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Biomedical subjects

M J White

Publications and source records attributed to M J White.

At least 19 recordsLinked to original sources
PubMed1992

CD7- T cells in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by decreased expression of CD7 in the peripheral blood and in the synovium. The present study was designed to identify the basis for and functional consequences of this decreased expression. METHODS: Peripheral blood lymphocytes from normal controls and from patients with RA or systemic lupus erythematosus (SLE), and T cell lines derived from rheumatoid synovium, were evaluated using 3-color fluorescence-activated cell sorter analysis. RESULTS: Normal subjects and most SLE patients expressed homogeneous, bright CD7 on CD4+, CD45RA+ cells, whereas RA patients demonstrated a significantly increased proportion of CD7- cells. T cell lines derived from rheumatoid synovium demonstrated a striking deficiency of CD7 on CD4+, CD45RA- cells. CD4+, CD45RA+ cells from RA patients changed phenotype after in vitro activation to CD45RA negativity, with up-regulation of CD7. CD7-, CD4+, CD45RA- cells were assessed for their ability to induce pokeweed mitogen-driven IgM and IgM-rheumatoid factor synthesis, and they were found to be potent helper/inducer cells. An increased population of CD7-, CD4+ cells in peripheral blood was found to predict a low response to recall antigens. CONCLUSION: The low expression of CD7 in RA may explain some of the immune abnormalities which may contribute to the pathogenesis of this disease.

Adult↗
PubMed1992

Side effects during continuous epidural infusion of morphine and fentanyl.

Respiratory effects, nausea, somnolence, and pruritus were compared during a 48-hr period of continuous epidural morphine (n = 34) and fentanyl (n = 32) infusion in 66 patients following elective total replacement of the hip or knee joint. Respiratory effects were assessed by PaCO2. Side effects were assessed by visual analogue scale and considered to be present when the score was above 30. Assessment was made at preoperative visits then 3, 6, 12, 24, 36, and 48 hr after the epidural injection. The bolus dose and subsequent infusion rate were 3,900 +/- 1,300 micrograms and 427 +/- 213 micrograms.hr-1 for morphine, and 85 +/- 46 micrograms and 56 +/- 27 micrograms.hr-1 for fentanyl. Pain relief was similar in both groups. In the morphine group, PaCO2 elevation and nausea occurred over a period of more than 12 hr (P less than 0.05). In the fentanyl group, there was no PaCO2 change, and nausea was confined to the first few hours. Nausea was more severe (P less than 0.01 at six hours and more frequent (24 hr cumulative incidence, 53 vs 28%, P less than 0.05) in the morphine group. Somnolence was prominent within several hours in two-thirds of patients in both groups. Somnolence continued to decline thereafter in the morphine group, but it was demonstrable in approximately half of the patients throughout the second day in the fentanyl group. The incidence was higher in the fentanyl group at the 48th hr (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Sexual activities, concerns and interests of men with spinal cord injury.

A representative sample of 79 men with spinal cord injury, drawn from a sampling frame of 661 women and men who reside in the community, was studied in terms of sexual activity, concerns and interests. Participants responded to a questionnaire and rating scales and were physically examined to establish their neurologic status. With respect to eleven other areas of life, sex life ranked the lowest in terms of satisfaction and fifth in terms of importance. Of the sample, 67% reported having had a physical relationship (not necessarily including intercourse) in the past 12 months. Areas of sexual activity about which respondents were most concerned were not satisfying a partner, getting or giving a sexual disease, urinary accidents, and not getting enough personal satisfaction. From among seven topics related to sexuality, the three in which there was greatest interest were methods and techniques to achieve sexual satisfaction, helping a partner cope emotionally with limitations on sexual activity and ability to have children.

Adult↗
PubMed1992

Inhibition of alloreactivity in vitro by monoclonal antibodies directed against restricted isoforms of the leukocyte-common antigen (CD45).

