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H Lai

Publications and source records attributed to H Lai.

At least 91 records · Page 5Linked to original sources

Opioid receptor subtypes that mediate a microwave-induced decrease in central cholinergic activity in the rat.

We performed experiments to investigate subtypes of opioid receptors in the brain involved in the effect of acute (45 min) pulsed microwave exposure (2,450-MHz, 2-microseconds pulses, 500 pps, average power density 1 mW/cm2, peak-power density, 1 W/cm2, average whole body SAR 0.6 W/kg) on cholinergic activity in the rat brain. Rats were pretreated by microinjection of specific antagonists of mu, delta, and kappa opioid-receptors into the lateral cerebroventricle before exposure to microwaves. The data showed that all three subtypes of opioid receptors are involved in the microwave-induced decrease in cholinergic activity in the hippocampus. However, the microwave-induced decrease in cholinergic activity in the frontal cortex was not significantly affected by any of the drug treatments, confirming our previous conclusion that the effect of microwaves on the frontal cortex is not mediated by endogenous opioids.

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Research on the neurological effects of nonionizing radiation at the University of Washington.

This paper reviews research on neurological effects of low-level microwave irradiation, which was performed at the University of Washington, during the decade of the 1980s. We studied in the rat the effects of microwave exposure on the actions of various psychoactive drugs, on the activity of cholinergic systems in the brain, and on the neural mechanisms involved. Our results indicate that endogenous opioids play an important mediating role in some of the neurological effects of microwaves, and that parameters of microwave exposure are important determinants of the outcome of the microwave effects.

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Opioid receptor subtypes mediating the noise-induced decreases in high-affinity choline uptake in the rat brain.

Acute (20 min) exposure to 100-dB white noise elicits a naltrexone-sensitive decrease in sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. In the present study, the subtypes of opioid receptors involved were investigated by pretreating rats with microinjection of specific opioid-receptor antagonists into the lateral cerebroventricle before noise exposure. We found that the noise-induced decrease in high-affinity choline uptake in the hippocampus was blocked by pretreatment with either mu-, delta-, or kappa-opioid-receptor antagonists, whereas the effect of noise on frontal cortical high-affinity choline uptake was blocked by a mu- and delta- but not by a kappa-antagonist. These data further confirm the role of endogenous opioids in mediating the effects of noise on central cholinergic activity and indicate that different neural mechanisms are involved in the effects of noise on the frontal cortical and hippocampal cholinergic systems.

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Naltrexone pretreatment blocks microwave-induced changes in central cholinergic receptors.

Repeated exposure of rats to pulsed, circularly polarized microwaves (2,450-MHz, 2-microseconds pulses at 500 pps, power density 1 mW/cm2, at an averaged, whole-body SAR of 0.6 W/kg) induced biphasic changes in the concentration of muscarinic cholinergic receptors in the central nervous system. An increase in receptor concentration occurred in the hippocampus of rats subjected to ten 45-min sessions of microwave exposure, whereas a decrease in concentration was observed in the frontal cortex and hippocampus of rats exposed to ten 20-min sessions. These findings, which confirm earlier work in the authors' laboratory, were extended to include pretreatment of rats with the narcotic antagonist naltrexone (1 mg/kg, IP) before each session of exposure. The drug treatment blocked the microwave-induced changes in cholinergic receptors in the brain. These data further support the authors' hypothesis that endogenous opioids play a role in the effects of microwaves on central cholinergic systems.

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Effects of noise on high-affinity choline uptake in the frontal cortex and hippocampus of the rat are blocked by intracerebroventricular injection of corticotropin-releasing factor antagonist.

Acute exposure (20 min) to loud noise (100 dB) decreased sodium-dependent high-affinity choline uptake activities in the frontal cortex and hippocampus of the rat. These effects were blocked by intracerebroventricular (i.c.v.) administration of the corticotropin-releasing factor (CRF) antagonist alpha-helical-CRF9-41 (alpha-HCRF) immediately before noise exposure. Intracerebroventricular injection of CRF (1 microgram) also decreased high-affinity choline uptake in the frontal cortex and the hippocampus of the rat, and these effects of CRF could be blocked by pretreating the animal with the narcotic antagonist naltrexone (1 mg/kg, i.p.). These results indicate that the effects of noise on central cholinergic systems are mediated by CRF and suggest a stressor-CRF-endogenous opioid-acetylcholine sequence of effects in the brain.

Acoustic Stimulation↗

Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy.

