Inhibition of the ATP-sensitive potassium channel by class I antiarrhythmic agent, cibenzoline, in rat pancreatic beta-cells.

1. Cibenzoline, a class I antiarrhythmic agent, was investigated for its effect on the ATP-sensitive K+ channel of pancreatic beta-cells by the patch clamp technique. 2. In perforated patch clamp experiments, cibenzoline depolarized the membrane of single beta-cells and thereafter, caused firing of action potentials in the presence of 2.8 mM glucose. 3. Cibenzoline inhibited the activity of the ATP-sensitive K+ channel in cell-attached recordings in the presence of 2.8 mM glucose and evoked repetitive fluctuations of the baseline current, apparently reflecting the action potentials of the beta-cell. 4. In whole-cell clamp experiments, time-independent outward current was induced by depleting cytoplasmic ATP with 0.1 mM ATP and 0.1 mM ADP in the solution contained in the pipette. The outward current was inhibited by cibenzoline in a dose-dependent manner in the concentration range of 1 microM to 100 microM and half maximum inhibition occurred at 1.5 microM. 5. Cibenzoline blocked substantially the ATP-sensitive K+ channel current when applied at the inner side of the membrane in isolated inside-out membrane patches. 6. It is concluded that cibenzoline blocks the ATP-sensitive K+ channel of pancreatic beta-cells and, thereby, stimulates insulin secretion at sub-stimulatory levels of glucose.

Effect of internally loaded iodide, thiocyanate, and perchlorate on sodium-dependent iodide uptake by phospholipid vesicles reconstituted with thyroid plasma membranes: iodide counterflow mediated by the iodide transport carrier.

Na+-dependent I- transport and I- counterflow were studied using phospholipid vesicles (P-vesicles) made of porcine thyroid plasma membranes and soybean phospholipid by sonication. 1) I- uptake by P-vesicles incubated in the presence of external Na+ was higher than that by P-vesicles incubated in choline+ instead of Na+. The vesicles exhibited Na+-dependent I- uptake. When P-vesicles were internally loaded with I- prior to incubation in Na+, a further increase in Na+-dependent I- uptake was observed, although the concentration of internal I- was very much higher than that outside. In the absence of external Na+, I- uptake by P-vesicles preloaded with I- was comparable to baseline uptake. 2) Na+-dependent I- uptake by P-vesicles not loaded with I- and enhanced Na+-dependent I- uptake by P-vesicles preloaded with I- were both inhibited by either of SCN- and ClO4- added outside the vesicles. 3) When P-vesicles were loaded with SCN- instead of I- and incubated in Na+, I- uptake by these vesicles was also higher than baseline Na+-dependent I- uptake. However, a ClO4- load did not result in an increase in I- uptake. These results indicate that Na+-dependent I- transport including Na+-dependent I- counterflow is specifically mediated by the thyroid I- carrier. SCN- - I- counterflow in addition to I- - I- counterflow occurs dependently on Na+, but ClO4- - I- counterflow does not.

Prognostic value of EGFR and TGF-alpha in early laryngeal cancer treated with radiotherapy.

The purpose of this study was to determine the overexpression of both epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) (a ligand of EGFR) in early laryngeal squamous cell carcinoma. In addition, we attempted to evaluate the prognostic values of our findings. Expression of EGFR and TGF-alpha in tumor tissue was examined immunohistochemically in 68 patients who had been treated with radiotherapy for early laryngeal cancer. Overexpression of the two factors was noted in 42.6% and 55.9%, respectively. No significant differences due to age, tumor size, and location or grade of cancer tissues were seen. Higher survival rates, found in patients with EGFR (-) and TGF-alpha (-) tumors as compared with those with EGFR (+) and TGF-alpha (+) (97.4%, 100% and 86.2%, 86.8%, respectively), were not statistically significant. The recurrence rates were similar between EGFR (+) and EGFR (-) (37.9% and 35.9%, respectively). However, the recurrence rate in patients with TGF-alpha (+) was significantly higher (57.9%) than in those with TGF-alpha (-) (10%; P<.01). Therefore overexpression of TGF-alpha may be an important indicator for recurrence in patients with early laryngeal squamous cell carcinoma treated by irradiation.

Clinical trial of intravenous infusion of bromodeoxyuridine (BUdR) for radiosensitization of malignant brain tumors.

