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Biomedical subjects

M White

Publications and source records attributed to M White.

At least 253 records · Page 14Linked to original sources
PubMed1994

Simple procedures can markedly enhance automated immunoassay performance.

Theoretically, optimal performance for an immunoassay system is achieved when both the interassay and within-run precisions are identical. Using the Ciba Corning ACS:180 automated immunoassay system, the authors made two simple changes to the operating procedures that allowed near-optimal analytic performance (as assessed with the interassay coefficient of variation determined by the protocol of the National Committee for Clinical Laboratory Standards) for four of six hormones: thyroid-stimulating hormone, luteinizing hormone, prolactin, and human chorionic gonadotropin. At low hormone concentrations, the 20% interassay coefficients of variation for the hormones assayed were as follows: free tetraiodothyronine, 1.74 pM; thyroid-stimulating hormone, .033 mIU/L; luteinizing hormone, .21 U/L; follicle-stimulating hormone, .69 U/L; prolactin, 5.03 mU/L; and human chorionic gonadotropin, 1.52 mU/L. The operational enhancements improved the analytic performance of the assay for all hormones assessed compared with the performance of previously used isotopic immunoassays.

Autoanalysis↗
PubMed1994

Unilateral renal aplasia in X-linked Kallmann's syndrome.

Unilateral renal agenesis is an uncommon association with Kallmann's syndrome (KS) (hypogonadotrophic hypogonadism and olfactory defect). We have investigated affected individuals from six pedigrees: five with X-linked KS, and one with X-linked KS and X-linked ichthyosis (XLI). Seventeen affected individuals have had renal imaging performed, and six scans demonstrated only one kidney. In addition, two pedigrees had males who died in the neonatal period with bilateral renal agenesis. Only two of the four affected individuals in the family with X-linked KS and X-linked ichthyosis (Pedigree 6) showed unilateral renal agenesis, despite all four patients demonstrating an interstitial deletion within the short arm of the X-chromosome. These data indicate that unilateral renal agenesis is much commoner than previously suspected in patients with X-linked Kallmann's syndrome, but that it may have incomplete penetrance within a family.

Genetic Linkage↗
PubMed1994

Guanylhydrazones in therapy of Pneumocystis carinii pneumonia in immunosuppressed rats.

Guanylhydrazones are cationic heteroaromatic drugs similar to the diamidines which are effective in the treatment of African trypanosomiasis and pneumocystosis. On the basis of their antitrypanosomal activity, different guanylhydrazones were selected for evaluation in a rat model of Pneumocystis carinii pneumonia. The most active compounds were the 2-(4'-formylphenyl)-1-methylimidazo-[1,2-a] pyridinium guanylhydrazones which, at a dose of 2 mg/kg/day, were about as effective as trimethoprim-sulfamethoxazole at a dose of 50 mg of trimethoprim per kg/day plus 250 mg of sulfamethoxazole per kg/day. The anti-P. carinii activity of these guanylhydrazone derivatives was found with parenteral but not with oral administration. The 1,3-arylene diketone bis(guanylhydrazones) were generally ineffective, although a triacetyl derivative showed some anti-P. carinii activity. Nitroimidazole guanylhydrazone derivatives were also ineffective. Attempts to improve the therapeutic efficacy of the different guanylhydrazones were limited by problems of toxicity. We conclude that some guanylhydrazone derivatives are potent anti-P. carinii drugs and that further studies should be pursued to develop safer compounds and investigate structure-activity relationships.

Animals↗
PubMed1994

Concerted action of RAS and G proteins in the sexual response pathways of Schizosaccharomyces pombe.

