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Biomedical subjects

A A Martin

Publications and source records attributed to A A Martin.

At least 37 records · Page 2Linked to original sources
PubMed1994

Transfer of insulin-like growth factor (IGF)-I from blood to intestine: comparison with IGFs that bind poorly to IGF-binding proteins.

The net transfer of 125I-labelled insulin-like growth factor (IGF)-I from the blood to the distal small intestine was measured in anaesthetized lambs using a non-recirculating vascular-perfused intestine. To determine whether IGF-binding proteins (IGFBPs) reduce net IGF transfer, radiolabelled IGF-I was compared with two analogues, des(1-3)IGF-I and LR3IGF-I, which show reduced affinity for IGFBPs. Radiolabelled IGF-I, des(1-3)IGF-I or LR3IGF-I (1 ng/ml plasma) was infused for 45 min into the arterial supply of a 10 cm intestinal segment, either in the absence of added unlabelled peptide (high specific activity) or in the presence of a 100-fold excess of unlabelled homologous peptide (low specific activity) to achieve different proportions of free and complexed peptide. Very little degradation of radiolabelled peptides was detected in plasma, with 3-10% degradation in the intestinal tissue. Less than 5% of radiolabelled IGF-I remained as free peptide in the efferent venous plasma of the perfused segment at both specific activities. Bound radiolabelled IGF-I was found by size-exclusion chromatography mainly in the 30-50 kDa region, with a smaller proportion in the 150 kDa peak. The net intestinal transfer of IGF-I, calculated as the sum of the proportions of infused tracer recovered from intestinal tissue, luminal contents and lymph, was 3.46 +/- 0.22% (S.E.M.) and 3.49 +/- 0.93% when infused at high and low specific activities respectively. The analogues differed from IGF-I with up to ninefold higher concentrations of free radiolabelled peptide in venous plasma of the perfused intestinal segment, and corresponding decreases in binding to the 30-50 kDa binding proteins. Notwithstanding these marked differences in the plasma levels of free peptide, net intestinal transfer was very similar for the three peptides, as was the extent of degradation in the intestinal tissue. The lack of correlation between binding to 30-50 kDa binding proteins and net intestinal transfer suggests that association with 30-50 kDa plasma binding proteins is not a rate-limiting determinant of net IGF transfer to intestinal tissue.

Animals↗
PubMed1994

Treatment with IGF-I peptides improves function of the remnant gut following small bowel resection in rats.

The effects of 7 days' s.c. infusion of 111-700 micrograms/day IGF-I on gut growth and absorptive function were examined in growing rats following removal of 70 or 80% of the jejuno-ileum, and compared with the responses to the analogues, LR3IGF-I and des(1-3)IGF-I, which bind poorly to IGF binding proteins. Administration of 278 micrograms/day IGF-I, LR3IGF-I or des(1-3)IGF-I following 70% jejuno-ileal resection significantly attenuated malabsorption of fat and nitrogen. Responses in rats with 80% resection were less substantial, but a dose-responsive reduction in malabsorption was apparent with LR3IGF-I. Both IGF-I and LR3IGF-I were shown to increase body weight gain and food conversion efficiency in a dose-dependent manner following 80% jejuno-ileal resection. Total gut weight was increased by up to 21%, due predominantly to increased weight of the stomach and proximal small bowel, with the latter effect attributable at least in part to an increased bowel length. LR3IGF-I was more potent than IGF-I at stimulating body weight gain and food conversion efficiency, but its potency advantage on gut absorptive function and small intestinal re-growth was less marked. We conclude that administration of IGF-I peptides improves gastro-intestinal absorptive function following partial gut resection, most likely reflecting, at least in part, an increase in gut absorptive surface area.

Adaptation, Physiological↗
PubMed1993

Tracheobronchopathia osteochondroplastica: a case report and a review of the literature.

