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Biomedical subjects

D A Wilson

Publications and source records attributed to D A Wilson.

At least 163 records · Page 9Linked to original sources

Long-term potentiation in the interpositus and vestibular nuclei in the rat.

Previous unpublished experiments from this laboratory had revealed only post-activation depression effects in the cerebellar cortex when its inputs were activated by high frequency trains. In the experiments reported in this paper, we found reliable long-term potentiation (LTP) effects in the deep nuclei (interpositus and vestibular) when stimulation trains were applied to the white matter at the point where inferior peduncle fibers enter the cerebellum. LTP effects were found in both acute and chronic preparations. In the chronic preparations, LTP lasted for at least 8 days in all but one animal.

Animals↗

Early appearance of inhibition in the neonatal rat olfactory bulb.

The functional development of inhibition in the rat olfactory bulb was examined in the present study. Inhibition of presumed mitral cell spontaneous activity following stimulation of the lateral olfactory tract was present by postnatal day 5, the youngest age tested. The duration of this inhibition was greatest in young animals, decreasing after postnatal day 15. Possible mechanisms of this enhanced inhibition in neonates were discussed.

Action Potentials↗

Early handling increases hippocampal long-term potentiation in young rats.

The hippocampal formation undergoes major anatomical and physiological changes postnatally, and thus might be expected to be particularly sensitive to early handling effects. Long-term potentiation (LTP) in the hippocampal formation, a form of brain plasticity thought to be important in learning and memory, was examined in young rats following early handling or control treatments. The amplitude of LTP was reliably greater in rats receiving the early handling regime. Possible mechanisms and consequences of enhanced LTP were discussed.

Animals↗

In vivo skeletal localization properties of 99mTc complexes of large phosphonate ligands.

Tetramethylenephosphonate derivatives of norborane (TPNB) and dicyclopentadiene (TPDCPD) were shown to readily form stable chelates with 99mTc that had high and selective bone uptake. The skeletal uptake and blood clearance properties of 99mTc-TPNB were similar to 99mTc-MDP in both rats and rabbits. This suggests additional studies to further evaluate 99mTc-TPNB or perhaps other large-organic based multidentate phosphonate ligands as potential bone imaging agents is warranted.

Animals↗

Periventricular leukomalacia: evaluation with MR imaging.

We reviewed 24 magnetic resonance (MR) images of 12 infants diagnosed as having periventricular leukomalacia based on ultrasound results. Abnormalities were identified on the MR images of every patient and were divided into three categories: distribution of low-signal-intensity areas within the cerebral white matter, degree of ventriculomegaly and brain atrophy, and extent of myelination. Follow-up examinations on six patients were also compared for significant changes. Abnormalities noted on MR images that most consistently related to poor outcome for the patient were low-signal-intensity lesions involving all four cerebral lobes, moderate to severe delays in myelination, lack of progression of myelination, and moderate to severe cortical atrophy. MR imaging was able to depict the extent and progression of myelination, and it may be used to continue follow-up of these patients beyond the time of fontanel closure.

Brain Ischemia↗

Effect of hypoxia and hypercapnia on neurohypophyseal blood flow.

Neurohypophyseal blood flow responses to hypoxia and hypercapnia were studied in pentobarbital anesthetized, paralyzed dogs. Arterial O2 content was lowered from control (18 +/- 2 vol%) to 8 +/- 1 vol% by either decreasing O2 tension (hypoxic hypoxia, HH) or by increasing carboxyhemoglobin saturation (carbon monoxide hypoxia, COH) at normal O2 tension. In all animals HH and COH resulted in similar increases in total cerebral blood flow (239 and 300%, respectively). Regional cerebral blood flow showed a similar increase for all brain regions except the neurohypophysis (NH). The NH increased its blood flow with HH (approximately 320% of control) but was unchanged with COH (117% of control). The responsiveness of NH blood vessels was tested under conditions of hypercapnia (10% CO2) and HH with blood pressure controlled by concurrent hemorrhage. The response of NH vessels to altered arterial O2 tension occurs independently of blood pressure. Systemic [H+] or CO2 tension produce only small changes in NH blood flow. These data suggest that hypoxic and hypercapnic regulatory mechanisms for the NH are different from those of other brain regions. The precise mechanism by which the NH hypoxic response occurs remains unclear, but our data suggest an important role for systemic arterial O2 tension and chemoreceptors.

Animals↗

Impotence in scleroderma.

