Biomedical subjects
T Peterson
Publications and source records attributed to T Peterson.
Systematic evaluation of microangiopathy in diabetic Chinese hamsters. I. Morphometric analysis of minimal glomerular basement membrane thickness in 11- to 15- and 19- to 23-month-old Chinese hamsters.
Renal glomeruli of 11- to 15- and 19- to 23-month-old nondiabetic (M) and diabetic (XA and AC) genetic sublines of Chinese hamsters were morphometrically analyzed to determine if minimal capillary basement membrane thickening (CBMT) is a microvascular complication in this animal model. Minimal glomerular capillary basement membrane thickness was significantly elevated in the AC diabetic subline (117.2 nm +/- 5.0, P less than 0.004) compared with the M nondiabetic subline (99.0 nm +/- 14.0) in the 11- to 15-month age span. However, in the 19- to 23-month age range, both the XA (140.2 nm +/- 20.0, P less than 0.02) and AC (140.1 nm +/- 12.4, P less than 0.04) diabetic sublines displayed significantly greater glomerular capillary basement membrane thickness in comparison with the M nondiabetic subline (119.0 nm +/- 13.4). The greatest influence on CBMT in the diabetics was shown to be a combination of the aging process and severity of hyperglycemia. This initial systematic morphometric study has demonstrated that glomerular CBMT is a characteristic microvascular lesion in 11- to 15-month-old diabetic AC and 19- to 23-month-old diabetic XA and AC Chinese hamsters in comparison with age-matched nondiabetics. Furthermore, this investigation suggests that the Chinese hamster appears to be an acceptable model for the study of chronic complications associated with diabetic nephropathy.
Ciglitazone, a new hypoglycemic agent. 5. Effect on renal lesions in C57BL/KsJ-db/db mice.
Kidneys of treated and control C57BL/KsJ-db/db mice were analyzed by semiquantitative light microscopy to determine the effects of ciglitazone on the deposition of fluorescein-conjugated IgM and IgG and of PAS-positive material in the glomerular mesangium and renal tubules. Long-term administration (12 and 20 weeks) of ciglitazone significantly improved the blood glucose of most of the treated db/db mice. There appeared to be a reduction of glomerular IgM and IgG in the treated compared with the control group, although IgM did not achieve statistical significance due to heavy stain deposition in two of the treated mice with continuous and severe hyperglycemia. Treated and control mice displayed a similar diffuse expansion and mild thickening of the glomerular mesangium characterized by moderate deposition of PAS-positive material. Expansion of the mesangium was probably not retarded or prevented by ciglitazone therapy since this pathologic process may be controlled by an interaction of metabolic factors other than hyperglycemia per se in the db/db mouse. Glycogen vacuolization (Armeni-Epstein lesion) of the renal tubules was completely ameliorated in the treated mice which showed a reduction of hyperglycemia. The results of this study suggest that prolonged treatment with ciglitazone elicits an improvement of hyperglycemia which seems to retard or reverse glomerular immunopathology and completely reverse tubular derangement but does not prevent expansion of the glomerular matrix in severely diabetic C57BL/KsJ-db/db mice.
[Effect of anoxia, flow-stop and cardioplegic solutions on the liberation of noradrenaline from the isolated rabbit heart in comparison to clinical findings].
