No associations between five polymorphisms in COMT gene and migraine.

OBJECTIVES: The pathophysiology of migraine headaches is not clearly understood yet. The dopaminergic system has been hypothesized to be involved in migraine pathogenesis. The aim of this study was to investigate catechol-O-methyltransferase (COMT) polymorphisms and chronic headaches. We analyzed five single nucleotide polymorphisms (SNPs) in COMT. MATERIALS & METHODS: The study population consisted of 71 patients with migraine with aura, 152 patients with migraine without aura, 86 patients with tension-type headache, and 191 healthy controls. The selected polymorphic markers included one causing His62His (rs4633) and two non-synonymous SNPs, Ala72Ser and Val158Met (rs6267, rs4680 respectively). Two other non-polymorphic SNPs (rs6270, rs740602) were examined. RESULTS: We found no significant differences in any genotypes, allele frequencies, or haplotypes among the patient groups and controls. CONCLUSIONS: Our results indicate that the five polymorphisms in COMT have no association with migraineurs in Western Japan. The possibility that segments elsewhere in the gene may contain a mutation responsible for modifying the expression of COMT or the activity of the enzyme is important. We cannot conclusively exclude the entire COMT gene from being involved in migraine pathogenesis.

A case of pelvic malignant paraganglioma.

We report a rare case of pelvic malignant paraganglioma that was treated with surgery, combination chemotherapy and radiation. A 47-year-old man was diagnosed with pelvic malignant paraganglioma that had metastasised to the thoracic vertebrae. The pelvic mass, which was 6 cm in size, was on the posterior side of the bladder and had invaded the prostate, seminal vesicle and bladder neck. We resected the intrapelvic tumor and lymph nodes using cystoprostatectomy. Metastases to bilateral obturator lymph nodes and the right internal iliac lymph node were shown by pathology. Adjuvant therapies included six courses of the combination chemotherapy (cyclophosphamide, vincristine and dacarbazine), and 12 courses of VP-16 therapy. Radiation therapy was done for metastasis of the thoracic vertebrae. Local recurrence, progression of bone metastasis and new metastasis have not been detected since these treatments. The patient has been clinically stable during 20 months of follow-up. Chemotherapy of cyclophosphamide, vincristine and dacarbazine and VP-16 with radiation appears to be effective in treating advanced malignant paraganglioma.

[Manifestation of primary biliary cirrhosis and Basedow's disease caused by exposure to carbon monoxide in a patient with HTLV-1 associated myelopathy].

A 55-year-old woman with HTLV-1 associated myelopathy (HAM) was discovered in a rentan kotatsu (Japanese foot warmer with a frame and a coverlet by burning briquet) with conscious disorder and admitted to an emergency hospital. Her conscious disturbance waned the 3rd day after admission with gradual improvement of communication and food intake. However, on the 18th day after admission, her orientation was poor again and she was unable to take food for herself and keep sitting. She was diagnosed as suffering from an interval form of acute carbon monoxide (CMO) poisoning and transferred to our hospital for the purpose of hyperbaric oxygen therapy on the 20th day after exposure to CMO. In the course of treatment she recovered but showed jaundice, pruritus, liver dysfunction and elevation of antimitochondrial antibody. She received liver biopsy and was found to have primary biliary cirrhosis (PBC). On the 150th day, she manifested perspiration and hypertension. The clinical and immunological feature revealed her Basedow's disease. The relationship between HAM and PBC due to the autoimmune process has been predicted by investigators. The implication of autoimmune disease and HLA haplotype is a main focus of attention. Our case supports their hypothesis, and suggested that the complication occurred with immunological and genetic correlation. Anti-HTLV-1 antibody was positive at a titer of 1:8192 before exposure to CMO. On transferring to us, it was negative and revealed excessive positive at a titer of 1:20,480 on the 80th day. Immunoglobulin analysis was normal on admission and increased during hospitalization. It was reported that prenatal exposure to relatively mild concentrations of CMO in rats reduces splenic macrophage phagocytosis and killing ability as well as macrophage respiratory burst. These data suggested that PBC and Basedow's disease were manifested by exposure to carbon monoxide.

Regiospecific internal desaturation of aliphatic compounds by a mutant Rhodococcus strain.

