Immunohistochemical study of HLA antigens and lymphocyte infiltration in melanocytic tumors.
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Biomedical subjects
Publications and source records attributed to T Ono.
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The pullback pressure from the left renal vein (LRV) to the inferior vena cava was studied in 16 patients with left renal bleeding of unknown origin (group A), 15 patients with hematuria of miscellaneous laterality (group B), and nine control subjects (group C). The mean pressure gradients were 5.0 +/- 2.0 mm Hg (mean +/- SD) in group A, 1.9 +/- 1.0 mm Hg in group B, and 1.1 +/- 0.9 mm Hg in group C. The mean pressure gradient of group A was significantly higher than that of groups B and C (P less than .001). From the results of control studies, we regarded pressure gradients greater than or equal to 3.0 mm Hg as indicative of LRV hypertension. With this criterion, 88% (14 of 16) of the patients in group A had LRV hypertension, which was considered a cause of hematuria. Analysis of the results of renal angiography in the 31 patients revealed that opacification of collateral pathways of the LRV was a significant angiographic finding in LRV hypertension.
Effects of postnatal development, surgical cryptorchidism, and hypophysectomy on the activity of calmodulin and of a 32,000-molecular weight (32) calmodulin-binding protein (Ono et al., J. Biol. Chem. 259: 9011-9016, 1984) were examined in rat testis. In adult rats, approximately 95% of their activities distributed in seminiferous tubule preparation, and most of them were in the 105,000-g supernatant. Both activities were low early in the development, but the calmodulin activity increased between 25 and 45 days of age, and the 32 K calmodulin-binding protein activity increased between 35 and 45 days of age. In contrast, surgical cryptorchidism caused a rapid decline in their activities in the abdominal testis, whereas their activities in a scrotal testis did not decline. Hypophysectomy similarly resulted in a gradual decline in their activities. Replacement of follicle-stimulating hormone or testosterone for 7 days from 30 days after hypophysectomy did not quantitatively restore either the testes weight or the activities of the proteins. The results indicate a primary distribution of both proteins in mature germ cells.
The involvement of the ventromedial hypothalamus (VMH) in thermoregulatory responses, which include heat production and heat loss responses, was investigated by the method of electrical stimulation. Electrical stimulation of the VMH caused a rise in rectal temperature, accompanied by the enhancement of heat production: O2 consumption and shivering. In addition, a reduction in heat loss was observed, including decreases in skin temperature (Ts), respiratory rate, and body surface area resulting from a huddled posture. In this study, stimulation of the lateral hypothalamus and other regions near the VMH had no effect on thermoregulatory responses. beta-Blocker (propranolol, 1 mg/kg iv) injected 20 min before stimulation lessened O2 consumption by approximately 10% and attenuated the reduction in Ts during VMH stimulation, whereas alpha-blockade (phentolamine, 1 mg/kg iv) was ineffective. These results indicate that most of the increase in O2 consumption during VMH stimulation was due to the occurrence of shivering but that some component of it could be due to nonshivering thermogenesis. They also indicate that the VMH, either directly or by converging influences, is involved in the activation of thermoregulatory responses to cold stress.
Rat endogenous pyrogen (EP), prepared from the white blood cells of lipopolysaccharide-pretreated rats, produced a fever in both rabbits and rats. The effects of human, rabbit, and rat EP on the body temperatures of rabbits and rats were investigated to clarify differences in the febrile response to each kind of EP. The latency to fever onset and the time to peak fever induced by rat EP in rabbits and rats were significantly greater than those induced by human and rabbit EP. The maximum elevation of the body temperature induced by rat EP in both animals was almost identical to that induced by human and rabbit EP. In a comparison of the febrile responses to various EPs between rabbits and rats, the latency to fever onset, the time to peak, and the maximum elevation of fever in rats were approximately half those observed for rabbits. Furthermore, the threshold dosage to induce a fever response in rats was greater than that necessary for rabbits. It is concluded that rat EP could be obtained by in vitro techniques and that rats have the physiological mechanisms to develop a fever through production of EP.
The febrile responses in rats to an intravenous injection of the bacterial endotoxin Salmonella typhosa were investigated under normally hydrated and dehydrated conditions. When endotoxin was injected intravenously into the dehydrated rats, a biphasic-patterned fever resulted, whereas in normal rats an intravenous injection of endotoxin did not induce fever. No significant differences in febrile responses to the intravenous endogenous pyrogen (EP), prostaglandin E2, and intracerebroventricular prostaglandin E2 between normal and dehydrated rats were observed. When the blood plasma obtained from rats with endotoxin-induced fever under dehydrated conditions was transferred to the normal rats, a significant rise in the body temperature was induced. The effect of hydration by an administration of the hypotonic solution after dehydration was examined in endotoxin-induced fever and in changes of the basic blood parameters. It is concluded that febrile responses to endotoxin during dehydrated condition are caused by an increased production of EP. The migration of leukocytes from circulation to any other tissue will be an important factor in producing EP under dehydrated conditions. Furthermore, under dehydrated condition, EP may be produced by numerous macrophages in tissues in vivo, where many kinds of leukocytes migrate and exchange signals with each other in developing an immune response.
