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Biomedical subjects

J Hicks

Publications and source records attributed to J Hicks.

At least 19 recordsLinked to original sources
PubMed1991

Kinesin heavy chain is essential for viability and neuromuscular functions in Drosophila, but mutants show no defects in mitosis.

The in vivo function of the microtubule motor protein kinesin was examined in Drosophila using genetics and immunolocalization. Kinesin heavy chain mutations (khc) cause abnormal behavior and lethality. Mutant larvae exhibit loss of mobility and tactile responsiveness in the most posterior segments, followed by general paralysis and death during larval or pupal development. Adults homozygous for a temperature-sensitive allele also exhibit a loss in mobility and sensory responses. The data indicate that kinesin function is essential and suggest that kinesin has an important role in the neuromuscular system, perhaps as a motor for axonal transport. The possibility of more general cellular functions remains open, but observation of embryogenesis and morphogenesis in khc mutants suggests that mitosis and the cell cycle can proceed in spite of impaired kinesin function. Immunolocalization suggests that kinesin may have some general cellular functions but that it is not a major component of mitotic spindles.

Adenosine Triphosphatases↗
PubMed1991

The effect of HCO3- on anion-stimulated ATPase from rat parotid granules.

ATPase from isolated secretory granules was stimulated in a concentration-dependent manner by HCO3- above 0.9 mM. Maximal stimulation was found at about 16 mM HCO3- and was about half of that with sulphite (SO3(2-)). The activation site(s) appeared to be similar to at least one class of SO3(2-) sites, HCO3(-)-stimulate ATPase was inhibited by SITS. Furthermore, maximal stimulation with SO3(2-) was not enhanced with HCO3-. At low Mg2+ concentrations, Ca2+ stimulated granule ATPase. At higher concentrations of Mg2+ (0.5 mM and above), Ca2+ at 0.1 mM or less had little effect on HCO3(-)-ATPase, and Ca2+ at 4 mM inhibited HCO3(-)-ATPase. At concentrations of Ca2+ above 0.44 mM, the enzyme was partially stimulated in the absence of Mg2+ and presence of HCO3-. Mitochondrial contamination did not account for the presence of ATPase in the isolated granule fraction. The granule ATPase may be regulated by HCO3- and calcium and this could be related to changes in the granule environment during exocytosis.

Adenosine Triphosphatases↗
PubMed1991

Significance of anti-phospholipid antibodies in patients with lupus nephritis.

Anti-phospholipid antibodies (APA) as markers or mediators of thrombosis in lupus could be of pathogenetic significance in nephritis, since glomerular capillary thrombi are an indicator of subsequent renal dysfunction. Isotype specific APA antibodies were measured, using cardiolipin as the antigen, in 76 patients with lupus nephritis. Twenty-nine percent of the patients had elevated IgG APA. Overall, 43% of patients showed raised levels of at least one isotype. In general, APA had specificity for anionic phospholipids. In vitro lupus anticoagulant activity was associated with all three isotypes of APA, but only the IgM isotype correlated with the biological false positive test for syphilis. APA were not associated with thromboses or neurological involvement, and only the IgA isotype correlated with thrombocytopenia. We confirmed an association between the presence of intraglomerular thrombi and serum IgG APA. However, we found no association between APA and renal histological pattern, or long-term renal function. Our data, therefore, do not support a major pathogenetic role for APA in the nephritis of lupus in treated patients.

Antibodies↗
PubMed1991

The outcome of pregnancy in women with lupus nephritis.

