Preference for corn oil in olfactory-blocked mice in the conditioned place preference test and the two-bottle choice test.

We studied the effects of olfactory stimuli on preference for corn oil in mice. In the conditioned place preference test, voluntary intake of 100% corn oil by both olfactory normal and ZnSO4-induced olfactory-blocked (anosmic) mice resulted in their place preference for the corn oil-related box. In the olfactory normal mice, place preference was also observed by voluntary intake of linoleic acid as well as of corn oil. In the two-bottle choice test, normal mice showed significant preference for test fluids that contained corn oil at all concentrations (1-10%) tested relative to vehicle alone. However, the lower concentrations (1 and 3%) of corn oil were not preferred in the anosmic mice. These results suggested that stimuli other than olfaction contributed to the rewarding effects of corn oil, but at lower concentrations olfactory stimuli might act as a signal for the oil.

Opioidergic contribution to conditioned place preference induced by corn oil in mice.

We previously reported that voluntary intake of corn oil in the light box showed place preference in the conditioned place preference (CPP) test in mice. In the present study, we investigated the contribution of opioidergic systems to the corn oil-induced CPP in mice. Acquisition of the place preference by corn oil intake was blocked by i.p. injections of an opioid mu antagonist, naloxone (0.1 and 0.3 mg/kg), and delta antagonists, 7-benzylidenenaltrexone (0.5 mg/kg) and naltriben (0.5 mg/kg) 15 min before conditioning. The opioid kappa agonist U-50488H (1 and 3 mg/kg i.p.) also blocked corn oil-induced CPP. Naloxone (1 mg/kg, i.p.) and naltriben (0.5 mg/kg, i.p.) did not affect corn oil intake in the home cage. However, 7-benzylidenenaltrexone (0.5 mg/kg, i.p.) and U-50488H (1 mg/kg i.p.) decreased and increased the corn oil intake, respectively. These results suggested that the rewarding effects of corn oil in the CPP test are at least partially mediated via opioidergic systems through mu and delta receptors. Further, we showed that an opioid kappa agonist reduced the rewarding effects of corn oil in the CPP test in mice, although it increased corn oil intake.

Long-term optional ingestion of corn oil induces excessive caloric intake and obesity in mice.

Corn oil is well tolerated by mice but tolerance may decrease with excessive ingestion. In the present study, we compared the effects of optional ingestion of excessive corn oil with ingestion of water (control) or a 20% sucrose solution in mice. During the entire study, mice consistently ingested 100% corn oil and incrementally ingested 20% sucrose. Food intake in the corn-oil group was approximately constant but that in the sucrose group was slightly decreased. Body-weight gains in the corn-oil group were higher than those in the control and sucrose groups. At the end of the study, hepatic hypertrophy and fatty liver were present, especially in the corn-oil group, and the visceral fat of mice fed corn oil increased significantly compared with the other two groups. These results suggest that mice, when given a choice, will continue to overeat corn oil over the long term, inducing excessive caloric intake and obesity.

Biochemical studies of dopaminergic activation by stimuli of corn oil in the oral cavity in mice.

We investigated the effects of corn oil stimuli in the oral cavity on monoaminergic neurones by measuring the amount of monoamines and their metabolites in brains of mice. Intraoral injection of corn oil (0.1 ml) increased dopamine (DA) turnover rate in the cortex 3, 5 and 10 min after injection in mice. A significant increase of DA turnover rate was also observed in midbrain 10 min after the corn oil injection. Turnover rates of noradrenaline (NA) and serotonin (5-HT) were not affected by the corn oil injection in any of the regions or times tested. In the chronic study, DA and 5-HT contents in the left and right cortexes and 5-HT contents in diencephalon in the chronic corn oil-fed group were significantly higher than those in the-control but NA contents were not significantly different between the two groups in all regions. In conclusion, the present results suggested that the stimuli of corn oil in the oral cavity might activate dopaminergic systems in the brain of mice and its chronic stimuli might increase DA contents in the brain. Although 5-HT contents increased in the brains of mice by the chronic corn oil intake, its physiological implication remains to be elucidated.

Grooming behavior in mice induced by stimuli of corn oil in oral cavity.