The effect of endogenous pyrogen (EP, from rabbit) and endotoxin (Salmonella typhosa) on rectal temperature (Tre) was investigated in normal and dehydrated rats of both sexes. Intraperitoneal injection of either EP or endotoxin did not affect body temperature. In addition, no changes in Tre were observed when endotoxin was injected intravenously in normally hydrated male rats, but significant falls in Tre occurred in normal female rats. However, intravenous injection of EP produced fever in both sexes, but females generally showed smaller responses. A second intravenous injection of endotoxin, given 3 days after the first injection, always produced fever in normally hydrated rats. The pattern of this febrile response was monophasic. In contrast to the response in normal rats, intravenous endotoxin produced significant fevers with a biphasic pattern in dehydrated rats of either sex, but the febrile responses of male rats were greater than those of female rats. On the other hand, there were no significant differences between febrile responses to intravenous EP exhibited by normal and dehydrated animals. These results show that rats of both sexes possess physiological mechanisms capable of producing a fever following intravenous injections of EP.
Involvement of rat lateral hypothalamus (LHA) neurons in integration of motivation, reward, and learning processes was studied by recording single-neuron activity during cuetone discrimination, learning behavior to obtain glucose, or electrical rewarding intracranial self-stimulation (ICSS) of the posterior LHA. To relate the activity of an LHA neuron to glucose, ICSS, and anticipatory cues, the same licking task was used to obtain both rewards. Each neuron was tested with rewards alone and then with rewards signaled by cuetone stimuli (CTS), CTS1+ = 1,200 Hz for glucose, CTS2+ = 4,300 Hz for ICSS, and CTS- = 2,800 Hz for no reward. The activity of 318 neurons in the LHA was analyzed. Of these, 212 (66.7%) responded to one or both rewarding stimuli (glucose, 115; ICSS, 193). Usually, both rewards affected the same neuron in the same direction. Of 96 neurons that responded to both rewards, the responses of 72 (75%) were similar, i.e., either both excitatory or both inhibitory. When a tone was associated with glucose or ICSS reward, 81 of the 212 neurons that responded to either or both rewards and none of 106 neurons that failed to respond to either reward acquired a response to the respective CTS. Usually, the response to a tone was in the same direction as the reward response. Of 45 neurons that responded to both glucose and CTS1+, 38 (84.4%) were similar, and of 66 that responded to both ICSS and CTS2+, 47 (71.2%) were similar. The neural response to a tone was acquired rapidly after licking behavior was learned and was extinguished equally rapidly before licking stopped in extinction. The latency of the neural response to CTS1+ was 10-150 ms (58.7 +/- 40.9 ms, mean +/- SE, n = 31), and that of the first lick was 100-370 ms (204.8 +/- 59.1 ms, n = 31). The latency of neural responses to CTS2+ was 10-230 ms (68.3 +/- 53.5 ms, n = 33), and that of the first lick was 90-370 ms (212.4 +/- 58.5 ms, n = 33). There was no significant difference between the neural response latencies for the two cue tones nor between the lick latencies for the different rewards. Neurons inhibited by glucose or ICSS reward were distributed widely in the LHA, whereas most excited neurons were in the posterodorsal subarea; fewer were in the anteroventral subarea. Neurons responding to the CTS for glucose or ICSS were found more frequently in the posterior region.(ABSTRACT TRUNCATED AT 400 WORDS)
The lateral hypothalamus (LHA) is involved in integrative functions related to emotion, reward, aversion, and learning. It is, however, unclear whether the medial forebrain bundle (MFB) forms a substrate common to the anterior and posterior hypothalamic areas or whether information regarding rewarding and aversive stimuli converges on and is integrated by the same hypothalamic neuron. In the present study, unit activity in the LHA and lateral preoptic-anterior hypothalamic area (lPOA-AHA) of the rat was recorded during discrimination learning of cue tone stimuli (CTS) that predicted glucose or intracranial self-stimulation (ICSS) as rewarding stimuli, or electric shock or tail pinch as aversive stimuli, using identical behavior, licking. We examined functional differences between the LHA and lPOA-AHA. In positive reinforcement experiments a rat was rewarded by glucose or ICSS only when it licked a spout presented in front of its mouth. The threshold current for ICSS was used. In negative reinforcement experiments an aversive stimulus, either electric shock or tail pinch was applied if the rat did not lick the spout. The strengths of electric shock and tail pinch were selected to produce an avoidance ratio less than 20-30%, averaged in all trials. The activity of 507 LHA and 249 lPOA-AHA neurons was analyzed during both glucose and ICSS trials. The effects of both glucose and ICSS on the same LHA or lPOA-AHA neuron were usually in the same direction, i.e., either both excitatory or both inhibitory. Of 143 LHA and 44 lPOA-AHA neurons that responded to both rewards, the