A mutant Rhodococcus strain lacking the ability to utilize 1-chlorohexadecane was found to cis-desaturate aliphatic compounds, such as 1-chlorohexadecane, n-hexadecane, and heptadecanonitrile, yielding corresponding products with a double bond mainly at the ninth carbon from the terminal methyl groups. A new oxidative pathway involving the cis-desaturation step was suggested for alkane utilization by Rhodococcus spp.

[Clinical statistics of stage I testicular tumor].

PURPOSE: A survey of stage I testicular tumors in the Chugoku-Shikoku district was taken in order to explore the clinical characteristics. PATIENTS AND METHODS: Three hundred and forty eight cases of stage I testicular tumor treated at 46 facilities in the Chugoku-Shikoku district between 1984 and 1992 were collected. Subjects' background factors, treatment methods and prognosis were studied. RESULTS: Tissue types were 249 (71.6%) seminoma and 99 (28.4%) non-seminoma. Adjuvant therapy for seminoma cases included 138 post-operative radiotherapy (4 recurrences, 3 cancer deaths), 57 chemotherapy (no recurrences, 2 contralateral testis tumor cases) and 48 were under surveillance (no recurrence). Adjuvant therapy for non-seminoma cases included 47 chemotherapy (1 recurrence) and retroperitoneal lymph node dissection was performed on 6 cases. Forty cases were under surveillance (1 recurrence). Of 8 (2.3%) cases with recurrence, 6 showed onset within two years and 2 after two years. Four of the 8 cases with recurrence were seminoma (1.1% of seminoma cases) and the other 4 were non-seminoma (4.0% of non-seminoma cases). All 3 (0.9% of all cases) of the cancer death cases were seminoma that received post-operative radiotherapy, while there were no cancer deaths in non-seminoma cases. CONCLUSION: Prognosis of stage I testicular tumor is good. Although the recurrence rate was higher in non-seminoma cases, cancer deaths were only observed in seminoma cases.

[Voiding condition in elderly males examined prostate cancer screening in total health check and the effect of subjective urinary symptoms on quality of life].

PURPOSE: We investigated the prevalence of lower urinary tract symptoms and the effect of subjective urinary symptoms on quality of life (QOL) in elderly males examined prostate cancer screening in total health check from April 1996 to March 1997. PATIENTS AND METHODS: A total of 922 eligible examinees 50 to 70 years old completed a questionnaire with questions worded similarly to those of the international prostate symptom score (I-PSS) and AUA Impact index score and so on. RESULTS: The prevalence of moderate to severe symptoms was 19.6%, which increased with age. I-PSS was well correlated aging but not prostate size. The most prevalent symptoms were nocturia (61.1%), frequency (50.0%) and weak stream (47.7%). There was good correlation between symptom severity and QOL and AUA Impact index scores. While QOL was correlated with obstructive and irritative symptom scores, wish for treatment was associated mainly with irritative symptoms by multiple regression analyses. However, some examinees (15.5%, 28/181), who had moderate to severe symptoms, did not feel a decrease of QOL in daily life. CONCLUSIONS: A large percentage of elderly men 50 years old or older experienced symptoms. However, subjective urinary symptoms did not always correlate with QOL in some individuals. We should independently consider not only symptom severity but also QOL and AUA Impact index score in clinical decision making.

Near-UV, circular dichroism, and fluorescence spectra of a rigid rodlike helical polysilane bearing trietheral moiety in ethanol/water.

An optically active, rigid rodlike helical polysilane with 6, 9, 12-trioxatetradecyl and (S)-2-methylbutyl substituents (1) was newly obtained as a very high molecular weight polymer of several million. Due to the presence of trietheral substituent, 1 was readily soluble in a polar solvent such as ethanol and a mixture of ethanol and water, but was insoluble in pure water. Polysilane 1 in pure ethanol at room temperature exhibited an intense and narrow ultraviolet (UV) and circular dichroism (CD) absorptions at 323 nm, associated with an almost mirror imaged fluorescence (FL) at 328 nm, that are characteristics of rigid rodlike, single-screw-sense helical polysilanes reported previously. When solution temperature was changed from 60 degrees C to -104 degrees C, a global shape of 1 expanded associated with an increase of segment length, whereas a screw pitch tended to be wound tightly. On the other hand, as a solvent polarity became poor, a global shape of 1 shrunk associated with an decrease of segment length and formed a chiral motif with an M-helicity between two helical segments with a kink. At a ratio of 50% of ethanol/water of 50:50 (v/v), 1 became insoluble and formed aggregates.