Mice show a strong preference for corn oil, which was thought to be elicited by stimulation in the oral cavity. Grooming behavior is known to be induced by dopamine D(1) stimulation in rodents. Therefore, we evaluated stimulation by corn oil in the oral cavity and the contribution of D(1) receptors to corn-oil-induced grooming in mice. Intraoral injection (0.1 ml) of corn oil induced grooming behavior similarly to SKF 38393 (10 mg/kg i.p.), a D(1) agonist, and both were antagonized by pretreatment with SCH 23390, a D(1) antagonist. However, a higher dose was needed for antagonism of the corn-oil-induced grooming compared with that induced by SKF 38393. Long-chain fatty acids, their methyl esters and alcohol, their triglycerides, mineral oil and silicone oil but not glycerin, a short-chain triglyceride, xanthan gum solution, or sucrose solution also induced grooming in mice. Xanthan gum solution, which was suggested to mask oil-like texture, attenuated the silicone-oil- but not corn-oil-induced grooming when injected intraorally as a mixture with an equal volume of the oil (50% suspension). The silicone-oil-induced grooming was reduced by SCH 23390 similarly to that induced by corn oil. These results suggested that stimulation by the oil-like texture in the oral cavity in mice induced grooming behavior and that it might be mediated at least partially via D(1) receptors. Moreover, stimuli other than texture might also contribute to the corn-oil-induced grooming.

Enhanced resistance to bacterial diseases of transgenic tobacco plants overexpressing sarcotoxin IA, a bactericidal peptide of insect.

Sarcotoxin IA is a bactericidal peptide of 39 amino acids found in the common flesh fly, Sarcophaga peregrina. Many agronomically important bacteria in Japan are killed by this peptide at sub-micro molar levels, and the growth of tobacco and rice suspension cultured cells is not inhibited with less than 25 microM. Transgenic tobacco plants which overexpress the peptide, i.e. over 250 pmol per gram of fresh leaf, under the control of a high expression constitutive promoter showed enhanced resistance to the pathogens for wild fire disease (Pseudomonas syringae pv. tabaci) and bacterial soft rot disease (Erwinia carotovora subsp. carotovora).

The results of transsphenoidal surgery for 44 consecutive acromegalic patients.

A series of 44 patients with acromegaly underwent transsphenoidal surgery between 1987 and 1996. The early postoperative mean basal GH level < 5 ng/ml or < 3 ng/ml was achieved in 43 (97.7%) or 38 (86.4%) out of 44 patients, respectively. Preoperative abnormal GH secretory response to TRH, GnRH and oral glucose administration was restored to normal both after surgery and at the time of the final follow-up in all patients whose early postoperative mean basal GH levels were reduced to < 3 ng/ ml, whereas they remained abnormal in those with mean basal GH levels of > or = 3 ng/ml. In contrast, insulin-like growth factor 1 (IGF-1) levels, when measured by the extraction method, tended to be reduced gradually to normal between 6 months and 2 years after surgery in some patients with a successful operation. Therefore, 34 (87.1%) out of 39 patients who have been followed up longer than 6 months met the following stringent criteria at the time of the final follow-up: mean basal GH level < 3 ng/ml, a normal IGF-1 level, and normal GH response to TRH, GnRH and oral glucose administration. In this series, the most unfavorable preoperative factor influencing operative outcome is tumor invasion of the cavernous sinus. Our results clearly indicate that selective adenomectomy by transsphenoidal surgery is the therapy of first choice in any patient with acromegaly and that the complete biochemical cure of acromegaly can be achieved in 87% of patients by surgery alone with an acceptable low surgical morbidity.

[Uterine cervical carcinoma after radiotherapy: comparison between MR imaging and histopathological findings].

The findings of MRI and pathologic investigation were correlated in curatively irradiated uterine cervical carcinoma. Four patients having residual carcinoma diagnosed by biopsy underwent hysterectomy. MRI demonstrated the mass lesion in one patient with pathologic confirmation of massive viable cancer cells (case I). Of the other three patients, MRI demonstrated normal configuration of the uterine cervix. Cervical signal intensity, however, varied. Hyperintensity was noted in an area of the posterior wall on T2WI in case 2. The anterior wall of the case 2 and the other two cases showed hypointensity. Cervical specimens with normal intensity showed only a small number of degenerated cancer cells. On the other hand, pathologic examination of the posterior wall of the case 2 revealed both cancer cells with varying degrees of degeneration and necrotic tissues. Degeneration of cancer cells was stronger in the superficial layer than the deeper layer. Fibrosis, hemorrhage, granulation and hyalinization were hypointense on T2WI. T2 elongation reflected not only the residual tumor but the post-irradiation changes. Post-irradiated cervix with normal intensity indicated that only a small number of degenerated cancer cells may persist even if the biopsy was positive. We conclude that MRI is useful in evaluating tumor response to radiotherapy.