Bromodeoxyuridine (BUdR) is a radiosensitizer that can be incorporated into cellular DNA as a substitute for thymidine at the time of DNA synthesis. As the steady-state arterial concentration of BUdR given by means of intravenous infusion was recently presented, the possibility of revival of BUdR as a radiosensitizer administered by the intravenous route was suggested. Based on the experience of BAR therapy and phase-I studies by NIH and UCSF, 12 hours of BUdR at a dose of 800-1,000 mg/m2 for five days a week was given to 23 patients with primary and secondary malignant brain tumors during radiation therapy. Radiation therapy was planned at a weekly dose of 10 Gy for five to six weeks. Fifteen patients received 1,000 mg/m2 of BUdR; six of them tolerated more than three weeks of treatment. In eight patients given doses of 800 mg/m2, five patients tolerated more than three weeks. The most remarkable toxic effects were myelosuppression and stomatitis, which were major obstacles to maintaining the schedule. More than 50% reduction of tumor volume was obtained in five of 12 cases of evaluated gliomas (42%) and three of four cases of metastatic tumors (75%). The median time to tumor progression in seven patients with glioblastoma was 37 weeks.

Intratemporal facial nerve neurinoma without facial paralysis.

A 38-year-old man was referred by his general practitioner to our department on 28 October 1991, with a 2-week history of vertigo. A left aural polyp was identified. The audiogram showed a moderate conductive loss on the left side. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of the expanding lesion in the descending portion of the facial nerve. However, there was no seventh nerve paresis. At operation, the neurinoma (Schwannoma) filled the middle ear cleft and extended from the genu to the stylomastoid foramen. The floor of the middle ear had been eroded, exposing the jugular bulb. Facial nerve paresis is the usual presenting feature of a facial neurinoma. The case is presented for the reason that the absence of facial palsy as a presenting feature is rather rare, especially in the cases with large tumor and extensive bone erosion.

Squamous cell carcinoma of the nasal septum with Wegener's granulomatosis treated with cyclophosphamide and corticosteroids.

Well differentiated squamous cell carcinoma of the nasal septum developed in a 55-year old man with Wegener's granulomatosis. It is suggested that the malignancy was induced by immunosuppressive state from an increased and prolonged use of cyclophosphamide and corticosteroids. Although the efficacy of the therapeutic concept using cyclophosphamide and corticosteroids is well established, there have been some few reports that cyclophosphamide could be implicated in the genesis of malignancies. The pathophysiology of Wegener's granulomatosis should be better understood, and effective and less toxic alternative protocol should be established.

Malignant schwannoma arising in a paranasal sinus.

A case of malignant schwannoma arising in a paranasal sinus is reported. In this case, histological hallmarks were lost because of the poorly differentiated nature of the tumour. Immunohistological techniques were applied to the diagnosis, confirming the neural origin of this tumour. Malignant schwannoma is a relatively rare disease in the nasal cavity and paranasal sinuses. For the treatment of this tumour, wide resection is recommended. In this patient, radical resection of the maxilla with orbital and ethmoid exenteration was performed. The patient recovered uneventfully with no evidence of disease three years after surgery.

Importance of pre-operative recognition of the nonrecurrent laryngeal nerve.

The nonrecurrent laryngeal nerve is vulnerable during thyroid surgery. Pre-operative recognition of this nerve allows surgeons to avoid injuring the nerve. This anomaly depends upon the aortic arch anomaly and, therefore, in some cases, surgeons are able to predict the presence of this nerve pre-operatively by chest X-ray or barium swallow. Two patients with nonrecurrent laryngeal nerve are reported, one of whom, a 48-year-old man, had an abnormal shadow of the aortic arch, which led to confirmation of a right aberrant subclavian artery. Barium swallow plays a decisive role in the diagnosis of nonrecurrent laryngeal nerve, and this test is mandatory in patients who complain of difficulty in swallowing.

View from beneath: pathology in focus. Renal cell carcinoma metastasis to the tongue.

Metastases to the tongue from distant primaries are very rare. A case of renal cell carcinoma metastasis to the tongue, occurring in a 58-year-old man, is presented and previously reported cases are reviewed.

Patient with primary tonsillar and gastric syphilis.

A male patient with syphilitic lesions in the tonsil and stomach is presented. The patient was infected while practising oral sex with heterosexual friends. He complained of nausea and snoring; his left tonsil was enlarged. Spirochetes were detected in a smear preparation from the left tonsil. As a gastric lesion, initially believed to be cancer, appeared to result from spirochete ingestion, the case is considered to represent primary syphilis. After antibiotic therapy with ampicillin, the left tonsil returned to normal size and gastric changes were no longer evident endoscopically. Gastroscopy should be considered if syphilis of the tonsil is observed, particularly when gastrointestinal symptoms are present. Both the oral and the gastric lesion can be mistaken for malignant neoplasm.

Expression of EGF, EGFR and PCNA in laryngeal lesions.