Experiments with isolated hearts. The results include the effects of anoxia, flow-stop and cardioplegic solutions (CPL) on the efflux of noradrenaline (NA) from isolated rabbit hearts preperfused with 3H-noradrenaline. 1.) Anoxic Tyrode solution did not enhance 3H-NA efflux into the perfusion medium. 2.) 3H-NA efflux was greatly enhanced after a flow-stop period of 20 min in normothermia (34 degrees C), but only to a small amount after a flow-stop period of 30 min in hypothermia (10 degrees C). 3.) In flow-stop experiments in hypothermia all CPL solutions enhanced the 3H-NA efflux. This effect is due to sodium deprivation (most CPL) or to high potassium concentration.--Studies on cardiosurgical patients. NA-concentration was determined in blood samples from vena cava superior (zv), radial artery (art) and coronary sinus (cv). 1.) cv NA-level continuously rose from 0.27 ng/ml after induction of anaesthesia to 0.77 ng/ml at onset of complete extracorporeal circulation. 2.) In 19 patients cardioplegia was induced by CPL HTP Bretschneider. Immediately after the cardioplegic period art und cv samples were collected at short intervals. NA-concentrations were not elevated in cv samples. 3.) An increase of NA in cv blood was distinct in two patients with extremely long periods of cardioplegia. In summary, after perfusion of isolated rabbit hearts with hypothermic CPL and subsequent flow-stop, an enhanced NA efflux is evident during reperfusion with Tyrode's solution. The effect of CPL on the NA release seems of minor importance in patients undergoing cardiosurgical procedures.
Elevated levels of vasoactive intestinal peptide in the eye and urinary bladder of diabetic and prediabetic Chinese hamsters.
The eyes and urinary bladder of non-diabetic, prediabetic and diabetic Chinese hamsters were evaluated by radioimmunoassay and immunocytochemistry to determine the content and distribution of vasoactive intestinal peptide (VIP). The average concentration of VIP was increased in the eyes of all diabetic (pmol/g = 68%, pmol/organ = 50%) and prediabetic (pmol/g = 152%, pmol/organ = 115%) hamsters compared with age-matched non-diabetic animals. Immunocytochemistry showed that the elevation of VIP was primarily related to greater intensity of fluorescence of the nerve fibres in the vasculature of the choroid. The average content of VIP in the urinary bladder was greater in diabetic animals only on the basis of pmol/organ (135%) and in prediabetics on the basis of pmol/g (87%) compared with non-diabetic animals. Qualitative immunocytochemistry suggested that the elevated level of VIP was related to a larger distribution of nerve fibres in the urinary bladder of diabetic hamsters. The high level of VIP in the eyes and urinary bladder of diabetic and prediabetic hamsters is an interesting observation which should receive further study to determine whether it is an aetiological agent underlying the pathogenesis of ophthalmic complications and neurogenic bladder or the result of some pathological process which affects these organs.
Hemodynamic effects of rapid and slow infusions of manganese chloride and gadolinium-DTPA in dogs.
The acute hemodynamic effects of two paramagnetic contrast materials, manganese chloride and gadolinium-DTPA, were examined in dogs using ultrasonic dimension gauge crystals. Slow infusions (more than 15 minutes) of MnCl2 (0.1 mm/kg) or Gd-DTPA (0.1 mm/kg) via an infusion pump had no significant hemodynamic effects. When given in just over 1 minute, Gd-DTPA produced elevated left ventricular (LV) end diastolic pressure and minor dilation of the ventricle and slowed diastolic filling. MnCl2, given rapidly, reduced systemic vascular resistance, resulting in hypotension. It also reduced LV volume and had less marked diastolic effects (probably secondary to the amount of hypotension created). With both agents, these side effects waned after 5-10 minutes. It is concluded that both Gd-DTPA and MnCl2 can be given safely in 0.1-mm/kg doses when administered as a slow, continuous infusion. The acute hemodynamic effects of Gd-DTPA are consistent although minor. While the acute effects of Gd-DTPA are small, neither agent is sufficiently innocuous to be given as a rapid injection in clinically unstable patients. Slow, intravenous infusion of Gd-DTPA or MnCl2 is likely to be tolerated well by even severely ill individuals.
Ciglitazone, a new hypoglycaemic agent. 4. Effect on pancreatic islets of C57BL/6J-ob/ob and C57BL/KsJ-db/db mice.
