Sesame lignans increase sympathetic nerve activity and blood flow in rat skeletal muscles.

Beneficial effects of sesame lignans, especially antioxidative effects, have been widely reported; however, its potential effects on autonomic nerves have not yet been investigated. Therefore, the current study aimed to investigate the effect of sesame lignans on the autonomic nervous system. The sympathetic nerve activity in rat skeletal muscle was measured using electrophysiological approaches, with blood flow determined using the laser Doppler method. Sesame lignans were administered intragastrically at 2 and 20 mg/kg, and after 60 min, the sympathetic nerve activity was observed to increase by 45.2% and 66.1%, respectively. A significant increase in blood flow (39.6%) was also observed for the 20-mg/kg dose when measured at 55 min after administration. These sympathomimetic effects were completely prevented by subdiaphragmatic vagotomy, and the increase in blood flow was eliminated in the presence of the beta2-adrenergic receptor inhibitor butoxamine. Thus, it is proposed that sesame lignans can increase the blood flow of skeletal muscle, possibly by exciting sympathetic nerve activity through the afferent vagal nerve.

Spinal cord hemangioblastomas in von Hippel-Lindau disease.

STUDY DESIGN: Retrospective data analysis. OBJECTIVE: To clarify the clinical features and surgical management of spinal cord hemangioblastomas in patients with von Hippel-Lindau disease (VHL). SETTING: Clinical VHL Research Group in Japan, Japan. METHODS: Forty-eight out of 66 patients with associated spinal cord hemangioblastoma among 142 VHL patients were retrospectively examined with respect to clinical features, accompanying lesions and outcome of surgical treatment. RESULTS: Among these 48 patients, 46 of them (95.8%) also had a central nervous system (CNS) hemangioblastoma at another site: 42 (87.5%) with cerebellar hemangioblastoma and 11 (22.9%) with brain stem hemangioblastoma. Twenty-three patients (47.9%) had more than one spinal cord hemangioblastoma. The 48 patients with spinal cord hemangioblastomas collectively had a total of 74 tumors. The tumor was accompanied with a syrinx in 64 and without it in 10 patients. Forty of the 48 patients underwent surgical treatment for their spinal cord hemangioblastomas, and 7 of these 40 underwent surgical treatment twice. When functional changes in the patients after these 47 operations were examined by postoperative evaluation by McCormick's classification, 39 of these operations (83.0%) resulted in improvement/no change and 8 (17.0%) in aggravation of symptoms. CONCLUSION: Von Hippel-Lindau disease patients bearing spinal cord hemangioblastomas mostly had a CNS hemangioblastoma at another site. These tumors can be removed in the majority of VHL patients without aggravation. In these patients, when the timing of treatment for spinal cord hemangioblastoma is determined, the probability of occurrence and treatment of other lesions should be considered.

Intracerebroventricular administration of GABA-A and GABA-B receptor antagonists attenuate feeding and sleeping-like behavior induced by L-pipecolic acid in neonatal chicks.

It has been demonstrated that L-pipecolic acid (L-PA), a major metabolic intermediate of L-lysine (L-Lys) in the mammalian and chicken brain, is involved in the functioning of the GABAergic system. A previous study has shown that intracerebroventricular (i.c.v.) injection of L-PA suppressed feeding and induced sleep-like behavior in neonatal chicks; however, the precise relationship between the GABAergic system and L-PA has not been clarified. In the present study, the role of the GABA-A or GABA-B receptors in the suppression of food intake and induction of sleeping-like behavior by L-PA was investigated. Chicks were injected i.c.v. with the GABA-A antagonist picrotoxin or GABA-B antagonist CGP54626 along with L-PA. Although suppression of food intake by L-PA was restored partially by co-injection with CGP54626, but not picrotoxin, sleep-like behavior induced by L-PA was suppressed significantly by both antagonists. These results suggested that L-PA activated both GABA-A and GABA-B receptors, and GABA-B receptors alone contributed to food intake whereas both receptors contributed to sleep-like behavior.

Fluorescence in situ hybridization to assess transitional changes of aneuploidy for chromosomes 7, 8, 10, 12, 16, X and Y in metastatic prostate cancer following anti-androgen therapy.