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P less than 0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P less than 0.01) and thymidine kinase activity (P less than 0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P less than 0.05) in the rats treated with cyclosporine as compared to the vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

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Cyclosporine augments hepatic regenerative response in rats.

A number of mechanisms participate in the hepatic injury that occurs during and following liver transplantation. A normal allograft regenerative response is probably essential for a successful transplant outcome. In this study, the effect of cyclosporine, a potent immunosuppressant used routinely after liver transplantation, on the regenerative response of the liver after partial hepatectomy was investigated. Male Wistar rats were pretreated for one week with either cyclosporine or the olive oil vehicle and were subjected to either a two-thirds partial hepatectomy or a sham operation. Animals were sacrificed at various times postoperatively and the remnant livers were weighed to determine the liver weight to body weight ratio, two biochemical measures of a regenerative response (cytosolic ornithine decarboxylase activity and thymidine kinase activity), and the hepatic content of estrogen and androgen receptors, as the content of these receptors has been shown to modulate, at least in part, the subsequent hepatic regenerative response. The preoperative hepatic cytosol content of ornithine decarboxylase, thymidine kinase, and estrogen receptor was significantly greater (P less than 0.05) in rats pretreated with cyclosporine than in those treated with the vehicle alone. A significant increase in ornithine decarboxylase and thymidine kinase activities occurred after partial hepatectomy in both the cyclosporine-pretreated and vehicle-pretreated animals. The absolute levels for each parameter were also greater in the cyclosporine-treated animals than in the vehicle-treated controls at 24 hr after partial hepatectomy (P less than 0.05). The pattern of change in the hepatic cytosolic content of estrogen and androgen receptors in both groups of animals was comparable with those described previously for regenerating liver.(ABSTRACT TRUNCATED AT 250 WORDS)

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Acute white noise exposure affects the concentration of benzodiazepine receptors in the brain of the rat.

Rats were acutely (45 min) exposed to 100-dB white noise, and benzodiazepine receptors in the cerebral cortex, hippocampus, and cerebellum were studied immediately after exposure by the receptor-binding assay using 3H-flunitrazepam as the ligand. An increase in the concentration of receptors was observed in the cerebral cortex, whereas no significant change in receptor concentration was seen in the hippocampus and cerebellum. No significant effect of noise on receptor binding affinity was detected in the three brain regions studied. Experimental handling also did not significantly affect the benzodiazepine receptor properties. These data confirm previous reports that acute exposure to stressor can cause rapid changes in benzodiazepine receptors in the brain.

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Corticotropin-releasing factor antagonist blocks microwave-induced decreases in high-affinity choline uptake in the rat brain.

Acute (45-min) irradiation with pulsed low-level microwaves (2450-MHz, 2 microseconds pulses at 500 pps, average power density of 1 mW/cm2, whole-body average specific absorption rate of 0.6 W/kg) decreased sodium-dependent high-affinity choline uptake (HACU) activity in the frontal cortex and hippocampus of the rat. These effects were blocked by pretreating the animals before exposure with intracerebroventricular injection of the specific corticotropin-releasing factor (CRF) receptor antagonist, alpha-helical-CRF9-41 (25 micrograms). Similar injection of the antagonist had no significant effect on HACU in the brain of the sham-exposed rats. These data suggest that low-level microwave irradiation activates CRF in the brain, which in turn causes the changes in central HACU.

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Neuroanatomic and neurochemical abnormalities in nonhuman primate infants exposed to weekly doses of ethanol during gestation.

Ethanol was orally administered once per week to 54 gravid pigtailed macaques (Macaca nemestrina) in doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5 or 4.1 gm/kg from the 1st week in gestation or in doses of 2.5, 3.3 or 4.1 gm/kg from the 5th week. Mean maternal peak plasma ethanol concentrations (MPPEC's) ranged from 24 +/- 6 mg/dl at the 0.3 g/kg dose to 549 +/- 71 mg/dl at the 4.1 g/kg dose. Thirty-three live born infants were assessed for abnormalities of physical and behavioral development. Ocular pathology, neuropathologic and neurochemical assessements were done on 31 animals at 6 months postnatal age. Microphthalmia was noted in three of the 26 animals exposed to ethanol. Retinal ganglion cell loss was significantly associated with intra-uterine ethanol exposure. Microphthalmia and retinal ganglion cell loss was observed in both the delayed and full-gestational exposed animals. No structural anomalies were found in the brains via gross inspection or light microscopy. Chemical abnormalities in the striatal nuclei were identified. Striatal dopamine concentrations increased with increasing MPPEC exposure (0-249 mg/dl) among animals exposed weekly to ethanol throughout gestation. Striatal dopamine concentrations decreased with increasing MPPEC exposure (260-540 mg/dl) among animals whose weekly exposure to ethanol was delayed until the 5th week of gestation. The same pattern of association was also noted between MPPEC and ultrastructural alterations in the caudate nucleus. The extent of ultrastructural alterations increased with increasing MPPEC among the full-gestational exposed animals and decreased with increasing MPPEC among the delayed-dose animals.

