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Biomedical subjects

J Clark

Publications and source records attributed to J Clark.

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

The t(X;18)(p11.2;q11.2) translocation found in human synovial sarcomas involves two distinct loci on the X chromosome.

A high proportion of synovial sarcomas contain the reciprocal translocation t(X;18)(p11.2;q11.2). We have previously localized the breakpoint on the X chromosome between the X chromosome marker DXS255 and an ornithine aminotransferase (OAT) pseudogene region designated OATL2. Subsequently by fluorescence in situ hybridization (FISH) we provided evidence that YACs corresponding to the OATL2 locus spanned the break-point. In order to confirm the position of this breakpoint cosmids corresponding to the OATL2 region were isolated. Most of these cosmids mapped to four cosmid contigs designated C1-C4. Analysis of two contigs, C1- and C4, using FISH established that in four of six synovial sarcomas examined the breakpoint occurs between these two contigs: C1 lies distal to the break-point while C4 is proximal. In contrast we provide evidence that the breakpoint in the remaining two tumours mapped to a second pseudogene region called OATL1 that is telomeric to the OATL2 locus. This heterogeneity of the breakpoint position on the X chromosome explains why in previous mapping studies there have been discrepancies between the results obtained by different laboratories.

Chromosome Mapping↗
PubMed1993

From synapse to vesicle: the reuptake and storage of biogenic amine neurotransmitters.

Biogenic amine transport systems in the presynaptic plasma membrane and the synaptic vesicle provide a mechanism for rapidly terminating the action of released transmitters and for recycling neurotransmitters. Alterations in the activity of these transporters, either by endogenous regulatory mechanisms or by drugs, affect the regulation of synaptic transmitter levels. For drugs such as antidepressants and stimulants that interact with these transport systems, the therapeutic and behavioral consequences are profound. Now that the cDNAs encoding the transporters have been isolated, we can expect rapid progress in understanding how the individual proteins work at the molecular level to couple ion gradients to the reuptake and storage of biogenic amine neurotransmitters.

Amino Acid Sequence↗
PubMed1993

Selective amplification of additional members of the ADP-ribosylation factor (ARF) family: cloning of additional human and Drosophila ARF-like genes.

The ADP-ribosylation factor (ARF) family is one of four subfamilies of the RAS superfamily of low molecular weight GTP-binding proteins (G proteins). Highly degenerate oligonucleotides encoding two conserved regions were used in a PCR reaction to amplify cDNAs encoding each of the known ARF proteins and eight additional cDNA fragments encoding previously unreported human members of the ARF family. Additional sequences were obtained from yeast or fly libraries by using this technique. These oligonucleotides specifically amplify members of the ARF family but not the structurally related G protein alpha subunits or members of the other three subfamilies of the RAS superfamily. Fragments obtained by PCR were used to obtain full-length sequences encoding highly homologous ARF-like (ARL) gene products from human and Drosophila melanogaster libraries, termed ARL2 and Ar184F, respectively. The encoded proteins are each 184 amino acids long and are 76% identical, with 40-45% identity to human ARF1 and Drosophila arf-like (arl) proteins. These genes appear to be generally expressed in human tissues and during Drosophila development. The purified human ARL2 protein differed in several biochemical properties from human ARF proteins, including the complete absence of ARF activity. Thus, the ARF family of low molecular weight GTP-binding proteins includes at least 15 distinct but structurally conserved members, including both the functionally conserved ARF proteins and the functionally disparate ARL proteins. The latter proteins currently comprise two distinct gene products in Drosophila (arl and ARL84F) and one in man (ARL2).

ADP-Ribosylation Factor 1↗
PubMed1993

Randomized double-blind trial of high- and low-dose fleroxacin versus norfloxacin for complicated urinary tract infection.

