Biomedical subjects

J G Wood

Publications and source records attributed to J G Wood.

At least 19 recordsLinked to original sources

PubMed1995

Ischemia-reperfusion increases gastric motility and endothelin-1-induced vasoconstriction.

The purpose of our study was to 1) examine the effect of ischemia-reperfusion on gastric vascular resistance and motility, 2) determine whether endothelin-1 (ET-1)-induced vasoconstriction is enhanced after ischemia-reperfusion, and 3) assess the effect of superoxide dismutase (SOD) on these ischemia-reperfusion-induced alterations. These experiments used a mechanically perfused ex vivo gastric segment of chloralose-anesthetized dogs. We first evaluated the effect of varying the duration of total ischemia on reperfusion-induced changes in gastric vascular resistance and motility. In other experiments, responses to ET-1 (10(-10) M) were compared before and after 30-min ischemia and 30-min reperfusion, with saline or SOD (10 U/ml) infused intra-arterially to the stomach during reperfusion. Our results show that 1) after ischemia, vasodilation is seen initially on reperfusion followed by a slowly developing, progressive increase in vascular resistance, 2) the force of gastric contractions was reduced during ischemia but elevated immediately on reperfusion, 3) vasoconstrictor responses to ET-1 are enhanced after ischemia-reperfusion, and 4) SOD reduced the enhanced response to ET-1 and force of contractions. Our findings support the hypothesis that reactive oxygen metabolites contribute to augmented vascular reactivity and hypercontractility after ischemia-reperfusion.

Animals↗

PubMed1992

Evidence that the earliest generated cells of the murine cerebral cortex form a transient population in the subplate and marginal zone.

We used bromodeoxyuridine to label the earliest generated cells of the murine cerebral cortex while they were dividing, and then observed their distributions at several instances later in development. Shortly before birth, many of the labelled cells were either above the cortical plate, in the marginal zone, or below it, in the region known as the subplate in other species. These cells had disappeared by postnatal day 21.

Animals↗

PubMed1992

Platelet activating factor-induced changes in gastric motility and vascular resistance.

Our study evaluated the hypothesis that gastric contractions may contribute to ischemia by increasing vascular resistance. Using an ex vivo segment of the dog's stomach as the experimental model, contractions were induced with platelet activating factor (PAF) and bethanechol, a cholinergic vasodilator. Spontaneous contractions produced slight increases in luminal pressure and corresponding increases in vascular resistance. PAF caused statistically significant, dose-dependent increases in the force of gastric contractions that were highly correlated with phasic changes in vascular resistance. To ensure that the relationship between contractions and vascular resistance was independent of vascular tone, we next examined responses to bethanechol. Bethanechol stimulated contractions that also transiently increased both luminal pressure and vascular resistance. Our results demonstrate that gastric contractions markedly increase vascular resistance and support the hypothesis that hypercontractility may contribute to the development of mucosal ischemia during ulceration.

Animals↗

PubMed1992

Identifying acoustic scattering sources in normal renal parenchyma in vivo by varying arterial and ureteral pressures.

Ultrasonic backscatter properties of normal dog kidney parenchyma are examined in vivo to determine sources of acoustic scattering. We systematically varied the renal perfusion and ureteral pressures to obtain detailed information about scattering sources that could not be seen under in vitro conditions. These data suggest that in normal parenchyma the principal sources of backscatter are Bowman's capsule at low frequencies (2.5-5.0 MHz) and glomerular arterioles at high frequencies (5.0-15.0 MHz). We found that the integrated backscatter coefficient (IBC) in normally perfused kidney cortex is approximately half that measured in the ischemic organ at all frequencies. Ischemia was found to reduce scatterer size estimates (D) by 10% at low frequencies and increase D54% at high frequencies. Acute obstruction of the kidney, under diuresis, produced an 11% increase in D at low frequencies, and no significant change in D at high frequencies. These variations in backscatter measurements are explained in terms of changes in the microscopic anatomy of the kidney.

Animals↗

PubMed1992

Functional consequences of unilateral olfactory deprivation: time-course and age sensitivity.

