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Biomedical subjects

M Girotti

Publications and source records attributed to M Girotti.

At least 19 recordsLinked to original sources
PubMed1994

Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic beta-cells. Potential role in nutrient sensing.

Nutrient metabolism was examined with regard to insulin secretion in purified rat islet beta- and non-beta-cells, beta-cell lines, and hepatocytes. Lactate dehydrogenase (LDH) activity (nanomoles.min-1.mg protein-1) was remarkably low in the glucose-sensitive INS-1 cell line (15.7) and in beta-cells (22.3). Thus, beta-cell LDH was respectively 8-, 122-, 17-, and 136-fold lower than in islet non-beta, liver, HIT-T15, and RINm5F cells. Plasma membrane lactate transport activity was 3-10-fold lower in beta- or INS-1 cells than in the other cell types. Conversely, mitochondrial glycerol phosphate dehydrogenase was strongly expressed only in beta- and INS-1 cells. The significance of these findings to nutrient recognition was explored using INS-1 cells as a model of native beta-cells. Glucose-stimulated lactate output and glucose utilization were, respectively, 12- and 5-fold lower in INS-1 than in RINm5F cells. Each process was entirely blocked by respiratory chain inhibitors in INS-1 cells, whereas glucose utilization was barely affected and lactate output stimulated in RINm5F cells. Glucose oxidation represented 73% of total utilization in INS-1 cells, but only 9% in RINm5F cells. Absolute rates of glucose oxidation, and the extent of mitochondrial NAD(P) reduction, were similar in the two cell types, and glucose stimulated insulin secretion 1.9-fold in INS-1 and 1.4-fold in RINm5F cells. The mitochondrial substrates, monomethyl succinate, pyruvate, and leucine, each triggered secretion in INS-1 cells. The balance of LDH, plasma membrane lactate transport, and mitochondrial glycerol phosphate dehydrogenase activities therefore appear to be important in beta- and INS-1 cell glucose recognition to ensure that mitochondrial oxidation is the principle fate of pyruvate and NADH produced by glycolysis. The resultant close coupling of glycolysis with mitochondrial oxidation explains the absence in beta-cells of Crabtree and Pasteur effects.

Animals↗
PubMed1994

Timing of surgery influences survival in receptor-negative as well as receptor-positive breast cancer.

Analysis of oestrogen and progesterone receptor (ER, PR) status was interpreted in relation to menstrual phase at the time of surgery and survival in 84 women diagnosed with breast cancer between 1975 and 1988. We showed previously (Br J Surgery 1994, 81, 217-220) that long-term survival was significantly poorer when surgery was performed during the follicular phase of the menstrual cycle compared to luteal phase; we now demonstrate that this effect on survival is at least as important in receptor-negative as receptor-positive patients. At 10 years, overall survival (OS) of ER-positive patients who had their biopsy during the follicular phase was significantly poorer than for those whose biopsy was performed during the luteal phase of their menstrual cycle (52 versus 88%, P = 0.02). OS for the ER-negative follicular phase group was also significantly poorer than that for the ER-negative luteal phase group (33 versus 76%, P = 0.009). The OS difference between the PR-positive follicular phase group and PR-positive luteal phase group was of borderline significance (60 versus 87%, P = 0.06), while the difference in OS between the PR-negative follicular phase group and that of the PR-negative luteal phase group was highly significant (13 versus 76%, P = 0.001). Disease-free survival for these groups followed a similar trend. The survival differences in receptor-negative women suggest that hormonal fluctuations at the time of surgery may have complex indirect effects on tumour growth and metastasis. The mechanism, if indeed independent of the tumour steroid receptors, could also apply in other cancers.

Adult↗
PubMed1992

Structure and expression of the rat epididymal secretory protein I gene. An androgen-regulated member of the lipocalin superfamily with a rare splice donor site.

The complete rat epididymal secretory protein I (ESP I) gene was isolated from a genomic library constructed in bacteriophage lambda Charon 4A. The complete nucleotide sequence of the gene and its immediate 5' and 3' flanking sequences were determined. Interesting features include the presence of a rare, but functional, splice donor site (...GC) and the presence of a putative androgen-receptor-binding element. A detailed analysis of ESP I regulation was carried out after castration and subsequent testosterone treatment, demonstrating the requirement for androgens. Efferent-duct ligation and cryptorchism, on the other hand, had no effect on the steady-state concentrations of ESP I transcripts. Comparison of the exon/intron organization of the ESP I gene with those of members of the lipocalin superfamily provides strong support for a common ancestral origin.

Amino Acid Sequence↗
PubMed1992

Is a full team required for emergency management of pediatric trauma?

Pediatric trauma centers often do not meet the guidelines requiring a trauma team as recommended by the American Academy of Pediatrics (AAP). We reviewed our experience with a team consisting of a pediatric emergency physician, resident, nurse, and respiratory therapist. The surgical and pediatric critical care residents and staff were available within 5 minutes. We conducted a retrospective chart review of 146 patients (aged 8.1 +/- 4.8 years) between 1987 and 1989, with Injury Severity Scores (ISS) greater than or equal to 16 or admitted to the pediatric critical care unit. The time of presentation, surgical services consulted, and the nature of the injury were obtained from chart review. The Pediatric Trauma Score (PTS), the Revised Trauma Score (RTS), the Injury Severity Score (ISS), Glasgow Coma Scale (GCS) score, and Pediatric Risk of Mortality (PRISM) were used to determine the severity of insult and physiologic derangement on admission. The Modified Injury Severity Score (MISS) was determined and the Delta score for Disability Assessment was assigned at discharge. The Delta score was also determined at 3-month intervals up to one year. The probability of survival (Ps) was calculated, using the ISS and RTS. The Z statistic for this group of patients was then determined, using the Major Trauma Outcome Study (MTOS) methodology. The percentages of patients who were normal, disabled, and dead were 61%, 31.5%, and 7.5%, respectively, at 6 months follow-up. Eleven deaths were expected based on PRISM and TRISS analysis. Our mortality and morbidity figures were comparable with those of centers with teams based on AAP guidelines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Periampullary tumors: which ones should be resected?

Resection was carried out in 118 patients for periampullary lesions. Ninety-eight of these were adenocarcinomas and were treated by the Whipple operation, total pancreatectomy, or local resection (87 patients, 7 patients, and 4 patients, respectively). Diagnosis of pancreatic head carcinoma before resection was falsely positive in 27 percent of the patients. Mortality for radical resection was 4 percent. Five year survival for ampullary carcinoma was 32 percent, and for pancreatic head carcinoma it was 7 percent. Resection of all periampullary tumors is recommended, with the Whipple operation being the standard in most cases.

Actuarial Analysis↗
PubMed1985

Single-layer large-bowel anastomosis: a report of 250 cases.

Single-layer mucosa-excluding intestinal anastomoses involving the large bowel were evaluated in 249 patients (250 procedures). All patients operated on electively had mechanical bowel preparation but not all received antibiotics. Forty-nine anastomoses were performed as part of emergency procedures in which antibiotics were given intravenously. Three leaks were noted in two patients, a rate of 1.2%. There were no deaths attributable to anastomotic dehiscence. These results compare favourably with both hand-sewn and stapled anastomoses described in the literature.

Adolescent↗