Ascending contraction and descending relaxation in the distal colon of mice lacking interstitial cells of Cajal.

Recently an essential role of interstitial cells of Cajal (ICC) within myenteric plexus (ICC-MY) was suggested in ascending contraction and descending relaxation in the mouse ileum. The role of ICC in these neural reflexes was examined in the distal colonic segments prepared from the wild type and c-kit mutant, W/W(V) mice, in the present study. Localized distension of the segments from the wild type mice by using a small balloon resulted in ascending contraction and descending relaxation. In the segments from the mutant mice, localized distension also induced these neural reflexes similar to those observed in the wild type mice. Immunohistochemical examination demonstrated that ICC-MY and ICC present in muscle layers (ICC-IM) were severely disrupted in the mutant mouse, but only ICC, present within submucosal plexus (ICC-SMP), remained unchanged. In the small strips with ICC-SMP absent prepared from the mutant mouse, electrical field stimulation induced contraction or relaxation in the absence or presence of atropine, respectively. It was suggested that ICC have no important role in the ascending and descending neural reflexes in the mouse distal colon, this is in direct contrast to the role of ICC-MY in the ileum.     

Anti-tumor activity of human recombinant TNF against human malignant glioma cell lines and combined effect with Hu INF-beta

Human TNF was detected fairly recently and at present the anti-tumor activity of human recombinant TNF is being examined against various malignant tumors of human origin. In the present study, we report the anti-tumor activity of recombinant human TNF against human malignant glioma cell lines in vitro and in vivo, in addition to its combined effects with HuIFN-beta. The in vitro study was conducted as follows. Thirteen human glioma cell lines were exposed to 100 U/ml TNF, 1,000 IU/ml HuIFN-beta, or both, and the suppression rate was calculated on days 3, 5 and 7. In the in vivo study, nude mice carrying a human glioma cell line, KMS II, in the subcutaneous tissues were divided into groups and drugs were administered intratumorally as described below. 1) control, 2) TNF 5,000 U single administration, 3) TNF 5,000 U, intermittently administered (once/week for two weeks), 4) TNF 5,000 U, continuously administered (3/week for two weeks), 5) HuIFN-beta 50 X 10(4) IU (3/week for two weeks), and 6) combination of 4) with 5). Results of the in vitro study revealed some suppressive effects on proliferation of tumor cells on day 7 in all 13 glioma cell lines examined with 100 U/ml TNF. And also, especially in 8 of 13 cell lines, the suppression rate was more than 30%. The suppressive effects of TNF were augmented by combined use of HuIFN-beta in all cell lines, giving a range of suppression of 67.8 to 99.3%. The in vivo study revealed that the mean tumor weight ratios (control = 100%) on day 19 (the end of the experiment) were as follows; single administration of TNF: 41.3%, intermittent: 46.7%, continuous: 26.7%, HuIFN-beta: 65.9%, combination: 18.5%. Statistical analysis disclosed significant suppressive effects on tumor proliferation between the control group and 3 TNF-administered groups (single, intermittent, and continuous) and that suppression in the continuously administered group was more severe in comparison with the group given single administration. Moreover, it was suggested that combination therapy with TNF and Hu IFN-beta was more effective than a single therapy with TNF only or HuIFN-beta only. From the results described above, it was found that human recombinant TNF had some cytotoxic effects against human malignant gliomas in vitro and in vivo, although the degree of cytotoxicity was not always higher in comparison with the effects of TNF.     

Obstinate cough as a sole presenting symptom of non-metastatic renal cell carcinoma

Renal cell carcinoma (RCC) causes many kinds of symptoms such as hypercalcemia, hypertension, polycythemia and fever. Here we describe a rare case of RCC presenting with a persistent cough. After radical nephrectomy, the obstinate cough disappeared. When the tumor recurred locally, the cough also recurred. Furthermore, the cough disappeared completely again after the removal of the recurrent tumor. Although all the clinical findings suggested that the RCC caused the cough, we could not identify a specific humoral substance responsible for the cough.     

Sequential bilateral minimum incision endoscopic radical nephrectomy in dialysis patients with bilateral renal cell carcinomas

Since 1998, we have performed minimum incision endoscopic surgery (MIES) for renal cell carcinoma (RCC). For seven dialysis patients with bilateral RCC, we have performed sequential bilateral MIES radical nephrectomy. It was carried out by retroperitoneal approach through a single minimum incision that narrowly permitted extraction of the specimen using endoscopy and direct stereovision, without trocar ports, without gas insufflation and without the insertion of the hands of operators into the operative field. Although six of the seven patients had multiple complications in addition to chronic renal failure (CRF), bilateral kidneys were successfully removed by sequential MIES radical nephrectomy without major operative complication. Postoperative recovery was prompt with all patients resuming oral feeding and walking by the second postoperative day. Sequential bilateral MIES radical nephrectomy, leaving the peritoneal cavity intact and without imposing circulatory stress caused by gas insufflation, is a feasible treatment for bilateral RCCs in dialysis patients.     

