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Biomedical subjects

K Hioki

Publications and source records attributed to K Hioki.

At least 91 records · Page 5Linked to original sources

Cytokine gene expression in the foot pad and spleen of BALB/cAJcl mice infected with M. leprae.

The cytokine mRNAs expressed in the foot pads and spleens of BALB/cAJcl mice infected with Mycobacterium leprae were studied by the reverse transcriptase-polymerase chain reaction (RT-PCR) method using cytokine-specific primers for interleukin-1 alpha (IL-1 alpha), -2, -4, -6, -10, -12-(p40), gamma interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and TNF-beta, and then for CD4 and CD8 markers. The pattern of cytokine gene expression in the foot pad which supports M. leprae growth was different from the expression in the spleen which does not permit M. leprae multiplication in mice. Before BALB/cAjcl mice were infected with M. leprae, IL-1 alpha and TNF-beta mRNAs were expressed physiologically in the foot pad while all of the cytokine genes examined were expressed in the spleen. In the foot pads of mice inoculated with M. leprae, in addition to the physiological appearance of IL-1 alpha and TNF-beta mRNAs, these signals were intensified. TNF-alpha expression was induced by the infection. On the other hand, in the spleens of mice inoculated with M. leprae, CD4 mRNA expression disappeared on day 1 of the infection, which was accompanied by the reduced expression of IL-2, -4, -6, and -12 mRNAs. The recovery of CD4 mRNA expression at a latter stage was accompanied by a corresponding increase of the cytokine mRNA expression. It was suspected that these results might permit restricted growth of M. leprae in the foot pads of normal mice. Furthermore, our study suggests that tissue-specific, local, immunologic characteristics are important in M. leprae growth.

Animals↗

[Jejunal pouch and interposition reconstruction after a total gastrectomy for cancer].

The authors modified the operative procedures used in pouch and interposition (PI) reconstruction in an attempt to improve the surgical results after a total gastrectomy, because a randomized controlled trial had revealed that the clinical assessment of PI was quite poor, even though it is a physiological route. In most of the treated patients, the gastric emptying test revealed delayed emptying, and an X-ray video film showed folding and twisting of the jejunal conduit between the pouch and duodenum, which disturbed the transmission of the nutrition. Modified PI (m-PI) was performed by decreasing the length of the jejunal conduit and widening the jejunal pedicle to preserve the blood and nerve supply. The m-PI group showed a lower incidence of symptoms, a greater food intake, and a greater weight recovery than the PI group. The gastric emptying test also revealed an acceptable degree of emptying. We conclude that the m-PI reconstruction is more useful for improving the postoperative quality of life than the previously used method of PI reconstruction.

Anastomosis, Surgical↗

Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.

The present study demonstrated that a short-term administration of mAbs against leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) at critical periods resulted in complete protection of autoimmune diabetes in non-obese diabetic (NOD) mice. When these mAbs were administered for only 6 days at 2 wk of age, neither diabetes nor insulitis was observed at 30 wk of age. It appears that the tolerance against beta cell Ag(s) was induced by this transient blockade of the LFA-1/ICAM-1 pathway. Protective suppressor activity was not enough to prevent diabetes because co-transfer of splenocytes from female NOD mice, which had received these mAbs at 2 wk of age, resulted in only a short delay of the diabetic onset caused by adoptive transfer of splenocytes from acutely diabetic NOD mice. Transfer of these splenocytes to young NOD mice could not also abrogate the spontaneous diabetes and insulitis. Furthermore, cyclophosphamide treatment could not abrogate the protection. When splenocytes from the treated NOD mice were transferred to NOD-SCID mice, none of the recipient mice developed significant insulitis and subsequent overt diabetes, suggesting the absence or the inactivation of diabetogenic effector T cells. However, splenic T cells from the insulitis-free NOD mice that had received the mAb treatment preserved proliferative responses to both islet cells and 65-kDa glutamic acid decarboxylase (GAD65) in vitro. These results suggest that a unique peripheral tolerance was induced by the transient blockade of the LFA-1/ICAM-1 pathway in an early age of NOD mice.