Hormonal, neurologic, and vascular factors affecting potency were evaluated in 10 men with scleroderma and in 10 age-matched men with rheumatoid arthritis. Impotence was reported by 6 of the patients with scleroderma and none with rheumatoid arthritis. Studies of serum testosterone, free testosterone index, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, thyroxine, and thyrotropin did not show a hormonal basis for impotence in any patient. Neurologic causes were not found on physical examination. Penile blood pressures were markedly abnormal in 4 impotent patients, intermediate in 2 impotent and 3 potent patients, and normal in 11 potent patients. A history of claudication and diminished ankle blood pressures indicated large vessel disease in 2 impotent patients; the remaining 4 impotent men had normal ankle pressures, suggesting that their poor penile blood pressures and impotence were due to small vessel disease, perhaps the small artery lesions of scleroderma.

Adult↗

Sonography of the adrenal glands in chronic disseminated histoplasmosis.

In this retrospective study, the findings on abdominal sonograms in six patients newly diagnosed as having chronic disseminated histoplasmosis are reported. Five of six patients showed bilateral adrenal gland enlargement that was similar in degree from side to side. The most characteristic feature was the maintenance of a triangular shape in five glands and a cylindrical shape in two glands. Four glands had a nonspecific round or oval shape. All sonographic findings correlated well with the computed tomographic (CT) findings on each patient except that CT detected the one enlarged right adrenal gland not demonstrated sonographically. Abdominal sonography may provide the initial important clue to the diagnosis of chronic disseminated histoplasmosis.

Adrenal Gland Diseases↗

Barbiturate-enhanced paired-pulse depression in neonatal rats.

Paired-pulse depression of the population spike in the hippocampal formation of barbiturate anaesthetized mature rats is increased compared to that in urethane unanaesthetized rats. This barbiturate-induced increase in depression is greatly enhanced in immature animals, which are also known to be behaviorally more sensitive to barbiturates. These results suggest an increased sensitivity of the recurrent inhibitory (possible GABAergic) system to barbiturates in the immature central nervous system.

Age Factors↗

Suppressor T-cell activity in MRL/Mp-lpr/lpr mice: differential effects on primary and memory antibody responses of MRL/Mp-lpr/lpr and MRL/Mp-+/+ spleen cells to thymus dependent and thymus independent antigens in vitro.

We have previously shown that suppressor-T-cell (TS) activity in the spleens of autoimmune MRL/Mp-lpr/lpr (MRL/l) mice is increased after 2 months of age. The TS suppress the in vitro primary IgM response to the thymus-dependent (TD) antigen sheep erythrocytes (SRBC) of B and T cells from young congenic MRL/Mp-+/+ (MRL/n) mice which lack the lymphoproliferation (lpr) gene. The TS are nylon wool nonadherent, Thy 1.2 positive, and radiation sensitive. The studies presented here were done to further characterize the TS and to attempt to determine the mechanism of action of these cells. We found that increased TS activity was also present in the proliferating lymph nodes of old MRL/l mice but not in lymph nodes of young MRL/l or MRL/n mice. The splenic TS equally suppressed the primary IgM SRBC response of both young MRL/l and MRL/n B and T cells, indicating that MRL/l SRBC-specific B and T cells are not resistant to suppression. The IgM response of MRL/n B and T cells to the T-independent (TI) antigen trinitrophenyl conjugated to Brucella abortus (TNP-BA) was not suppressed by the TS, although the IgM response to TNP was suppressed when TNP was coupled to the TD carrier SRBC. The results of kinetics studies of TS expression showed that when the TS were added on Day 0 of culture the SRBC response was suppressed as early as Day 2 of culture; however, when the TS were added on Days 1, 2, or 3 of culture, the suppression was reduced. The TS suppressed the in vitro memory IgG response of spleen cells from MRL/n mice which had been primed with SRBC; the memory IgG responses of spleen cells from MRL/l mice were variably suppressed. Taken together, these results suggest that the TS suppress TH function in early events of antibody production and that some activated B or T cells may be resistant to the effects of the TS. Increased TS activity was not present in the spleens of aged New Zealand Black X NZ White (NZB/W) F1 mice. Possible reasons for the presence of increased TS activity in MRL/l mice and its relation to autoimmune disease is discussed.

Age Factors↗

Odor familiarity alters mitral cell response in the olfactory bulb of neonatal rats.

Previous studies have shown that rat pups have an enhanced metabolic activity to familiar odors in specific glomeruli of the olfactory bulb. The present study examined extracellularly recorded mitral cell responses to odors in this glomerular region, in odor-familiar and odor-unfamiliar pups. Mitral cells in odor-familiar pups had significantly fewer excitatory and more inhibitory responses to the familiar odor than controls. There were no differences between groups in responses to a novel odor. These results demonstrate that neonatal exposure to odors selectively alters subsequent mitral cell responsiveness to that odor.