Unilateral olfactory deprivation in the rat profoundly modifies olfactory bulb anatomy, chemistry and function. The present report examined the time-course of the functional effects of unilateral deprivation on inhibition in the olfactory bulb using paired-pulse stimulation of the lateral olfactory tract and olfactory nerve. In addition, an attempt was made to correlate these physiological measures with olfactory bulb dopamine and norepinephrine levels and tyrosine hydroxylase immunoreactivity. Deprivation from postnatal day 1 to postnatal day 20 or postnatal day 40 significantly enhanced lateral olfactory tract paired-pulse depression, while late onset deprivation (postnatal day 20) had no effect. Olfactory nerve paired-pulse depression was enhanced by 40 days of deprivation regardless of the age at onset. The time-course of these deprivation-induced physiological changes did not correlate well with reductions in dopamine. Dopamine levels were reduced in all deprivation conditions by 70-80% compared with control bulbs. Norepinephrine content was slightly elevated in deprived bulbs. These results suggest that early olfactory deprivation modifies olfactory bulb synaptic activity and further, as with other sensory systems, these effects are age and duration dependent.

Aging↗

PubMed1992

Gastric microvascular actions of platelet-activating factor: role of leukocytes.

This study examined the effects of platelet-activating factor (PAF) on the gastric microcirculation. We measured changes in vascular resistance and filtration during intra-arterial infusion of graded doses of PAF and its metabolite, lyso-PAF, to an ex vivo gastric segment of alpha-chloralose-anesthetized dogs. PAF produced dose-related sustained increases in vascular resistance (2-150 nM; n = 6). Filtration and venous hematocrit were also both significantly increased by PAF. In contrast, there were no statistically significant changes in these measurements with lyso-PAF (n = 6). Filtration and venous hematocrit were not significantly changed by norepinephrine at doses that increased perfusion pressure to the same degree as PAF (n = 4). PAF also increased filtration in the absence of changes in perfusion pressure (during maximal vasodilation induced with papaverine). Finally, removal of leukocytes from gastric arterial blood significantly attenuated these responses to PAF. Our results suggest that PAF-induced mucosal ischemia is primarily due to vasoconstriction and may involve edema formation due to increased filtration as well. In addition, these responses to PAF appear to be largely dependent on circulating leukocytes.

Analysis of Variance↗

PubMed1992

Relative potency of endothelin analogues on changes in gastric vascular resistance.

The purpose of this study was to examine the effects of several endothelin analogues on the gastric microcirculation. We measured changes in vascular resistance of an ex vivo gastric segment of chloralose-anesthetized dogs. Changes in luminal pressure were used to quantitate contractile force. Graded doses of endothelin-2 (ET-2), endothelin-3 (ET-3), [Ala3,11]endothelin (Ala-ET), and the COOH-terminal hexapeptide (ET-C) were infused intra-arterially to the stomach. ET-2 and Ala-ET produced dose-related sustained increases in vascular resistance (10(-10) to 10(-8) M), with Ala-ET less potent than ET-2. In contrast, ET-3 was a weak vasoconstrictor while ET-C had no significant effects. There were no detectable changes in filtration with any of these analogues. However, the force of gastric contractions was significantly attenuated by both ET-2 and Ala-ET in a dose-dependent manner. We found that endothelin analogues produced sustained vasoconstriction of the gastric segment with a potency order of ET-2 greater than Ala-ET-3 much greater than ET-C. Our results suggest that endothelin analogues are potent vasoconstrictors but have little effect on filtration across the gastric vasculature.

Animals↗

PubMed1991

Tyrosine phosphorylation systems in Alzheimer's disease pathology.

Immunohistochemical techniques have been used to assess the distribution of phosphotyrosine-containing compartments in Alzheimer's disease (AD) pathology. Elevated levels of phosphotyrosine are apparent in the somatodendritic compartment of tangle-bearing neurons, in the neuritic plaque (NP) and in dystrophic neurites coursing through the neuropil. The only neuronal staining observed in non-AD tissue is in developing neurites. This suggests that some neuronal elements involved in AD pathology may be recapitulating a developmental profile or, alternately, that elevated phosphotyrosine levels may reflect a role for tyrosine kinase/phosphatase systems in the degeneration process directly. Cells in the neuritic plaque which strongly resemble microglia also contain elevated levels of phosphotyrosine compared to non-activated ramified microglia in the same tissue section. Thus, tyrosine phosphorylation systems may be involved in the response of microglia to degeneration in AD pathology. Implications of these results are discussed.