Pancreases of treated and control male C57BL/6J-ob/ob and C57BL/KsJ-db/db mice were evaluated by qualitative and morphometric microscopic techniques to determine the effects of chronic ciglitazone treatment on the morphology of beta cells and surface area and number of pancreatic islets. The beta cells of treated ob/ob and db/db mice displayed moderate to heavy granulation whereas most beta cells of untreated obese and diabetic mice were extensively degranulated. Although moderate proliferation of the rough endoplasmic reticulum and Golgi apparatus was evident in some beta cells of treated db/db mice, both groups of treated ob/ob and db/db mice displayed an improved pattern of insulin synthesis and storage. In contrast, the beta cells of untreated ob/ob and db/db mice were in a severe state of stress which was indicated by extensive hypertrophy of the rough endoplasmic reticulum, Golgi apparatus and mitochondria. Some beta cells of untreated db/db mice also displayed lysosome aggregates indicative of early stages of necrosis. Morphometric analysis revealed that the surface area of islets of treated ob/ob mice was significantly smaller in comparison with that of untreated ob/ob mice. Since the surface area of islets of treated C57BL/6J-+/? mice (lean littermates of ob/ob mice) was less than that of treated ob/ob mice, the progression of islet hypertrophy in the obese mice was probably arrested or attenuated but not to the level of the treated +/? mice. The number of pancreatic islets was significantly greater in treated than in untreated db/db mice. A majority of the islets of untreated db/db mice were atrophic and consisted of acinar and endocrine cells whereas most of the islets of treated db/db mice appeared to be intact and unremarkable. The results of this study suggest that ciglitazone is an effective hypoglycaemic agent which may directly or indirectly promote beta-cell regranulation and an improved pattern of insulin synthesis and storage in ob/ob and db/db mice. However, in treated db/db mice, there still was some evidence of stress in the beta cells. Overall, the prolonged treatment with ciglitazone also seemed to inhibit the hypertrophy of islets in ob/ob mice and protect the structural integrity and viability of islets in db/db mice.
Morphometric analysis of the vagus nerve in non-diabetic and ketonuric diabetic Chinese hamsters.
Morphometric analysis of axons from the ventral division of the vagus nerve of ketonuric diabetic Chinese hamsters and age-sex matched non-diabetic controls was performed to determine the frequency distribution and numerical and volume density. Myelinated fibres of diabetics displayed a significant reduction in diameter (P less than 0.001) compared with controls, which was correlated inversely with progressive ketonuria (P less than 0.05). The reduced calibre of myelinated fibres was the result of thin myelin sheaths rather than a reduction in axon diameter. A marked decrease in numerical density (P less than 0.05) and volume density (P less than 0.005) was found in the myelinated fibres of diabetics compared with controls. Non-myelinated axons showed a significant shift to smaller diameter (P less than 0.001) in diabetics, which was correlated inversely with duration of ketonuria (P less than 0.05). Numerical density of non-myelinated axons was increased (P less than 0.01) in diabetic hamsters whereas volume density was comparable in diabetic and control animals. These data provide morphological evidence of impairment in the parasympathetic nervous system which may be a major factor underlying previously reported gastrointestinal and pancreatic islet dysfunction in the diabetic Chinese hamster.
Experimental observations on the mode of action of "intracellular" flush solution.
Experiments were conducted using rabbit kidneys stored on ice for 48 hr to elucidate the mode of action of "intracellular" flush solutions. Measurements were made of renal function on a shunt and they were correlated with blood flow and the efficiency of the mechanical expulsion of red cells. By comparison with unflushed, ice-stored kidneys, near complete mechanical expulsion of blood by 30 to 60 min of continuous perfusion with hypertonic Ringer's albumin resulted in significantly higher blood flow with little gain in function. Similarly, increasing the content of nonelectrolyte in Ringer's albumin improved blood flow but not function. A simple flush with a low ionic strength sodium solution (LIE), containing impermeant anions and glucose was superior to that with Ringer's albumin. A high-potassium version of the low ionic strength solution (LIC) was in turn significantly better than LIE for kidney preservation by simple flushing and ice storage. These results were interpreted to mean that whereas mechanical flushing is a relatively minor component of the action of flush solutions, the major benefit results from a reduced sodium and elevated potassium content in the presence of impermeant anions. The primary importance of prevention of cell swelling by the inclusion of nonelectrolytes in "extracellular" flush solutions, is questioned.
Aphasia in subdural hematoma.
