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Biomedical subjects

M Haraguchi

Publications and source records attributed to M Haraguchi.

At least 19 recordsLinked to original sources

Alcohol self-administration: role of mesolimbic dopamine.

It appears clear that ethanol reinforcement, like that of many abused drugs, utilizes the mesolimbic DA pathways. From the data presented on microinjection of DA agonists and antagonists, it would seem that only part of the regulatory process controlling ethanol drinking is directly involved with this pathway. Once drinking has begun, the DA antagonist raclopride results in a rapid termination of drinking. This appears to be a blocking effect of what may be conditioned reinforcement resulting from prior ethanol reinforcement initiation procedures. Microinjection of the DA agonists d-amphetamine and quinpirole prolonged drinking, with little signs of normal termination apparent in the 30-min session in many animals. This appeared to be the result of interference with normal termination processes. While it remains to be demonstrated that oral ethanol consumption results in the release of DA in the nucleus accumbens, evidence from prior work and the present studies support a role for the mesolimbic DA system in ethanol reinforcement.

Alcoholism

Angiogenic factor.

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Escherichia coli

Heterogeneity in gastric carcinoma with special reference to DNA content and mitotic activity: histopathologic differentiation.

DNA ploidy and mitotic activity were microspectrophotometrically investigated in 46 patients with gastric carcinoma. Measurements of DNA content and mitotic index (M.I.) were examined in the mucosal, submucosal, muscularis propria, and serosal layers of tumors, respectively. The frequency of cells with values exceeding hexaploid chromosome (6c) and mitotic counting analysis revealed a significant higher value in serosa, compared with findings in the mucosa. This tendency was not evident in cases of a differentiated type adenocarcinoma but was noted in those with the undifferentiated type. There were 37 tumors (80.0%) with the same DNA distribution patterns in every layer of the stomach (homogeneous DNA ploidy). Heterogeneity of DNA ploidy was observed in nine tumors (20.0%). Carcinoma with a heterogeneous DNA ploidy manifested a significantly higher incidence of metastasis to the lymph nodes than did those with homogeneous type. Characteristically, there was venous permeation preponderance in the differentiated type and peritoneal dissemination preponderance in the undifferentiated type. This evidence of DNA heterogeneity in gastric carcinoma tissues suggests a possible correlation with the metastatic behavior.

Cytophotometry

Microinjections of dopamine agonists in the nucleus accumbens increase ethanol-reinforced responding.

Long-Evans rats (N = 3) were trained to lever press on a fixed-ratio 4 (FR 4) schedule with ethanol (10% v/v) presented as the reinforcer. Each rat received a total of six bilateral nucleus accumbens microinjections, one per week. They were tested with one physiological saline control, three 20.0-microgram/brain d-amphetamine, and two 6.0-microgram/brain quinpirole injections given 10 min prior to operant sessions. Ethanol-reinforced responding terminated after approximately 10 min during control sessions. Microinjections of the D2 agonist quinpirole and the nonspecific dopamine (DA) agonist d-amphetamine increased total responding but produced slowed response rates that continued for 45-60 min. The slowed response rate produced by d-amphetamine resulted in a peak increase in interresponse times (IRTs) between 8-10 s, whereas quinpirole increased IRTs in the 14- to 16-s range, indicating that nonspecific DA activation resulted in higher rates of ethanol-reinforced responding than specific D2 activation although both drugs decreased local response rates. These data indicate that the amount and temporal extent of ethanol-reinforced responding are increased by microinjections of DA agonists in the nucleus accumbens and support the hypothesis that DA activity in this region is involved in the regulation of ethanol-reinforced responding.

Animals

Evaluation of a protease activation mutant of Sendai virus as a potent live vaccine.

A protease activation mutant of Sendai virus, TR-5, was investigated as a candidate for a live vaccine. Vaccination with TR-5 which had been activated by chymotrypsin beforehand (active TR-5) elicited protective immunity against otherwise lethal challenge infection with wild-type Sendai virus in DBA/2, C3H and ICR strains of mice. Less of the active TR-5 was required to confer protection on mice compared with an ordinary ether-inactivated Sendai virus vaccine (split vaccine). The protective immunity elicited by TR-5 lasted longer and the booster effect was more prominent compared to the split vaccine. No seroconversion was observed with contact mice when housed in a cage with mice vaccinated with the active TR-5. The overall results show that the active TR-5 is an effective and safe live vaccine of Sendai virus in mice.