3,4-Dihydroxyphenylacetic Acid↗

Repeated noise exposure affects muscarinic cholinergic receptors in the rat brain.

We examined the effect of repeated exposure to 100-dB white noise (10 daily 45-min sessions) on muscarinic cholinergic receptors in different regions of the rat brain. Twenty-four hours after the last exposure session, increase in concentration (Bmax) of [3H]quinuclidinyl benzilate ([3H]-QNB) binding sites was observed in the hippocampus, but no significant change was seen in the striatum, frontal cortex, and hypothalamus. No significant effect of noise on receptor binding affinity (Kd) was found. Pretreating the rats with naltrexone (1 mg/kg, IP) before exposure blocked the noise-induced increase in cholinergic receptors in the hippocampus.

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Low-level microwave irradiation and central cholinergic activity: a dose-response study.

Rats were irradiated with circularly polarized, 2,450-MHz pulsed microwaves (2-microseconds pulses, 500 pulses per second [pps]) for 45 min in the cylindrical waveguide system of Guy et al:(Radio Sci 14:63-74, 1979). Immediately after exposure, sodium-dependent high-affinity choline uptake, an indicator of cholinergic activity in neural tissue, was measured in the striatum, frontal cortex, hippocampus, and hypothalamus. The power density was set to give average whole-body specific absorption rates (SAR) of 0.3, 0.45, 0.6, 0.75, 0.9, or 1.2 W/kg to study the dose-response relationship between the rate of microwave energy absorption and cholinergic activity in the different areas of the brain. Decrease in choline uptake was observed in the striatum at a SAR of 0.75 W/kg and above, whereas for the frontal cortex and hippocampus, decreases in choline uptake were observed at a SAR of 0.45 W/kg and above. No significant effect was observed in the hypothalamus at the irradiation power densities studied. The probit analysis was used to determine the SAR50 in each brain area, i.e., the SAR at which 50% of maximum response was elicited. SAR50 values for the striatum, frontal cortex, and hippocampus were 0.65, 0.38, and 0.44 W/kg, respectively.

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Low-level microwave irradiation and central cholinergic systems.

Our previous research showed that 45 min of exposure to low-level, pulsed microwaves (2450-MHz, 2-microseconds pulses, 500 pps, whole-body average specific absorption rate 0.6 W/kg) decreased sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. The effects of microwaves on central cholinergic systems were further investigated in this study. Increases in choline uptake activity in the frontal cortex, hippocampus, and hypothalamus were observed after 20 min of acute microwave exposure, and tolerance to the effect of microwaves developed in the hypothalamus, but not in the frontal cortex and hippocampus, of rats subjected to ten daily 20-min exposure sessions. Furthermore, the effects of acute microwave irradiation on central choline uptake could be blocked by pretreating the animals before exposure with the narcotic antagonist naltrexone. In another series of experiments, rats were exposed to microwaves in ten daily sessions of either 20 or 45 min, and muscarinic cholinergic receptors in different regions of the brain were studied by 3H-QNB binding assay. Decreases in concentration of receptors occurred in the frontal cortex and hippocampus of rats subjected to ten 20-min microwave exposure sessions, whereas increase in receptor concentration occurred in the hippocampus of animals exposed to ten 45-min sessions. This study also investigated the effects of microwave exposure on learning in the radial-arm maze. Rats were trained in the maze to obtain food reinforcements immediately after 20 or 45 min of microwave exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

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Mode of alloantibody-mediated blockade of allo-sensitization for tumor allograft rejection.

The mode of alloantibody-mediated inhibition of allo-sensitization for tumor allograft rejection was studied. Relatively small amounts of anti-H-2d alloantiserum administered shortly before or after injection of allogeneic spleen cells blocked the allo-sensitization for second-set tumor allograft rejection. In contrast, the alloantiserum injected shortly before inoculation of tumor barely enhanced the tumor growth. The passively administered alloantiserum inhibited the sensitization for allospecific cytotoxic T lymphocyte responses in vitro. Further study revealed that the allo-sensitization could be blocked with antiserum specific against only one of the expressed H-2 antigens on stimulator cells. Correspondingly, H-2Dd-monospecific monoclonal antibody (IgG2a) was effective in inhibiting the sensitization with cells expressing multiple H-2 alloantigens. These results suggest that antibody-mediated inactivation of stimulator cells as a whole is an important mechanism of the allograft enhancement.