We have shown that the expression of mam2, the gene encoding the Schizosaccharomyces pombe P-factor pheromone receptor, is dependent upon components of the pheromone signal transduction pathway, including Ras1, Gpa1, Byr1 and Byr2, each of which is required for both conjugation and sporulation. Studies of the expression of mam2 in mutant S. pombe cells confirm previous conclusions, based on the ability of cells to sporulate, that the Byr1 protein kinase acts downstream of the Byr2 protein kinase and that both act downstream of Ras1, the S. pombe RAS homolog, and Gpa1, the G alpha component that mediates the occupancy of the mam2 receptor. In addition, our present studies show that Ras1 and Gpa1 each act downstream from the other and hence act in concert. The Spk1 kinase, which is required for conjugation and sporulation and which is a structural and functional homolog of the vertebrate MAP kinases, is not required for mam2 expression.

Base Sequence↗
PubMed1994

Age-related changes in beta-adrenergic neuroeffector systems in the human heart.

BACKGROUND: Aging decreases cardiac beta-adrenergic responsiveness in model systems and in humans in vivo. The purpose of this study was to comprehensively evaluate the age-related changes in the beta-receptor-G protein-adenylyl cyclase complex in nonfailing human hearts. METHODS AND RESULTS: Twenty-six nonfailing explanted human hearts aged 1 to 71 years were obtained from organ donors and subjected to pharmacological investigation of beta-adrenergic neuroeffector systems. When the population was subdivided into the 13 youngest and 13 oldest subjects, total beta-receptor density assessed by maximum [125I]ICYP binding (beta max) was reduced in older hearts by 37% in left ventricles and 31% in right ventricles (both P < .05), and the downregulation was confined to the beta 1 subtype (r = .78 left ventricle beta 1 density versus donor age). Older donor hearts exhibited a 3- to 4-fold rightward shift of ICYP-isoproterenol (ISO) competition curves and demonstrated 43% fewer receptors in a high-affinity agonist binding state (P < .05). Older hearts exhibited decreased adenylyl cyclase stimulation by ISO, by zinterol (beta 2-agonist), and by the G protein-sensitive probes forskolin, Gpp(NH)p, and NaF. In contrast, there was no change in response to manganese, a specific activator of the adenylyl cyclase catalytic subunit. Toxin-catalyzed ADP ribosylation in membranes prepared from older versus younger hearts revealed a 29% to 30% reduction (P < .05) with cholera toxin (Gs) but no difference with pertussis toxin (Gi). The systolic contractile response of isolated right ventricular trabeculae to ISO was decreased by 46%, with a 10-fold increase in ISO EC50 in older relative to younger donor hearts. CONCLUSIONS: There is a profound decrease in cardiac beta-adrenergic responsiveness with aging. This occurs by multiple mechanisms including downregulation and decreased agonist binding of beta 1-receptors, uncoupling of beta 2-receptors, and abnormal G protein-mediated signal transduction.

Adenylyl Cyclases↗
PubMed1994

A role for case managers in the physician office.

Independent primary care physicians continue to be important gatekeepers for health care services needed by older patients. There is a natural role for case management in the physician office as a link to nonmedical support services that can help the elderly maintain their independence. In this article, the authors describe a model partnership between primary care physicians and a community-wide case management program that was developed to enhance the continuum of care and improve integration of service systems. Rapid response for assessments, brief interventions, and linkage to home and community services are provided through a case manager/liaison who is on-call to physician offices. Patients are seen in the physician office or in their homes or contacted by telephone. The liaison assesses and provides immediate information and referral, maintains short-term contact, or refers patients with complex situations or long-term case management needs to agency or community case management programs. The liaison also makes regular office rounds to maintain visibility, discuss cases, and educate staff about patient risk factors. Physicians and patients have been pleased with the model.

Aged↗
PubMed1994

Mediastinal and pericardial complications after heart transplantation. Not-so-unusual postoperative problems?