Administration, Inhalation

[Apparent depth by the stereograms without binocular retinal disparity: is Lau effect artifact?].

We examined the idea that, when the Zöllner figure in one eye and the principal lines in the figure in the other eye were presented, the perceived depth is due to "phenomenal" disparity. The phenomenal disparity is defined as apparent displacement between two illusory "oblique" principal lines in one eye and two "parallel" principal lines in the other. Observes were asked whether depth was seen or not at upper or lower part of the two perceived lines and, if seen, which line was closer. Seventeen observers showed that only 9% of their responses was consistent with the idea, although they reported depths for disparity stimuli. This suggests that the dichoptic presentation of such figures should not be considered as that requires the processing of binocular disparity.

Adult

[The effect of sustained-release theophylline granules in the inhibition of exercise-induced asthma].

We studied the protective effect of sustained-release theophylline granules on early or late response in exercise-induced asthma (EIA) in 16 patients ranging in age from 7 to 18 years. A standardized exercise test was examined 2 hours after administration of theophylline granules on one day and after no medication on another day. On both days, the lung functions and the serum theophylline and cortisol concentrations of the patients were examined before exercise and over a period of 8 hours after exercise. On days without medication, early response was seen in 16 patients and late response in 6. On days with medication, the theophylline granules inhibited early response in 13 of the 16 patients and late response in 5 of the 6 patients. This suggests that theophylline preparation is a useful drug for inhibiting the dual responses of EIA.

Adolescent

Trends in survival rates in Japanese patients with advanced carcinoma of the stomach.

From 1965 to 1985, 1,150 patients underwent gastrectomy for carcinoma of the stomach invading beyond the submucosa. One thousand, one hundred and forty-one patients were studied for five years or longer. The patients were classified into two groups--those treated from 1965 to 1974 (n = 622) and those treated from 1975 to 1985 (n = 519). In the more recent group, there was a significant increase in the number of patients more than 70 years of age, in the number of female patients, of carcinomas present in the upper two-thirds of the stomach, in tumors exceeding 10 centimeters and diffusely infiltrative type and in early cancer-simulating type of advanced carcinoma in gross appearance and in undifferentiated type adenocarcinomas in histology. Although differences in the incidence of patients treated by radical procedures, such as extensive lymph node dissection and combined resection of adjacent organs, were not statistically significant, the incidence for those who underwent total gastrectomy was significantly increased. The over-all long term survival rate remained unchanged during 1965 to 1985 (five year survival rate of 31.3 versus 32.8 per cent). However, there was a significantly longer survival period for patients who underwent total gastrectomy (five year survival rate of 22.9 versus 28.3 per cent) (p less than 0.05). Much of the improvement can be attributed to an increase in the detection of relatively small advanced carcinomas and of advanced carcinomas of the stomach simulating early carcinoma in the upper one-third of the stomach. Therefore, we emphasize the need to diagnose advanced carcinoma of the stomach when the lesion is in an earlier stage of disease.

Adenocarcinoma

Lower survival rate for patients with carcinoma of the stomach of Borrmann type IV after gastric resection.

Between 1965 and 1985, 194 of 1,113 patients (17.4 percent) with advanced carcinoma of the stomach who underwent gastric resection had Borrmann type IV carcinoma of the stomach, a macroscopically evident and diffusely spreading tumor. These patients tended to be younger and female and to have larger tumors that involved the entire stomach, as compared with patients with other types of carcinomas. Tissues were commonly undifferentiated, serosal invasion was prominent with infiltrative growth and high rates of metastasis to the lymph nodes and peritoneal dissemination were evident. In most instances, the disease was advanced; therefore, total gastrectomy was performed upon 82.0 percent of the patients and a palliative resection was done in 64.4 percent. The survival rate was lower than for patients with carcinoma of the stomach of other types (p less than 0.01). A multivariate analysis indicated that curative resection is an independent favorable prognostic event, while other factors are dependent covariates. Early detection of this carcinoma is crucial to extend survival time of patients with Borrmann type IV carcinoma of the stomach. Aggressive postoperative chemotherapy should be considered when a noncurative resection is done.