The expression of EGF/EGFR in 47 laryngeal surgical specimens from 44 patients was examined. PCNA analysis as an index of proliferating cells was also performed in 32 cases of laryngeal cancer, six cases of pre-cancerous lesions and nine cases of normal laryngeal mucosa. EGFR failed to show a significant correlation with tumour behaviour, but EGF expression was statistically significantly higher in malignant (SCC) than in non-malignant tissues (pre-cancerous and normal tissues) (p < 0.006), and PCNA also showed a statistically significant difference (p < 0.016) between the two. In malignant tissues when EGF/EGFR in 'double-positive' and 'double-negative' cases was compared, a statistically significant difference in PCNA was found (p < 0.029); but this was not seen in non-malignant tissues. Our results support the hypothesis that an autocrime mechanism exists in laryngeal cancer and in this mechanism EGF may play an important role in tumour progression, especially when EGFR is overexpressed.

[Tuberculoma and tuberculous meningitis mimicking metastatic brain tumor and meningeal carcinomatosis--case report].

A 45-year-old man was well until February 1986, when he experienced gait disturbance and psychiatric symptoms. On February 11 he fell down several times and developed generalized convulsion on the following day. He was admitted to a hospital in a delirious condition. The chest X-ray film showed infiltration in the left upper lobe, but computed tomographic (CT) scan of the head revealed no abnormality. Cerebrospinal fluid obtained by lumbar puncture contained 155 cells/mm3, all of which were lymphocytes, and protein and glucose concentrations were 372 mg/dl and 68 mg/dl respectively. In spite of negative smear tests of sputum and cerebrospinal fluid for tubercle bacilli he was administered antituberculosis drugs on the suspicion of pulmonary tuberculosis and tuberculous meningitis. His level of consciousness gradually returned to normal but the follow-up CT scans showed a low density area with contrast enhancement in the right thalamus and obliteration of the right quadrigeminal cistern which was also enhanced with contrast medium. He was transferred to our hospital on March 28 for further evaluation. On admission to our hospital he was alert and oriented, his pupils were equal and reactive to light and he had mild left hemiparesis, left hyperreflexia and left hemihypesthesia. Cell count of the cerebrospinal fluid was 243/mm3, 90% of which were lymphocytes and protein and glucose contents were 340 mg/dl and 42 mg/dl respectively. Both smear and culture of the cerebrospinal fluid were negative for tubercle bacilli and other organisms. Cytological examination of the cerebrospinal fluid demonstrated clusters of cells of various sizes with high N/C ratio which suggested these cells were malignant.(ABSTRACT TRUNCATED AT 250 WORDS)

[Efficacy of intracisternal papaverine on symptomatic vasospasm].

This study reports the effect of intracisternal administration of papaverine in 15 patients with vasospasm due to rupture of aneurysm. All patients had undergone clipping of aneurysm and had neurological deterioration and decreasing level of consciousness. Bolus injection of 40 mg of 1% papaverine hydrochloride was started on day 6.3 +/- 1.7 and continued for 4.4 +/- 1.6 days. In seven cases serial angiogram after initial dose revealed dilatation of IC and/or anterior, middle cerebral arteries at 30 min and further dilatation up to 85% increase in diameter at 60 min, which continued at least 90 min. Arteries with marked vasospasm responded more to papaverine than those with less vasospasm. There was a close correlation between degree of vasospasm and vasodilatation effect (r = 0.88, p less than 0.01). In all but two cases vasodilatation tended to become prominent by repeat doses, twice a day, for two to seven days (r = 0.87, p less than 0.01). Vasodilatation was observed only in IC and proximal trunks of ACA and MCA where papaverine could make direct contact, but not in the distal branches beyond A3 or M3. Neurological examination showed improvement of paresis or level of consciousness in 7 cases but no effect in 6 cases. Intracerebral hematoma occurred in two cases (one by high concentration 4% papaverine) during the treatment. Therefore intracisternal papaverine is the treatment of choice in cases with symptomatic vasospasm with some cautions on concentration to be administered.

[Clinical application of microfibrillar collagen hemostat (Avitene) in neurosurgical field].

Microfibrillar collagen hemostat (Avitene) is a new absorbable hemostatic agent, of which mechanisms are adhesion to the bleeding site and platelet aggregation. Histopathological examinations revealed that Avitene was biocompatible with cerebral cortex in an animal experiments. Our previous studies indicated that Avitene is very effective and safe to use as a topical hemostatic agent during craniotomy in an experimental animal. Avitene was used as a topical hemostatic agent during craniotomy in 36 patients with intracranial organic lesions. Its effectiveness of hemostasis was revealed in 95%. This agent was especially useful to prevent oozing during craniotomy. Side effect of this agent was not reported in this study. Therefore, Avitene is very effective and safe to use as a topical hemostatic agent in the neurosurgical field.

[The effects of individual milk-drinking habits on nutrient intake and dietary patterns in men and women in Tottori Prefecture].