Tracheobronchopathia osteochondroplastica is characterized by osseocartilaginous submucosal nodules projecting into the lumen of the larynx, trachea, and bronchi. Its etiology is unknown. Most cases are asymptomatic and frequently diagnosed incidentally during intubation or endoscopy. The diagnosis is made on the basis of endoscopy, CT scan, and histopathology. Fragments of adipose tissue, deposits of calcification and ossification often with foci of bone marrow and active hemopoiesis are present in the submucosa. Surgical treatment is indicated for airway obstruction and recurrent infections.

Aged↗
PubMed1992

Insulin-like growth factor-I and its N-terminal modified analogues induce marked gut growth in dexamethasone-treated rats.

The effects of insulin-like growth factor-I (IGF-I) on the gut of 150 g dexamethasone-treated rats were compared with those of two analogues with reduced affinity for IGF-binding proteins, des(1-3)IGF-I and LR3IGF-I, an N-terminal-extended variant. Administration of IGF-I for 7 days to rats made catabolic by co-treatment with dexamethasone induced a dose-dependent increase in total gut weight, with the highest dose of IGF-I (695 micrograms/day) increasing gut weight by up to 60%, and gut weight as a fraction of body weight by up to 32%. Effects were apparent in all regions of the gut examined, including the stomach, small intestine and colon. Histological and biochemical analyses of the intestine showed that cross-sectional mass, rather than gut length, was increased, and proportional increases in wet weight, protein and DNA content per unit length were measured in both the mucosa and muscularis layers. The rate of duodenal protein synthesis measured on day 7 of treatment was not increased by IGF-I treatment. The IGF-I analogues had qualitatively similar effects to IGF-I, but were consistently severalfold more potent, providing evidence that IGF-binding proteins reduce the biological activity of exogenous IGF-I in the gut. The results indicate that the gut is one of the most sensitive IGF-I target tissues, and that potency in vivo correlates with a reduced interaction with IGF-binding proteins.

Animals↗
PubMed1992

Insulin-like growth factor I and its variant, des(1-3)IGF-I, improve nitrogen balance and food utilization in rats with renal failure.

The growth-promoting effects of IGF-I were examined in rats following partial nephrectomy and compared with the effects of the des(1-3) variant of IGF-I. Four groups of rats were subjected to 5/6 nephrectomy (n = 8 per group) and treated for 7 days with IGF-I (0.9 or 2.2 mg/kg BW/day), des(1-3)IGF-I (0.9 mg/kg/BW/day), or vehicle (0.1 M acetic acid) administered subcutaneously by osmotic pump. A group of vehicle-treated, sham-operated control rats (n = 7) was included. Food utilization was significantly improved in all three peptide-treated groups, by 13-16% compared with the vehicle-treated nephrectomized group. Also, nitrogen balance was enhanced, particularly in the des(1-3)IGF-I group, in which nitrogen excretion was reduced by 24%, with the low- and high-dose IGF-I groups showing 16 and 18% reductions, respectively. Serum urea levels were significantly decreased, by 25%, in the des(1-3)IGF-I group, with 20 and 17% reductions being observed in the low- and high-dose IGF-I groups. Muscle protein degradation was found to be significantly attenuated with des(1-3)IGF-I treatment but was not significantly affected in the two IGF-I-treated groups. While carcass composition was not altered with IGF peptide treatment, absolute mass of protein in the carcass was improved in rats treated with the high dose of IGF-I. These results show that IGF-I or, more particularly, des(1-3)IGF-I may be efficacious in overcoming impaired growth in renal failure.

Animals↗
PubMed1991

IGF-I and the truncated analogue des-(1-3)IGF-I enhance growth in rats after gut resection.