Female

DNA ploidy is associated with growth potential in gastric carcinoma.

To correlate growth potential with DNA ploidy 109 patients with early gastric carcinoma and 132 patients with advanced gastric carcinoma were studied. Early gastric carcinomas were classified by growth potential into the small mucosal type, the superficially spreading (super) type, or the expansively penetrating (Pen A)/infiltratively penetrating (Pen B) types. Advanced gastric carcinomas were classified into funnel, column, or mountain types, each of which was divided further into expanding and infiltrative types. Cell nuclear DNA content was measured by microspectrophotometric study and classified as either low or high ploidy according to the degree of dispersion on the DNA histogram. Super type early and funnel type advanced carcinomas, characterized by superficially spreading growth, were more likely to have low DNA ploidy. In contrast, Pen A type early and column-expanding type advanced carcinomas, characterized by expansively penetrating growth, were more likely to have high DNA ploidy.

DNA, Neoplasm

Predictive value of Ki-67 and argyrophilic nucleolar organizer region staining for lymph node metastasis in gastric cancer.

Proliferative activities in 91 primary gastric carcinomas and 36 corresponding metastatic perigastric lymph nodes were investigated using Ki-67 labeling percentage and an argyrophilic nucleolar organizer region (AgNOR) count. Tumors with a high proliferative activity often metastasized to lymph nodes, and the proliferative activities of the primary lesion and the perigastric lymph node metastases were similar. A significant correlation was recognized between the Ki-67 labeling percentage and the AgNOR count (r = 0.744; P less than 0.001). The Ki-67 labeling percentage and AgNOR count proved to be useful predictors of nodal metastasis regardless of tumor size, depth of invasion, and histological type. Even when tumors are smaller (less than 7 cm) or the stage of the disease is early (pT1, 2), the formation of metastasis increased with an increased Ki-67 labeling percentage or AgNOR count. The combination analysis of depth of invasion with Ki-67 labeling percentage or AgNOR count gives a more precise prediction of nodal metastasis, compared with histological analysis alone.

Antibodies, Monoclonal

Comparison of R1 and R2 gastrectomy for gastric cancer in patients over 80 years of age.

To evaluate the benefit of R2 gastrectomy for gastric cancer in Japanese patients over 80 years of age, data on 93 patients who underwent gastrectomy between 1967 and 1989 were collected retrospectively from charts filed in the Kyushu University Hospital and two affiliated national hospitals. Of 93 patients, 62 had a localized tumor without evidence of metastatic spread. These 62 patients were classified into two groups according to the procedures performed: 35 underwent R1 gastrectomy and 27, R2 gastrectomy. The clinical and pathological characteristics of the patients in the two groups were comparable at the time of surgery, except that the group who underwent R1 gastrectomy was older. R2 gastrectomy involved a significantly longer operation time (P less than 0.01) and greater intraoperative blood loss (P less than 0.05) when compared to R1 gastrectomy, but no patient undergoing this extensive surgery died. The difference in the morbidity rate between the two groups was not statistically significant. The 5-year survival rate was 55.8% in the R1 group and 65.4% in the R2 group. When gastric cancer invaded the serosa and/or secondary nodes, a substantial increase in survival time was gained with R2 gastrectomy when compared to an R1 operation. These findings suggest that an R2 gastrectomy is feasible, even for patients over 80 years, but is indicated mainly when the carcinoma had invaded the serosa and/or secondary nodes and the patients are at good risk for major surgery.

Aged

Nonspecific giant ulcer of the sigmoid colon--a case report.

An unusual case of a 44 year old woman who developed a nonspecific ulcer of the sigmoid colon is reported herein. She presented with lower abdominal pain and fever and colonoscopy revealed a large, sigmoid colon ulcer with normal surrounding mucosa and a well-defined margin. A temporary sigmoidostomy was done to decompress the bowel content and, after the abdominal pain and fever had subsided, the involved segment with an ulcer of 6.1 X 2.5 cm was resected. Her postoperative course was uneventful and she has remained well since.

Adult

Effects of d-amphetamine injected into the nucleus accumbens on ethanol reinforced behavior.