The occurrence of aphasia as the only or dominant symptom of subdural hematoma (SDH) has not been emphasized in the literature. The possible confusion of traumatic aphasia with transient ischemic attacks or stroke has been the object of most recent investigations. Four patients with subacute SDH had aphasia as an initial symptom; the relevant pathophysiologic characteristics were noted in each. These patients had a rapid response to decompression with marked resolution of the aphasia irrespective of immediate or delayed drainage.
Islet innervation of nondiabetic and diabetic Chinese hamsters. I. Acetylcholinesterase histochemistry and norepinephrine fluorescence.
Cholinergic and adrenergic innervation of pancreatic islets from age- and sex-matched nondiabetic (M subline) and diabetic (AC subline) Chinese hamsters was analyzed by acetylcholinesterase (AChE) histochemistry and norepinephrine fluorescence. The AChE activity was significantly diminished in islets of diabetic animals compared with that of nondiabetic controls. The reduction in cholinergic innervation displayed an inverse relationship with respect to nonfasting plasma glucose and ketone levels. On the basis of qualitative analysis, adrenergic activity also appeared to be depressed in islets of diabetic animals. These date suggest that autonomic control of islet function is altered in diabetic Chinese hamsters when plasma glucose and ketone levels arae elevated and may exacerbate metabolic complications in this animal model.
Ciglitazone, a new hypoglycemic agent. I. Studies in ob/ob and db/db mice, diabetic Chinese hamsters, and normal and streptozotocin-diabetic rats.
Ciglitazone, 5-[4-(1-methylcyclohexylmethoxy) benzyl]-thiazolidine-2,4-dione, is a new hypoglycemic agent orally active in the obese-hyperglycemic animal models. In C57BL/6J-ob/ob mice, treatment with 100 mg/kg ciglitazone for 2 days elicited a drastic fall in blood glucose. It also decreased plasma insulin, triglycerides, and free fatty acids and food intake without affecting the body weight. Its hypoglycemic activity was independent of its effect on food intake. Regranulation of islet beta-cells and increased pancreatic insulin content were observed in ob/ob mice treated for 41-44 days with 100 mg/kg/day ciglitazone. Ciglitazone showed no effect on food intake, blood glucose, or pancreatic islet beta-cells in a group of lean C57BL/6J-+/? mice concomitantly treated at a dose of 150 mg/kg/day. In C57BL/KsJ-db/db mice, ciglitazone decreased blood glucose and food intake. The untreated db/db mice lost weight despite hyperphagia, whereas the ciglitazone-treated db/db mice gained weight. In the spontaneously diabetic Chinese hamsters, ciglitazone showed no significant effect on food intake, body weight, blood glucose, or insulin content in either plasma or pancreas, but it lowered plasma lipids. In normal rats, ciglitazone failed to affect fasting blood glucose but improved glucose tolerance without increasing insulin secretory response to glucose. In streptozotocin-diabetic rats, it showed no effect on blood glucose or glycemic response to exogenous insulin. The hypoglycemic activity of ciglitazone was specific for obese-hyperglycemic and insulin-resistant animals.
Justifying a full-time pharmacist in your smaller hospital.
Explore the source record for details and available documents.
Localization of S-100 protein in Müller cells of the retina--1. Light microscopical immunocytochemistry.
S-100 is an acidic brain protein previously found to be present in glial cells of the brain and the nervous system of gut and respiratory tract. Immunocytochemistry at the light microscopical level localized immunoreactivity for S-100 in the Müller cells in the retina of rat, guinea pig, and Chinese hamster. The Müller cells represent the main glial component of the retina, with a structural role in the support and insulation of neurons and sensory elements. The use of S-100 protein as an immunocytochemical marker of Müller cells may be useful in the study of pathologic conditions of the retina where glial cell proliferation could reflect the index of neuronal injury.
Agrobactin, a siderophore from Agrobacterium tumefaciens.
