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Biomedical subjects

B Barton

Publications and source records attributed to B Barton.

At least 19 recordsLinked to original sources
PubMed1999

Genes specific for the biosynthesis of clavam metabolites antipodal to clavulanic acid are clustered with the gene for clavaminate synthase 1 in Streptomyces clavuligerus.

Portions of the Streptomyces clavuligerus chromosome flanking cas1, which encodes the clavaminate synthase 1 isoenzyme (CAS1), have been cloned and sequenced. Mutants of S. clavuligerus disrupted in cvm1, the open reading frame located immediately upstream of cas1, were constructed by a gene replacement procedure. Similar techniques were used to generate S. clavuligerus mutants carrying a deletion that encompassed portions of the two open reading frames, cvm4 and cvm5, located directly downstream of cas1. Both classes of mutants still produced clavulanic acid and cephamycin C but lost the ability to synthesize the antipodal clavam metabolites clavam-2-carboxylate, 2-hydroxymethyl-clavam, and 2-alanylclavam. These results suggested that cas1 is clustered with genes essential and specific for clavam metabolite biosynthesis. When a cas1 mutant of S. clavuligerus was constructed by gene replacement, it produced lower levels of both clavulanic acid and most of the antipodal clavams except for 2-alanylclavam. However, a double mutant of S. clavuligerus disrupted in both cas1 and cas2 produced neither clavulanic acid nor any of the antipodal clavams, including 2-alanylclavam. This outcome was consistent with the contribution of both CAS1 and CAS2 to a common pool of clavaminic acid that is shunted toward clavulanic acid and clavam metabolite biosynthesis.

Amino Acid Sequence↗
PubMed1998

Cerebral blood flow velocity in patients with subclinical portal-systemic encephalopathy.

UNLABELLED: Alterations in cerebral blood flow (CBF) are implicated in the etiology of portal-systemic encephalopathy. We hypothesized that CO2 reactivity of the cerebral circulation may be impaired in subjects with chronic liver disease (CLD) who also had subclinical portal-systemic encephalopathy (SPSE). We compared the relationship between PETCO2 and cerebral blood flow velocity in 10 patients with CLD with those of 10 healthy control subjects. Middle cerebral artery mean blood flow velocity (MCAMFV) was measured using transcranial Doppler during rest, hyperventilation, and hypoventilation. The degree of SPSE was quantified by using psychometric testing. Patients with CLD had poorer psychometric test scores compared with control subjects. Patients with CLD had lower PETCO2, MCAMFV, and blood pressure values and higher heart rates, differing from control subjects in all ventilation states. However, CO2 reactivity, the rate of change in MCAMFV to changes in ventilation (expressed as percent change in CBF velocity per mm Hg change in PETCO2) was similar for both groups (4.6% +/- 0.6% vs 4.2% +/- 0.5% for patients with CLD versus control subjects, P = 0.15). IMPLICATIONS: Psychometric test scores in patients with chronic liver disease revealed subclinical impairment compared with control subjects. Transcranial Doppler measurements of middle cerebral artery blood flow with varying PETCO2 were conducted, but the CO2 response of patients with liver disease was within the range of control subjects.

Adult↗
PubMed1997

Analysis of a commercially improved Penicillium chrysogenum strain series: involvement of recombinogenic regions in amplification and deletion of the penicillin biosynthesis gene cluster.

Several commercially improved strains of Penicillium chrysogenum have been shown to carry amplifications of the entire penicillin biosynthesis gene cluster. Analysis previously carried out using the strain BW 1890 has here been extended to the characterisation of other members of the SmithKline Beecham strain improvement series. We have determined the length of the amplicon to be 57.4 kb and shown a general increase in copy number and penicillin titre through the series. Sequence analyses of the promoter regions of the acvA, ipnA and aat genes in the high titre strain BW 1901, and comparisons with wild-type sequences have not identified any potentially titre-enhancing mutations. In addition, cDNA screening has failed to identify any further transcribed elements within the co-amplified region. The homogeneity of hybridisation patterns and the identification and analysis of a single copy revertant has shown that the amplification is of a direct tandem nature and we propose a model of chromatid misalignment and recombination as its mode of generation. Hybridisation analysis of penicillin non-producing mutants has indicated the loss, in all those investigated, of the entire penicillin biosynthesis gene cluster, similarities between the deletion junctions in these strains and comparison with previously published data indicating the presence of recombinogenic regions flanking the penicillin biosynthesis gene cluster.

