Assay of laminin fragments in the assessment of renal disease.
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Adult↗
Biomedical subjects
S A Taylor
Publications and source records attributed to S A Taylor.
Early urinary markers of target nephron segments as studied in cadmium toxicity.
A number of chemicals may adversely affect one or more of the anatomical structures of the kidney, such as the glomerulus, the tubular apparatus, the medullary, or interstitial cells. To recognize subclinical renal dysfunction, a battery of new, non-invasive tests was applied in comparison to established ones. The study on cadmium exposed subjects, performed within the framework of a collaborative European research project, exemplifies the concept of target selectivity within a nephron. One hundred seventy-two subjects were classified according to urinary cadmium excretion as controls (< 1.5 micrograms/g creatinine), or subjects with moderate or high cadmium body burden (1.5 to 5 micrograms/g creatinine, > 5 micrograms/g creatinine). Twenty-six urinary analytes (such as serum derived proteins, tubular enzymes, eicosanoids) and four plasma markers, related to the function or integrity of specific nephron segments, were investigated in a cross-sectional study. The group with the moderate cadmium body burden showed alterations of proximal tubular integrity, that is, increased excretion of tubular brush-border antigens. The group with higher cadmium body burden revealed an involvement of the whole nephron. The most prominent quantitative changes were found for the glomerular markers high molecular weight proteins, and thromboxane B2 and for the proximal tubular markers retinol binding protein, alpha 1-microglobulin, N-acetyl-beta-D-glucosaminidase, and the intestinal alkaline phosphatase. A diagnostic approach to screen for nephrotoxicity due to environmental hazards like cadmium should include proximal tubular markers (alpha 1-microglobulin and tubular enzymes, that is, intestinal alkaline phosphatase) but the measurement of glomerular markers is also advisable.
Adult↗
Nicotine addiction. How can we help?
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Family Practice↗
Comparison of several new chromogenic galactosides as substrates for various beta-D-galactosidases.
The kinetic characteristics of beta-galactosidases from bovine liver and testes, Escherichia coli, Aspergillus niger and Jack bean were studied using five newly-developed colorimetric substrates. All the chromophores released by enzyme hydrolysis had high extinction coefficients in the visible region of the spectrum. Varying amounts of substrate inhibition were found with each of these substrates (VBzTM-Gal, VLM-Gal, VLPr-Gal, VQM-Gal and VQPr-Gal), but this was not a significant problem if the correct assay conditions were used. The substrates attached particularly tightly to the active centre of E. coli beta-D-galactosidase resulting in low Km values. The data suggest that the chemical properties of the heterocyclic portion of the aglycone distant from the glycosidic oxygen do not affect the substrate specificity and the substrate inhibition can be attributed to interactions not involving the catalytic site. When the product of the maximum observed velocity (Vm) and the molar absorption coefficient is calculated for each substrate, the relative merits of the substrates for the assay of each enzyme can be assessed. The beta-D-galactosidases from fungal and bacterial sources hydrolysed the substrates most efficiently, indicating that they may be of particular value in areas of molecular biology and biotechnology.
Animals↗
Evaluation of combination chemotherapy and phase II agents in pancreatic adenocarcinoma. A Southwest Oncology Group study.
BACKGROUND: Pancreatic carcinoma responds poorly to conventional chemotherapy. To identify potentially useful agents, a sequence of clinical trials were done. METHODS: A series of Phase II randomized trials were done by the Southwest Oncology Group in which patients with metastatic or advanced pancreatic cancer were randomized to receive single agents (methylglyoxal-bis-guanylhydrazone [MGBG], dihydroxyanthracenedione [DHAD], and aziridinylbenzoquinone [AZQ]) or a combined regimen of 5-fluorouracil, doxorubicin, mitomycin C, and streptozotocin (FAM-S). Toxicity, response, and survival were determined. RESULTS: Seventy-one patients received FAM-S and 82, the Phase II single agents. Response rates (95% confidence intervals) for the various treatments were: FAM-S, 11% (0%, 21%); MGBG, 6% (0.8%, 21%); DHAD, 0% (0%, 12%); and AZQ, 0% (0%, 16%). The median survival times were: FAM-S Group, 4.8 months and Phase II agent Group, 3.4 months. CONCLUSIONS: The FAM-S regimen and the Phase II agents tested did not have substantial antitumor activity in pancreatic cancer. The use of new agents as initial therapy is reasonable.
Adenocarcinoma↗
Phase II evaluation of echinomycin (NSC-526417) in patients with central nervous system malignancies. A Southwest Oncology Group study.
The objective of this trial was to determine the efficacy of echinomycin (1.2 mg/m2) administered on a weekly times four schedule in the treatment of patients with recurrent or progressive central nervous malignancies despite adequate radiotherapy. Thirty-five patients were registered on study. The majority of patients (20) had glioblastoma multiforme. Ten had anaplastic astrocytoma. Eight patients had received prior nitrosoureas. SWOG performance status was 1 in 11 patients and 2 in 22. The median age was 51 years (25-75 years). One patient had a partial remission (3%:95% confidence interval: 1%-16%). Twenty two patients had progressive disease. The median survival was 5.9 months. Toxicity was primarily gastrointestinal with nausea and vomiting in 13 patients and nausea only in 11 patients. Hepatotoxicity occurred in 10 patients. Echinomycin given at this dose and schedule is not effective in treating patients with recurrent or progressive glioblastoma multiforme or anaplastic astrocytomas.
