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Biomedical subjects

S M Miller

Publications and source records attributed to S M Miller.

At least 127 records · Page 7Linked to original sources
PubMed1990

Induction of MHC class II expression in recipient tissues caused by allograft rejection.

MHC class II antigens (DR) are not commonly expressed on parenchymal cells of kidney and liver except when they are allografts undergoing rejection. The objective of this study was to determine whether allograft rejection can also induce DR upregulation in parenchymal cells of autologous recipient organs. Dogs had unilateral renal autografts to facilitate kidney sampling. All kidneys were tubular cell DR-negative. After 8-14 days each dog received a tubular cell DR-negative allograft. Tubular cell DR became positive in both allograft and autograft simultaneously, its onset and intensity correlating with blast cell infiltration and rejection in the allograft. Blast cells were first detected in the autograft after allograft nephrectomy, and then disappeared as autograft tubular cell DR diminished over the next 6-8 days. This was reproduced on repeat allografting. In 2 untreated dogs hepatocytes became positive on day 4, with no hepatic blast infiltrate. Four other dogs received cyclosporine immunosuppression. Allograft and autograft tubular cell DR, and hepatocyte DR, increased in all dogs, but were delayed while on CsA until onset of rejection despite transient earlier allograft blast infiltration. Downregulation in autograft and liver occurred together after allograft nephrectomy. An interferon-like substance appeared in plasma after allografting in association with the DR changes in native kidney and liver. Renal allorejection therefore induces upregulation of parenchymal DR expression in autologous liver and kidney of the recipient. It is probably mediated by an interferon-like substance derived from cells infiltrating the allograft. The effect is modified by CsA.

Animals↗
PubMed1990

Role of NAD-linked glutamate dehydrogenase in nitrogen metabolism in Saccharomyces cerevisiae.

We cloned GDH2, the gene that encodes the NAD-linked glutamate dehydrogenase in the yeast Saccharomyces cerevisiae, by purifying the enzyme, making polyclonal antibodies to it, and using the antibodies to screen a lambda gt11 yeast genomic library. A yeast strain with a deletion-disruption allele of GDH2 which replaced the wild-type gene grew very poorly with glutamate as a nitrogen source, but growth improved significantly when the strain was also provided with adenine or other nitrogenous compounds whose biosynthesis requires glutamine. Our results indicate that the NAD-linked glutamate dehydrogenase catalyzes the major, but not sole, pathway for generation of ammonia from glutamate. We also isolated yeast mutants that lacked glutamate synthase activity and present evidence which shows that normally NAD-linked glutamate dehydrogenase is not involved in glutamate biosynthesis, but that if the enzyme is overexpressed, it may function reversibly in intact cells.

Alleles↗
PubMed1989

Evidence for the participation of Cys558 and Cys559 at the active site of mercuric reductase.

Mercuric reductase, with FAD and a reducible disulfide at the active site, catalyzes the two-electron reduction of Hg(II) by NADPH. Addition of reducing equivalents rapidly produces a spectrally distinct EH2 form of the enzyme containing oxidized FAD and reduced active site thiols. Formation of EH2 has previously been reported to require only 2 electrons for reduction of the active site disulfide. We present results of anaerobic titrations of mercuric reductase with NADPH and dithionite showing that the equilibrium conversion of oxidized enzyme to EH2 actually requires 2 equiv of reducing agent or 4 electrons. Kinetic studies conducted both at 4 degrees C and at 25 degrees C indicate that reduction of the active site occurs rapidly, as previously reported [Sahlman, L., & Lindskog, S. (1983) Biochem. Biophys. Res. Commun. 117, 231-237]; this is followed by a slower reduction of another redox group via reaction with the active site. Thiol titrations of denatured Eox and EH2 enzyme forms show that an additional disulfide is the group in communication with the active site. [14C]Iodoacetamide labeling experiments demonstrate that the C-terminal residues, Cys558 and Cys559, are involved in this disulfide. The fluorescence, but not the absorbance, of the enzyme-bound FAD was found to be highly dependent on the redox state of the C-terminal thiols. Thus, Eox with Cys558 and Cys559 as thiols exhibits less than 50% of the fluorescence of Eox where these residues are present as a disulfide, indicating that the thiols remain intimately associated with the active site.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1989

Coping style in hypertensive patients: nature and consequences.

Examined the coping styles and health behaviors of hypertensive and normotensive patients visiting a primary care setting for acute medical problems. Hypertensive individuals were far more likely to display a "high-monitoring" (information-seeking) mode of coping than normotensive individuals, who tended to be "low monitoring" (information avoiding) in their coping. Although hypertensive patients reported less dysfunction in their current medical problems than did normotensive patients, they nonetheless reported greater concerns about their condition and its impact. Finally, hypertensive patients were rated by physicians as more likely to desire help with both their presenting medical problem and their stress-related problems. Future research should help to specify the exact relations among coping style, stress, and symptom reporting in hypertension.

Adaptation, Psychological↗
PubMed1989

The relationship between patients' satisfaction with their physicians and perceptions about interventions they desired and received.

This study was designed to determine the relationship between patients' satisfaction with their physician, the types of interventions that patients reported they received, and the congruence between those interventions and the types of interventions they desired. One hundred eighteen symptomatic adult primary-care patients completed questionnaires before and after their respective medical visits. Patients who indicated they received any one of the three nontechnical interventions: education (P less than 0.001), stress counseling (P less than 0.05), and negotiation (P less than 0.01), were significantly more satisfied than those who had not received these interventions. Patient perceptions about receiving technical interventions, i.e., examination, tests, medications, and nondrug therapy, were not related to patient satisfaction. The congruence between patient-intervention desires and perceptions about interventions received generally were not significantly related to satisfaction except for the interaction between receiving a medication and postvisit-medication desires (P less than 0.001). A series of multiple regression analyses revealed that, in general, perceptions about nontechnical interventions were better predictors of patient satisfaction than perceptions about technical interventions.