The leukocyte common antigen (LCA) is a protein tyrosine phosphatase and is identified by the CD45 cluster of monoclonal antibodies. CD45 is expressed in high-density on cells of hematopoietic lineage and generally is immunoprecipitated as 4 bands (220, 205, 190, and 180 KDa). Genetic studies have shown that a single gene produces additional forms of the molecule by alternate splicing including CD45RA (220, 205), CD45RO (180), and CD45RB (220, 205, 190). We have prepared a CD45RB Mab termed "MT3" that binds to a sialic acid dependent epitope. Since the LCA is one of the major targets of antilymphocyte globulin, we assessed a panel of CD45 and CD45R Mab for their ability to inhibit alloreactivity in vitro. MT3 (CD45RB) inhibits the allogeneic MLR and inhibits CD4+ T cells from expressing interleukin 2 receptors, and prevents CD4+ CD45RA- T cells from entering the proliferative phase of the cell cycle. Mem 93 (CD45RA) inhibits the generation of cytotoxic T cells. These data suggest that the CD45RB and CD45RA isoforms of the LCA may be appropriate targets for in vivo immunotherapy.

Antibodies, Monoclonal↗
PubMed1992

Initial characterization of a pea mutant with light-independent photomorphogenesis.

We have identified a mutant of pea cultivar Alaska that has many of the characteristics normally associated with light-grown seedlings even when grown in complete darkness. We have designated this mutant lip1, for light independent photomorphogenesis. Etiolated wild-type pea seedlings are white to slightly yellow in color and have a distinct morphology characterized by elongated epicotyls and buds containing unexpanded leaves with small, undifferentiated cells. In contrast, mutant seedlings grown under the same conditions are yellow in color and have short epicotyls and expanded leaves showing clear cellular differentiation. Transmission electron microscopy revealed partially developed, agranal plastids in the dark-grown mutant, unlike wild-type seedlings that contain etioplasts with prolamellar bodies. The mutant also exhibits a much shorter lag period for chlorophyll accumulation when etiolated seedlings are transferred from darkness to white light. The dark-grown mutant has 10-fold less spectrally detectable phytochrome, which can be attributed to a 10-fold reduction in the level of the PHYA polypeptide. Cab, Fed1, and RbcS transcripts are present in dark-grown mutant seedlings at levels comparable to those produced in light-grown material. The levels of these transcripts show a normal decrease when green plants grown for 15 days in a light/dark cycle are transferred to continuous darkness. However, transcript levels remain high during dark treatment of seedlings grown for 9 days in continuous light, indicating that the dark adaptation response in this mutant is developmentally plastic. The lip1 mutant has several features in common with the deetiolated Arabidopsis mutants det1, det2, and cop1. However, there are also several important differences, including varying effects on phytochrome levels, organ-specific gene expression, plastid development, and response to dark adaptation.

Cytokinins↗
PubMed1991

The OPI1 gene of Saccharomyces cerevisiae, a negative regulator of phospholipid biosynthesis, encodes a protein containing polyglutamine tracts and a leucine zipper.

In Saccharomyces cerevisiae, recessive mutations at the OPI1 locus result in constitutively derepressed expression of inositol 1-phosphate synthase, the product of the INO1 gene. Many of the other enzymes involved in phospholipid biosynthesis are also expressed at high derepressed levels in opi1 mutants. Thus, the OPI1 gene is believed to encode a negative regulator that is required to repress a whole subset of structural genes encoding for phospholipid biosynthetic enzymes. In this study, the OPI1 gene was mapped to chromosome VIII and cloned. When transformed into an opi1 mutant, the cloned DNA was capable of complementing the mutant phenotype and restoring correct regulation to the INO1 structural gene. Construction of two opi1 disruption alleles and subsequent genetic analysis of strains bearing these alleles confirmed that the cloned DNA was homologous to the genomic OPI1 locus. Furthermore, the OPI1 gene was found to be nonessential to the organism since mutants bearing the null allele were viable and exhibited a phenotype similar to that of previously isolated opi1 mutants. Similar to other opi1 mutants, the opi1 disruption mutants accumulated INO1 mRNA constitutively to a level 2-3-fold higher than that observed in wild-type cells. The cloned OPI1 gene was sequenced, and translation of the open reading frame predicted a protein composed of 404 amino acid residues with a molecular weight of 40,036. The predicted Opi1 protein contained a well defined heptad repeat of leucine residues that has been observed in other regulatory proteins. In addition, the predicted protein contained polyglutamine residue stretches which have also been reported in yeast genes having regulatory functions. Sequencing of opi1 mutant alleles, isolated after chemical mutagenesis, revealed that several were the result of a chain termination mutation located within the largest polyglutamine residue stretch.