Characteristics of young-onset hypertension identified by targeted screening performed at a university health check-up.

Since the prevalence and clinical characteristics of young-onset hypertension are still to be elucidated, we performed targeted-screening at an annual university health check-up for two consecutive years. Out of 16,464 subjects in 2003 and 17,032 in 2004 that were aged less than 30 years, 22 and 26 students (all males) exhibited high blood pressure (BP), respectively, on three occasions during casual BP measurements at the Tohoku University Health Center (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively). These students were asked to measure their BP at home, and 9 subjects in total were diagnosed as having essential hypertension (EH). The remaining students were diagnosed as having white coat hypertension (WCH). In 8 out of 9 EH students, their father and/or mother had also been treated with antihypertensive medication. Adjustment by attendance ratio for each BP measurement suggested that the incidence of EH was around 0.1% and that of hypertension (EH and WCH) was around 0.5% in university students aged less than 25 years, since most of the subjects and hypertensive students were between 18 and 24 years old. Body mass index of the EH, which was more than 25 kg/m2 (overweight), was significantly higher than that with WCH. In conclusion, the combination of repeated casual BP measurements and home BP effectively identified young-onset EH. The clinical parameters indicated that male gender, genetic background, and excessive weight were risk factors for young-onset hypertension.     

Skull metastasis of thyroid papillary carcinoma.

Skull metastasis of thyroid carcinoma is rare. The majority of skull metastases of thyroid carcinoma are of the follicular subtype, rather than thyroid papillary carcinoma. In this report, a 55-year-old woman with skull metastasis from thyroid papillary carcinoma is presented. The metastatic lesion of the skull was hypervascular and osteolytic, and the bleeding was profuse during resection. There have been only four reports of skull metastasis from thyroid papillary carcinoma. The mean period from the initial diagnosis of thyroid carcinoma until the detection of skull metastasis is 23.3 years, whereas in this patient, it was about 2 years. Therefore, in the clinical course of thyroid papillary carcinoma, skull metastasis should be considered, and the patient should be meticulously followed up.     

Familial spontaneous pneumothorax in three generations and its HLA

We experienced a case of familial spontaneous pneumothorax in three generations. Six of 13 family members had episodes of spontaneous pneumothorax. It is well established that there are some diseases associated with human leukocyte antigen (HLA). We performed HLA phenotyping for HLA of A, B and C. In our study, we detected the HLA haplotype A2, B61 in three of 4 who had episodes of spontaneous pneumothorax. The HLA haplotype A2, B70 were also detected in three of 4 who had episodes. This suggests that familial spontaneous pneumothorax might have hereditary factors.     

K-ras activation and ras p21 expression in latent prostatic carcinoma in Japanese men.

Twenty-three clinically silent prostatic carcinomas discovered in Japanese men at autopsy were surveyed for ras proto-oncogene mutations by mutation-specific oligonucleotide probe hybridization after polymerase chain reaction (PCR) amplification from a section of formalin-fixed, paraffin-embedded tissue. Six of the 22 that were satisfactory amplified contained activating point mutations in codon 12 of K-ras, a significantly higher frequency than has been reported in patients with clinically advanced disease in the United States. Of the six cases with activating point mutations in codon 12 of K-ras, one had a GGT----GAT transition, four had GGT----GTT transversions, and one had both GGT----GAT and GGT----GTT mutations. Sections from the same tissues were immunohistochemically stained with an anti-ras p21 antibody. Carcinoma cells stained for ras p21 to some degree in 13 cases. Immunohistochemically detectable expression of p21 was always focal and was not necessarily associated with K-ras mutation. K-ras oncogene activation in prostatic carcinoma appears to merit additional study as a significant event in the pathogenesis of this neoplasm.     

The effect of FK506 on segmental pancreas allograft in mongrel dogs]

FK506 is a potent immunosuppressive agent on experimental and clinical organ transplantation. We studied the the effect of this agent on segmental pancreas allograft in mongrel dogs. Graft survival was prolonged significantly with continuous administration of FK506, 0.3mg/kg/day intramuscular and 1.0mg/kg/day orally. However such symptoms as loss of appetite, nausea and extreme emaciation were observed and caused death. While bolus therapy of FK506 (3 days administration with the dose of 1.0mg/kg i.m. from 4 to 6 day postoperatively) showed the same immunosuppressive effect as continuous therapy and less side effect. Furthermore it was suggested that FK506 plasma levels were concerned with the appearance of side effect. In conclusion, the administration of FK506 with plasma level monitoring was thought to be useful on pancreas transplantation.