Adult↗
De novo expansion of a (CAG)n repeat in sporadic Huntington's disease.
Huntington's disease (HD) chromosomes contain an expanded unstable (CAG)n repeat in chromosome 4p16.3. We have examined nine families with potential de novo expression of the disease. With one exception, all of the affected individuals had 42 or more repeat units, well above the normal range. In four families, elderly unaffected relatives inherited the same chromosome as that containing the expanded repeat in the proband, but had repeat lengths of 34-38 units, spanning the gap between the normal and HD distributions. Thus, mutation to HD is usually associated with an expansion from an already large repeat.
Adult↗
The isolation of cDNAs within the Huntington disease region by hybridisation of yeast artificial chromosomes to a cDNA library.
Flanking recombination events have defined the Huntington Disease gene candidate region to between D4S10 and D4S98, about 2.2Mb. Because of the large size of the candidate region and the likely large number of genes within it we decided to screen cDNA libraries with probes generated from whole Yeast Artificial Chromosomes (YACs) containing parts of this region. We have thus far used 4 YACs ranging in size from 180kb to 600kb covering 880kb and have isolate 13 cDNA clones, 7 of which are unique. Three of the 13 clones contain parts of the 3' untranslated region of the alpha-adducin gene. One YAC of 600kb could not be purified from two yeast chromosomes, therefore this YAC probe had a net complexity of 1.8Mb. Even so this probe identified a cDNA from the HD candidate region indicating that very large YACs may be used as probes.
Chromosome Mapping↗
A gene from chromosome 4p16.3 with similarity to a superfamily of transporter proteins.
We have previously used exon amplification to identify the ADD1 gene in cosmid Y24 from the Huntington's disease (HD) region of 4p16.3. The same technique has now yielded a second gene from this cosmid. This gene appears to encode a novel member of a superfamily of transporter proteins that includes active and passive transporters in a number of species. The predicted protein of 455 amino acids displays sequence similarity with the E. coli tetracycline resistance efflux protein encoded by cloning vector pBR322, and with a number of related transporters. This gene should open a route to isolating additional mammalian members of this growing superfamily.
Amino Acid Sequence↗
Urea inhibition of urinary N-acetyl-beta-D-glucosaminidase is mixed-type and sensitive to changes of pH away from the optimum.
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Acetylglucosaminidase↗
Characterization of the original Christmas disease mutation (cysteine 206----serine): from clinical recognition to molecular pathogenesis.
Christmas disease was first reported as a distinct clinical entity in two manuscripts published in 1952. The eponym associated with this disorder, is the surname of the first patient examined in detail and reported by Biggs and colleagues in a paper describing the clinical and laboratory features of seven affected individuals. This patient has severe factor IX coagulant deficiency (less than 0.01 units/ml) and no detectable circulating factor IX antigen (less than 0.01 units/ml). Coding sequence and splice junctions of the factor IX gene from this patient have been amplified in vitro through the polymerase chain reaction (PCR). One nucleotide substitution was identified at nucleotide 30,070 where a guanine was replaced by a cytosine. This mutation alters the amino acid encoded at position 206 in the factor IX protein from cysteine to serine. The non conservative nature of this substitution, the absence of this change in more than 200 previously sequenced factor IX genes and the fact that the remainder of the coding region of this gene was normal, all provide strong circumstantial evidence in favour of this change being the causative mutation in this patient. The molecular characterization of this novel mutation in the index case of Christmas disease, contributes to the rapidly expanding body of knowledge pertaining to Christmas disease pathogenesis.
Amino Acid Sequence↗
Differential termination of primer extension: a novel, quantifiable method for detection of point mutations.
We have developed a novel technique that is useful for the rapid detection of previously characterized point mutations in the human genome. The method relies on the differential termination of primer extension being performed simultaneously on normal and mutant template molecules in the presence of a selectively limited complement of deoxynucleotide triphosphates. We have used this technique to determine the carrier status of two potential carriers of a hemophilia B mutation at codon 145 in the factor IX gene. In addition, the technique has been used to quantify the levels of mutant sequence in several tissues of a hemophilia B patient who is a somatic mosaic for a point mutation at codon 350.
Base Sequence↗
Phase II evaluation of didemnin B in advanced adenocarcinoma of the kidney. A Southwest Oncology Group study.
The Southwest Oncology Group studied the response rate and toxicity of didemnin B (3.47 mg/m2 i.v. q 28 days) in patients with advanced renal cell carcinoma. There were no responses in 22 response evaluable patients. Toxicity was significant with 10 patients having grade 3 or 4 toxicity. Toxicity seen included nausea and vomiting, exacerbation of coronary artery disease, hyperglycemia, anorexia, diarrhea and hepatitis. Didemnin B was toxic but inactive in patients with renal cell treated at this dose.