We analysed the outcome of pregnancy in patients with pre-existing lupus nephritis, seen in a tertiary referral centre for nephrology. Fifty-three pregnancies in 25 patients who already had clinical and histological evidence of lupus nephritis were recorded between January 1970 and June 1989, and data were analysed retrospectively. All 53 pregnancies occurred in patients with more or less stable disease, while three pregnancies during which lupus first presented were excluded. Six pregnancies were ended by therapeutic abortions (four for social reasons), and in eight spontaneous abortion occurred. Thus, 39 deliveries occurred, 28 at 36 weeks or more, while 11 were delivered prematurely, of which one was a stillbirth. After allowance was made for therapeutic abortions, the fetal loss rate (9/47) was 19%. Seventeen Caesarian sections were performed in the 39 completed pregnancies (44%), 11 as emergencies. Although the overall fetal loss, incidence of premature births and Caesarian section rate were all higher than expected for a population of normal women, neither initial histology, treated hypertension, the presence of proteinuria or a nephrotic syndrome showed statistically significant relationships with the outcome of completed pregnancies. In no case was maternal renal function affected irreversibly, although proteinuria increased substantially during pregnancy in six patients, and creatinine clearance fell during pregnancy, also in six patients. No 'flares' in systemic disease were seen, but all patients save five were treated with a brief period of high-dose oral corticosteroids or intravenous methylprednisolone in the postpartum period. No case of neonatal lupus or congenital heart block was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1989

Switching of Candida albicans during successive episodes of recurrent vaginitis.

Strain relatedness and switching were monitored in Candida albicans strains isolated from different body locations through three episodes of recurrent vulvovaginal candidiasis separated by two treatment-latency periods in a single patient. Strain relatedness was assessed by comparing Southern blot hybridization patterns with the relatively immobile mid-repeat sequence Ca3. The following conclusions are demonstrated. (i) Three different strains of C. albicans colonized the mouth, the area under the breasts, and the vulvovaginal, anal, and rectal regions, respectively, at the time of the first infection. (ii) The same strain of C. albicans was responsible for the three vaginal infections. (iii) Switching of colony phenotype occurred with each new vaginal infection. (iv) Enrichment of drug-resistant switch phenotypes (assessed in vitro) was unlikely the basis for the changes in the switch phenotypes of the strain found in the vulvovaginal, anal, and rectal areas after treatment of the first infection with clotrimazole. (v) The same strain of C. albicans was responsible for the recurrent increases in mouth colonization and was distinct from the recurrent vaginal strain. The results of this case study demonstrate the need for further detailed analyses of full-body mycofloras, strain relatedness, switching repertoires, and changes in drug susceptibility during successive episodes of recurrent vulvovaginal candidiasis.

Antifungal Agents↗
PubMed1988

a/Alpha-specific repression by MAT alpha 2.

The product of the MAT alpha 2 gene is a DNA-binding protein that acts as a repressor of two different sets of cell type-specific genes. In alpha cells, the alpha 2 protein represses the transcription of several a-specific genes. In a/alpha cells, the alpha 2 protein acts together with the product of the MATa1 gene, the a1 protein, to repress several genes used by haploids in the mating process. In addition to the mat alpha 2 mutations that result in defects in both types of regulation, other mat alpha 2 alleles have been described that result in defects in the repression of a-specific genes but that do not affect the ability of the alpha 2 and a1 proteins to interact to repress the haploid-specific genes. We report here the isolation of a new class of mat alpha 2 mutations that do not affect the ability of the alpha 2 protein to repress a-specific genes, but that interfere with the ability of the alpha 2 protein to interact with the a1 protein to repress the haploid-specific genes and establish the a/alpha cell type. These mutations may help determine the means by which the a1 protein interacts with alpha 2 to expand the set of genes under its control.

Amino Acid Sequence↗
PubMed1988

Multiple Candida strains in the course of a single systemic infection.

