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Biomedical subjects

M J Wilson

Publications and source records attributed to M J Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1995

X linked fatal infantile cardiomyopathy maps to Xq28 and is possibly allelic to Barth syndrome.

A number of families with X linked dilated cardiomyopathy with onset in infancy or childhood have now been described, with varying clinical and biochemical features. Of these, one condition, Barth syndrome (BTHS), can be diagnosed clinically by the characteristic associated features of skeletal myopathy, short stature, and neutropenia, but not all of these features are always present. Molecular genetic studies have delineated the gene for BTHS, which maps to distal Xq28, from the gene for so called X linked dilated cardiomyopathy (XLCM), a teenage onset dilated cardiomyopathy, recently mapped to the 5' portion of the dystrophin locus at Xp21. We report a large family in which male infants have died with congenital dilated cardiomyopathy, and there is a strong family history of unexplained death in infant males over at least four generations. Death always occurred in early infancy, without development of the characteristic features associated with Barth syndrome. Molecular analysis localised the gene in this family to Xq28 with lod scores of 2.3 at theta = 0.0 with dinucleotide repeat markers, p26 and p39, near DXS15 and at F8C. The proximal limit to the localisation of the gene in this family is defined by a recombinant at DXS296, while the distal limit could not be differentiated from the telomere. This localisation is consistent with a hypothesis of allelic and clinical heterogeneity at the BTHS locus in Xq28.

Alleles↗
PubMed1995

Effects of aging and castration on plasminogen activator and metalloprotease activities in the rat prostate complex.

Pathology of the prostate gland in rats and humans is associated with aging. Our objective was to examine the effects of aging on the activities of plasminogen activators and metalloproteases in the prostatic complex of rats. Plasminogen activator activities (very low in the anterior, lateral, and dorsal lobes, in contrast to higher activities in the ventral lobe of 4-month-old adult rats) increased with aging in the dorsal and anterior prostate lobes of 31-month-old rats; these activities also increased in the dorsal and lateral lobes upon castration of 18-month-old rats. The plasminogen activator activities in the ventral lobe did not increase with aging to 18 months but did increase 3-5-fold after castration of either young or old rats. Metalloprotease activities of 70 and 76 kDa were observed in the anterior and lateral lobes of 4 month untreated adult rats, whereas the dorsal lobe showed MP of 70 and 92 kDa. Castration of young adult rats increased activities of all three molecular forms of metalloprotease in these three lobes. Increased expression of metalloprotease activities was also found with aging to 31 months in the anterior, lateral, and dorsal lobes. However, changes in metalloprotease activities associated with age were most striking in the lateral lobe and included activities of 52, 55, 81, 93, 113, and 117 kDa at 18 months of age. Castration for 30 days at this age resulted in a decline in the 52, 55, 113, and 117 kDa activities and an increase in activities of the 70, 81, and 93 kDa forms. These latter metalloprotease activities were also increased in the dorsal lobe after castration. Our results suggest that some metalloprotease activities increased in the dorsal lobe after castration. Our results suggest that some metalloprotease activities increased in the lateral lobe with age possibly result from an increased accumulation of secretory proteins (i.e., 52, 55, 113, and 117 kDa), whereas the 70, 81, and 93 kDa metalloprotease activities may be related to possible prostatitis and/or involved in changes in tissue organization. The increased expression of metalloprotease activities in the lateral and dorsal prostate lobes with aging, and castration upon aging, may be indicative of altered hormonal regulation of these proteases in these lobes.

Aging↗
PubMed1994

Objective detection of 40 Hz auditory evoked potentials: phase coherence vs. magnitude-squared coherence.

The relative performance of phase coherence (PC) and magnitude-squared coherence (MSC) for detection of steady-state evoked potentials was studied using 40 Hz auditory evoked potentials (AEPs) in 10 normal human subjects. In addition, simulation experiments were carried out to determine the effects of signal amplitude and phase variability on detection performance. All simulations showed MSC performance to be better than PC performance, with further improvements when MSC was supplemented with weighted averaging. However, human 40 Hz AEP data showed essentially identical detection performance for PC and MSC, with or without weighted averaging. These data support a "phase aggregation" model (at least near threshold) over the more usual model in which an AEP signal is added to a stationary noise. Human data collected under "no-stimulus" conditions agree well with theoretical distributions for both PC and MSC. For equal test time, long analysis periods (with less averaging) yielded equal performance to short analysis periods (with more averaging), for both PC and MSC.