Adoptive Transfer↗

Inhibitory Effect of the Angiogenesis Inhibitor O-(Chloroacetyl-carbamoyl)fumagillol(TNP-470) on Tumor Growth and Metastasis of Murine Mammary Tumor Cell Line (JYG-B)Inoculated in Female Nude Mice.

The effect of the potent angiogenesis inhibitor O-(chloroacetyl-carbamoyl) fumagillol(TNP-470), a semisynthetic analogue of fumagillin on tumor growth and metastasis was studied using murine mammary tumor cells (JYG-B) inoculated into female nude mice. Injection of TNP-470 at 10 and 30 mg/kg doses, 3 times a week, until the end of the experiment (41 days)inhibited the s.c.inoculated primary tumor growth in a dose-dependent manner (45%and 65% in volume, respectively). TNP-470 at 30 and 60 mg/kg doses, 3 times a week, until the end of the experiment (35 days), reduced the weight of the i.p. inoculated total tumor mass of abdominal dissemination in a dose-dependent manner (54% and 76%, respectively). Pulmonary metastasis was found in all mice but TNP-470 significantly reduced the lung weight reflecting the total volume of the metastatic foci, and the numbers of metastatic foci in the liver and kidneys was reduced by TNP-470 treatment. These findings show that the angiogenesis inhibitor (TNP-470)has a strong inhibitory effect on tumor grwoth and metastasis in vivo.

Journal Article↗

Angiosarcoma of the Breast: Immunohistochemical Demonstration of Steroid Receptors and Literature Review.

A 44-year-old female with bilateral angiosarcoma of the breast with multiple skin metastases is reported. She presented with a 6x8 cm and 1x1 cm mass in her left and right breasts, respectively, and multiple skin lesions around the chest. Histologically, the excised tumor was diagnosed as angiosarcoma of the breast with skin metastasis. Tumor cells were immunohistochemically positive with factor VIII-related antigen, CD34, alpha-smooth muscle actin and vimentin, and positive with UEA-I lectin. The majority of tumor cell nuclei expressed progesterone receptor (PgR) protein but estrogen receptro (ER) protein and androgen receptor (AR) protein were nagative. According to the literature, angiosarcoma of the breast mostly affects females in their fourth (33%) and fifth (40%) decades (mean age, 39.5 +/- 10.7 years). The survival rate depends on tumor size and tumor differentiation. The 3-year survival rate is 86% in patients with a tumor size less than 5 cm, and 90% in well-differentiated group I lesions.

Journal Article↗

A poliovirus-susceptible transgenic mouse model as a possible replacement for the monkey neurovirulence test of oral poliovirus vaccine.

Two poliovirus-susceptible transgenic mouse (Tg PVR) strains, Tg1 and Tg21, were compared with the monkey test for their sensitivity to neurovirulence of live oral poliovirus vaccine (OPV). Intracerebral (i.c.) and intraspinal (i.s.) routes of inoculation were investigated to determine the most suitable combination of mouse strain and route. Evaluation of the mouse tests was performed using several indicators; clinical score and failure time were selected as the most efficient. Tg1 and Tg21 mice inoculated i.s. with type 2, and Tg21 mice inoculated i.s. with type 3 OPV were determined to be the most appropriate systems, whereas they are shown not to be suitable for type 1 OPV. The sensitivity of each of the two mouse models was at least equal to that of the monkey test, suggesting that these mouse systems might be considered as a potential replacement for the monkey test of OPV. However, more data are needed to establish regulatory criteria of acceptability for vaccine lots tested in Tg PVR mice. This is the first study conducted with Tg PVR mice with all three types of poliovirus vaccine preparations.

Animals↗

Anorectal stenosis in a neonate: report of a case and review of the Japanese literature.