Chromosome Mapping↗
PubMed1994

The effect of caffeine on digital haemodynamics.

Caffeine has been shown to increase mean blood pressure, but studies documenting the effect of caffeine on digits are lacking. We evaluated the effect of caffeine on digital blood pressure and pulse volume in normal volunteers. In the first part of the study, 24 subjects were given water containing either 200 mg of caffeine or placebo. Bilateral brachial and middle finger digital pressures were measured at room temperature before ingestion and at 30 and 60 minutes after ingestion. In the second part of the study, pulse volume recordings (PVRs) were obtained in 24 subjects at the level of the distal phalanx of the middle finger of one hand immediately prior to beverage ingestion and at 10 minute intervals for 90 minutes. Differences in mean digital systolic pressure, digital/brachial index, or PVR amplitude between the control and caffeine groups were not statistically significant. The administration of caffeine was found not to alter the haemodynamics of digital blood flow or digital pressure in this population.

Adolescent↗
PubMed1994

Sexual maturation and obesity in 9- and 10-year-old black and white girls: the National Heart, Lung, and Blood Institute Growth and Health Study.

OBJECTIVE: To assess the relationship between pubertal maturation and obesity in 9- and 10-year-old black and white girls. METHOD: Cross-sectional analysis of cohort baseline data. SUBJECTS: A cohort of 2379 girls recruited from selected schools in Richmond, Calif., and greater Cincinnati, Ohio, and from the membership rolls of a prepaid group practice in greater Washington, D.C. RESULTS: Sixty-four percent of black girls had begun pubertal maturation compared with 33% of white girls. In prepubertal girls, racial differences in height, weight, body mass index (kilograms per square meter) and skin-fold thickness were not significant. Within each race, onset of pubertal maturation was associated with greater height, weight, body mass index, and skin-fold measurements. Within 9-year-old girls who had begun pubertal maturation but not reached menarche, black girls were taller and heavier than white girls. Among pubertal but premenarcheal 10-year-old subjects, black girls were taller and heavier and had greater body mass index and subscapular skin-fold values. After analyses were adjusted for pubertal maturation stage by means of pubic hair development, 10-year-old pubertal black girls remained taller and heavier, but racial differences in body mass index and the sum of skin-fold measurements ceased to be significant. CONCLUSIONS: These findings suggest that the initiation of racial differences in obesity are related, at least temporally, to pubertal maturation.

Black People↗
PubMed1990

Beta-lactam antibiotic biosynthetic genes have been conserved in clusters in prokaryotes and eukaryotes.

A cosmid clone containing closely linked beta-lactam antibiotic biosynthetic genes was isolated from a gene library of Flavobacterium sp. SC 12,154. The location within the cluster of the DNA thought to contain the gene for delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), the first step in the beta-lactam antibiotic biosynthetic pathway, was identified by a novel method. This DNA facilitated the isolation, by cross-hybridization, of the corresponding DNA from Streptomyces clavuligerus ATCC 27064, Penicillium chrysogenum Oli13 and Aspergillus nidulans R153. Evidence was obtained which confirmed that the cross-hybridizing sequences contained the ACVS gene. In each case the ACVS gene was found to be closely linked to other beta-lactam biosynthetic genes and constituted part of a gene cluster.

Anti-Bacterial Agents↗
PubMed1988

Intravesical thiotepa versus mitomycin C in patients with Ta, T1 and TIS transitional cell carcinoma of the bladder: a phase III prospective randomized study.

A prospective randomized clinical trial was conducted by the National Bladder Cancer Group to compare thiotepa and mitomycin C in ablating residual Ta, T1 and TIS transitional cell carcinoma of the bladder. Eight weekly instillations were given followed by cystoscopy 4 weeks after the treatment was stopped. The over-all complete response rate based on cystoscopy and either biopsy or cytology was 26 per cent for thiotepa versus 39 per cent for mitomycin C (p equals 0.08). The greatest efficacy was seen in the Ta group with mitomycin C demonstrating superiority over thiotepa. Patients with negative cystoscopy and biopsy but who had positive cytology were considered to be partial responders. When partial and complete responders were combined the over-all response rate was 53 per cent for thiotepa and 63 per cent for mitomycin C (p equals 0.23). Patients with TIS appeared to respond equally to thiotepa and mitomycin C. Toxicity included urinary frequency in 22 of the 73 patients in the thiotepa arm and 31 of the 76 patients receiving mitomycin C. A rash was observed in 2 of the thiotepa group versus 14 of the mitomycin C group. Bone marrow depression occurred in 15 patients receiving thiotepa and in 12 receiving mitomycin C.