Patients were entered in a double-blind, placebo-controlled, multicenter study to compare low- and high-dose fleroxacin with norfloxacin for the treatment of complicated urinary tract infection (UTI). A total of 296 patients were enrolled; 102, 97, and 97 patients were randomized to receive 200 mg of fleroxacin (low-dose), 400 mg of fleroxacin (high-dose), both once daily, or 400 mg of norfloxacin twice daily, respectively, for 10 days. Of these patients, 101, 94, and 95 were included in the safety analysis, and 71, 61, and 58 in the efficacy analysis. The main reason for exclusion from the efficacy analysis was failure to isolate a pathogen at baseline. The groups were comparable with respect to demographics. In the low-dose fleroxacin group, 68 (96%) of 71 patients had bacteriologic cures (eight with superinfection), compared with 56 (92%) of 61 in the high-dose fleroxacin group (two with superinfection) and 52 (90%) of 58 in the norfloxacin group (four with superinfection). Escherichia coli was the most frequent isolate in all groups. In the low-dose fleroxacin group, clinical cure was recorded in 61 (86%) of 71, improvement in six, and failure in four. In the high-dose group, clinical cure was noted in 58 (95%) of 61 patients, improvement in two, and failure in one. In the norfloxacin group, 50 (86%) of 58 patients were clinically cured, four were improved, and four failed. Clinical adverse events were reported by 22 (22%) of 101, 36 (38%) of 94, and 19 (20%) of 95 patients in the low-dose fleroxacin, high-dose fleroxacin, and norfloxacin groups, respectively. Insomnia and nausea were reported most frequently in the fleroxacin groups, and nausea and headache were most common in the norfloxacin group. The efficacy and safety of low-dose fleroxacin are comparable to those of norfloxacin for treatment of complicated UTI.

Adult↗
PubMed1993

Apoptotic bodies in a murine model of alcoholic liver disease: reversibility of ethanol-induced changes.

The aim of this study was to investigate the effects of ethanol exposure on the location and number of apoptotic bodies in murine liver. Livers from 21 control mice were compared with those of 41 animals exposed to ethanol vapour by inhalation for up to 23 days. In the control livers, apoptotic bodies were identified in association with 36 per cent of the terminal hepatic venules examined and 88 per cent of these bodies were located in the first two rows of perivenular hepatocytes. By comparison, in the ethanol-exposed group, apoptotic bodies were observed in association with 72 per cent of the terminal hepatic venules examined and more were found further from them. This increase in the number of apoptotic bodies was shown to depend on the duration of ethanol exposure and, furthermore, the effects of ethanol were shown to be completely reversed by a period of abstinence. These results indicate that ethanol exposure has time-dependent, reversible effects on both the location and the number of apoptotic bodies in murine liver. This extends knowledge gained from previous work on rat livers.

Animals↗
PubMed1993

Isolation and analysis of a cDNA clone encoding the small subunit of ADP-glucose pyrophosphorylase from wheat.

A full-length cDNA clone from hexaploid bread wheat, encoding the small subunit of ADP-glucose pyrophosphorylase, has been isolated from an endosperm cDNA library. The cDNA insert has an open reading frame which encodes a protein of 473 amino acids (52.1 kDa). The presence of a chloroplast/amyloplast transit peptide of 22 amino acids is proposed. The deduced amino acid sequence exhibits a high degree of homology with the small subunit ADP-glucose pyrophosphorylase proteins from rice (with 90% of identical amino acids) and potato (with 86% of identical amino acids) and contains conserved sequence elements which are thought to represent the substrate binding and allosteric activator sites. The genes are organised as single-copy loci on chromosomes 7A, 7B and 7D in the wheat genome and are highly expressed during grain development. Homologous transcripts are expressed in leaves and roots.

Amino Acid Sequence↗
PubMed1993

Expression, organisation and structure of the genes encoding the waxy protein (granule-bound starch synthase) in wheat.

A full-length cDNA clone representing the waxy protein (GBSSI) isolated from a hexaploid wheat developing grain cDNA library has been used to characterise the organisation and expression of the waxy genes in wheat. The genes are organised as a triplicate set of single copy homeoloci on chromosome arms 4AL, 7AS and 7DS. The genes are active throughout grain filling where the main 2.3 kb transcript accumulates to high levels. The 2.3 kb transcript is not expressed in leaves where the presence of a related, but less homologous, transcript of 1.6 kb suggests that a different set of genes operates. Gel analysis and purification of the waxy protein isolated from starch granules, followed by N-terminal amino acid sequencing in conjunction with data from hybrid select translation experiments and sequence analysis of the cDNA, shows that the mature protein has a molecular weight of 60kDa (615 amino acids) and that the preprotein includes a chloroplast/amyloplast transit peptide of 7kDa (75 amino acids). Analysis of the derived amino acid sequence and alignment with five other plant waxy proteins shows that they exhibit substantial homology. The wheat protein differs from all others in that it contains an 11 amino acid insertion towards the N-terminus. The protein contains the conserved motif KTGGL found in other waxy proteins and which has been implicated as the active site in glycogen synthase.