Aged↗

PubMed1991

200 kD neurofilament protein and synapse elimination in the rat soleus muscle.

We studied the distribution and appearance of the phosphorylated form of the 200 kD neurofilament protein in the rat soleus muscle during the period of postnatal synapse elimination. Unlike many muscles, the appearance of singly innervated muscle cells in soleus occurs well after myogenesis has been completed, so that synapses are eliminated from a stable population of muscle cells. Immunoreactivity to the 200 kD neurofilament protein is present in the terminals of neuromuscular synapses of animals at all postnatal ages from 0 to 21 days. Before postnatal day 10, when physiological studies indicate that all soleus muscle cells receive more than one synaptic input, as many as 30% of soleus muscle cells contain phosphorylated 200 kD neurofilament protein immunoreactivity in only one synaptic terminal. At older ages the number of polyneuronally innervated muscle cells observed using immunostaining is similar to that observed physiologically. These findings suggest that not all developing neuromuscular synapses contain phosphorylated 200 kD neurofilament protein, and that those terminals lacking it comprise most of those eliminated early in the postnatal period. We conclude that the presence of phosphorylated 200 kD neurofilament protein might be highly correlated with the survival of motor nerve terminals during postnatal neuromuscular synapse elimination.

Animals↗

PubMed1991

Gastric contractions produce phasic changes in perfusion pressure.

This study examined the relationship between motility and perfusion pressure of an ex vivo segment of the canine stomach perfused at constant flow. Changes in luminal pressure were used to quantitate contractile force. Under control conditions, spontaneous contractions increased luminal pressure by 18.8 +/- 1.1 mmHg and gastric perfusion pressure by 14.2 +/- 0.8 mmHg. Changes in luminal and perfusion pressures during contractions were highly correlated (r2 = 0.963, P less than 0.0001, 109 observations in 5 dogs). In separate studies, we assessed the effects of atropine, neostigmine (an acetylcholinesterase inhibitor), and bethanechol (a muscarinic cholinergic agonist). Atropine attenuated the peristaltic-induced changes in perfusion pressure in a concentration-dependent manner (10(-9) to 10(-6)M) with nearly total inhibition at the highest dose. Neostigmine (10(-9) to 10(-6) M) and bethanechol (10(-8) to 10(-5) M) stimulated contractions, resulting in dose-related increases in luminal and perfusion pressures. Our results demonstrate that cholinergic-dependent contractions produce marked, phasic changes in gastric perfusion pressure.

Animals↗

PubMed1990

Effect of secretin on growth of stomach, small intestine, and pancreas of developing rats.

Secretin is present in the intestine of a number of developing species, and plasma secretin levels are elevated in newborn pigs and humans. Secretin stimulates the growth and affects the enzymatic composition of the stomach, small intestine, and pancreas in adult rats. This suggests a possible role for secretin in the rapid postnatal growth of these organs. We investigated this hypothesis by injecting rats subcutaneously with secretin (100 micrograms/kg) every 12 hr for seven days beginning on postnatal day 3, 6, 13, or 24. Growth parameters (weight, content of protein, DNA) as well as the composition of organ-specific enzymes of the stomach, small intestine, and pancreas were measured. Secretin increased growth parameters of the stomach and small intestine in a similar pattern, and in a quantitatively different fashion from that observed in the pancreas. Secretin's effects were also dependent on postnatal age for all organs studied. These data demonstrate that secretin can influence organ growth and enzyme composition of the stomach, small intestine, and pancreas of developing rats and may be one factor regulating growth and development of these organs.

Aging↗

PubMed1990

Effect of histamine and 1,4-methylhistamine on gastric vascular resistance in dogs.