There have been few detailed studies conducted on the cell population in relation to cytogenetic changes between the pre- and post-treatment periods in patients with prostate cancer. We investigated numerical chromosome changes associated with anti-androgen therapy, using fluorescence in situ hybridization (FISH). FISH using chromosome-specific centromeric probes was used to assess transitional changes in the frequency of aneuploidy for chromosomes 7, 8, 10, 12, 16, X, and Y in prostate cancer during the pre- and post-treatment periods. Gains of chromosomes 7, 8 and 12 were notable in the pre-treatment samples (8 out of 9 cases in chromosome 7; 8 out of 9 cases in chromosome 8; 7 out of 9 cases in chromosome 12), while a notable reduction in the number of cells with extra copies of these chromosomes was observed in post-treatment specimens. Other chromosomes did not show noticeable change in their FISH signals at each phase of clinical treatment in all 9 cases. Changes in cell number with high ploidies of chromosome 7, 8 and 12 reflect the clinical effects of anti-androgen therapy at the early phase, which might explain the androgen dependency of metastatic prostate cancer cells.

[Two cases of successful treatments with steroid for local and systemic hypersensitivity reaction following intravesical instillation of Bacillus Calmette-Guerin].

We have found steroid pulse therapy to be effective and safe for local and systemic adverse reactions of BCG therapy. Two cases are reported. Case 1: A 57-year-old woman with initial recurrence of urinary bladder carcinoma was treated with transurethral resection. The histopathological findings were transitional cell carcinoma (TCC), G2 > G1, pT1a. To prevent a second recurrence, she was administered Bacillus Calmette-Guerin (BCG) instillation therapy: 80 mg of BCG, (Tokyo strain) suspended in 40 ml of normal saline, instilled into her bladder weekly. After the fifth week of instillation, she was found to have a cough, sputum, edema of the eyelids, congestion of palpebral conjunctive, severe pain on micturition and pollakisuria. Although she was administered antituberculus, antibiotics and antiallergic drugs, all sign and symptoms were aggravated. Blood, urine and sputum cultures remained negative for mycobacterium. She was later diagnosed as having hypersensitive reactions against BCG and treated with steroid pulse therapy. The signs and symptoms mentioned above were decreased immediately and disappeared after a week. Case 2: A 76-year-old man with initial recurrence of urinary bladder carcinoma was treated with transurethral resection. To prevent a second recurrence, he was instilled the BCG six (6) times. Although no adverse reaction was observed, urinary cytology remained positive (class V) and small papillary tumor was detected at the dome of the bladder. Transurethral biopsy was then performed. The histopathological findings showed TCC, G3, CIS on the dome of bladder. Then he was again administered the same BCG instillation therapy. After the fifth instillation, he complained of severe pain of micturition, pollakisuria and dysuria. Although he was administered antibiotics and antiinflammatory drugs, all signs and symptoms were aggravated. Urine culture remained negative for mycobacterium. He was diagnosed as having hypersensitive reactions against BCG and was treated with two times of steroid pulse therapy. The signs and symptoms mentioned above were decreased immediately and disappeared after the second steroid pulse therapy.

Vinculin: its possible use as a marker of normal collecting ducts and renal neoplasms with collecting duct system phenotype.

Vinculin is a cytoskeletal protein associated with membrane actin-filament-attachment sites of cell-cell and cell-matrix adherens-type junctions. In this article, we examine the expression of vinculin to elucidate its role in human renal neoplasms. We reviewed surgically resected specimens and selected available tissue from 79 renal tumors in 78 patients. There were 55 men and 23 women. Their mean age was 61 years and the mean size of the renal tumors was 6.1 cm. All renal tumors were examined by immunohistochemistry using a monoclonal antibody against vinculin. Overall, 17 (21.5%) renal tumor samples reacted with vinculin. The positive ratio in various types of renal tumors was as follows: conventional-type (clear cell), 0/54; papillary-type, 5/12; chromophobe-type, 5/5; sarcomatoid-type, 3/4; collecting duct carcinoma, 3/3; and oncocytoma, 1/1. The positive rate of conventional-type renal cell carcinomas (RCCs) is significantly different from that of other renal tumors (P < .01). Normal kidney, conventional, and papillary-type RCCs exhibited positive signals in Western blot analysis. These results suggest that vinculin may serve as a useful marker of renal neoplasms with collecting duct system phenotype such as chromophobe-type RCC.