This study was performed to determine the actual conditions of milk-drinking habits in men and women, and to ascertain their effects on nutrient intake and dietary patterns. The 809 subjects were over 20 years of age and were obtained from the Tottori Prefecture Dietary Survey. The results are summarized as follows: 1. Over 40 percent of the subjects did not consume any milk during the three days of the dietary survey. Furthermore, only 38 percent of men and 46 percent of women have daily milk-drinking habits according to the results of the questionnaire. 2. Calcium and Vitamin B2 intake level and total serum cholesterol level were higher in milk-drinkers than non-milk-drinkers, in both men and women. The regression of total calcium intake from 6 groups of food was analyzed by multiple regression analysis. For both men and women who were milk-drinkers, total calcium intake was determined mostly by milk. In the case of non-milk-drinkers, total calcium intake came mostly from green vegetables for men, and other vegetables for women. 3. The ratios of both animal proteins and animal fats were higher in milk-drinkers. For women, energy percentage of fats was high and that of carbohydrates was low in milk-drinkers. The results seem to suggest that differences in dietary patterns is based on milk-drinking habits. Using the Hayashi's quantification method 3, dietary patterns were classified into two groups based on milk-drinking habits. Dietary patterns of milk-drinkers included the characteristic of eating bread, meats, and fats more frequently in men, fresh vegetables, eggs, fats and bread in women. In men, milk-drinking habits had a lesser influence on diet than in women.

[Relationship between dietary fiber intake and food intake patterns of the general population, evaluated by a regional nutrition survey].

This study was performed to estimate the dietary fiber intake calculated using individual food intake data and the dietary fiber tables, and to ascertain the relationship between food intake patterns and dietary fiber intake of the general population. The 805 subjects over 15 years old were obtained from the Tottori Prefecture Nutrition Survey. The results are summarized as follows: 1. The average dietary fiber intake per capita per day was 18.19 g; 18.67 g in men, and 17.81 g in women. Dietary fiber intake per energy was different among sexes and ages: women had more dietary fiber than men and the aged had more than the young. Those who had high fiber intake per energy took green vegetables, fruits, milk, soybean products, seaweed and potatoes more frequently, and did not take oil so frequently. 2. Total dietary fiber intake from 20 food-group sources was analyzed by Multiple Regression Analysis. For both men and women fruits, vegetables and soybean products mostly influenced dietary fiber intake. 3. Based on the intake of the 20 food-groups obtained from 356 men and 449 women, the correlation matrix among these foods was calculated. The correlation matrix was also submitted to a Principal Component Analysis. The result of the Principal Component Analysis told that food intake patterns were different among the levels of dietary fiber intake. Food intake patterns of men and women who had high fiber intake per energy had an eating pattern characterized by relatively more non-processed vegetable food, bread and milk. 4. The level of blood pressure was significantly related to dietary fiber intake per energy in men over 60 years old. In the hypertensive men over 60 years old, 23.3% were in the low fiber intake group, 37.2% in the middle group, and 39.5% in the high group. But in the normal blood pressure men over 60 years old, 50.0% were in the low fiber intake group, 8.3% in the middle group, and 41.7% in the high group.

[Interaction between Epstein-Barr virus (EBV) gene expression and antibodies to EBV in nasopharyngeal carcinomas].

In situ hybridization using EBERs and BHLF oligonucleotide probes and immunohistochemistry using monoclonal antibodies against LMP1, EBNA2, BZLF1 protein, p53 protein and bcl-2 protein were performed on 56 primary nasopharyngeal carcinomas. EBERs was detected in 46 cases (82%), and LMP in 17 cases (30%), but EBNA2 was not detected. While 30 of 32 cases (94%) in differentiated non-keratinizing carcinoma (NKC) and 16 of 17 cases (94%) in undifferentiated carcinoma (UNPC) showed EBERs, neither 5 cases of squamous cell carcinoma (SCC) nor 2 cases of adenocarcinoma showed EBERs. This finding confirms latent infection of EBV, especially phenotypical latency II, in NKC and UNPC but not in SCC. Bcl-2 protein was positive in 50 cases (89%), but its expression did not depend on expression of LMP1, which did not demonstrate induction of bcl-2 by LMP1 as seen in vitro. Cytoplasmic BZLF1 expression was detected in 18 cases (32%) whereas BHLF was positive only in 6 cases (11%). This suggests dysfunction of BZLF1, which disrupts viral latency despite its expression. p53 protein was positive in 31 cases (55%), and there was a distinct correlation between expression of BZLF1 and p53 protein (p < 0.001). This suggests that the interaction between BZLF1 protein and p53 protein, which inactivate each other, is one of the tumorigenic factors in NPC.