Acoustic Stimulation↗
PubMed1994

Phase weighting: a method to improve objective detection of steady-state evoked potentials.

Objective response detection statistics such as magnitude-squared coherence (MSC) reflect the degree to which subaverage phases are clustered or dispersed, but not their agreement with an expected, or target, phase. Using signal-plus-noise simulations and human 40-Hz auditory evoked potentials, we tested MSC performance with and without phase weighting, in which MSC values were multiplied by weights related to the phase error between measured phase and target phase. Phase weighting improved MSC performance for both simulated and 40-Hz auditory evoked potential data. However, the improvement was greater for the simulations, probably because target phase was precisely known.

Acoustic Stimulation↗
PubMed1994

Identification of a novel antigen from Corynebacterium pseudotuberculosis that protects sheep against caseous lymphadenitis.

A 40-kDa protein antigen from Corynebacterium pseudotuberculosis has been identified by application of a strategy that employs locally derived antibody-secreting cells (ASC). ASC probes generated by culture of ASC obtained from the lymph node draining the site of infection showed a specificity restricted to a 40-kDa antigen. Analysis of immunoblots with sequential serum samples taken from sheep during the course of experimental primary infection with C. pseudotuberculosis also revealed the 40-kDa antigen as an early immunodominant antigen. Sheep vaccinated with two 100-micrograms doses of a 40-kDa antigen preparation in aluminium hydroxide adjuvant were protected against infection with C. pseudotuberculosis, with an 82% reduction in the proportion of infected sheep and a 98% reduction in lung lesions. Sera from vaccinated sheep exhibited a strong response only to the 40-kDa antigen on immunoblots. These results strongly suggest that the 40-kDa antigen plays a major role in immunity to caseous lymphadenitis.

Animals↗
PubMed1994

Identifying hearing loss in the intensive care nursery: a 20-year summary.

The outcome of a study on hearing loss in graduates of one third-level and two second-level intensive care nurseries (ICN) is reported. The goals were to identify, test, and fit hearing aids on those who need them. Initial hearing-threshold estimates were obtained by auditory brainstem response (ABR) analyses at the time of discharge from the hospital; the mean percentage of failures to respond to 30-dB nHL clicks (in one or both ears) was 19.8 percent for the third-level ICN graduates (N = 4374), and 12.0 percent for the second-level graduates (N = 1527). About half of those with hearing loss at the initial Test were returned for a ReTest 6-20 weeks later, at which time 48.7 percent of the third-level and 44.0 percent of the second-level group were judged normal because they delivered 25-dB click ABRs bilaterally. Following conventional audiological work-ups of the ones with unilateral or bilateral hearing loss, hearing aids were fitted to 92 in the third-level group (2.1% of those Tested) and 22 of the second-level group (1.4%). Not quite half of these fittings occurred within 1 year of the hospital Test that initially diagnosed the loss.

Acoustic Stimulation↗
PubMed1993

Hyperglycemia induces a loss of phospholipid asymmetry in human erythrocytes.

