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Biomedical subjects

T J Nemeth

Publications and source records attributed to T J Nemeth.

14 recordsLinked to original sources
PubMed1992

Serial injections of MK 801 (Dizocilpine) in neonatal rats reduce behavioral deficits associated with X-ray-induced hippocampal granule cell hypoplasia.

MK 801 (NMDA antagonist) has been shown to protect newborns from hypoxia-induced brain damage. Here, we determined if (+)-5-methyl-10,11-dihydroxy-5h-dibenzo (a,d)cyclohepten-5,10-imine (MK 801) could attenuate behavioral deficits associated with early radiation-induced hypoplasia of fascia dentata granule cells. We pretreated neonatal rats (n = 20) with MK 801 (0, 0.1, or 0.2 mg/kg, IP) before each of eight fractionated, head-only doses of X-rays (13 Gy total) administered during the first 16 days postpartum. Other rats (n = 18) received the same drug treatments but were sham irradiated. At age 16 months, water-escape latencies to a submerged platform were measured in a water maze. Irradiated rats with hippocampal damage exhibited impaired learning (longer latencies to find the platform) than did sham-irradiated subjects. Moderate doses of MK 801 (0.1 mg/kg) facilitated the learning of the water maze by irradiated subjects but did not enhance the number of their fascia dentata granule cells. Higher doses (0.2 mg/kg) of MK 801 provided no behavioral benefits. In fact, this dose significantly impaired the learning of the water maze by sham-irradiated rats and potentiated the granule cell hypoplasia observed in irradiated subjects. Thus, early MK 801 treatment produces dose-dependent behavioral protection for rats with radiation-induced hippocampal damage. Future studies may reveal the neurophysiological and neuroanatomic substrates of this behavioral recovery.

Animals↗
PubMed1991

Early neural grafts transiently reduce the behavioral effects of radiation-induced fascia dentata granule cell hypoplasia.

X-irradiation of the neonatal rat hippocampus produces a selective hypoplasia of fascia dentata granule cells, locomotor hyperactivity, perseverative movements and deficits in passive avoidance. We previously reported that transplantation of fetal hippocampal tissue into the adult (age = 182 +/- 4 days) brain produced a partial recovery of these behavioral deficits. Since graft/host interconnections are more prominent when transplants are conducted soon after radiation-induced hippocampal damage, in this study we transplanted hippocampal or cerebral cortex neurons when host rats were 33 +/- 5 days of age (i.e. only 16 days after radiogenic brain damage). Behavioral evaluations were conducted 80 and 182 days after transplantation or surgical control procedures. In the first test series only, selective components of locomotion (e.g. stereotypy and total distance traveled) and perseverative turning (e.g. mean bout length and turning speed topography) were normalized by the hippocampal grafts. Radiation-induced changes in passive avoidance were less prominent in these studies than in past experiments. Still, transplantation of hippocampal tissue improved performance on this learning task as well. Cerebral cortex grafts did not produce reliable improvements in most behavioral measures. These data suggest that hippocampal grafts placed soon after X-ray induced fascia dentata hypoplasia reduce a broad range of behavioral deficits. However, these benefits are transient and, for the most part, depend on the use of transplant tissues homologous with those damaged.

Animals↗
PubMed1990

Neural grafts attenuate behavioral deficits produced by early radiation-induced hypoplasia of fascia dentata granule cells.

Localized X-irradiation of the mitotic cells in the neonatal rat hippocampus produces a discrete hypoplasia of the fascia dentata granule cell layer. This brain damage inhibits the acquisition of a passive avoidance task, and stimulates spontaneous perseverative turning (without reversals) in a plastic hemisphere apparatus. Here we report how transplantation of fetal brain tissue can attenuate these radiation-induced behavioral deficits. The partially shielded cerebral hemispheres of neonatal rats received fractionated exposures to 13 Gray (Gy) of X-rays during the first 16 days post partum. This procedure depleted 90% of the hippocampal granule cells while sparing other brain areas. Control animals were sham irradiated. Baseline behavioral tests were conducted when subjects reached an average age of 147 +/- 4 days. We recorded behavioral parameters known to be sensitive to hippocampal damage: (1) passive avoidance performance, and (2) perseverative spontaneous turning without reversals. Irradiated subjects later (average age = 182 +/- 4 days) received intracerebral transplants of either fetal (E20-21) neurons/neuronal precursors from the fascia dentata or cerebral cortex (control grafts). Additional controls (both irradiated and sham-irradiated) experienced sham surgical procedures or received no surgical manipulation. Two post-surgical behavioral retests were accomplished when rats were 265 +/- 5 and 351 +/- 6 days old. Rats were then sacrificed and brains were treated histologically to assess radiation-induced brain damage, graft survivability and graft locus. Both hippocampal and cerebral cortex grafts generally facilitated performance on the passive avoidance task. This effect was most prominent during the first post-surgical test. Hippocampal transplants (especially those found to reside in the damaged hippocampus) also significantly attenuated perseverative spontaneous rotation at the time of the final post-surgical test series. Cortex grafts found within the damaged hippocampus did not ameliorate perseverative movements, while cortex grafts located outside the hippocampus significantly reduced this behavioral deficiency. These data suggest that selected behavioral deficits may be attenuated by transplanting fetal neural tissue long after early radiation-induced brain damage. The success of these procedures depends on a number of factors including: (1) the behaviors chosen for analysis, (2) the time after transplantation that behavioral tests are conducted, and (3) the source and final location of the donor neural tissue.