Prostatic signet-ring cell carcinoma: case report and literature review.

Signet-ring cell carcinoma (SRCC) of the prostate is a very rare neoplasm and there have been only 38 cases reported to date. Here the 39th case of prostatic SRCC containing a small amount of neutral mucin, prostatic specific antigen (PSA) and prostatic specific acid phosphatase (PSAP) in the signet-ring cells is reported. It was also found that some intracytoplasmic lumina were derived from the shallow or deep invagination of luminal membranes of cancer cells that formed the neoplastic glands. Using immunohistochemistry, a combination of monoclonal antibodies against cytokeratins 7 and 20 as well as PSA and PSAP may be useful in differentiating prostatic primary SRCC from metastatic SRCC originating in the gastrointestinal tract.

Human mismatch repair gene (hMSH2) product expression in relation to recurrence of transitional cell carcinoma of the urinary bladder.

BACKGROUND: Several convincing studies have shown that the hMSH2 gene plays major roles in mismatch repair by recognizing mismatched bases and preventing mutations during DNA replication. Loss of this function may result in the accumulation of DNA replication errors or even the mutator phenotype (which may be responsible for the multiple mutations required for multistep carcinogenesis), and it has been found to affect the prognosis of patients. Thus, the authors felt that it would be of interest to study the expression patterns of hMSH2 protein in malignant tumors and to assess the correlation of hMSH2 protein to various clinical and pathologic features in these patients. METHODS: The authors examined the expression patterns of hMSH2 protein in 115 patients with transitional cell carcinoma (TCC) of the urinary bladder by immunohistochemical technique using monoclonal antibody to hMSH2 protein. RESULTS: The group in which hMSH2 was preserved (>20% of nuclei were positive for staining by anti-hMSH2 antibody) included 86 of 115 (75%) of the TCCs, whereas the remaining 29 cases (25%) belonged to the group in which hMSH2 was preserved (< or = 20% of tumor nuclei were positive), including 2 negative cases. Univariate analysis indicated that reduced expression of hMSH2 protein was significantly more frequent in high grade tumors than in low grade tumors (P = 0.04). Furthermore, statistical multivariate analysis revealed that hMSH2 reduction was significantly related to the recurrence (P = 0.02). CONCLUSIONS: These results suggest that abnormal expression of hMSH2 protein might be involved in tumorigenic processes and in the progression of some TCCs, and that the loss of hMSH2 protein expression might be a useful predictor of recurrence of TCC.

Projection map of the reaction center-light harvesting 1 complex from Rhodopseudomonas viridis at 10 A resolution.

The photosynthetic reaction center-light harvesting 1 complex from Rhodopseudomonas viridis was purified and reconstituted into two-dimensional crystals. The single-layered crystalline sheets with lattice parameters a=b=133.3 A and gamma=120 degrees were investigated by electron cryo-microscopy and the projection map at 10 A resolution was calculated. The opening diameter of the light-harvesting ring of 72 A is sufficient to allow slight movement of the reaction center within the ring. Based on characteristic features observed in the projection map, the mechanism of energy transfer from the light-harvesting 1 complex to the reaction center was discussed.

[Microscopic foci of urachal carcinoma in an incidentally detected urachal cyst: a case report].

A 33-year-old man who had been treated for chronic prostatitis was diagnosed to have urachal cysts by transabdominal ultrasonography. Cystoscopy revealed protuberance at the dome of the bladder. Computerized tomography scan and magnetic resonance imaging showed the mass to be mostly cystic but partly solid. Resection of the urachal cysts and partial cystectomy were performed. Histopathologically, most cysts had a normal cylindrical epithelium with retention of mucinous substance. However, several small cysts contained epithelial cells resembling tubulo-villous adenoma and showing mitotic figures. This case was concluded as urachal carcinoma detected in its very early stage.