Retrospective analysis of long-term surgical results in acromegaly: preoperative and postoperative factors predicting outcome.

OBJECTIVE: Sixty-one of 83 patients with acromegaly treated between 1969 and 1993 were analysed retrospectively to clarify which early postoperative factors were significant predictors of a successful long-term outcome and which preoperative factors significantly influenced the early postoperative results. PATIENTS: Of the 61 patients, 30 were operated on before 1987 and 31 afterwards. A successful long-term surgical outcome was defined as a long-term mean basal GH level < 6 mU/l (comparable to < 3 micrograms/l), a normal IGF-I level, and normal GH dynamics. RESULTS: Overall, 59% of patients (37% before 1987 and 81% after) had an early postoperative mean basal GH level < 6 mU/l, and 56% (29% before 1987 and 77% after) met all three of the specified criteria for a successful long-term surgical outcome. Statistical analysis confirmed that GH dynamics and postoperative mean basal GH level < 6 mU/l were significant predictors of the long-term surgical outcome, whereas the postoperative IGF-I level alone was not. On the other hand, abnormal preoperative GH dynamics were normalized in all patients with a postoperative mean basal level < 6 mU/l. In addition, there were no patients showing an unsuccessful long-term outcome in those associated with both the early postoperative mean basal GH level < 6 mU/l and normalization of the IGF-I level. Therefore, measurement of the early postoperative mean basal GH level and the IGF-I level may be an economical and simple guide to predict the long-term surgical outcome. Moreover, multivariate analysis indicated that cavernous sinus invasion was an independent significant factor influencing the early postoperative outcome. CONCLUSIONS: Successful long-term surgical outcome may be predicted if early postoperative mean basal GH level is reduced to < 6 mU/l (< 3 micrograms/l) and IGF-I level becomes normal. This study also confirms that early diagnosis and treatment by an experienced endocrinologist and neurosurgeon can improve the operative results in patients with acromegaly.

Scintigraphic detection of recurrence of medullary thyroid cancer.

A case of recurrent medullary thyroid cancer (MTC) was evaluated with 123I-MIBG, 99mTc(V)-dimercaptosuccinic acid (DMSA), and 201Tl scintigraphy. This patient had been operated on for MTC in the right thyroid. Recently a left neck mass was noticed, and was suspected of being a recurrence of MTC based on increased plasma calcitonin (CT) and carcinoembryonic antigen (CEA). He was operated on for the neck mass which revealed MTC, and papillary thyroid cancer was incidentally found in the left thyroid, but the CT and CEA levels remained high, and remaining MTC tumor was suspected. But the location of the tumor was unknown. Although 99mTc(V)-DMSA scintigraphy is generally believed to be superior in sensitivity to 123I-MIBG scintigraphy, it did not demonstrate the tumor site but 201Tl and 123I-MIBG did. Furthermore, 123I-MIBG scintigraphy has greater specificity for tumors which arise in the neural crest. Judging from the results of this case and cases reported in the literatures, both 123I-MIBG and 99mTc(V)-DMSA should be performed in the detection of recurrent MTC.

[Prognostic factors of radiation therapy for patients with non-operative stage III non-small cell lung cancer].

Records of patients with non-operative stage III non-small cell lung cancer registered at the Department of Radiotherapy, Cancer Institute Hospital, from January 1978 to June 1980 were examined in order to present prognostic information on survival. The data were derived from 100 carefully staged patients and include results from the patients' history, physical examination, pretreatment laboratory tests, radiological findings, nature of radiotherapy and response to treatment. Serum albumin, tumor site, performance status (PS), hemoglobin, TDF and response were identified as important prognostic factors in the univariate analyses. On the other hand, tumor site, PS and serum albumin were significantly related with survival in the multivariate analyses. However it was found that TDF and response significantly affected survival when posttreatment variables were taken into account. These patients were classified into low, intermediate and high risk groups according to those three pretreatment factors (tumor site, PS and serum albumin), and the median survival times for the groups were 10.3 months, 10.4 months and 2.5 months, respectively. These results suggest that high risk patients with stage III non-small cell cancer generally might be treated palliatively.

Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology.