Animals↗

Transient analysis of the canine cerebrovascular response to carbon dioxide.

Cerebral venous outflow and carbon dioxide transients were studied during five different transitional states: (1) on and off 10% carbon dioxide breathing, (2) on and off hyperventilation, (3) on 7% carbon dioxide breathing, (4) on 10% carbon dioxide breathing initiated from 7% carbon dioxide breathing, and (5) on 10% carbon dioxide breathing initiated during intracarotid papaverine infusion, in pentobarbital anesthetized, paralyzed, mechanically ventilated dogs. Plots of the temporal relationships between these variables indicated that cerebral blood flow is closely related with cerebral venous carbon dioxide tension but not arterial carbon dioxide tension. The rate at which flow changed upon transition from one steady state to another was phase dependent, in that longer times were required to establish stable conditions in the on phase than in the off phase. The magnitude of the maximum rates of change in cerebral blood flow achieved during transition was influenced both by the size of the forcing function and the level of flow present at the time the response was initiated. Directional changes had no effect upon the maximum rate of the flow change as long as equivalent-sized forcing functions were employed and the initial blood flow levels were similar between responses. However, faster flow transients could be produced by increasing either of the latter two factors. These findings are consistent with the hypothesis that it is either tissue carbon dioxide tension or cerebral venous carbon dioxide tension that is the important variable regulated by cerebral blood flow. The rate-limiting factor in the response appears to be carbon dioxide delivery rate and not the rate of carbon dioxide diffusion.

Animals↗

Hormonal modulation of responses to thymus-independent and thymus-dependent antigens in autoimmune NZB/W mice.

Previous work suggested that gonadal steroids influence immunity through the thymus, but the mechanisms were unclear. To investigate the effects of these hormones on immune responses to T1 and TD antigens in autoimmune mice, we studied hybrid NZB/W mice and the nonautoimmune DBA/2 strain. Mice castrated at 14 days of age were implanted with Silastic capsules releasing, in adults, physiologic levels of E2 in males or Te in females. Sham-operated controls received empty capsules. Splenic PFC were quantified 4 to 5 days after challenge with the TI2 antigen TNP-Ficoll, the TI1 antigen TNP-LPS, or the TD antigen SRBC. Young castrated NZB/W males implanted with E2 had striking enhancement of IgM responses to TNP-Ficoll when compared to castrated Te-treated females and comparable sham-operated controls of both sexes. E2 also stimulated responses to TNP-LPS. In response to challenge with SRBC, young E2-treated NZB/W males had a consistent trend to increased IgM PFC, and the stimulatory effect of E2 on IgG plaques was variable. Physiologic doses of Te had no consistent effect on responses in young mice. In old female NZB/W mice, Te caused PFC response after immunization with TNP-Ficoll to resemble age-matched NZB/W males. As sham-operated NZB/W females grew older, PFC responses to SRBC fell. This age-related phenomenon was delayed, however, in female castrates implanted with Te. In contrast, Te clearly suppressed responses to TNP-LPS. Implantation of E2 did not alter responses to TNP-Ficoll, TNP-LPS, or SRBC in nonautoimmune DBA/2 males. This finding suggested that exogenous E2 given in physiologic doses did not influence immunologic responsiveness in a normal strain to the degree seen in hormone-sensitive NZB/W mice. It was concluded that E2 enhanced responses to a variety of exogenous antigens in autoimmune NZB/W mice. The most consistent E2-induced increase in PFC response was observed with TI antigens, suggesting that E2 exerted its effects on B cells or Ts.

Animals↗

Amplifier T cell activity is decreased in MRL/1 mice: failure of concanavalin A and anti-lymphocyte serum to enhance antibody responses to thymus-independent antigens.

In order to indirectly assess T and B cell function in vivo in spontaneously autoimmune MRL mice, IgM plaque forming cell (PFC) responses to the thymus-independent antigens type III pneumococcal polysaccharide (S3) and polyvinylpyrrolidone (PVP) were determined. Both MRL/Mp-lpr/lpr (MRL/l) and MRL/Mp+/+ (MRL/n) mice responded well to S3 and, in fact, low doses of S3 which are not immunogenic in normal strains of mice elicited good responses in MRL mice. PVP was less immunogenic than S3, however, doses of PVP which are considered sub-immunogenic in normal mice did elicit responses in MRL mice. The effect of ageing on S3 and PVP responsiveness in MRL mice was also determined. Responses to S3 and PVP declined minimally in MRL/l mice and were unchanged in MRL/n mice. Amplifier T cell (TA) activity in MRL mice was indirectly assessed by determining the effect on concanavalin A or anti-lymphocyte serum on PFC responses to S3 and PVP. Whereas significant enhancement of the S3 and PVP IgM PFC responses occurred in MRL/n mice, neither method elicited remarkable enhancement in MRL/l mice. The lack of IgM enhancement was not due to altered kinetics of activation nor to a switch to IgG PFC responses. Possible reasons for the apparent dysfunction of TA in MRL/l mice are discussed.