Administration, Intravesical↗
PubMed1986

Fibrin glue as a biologic vascular patch--a comparative study.

Fibrin glue is a biologic two component hemostatic adhesive. Fibrin glue acts as an effective vascular plus after arterial injury without suture at pressures twice systolic. It is also effective on vein at physiologic pressures, however, venous distensibility precludes its efficacy beyond these limits. Recent studies have documented its utility as a preclot material on vascular grafts and as a seal for sutured vascular anastomoses. This study was designed to characterize the glue's sealant ability when applied to open arterial and venous injuries, and to compare its efficacy with currently available hemostatic agents. Segments of canine peripheral artery and vein were isolated and perforated with a 16-gauge needle. This injury was treated by random application of either fibrin sealant (FS), oxidized cellulose (OC), microcrystalline collagen (MC), or MC plus thrombin (MCT). Five minutes after patch application, intralumenal pressure was increased progressively with saline infusion to ascertain bursting threshold. The arterial bursting threshold was significantly higher for FA (250 +/- 59.7 mm Hg) than for OC (12.5 +/- 6.1 mm Hg), MC (17.2 +/- 21.9 mm Hg) or MCT (10.8 +/- 13.8 mm Hg) (P less than 10(6)). The bursting threshold of FS applied to vein (17.5 +/- 11.7) was not significantly different from other agents (P less than 0.05).

Animals↗
PubMed1985

Mitomycin for patients who have failed on thiotepa. The National Bladder Cancer Group.

The National Bladder Cancer Group undertook a study to determine the effectiveness and toxicity of mitomycin in patients who failed on thiotepa. A total of 117 patients with residual superficial transitional cell bladder cancer (Ta, T1, Tis) who had previously failed on intravesical thiotepa were treated with 40 mg of mitomycin instilled intravesically weekly for eight weeks. Four to six weeks after the last treatment, tumor response was evaluated by cystoscopy, biopsy of the site of the index lesion, and cytology. In 57 patients (48.7%), visible tumor had been ablated. Results of cystoscopy, biopsy, and cytology were negative in 32 (27.4%) patients. Eleven patients (9.4%) had no visible tumor and negative cytology unconfirmed by biopsy. In 14 patients (12%) who had complete destruction of the tumor at cystoscopy, and biopsy specimen was negative for tumor, cytology was positive, indicating a partial response. Six patients (5.1%) withdrew from the study before the first evaluation because of local toxicity (cystitis).

Administration, Topical↗
PubMed1980

Pathologic findings from the National Surgical Adjuvant Breast Project (protocol no. 4). VI. Invasive papillary cancer.

Although papillary forms of intraductal cancer are a common component of amny mammary cancers, invasive papillary cancer of the breast is relatively rare. Only 35 examples were encountered in the specimens obtained from 1603 women participating in a prospective randomized study of invasive mammary cancer. Contingency-table analysis disclosed that invasive papillary cancer, as opposed to the non-papillary histologic types, is significantly more likely to show circumscription, cytoplasmic oxyphilia, microcalcification, intermediate histologic grade, moderate or marked mucin and an intraductal component of papillary type. Although patients who have invasive papillary cancer are frequently judged by clinical criteria to have regional nodal metastases, in pathologic analysis these metastases are not commonly found and, if present, involve fewer than four nodes. There is a significant frequency of marked sinus histiocytosis in regional nodes. The lesion occurs with a significantly high frequency among non-Caucasian and postmenopausal women. Only three patients with invasive papillary cancer experienced treatment failure after five years of observation. Life-table probabilities showed that the treatment failure rate was significantly lower for the group of patients who had any other histologic type, and in this regard invasive papillary cancer was similar to the tubular and mucinous varieties. Although apocrine metaplasia, fibrous supporting stalks and cellular differentiation have been espoused as important criteria distinguishing intraductal papi-loma from intraductal cancer, these features were also not uncommonly observed in the examples of invasive papillary cancer studied. It is concluded that invasive papillary cancer represents a unique histologic type of invasive mammary cancer attendant with a favorable prognosis.

Breast Neoplasms↗