In this study, we compared the clinical and endocrinological characteristics, neuroimaging findings, surgical outcome, and conventional histological findings (including immunohistochemistry) with the electron microscopic appearance of 31 growth hormone (GH)-producing adenomas. By electron microscopy, these 31 tumors were divided into 23 densely granulated somatotroph adenomas (DG adenomas) and 8 sparsely granulated somatotroph adenomas (SG adenomas). SG adenomas more frequently affected younger women, but no significant correlation was found between the adenoma type and the characteristic signs and symptoms of acromegaly, the incidence of diabetes mellitus or hypertension, or the basal serum GH and insulin-like growth factor I levels. A distinct response of GH to thyrotropin-releasing hormone, bromocriptine, or GH-releasing hormone was significantly more common in patients with DG adenomas than in those with SG adenomas, whereas the incidence of a response to gonadotropin-releasing hormone or oral glucose was not significantly different between the two groups. An analysis of neuroimaging findings and surgical results indicated that SG adenomas were more likely to be macroadenomas with suprasellar extension or invasive tumors and had a lower surgical cure rate. However, postoperative radiotherapy seemed to be similarly effective in both types of adenoma to prevent a tumor recurrence and to reduce postoperative GH basal level in serum. Light microscopy showed that DG adenomas were mainly acidophilic and were immunopositive not only for GH but also for prolactin (43%), the beta subunit of thyroid-stimulating hormone (26%), and the alpha subunit of glycoprotein hormone (87%), whereas SG adenomas were almost all chromophobic and only revealed immunopositivity for GH.(ABSTRACT TRUNCATED AT 250 WORDS)

[Sequential MR images of the uterus after Gd-DTPA injection--studies of normal volunteers and uterine endometrial malignant tumors].

To investigate the sequential changes in signal intensity (SI) of normal and abnormal uteri, T1 WIs were taken repeatedly after the injection of Gd-DTPA. Six volunteers and 19 patients with known uterine body malignancy (18 carcinomas, one carcinosarcoma) were examined. The results in volunteers were as follows. In the secretory phase, SI of the endometrium was stronger in the late images than in the early ones, whereas in the proliferative phase, SI was stronger in the early images. SI of the myometrium decreased rapidly and there were no differences in SI between menstrual phases. In 17 of 18 endometrial carcinomas, the tumors showed hypointensity relative to the myometrium, and the contrast between the tumor and the myometrium was better in the early images. In the remaining two cases, the tumor showed hyperintensity and the contrast was better in the late images. After the injection of Gd-DTPA, the endometrium appeared differently according to the menstrual cycle in normal volunteers, and the appearance of uterine structures and endometrial malignant tumors changed sequentially. These findings must be kept in mind when evaluating uterine diseases by Gd-DTPA enhanced MRI.

Endocrine and morphological study of a clinically silent somatotroph adenoma of the human pituitary.

Silent somatotroph adenomas are defined as tumors showing morphological features consistent with GH production, but no clinical evidence of GH excess. We report here the case of a 46-yr-old woman with a large pituitary macroadenoma, slightly elevated serum GH levels, high serum insulin-like growth factor-I levels, and abnormal GH dynamics, but no acromegaly. The endocrinological abnormalities receded after transphenoidal surgery despite tumor persistence, as shown by neuroimaging. The reverse hemolytic plaque assay, performed for the first time in a silent GH cell adenoma, demonstrated that the number of GH cells releasing GH and the amount of GH discharged from individual cells were less than those in clinically functioning somatotroph adenomas. Thus, it is conceivable that this tumor secreted only small quantities of GH and for only short periods, providing an explanation for the lack of acromegaly. It appears that silent somatotroph adenomas do not represent a distinct entity. It is more likely that there is a continuous spectrum from clinically functioning, sparsely granulated somatotroph adenomas with high serum GH levels to silent somatotroph adenomas with normal serum GH levels. The cause of the lack of GH oversecretion in silent GH cell adenomas has yet to be elucidated.

[Intra-arterial COMPA chemotherapy for invasive bladder cancer].