Effects of insulin-like growth factor I (IGF-I) administration and that of the truncated analogue des-(1-3)IGF-I have been examined in 170-g rats over a 7-day period after surgery to remove 80% of the jejunum plus ileum. The doses administered via osmotic infusion pumps were 0.96 and 2.4 mg.kg-1.day-1 IGF-I and 0.96 mg.kg-1.day-1 des-(1-3)IGF-I. All groups lost weight on the day after surgery, but over the next 3 days the des-(1-3)IGF-I and high-dose IGF-I groups stabilized better and subsequently gained significantly (P less than 0.05) more weight than the vehicle or low-dose IGF-I groups over the last 3 days. The weight gains (mean +/- SE) for the groups over this last 3-day period were 14.0 +/- 1.7, 14.4 +/- 2.9, 21.9 +/- 1.7, and 20.8 +/- 1.0 g for the vehicle, low-dose IGF-I, high-dose IGF-I, and des-(1-3)IGF-I groups, respectively. The nitrogen balances over the last 3 days for the high-dose IGF-I and des-(1-3)IGF-I groups, at 242 +/- 14 and 217 +/- 13 mg/d, respectively, were significantly (P less than 0.05) more positive than the control group at 153 +/- 21 mg/d. These differences could at least partially be explained by changes in muscle protein breakdown, as assessed by 3-methyl-L-histidine excretion. The kidneys were heavier in all treatment groups and the thymus after administration of des-(1-3)IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

IGF-I and its variant, des-(1-3)IGF-I, enhance growth in rats with reduced renal mass.

The efficacy of insulin-like growth factor I (IGF-I) in enhancing growth in animals with reduced renal mass was investigated in subtotally nephrectomized young male rats. Recombinant human IGF-I was administered by osmotic minipumps for 7 days at two doses, 0.9 and 2.2 mg.kg body wt-1. day-1, and the truncated analogue of IGF-I, des-(1-3)IGF-I, was given at a dose of 0.9 mg.kg body wt-1.day-1. The partial nephrectomy procedure resulted in significantly impaired renal function as evidenced by elevated serum urea and creatinine concentrations, reduced creatinine clearance, and increased average daily urine output. Carcass composition was significantly altered in animals with reduced renal mass; water content increased and fat content decreased, while protein content remained unchanged. Carcass composition was not affected by IGF treatment. Body weight gain, food utilization, and nitrogen balance during the treatment period were significantly increased in rats treated with IGF-I at both the lower and higher doses and in those treated with des-(1-3)IGF-I. The improved nitrogen balance in the des-(1-3)IGF-I group could at least partly be explained by a diminished rate of muscle protein breakdown, as indicated by the reduced urinary excretion rate of 3-methylhistidine. Compensatory hypertrophy of the remnant kidney was significantly increased in the group treated with the high dose of IGF-I. These results suggest that IGF-I may have beneficial effects on somatic growth and nitrogen balance in renal insufficiency, with des-(1--3)IGF-I being particularly effective in reducing the rate of muscle protein breakdown.

Animals↗
PubMed1991

Insulin-like growth factor-binding proteins in tissue fluids from the lamb.