Phospholipid asymmetry in biological membranes is maintained by an aminophospholipid-specific Mg(2+)-ATPase that transports PS and PE from the outer to the inner monolayer. Recent evidence indicates that a loss of phospholipid asymmetry occurs in erythrocytes from diabetic individuals, resulting in the appearance of PS in the membrane outer leaflet. We show that hyperglycemic treatment of normal erythrocytes duplicates this effect. Erythrocytes incubated for 18-24 h in the presence of glucose were assayed for PS transport and transmembrane phospholipid asymmetry. Phospholipid asymmetry in erythrocytes treated with high concentrations of glucose (> 5 mM) showed a time-dependent (t1/2 approximately 12 h) and concentration-dependent (half-maximal concentration approximately 7.5 mM) increase in the accessibility of PS and PE, and a decrease in the accessibility of SM and PC, to exogenous phospholipases. After an 18 h incubation with 20 mM glucose, 40% of the endogenous PS and PE was found in the outer monolayer concomitant with a decrease in the outer monolayer content of SM (from 80% to 50%) and PC (from 75% to 65%). These values are consistent with an almost complete transbilayer scrambling of erythrocyte phospholipids. The loss of PS asymmetry was verified using an assay based on the activation of the prothrombinase complex. The observed loss of asymmetry is not due to inhibition of PS transport or glucose-induced Ca2+ influx.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Barth syndrome: clinical features and confirmation of gene localisation to distal Xq28.

Barth syndrome is an X-linked disorder characterised by cardioskeletal myopathy of variable severity usually fatal in childhood, and neutropenia. We ascertained a large pedigree with affected males in 3 generations. All affected males had dilated cardiomyopathy, with endocardial fibroelastosis (EFE) in some. The locus for Barth syndrome in this family was found to be closely linked to DXS52 (z = 2.78, theta = 0.0). The family was nonrecombinant for DXS52 in distal Xq28, but recombinant for DXS374 which maps proximal to DXS52. This localised Barth syndrome distal to DXS374, confirming a previous localisation to distal Xq28. As yet there is no evidence for genetic heterogeneity of Barth syndrome.

Cardiomyopathies↗
PubMed1993

Localization of a biotinylated cathepsin B oligonucleotide probe in human prostate including invasive cells and invasive edges by in situ hybridization.

The cysteine endopeptidase cathepsin B (CB) can degrade basement membrane (BM) proteins (such as laminin, type IV collagen, and fibronectin) at both acid and neutral pHs suggesting that CB has a role in tumor invasion and distant metastasis. The distribution and intensity of CB protein localization vary in normal prostate, benign prostatic hyperplasia (BPH), and neoplastic prostate. These considerations have led us to examine whether the distribution of CB localization in malignant and normal cells is due to storage or active synthesis of CB. In the present study, we examined the localization patterns of CB at the mRNA level in normal prostate, BPH, and well to moderately differentiated neoplastic prostate, focusing on invasive groups of cells and invasive edges of malignant tumors. We used a 25-base biotinylated oligonucleotide CB cDNA "sense" probe to localize CB message in prostate samples obtained from radical prostatectomies. We have determined that CB is actively synthesized by the epithelia of normal, hyperplastic, and neoplastic prostate including some invasive cells in the invasive edges. In both normal and BPH, CB mRNA was localized predominantly in acinar basal cells with some localization in cuboidal/columnar cells. In contrast, in neoplastic prostate, CB mRNA was localized predominantly in columnar cells and in groups of invasive cells and invasive edges. Thus, in malignant prostate the predominant cell types expressing CB differed from those of the normal prostate and BPH. Analysis of CB mRNA localizations indicated a heterogeneity in staining distribution in prostate cancer with some invasive groups of cells and invasive edges exhibiting CB mRNA and others exhibiting little or no reaction products.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1993

Gelatinolytic and caseinolytic proteinase activities in human prostatic secretions.