Animals↗
PubMed1989

Spontaneous perseverative turning in rats with radiation-induced hippocampal damage.

This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage.

Animals↗
PubMed1984

In vivo evaluation of pyridoxalated-polymerized hemoglobin solution.

Previous evaluations of stroma free hemoglobin solutions (SFHS) revealed two problems, a low P50 (13 to 15 torr) which theoretically limits oxygen off-loading to tissues, and a short intravascular half time of only 3.5 hours. To correct these problems the hemoglobin molecule was pyridoxalated and polymerized to raise the P50 (20 to 22 torr) and to increase the plasma half-disappearance time to 25 hours. In the current investigation, rats exchange transfused to 75 per cent of their initial blood volume with SFHS exhibited centrilobular liver necrosis 12 and 24 hours after the transfusion as a result of the hypovolemic state induced by the hemoglobin diuresis. In contrast, animals administered pyridoxalated polymerized hemoglobin solution (Pr-Pl-Hb) displayed a normal hepatic morphologic finding. Renal morphologic findings in the two groups were similar except for the smaller quantities of hemoglobin observed in the proximal and distal tubules of Pr-Pl-Hb animals. This finding may be a result of the slower degradation of Pr-Pl-Hb in the intravascular compartment. Renal function in Pr-Pl-Hb remained normal after exchange transfusion, while the BUN in SFHS treated animals increased significantly due to the state of dehydration. Thus, Pr-P1-Hb represents an improvement over the previously tested SFHS in both P50 and intravascular half-time and, because of lowered osmotic and oncotic activities, it may be used in higher concentration to improve oxygen carrying capacity.

Animals↗
PubMed1982

Progressive ultrastructural changes after peripheral nerve transection and repair.

Six rhesus monkeys (Macaca mulatta) underwent sharp transection and repair of the intrinsic motor fascicles of both ulnar nerves in order to determine the sequential events during reinnervation of the distal stamp. Light and electron microscopic sections were made at 2.0 mm increments distal to the neurorrhaphy at weekly intervals in separate monkeys. Neurite sprouts could be identified distal to the neurorrhaphy by 1 week and were clearly evident 40 mm distal by 3 weeks. Although some old endoneurial tubules persisted, they were less often used as conduits or scaffolds for the regenerating neurites than previously described. Most new fibers, whether myelinated or unmyelinated, passed down new endoneurial tubules, thus precluding perfect end-organ specificity because the regenerating neurites seldom utilized old endoneurial tubules. The clinical implication suggested by this study is that the ideal situation is the immediate repair of transected nerves. This allows neurite sprouts to cross a neurorrhaphy rapidly and reinnervate end organs.

Animals↗
PubMed1981

The mucosal response in the excluded limb after jejunoileal bypass for morbid obesity.

Twelve patients underwent a takedown of the jejunoileal bypass with restoration of normal continuity of the intestine. Specimens were obtained for biopsy from the excluded proximal jejunum and distal ileum as well as the distal in continuity jejunum. Hypertrophy of the mucosa was observed in the in continuity segment, as previously described. Villi of the bypassed jejunum displayed no evidence of hypertrophy or of atrophy and were identical in size to villous measurements prior to creation of the jejunoileal bypass. At the ultrastructural level, absorptive cells of bypassed jejunal segments exhibited normal morphologic characteristics. There was no indication of cellular immaturity above the level of the intestinal crypts. In contrast, villi of bypassed ileum, near the colonic anastomosis, demonstrated hypertrophy, presumably reflecting reflux of luminal material into this segment of bypassed intestine. The results of this investigation support the concept that significant morphologic alterations of the mucosa do not occur in totally bypassed segments of intestine after the jejunoileal bypass procedures with attainment of weight stabilization.

Atrophy↗
PubMed1979

The ultrastructural changes of prostate adenocarcinoma following external beam radiation therapy.

Ultrastructural studies were done to determine the effects of radiation therapy on prostatic adenocarcinoma. Twenty patients were included in the study: 6 with benign hyperplasia, 4 with untreated adenocarcinoma and 10 with adenocarcinoma who had received radiation therapy. Benign and malignant ultrastructural characteristics were established. On the basis of these characteristics 6 of the 10 radiated prostates were believed to have tumor cells present after therapy. Of the remaining 4 patients 3 had ultrastructural changes suggesting radiation effects and a possibly altered malignant potential.

Adenocarcinoma↗
PubMed1978

Alterations in intestinal structure, fat absorption and body weight after intestinal bypass for morbid obesity.