Heparinized samples of plasma, cerebrospinal fluid (CSF) and lymph from intestinal, prescapular and popliteal lymph nodes were collected from young lambs in order to characterize and compare the insulin-like growth factor-binding proteins (IGFBPs) in extracellular fluids with those from the circulation. Prior to collection and analysis, the superiority of heparin for plasma preparation was established over EDTA and citrate or the use of serum, according to the extent of IGF-I and IGF-II binding achieved in the high molecular mass IGFBP region in vitro. The IGFBPs were characterized by ligand blotting and competitive binding techniques using radiolabelled IGF-I, IGF-II and the truncated IGF analogue, des(1-3)IGF-I, as well as by ligand blotting of fractions after Superose 6 chromatography of incubations of fluids with labelled factors. This combined analysis demonstrated an IGF-II-specific binding protein at approximately 250 kDa that was present in plasma and each lymph type and presumably represented the soluble type-2 IGF receptor; a complex of 130 kDa containing 52 kDa and 46 kDa binding proteins that was labelled by all three IGF peptides was particularly evident in plasma and intestinal lymph and was probably a complex between IGFBP-3 and the acid-labile subunit; and a group of binding proteins that chromatographed as IGF complexes at approximately 50 kDa. This last group contained IGFBP bands of 52, 46, 32, 28 and 23.5 kDa in plasma and all lymphs as well as an IGF-II-specific band of 22 kDa in prescapsular and popliteal lymphs. CSF differed qualitatively from plasma and lymph in that the 52/46 kDa IGFBP bands were undetectable in this fluid; the 35 kDa band was the predominant binding protein, and neither this nor the 28, 23.5 and 22 kDa proteins bound des(1-3)IGF-I to any significant extent. The 52, 46 and 28 kDa bands in plasma and lymph did bind this ligand. Immunoblots using antisera against bovine IGFBP-2 showed binding at 35 kDa in all fluids as well as several bands at lower molecular masses. Taken together these results show not only marked differences in the binding protein profiles of sheep plasma, lymph and CSF, but both qualitative and quantitative differences between intestinal, prescapular and popliteal lymphs. We speculate that the differences between lymphs may result from tissue-specific release of binding proteins into extracellular fluid.

Animals↗
PubMed1991

Superior vena cava syndrome associated with malignant mesothelioma.

A 70-year-old former shipyard worker presented with dyspnea and edema of the upper thorax suggesting the diagnosis of superior vena cava syndrome. Further evaluation revealed mesothelioma with both epithelial and spindled histologic patterns. The extensive mesothelioma had invaded the adventitia of the superior vena cava, the pleura of the lungs bilaterally, the superficial myocardium, and the liver. A terminal hyercoagulable state with great vein thrombosis was also contributory. To our knowledge this is the first documented case of superior vena cava syndrome associated with malignant mesothelioma.

Aged↗
PubMed1990

Sleep and respiratory patterns in the Djungarian hamster.

Djungarian hamsters adapted to a 12/12-h L/D photoperiod at 28 +/- 1 degrees C Tamb, implanted with electroencephalogram and electromyogram electrodes and fitted with pneumomanometers were monitored for 4 h on 5 consecutive days to obtain baseline sleep stages and respiration in the nontorpid hamster. Fifty-seven percent of recording time was spent in the sleep state with rapid eye movement (REM) sleep occupying 11% of the total sleep time. An analysis of successive 30-min epochs revealed that REM percentage and REM period (REMP) frequency in the first 30 min were significantly (p less than 0.0001) lower compared to the last 150 min, while REMP duration remained unchanged throughout the recording session. Respiratory frequency was significantly higher (p less than 0.01) by 24% in REM sleep as compared to Non-REM sleep. The euthermic sleep pattern in the non-torpid Djungarian hamster, adapted to a steady-state photoperiod, contained alternating periods of non-rapid eye movement (Non-REM) and REM sleep, similar to that seen in other rodents. REM sleep pattern regulation became steady after the initial 90-min transition period during which REM frequency but not duration increased. This transition to a steady REM sleep pattern might allow flexibility in entering the torpor state during the presence of unfavorable environmental stimuli.

Animals↗
PubMed1989

Localization of prolactin-like immunoreactivity in grafted human sweat glands.

Using a double-antibody immunoperoxidase technique, we demonstrated human prolactin-like material in some cells of the secretory coil and in luminal duct cells of sweat glands of human skin which had been carried as grafts on mice for 32-35 weeks. It therefore seems likely that a population of cells in the secretory coil synthesizes prolactin and can be considered as diffuse peripheral endocrine cells. The prolactin may function locally to regulate sweat electrolyte concentration.

Animals↗
PubMed1987

Hormonal factors in the control of heart rate in normoxaemic and hypoxaemic fetal, neonatal and adult sheep.