Alleles↗
PubMed1991

Chlorophyll a/b binding (CAB) polypeptides of CP29, the internal chlorophyll a/b complex of PSII: characterization of the tomato gene encoding the 26 kDa (type I) polypeptide, and evidence for a second CP29 polypeptide.

CP29, the core chlorophyll a/b (CAB) antenna complex of Photosystem II (PSII), has two nuclear-encoded polypeptides of approximately 26 and 28 kDa in tomato (Lycopersicon esculentum). Cab9, the gene for the Type I (26 kDa) CP29 polypeptide was cloned by immunoscreening a tomato leaf cDNA library. Its identity was confirmed by sequencing tryptic peptides from the mature protein. Cab9 is a single-copy gene with five introns, the highest number found in a CAB protein. In vitro transcription-translation gave a 31 kDa precursor which was cleaved to about 26 kDa after import into isolated tomato chloroplasts. The Cab9 polypeptide has the two highly conserved regions common to all CAB polypeptides, which define the members of this extended gene family. Outside of the conserved regions, it is only slightly more closely related to other PSII CABs than to PSI CABs. Sequence analysis of tryptic peptides from the Type II (28 kDa) CP29 polypeptide showed that it is also a member of the CAB family and is very similar or identical to the CP29 polypeptide previously isolated from spinach. All members of the CAB family have absolutely conserved His, Gln and Asn residues which could ligate the Mg atoms of the chlorophylls, and a number of conserved Asp. Glu, Lys and Arg residues which could form H-bonds to the polar groups on the porphyrin rings. The two conserved regions comprise the first and third predicted trans-membrane helices and the stroma-exposed segments preceding them.

Amino Acid Sequence↗
PubMed1991

Concatemer chain reaction: a Taq DNA polymerase-mediated mechanism for generating long tandemly repetitive DNA sequences.

The concatemer chain reaction (CCR) uses Taq DNA polymerase to synthesize double- or single-stranded DNA concatemers whose length and yield can be controlled by varying the number of thermal cycling steps. Although the reactions which occur in CCR are slower and more complex than in polymerase chain reaction (PCR), the practical application of the CCR technique is simple. The CCR technique is less expensive, faster, and easier than conventional methods for producing concatemers and gives greatly improved yields. The templates used in CCR may be: (i) double-stranded concatemer templates produced by ligation, (ii) double-stranded concatemers from previous CCRs, or (iii) single-stranded oligonucleotides consisting of one copy of the sense strand repeat and a complementary but overlapping repeat for the antisense strand. Different molar ratios and lengths (masses) of the two strands of the helix may be obtained. We have used both single-stranded and double-stranded concatemers as targets for RNA hybridization. Applications of this concatemer technology are discussed, including the use of concatemers as hybridization probes or targets in applications such as run-on transcription or analysis of repetitive DNA sequences.

Base Sequence↗
PubMed1991

Mechanisms of rejection during OKT3 therapy: propagation and characterization of CD3 resistant allospecific cytotoxic T cells from a rejecting liver allograft.

Allograft rejection remains the single largest impediment to success in the field of transplantation. While OKT3 therapy has proven to be a significant advancement, many grafts are still lost. Late treatment, subtherapeutic OKT3 levels, anti-OKT3 antibodies, and OKT3-induced class II antigen expression are possible explanations. To determine the mechanism of OKT3 resistant rejection we propagated and characterized infiltrating T cells from the biopsy of a liver transplant patient who was rejecting while on prophylactic OKT3. The T lymphocytes demonstrated allospecific proliferation and interleukin 2 (IL2) production and showed a high degree of cytolysis of donor splenocytes. CD3 epsilon monoclonal antibodies (Mab) in concentrations up to 100 micrograms/ml did not inhibit lysis. In contrast, T lymphocytes derived from rejecting allografts of patients receiving cyclosporine and prednisone were readily inhibited from killing by CD3 epsilon Mab at doses of 1 microgram/ml. Furthermore, allospecific proliferation and IL2 production were not inhibited in the OKT3-treated patient by the addition of CD3 epsilon MaB. Incomplete modulation of the CD3-TCR complex was noted after a 72-hr incubation with CD3 epsilon Mab. The T cells did demonstrate other intact CD3-mediated functions such as a rise in intracellular calcium and CD3-dependent cytotoxicity. These results should alert clinicians that CD3 resistant cytotoxic T cells can emerge during OKT3 therapy and may cause rejection. Immunotherapy that targets additional cell surface structures may be of benefit.