The goal of this study was to compare the relative potency of histamine and its metabolite, 1,4-methylhistamine, as vasodilators of the gastric circulation. Changes in vascular resistance were measured during local intra-arterial infusion of graded doses of histamine and 1,4-methylhistamine to an ex vivo segment of dog stomach. Infusate concentrations were adjusted to deliver calculated arterial blood concentrations of 0, 3.7, 11, 33, 100, 300, and 900 ng/ml of each substance to the stomach segment. We found that histamine caused rapid dose-related decreases in gastric vascular resistance of up to -47.6 +/- 1.3% compared with control values. The effects of histamine were reversible when infusions ended. In contrast, there were no statistically significant changes in vascular resistance at any dose of 1,4-methylhistamine. In addition, modifications to previous methods using histamine antagonists resulted in greater attenuation of histamine-induced gastric vasodilation. Our results support a role for locally released histamine, but not for 1,4-methylhistamine, as a mediator of gastric vasodilation.

Animals↗

PubMed1989

Subcellular distribution and immunocytochemical localization of protein kinase C in myocardium, and phosphorylation of troponin in isolated myocytes stimulated by isoproterenol or phorbol ester.

Protein kinase C (PKC) catalytic activity was found in the cytosol, sarcolemma and sarcoplasmic reticulum, and PKC immunoreactivity was found in the striated regions and sarcolemma of rat hearts. Enhanced phosphorylation of troponin T and, to a lesser extent, troponin I was noted in isolated rat cardiac myocytes incubated with PKC activator phorbol ester, but only the phosphorylation of troponin I was stimulated by isoproterenol. It is suggested that PKC-mediated phosphorylation of troponin might be involved in regulation of myocardial function or in pathophysiology of the heart.

Animals↗

PubMed1989

Tyrosine phosphorylation in the postnatal rat brain: a developmental, immunohistochemical study.

We have used antibodies against phosphotyrosine to probe 50-microns cerebellar sections from rats of various ages as well as sections of adult brainstem, cerebrum, and olfactory bulb to investigate the developmental appearance of this phosphorylation system as revealed by light microscopy. While the overall intensity of staining in the cerebellum was highest at 7 days, the pattern of staining in the adult is quite disparate from that seen in younger animals. From 10 to 21 days postnatal, staining is associated primarily with the white matter and/or the lower premigratory zone of the external granular layer and adjacent formative molecular layer. While the temporal and spatial appearance of phosphotyrosine immunoreactivity corresponds well to the established patterns of axonal growth in these areas, we cannot at the light level ascertain whether the immunoreactivity is intrinsic or extrinsic to the growing fibers. In animals 28 days and older, however, staining is restricted to a subpopulation of multipolar cells distributed throughout the cerebellum, as well as the olfactory bulb, cerebrum, and brainstem. The phosphotyrosine-positive cells in the adult cerebellum are not comparable to glial-fibrillary-acidic-protein-immunoreactive elements with regard to morphology or distribution, and they fail to colocalize with neuronal somata stained with anti-microtubule-protein-2 antibodies. While it appears that the radial fibers of the Bergmann glia in the external granular layer stain at 7 days, there is no staining detected in the mitotically active neuroblasts of this layer at any age. We conclude that in the immature cerebellum, the majority of tyrosine phosphorylation detectable by this method may be involved in the formation and growth of axonal processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1989

Phosphotyrosine antibodies specifically label ameboid microglia in vitro and ramified microglia in vivo.

Using an affinity-purified, polyclonal antibody to phosphotyrosine (Wang: Molecular and Cellular Biology 5:3640-3643, 1985) we have previously demonstrated that phosphotyrosine immunoreactivity is restricted to a population of multipolar GFAP-negative neuroglia in adult rat brain (Tillotson and Wood: Journal of Comparative Neurology 282:133-141, 1989) and retina (Tillotson and Wood: Journal of Cell Biology 107:724a, 1988). In this study, we show that the phosphotyrosine-immunoreactive cells are microglia. This conclusion is supported by numerous morphological and ultrastructural similarities between the phosphotyrosine-immunoreactive cells and microglia. Furthermore, phosphotyrosine co-localizes with the microglial-specific B4 isolectin of Bandeiraea simplifolia-1 lectin. Phosphotyrosine antibodies also stain ameboid microglia in primary cultures of neonatal rat brain. In addition, after 7 days in vitro, microglia are the only phosphotyrosine-immunoreactive element in the cultures. This temporal pattern of staining in vitro mimics the developmental progression of phosphotyrosine immunoreactivity in situ, in which a variety of structures stain during postnatal neural development (Tillotson and Wood: Journal of Comparative Neurology 282:133-141, 1989), but only microglia stain in mature brain. The significance of phosphotyrosine-containing proteins potentially expressed in a microglial-specific manner is discussed.