Seminal fluid contains a number of proteinase activities, many of which are secreted by the prostate gland. Our objective was to determine proteinase activities in human prostatic secretions which can degrade gelatin and/or casein. Prostatic secretions were collected by prostate massage from men with benign prostatic hyperplasia prior to surgery to relieve obstruction. Significant proteinase activities towards gelatin of about 81, 86, 94, 111, 115 and 163 Kd as well as less active forms of 23, 36, 38, 132, 137, and 148 Kd were detected using protein substrate-polyacrylamide gel zymography. In addition, Ca2+ stimulated activities of approximately 64, 66, 71 and 76 Kd; however, EDTA and EGTA inhibited all activities but the 23, 36 and 38 Kd forms (these were inhibited by benzamidine and epsilon-amino caproic acid). This suggests that the gelatinolytic activities of 64 Kd and greater were metalloproteinases and those of 23, 36, and 38 Kd were serine proteinases. Significant caseinolytic activities of 22, 25, 35, 37, 57, 90, 96, 102 and 116 Kd were found as well as several less active forms and a 12 Kd activity stimulated by Ca2+. Caseinolytic activities of 12, 14, 16, 96, 102, 116, and 126 Kd were inhibited by EDTA and EGTA indicating they are metalloproteinases. The 35, 37, 57 and 58 Kd caseinolytic activities were inhibited by benzamidine, and the 57 and 58 Kd forms by epsilon-aminocaproic acid suggesting they were serine proteinases. There was considerable variability among individuals in the molecular forms of proteinase activity expressed as well as the level of their activity. A significant decrease in the frequency of expression of the 132 Kd gelatinolytic activity was found in secretions from men with atypia or adenocarcinoma, as compared with men with benign prostatic hyperplasia alone. Our results show that human prostatic secretion contains a variety of proteinase activities. The expression of the 132 Kd gelatinolytic activity could prove useful in further evaluation of neoplastic prostatic disease.

Caseins↗
PubMed1993

Design of a californium-based epithermal neutron beam for neutron capture therapy.

The potential of the spontaneously fissioning isotope, 252Cf, to provide epithermal neutrons for use in boron neutron capture therapy (BNCT) has been investigated using Monte Carlo simulation. The Monte Carlo code MCNP was used to design an assembly composed of a 26 cm long, 11 cm radius cylindrical D2O moderator followed by a 64 cm long Al filter. Lithium filters are placed between the moderator and the filter and between the Al and the patient. A reflector surrounding the moderator/filter assembly is required in order to maintain adequate therapy flux at the patient position. An ellipsoidal phantom composed of skull- and brain-equivalent material was used to determine the dosimetric effect of this beam. It was found that both advantage depths and advantage ratios compare very favourably with reactor and accelerator epithermal neutron sources. The dose rate obtainable, on the other hand, is 4.1 RBE cGy min-1, based on a very large (1.0 g) source of 252Cf. This dose rate is two to five times lower than those provided by existing reactor beams and can be viewed as a drawback of using 252Cf as a neutron source. Radioisotope sources, however, do offer the advantage of in-hospital installation.

Californium↗
PubMed1993

Gelatinolytic and caseinolytic proteinase activities in the secretions of the ventral, lateral, and dorsal lobes of the rat prostate.

The ventral, lateral, and dorsal lobes of the rat prostate produce secretions rich in protein. We examined these secretions for proteinase activities, using gelatin- and casein-containing SDS-polyacrylamide gel zymographies. The ventral lobe demonstrated both higher activities and more molecular forms of proteinase activities that cleaved these two protein substrates than did the other lobes. Ca(2+)-stimulated gelatinolytic activities of approximately 48, 51, 58, 64, 74, and 80 kDa were found in ventral prostate secretions in addition to activities detected in the absence of added Ca2+: a very strong 27-kDa activity; prominent 22-, 86-, 90-, and 94-kDa activities; and less active 36-, 41-, 100-, 130-, and 140-kDa activities. Ca(2+)-stimulated gelatinolytic activities of 51, 58, 74, 80, 86, 90, and 94 kDa were present in lateral prostate secretions (none were detected in secretions of the dorsal lobe), and Ca(2+)-independent activities of 25, 27, and 100 kDa were found in secretions of both the lateral and dorsal lobes. The Ca(2+)-stimulated activities were inhibited by EGTA and EDTA. Benzamidine inhibited all gelatinolytic activities except for the 22-, 25-, and 27-kDa Ca(2+)-independent forms when Ca2+ was not added to the reaction buffer. However, in the presence of 5 mM CaCl2, the Ca(2+)-stimulated forms of proteinase were unaffected by benzamidine, whereas the other activities sensitive to benzamidine were inhibited. Prominent Ca(2+)-independent caseinolytic activities of 20, 23, 31, 37, 83, 89, and 94 kDa were detected in ventral lobe secretions along with less active forms of about 39, 48, 53, 57, 60, 63, 80, 103, 110, 125, and 160 kDa. Caseinolytic activities of approximately 23, 31, 53, 89, 94, 103, 120, and 125 kDa were found in lateral prostate secretions, and 89, 94, and 103 kDa activities were found in secretions of the dorsal lobe. Quantitatively, most gelatinolytic and caseinolytic activities were present in the soluble portion of the secretion of each prostatic lobe. The ventral, lateral, and dorsal prostate lobes all secrete gelatinolytic and caseinolytic proteinase activities; however, quantitatively the ventral lobe is the most notable in this function since its secretions contain more molecular forms and greater activities of these proteinases.