The relationship of plasma levels of adrenaline, noradrenaline, arginine vasopressin (AVP) and plasma renin activity (PRA) to heart rate were studied in normoxaemic and hypoxaemic fetal, neonatal and adult sheep. The mean heart rate response of fetuses at the end of a 30 minute period of 10% oxygen delivery to the maternal ewe was tachycardia. However bradycardia, usually of a transient nature, was observed in 9 of the 12 fetuses (P less than 0.05). Multiple regression analysis was used to determine the contribution of blood gas, blood pressure and plasma hormone levels to the variance in heart rate in the perinatal sheep. 22% of the variance in fetal heart rate was provided by PRA and age from conception (P less than 0.001). Tachycardia was the invariable heart rate response of the neonates and adults to hypoxaemia. 61% of the variance in neonatal heart rate was contributed by PaO2, PaCO2, AVP, PRA and systolic blood pressure (SBP, P less than 0.001). PaO2 and plasma levels of adrenaline were significantly related to adult heart rate (P less than 0.001). Those fetuses which developed bradycardia had lower PaO2 but higher AVP and PRA during hypoxaemia than those which did not develop bradycardia. The major determinant of the area of the fetal bradycardia response was found, by multiple regression analysis, to be plasma adrenaline concentration (P less than 0.05). Thus different hormonal factors may play a role in the regulation of heart rate in normoxaemic and hypoxaemic fetal, neonatal and adult sheep.

Aging↗
PubMed1986

Age dependent heart rate responses to prostacyclin (PGI2) in unanaesthetized fetal and neonatal sheep.

Intravenous injections of PGI2 (1.5-12 X 10(-5) nmol/ml blood volume) caused hypotensive responses which increased with dose in both fetal and neonatal sheep. In the fetus, as gestation advanced and basal heart rate declined, the predominant heart rate response to PGI2 changed progressively from bradycardia to tachycardia. In the neonate, PGI2 always induced tachycardia and the effect was unrelated to postnatal age. The bradycardia induced by PGI2 in young fetal sheep (123-132 days) was converted to tachycardia following either bilateral vagotomy or cervical cord transection. Heart rate was unchanged by PGI2 in fetal sheep subjected to both procedures. The depressor response to PGI2 was enhanced by cervical cord transection but was essentially unchanged in fetal sheep subjected to either bilateral vagotomy alone or combined vagotomy and cord section. Despite increased plasma renin activity following PGI2, the cardiovascular response was not modified by bilateral nephrectomy. It is concluded that while intravenous PGI2 has a similar depressor effect in both fetal and neonatal sheep the heart rate response is age-dependent. Bradycardia is the principal response in young fetal sheep and is mediated by vagal pathways while tachycardia, which is the more usual response in older sheep, is probably sympathetic in nature.

Animals↗
PubMed1981

Subdural hematomas in neonates. Surgical treatment.

7 cases of acute subdural hematomas diagnosed and surgically treated during the first week of life are presented. 5 of them are alive and well at 6 and 7 months and 3, 4 and 6 years of follow-up. Free interval, raised intracranial pressure, lateralizing signs, fall of hematocrit and presence of blood in CSF were constant. Subdural puncture was negative in 6 cases, including a hemophilic patient (hemophilia B). Clinical diagnosis was ratified by means of neuroradiological procedures. The authors conclude that craniectomy is the treatment of choice and subdural tapping a useless procedure.

Brain Edema↗
PubMed1980

Giant arteriovenous fistula of the vein of Galen in early infancy treated successfully with surgery. Case report.

A giant arteriovenous fistula in a newborn infant was treated by surgical occlusion of the feeding vessels at 20 days of life. Congestive heart failure responded favorably to operative treatment. Because of persistent hydrocephalus, a shunt was inserted at 2 months of age. At 9 months of age, the child remained without signs of cardiac failure. Cerebral damage was manifested by a mild left hemiparesis. Successful surgical treatment of this unusual lesion in a neonate is exceptional.

Cerebral Angiography↗