A siderophore (microbial iron transport compound) was isolated from low iron cultures of Agrobacterium tumefaciens B6. The substance was characterized as a threonyl peptide of spermidine acylated with 3 residues of 2,3-dihydroxybenzoic acid, the carbonyl group of 1 residue of the latter participating in an oxazoline ring with the beta-hydroxyl of the threonine moiety. The compound, N-[3-(2,3-dihydroxybenzamido)propyl]-N-[4-(2,3-dihydroxybenzamido)butyl]-2-(2,3-dihydroxyphenyl)-trans-5-methyl-oxazoline-4-carboxamide, was given the trivial name agrobactin. Exposure to acid opened the oxazoline ring to afford agrobactin A. Ferric agrobactin A and agrobactin A itself, but not agrobactin or its ferric complex, had some capacity to feed iron to enterobactin-deficient strains of Escherichia coli and Salmonella typhimurium. Agrobactin was produced by A. tumefaciens in response to iron deficiency and was able to reverse the iron starvation in this organism precipitated by the presence of a ferric complexing agent not utilized by the cells.
Ischemic myocardial injury after exercise stress in the pressure-overloaded heart.
Systemic hemodynamics and regional myocardial blood flows were determined in 18 miniswine during the development of pressure-overload hypertrophy induced by supravalvular aortic constriction. Nine miniswine served as control animals. Regional myocardial blood flows were measured at rest and during exercise stress with radioactive microspheres after 2 days and 1 month of aortic constriction. Exercise stress, causing the heart rate to increase to 85% of its maximum, was imposed twice weekly for 5 minutes on 13 pressure-overloaded animals to elicit differences between the control and experimental groups that might not occur at rest. At rest, regional myocardial blood flows of pressure-overloaded animals were similar to those of control animals. When exercise stress was imposed after 2 days and 1 month of pressure overload, endocardial blood flows decreased 45% below control exercise levels, although epicardial blood flows were unchanged. During the first 2 weeks of pressure overload epicardial and endocardial electrocardiograms showed S-T segment elevation with exercise stress but not at rest. Postmortem examinations after 1 month of pressure overload showed significant histologic evidence of myocardial injury, namely, fibrosis, which was subendocardially located. These findings indicate that the pressure-overloaded heart is at risk for ischemic injury, particularly during the early, uncompensated stage.
Calcium, magnesium, phosphorus, copper, and manganese balance in adolescent females.
Calcium, magnesium, phosphorus, copper, and manganese balances were determined in 14 girls (12.5 to 14.5 years of age) during a 30-day period. Menus were composed of ordinary foods and were typical of subjects' usual dietary habits. The diets contained 1.07 g calcium, 193 mg magnesium, 0.85 g phosphorus, 2.8 mg copper, 3.0 mg manganese, and 7.4 or 13.4 mg zinc daily. Defatted soy was substituted for 0, 15, or 30% of the meat in lunch menus. Neither the alteration of dietary zinc levels or the partial substitution of soy for meat significantly affected retention of the five minerals. Retentions of calcium (r = 0.654), magnesium (r = 0.786), phosphorus (r = 0.560), copper (r - 0.805), and manganese (r = 0.855) by subjects were all significantly (P less than 0.001) correlated to retention of zinc. These correlations probably reflect the correlations between fecal losses of calcium (r = 0.438), magnesium (r = 0.434), phosphorus (r = 0.377), copper (r = 0.318), and manganese (r = 0.318) and the volume of feces. On these dietary regimes adolescents were in positive balances for calcium, phosphorus, and copper, but were in negative balances for magnesium and managenese.
Motorized minitrack for exercising large animals.
A simply constructed device for exercise training large animals, e.g., swine, is described. Basically the device is a small, circular, enclosed track constructed of plywood and metal fence material. A centrally located, vertical shaft powered by a DC motor rotates at a variable speed. Attached to each of four horizontal metal beams extending from the shaft are four suspended partitions which hang freely above the enclosed track surface. As the shaft rotates, the four partitions move in unison, thus forcing animals in each compartment to move at the same pace. The advantages of this device are its cost, low maintenance, and the flexibility to train eight animals by one person. Preliminary results of a study on training pigs are discussed.