Of a total of 133 patients who underwent heart transplantation, 16(12%) had pericardial and mediastinal complications. Non-infectious pericardial complications, pericardial effusion and constriction were noted in ten patients, and infectious pericarditis or mediastinitis in six. Cardiac echocardiography, catheterization and magnetic resonance imaging were useful in assessing these problems. All patients underwent surgical treatment, pericardial drainage, pericardectomy or muscle flap closure. Twelve (75%) of these 16 patients are long-term survivors. In conclusion, pericardial and mediastinal complications are common after heart transplantation, and aggressive surgical treatment is most often effective in their control.

Adult↗
PubMed1993

IRS-1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells.

Although several interleukin-3 (IL-3)-dependent cell lines proliferate in response to IL-4 or insulin, the 32D line does not. Insulin and IL-4 sensitivity was restored to 32D cells by expression of IRS-1, the principal substrate of the insulin receptor. Although 32D cells possessed receptors for both factors, they lacked the IRS-1--related protein, 4PS, which becomes phosphorylated by tyrosine in insulin- or IL-4--responsive lines after stimulation. These results indicate that factors that bind unrelated receptors can use similar mitogenic signaling pathways in hematopoietic cells and that 4PS and IRS-1 are functionally similar proteins that are essential for insulin- and IL-4--induced proliferation.

Animals↗
PubMed1993

Clinical and prognostic significance of in vivo differentiation in acute myeloid leukemia.

Bromodeoxyuridine (BrdU) was administered to 86 newly diagnosed patients with standard risk acute myeloid leukemia (AML) prior to starting induction therapy and the labeling index (LI), durations of S-phase (Ts), and the cell cycle (Tc) of myeloblasts were determined. Induction therapy with cytosine arabinoside and daunomycin was subsequently started. Bone marrow biopsies were obtained on days 6 and 17 and weekly thereafter, and were treated with a monoclonal anti-BrdU antibody to determine the fate of cells labeled on day 0 by BrdU. BrdU labeled granulocytes indicating the presence of in vivo differentiation (Diff+) were identified in 48 patients ranging from 1+ (1-10 labeled cells) to 4+ (greater than 31 labeled granulocytes). When compared to 38 differentiation negative (Diff-) patients, Diff+ group had longer Ts (14.5 hr vs. 10.95 hr, P = 0.015) and Tc (59.7 hr vs. 41.7 hr, P = 0.017). Remission duration was significantly longer (no median) for 3-4+ Diff+ as compared to Diff- (median = 220 days) patients (Wilcoxon P = 0.04). We conclude that the detection of in vivo differentiation in AML patients indicates a favorable long-term prognosis either due to the presence of a substantial amount of normal residual hematopoiesis prior to starting induction therapy or due to the ability of leukemic cells to undergo differentiation.

Acute Disease↗
PubMed1993

In vitro high resolution 1H-spectroscopy of the human prostate: benign prostatic hyperplasia, normal peripheral zone and adenocarcinoma.

1H-spectra at 360 MHz from perchloric extracts of 35 human prostate specimens were obtained. First, we sought to define what peaks can be assigned in vitro, and thus, potentially seen in vivo. Second, we sought to try to discriminate between adenocarcinoma, normal peripheral zone and benign prostatic hyperplasia using spectral fingerprints. Thirteen samples of adenocarcinoma, 11 samples of benign prostatic hyperplasia, and 11 samples of normal contralateral peripheral zone were analyzed by obtaining a ratio from the maximum area of each major peak and the area of an added standard (3-trimethyl-silyl-propionic acid). There was a significantly larger benign prostate hyperplasia citrate standardized peak area when compared to the adenocarcinoma citrate standardized peak area for each patient (P < 0.05). However, the citrate standardized peak areas from the normal peripheral zones were not significantly different from those found in the adenocarcinomas. Four out of 13 cases of stromal hyperplasia had similarly low levels of citrate as their respective gland's adenocarcinoma. We also found a sharp peak at 2.05 ppm that was seen in 4 out of 13 adenocarcinoma samples and in only 1 out of 13 of the benign prostate hypertrophy samples which has tentatively been assigned to N-acetyl neuraminic acid. Further studies are required to assess whether low citrate levels alone can serve to exclusively diagnose adenocarcinoma of the prostate.