Species and strain variabilities have been monitored during the history of a prolonged Candida infection in a single compromised bone marrow transplant patient by analyzing sugar assimilation patterns, high-frequency switching repertoires, and Southern blot hybridization patterns with two cloned mid-repeat sequences (Ca3 and Ca7) which are species specific for Candida albicans and one cloned mid-repeat sequence (Ct13-8) which is species specific for Candida tropicalis. Evidence is presented that during the course of this infection (i) two strains of C. albicans and three strains of C. tropicalis were distinguished by their switching repertoires, Southern blot hybridization patterns, and sugar assimilation patterns; (ii) the three C. tropicalis strains were in a high-frequency mode of switching; (iii) two C. tropicalis strains coexisted in the blood and three C. tropicalis strains coexisted in the throat at different times during the history of the infection; (iv) amphotericin B treatment selectively removed one of two C. tropicalis strains coexisting in the blood and this strain exhibited greater susceptibility to amphotericin B in vitro (the remaining strain was subsequently removed from the blood by flucytosine treatment); and (v) both the strain removed from the blood by amphotericin B and the strain removed from the blood by flucytosine reappeared several days later at another site of infection. It is demonstrated for the first time that C. tropicalis is capable of high-frequency switching of colony morphology just as C. albicans is, that there is more than one strain-specific switching repertoire in C. tropicalis, and that a C. tropicalis mid-repeat sequence can be used for discriminating species and assessing strain relatedness, as previously demonstrated for C. albicans mid-repeat sequences.

Adult↗
PubMed1987

Midazolam, diazepam, and placebo as intravenous sedatives for dental surgery.

This study was a comparison of the sedative and amnestic properties of midazolam and diazepam when administered for relief of patient discomfort during dental surgery. It was a double-blind placebo-controlled group study, which entailed the analysis of 60 patients randomly assigned to the three groups: midazolam, diazepam, and placebo. There were 20 patients in each group. Midazolam patients showed superior performance in the parameters of sedation and amnesia when compared to patients who were administered diazepam. Both groups showed better results than the placebo group, which had the best results with the Digit Symbol Substitution Test and the Trieger Test.

Adolescent↗
PubMed1987

High-frequency switching in Candida strains isolated from vaginitis patients.

High-frequency switching and strain variability at the site of infection was assessed in 11 patients with acute Candida albicans vaginitis. By cloning cells directly from the site of infection, it was demonstrated that 4 of the 11 isolates contained multiple-switch phenotypes at the site of infection and that 9 of the 11 isolates were in a high-frequency mode of switching (10(-2) to 10(-3)). Isolates could be separated into four general categories of switching repertoires. To demonstrate that multiple phenotypes at the site of a single infection represented the same strain, EcoRI digests of total cell DNA were separated on agarose gels, and Southern hybridization patterns with two cloned midrepeat sequences were compared.

Candida albicans↗
PubMed1987

Urinary cannabinoids in monitoring abstinence in a drug abuse treatment program.

Urine specimens from 162 adolescents entering a drug treatment program were tested for cannabinoids using a photometric immunoassay (EMITst) and thin-layer chromatography (TLC). The EMITst has a cutoff point of detection 25 ng/mL or less of 9-carboxy-tetrahydrocannabinol. When reported as positive, both tests appeared to be reliable. There were two false-positive EMITst results and three false-positive TLC results in the 67 urine specimens that did not contain cannabinoids. When reported as negative, however, the EMITst with its 100 ng/mL cutoff failed to detect almost 40% of all cannabinoid-positive specimens. Of the 65 chronic marijuana smokers in the present study who stated that they had smoked within two days of their admission into the treatment facility, 17 (26%) went undetected by the 100 ng/mL cutoff used by the EMITst method. In clinical settings such as drug treatment programs, tests for urinary cannabinoids should use a detection threshold at 20 ng/mL or less.

Adult↗
PubMed1986

Development of a competitive enzyme-linked immunosorbent assay for detecting cytomegalovirus antibody.

A competitive enzyme-linked immunosorbent assay (ELISA) for detecting cytomegalovirus (CMV) antibody was developed. The competitive ELISA was five times more sensitive than the complement fixation test (CFT) and twice as sensitive as indirect ELISA. Testing of paired sera from cardiac transplant patients taken before and after transplantation showed good correlation between results of competitive and indirect ELISA and CFT. The competitive ELISA was more successful than CFT or indirect ELISA in detecting passively acquired antibody, but detection of CMV antibody by competitive ELISA immediately after primary CMV infection was unreliable, possibly because of the high affinity of the monoclonal antibody chosen for the horseradish peroxidase conjugate. However, competitive ELISA may well prove to be more suitable than indirect ELISA for detecting CMV antibody in blood donations.