Animals↗

PubMed1989

Immunohistochemical evidence for reorganization of tau in the plaques and tangles in Alzheimer's disease.

Cytochemical and biochemical techniques have been used to assess the relationship of epitopes on the microtubule-associated protein, tau, to the cytoskeletal pathology of Alzheimer's disease. The main probes were Tau-1 and Alz-50, two monoclonal antibodies which recognize tau and a potentially related 68 kDa protein. Sequential treatment of tissue slices with combinations of the antibodies showed that each blocked the binding of the other to neurofibrillary tangles and neuritic plaques but not to normal axons. Western blot analysis of tau proteins isolated from Alzheimer's disease brains did not reveal such blocking patterns. The issue of steric hindrance affecting antibody binding in tissue sections was addressed by using Alz-50 in combination with Tau-2, another monoclonal antibody recognizing tau on blots and in Alzheimer's disease pathology. Neither antibody blocked the binding of the other to neurofibrillary tangles and neuritic plaques. These data suggest that the Alz-50 and Tau-1 epitopes are selectively organized in the tangles and plaques to be in close proximity which supports the hypothesis that in Alzheimer's disease pathology, tau is modified.

Aged↗

PubMed1989

Elevated gastrin levels in patients with colon cancer or adenomatous polyps.

Gastrin has been shown to stimulate the growth of carcinogenic-induced colon cancer in animals, and some human colon cancers grown in vitro or as xenografts in nude mice. We determined fasting plasma gastrin levels in control subjects and patients with adenomatous polyps or adenocarcinoma of the colon to determine whether abnormal levels occurred in either patient group. Blood samples were obtained from 73 patients undergoing colonoscopy, primarily for evaluation of Hemoccult-positive stools. Fasting plasma gastrin was significantly greater in patients with adenomatous polyps (24.2 +/- 5.7 pM, N = 25) or colon cancer (84.5 +/- 28.5 pM, N = 20) than in controls (9.9 +/- 0.9 pM, N = 28). Elevations were due to gastrin values greater than control mean + 2 SD in nine patients with polyps (19.5-150.2 pM) and eight with cancer (20.7-403.2 pM). None of the patients had identifiable causes (drugs, prior surgery) for elevated gastrin levels. Our results indicate that elevated plasma gastrin occurs in subgroups of patients with adenomatous polyps or adenocarcinoma of the colon. The cause and potential role of elevated gastrin for polyp and tumor growth in these patients is not known.

Adenocarcinoma↗

PubMed1989

Cytolysis by tumor necrosis factor is preceded by a rapid and specific dissolution of microfilaments.

Tumor necrosis factor (TNF) is cytotoxic to certain transformed cells, whereas normal cells are resistant to its effects. The resistance of normal cells can often be overcome by treatment with inhibitors of transcription or translation such as actinomycin D or cycloheximide (CHI), suggesting that normal cells produce a protein(s) that protects them from TNF-induced cytolysis. In this report, we examine the mechanism of cytolysis in a 3T3-like mouse cell line, C3HA, which was sensitized to TNF by treatment with CHI. We found that an early change in TNF/CHI-treated cells was a significant loss of stress fibers in perinuclear areas of the cytoplasm. The disruption of microfilaments, which was observed within 15 min of treatment, was not seen in untreated cells or in cells treated with either TNF or CHI alone. The dissolution of microfilaments spread peripherally over time and preceded other TNF/CHI-induced effects such as cytoplasmic "boiling," decrease in cell volume, and lysis of the plasma membrane. The breakdown of stress fibers occurred without a change in microtubules or intermediate filaments. Cytochalasin E, which disrupts microfilaments, induced cytolysis of TNF-treated cells even in the absence of CHI; however, demecolcine, which depolymerizes microtubules, did not sensitize cells to TNF. We propose that the TNF-induced cytolysis of certain cell types is preceded by a selective disruption of the microfilament lattice.

Actin Cytoskeleton↗