[A case of Cushing's syndrome due to bilateral multiple adrenal adenomas].

We report a case of Cushing's syndrome due to bilateral adrenal adenomas. A 45-year-old woman was found to have Cushing's syndrome during the course of treatment for diabetes mellitus. The diagnosis of Cushing's syndrome was based on the absence of a diurnal rhythm in plasma cortisol and failure to suppress plasma cortisol by 1 or 4 mg of dexamethasone. The plasma level of adrenocorticotropic hormone (ACTH) was below the normal range, and plasma cortisol responded normally to rapid ACTH injection. Abdominal computed tomography revealed bilateral adrenal tumors. Bilateral uptake of radiocholesterol by the adrenal cortex was observed in adrenal scintigraphy. Bilateral adrenalectomy was performed. Microscopic examination and analysis of steroid contents by high performance liquid chromatography showed that the tumor was cortisol-producting adenoma.

[The prognostic factors in astrocytic tumors: analysis by the Kaplan-Meier method and the Weibull log-linear model].

As the prognosis of astrocytic tumors depends on various factors, identifying prognostic factors should be useful for developing strategies to cope with them. Between 1975 and 1994, more than 200 patients with astrocytic tumors were treated in Kagoshima University. Of these patients, 149 (grade I: 17, grade II: 42, grade III: 41, grade IV: 42, unproven: 7) have been followed up. Records of these patients were retrospectively reviewed for age at the time of initial symptoms, gender, histological grade (WHO), extent of tumor resection, radiation therapy, and administration of anticancer agents. We used the Kaplan-Meier method and the Weibull log-linear model to analyze the relation between survival time and these prognostic factors. Survival time was counted from onset of symptoms, and age of initial treatment was used as a covariant. The mean age of males at the initial diagnosis was 40.8 years (n = 77), and that of females was 39 years (n = 72). Using the Kaplan-Meier method, the mean survival time of the 149 patients was 101 months (males; 72.7 months, females; 134.5 months). Mean survival time of grade II was 144.3 months, that of grade III was 95.2 months, and grade IV (glioblastoma) was 15.9 months. Histological grades and mean ages of the groups showed a positive correlation. Among grades II, III and IV, the Kaplan-Meier survival curves were significantly different (p < 0.0001) according to the log-rank test. By the extent of surgical resection (subtotal or greater resection, partial resection, and less than partial resection), the mean survival time showed a significant difference (p < 0.05) on the log-rank test. However, we could not detect a significant difference in survival time between the group that received chemotherapy and the group which did not. The Weibull log-linear analysis indicated that gender, age, histological grade (WHO), extent of surgery, and dose of radiation therapy were prognostic factors. Covariants of grades II, III, and IV made survival time 0.314, 0.179, and 0.069 times as long as that of grade I. The survival time after "partial resection" became 1.415 times as long as the survival time after "less than partial resection". The covariant of "greater than subtotal resection" showed a prolonged survival time of 2.916 compared with that of "less than partial resection". As for age at treatment, the older the patient was, the shorter the survival time. The rate was 0.986 for each year of age. Irradiation of one Gy increased survival time by 1.015 times. Chemoimmunotherapy (dose of ACNU and interferon beta) could not be confirmed as an effective covariant.

Overexpression of MDM2 and p53 protein is infrequently but significantly associated with progression of human prostatic adenocarcinoma.

In the present immunohistochemical study using anti-p53 (DO-7) and anti-MDM2 (IF2) antibodies, we determined the frequency of p53 and MDM2 protein expression in a series of 115 primary prostatic adenocarcinomas (stage A1 to D2) and evaluated the reliability of p53 and MDM2 immunoreactivity as an indicator for tumor progression. Overall, 13.9% (16/115) of surgically resected tumors were positive for anti-p53 antibody. A significantly higher association of immunoreactivity for p53 was detected in both high-grade (4/16, 25%; p<0.05) and advanced stage tumors (14/73, 19.1%; p<0.05) compared with that of other grade or stage. Positive staining for anti-MDM2 antibody was observed in only 4.3% (5/115) of the tumors examined. However, nuclear MDM2 protein overexpression, detected as focal and markedly heterogeneous staining, was sometimes observed especially in advanced stage tumors (4 stage C and 1 stage D tumors), and was significantly more common in locally advanced cancers (p<0.05) than in those of other stage. Only 2 cases (1.7%) exhibited positive staining with both p53 and MDM2 antibodies. These findings suggest that p53 and MDM2 alterations might play significant roles in the development and progression of some advanced stage or high-grade prostatic cancers, although MDM2 and p53 protein overexpression is infrequent in prostatic adenocarcinoma.