Development of centrifugal phytotron to study the gravity effect on vegetable plant growth.

The present Spacetron is used to cultivate plants over a long term by controlling environment condition. The cultivation drum was rotated in perpendicular direction creating fluctuation in gravity. Centrifugal force plus 1 G ground gravity, are distributed unevenly over the cultivation drum. This fluctuation effect on plant growth was not clear. In the modified Spacetron the cultivation drum rotates horizontally whereas the plant stage rotated in the perpendicular direction. To find the basic information for design of centrifugal phytotron the two axes Spacetron Junior (clinostat) was developed to formulate the micro and hypergravity environment. It would be used to study the effect on a plant growth process of different gravity conditions. In order to produce the different values of gravity, the clinostat's axis was rotated with a stepping motor at different angular velocity. The axis rotated at 5.2 revolutions per minute (rpm) to create a centrifugal force equivalent to 0.01 G and the plant stage was rotated at 5.2 rpm. The chlorophyll value is higher in the plants under microgravity condition of 0.01 G whereas the fresh weight and dry weight are higher in the plants under control condition of 1 G earth gravity. The result of this study showed that the plant growth was affected by microgravity along with other known factors such as vibration and unknown factors.

[Efficacy of granisetron rescue therapy for nausea and vomiting induced by cancer chemotherapies in urogenital malignant tumor].

In this study, the usefulness of granisetron rescue therapy for nausea and vomiting induced by cancer chemotherapies, including CDDP, was examined. Granisetron was given to twenty patients with urogenital malignant tumor by iv infusion for thirty minutes after the onset of nausea or vomiting. Nausea disappeared in 15 out of 20 patients (75%), 8 of whom (40%) experienced its disappearance while the granisetron was being administered. Vomiting was perfectly controlled in 5 out of 20 patients (25%) for 24 hours after the granisetron administration. No adverse event seemingly due to granisetron was observed. The result of this study confirmed the speedy effect granisetron on nausea induced by cancer chemotherapy including CDDP, but it stopped short of demonstrating sufficient efficacy for vomiting. Prophylactic use, therefore, seems more desirable in view of the patient's QOL, when a highly emetogenic anti-tumor drug, such as CDDP, is used.

Enhancement of muscarinic receptor-coupled phosphatidyl inositol hydrolysis in diabetic bladder.

We previously have shown an increase in muscarinic receptor density in streptozotocin (STZ)-induced diabetic and sucrose-fed diuretic rat detrusor that correlates with an increase in the contractile response to muscarinic agonist (J Pharmacol Exp Ther 248:81, 1989; Diabetes 40: 265, 1991). To investigate the signal transduction pathway involved in this altered functional response, we examined muscarinic receptor-coupled phosphatidylinositol metabolism in STZ-diabetic, sucrose-fed diuretic and age-matched control rat bladders. [3H]myo-inositol uptake was similar in all groups, but incorporation of myo-inositol into phosphatidylinositol (PI) was significantly increased in the diabetic bladder compared to the sucrose-fed and control rat bladders. Carbachol-induced increase in inositol phosphate (IPs) production was higher in the diabetic bladder than in bladders from control and sucrose-fed animals although the EC50 values were similar for all groups. Enhanced inositol phosphate production after muscarinic agonist stimulation may be due not only to the upregulation of muscarinic receptors but also the increased incorporation of myo-inositol into PI in the STZ-induced diabetic bladder.

[Molecular genetic analysis of a family with von Hippel-Lindau disease].

We analyzed germline mutations of the von Hippel-Lindau (VHL) gene located at chromosome 3p25 in a family of VHL disease by using single strand conformational polymorphism (SSCP) and Southern blot analyses. In 10 individuals including 2 patients with multiple renal cell carcinomas, multiple pancreatic cysts and cerebellar hemangioblastoma, there are no positive results in SSCP analysis. However, in 2 patients and one kindred, same abnormal band was observed in Southern blot analysis. Moreover, in this one kindred of 17 years old girl, multiple pancreatic cysts were found by computerized tomography (CT). These results shows the alteration in the VHL gene is a major rearrangement but not a small mutation and this alteration caused VHL disease in this family. Furthermore, presymptomatic diagnosis by direct mutation analysis seems to be very useful for early detection of this disease.