Rats, initiated to self-administer 10% (v/v) ethanol in an operant situation using the sucrose-fading procedure, received bilateral n. accumbens microinjections of d-amphetamine prior to operant sessions. Doses of 4 micrograms, 10 micrograms and 20 micrograms/brain were administered and some animals also received a 4 microgram/brain dose of LY171555. Three different effects were observed: increased, decreased and no change in total session responding. There was no clear relation between injection area in the n. accumbens and type of effect observed. For either an increase or decrease in total session responding, momentary response rates were decreased. Both d-amphetamine and LY171555 produced similar results. The data support the hypothesis that dopamine in the n. accumbens is involved with ethanol reinforced operant responding but in a complex manner.

Amphetamine

Lower survival rate for patients under 30 years of age and surgically treated for gastric carcinoma.

We analysed data on 38 patients with gastric cancer aged 30 years and younger who were surgically treated in the Department of Surgery II, Kyushu University Hospital, between 1965 to 1985. These younger patients comprised 2.6% of the total 1,470 patients treated for gastric cancer during this 21-year period. The durations and the kinds of symptoms in the preoperative period varied with the patient. In patients under 30 years of age, the female patients predominated, and in addition, undifferentiated lesions were more common than the differentiated type, tumours were larger, serosal invasion was more prominent, lymphatic involvement was more common, tumours showed infiltrative growth and the rate of peritoneal dissemination was higher. Consequently the survival rates for these younger patients were poor. Detection at an early stage of the disease is mandatory if the survival rates of younger patients with gastric cancer are to improve.

Adult

Effects of digoxin, propranolol, and verapamil on exercise in patients with chronic isolated atrial fibrillation.

STUDY OBJECTIVE: The aim was to evaluate the effects of digoxin, propranolol, and verapamil on exercise in patients with chronic isolated atrial fibrillation. DESIGN: Patients with chronic isolated atrial fibrillation underwent maximal exercise testing before and after the administration of digoxin, propranolol, or verapamil. Heart rate, oxygen uptake and oxygen pulse were observed at rest, at gas exchange anaerobic threshold, and at peak exercise. SUBJECTS: The subjects were 10 patients (aged 48-78 years, mean age 60, SD 9, years) with chronic isolated atrial fibrillation. MEASUREMENTS AND MAIN RESULTS: During exercise without medication, the heart rate was 85 (SD 8) beats.min-1 at rest, 127(19) at the level of anaerobic threshold, and 175(17) at peak exercise. With digoxin, heart rate was reduced to 75(9) beats.min-1 at rest (control v digoxin, p less than 0.01). However, reduction of heart rate was not seen at anaerobic threshold or at peak exercise. With propranolol, heart rate was 63(7) beats.min-1 at rest, 99(16) at anaerobic threshold, and 138(28) at peak exercise (control v propranolol, all p less than 0.01). Heart rate with verapamil was 70(13) beats.min-1 at rest, 107(30) at anaerobic threshold, and 138(28) at peak exercise (control v verapamil, p less than 0.05 at rest and at anaerobic threshold, p less than 0.01 at peak exercise. Neither digoxin, nor propranolol, nor verapamil changed the oxygen uptake during exercise. Without medication, oxygen pulse was 6.5(2.0) ml.beat-1 at anaerobic threshold and 7.7(2.1) ml.beat-1 at peak exercise. With digoxin, the change of oxygen pulse, versus without medication, was not significant at rest or at anaerobic threshold but was increased at peak exercise, at 8.3(2.1) v 7.7(2.1) ml.beat-1, p less than 0.05. With propranolol, oxygen pulse was increased to 8.2(1.9) ml.beat-1 at anaerobic threshold and 9.2(2.3) ml.beat-1 at peak exercise (control v propranolol, both p less than 0.01). With verapamil, oxygen pulse was increased to 8.7(1.8) ml.beat-1 at anaerobic threshold and 10.0(2.1) ml.beat-1 at peak exercise (control v verapamil, both p less than 0.01). CONCLUSIONS: Digoxin was effective in reducing heart rate at rest, but failed to reduce it during exercise. Propranolol and verapamil reduced heart rate at all levels of exercise as well as at rest. Oxygen uptake during exercise (total exercise capacity) was not reduced with propranolol or verapamil; this was thought to have been accomplished by an increased oxygen pulse.

Aged