Acetates↗
PubMed1993

Assessment of the value and pattern of use of a target controlled propofol infusion system.

Thirty one anaesthetists were supplied with a pharmacokinetic based target controlled propofol infusion system for evaluation. Twenty seven of 30 replies to a questionnaire sent to them indicated that the system had changed their use of propofol for maintenance of anaesthesia. The main reasons were greater ease of use and more confidence regarding the predictability of anaesthetic effects compared with manually controlled infusion. Data obtained from 770 patients anaesthetised with the system were analysed. The median maximum target concentration selected was 6.6 micrograms/ml. Younger patients (18-35 yr) required significantly greater target concentrations than older patients (65-80 yr). The mean time during which the system was in maintenance mode, when the predicted blood concentration of propofol was held constant for at least one minute, was 26.1 minutes. The median number of alterations in propofol concentration was 6. The target controlled infusion system provided an inexpensive and acceptable method of delivering intravenous anaesthesia.

Adolescent↗
PubMed1993

A cluster of four cases of Mycobacterium haemophilum infection.

Four cases of infection with Mycobacterium haemophilum occurred at a single hospital in a seven-month period. Only 22 cases have been reported since 1976. All four patients were immunocompromised; two had AIDS and two were the first known recipients of allogeneic bone marrow transplants (BMT) to develop the infection. One BMT recipient died of Mycobacterium haemophilum pneumonia. The organism requires hemin or ferric ammonium citrate and incubation of media at 30 degrees C for optimum growth. Clinicians and microbiologists should consider infection with Mycobacterium haemophilum, particularly when specimens are from immunocompromised patients with unexplained illness and/or when acid-fast bacilli are seen on smear.

AIDS-Related Opportunistic Infections↗
PubMed1993

Up-regulation of beta 2-adrenergic receptors in previously transplanted, denervated nonfailing human hearts.

OBJECTIVES: The purpose of this study was to examine beta-adrenergic receptor signal transduction in denervated, previously transplanted human ventricular myocardium. BACKGROUND: In model systems, surgical denervation typically results in both presynaptic and postsynaptic supersensitivity in beta-adrenergic receptor pathways and alteration in G protein-mediated signal transduction. METHODS: We examined beta-adrenergic receptor signal transduction in the left and right ventricles removed from nine subjects with a previous transplant and surgical denervation 25 +/- 4 months after their first transplantation. Twenty-six hearts removed from organ donors served as control hearts. RESULTS: Total beta-adrenergic receptor density and stimulation of muscle contraction in isolated right ventricular trabeculae by the nonselective agonist isoproterenol were similar in the transplant and donor groups. Beta 1-receptor density was not different in the left ventricles of the two groups but tended to be reduced (by 29%, p = 0.09) in transplant right ventricles. By contrast, beta 2-receptor density was higher in transplant left and right ventricles relative to the respective values in donor ventricles by 33% in left ventricles and 97% in right ventricles (both p < 0.05). Isoproterenol, which in particulate fractions of human heart stimulates adenylyl cyclase primarily via beta 2-receptors, produced a greater increase in cyclic adenosine monophosphate generation in membranes prepared from transplant left ventricles and right ventricles compared with donors. In contrast, guanosine 5'-[beta,gamma-imido]triphosphate, sodium fluoride and forskolin, which stimulate adenylyl cyclase through nonreceptor/G protein-sensitive mechanisms, yielded similar degrees of adenylyl cyclase stimulation in the two groups, and both pertussis toxin- and cholera toxin-catalyzed adenosine diphosphate ribosylation were not altered in transplanted left ventricles. CONCLUSIONS: These data indicate that the transplanted human heart exhibits an up-regulation of functional beta 2-adrenergic receptors.

Adenylyl Cyclases↗