The Camey-Le Duc antireflux technique for the Koch pouch: evaluation of the upper urinary tract.

Between November 1989 and June 1993, 41 patients (78 renal units) underwent Camey-Le Duc technique for prevention of reflux of a Kock pouch. In 30 patients the ileal reservoir was connected to the skin for cutaneous urinary diversion, and in 11 it was connected to the urethra for lower urinary reconstruction. The mean postoperative follow-up period was 23 months, with a range of 6-47 months. Postoperative excretory urography (IVP) was performed at least once a year to evaluate the upper urinary tract configuration, and ascending cystography was performed to evaluate the reflux. No urinary tract dilatation was observed in 73 renal units (93.6%), while slight dilatation was noted in 3 (3.8%), moderate dilatation in 1 (1.3%), and marked dilatation in 1 (1.3%). Reflux was not found in any patient. Of 23 renal units in 12 patients in whom the last IVP examination was performed 6 months postoperatively, dilatation was noted in 4 (17.4%). In contrast, of 55 renal units in 29 patients in whom the last IVP examination was performed 12 months or more after the Kock pouch operation, dilatation was noted in only 1 (1.8%). We conclude that the Camey-Le Duc antireflux technique is effective in terms of simplicity and reliability.

Analysis of nm23 gene expressions in human bladder and renal cancers.

We measured nm23-H1 and nm23-H2 mRNA levels in tissues from 22 human bladder cancers and 16 renal cell carcinomas, and in 7 bladder cancer and 6 renal cancer cell lines by Northern blot and slot blot hybridization analyses. Differences in mRNA levels were evaluated in primary tumor tissues and in paired normal tissues and cell lines. Moreover, nm23 gene expression in primary tumor tissues was compared with clinicopathological features. High nm23-H1 and nm23-H2 expression was observed in cancerous areas of human bladder tissue (nm23-H1: p = 0.001, nm23-H2: p = 0.001) and bladder cancer cell lines (nm23-H1: p = 0.001, nm23-H2: p < 0.001) compared with that in normal bladder mucosa. However, mRNA levels of both nm23 genes were not associated with histological grade, pathological stage, tumor metastasis or prognosis. On the other hand, in human renal cell carcinomas, levels of both nm23 mRNAs in tumor tissues were similar to those in paired normal kidneys, but elevated in cultured cell lines (nm23-H1: p = 0.002, nm23-H2: p = 0.014). Moreover, there was a tendency towards high nm23 gene expression in grade 2 tumors compared with grade 1 (grade 1 vs grade 2, nm23-H1: p = 0.107, nm23-H2: p = 0.008; no grade 3 tumors in this study) and in high stage renal cancers (< or = stage II vs stage III < or =, nm23-H1: p = 0.023, nm23-H2: p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum levels of a tissue inhibitor of metalloproteinases-1 (TIMP-1) in bladder cancer patients.

Tissue inhibitors of metalloproteinases (TIMP-1 and -2) are common inhibitors of matrix metallo-proteinases (MMPs), thereby blocking degradation of extracellular matrix components. TIMP-1 and -2 have been reported to exhibit inhibitory activities against tumor invasion and metastasis. We measured the serum TIMP-1 levels in 16 healthy volunteers and in 69 patients with bladder cancer using a sandwich enzyme immunoassay, and evaluated the correlation between serum TIMP-1 levels and clinicopathological features. Patients with bladder cancer showed significantly higher serum TIMP-1 levels (251.1 +/- 96.0 ng/ml; p < 0.01) than those of healthy volunteers (168.5 +/- 33.2 ng/ml), and a positive correlation between the TIMP-1 level and invasion and metastasis was observed. This is considered to be the result of the reactive production of TIMP-1 in cancerous tissues. Thus, serum TIMP-1 levels may become a reliable clinical marker of the progression of bladder cancer.

[Serum levels and gene expressions of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in human renal cell carcinomas].

