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Biomedical subjects

J Martin

Publications and source records attributed to J Martin.

At least 469 records · Page 26Linked to original sources

Changes in bone mass and metabolism after surgery for primary hyperparathyroidism.

BACKGROUND AND OBJECTIVE: Bone mass is often reduced in patients with primary hyperparathyroidism (pHPT) and is usually partially reversible after parathyroidectomy. However, site specific and overall skeletal benefits of surgery in mild asymptomatic pHPT remain uncertain. DESIGN: Cross-sectional and longitudinal studies. PATIENTS: Fourteen patients (12 women and 2 men) with pHPT. MEASUREMENTS: Baseline bone mass was assessed at the lumbar spine, left hip and whole body using dual-energy X-ray absorptiometry, and at the left os calcis using broad-band ultrasound attenuation. Changes in bone mass, serum intact PTH and osteocalcin, and urinary pyridinium cross-link excretion were recorded in 10 patients followed for 6 months after surgery. RESULTS: (1) Cross-sectional study: Baseline measurements at the lumbar spine and hip were inversely related to both the serum PTH concentration and the weight of the parathyroid gland removed at surgery. (2) Longitudinal study: Six months after adenectomy, bone mass had increased significantly at the femoral neck, greater trochanter, whole body and os calcis, but not at the lumbar spine or Ward's area. Serum PTH, osteocalcin and pyridinium cross-link excretion all fell significantly after surgery. The percentage increment in whole body bone mineral content at 6 months was proportional to the baseline PTH. CONCLUSION: In primary hyperparathyroidism, preoperative reductions and post-operative gains in bone mass are proportional to the initial serum PTH concentration. Mild primary hyperparathyroidism probably does not cause appreciable bone loss at clinically relevant fracture sites such as the spine and hip, and in such cases the overall skeletal benefits of surgery are likely to be negligible.

Aged↗

Expression of a cloned cellulase/xylanase gene from Prevotella ruminicola in Bacteroides vulgatus, Bacteroides uniformis and Prevotella ruminicola.

A new shuttle vector, pRH3 (8.7 kb), was constructed for use in Prevotella/Bacteroides host strains. This vector combines the pRRI2 replicon from P. ruminicola, pBluescript sequences and a tetQ marker gene for selection in Prevotella/Bacteroides hosts. Following insertion of a fragment carrying an endoglucanase/xylanase gene from P. ruminicola 23 into the multiple cloning site, the resulting construct, pRH3X, was introduced into B. vulgatus 1447, B. uniformis 1100 and P. ruminicola 2202. This resulted in increases of between 4 and 50-fold in CM-cellulase and xylanase activities in cells grown with glucose. In contrast activities were barely detectable for the same construct in E. coli DH5 alpha. Most of the total xylanase activity produced was found within the cell in P. ruminicola 2202 and B. vulgatus 1447 transformed with pRH3X, and in P. ruminicola 23. An osmotic shock experiment indicated that a significant proportion of the xylanase activity in B. vulgatus 1447 cells carrying pRH3X was periplasmic.

Bacteroides↗

A xylan hydrolase gene cluster in Prevotella ruminicola B(1)4: sequence relationships, synergistic interactions, and oxygen sensitivity of a novel enzyme with exoxylanase and beta-(1,4)-xylosidase activities.