Adenocarcinoma↗
The effect of grazing location and oronasal treatment with bull urine on reproductive performance and serum prolactin concentrations of beef heifers.
Grazing location and biostimulatory treatments were imposed on 55 Brangus and crossbred heifers in a 2x2x2 factorial arrangement. Grazing locations (postweaning) were semi-desert rangeland with supplementation or irrigated small grains pasture. Biostimulatory treatment involved either weekly oronasal application of bull urine or no treatment (control). The duration of bull urine treatments was 8 weeks. Grazing location affected heifer weights from February through August (P<0.01). Rate of weight gain on irrigated pasture exceeded native range (P<0.01). Cyclicity was similar between the location groups before the treatment period. Post-treatment cyclicity rates of heifers were 25 and 78% for native range and irrigated pasture, respectively (P<.01). Twenty-five percent of cyclic heifers grazing native range went into anestrus during this treatment period, while no loss of cyclicity was observed in the heifers on irrigated pasture (P<0.10). Heifers maintained on irrigated pasture exhibited more standing estrus following synchronization (P<0.10), higher pregnancy rates following breeding (P<0.05), heavier fall weights (P<0.01), higher body condition scores (P<0.01), and greater pelvic widths (P<0.05) than those on native range. Cyclic heifers grazing native range had prolactin levels twice those of irrigated pasture heifers. Serum growth hormone levels were not consistently affected by treatments. Heifers which became pregnant while grazing irrigated pasture had much lower prolactin concentrations in serum collected in January than the noncyclic heifers.
Journal Article↗
Combination cisplatin and dichloromethotrexate in patients with advanced bladder cancer. Phase 2. A Southwest Oncology Group study.
The combination of cisplatin and dichloromethotrexate is a pharmacologically rational strategy designed to avoid the nephrotoxicity associated with the systemic chemotherapy of bladder cancer. Of 97 patients with metastatic bladder cancer entered into this study 73 with good renal function received cisplatin and dichloromethotrexate, while 24 with impaired renal function received dichloromethotrexate alone. No responses were noted in the latter group. A 42% response rate (95% exact confidence interval 30.0 to 55.2%), including 9 patients (14%) who achieved a complete response, was observed in the combination group. The toxicity patterns in both groups of patients were consistent with the hypothesis that renal toxicity would be ameliorated with the use of the methotrexate analogue. However, the failure to achieve a higher overall response rate despite near maximum tolerated doses of dichloromethotrexate discourages future studies with this agent. New agents for metastatic bladder cancer should be tested as first line therapy.
Adult↗
Estrus induction in four species of voles (Microtus).
Male-induced estrus was examined in montane (Microtus montanus), meadow (M. pennsylvanicus), prairie (M. ochrogaster), and pine (M. pinetorum) voles. Duration of male contact needed for receptivity, effects of parity, and vaginal cytology were assessed. Among nulliparous females, montane voles attained receptivity with less male contact than prairie voles. Meadow and pine voles showed very low receptivity rates. Among parous females, montane and meadow voles did not differ in duration of male contact needed for receptivity and required less than prairie voles. Overall, parous females had higher receptivity rates than nulliparous females. When isolated from males, prairie and pine voles had more leukocytes and fewer cornified cells in vaginal smears than montane or meadow voles. Species differences in estrus induction are discussed in relation to species differences in social organization.
Animals↗
Ejaculate disruption in two species of voles (Microtus): on the PEI matching law.
We permitted male prairie and montane voles (Microtus ochrogaster and M. montanus) five thrusts, without ejaculation, with a female at variable times after a 1st male ejaculated. In both prairie and montane voles, there were fewer sperm, in relation to control conditions, in the female's tract 1 hr after ejaculation if the female received thrusts immediately or 15 min after the ejaculate. There was no such effect after a 50-min delay. There was no significant decrease in litter production in prairie voles caused by thrusts delivered either immediately or after a 15-min delay. Sperm transport in these species is susceptible to disruption for a longer period than in deer mice or rats. The proposal that the postejaculatory interval protects a male from disrupting its own sperm transport (the PEI matching law) appears not to hold for these species.
Animals↗
Cloning of the alpha-adducin gene from the Huntington's disease candidate region of chromosome 4 by exon amplification.
We have applied the technique of exon amplification to the isolation of genes from the chromosome 4p16.3 Huntington's disease (HD) candidate region. Exons recovered from cosmid Y24 identified cDNA clones corresponding to the alpha-subunit of adducin, a calmodulin-binding protein that is thought to promote assembly of spectrin-actin complexes in the formation of the membrane cytoskeleton, alpha-adducin is widely expressed and, at least in brain, is encoded by alternatively spliced mRNAs. The alpha-adducin gene maps immediately telomeric to D4S95, in a region likely to contain the HD defect, and must be scrutinized to establish whether it is the site of the HD mutation.
Alternative Splicing↗