We report herein the case of an infant with anorectal stenosis successfully treated by staged surgery. At 1 day of age, the anal orifice showed circumferential stenosis located 5 mm from the anal verge and extending into the anal canal for approximately 1 cm; however, no hypertrophic raphe or bucket handle appearance were observed, and no associated anomalies such as a presacral mass or sacral dysgenesis were found. At 2 days of age, the infant underwent a sigmoid colostomy under the diagnosis of low anorectal stenosis, followed by a successful anorectoplasty, performed through a sacroperineal approach when he was 8 months old. An analysis of 13 other cases of anorectal stenosis from the Japanese literature indicates that this type of malformation should be treated by staged surgery, as an initial colostomy in the neonatal period, followed by anorectoplasty through a sacroperineal approach during infancy.

Anus Diseases↗

Rapid induction of more malignant tumors by various genotoxic carcinogens in transgenic mice harboring a human prototype c-Ha-ras gene than in control non-transgenic mice.

In this study, we investigated the carcinogenic response of transgenic mice carrying the human prototype c-Ha-ras gene, namely Tg rasH2/CB6F1 mice, to various genotoxic carcinogens and compared it with that of control non-transgenic CB6F1 mice (non-Tg mice). The present studies were conducted as the first step in the evaluation of the Tg rasH2/CB6F1 mouse as a model for the rapid carcinogenicity testing system. Short-term (< or = 6 months) rapid carcinogenicity tests of various genotoxic carcinogens, 4-nitroquinoline-1-oxide, cyclophosphamide, N,N-diethylnitrosamine, N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine and methylazoxymethanol, revealed that Tg rasH2/CB6F1 mice are more susceptible to these genotoxic carcinogens than control non-Tg mice. Tg rasH2/CB6F1 mice developed tumors more rapidly compared with non-Tg mice. Malignant tumors were observed only in the carcinogen-treated Tg rasH2/CB6F1 mice, but not in non-Tg mice treated with the same carcinogens. Each carcinogen induced tumors in corresponding target tissues of the Tg rasH2/CB6F1 mice. Only a very few lung adenomas but no other tumors were seen as spontaneous tumors during the 6 months of carcinogenicity tests. These results demonstrate that more rapid onset and higher incidence of more malignant tumors can be expected with high probability after treatment with various genotoxic carcinogens in the Tg rasH2/CB6F1 mice than in control non-Tg mice. The Tg rasH2/CB6F1 mouse seems to be a promising candidate as an animal model for the development of a rapid carcinogenicity testing system.

4-Nitroquinoline-1-oxide↗

[Comparative study of the combined effect of HCFU and dipyridamole (DP) in colorectal carcinoma--TS inhibition rate. Kinki Cooperative Study Group of Chemotherapy for Colorectal Carcinoma].

In the forty-seven medical centers in the Kinki district, a comparative trial was conducted to investigate the enhancement of the efficacy of HCEU due to dipyridamol (DP), which is a biochemical modulator in patients with colorectal cancer who have had a curative resection. The trial consisted of two comparative groups: one group (Group A) received HCFU only for five days before operation and for two years from the second week, and the other group (Group B) was given HCFU + DP for the same trial period as Group A. The total number of patients collected was 653 (Group A: 327 patients; Group B: 326 patients) during the two-year trial period from October, 1991. Thymidylate Synthetase (TS) activity in the primary lesions, which is an index of proximity effect, was measured, and the TS inhibition rate (TSIR) was calculated from the activities. The results showed that the TSIR in the primary lesions for the HCFU + DP group (Group B: 0.33) was significantly higher than that of the HCFU group (Group A: 0.27) (p = 0.0006). There was no increase in the side effects of HCFU due to combined administration with DP. From the above results, the therapy with HCFU + DP is expected to be useful for patients with colorectal cancer who have undergone curative resection.

Adult↗

Site of action of galanin in the cholinergic transmission of guinea pig small intestine.