Two genes concerned with xylan degradation were found to be closely linked in the ruminal anaerobe Prevotella ruminicola B(1)4, being separated by an intergenic region of 75 nucleotides. xynA is shown to encode a family F endoxylanase of 369 amino acids, including a putative amino-terminal signal peptide. xynB encodes an enzyme of 319 amino acids, with no obvious signal peptide, that shows 68% amino acid identity with the xsa product of Bacteroides ovatus and 31% amino acid identity with a beta-xylosidase from Clostridium stercorarium; together, these three enzymes define a new family of beta-(1,4)-glycosidases. The activity of the cloned P. ruminicola xynB gene product, but not that of the xynA gene product, shows considerable sensitivity to oxygen. Studied under anaerobic conditions, the XynB enzyme was found to act as an exoxylanase, releasing xylose from substrates including xylobiose, xylopentaose, and birch wood xylan, but was relatively inactive against oat spelt xylan. A high degree of synergy (up to 10-fold stimulation) was found with respect to the release of reducing sugars from oat spelt xylan when XynB was combined with the XynA endoxylanase from P. ruminicola B(1)4 or with endoxylanases from the cellulolytic rumen anaerobe Ruminococcus flavefaciens 17. Pretreatment with a fungal arabinofuranosidase also stimulated reducing-sugar release from xylans by XynB. In P. ruminicola the XynA and XynB enzymes may act sequentially in the breakdown of xylan.

Amino Acid Sequence↗

In vivo growth characteristics of leucine and methionine auxotrophic mutants of Mycobacterium bovis BCG generated by transposon mutagenesis.

Insertional mutagenesis in Mycobacterium bovis BCG, a member of the slow-growing M. tuberculosis complex, was accomplished with transposons engineered from the Mycobacterium smegmatis insertion element IS1096. Transposons were created by placing a kanamycin resistance gene in several different positions in IS1096, and the resulting transposons were electroporated into BCG on nonreplicating plasmids. These analyses demonstrated that only one of the two open reading frames was necessary for transposition. A library of insertions was generated. Southern analysis of 23 kanamycin-resistant clones revealed that the transposons had inserted directly, with no evidence of cointegrate formation, into different restriction fragments in each clone. Sequence analysis of nine of the clones revealed junctional direct 8-bp repeats with only a slight similarity in target sites. These results suggest that IS1096-derived transposons transposed into the BCG genome in a relatively random fashion. Three auxotrophs, two for leucine and one for methionine, were isolated from the library of transposon insertions in BCG. They were characterized by sequencing and found to be homologous to the leuD gene of Escherichia coli and a sulfate-binding protein of cyanobacteria, respectively. When inoculated intravenously into C57BL/6 mice, the leucine auxotrophs, in contrast to the parent BCG strain or the methionine auxotroph, showed an inability to grow in vivo and were cleared within 7 weeks from the lungs and spleen.

Animals↗

An extended Li-Fraumeni kindred with gastric carcinoma and a codon 175 mutation in TP53.

We present an extended family with Li-Fraumeni syndrome characterised by gastric and breast carcinoma, glioma, sarcoma, and leukaemia. This family showed strong evidence of linkage to TP53, and three of four tumours analysed showed loss of the wild type allele. A codon 175 missense mutation was identified in exon 5 in all available affected subjects. Counselling, screening, and issues surrounding presymptomatic testing are discussed.

Codon↗

Megakaryocytes from patients with coronary atherosclerosis express the inducible nitric oxide synthase.

Endothelial and platelet generation of nitric oxide (NO) plays an important role in the regulation of hemostasis. Alterations in NO biosynthesis are described in atherosclerosis. We have investigated the NO pathway in megakaryocytes and platelets from patients with atherosclerosis and age-matched control subjects. Megakaryocytes and platelets were isolated from patients with severe coronary atherosclerosis (n = 19) and normal coronary arteries (n = 9) as demonstrated by selective angiography. Constitutive (Ca(2+)-dependent) and inducible (Ca(2+)-independent) NO synthase (cNOS and iNOS, respectively) activities were measured by using the citrulline assay and by immunostaining techniques using an anti-peptide antibody to iNOS. Megakaryocytes from patients with atherosclerosis expressed significantly greater amounts of iNOS (1.28 +/- 0.46 pmol citrulline.mg-1.min-1) than cNOS (0.29 +/- 0.40 pmol.mg-1.min-1). In contrast, megakaryocytes from patients with normal coronary arteries expressed significantly more cNOS (1.48 +/- 0.23 pmol.mg-1.min-1) than iNOS (0.49 +/- 0.40 pmol.mg-1.min-1). Platelets isolated from both groups showed no significant difference in cNOS expression, and no iNOS was seen in either group. Immunostaining confirmed the presence of the iNOS in megakaryocytes. These results suggest there is a link between the expression of iNOS in the megakaryocyte and atherosclerosis.