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The effect of different types of hepatic injury on the estrogen and androgen receptor activity of liver.

Mammalian liver contains receptors for both estrogens and androgens. Hepatic regeneration after partial hepatectomy in male rats is associated with a loss of certain male-specific hepatic characteristics. In this study we investigated the effects of lesser forms of hepatic injury on the levels of estrogen and androgen receptor activity in the liver. Adult male rats were subjected to portacaval shunt, partial portal vein ligation, hepatic artery ligation, or two-thirds partial hepatectomy. Another group of animals was treated with cyclosporine. At the time of sacrifice the livers were removed and used to determine the estrogen and androgen receptor activity in the hepatic cytosol. A significant reduction (p less than 0.05) in the hepatic cytosolic androgen receptor activity and a slight increase in the estrogen receptor activity occurred following total portosystemic shunting. Partial ligation of the portal vein, which produces a lesser degree of portosystemic shunting, had no effect on the levels of the estrogen and androgen receptor activity present within hepatic cytosol. Cyclosporine-treated animals had significantly greater (p less than 0.01) levels of estrogen receptor activity in the hepatic cytosol compared to vehicle-treated control animals. Levels of estrogen and androgen receptor activity within the hepatic cytosol remained unchanged after ligation of the hepatic artery. The reduction in the cytosolic estrogen and androgen receptor activity in the liver after partial hepatectomy was confirmed. In summary, certain types of hepatic injury are associated with profound changes in the estrogen and androgen receptor content within the liver.

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Effects of repeated exposure to white noise on central cholinergic activity in the rat.

Acute (45 min) exposure to noise has been shown to decrease sodium-dependent high-affinity choline uptake activity in the frontal cortex and hippocampus of the rat. In the present experiment, the effects of repeated noise exposure on choline uptake in these two brain regions were studied. Rats were exposed to 100-dB white noise in ten 45-min sessions. Tolerance developed to the effects of noise on choline uptake. In addition, the effects were found to be classically conditionable to cues in the exposure environment. These data may have important implications in understanding the health hazard of noise exposure in both the public and occupational environments.

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Acute low-level microwave exposure and central cholinergic activity: studies on irradiation parameters.

Sodium-dependent high-affinity choline uptake was measured in the striatum, frontal cortex, hippocampus, and hypothalamus of rats after acute exposure (45 min) to pulsed (2 microseconds, 500 pps) or continuous-wave 2,450-MHz microwaves in cylindrical waveguides (Guy et al.: Radio Science 14:63-74, 1979) or miniature anechoic chambers (Guy: Journal of Microwave Power 14:327-338, 1979). In all exposure conditions, the average whole-body specific absorption rate was at 0.6 W/kg. Decrease in choline uptake was observed in the frontal cortex after microwave exposure in all of the above irradiation conditions. Regardless of the exposure system used, hippocampal choline uptake was decreased after exposure to pulsed but not continuous-wave microwaves. Striatal choline uptake was decreased after exposure to either pulsed or continuous-wave microwaves in the miniature anechoic chamber. No significant change in hypothalamic choline uptake was observed under any of the exposure conditions studied. We conclude that depending on the parameters of the radiation, microwaves can elicit specific and generalized biological effects.

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Neural mechanisms mediating the hyperthermia elicited by prostaglandin E2 injected into the preoptic-anterior hypothalamus.

The neuromechanism mediating the hyperthermia induced by injection of PGE2 into the preoptic/anterior hypothalamus (PO/AH) was investigated in the rat. Pretreatment of rats with intraperitoneal injection of atropine sulfate blocked, whereas pretreatment with atropine methyl bromide had no significant effect on the hyperthermia. In a second series of experiments, atropine sulfate was microinjected into different regions of the hypothalamus and the thalamus in an attempt to locate the central cholinergic synapses involved in the PGE2-induced hyperthermia. The hyperthermia was blocked by atropine injection into the dorsal/dorsomedial hypothalamic area (DH), but was not significantly affected by injection into the PO/AH, ventromedial hypothalamus, or the thalamic area above the DH. Moreover, microinjection of the cholinergic agonist carbachol (0.5 microgram) into the DH could also elicit hyperthermia. Thus, our data suggest that the hyperthermia induced by PGE2 administration into the PO/AH is mediated by a cholinergic mechanism in the DH.

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