Amino Acid Sequence↗
PubMed1993

The majority of G0 transgenic mice are derived from mosaic embryos.

Most transgenic mice are generated by the direct microinjection of DNA fragments into the pronuclei of fertilized eggs. It has been generally assumed that the majority of integration events occur prior to the first round of chromosomal DNA replication (Palmiter and Brinster, 1986). In this study we have determined by comparison of PCR, Southern blot and transmission frequencies that at least 62% of integration events generate a mosaic (somatic and/or germline) G0 transgenic mouse. Furthermore, the statistical probability of transgene-containing cells segregating to the various early embryo lineages implies that this is probably an underestimate of the true mosaic frequency. Thus, the majority of DNA injected into fertilized mouse eggs intergates after the first round of chromosomal DNA replication, therefore most G0 transgenic mice are derived from a mosaic embryo.

Animals↗
PubMed1993

Comparison of four methods in the diagnosis of Clostridium difficile disease.

Nine hundred forty-five stool specimens from patients suspected of having Clostridium difficile disease were examined using a cell culture cytotoxicity assay (CTA), two enzyme immunoassay (EIA) kits (Cytoclone for toxins A and B; VIDAS for toxin A) and a latex agglutination assay (CDT). One hundred nineteen specimens had positive titers (> or = 90) in the CTA; clinical review of 16 discordant samples and 49 controls supported the significance of 90 as the positive cut-off titer. The performance of the two EIAs and the latex assay was assessed relative to CTA titers of the samples. Sensitivity was < or = 50% for all three assays for the 24 specimens with CTA titers of 90, but it reached 97-100% for the two EIAs and 84% for the latex assay at titers of > or = 2,250. The Cytoclone EIA exhibited higher sensitivity at the lower positive titers. Overall, specificity of the methods ranged from 96.7% (CDT latex assay) to 99.1% (Cytoclone EIA).

Bacterial Proteins↗
PubMed1993

Aggressive angiomyxoma of the female pelvis and perineum: case report and literature review.

A rare neoplasm was described in young white women in 1983. Its gelatinous appearance, histologic characteristics, locally infiltrative nature, and local recurrence are discussed. Twenty-five cases have been previously reported, our case being the first one in the United Kingdom. The value of a preoperative computed tomographic scan and a systematic anatomic, microscopic, and pathologic identification of all perineal tumors are described.

Adult↗
PubMed1993

Dysplastic pleomorphic adenoma of the sublingual salivary gland.

All tumours of the sublingual gland are rare and paradoxically the large majority are malignant. A case of pleomorphic adenoma in the sublingual gland is described. The tumour showed areas of dysplasia and the difficulties in distinguishing this from benign pleomorphic adenoma or carcinoma in pleomorphic adenoma are considered, and the literature is reviewed.

Adenocarcinoma↗
PubMed1993

Morbidity with contemporary prostate biopsy.

To determine the incidence of complications associated with contemporary prostate biopsy, a review of 670 men undergoing transrectal prostate biopsy using 18 gauge biopsy needles was conducted. Of the men 580 received 1 to 3 days of ciprofloxacin antibiotic prophylaxis. A total of 16 patients (2.1%) suffered complications of whom 4 (0.6%) required hospitalization. These data demonstrate the low morbidity associated with contemporary transrectal prostate biopsy.

Adult↗
PubMed1993

Combined modality therapy for stage IIIA non-small cell carcinoma of the lung.

53 patients with stage IIIA non-small cell carcinoma of the lung (NSCCL) were treated with multimodality therapy consisting of induction radiotherapy (55.8 Gy) and two cycles of concurrent chemotherapy with cisplatin, 25 mg/m2 for 4 days by continuous infusion and bolus etoposide, 100 mg/m2 on days 2 and 4 of each cycle followed by surgery and adjuvant chemotherapy. Of 53 evaluable patients, 47 achieved clinical responses (9 complete response, 38 partial response) after induction therapy for a response rate of 89%. 47 patients were resectable after induction therapy, but 8 patients refused surgery and 6 patients were not eligible for surgery based on poor pulmonary function (medical contraindications). 33 patients underwent thoracotomy and in 6 patients, resection was technically unfeasible. Thus complete surgical resection was accomplished in 27 patients. After all therapy, 28 patients achieved a complete response (53%) and 19 patients a partial response (36%). Toxicities were mild. At a maximum of 75 months (median, 28 months) of follow-up, the median survival of the entire group is 24 months. The median survival of resected patients has not been reached; their 6-year survival rate is 55%. Unresected patients survived for a median of 11 months. This multimodality regimen is well-tolerated, induces a high response and resectability rate and prolongs survival in resected patients.