Amino Acid Oxidoreductases↗

Successful suicide by insulin injection in a non-diabetic.

We report the death of a young female non-diabetic after self-administration of insulin which led to the trial and conviction of her partner, who was himself an insulin-dependent diabetic. This brings out particular lessons for the pathologist in view of the rarity of such deaths, emphasizes the importance of careful laboratory analysis and illustrates a number of interesting legal points.

Adult↗

Improvement of impaired counterregulatory hormone response and symptom perception by short-term avoidance of hypoglycemia in IDDM.

OBJECTIVE: To test the hypothesis that impaired counterregulatory hormone response and symptom perception, induced by recurrent hypoglycemic episodes over 2 days, may be improved by short-term (2-day) avoidance of hypoglycemia. RESEARCH AND DESIGN: We examined two groups of insulin-dependent diabetes mellitus (IDDM) patients (n = 16), none of whom exhibited signs of peripheral or autonomic neuropathy. Two sequential euglycemic-hypoglycemic clamp studies were performed applying stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mmol/l, at which the patients' awareness of and responses to hypoglycemia were evaluated. In the intervention group (n = 11), three short-term hypoglycemic ( < 2.2 mmol/l) episodes (days 1-3) preceded the first clamp study (day 4), whereas the second clamp study (day 6) followed a 2-day interval of strict avoidance of hypoglycemia. A control group (n = 5) was introduced to detect adaptation effects caused by the study procedure per se. RESULTS: This short-term avoidance of hypoglycemia caused improvement of the impaired counterregulatory hormone response during insulin-induced hypoglycemia involving adrenaline (P < 0.05), adrenocorticotrophic hormone (P < 0.03), and cortisol (P < 0.05). Improvement of hypoglycemia symptom awareness encompassed overall symptom perception (multiple analysis of variance, P < 0.04) and the automatic symptoms of heart pounding (P < 0.05) and sweating (P < 0.05). CONCLUSIONS: The previously reported compromised neuroendocrine counterregulation and symptom awareness, occurring as a consequence of repetitive hypoglycemic episodes over 2 days, may be improved by a single 2-day interval of strict avoidance of hypoglycemia

Adult↗

The utility of outcomes information at the point of service.

A systemwide outcomes management plan is in the process of implementation at Dean Medical Center. Plans for data collection include a core data set of patient satisfaction, basic health, and functional and risk status along with specific clinical and clinically related functional status reported by patients and providers.

Asthma↗

[The "conclusions of Pharmacy" in Nancy, at the end of the 18th century: between "synthèses" and "thèses"].

A special requirement of the law for apothecaries in Nancy in 1764 imposed on the candidates for a master's degree was the written response to four questions following their practical examinations. Two documents heretofore unpublished show the results of this obligation: the Conclusions de Pharmacie by Joseph Pierson (1765) and the Conclusions de Pharmacie et de Chimie by François Mandel (1771). The authors of the present article comment on these documents and make an attempt to place them in the confused history of "synthèses" and "thèses".

Education, Pharmacy↗

Fatigue fracture of the sacrum in a child.

The authors describe a 9-year-old girl with stress fracture of the sacrum. Such fractures can cause low-back or hip pain in children but may not be evident on plain films. The appearance on scintigraphy is not diagnostic. Likewise, the findings on magnetic resonance imaging may be nonspecific or confusing, because changes in signal intensity in the marrow may not be sufficient to distinguish infection or malignancy from healing of the fracture. Computed tomography can be more specific in delineating a sclerotic fracture oriented parallel to the sacroiliac joint. Recognition of the characteristic radiographic findings in sacral fatigue fractures can prevent incorrect diagnosis and unnecessary diagnostic procedures or treatments.

Child↗