responses of 117 (81.8%) LHA and 35 (79.5%) lPOA-AHA neurons to both stimuli were similar. The activity of 131 LHA and 153 lPOA-AHA neurons was analyzed in both electric shock and tail pinch trials. The effects of both electric shock and tail pinch on the same LHA or lPOA-AHA neuron were usually in the same direction. Of 29 LHA and 27 lPOA-AHA neurons that responded to both aversive stimuli, the responses of 28 (96.6%) LHA and 25 (92.6%) lPOA-AHA neurons to both were similar. The activity of 170 LHA and 195 lPOA-AHA neurons in response to both rewarding glucose and/or ICSS stimulation and aversive electric shock and/or tail pinch was analyzed. About one-third of the neurons in each area were reward specific (57/170 in LHA; 63/195 in lPOA-AHA), whereas relatively few were aversion specific in each area (21/170 in LHA; 15/195 in lPOA-AHA).(ABSTRACT TRUNCATED AT 400 WORDS)
We encountered 11 patients with aluminum-associated bone disease (AABD), and treated them with deferoxamine (DFO). In 3 patients, a second bone biopsy was done during DFO treatment. Clinical features of AABD were compared with surgically proven secondary hyperparathyroidism (2 degrees HPT) with osteitis fibrosa on X-ray. Patients with AABD had disabling bone pain. This disease showed radiological signs ranging from normal, localized bone atrophy, to multiple fractures. It was characterized by increased soft tissue activity and localized abnormal uptake of 99mTc-MDP, detected by skeletal scintigrams. Patients with AABD had low levels of parathyroid hormone and alkaline phosphatase, but high aluminum (Al) levels compared to those with 2 degrees HPT. Serum Al increased after DFO administration, and the patients improved both clinically and histologically. 1-alpha-Hydroxyvitamin D3 (1-alpha-OH D3) was not effective for AABD. We concluded that the administration of antacids containing Al should be minimized in dialysis patients.
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Effects of SAMe on disturbances in trained hand movement tasks or a trained delayed response task after lesion in unilateral motor cortex (hand area) or bilateral dorsolateral prefrontal cortices were studied in the monkey. Following lesion, hand movement tasks or delayed response tasks were disturbed moderately or severely for one week to several months depending on the extent of lesion or nature of task. Although treatment with small doses of SAMe (10 mg/kg/day, i.m.) had no effect, treatment with moderate doses (SAMe, 20 or 30 mg/kg, i.m.) reduced impairment and promoted recovery from both disturbances. Even in the chronic stage (76-140 days after operation), SAMe (30 mg/kg/day, i.m.) facilitated recovery from delayed response deficits. Histological findings in the acute stage after cortical lesion in rats showed that SAMe (50 mg/kg/day, s.c.) augmented infiltration of activated phagocytic macrophages in lesioned sites. Data suggest that SAMe improves recovery from behavioral and histological disturbances due to brain damages.
In order to settle the question about whether or not opioid peptides stimulate or inhibit insulin secretion, we studied effects of rimorphin and dynorphin, two members of the preproenkephalin B group, on glucose-induced insulin secretion in the isolated, perfused rat pancreas. These peptides (3.95 X 10(-8) M), like morphine (3.95 X 10(-8) M), significantly inhibited the glucose-induced insulin secretion. The inhibitory effect of rimorphin was attenuated by naloxone (1.2 X 10(-6) M) and phentolamine (10(-6) M), suggesting an involvement of adrenergic alpha receptors in the inhibition of glucose-induced insulin secretion mediated through specific opiate receptors. Rimorphin also inhibited glucose-induced insulin secretion even in the cysteamine-treated rat pancreas from which somatostatin had been depleted. Thus, somatostatin does not appear to play a major regulatory role in the insulin secretion in the pancreas.
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Evidence has been accumulated that the phorbol ester receptor in intact cells is protein kinase C. However, it is not certain whether the various actions of 12-O-tetradecanoylphorbol-13-acetate (TPA) on cultured cells are all mediated by the activation of protein kinase C. Therefore, we examined the effects of inhibitors of protein kinase C, palmitoylcarnitine (PC) and phloretin (PH), on several actions of TPA on cells. PC at the concentration of 30 micrograms/ml completely prevented the inhibitory actions of TPA on differentiation of Friend leukemic cells (FLC) induced by hexamethylene bisacetamide (HMBA) and on metabolic cooperation of V79 cells. PC, however, did not prevent the TPA-induced promotion of the transformation of BALB/3T3 cells, even at the concentration of 40 micrograms/ml. On the other hand, PH at the concentration of 30 micrograms/ml did not inhibit the actions of TPA to inhibit differentiation of FLC and metabolic cooperation of V79 cells, but completely inhibited the transformation of BALB/3T3 cells and its promotion by TPA. These results indicate that protein kinase C possibly mediates some of the actions of TPA, such as the inhibition of differentiation and metabolic cooperation, but not that of the promotion of in vitro transformation.