p53 and human papillomavirus DNA in renal pelvic and ureteral carcinoma including dysplastic lesions.

Ninety-eight cases of transitional-cell carcinoma (TCC) of the renal pelvis and ureter, including dysplastic lesions, were studied for tumor incorporation of human papillomavirus (HPV) type-16 and type-18 DNA by in situ hybridization (ISH) with DNA probes for each HPV viral type. Immunohistochemical analysis of p53 expression was also performed. Fresh tumor tissues from 26 patients were also studied for p53 mutations in exons 4 through 9 by direct sequencing and for HPV infection by polymerase chain reaction (PCR). Thirty-two tumors were positive for HPV DNAs, including 6 double-positive cases. Among these tumors, adjacent dysplastic lesions in 21 cases (66%) also revealed identical reactivity. Overexpressed p53 was detected in 26 cases. Expression of p53 was also detected in dysplastic lesions in 19 out of these 26 cases (73%). Three cases were positive for both HPV DNA and p53 antibody. p53 point mutation was detected in 7 of 26 cases, 6 of which were also positive for p53. HPV type-16 DNA was detected in 6 cases by PCR, 4 of which were also ISH-positive. Overexpressed p53 was frequently detected in invasive and non-papillary tumors (p < 0.01) and in high-grade tumors (p < 0.05). HPV infection was more common in non-invasive and papillary tumors (p < 0.05). These findings suggest that HPV infection or overexpression (mutation) of p53 may be an early event and be related to phenotypes of tumor-cell growth patterns and progression.

[A clinico-pathological study of 69 cases after total cystectomy].

A clinico-pathological study was conducted on 69 patients with bladder cancer who underwent total cystectomy. The one, three and five-year actuarial survival rates for the 69 patients were 73.3%, 48.6% and 44.1%, respectively. Survival rate was not significantly associated with sex, the number of tumors or the size of tumors. The survival rate in those aged 70 years or more was slightly worse than in those who were much younger. Patients with papillary tumors had a more favorable survival rate than those with non-papillary tumors but we could find no significant difference between those with pedunculated tumors and those with sessile tumors. The actuarial 5-year survival rates by grade were 71.9% in G1 + G2, 22.6% in G3 and 32% in non-transitional cell carcinoma; the rates by stage were 86.5% in pTa + pT1, 85.7% in pT2, 20.8% in pT3a, 18.2% in pT3b and 0% in pT4. When the stage reached pT3a, the survival rate fell remarkably. The rate of INF alpha (93.8%) was significantly better than that of INF beta (28.1%) and INF gamma (15.2%). The rate of ly0 (76.2%) was also significantly better than that of ly1 (25.5%) and ly2 (18.8%). There was no significant difference in survival between v(-) (50.7%) and v(+) (25.9%). We could find no significant difference between patients who underwent pelvic lymph nodes dissection and those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of renal pelvic tumor due to phenacetin abuse].

An 80-year-old female had been taking phenacetin-containing analgesics due to severe pain in her legs and headache caused by SMON since 1957. The total accumulated dose of phenacetin that she had taken was about 2.3 kg. She visited the department of urology in our hospital complaining of gross hematuria in May, 1987. DIP showed that bilateral kidney were atrophic and her left pyelogram was non-visualized. A solid mass was located in her renal pelvis on the CT scan. Under the diagnosis of a left renal pelvic tumor, nephrectomy was performed on her left kidney in January, 1988. Histological diagnosis was interpreted as a transitional cell carcinoma, at a grade 1 greater than 2 and interstitial nephritis was detected. She died 8 months after the operation because of lung and bone metastasis. In autopsy, interstitial nephritis of the right kidney was also recognized. Our case is the fourth report of renal pelvic tumor due to phenacetin abuse in Japan.