Animals↗
PubMed1993

Plasminogen activator and metalloprotease activities of Du-145, PC-3, and 1-LN-PC-3-1A human prostate tumors grown in nude mice: correlation with tumor invasive behavior.

Proteolytic enzymes are required to mediate tumor cell invasion of adjacent tissues and spread of primary tumors to distant sites. Our objective was to examine the activities and molecular forms of plasminogen activator (PA) and matrix metalloproteases (MP) in primary and secondary growths of SC tumors of three human prostatic cell lines (Du-145, PC-3, and 1-LN-PC-3-1A [1-LN], a subline of PC-3) grown in nude mice. The plasminogen activator activities were 1.7 +/- 1.3 (+/- SD), 6.2 +/- 2.8, and 11.5 +/- 4.2 for Du-145, PC-3, and 1-LN in primary SC tumors, respectively. Urokinase was the predominant molecular form of PA found in each tumor as determined from its molecular size (predominantly 54 kDa with a minor activity of 33 kDa) and sensitivity to amiloride. Prominent MP activities of approximately 68, 76, and 96 kDa as well as lesser activities of about 56, 59, 63, 84, 165, and 180 kDa were found in 1-LN tumors, whereas only less active MP of 59, 68, and 96 kDa were detected in the parental PC-3 cells. Du-145 tumors expressed MP activities of 59 and 96 kDa. Treatment of 1-LN tumor extracts with p-aminophenylmercuric acetate (APMA) significantly reduced the MP activities of 76 and 165 kDa while increasing activities of 56, 59, 65, 68, and 84 kDa. The 76 and 165 kDa MP activities thus appear to be prominent proenzyme forms of MP expressed in the 1-LN tumor. Secondary growths of tumor were subsequently found near the site of initial injection of PC-3 and 1-LN cells following removal of the primary tumor. There was a 42% increase in PA activity in the PC-3 secondary tumors, but only an 8% increase in 1-LN secondary tumors. However, there was no difference in the activities or number of molecular forms of MP in extracts of PC-3 or 1-LN primary or secondary tumors. The substantial expression of MP activities in the more aggressive 1-LN subline of the human prostatic PC-3 cell line indicates that induction of certain MP may be an important regulatory event in prostate tumor progression.

Amiloride↗
PubMed1993

HIV-1 seroprevalence among women attending sexually transmitted disease clinics in California. California Family of Surveys and Sentinel Surveillance Consortia.

To evaluate the distribution of the human immunodeficiency virus type 1 (HIV-1) epidemic among California women, we analyzed HIV-1 seroprevalence and risk factors among women attending sexually transmitted disease (STD) clinics in 21 local health jurisdictions. Using standardized protocols developed by the Centers for Disease Control, we tested unlinked serum specimens from women attending participating STD clinics in 1989. We analyzed demographic characteristics, HIV risk exposure groups, and results of HIV-1 antibody testing on 17,210 specimens with an overall HIV-1 seroprevalence of 0.57%. Seroprevalence rates were highest for African-American women, women 25 to 29 years of age, injection drug users, and women attending STD clinics in San Francisco. After multiple logistic regression analysis, HIV-1 seropositivity remained highest for these four groups. The rate of HIV-1 infection among women attending STD clinics in California underscores the continued need to make HIV counseling and testing an integral component of routine services for women being evaluated for, or presenting with, sexually transmitted diseases.

Adolescent↗