Antibodies, Viral↗
PubMed1986

Adult-onset minimal change nephrotic syndrome: a long-term follow-up.

A series of 89 adult-onset nephrotic patients with minimal changes on renal biopsy was analyzed to compare the rate of response to corticosteroids and cytotoxic agents and the stability of remission or frequency of relapses at different ages. Severe hypertension and diminished renal function were more common in patients aged over 60 years, who formed 22.5% of the group. Seventy-five patients were given a first course of prednisolone in an initial dose of 60 mg/24 hr. After an eight week course of tapering doses of corticosteroids, only 45 of the 75 patients were in complete remission, 55 patients after 16 weeks and eventually 58 lost their proteinuria. The respective estimates of remission were 60%, 76% and 81%. Subsequently, of the 58 treated patients who responded, 24% never relapsed. Fifty-six percent of the patients relapsed on a single occasion or infrequently, and only 21% were frequent relapsers. Cyclophosphamide was used in 36 patients, in two as initial treatment, in 11 because of corticosteroid resistance, and in the remainder because of relapses. The time-course of loss of proteinuria was similar to that following treatment with corticosteroids, 25 (69%) losing proteinuria within 16 weeks. Only four patients failed to lose their nephrotic syndrome. Two of them had presented in acute renal failure and all four were over 60 years of age. The stability of remission after cyclophosphamide was better than that reported for children, only 13 of 36 showing relapses and 66% being in remission at five years, after which no further relapses were seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1985

Long-term outcome for children with minimal-change nephrotic syndrome.

A retrospective study was undertaken to assess the outcome of a cohort of 183 unselected children who presented with the nephrotic syndrome between 1963 and 1969. All subjects showed minimal glomerular changes in biopsy samples and were given conventional steroid therapy. Information was available on 152 children, now aged 14-32 years. Activity persisted longer in patients presenting at an early age. The outcome for most of the children was favourable. Only 10 patients (5.5%), all of whom presented with initial symptoms before their 6th birthday, continued to have steroid-responsive relapses in adult life. There were 11 deaths, of which 7 (4% of the series) were from avoidable complications of the disorder.

Adolescent↗
PubMed1985

Why do patients with lupus nephritis die?

Over 20 years 42 of 138 patients with systemic lupus erythematosus "died"--that is, suffered actual death or went into terminal renal failure, or both; data from 41 were available for analysis. In most patients the causes of death were multiple. Twenty seven patients went into terminal renal failure, of whom 25 were offered dialysis treatment. Three regained renal function later, 12 survived on dialysis or with functioning kidney allografts--almost all with inactive lupus--but 13 died after starting dialysis, most within a few weeks or months. The principal causes were active lupus or infection. In those patients with renal failure after rapid deterioration in renal function (n = 14) there were nine deaths, while of 10 patients with a slow evolution into renal failure, only four died. Four patients with impaired and 10 with normal renal function died, again most often from complications of lupus or from infection. Vascular disease was a major cause of death in seven patients, all but two of whom were young; of 15 postmortem examinations, eight showed severe coronary artery atheroma, and three surviving patients required coronary bypass operations. Analysis of the timing of death or entry into renal failure showed that in 12 out of 13 patients who died within two years of onset the lupus was judged to be active, while this was true in only eight out of 19 patients who died later. Six of the seven vascular deaths occurred later than two years from onset, while only nine of 26 renal "deaths" occurred before two years; deaths from infections (n = 13) were distributed equally. Despite this and aggressive treatment of active disease, the principal cause of actual death was uncontrolled lupus.

Adolescent↗