Aging↗

Effect of mefenidil on cerebral and peripheral hemodynamics in dogs.

Mefenidil (5-methyl-2-phenyl-4-imidazole-acetonitrile) has been reported to be a selective cerebral vasodilator. We examined the specificity of this vasodilator by using the radiolabeled microsphere technique to compare changes in cerebral blood flow (CBF) with those in other organs. Measurements were made in pentobarbital-anesthetized dogs at 10 min of continuous i.v. infusion of mefenidil at rates of 0.025, 0.25 and 2.5 mg/min/kg. Systemic vascular resistance decreased at 0.25 mg/min/kg without a change in CBF. At the highest infusion rate, CBF increased by 54 +/- 15% (+/- S.E.; n = 9) accompanied by a 9-mm Hg rise in intracranial pressure and a 14-mm Hg fall in mean aortic pressure. However, cardiac output increased by 68 +/- 8%, which was distributed primarily to right ventricle (541 +/- 95%), left ventricle (488 +/- 109%), small intestine (136 +/- 31%) and large intestine (57 +/- 15%). Within the brain, thalamic and brainstem regions had larger increases in blood flow than cerebellum and cerebrum. Caudate nucleus had a greater percentage of response than white matter. Using the cerebral venous outflow technique in another series of seven dogs, mefenidil (40-mg/kg i.v. bolus) produced a 20 +/- 8% increase in CBF with no change in O2 uptake. These data show that mefenidil is capable of increasing CBF in healthy brain without stimulating O2 uptake. However, the clinical usefulness of mefenidil as a cerebral vasodilator may be limited by the accompanying arterial hypotension due to systemic vasodilation, which was most prominent in heart and gut.

Animals↗

Effect of hypocalcemia on cardiac function in very-low-birth-weight preterm neonates: studies of blood ionized calcium, echocardiography, and cardiac effect of intravenous calcium therapy.

Traditionally, in infants, a serum calcium value less than 7.0 mg/dL is considered to impair cardiac function. In very-low-birth-weight infants, we studied the hypotheses that decline in serum calcium to 6.0 mg/dL (1) would not impair cardiac function and (2) ionized calcium would remain greater than 3.0 mg/dL. We also evaluated the effect of calcium infusion on cardiac function. We studied 15 normokalemic and normonatremic infants whose birth weights were 822 to 1,450 g and were less than 32 weeks' gestation. When serum calcium declined to less than 6.0 mg/dL, 18 mg/kg of calcium as 5% calcium gluconate was infused for 10 minutes. Serum total calcium concentration, blood ionized calcium concentration, ECG, and M-mode echocardiogram were obtained on entry into the study, when the infants were hypocalcemic, immediately after treatment with calcium, and eight hours after treatment. Ionized calcium values were calculated based on serum total calcium and serum protein, and corrected calcium values were calculated based on serum total calcium, serum albumin, and blood pH. In all infants, serum calcium value declined to less than 7.0 and in eight infants to less than 6.0 mg/dL. Assessment of heart rate, systolic blood pressure, ejection fraction, left ventricular systolic time interval, right ventricular systolic time interval, fiber shortening index, and left ventricular mean velocity of circumferential fiber shortening showed no significant alteration from baseline during hypocalcemia or in association with intravenous slow bolus infusion of 18 mg/kg of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

The reliable sonographic diagnosis of hypertrophic pyloric stenosis.

Fifty-five infants who presented to the Oklahoma Children's Memorial Hospital with vomiting and the clinical suspicion of hypertrophic pyloric stenosis (HPS) were evaluated using real-time ultrasound. Previously published criteria for the sonographic diagnosis of HPS were evaluated in these patients. The anterposterior diameter measurement of 1.5 cm or greater proposed by Strauss et al. had an accuracy of 36/50 (72%). The 4-mm or greater wall thickness measurement of Blumhagen et al. was correct in 46/50 (92%) of cases. A proposed criterion, the true pyloric muscle (TPM) length of 2.0 cm or greater was accurate in 33/33 cases. Application of the TPM length criterion should improve the reliability of sonographic diagnosis of HPS and decrease the need for radiographic studies.

Humans↗