Adult↗
PubMed1993

Detection of thirty-second cognitive activations in single subjects with positron emission tomography: a new low-dose H2(15)O regional cerebral blood flow three-dimensional imaging technique.

Positron emission tomography regional CBF (rCBF) studies of cognitive processes have traditionally required 30-60 mCi of H2(15)O per scan and intersubject averaging to achieve statistical significance. However, intersubject anatomical, functional, and disease variability can make such an approach problematic. A new method that produces significant results in single subjects is presented. It is based upon high-sensitivity three-dimensional imaging and a "slow" bolus administration of < 15 mCi of H2(15)O per scan. The method is validated in four normal volunteers using control and auditory-language activation tasks with four scans per condition and statistical parametric mapping analysis. It is demonstrated that the rCBF distribution associated with the cognitive state is detected during the arrival of radiotracer in the brain. This occurs over 30 s and constitutes a critical temporal window during which stimulation should be performed. A 90-s acquisition time is found to produce results of greater significance than a 60-s acquisition time. The implications of the results and the functional neuroanatomical findings are discussed. This method is suitable for the study of individual functional neuroanatomy in many neuropsychological, pharmacologic, and symptom states in normal subjects and in patients with psychiatric and neurologic disorders.

Adult↗
PubMed1993

Mortality among injecting drug users: a critical reappraisal.

STUDY OBJECTIVE: The aim was to quantify all cause mortality among injecting drug users. DESIGN: This was a retrospective analysis of 1989 data on injecting drug users and mortality obtained from three independent agencies: the Procurator Fiscal's Office, the General Register Office, and the Scottish HIV-test register. SETTING: Greater Glasgow, Scotland. SUBJECTS: Drug injectors, estimated population 9424. MAIN RESULTS: 81 names were found using the three sources to identify deaths. After removing duplicates, 51 deaths were found. This represented a mortality rate of 0.54% in the estimated population. Among female injectors the mortality rate was 0.85%, significantly higher than the rate of 0.42% among male injectors (95% CI for the true difference in mortality rates between female and male injectors was 0.31%-0.55%). Over 90% of deaths were attributed to overdose or suicide. Although AIDS caused only one death, 19% of cases (5/27) whose HIV antibody status could be ascertained were positive. The mortality rate among HIV positive injectors (3.8%) was significantly higher than among HIV negative injectors (0.49%). CONCLUSIONS: Comprehensive coverage using three data sources revealed a far greater annual number of all cause deaths among injectors than would have been expected from previous research. The observed mortality rate was lower than in previous studies where the denominators used to calculate rates had an element of underenumeration. For the foreseeable future it is unlikely that AIDS will have much impact on mortality among injectors in Glasgow, because of the low prevalence of HIV infection among injectors in the city, and because HIV positive injectors are dying for reasons other than AIDS; rather, overdose and suicide will continue to be the main causes of death.

Adolescent↗
PubMed1993

Toxicokinetics of pentachloroanisole in F344 rats and B6C3F1 mice.

1. Toxicokinetics of pentachloroanisole (PCA) were studied in F344 rat and B6C3F1 mouse of both sexes by gavage at doses of 10, 20 and 40 mg/kg and by i.v. at 10 mg/kg. 2. PCA was rapidly demethylated to pentachlorophenol (PCP) in both rat and mouse and the resulting PCP plasma concentrations were much higher than that of parent PCA due to the much smaller apparent volume of distribution of PCP. 3. Peak plasma concentrations of PCA and PCP increased with dose in both rat and mouse. 4. Bioavailability of PCA was low in both rat and mouse and was sex independent. 5. The high plasma concentrations and relatively long biological half-life of PCP in both species after both i.v. and oral dosing with PCA indicate possible bioaccumulation of PCP upon multiple oral administrations of PCA.

Animals↗