[Angiomyolipoma of the kidney: a case report and a statistical study of 429 cases in Japan].

A 40-year-old housewife was found to have a renal mass on her left side through an ultrasonogram at the hospital during a medical check up. The patient had a dull pain in her left flank intermittently for three years. She had no personal or family history of stigmas of tuberous sclerosis. The mass showed a high echogenicity on the ultrasonogram and a low density (-84HU) on the CT scan. Preoperative diagnosis was reported as renal angiomyolipoma and an enucleation of the tumor was performed with CUSA. A statistical study was done on data taken from 429 cases of renal angiomyolipoma in the Japanese literature, including our case. The male to female ratio was 1 to 2.9. Thirty three percent of the cases were associated with tuberous sclerosis. The ratio of bilateral cases to unilateral ones was 1:4. The main clinical signs were abdominal pain, abdominal mass and gross hematuria. Nephrectomy was done in 71.0% of the cases, partial nephrectomy and enucleation in 13.7% and embolization in 2.2%. Through the composition of the CT scan and the ultrasonogram, preoperative diagnosis has become possible in many cases, so recently the ratio of nephrectomy has been decreasing. We think partial nephrectomy and enucleation compose the most effective therapy for renal angiomyolipoma.

Establishment of a human megakaryoblastic cell line (T-33) from chronic myelogenous leukemia in megakaryoblastic crisis.

A megakaryoblastic cell line, termed T-33, was established from the peripheral blood of a patient with Philadelphia chromosome-positive chronic myelogenous leukemia in megakaryoblastic crisis. T-33 cells have been maintained in RPMI 1640 medium containing 10% fetal calf serum in a single cell suspension with a doubling time of 24-36 h for over 2 years. Giemsa-banded karyotypes were female hyperdiploid with a modal chromosomal number of 51, all cells including Philadelphia chromosome. The cells showed strong positivity for periodic acid-Schiff and alpha-naphthyl acetate esterase, and weak for alpha-naphthyl butyrate esterase, but were negative for myeloperoxidase. Flow cytometric analysis of cell surface markers showed the existence of HLA-DR, MY-7, MY-9, and a platelet antigen (Yukb), and no markers for T- or B-lymphocytes. Most of the cells fixed with acetone were positive for Factor VIII, platelet glycoprotein IIb-IIIa, IIIa (Yukb), and Ib, but negative for glycophorin A and hemoglobin. Ultrastructural platelet peroxidase was demonstrated in 2-3% of cells and the percentage of positive cells increased up to 20% after the treatment with 12-O-tetradecanoylphorbol-13-acetate. The cells contained small dense granules negative for platelet peroxidase, their number increasing threefold after 12-O-tetradecanoylphorbol-13-acetate treatment. Such treated cells frequently showed a complex of the demarcation membrane in the cytoplasm. T-33 responded thrombin to exhibit calcium influx. This cell line may be useful for the study of the early stage of megakaryocytic differentiation in human megakaryopoiesis.

[Study of clinical efficacy and safety of long-term cinoxacin therapy of chronic urogenital organ infection].

Thirty-five patients with chronic simple and complicated urogenital organ infections were treated with 400 mg/day Cinoxacin for 60 to 284 days. The effects were judged according to improvements of subjective symptoms, bacteriuria and pyuria before and after the complete administration. Overall clinical efficacy in 35 cases with urogenital organ infections was estimated as excellent: 54%, good: 26%, poor: 17%, and effectiveness rate: 80%. The clinical effectiveness rate in 12 cases of chronic simple urinary tract infection was 100%, and in 14 cases of chronic complicated urinary tract infections was 64%, and in 6 cases of chronic prostatitis the rate of effectiveness was 83%. No recurrence was observed during the treatment. No side-effects or toxicity were seen. Accordingly long-term Cinoxacin therapy seems to be useful in preventing recurrence in chronic infections encountered in the department of urology.