Antibodies, Monoclonal↗
PubMed1991

Factors encouraging cohort maintenance in a longitudinal study.

Maintenance of the cohort is one of the primary challenges of a longitudinal study. At the end of 3 years of follow up in the Framingham Children's Study, a longitudinal study of young children and their parents, 100 of the original 106 families (94.3%) have remained in the study. A questionnaire was administered to identify factors contributing to the high rate of follow up to this point in the study. The attitudes of the staff, feedback to the subjects, the staff's handling of questions and problems, and association with the Framingham Heart Study emerged as the most important factors influencing continued participation in the study. In addition, 99% of the subjects stated that they believed the medical research to be important. We conclude that the quality of the communication with study participants and the subjects' perceived importance of the research have been the key factors in maintaining the cohort in this longitudinal epidemiologic study.

Attitude of Health Personnel↗
PubMed1991

Influence of parents' physical activity levels on activity levels of young children.

To determine the relationship between activity levels of parents and those of their young children, we monitored physical activity with a mechanical device, the Caltrac accelerometer, in one hundred 4- to 7-year-old children and in 99 of their mothers and 92 of their fathers. During 1 year in the Framingham Children's Study, data were obtained for an average of more than 10 hours per day for 8.6 +/- 1.8 days for the children, for 8.3 +/- 2.1 days for their mothers, and for 7.7 +/- 2.3 days for their fathers. Children of active mothers (average Caltrac accelerometer counts per hour greater than the median) were 2.0 times as likely to be active as children of inactive mothers (95% confidence interval = 0.9, 4.5); the relative odds ratio of being active for the children of active fathers was 3.5 (95% confidence interval = 1.5, 8.3). When both parents were active, the children were 5.8 times as likely to be active (95% confidence interval = 1.9, 17.4) as children of two inactive parents. Possible mechanisms for the relationship between parents' and child's activity levels include the parents' serving as role models, sharing of activities by family members, enhancement and support by active parents of their child's participation in physical activity, and genetically transmitted factors that predispose the child to increased levels of physical activity.

Child↗
PubMed1991

Inositol metabolism in yeasts.

Because of its accessibility to genetic and molecular studies, Sacch. cerevisiae is an attractive organism in which to pursue studies of the complex roles of phosphoinositides and other inositol-containing metabolites. Biochemical studies have clearly demonstrated that PI, PIP, PIP2 and the inositol phosphates derived from them exist in Sacch. cerevisiae. It is clear that they are synthesized and turned over following pathways similar to those described in higher eukaryotes. Recent studies on yeast have also suggested that inositol phospholipids may play roles in complex signalling pathways similar to those detected in animal cells. In addition, inositol has been demonstrated to function in yeast as a global regulator of phospholipid synthesis. This regulation occurs on a transcriptional level and is highly complex. It is not yet known whether similar inositol-mediated regulation of phospholipid synthesis occurs in other eukaryotes.

Inositol↗
PubMed1991

Procurement and transplantation of colonized cadaver skin.

Cadaver skin is an important adjunct to burn care. This study was designed to measure the percentage of its contamination prior to grafting and to determine the clinical safety of its use. Cadaveric homografts from 19 donors were harvested, frozen, thawed, and used as a biological dressing. Cultures were obtained at the time of harvest, after incubation in antibiotics, and at actual transplantation. The homografts were 43 per cent, 68 per cent, and 50 per cent contaminant-free, respectively. Two of 14 patients lost their homografts due to infection. However, no patient developed an infection or lost the homograft due to an organism identified during the pretransplantation processing. Therefore, contaminant-free and slightly contaminated cadaver skin can be used safely as homografts.

Adolescent↗