Adult↗
PubMed1989

Improved propagation in myometrium associated with gap junctions during parturition.

The hypothesis that gap junction (GJ) formation between myometrial cells at term improves electrical coupling was tested. We measured the spread of electrical excitation from six extracellular electrodes aligned on uterine strips in either the longitudinal (axial) or transverse (circumferential) direction. Spontaneous bursts propagated over the entire 15-mm recording distance in the axial direction at both preterm and parturition and showed some characteristics of a system of coupled relaxation oscillators. However, individual spikes within the bursts propagated further and with higher velocity at parturition than at preterm. In the circumferential direction, both bursts and individual spikes propagated further at parturition than before. Propagation in this axis at parturition appeared to require an intact circular muscle layer. Spikes evoked by electrical stimulation also propagated further and with higher velocity in both axes at parturition. Electron microscopy showed many GJs between uterine smooth muscle cells during parturition, but few and sometimes no GJs at preterm. Thus improved propagation was associated with increased GJ contact between myometrial cells, consistent with the hypothesis that gap junction formation at term improves electrical coupling.

Action Potentials↗
PubMed1989

Fine-needle aspiration biopsy sampling in renal transplantation: interstitial cellular infiltrates and major histocompatibility complex class-II antigen expression in renal tubular cells.

The dynamics of major histocompatibility complex (MHC) class-II (DR) antigen products in renal tubular cells and cellular infiltrations in the interstitium of the kidney following renal transplantation without immunosuppressive therapy are presented. DR antigen in 27 normal kidneys and in 18 of 19 kidneys transplanted as autograft showed no DR-antigen expression on their tubular cells. These DR-antigen-negative tubular cells could be induced to express the antigen during courses of untreated rejection both in primary (n = 6) and repeat (n = 4) allografts. Parallel to the increasing DR-antigen expression in the allograft, the autologous kidney expressed this antigen with the same time dependency and with the same intensity. Graft infiltrating cells were evaluated by daily fine-needle aspiration biopsy and core biopsy. Induction of DR antigen was associated with a significant infiltration of blastogenic cells and monocytes/macrophages in the allograft. During rejection of the allograft no cellular infiltrate was noted in the autograft, but during an initial time period after allograft removal cellular infiltrates were seen. Following both courses of rejection DR antigen returns to negative by 6-8 days as did blastogenic cells and monocytes/macrophages in the autograft interstitium. Inducible antigen expression in normally DR-antigen-negative allograft parenchymal cells during rejection is shown to depend on inflammatory cells in the graft. The antigen expression is not restricted to the tissue transplanted, but also affects autologous tissue of the host organism.

Animals↗
PubMed1988

One-step gene disruption by cotransformation to isolate double auxotrophs in Candida albicans.

The Candida albicans LEU2 gene was disrupted by substituting lambda DNA for a small deletion within the LEU2 gene. Cotransformation with a selectable URA3 ARS vector was used to introduce a linear fragment containing the disruption into the genome of a C. albicans ura3 deletion mutant. Cotransformants containing the lambda DNA were identified by colony hybridization and the URA3 plasmid was subsequently cured. Leu2 disrupted heterozygotes were detected by Southern hybridization and one disruptant was subsequently treated with UV irradiation. Only one leu2 ura3 mutant (SGY-484) was isolated out of 11,000 mutagenized cells. SGY-484 was transformed to Leu+ with either the C. albicans or Saccharomyces cerevisiae LEU2 gene. Southern hybridization analysis revealed that the mutant is not homozygous for the disruption; the leu2 mutation reverts and is most likely a point mutation. Unexpectedly, an ade2 ura3 mutant was isolated from the same mutagenesis.

Bacteriophage lambda↗
PubMed1988

Styles of coping with threat: implications for health.

We explored individual differences in health-seeking behavior and health status in a primary care population. Specifically, we compared high monitors (those who typically scan for threat-relevant information) with low monitors (those who typically ignore threat-relevant information), while controlling for depression. Overall, high monitors came to the physician with less severe medical problems than did low monitors. Nevertheless, high monitors reported equivalent levels of discomfort, dysfunction, and distress compared with low monitors. Furthermore, during the week following their visit, high monitors expressed less symptom improvement in both physical and psychological problems than did low monitors. Finally, high monitors demanded more tests, information, and counseling during their visit than did their low monitoring counterparts, yet desired a less active role in their own care. The theoretical and practical implications of these findings are discussed.

Adaptation, Psychological↗
PubMed1988

Control of myometrial contractility: role and regulation of gap junctions.

In this review we have attempted to describe the morphology and electrophysiology of the myometrium and also the myogenic, neurogenic and hormonal systems which control its activity. The synthesis of myometrial gap junctions appears to play a significant role in the gradual evolution of uterine contractility during labour. We suggest that the development of myometrial gap junctions is physiologically regulated by the steroid hormones, their receptors and prostaglandins. Furthermore, the permeability or conductance of the gap junction channels as well as their degradation seems to be hormonally regulated (Figure 10.6). Thus, there are several sites for the control of the presence and function of the gap junctions and the management of uterine contractility.

Animals↗