Eleven patients underwent jejunoileal bypass for morbid obesity. Serial intestinal biopsies were obtained prior to, and at timed intervals following, operation in both fasted and fat-fed states. Villus height increased asymptotically, reaching a plateau one year after operation, with an increase of 80 per cent in mean villus length. The postbypass body weight reached a plateau at 63.9 per cent of initial body weight and correlated linearly with villus height following an asymptotic curvilinear course. The time required to attain 90 per cent of total body weight loss was 15.9 months. A study of intestinal fat absorption at both the light microscopic and ultrastructural levels showed that the enlarged villi are lined along the entire villus by functionally mature epithelium capable of transporting lipid. Villus hypertrophy is an important mechanism in the plateauing of weight loss after jejunoileal bypass for morbid obesity.

Body Weight↗
PubMed1977

Hepatic intramitochondrial filaments in morbidly obese patients undergoing intestinal bypass.

The characteristics of hepatocyte intramitochondrial filaments (IMF's) were studied in 16 patients undergoing jejunal ileal bypass for morbid obesity. At the time of bypass, all of the liver biopsies showed varying degrees of steatosis and IMF's were present in 13 of the 16 operative specimens. The IMF's were most prominent in the periportal cells, whereas the intracellular lipid was concentrated in centrilobular cells. Midzonal hepatocytes were intermediate in both respects. The IMF'S were more abundant in biopsies showing moderate steatosis than in those with marked lipid accumulation in which the IMF's were limited to hepatocytes in juxtaposition to portal triads. The IMF's appeared to originate from mitochondrial cristae. When steatosis resolved 12 to 18 months after intestinal bypass the prevalence of IMF's diminished also. It is hypothesized that the presence of IMF's is ultrastructural evidence of an adaption to an altered metabolic environment which resolves when the inciting influence is removed.

Biopsy↗
PubMedDate not supplied

Progressive behavioral changes during the maturation of rats with early radiation-induced hypoplasia of fascia dentata granule cells.

Localized exposure of the neonatal rat brain to X-rays produces neuronal hypoplasia specific to the granule cell layer of the hippocampal dentate gyrus. This brain damage causes locomotor hyperactivity, slowed acquisition of passive avoidance tasks and long bouts of spontaneous turning (without reversals) in a bowl apparatus. Here we report how these behavioral deficits change as a function of subject aging and behavioral test replications. Portions of the neonatal rat cerebral hemispheres were X-irradiated in order to selectively damage the granule cells of the dentate gyrus. The brains of experimental animals received a fractionated dose of X rays (13 Gy total) over postnatal days 1 to 16 and control animals were sham-irradiated. Rats between the ages of 71-462 days were tested 3 separate times on each of the following 3 behavioral tests: 1) spontaneous locomotion, 2) passive avoidance acquisition, and 3) spontaneous circling in a large plastic hemisphere. Rats with radiation-induced damage to the fascia dentata exhibited long bouts of slow turns without reversals. Once they began, irradiated subjects perseverated in turning to an extent significantly greater than sham-irradiated control subjects. This irradiation effect was significant during all test series. Moreover, in time, spontaneous perseverative turning was significantly potentiated in rats with hippocampal damage but increased only slightly in controls. Early radiation exposure produced locomotor hyperactivity in young rats. While activity levels of controls remained fairly stable throughout the course of the experiment, the hyperactivity of the irradiated animals decreased significantly as they matured.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

Effects of essential fatty acid deficiency on the induction of liver microsomal membranes by phenobarbital: an ultrastructural and biochemical investigation.

The essential fatty acids, particularly arachidonic, are important components of intracellular membrane systems. Their absence during dietary manipulation has been postulated to cause alterations in both composition and function of membranes and associated enzyme systems. In the current investigation, the effect of essential fatty acid deficiency on the induction of hepatic microsomal membranes my phenobarbital was studied. Control rats were fed a standard chow diet and either injected daily for 4 days with phenobarbital or with a placebo. Experimental animals were given an essential fatty acid-deficient (EFAD) diet and similarly injected with either phenobarbital or placebo. Following the above regimens, liver tissue was obtained for electron microscopy and biochemical membrane analysis. Control animals given phenobarbital displayed a marked proliferation of smooth endoplasmic reticulum in comparison to placebo controls. In contrast, EFAD rats did not exhibit an endoplasmic reticulum response to phenobarbital injection and appeared to recover from the drug administration injection more slowly than control animals. The alterations in fatty acid composition characteristic of an EFAD diet were observed in the microsomal membranes of the deficient animals. The concentrations of palmitic, palmitoleic, oleic, and 5,8,11-eicosatrienoic acids were significantly increased above that found in control animals. Concentrations of linoleic and arachidonic acids were reduced. Phenobarbital administration significantly increased the concentrations of palmitic, linoleic, and arachidonic acids in microsomal fractions of chow-fed animals but not in EFAD animals. Conversely, eicosatrienoic acid concentrations increased in phenobarbital-treated EFAD animals but not in chow-fed, drug-injected rats. The triene/tetraene ratio reflected these alterations. Essential fatty acid deficiency causes biochemical alterations of the hepatic microsomal membranes which are exaggerated by the administration of phenobarbital. These compositional changes appear to alter the functional ability of the membranes to proliferate in response to phenobarbital and, thereby, inhibit the efficaceous metabolism of this drug.

Animals↗