↗
PubMed1989

Clinical experience with zidovudine for patients with acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex.

We have treated 113 patients with zidovudine since its licensure, 80 with acquired immunodeficiency syndrome and 33 with acquired immunodeficiency syndrome-related complex. This paper reports on the efficacy and toxicity observed in these patients. Improved well-being, reduced frequency and severity of opportunist infections were notable in the first year of follow-up. More rapid improvement in pulmonary physiological tests during recovery from Pneumocystis carinii pneumonia was also observed in treated patients. Patients with lower initial platelet counts showed early increases in platelet counts. There was a consistent fall in human immunodeficiency virus (HIV) p24 antigen during treatment, although not always to undetectable levels. CD4 cell counts showed a rise in the first months of treatment but these were not sustained, despite continuing clinical benefit. Neuropsychological and clinical evidence of benefit in HIV encephalopathy are described. We have analysed the factors influencing marrow toxicity and have found that low CD4 count and the intercurrent use of ganciclovir and dapsone increase myelotoxicity. We describe the clinical and biochemical features of the myopathy associated with long-term use of zidovudine and summarise our findings on dose-reduction associated meningo-encephalitis.

AIDS-Related Complex↗
PubMed1989

Ath-2, a second gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice.

Strain C57BL/6J and A/J differ at two genes determining atherosclerosis susceptibility. The first gene, Ath-1, was described earlier and this report characterizes Ath-2. The alleles at Ath-2 are r for resistance and s for susceptibility to atherosclerosis. The resistant phenotype in female mice is characterized by high plasma high density lipoprotein-cholesterol levels (74 mg/dl +/- SEM 2) and very few lesions/mouse after 14 weeks of consumption of an atherogenic diet (0.1 +/- SEM 0.1 in a predetermined region of the aorta). The susceptible phenotype in female mice is characterized by low levels of high density lipoprotein-cholesterol (35 mg/dl +/- SEM 1) and 1.2 lesions/mouse +/- SEM 0.2 in the same region of the aorta. In Ath-2 heterozygotes, resistance is dominant to susceptibility. Recombinant inbred strains derived from C57BL/6 and A were characterized for Apoa 1, Apoa 2 and susceptibility to atherosclerosis. Ath-1 and Ath-2 interact with each other so that resistant alleles at either locus confer a resistant phenotype to the animal. The map position of Ath-2 is not known, but Ath-2 does not map near genes determining the apolipoproteins for A-I, A-II, or E.

Alleles↗
PubMed1989

Functional evidence for the recognition of endogenous peptides by autoreactive T cell clones.

The fine specificity of two human T cell clones responding to autologous HLA-DR1 expressing antigen-presenting cells (APC) in the absence of nominal antigen has been investigated using Epstein-Barr virus-transformed B cells (BCL) of known DR beta 1 domain sequence. It was found that responsiveness was markedly affected by changes in a limited number of residues in this domain. Substitution of the DR1 beta sequence at one residue, position 74, even conservatively, was found to be particularly significant. Located on the beta 1 domain alpha-helix, this residue is predicted to point into the antigen-binding groove and is therefore unlikely to make contact with the T cell receptor. This finding suggests that these T cells are specific for a bound endogenous peptide within the autologous major histocompatibility (MHC) binding groove. The autospecific T cell clones also responded to murine L cell transfectants expressing DR alpha DR1 beta as well as to transfectants expressing the mouse/human hybrid MHC molecule I-E alpha DR1 beta but not to the reciprocal combination DR alpha I-E beta, thus confirming the importance of the beta 1 domain to T cell recognition. In contrast to the autocytotoxicity observed with BCL, cytolysis of the murine L cells expressing the HLA-DR1 molecule was slight and only found at high effector-target ratios. In addition, although fixation enhanced the recognition of BCL, capacity of the murine L cells bearing the HLA-DR1 molecule to stimulate T cell clone proliferation was markedly reduced by aldehyde fixation. When taken together, these results suggest that the endogenous peptides recognized by these autoreactive T cells are of human origin.

Amino Acid Sequence↗
PubMed1989

Partial zona dissection of human oocytes when failure of zona pellucida penetration is anticipated.

Partial zona dissection (PZD) of human oocytes facilitates sperm penetration through mechanically made holes in the zona pellucida. Only 1 of 69 eggs was damaged when sucrose was used to shrink the ooplasm during micromanipulation. The fertilization rate of micromanipulated oocytes in 18 couples with male factor infertility was 68% (34/50), which compared favourably with insemination of non-micromanipulated controls (21/45, 47%). PZD was advantageous in oligozoospermic patients, but not in cases of asthenozoospermia, combined semen problems or immunological infertility. Three twin and two singleton pregnancies resulted following replacement of 23 micromanipulated and eight control embryos in 14 patients. No differences in embryo morphology and development rates were found between the micromanipulated and control groups. The incidence of polyspermy in couples with abnormal semen analyses was relatively low (less than 20%) possibly due to partial activation of the oocytes following exposure to sucrose. Polyspermy was high (57%) in normozoospermic patients with either immunological infertility (n = 3) or failure of fertilization in previous cycles (n = 4). In the three immunological patients, nine of 11 hyaluronidase and sucrose-exposed control embryos fertilized and six implanted, possibly indicating that cumulus and corona cells are contributing factors inhibiting fertilization in such cases.

Embryo Transfer↗
PubMed1989

Does 99Tcm human serum albumin alter the characteristics of nebulized pentamidine isethionate?

Nebulized pentamidine has been used as therapy for Pneumocystis carinii pneumonia. The lung dose delivered using different nebulizer systems and doses of pentamidine from 50-600 mg is unknown. To measure this a marker which does not alter the characteristics of the nebulized pentamidine solution must be found. We have assessed the aerosol characteristics of four jet nebulizers (System 22, System 22 Mizer, Optimist, Respigard II) and one ultrasonic device (Pulmosonic) using two concentrations of pentamidine isethionate (50 mg and 300 mg) in 3 ml of solution. The jet nebulizers were operated at a flow rate of 6 l min-1, a rate suitable for home use. These measurements were repeated with 99Tcm labelled human serum albumin (HSA) added to the solutions. A linear relationship between 99Tcm-HSA activity and pentamidine concentration was demonstrated by using a nine stage cascade impactor. The Respigard II and Optimist produced the best results in terms of particle size (96% less than 5 microns), but the addition of the tracer to the latter led to a smaller particle size range and a reduction in the amount of aerosol present at the mouthpiece. The Mizer system had 52% of particles less than 5 microns, the Pulmosonic 46%. The Respigard II had a total output of 8.7 mg for the 50 mg concentration and 30.9 mg for the 300 mg concentration. The System 22 produced corresponding outputs of 18.0 mg and 67.1 mg with 54% of the aerosol particles less than 5 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