We examined serum levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in 32 patients with renal cell carcinoma. Serum IL-1 beta was elevated in only one patient (3.1%), IL-6 in 17 (53.1%) and TNF-alpha in 6 (18.8%). Positive rate of serum IL-6 increased with progression of the stage (stage I and II: stage III and IV = 14.3%: 88.9%, p < 0.0001) and was higher for rapid growth type (slow and intermediate growth type: rapid growth type = 36.4%: 90.0%, p < 0.005). However, increased serum levels of IL-1 beta and TNF-alpha were not correlated with stage, grade, or growth type. Gene expressions of IL-1 beta, IL-6, IL-6 receptor and TNF-alpha in the tissues resected from 15 patients with renal cell carcinoma and 3 cell lines established from renal cancers were evaluated by Northern blot analysis. Gene expression of IL-1 beta and TNF-alpha were not detected in any of the tissues or cell cultures, but highly enhanced expressions of IL-6 were revealed in two tumor specimens (13.3%, 1 rapid and 1 slow growth type) and 2 of 3 cell lines. Expressions of IL-6 receptor in tissues and cells were weak. These results suggest that IL-6 plays an important role in the progression of renal cell carcinoma, and that measurement of IL-6 in patients with renal cell carcinoma may be useful clinically.

[Mental deterioration in childhood epilepsy. II. Investigation of intelligence of right-handed epileptic children with right-hemispheric dominance of language].

To clarify the pathogenesis of mental deterioration in epilepsy, we investigated the intelligence of right-handed epileptic children with right hemispheric dominance of language. On dichotic listening test, all 13 patients with right-handedness, 7 to 20 years of age, showed a left ear dominance suggesting right hemispheric dominance of language. Among 13 patients, 9 showed mental retardation, and 6 patients of them showed mental deterioration during the clinical course of epilepsy. Eight patients showed findings suggesting brain damage in the left hemisphere either in clinical feature, EEG or CT. A relationship was suspected between the right-hemispheric dominance of language and the epileptic focus in the left hemisphere. The usefulness of dichotic listening test was suggested both in disclosure of the brain damage and the investigation of mental retardation in childhood epilepsy.

Teratogenic effects of noise and cadmium in mice: does noise have teratogenic potential?

The teratogenicity of combined exposure to noise and cadmium was studied in mice. ICR mice were exposed to a wide octave-band of noise at 100 dB(C) for 6 h on d 7 of pregnancy in one of two ways: continuous exposure or intermittent (15 min on/15 min off). Cadmium sulfate at 1 or 2 mg/kg was intraperitoneally injected on d 7 of pregnancy. Four groups were exposed to both cadmium and noise. On d 18 of pregnancy, fetuses were examined for external and skeletal malformations. Another experiment was performed with two other patterns of noise exposure: continuous exposure for 3 h, and intermittent exposure (5 min on/5 min off) for 6 h on d 7 of pregnancy. In the groups exposed to continuous noise for 6 h, total percentages of malformed fetuses were significantly higher than that in the control group, but there were no significant increases of total percentages of fetal malformations in the combined treatment groups in comparison with the groups given the same dose of cadmium alone. The percentages of skeletally malformed fetuses in groups exposed to 6 h of continuous noise were significantly higher than in groups that received saline or the same dose of cadmium. There were no significant differences in the total percentages of malformed fetuses between the control group and the groups exposed to a total of 3 h of noise, whether continuously or intermittently. Although combined treatment with cadmium and noise resulted in an increase of total percentages of malformed fetuses compared to the same dose of cadmium alone, the interactions between cadmium and noise showed no synergistic effect on teratogenicity. The magnitude of teratogenicity due to noise is much weaker than that of cadmium, and is therefore easily masked by that of cadmium in statistical tests of the significance of differences.

[Two cases whose epileptic attacks disappeared at the time of infection].

Two cases with secondary generalized epilepsy whose epileptic attacks disappeared abruptly were reported. Permanent improvement was observed in case 1 with residual state of West syndrome, aged 4 years, after viral pneumonia, both epileptic attacks and epileptic discharges on EEG disappeared more than 3 years. Transient improvement was observed in case 2 with Lennox-Gastaut syndrome, aged 6 years, after an episode with insomnia, poor appetite and confusion for three days. After this episode epileptic attacks disappeared for 9 months and epileptic discharges on EEG were also markedly decreased. However, epileptic attacks relapsed following the reduction of phenytoin after 9 months. An effect resembling ketogenic diet therapy and a change of pharmacokinetics of antiepileptic drugs may be involved in the transient improvement of case 2. However, any effects involving an immunological effect and secretions of adreno-cortico-hormone following after stress may be not involved in the permanent improvement of case 1.