We presented 12 patients with invasive bladder cancer treated by the subselective intra-arterial COMPA chemotherapy. COMPA was administered up to an average of 3.3 courses (ranged from 2 to 6 courses) every 2 or 3 weeks, consisting of cisplatin: 15 mg/M2 on days 4 and 5; vincristine (oncovin): 0.6 mg/M2 on days 1 and 2; methotrexate: 5 mg/M2 on days 2 and 3; peplomycin: 5 mg/body on days 1, 2 and 3; and adriamycin: 10 mg/M2 on day 4. These were injected through a teflon catheter the tip of which was placed just proximal to the aortic bifurcation, and another tip was led through a subcutaneous tunnel from the inguinally punctured area to the anterior chest wall. The 12 patients, 7 men and 5 women, ranged in age from 53 to 73 (mean: 67) years. Histopathologically 11 had transitional cell carcinoma and one had adenocarcinoma. Malignant gradings were grade 2 in 8 patients, and grade 3 in 4. The stagings were T2 in 3 patients, T3 in 5, T4 in 4 and only one had bony metastasis. Of the 12 patients, 10 were alive at the last follow-up with a mean duration of 36 months (range: 16 to 49). Six patients achieved a complete remission, four achieved a partial remission and two were stable. One died of ileus after 16 months and another of progression after 36 months. All the patients received post-chemotherapeutic adjunctive therapies, which were transurethral resection, partial cystectomy, radiation and/or intravesical instillation. The toxicities were not severe, but anorexia, nausea, vomiting, hair loss, numbness of fingers and/or toes, subileus, and leukopenia were noticed.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary experience with gadolinium-enhanced dynamic MR imaging for uterine neoplasms.

Usefulness of gadopentetate dimeglumine in magnetic resonance (MR) imaging of uterine neoplasms was evaluated in 53 patients with endometrial carcinoma and 15 patients with cervical carcinoma. T1- and T2-weighted MR images were obtained before the contrast material was administered. After a bolus injection of gadopentetate dimeglumine, dynamic MR images were acquired, followed by static T1-weighted images. Gadolinium-enhanced MR images revealed relatively small endometrial carcinomas in the uterine cavity as high signal intensity in four cases and invasion of the myometrium as low signal intensity in 20 cases. In eight cases, endometrial tumors showed irregular, early enhancement compared with that of the myometrium on dynamic images; these cases were associated with poor prognosis. Tumor extension into the lower part of the uterus, parametrium, and paracervical fat was well seen on enhanced images in cases of cervical carcinoma. The authors believe that gadolinium-enhanced MR imaging will prove helpful in the staging of uterine neoplasms.

Masked Cushing's disease in an aged man associated with intraventricular hemorrhage and tuberculous peritonitis.

A 77-year-old man complained of headache, dizziness and tactile hallucination. Based on those clinical signs and the findings of computed tomography scanning and magnetic resonance imaging, he was diagnosed as having pituitary adenoma. Clinical signs and symptoms of Cushing's disease had not been apparent because of the occurrence of the disease at an old age. An increase in serum cortisol and adrenocorticotropic hormone indicated the presence of Cushing's disease. Physical findings obtained thereafter were also compatible with the disease. While the patient was being prepared for surgery, pituitary apoplexy and intraventricular hemorrhage occurred. Massive ascites appeared as a result of tuberculous peritonitis. In spite of treatment for these complications, his general condition progressively deteriorated and he died 39 days after the intraventricular hemorrhage. This case presents the difficulty in the treatment of masked Cushing's disease in the elderly population.

Paradoxical prolactin response to growth hormone-releasing hormone in a patient with hyperprolactinemia and empty sella.

In a 30-year-old woman with amenorrhea due to hyperprolactinemia, serum PRL increased to twice the basal amount in response to growth hormone-releasing hormone (GHRH). Roentgenological studies revealed no pituitary adenoma but empty sella. Bromocriptine therapy normalized serum PRL and made the paradoxical response to GHRH disappear. The paradoxical response did not occur in any of eight other patients with hyperprolactinemia due to prolactinoma. Although this case is rare, GHRH stimulates PRL as well as GH release remarkably in some cases with hyperprolactinemia without a GH-producing tumor.

[Studies on immunoreactive somatostatin and gastrin contents of the gastric mucosa in patients with duodenal ulcer--comparison to patients with fundic gland polyposis and normal subjects].

The immunoreactive gastrin (IRG) and somatostatin (IRS) contents in gastric mucosa were measured from the same biopsy specimen of the same patients with duodenal ulcer (DU) at the active stage and healing stage, and compared to those of patients with fundic gland polyposis (FP) and endoscopically normal subjects whose gastric mucosa had only slight atrophic change (Control). The IRS in both the antrum and the gastric body of DU were significantly lower than those of the other two groups, and those showed no difference between the two stages. In all groups, there was a significant positive relation between the IRG and IRS in the antrum. In DU, particularly at the active stage, the relative decrease of the IRS against the IRG was prominent compared to the other two groups. In FP, which has similar background gastric mucosa and ability of acid output to those of DU, it was found that somatostatin was secreted sufficient to control gastrin secretion and acid output. Whereas in DU, secretion of somatostatin was reduced and, particularly at the active stage, it was considered that somatostatin, which could control increased gastrin secretion and increased acid output, was not secreted.