The mode and site of action of galanin were examined in the guinea pig small intestine. Galanin (3 x 10(-9)-10(-7) M) inhibited the twitch contractions of longitudinally and circularly oriented muscle strips mediated by the stimulation of cholinergic neurons, but not the contractions mediated by direct stimulation of smooth muscle cells with carbachol. Galanin (3 x 10(-9)-10(-7) M) inhibited both the electrically stimulated and the tetrodotoxin-resistant high K+ (40 mM)-induced increase of [3H]acetylcholine outflow from the ileal strips preloaded with [3H]choline, in a concentration dependent fashion. The inhibitory effect of galanin was antagonized by galantide and produced self-desensitization. The spontaneous and stimulated outflow of [3H]noradrenaline and [3H]gamma-aminobutyric acid were not affected by galanin even at 10(-7) M. Thus, galanin inhibits the motility of guinea pig ileum by inhibition of acetylcholine release from the enteric cholinergic neurons. Galanin may act on the specific receptor located on soma-dendritic regions and nerve terminals of cholinergic neurons.

Acetylcholine↗

Immunohistochemically demonstrated expression of HLA-DR antigen in colorectal adenocarcinomas and its relation to clinicopathological features.

We studied 148 colorectal adenocarcinomas to clarify any correlation between HLA-DR antigen expression on tumor cells and histopathological features. Paraffin sections of formalin-fixed tissues were stained with HLA-DR antigen using the indirect immunoperoxidase technique. All the tumor tissues were divided into two groups, depending on the incidence of HLA-DR-positive cells (greater and lesser than 50%). Carcinoma tissues with a higher incidence showed less mural invasion, lymphoductal invasion, venous invasion, lymphonodular metastasis, and peritoneal metastasis. Tissues with a high HLA-DR reactivity were more often observed for Dukes' A and B stages, whereas those with a low HLA-DR positivity were frequently Dukes' C and D stages. As for the cumulative survival rate, the group with high HLA-DR expression demonstrated significantly better survival. We speculate that HLA-DR expression by colorectal cancer cells exerts a favorable influence on clinical course.

Adenocarcinoma↗

Surgical technique of laparoscopic pyloromyotomy for infantile hypertrophic pyloric stenosis.

We report herein a new method of performing laparoscopic pyloromyotomy for infantile hypertrophic pyloric stenosis, using refined surgical techniques. The pyloric tumor was immobilized by grasping the first portion of the duodenum and the anterior wall of the stomach, and electrocoagulation was used prior to incising the pyloric tumor to minimize bleeding during the procedure. Although this technique has been applied in only two patients so far, we present the details herein. We believe that with technical and instrumental refinements, the speed and safety of laparoscopic pyloromyotomy will improve and it will become an alternative to open surgery in pediatric patients.

Female↗

Spiral computed tomography for biliary dilatation.

Spiral computed tomography (SCT), which consists of rapid volumetric data acquisition and planar image display, was performed on 12 patients with biliary dilatation after excisional procedure. The technique was evaluated for image quality and impact on clinical practice. All patients safely underwent SCT scanning after intravenous cholangiography (IVC) without any sedations. In 11 of 12 patients reliable biliary images were obtained and three-dimensional (3D) reconstruction images of the biliary system with bilioenteric anastomosis were generally of diagnostic quality even in young children. As a consequence, IVC-SCT technique appears to have the potential for improving the efficacy and safety of diagnostic CT in investigation of the biliary system. In particular, this technique may be useful for detecting bilioenteric anastomotic conditions in follow-up studies of pediatric patients with biliary dilatation.

Adolescent↗

Jejunal pouch reconstruction after total gastrectomy for cancer. A randomized controlled trial.

OBJECTIVE: The authors determined the optimum reconstruction procedure after total gastrectomy in terms of the quality of life of the patients. SUMMARY BACKGROUND DATA: Gastric replacement with various enteric reservoirs has been used to improve the postprandial symptoms and nutrition of patients after total gastrectomy. However, the effect of each is uncertain because no prospective randomized studies have been conducted. METHODS: A randomized controlled trial was conducted to compare the usefulness of the three reconstruction procedures of simple Roux-en-Y (RY; N = 10), pouch and Roux-en-Y (PR; N = 10), and pouch and interposition (PI; N = 10). In each subject, the postprandial symptoms, food intake in a single meal, body weight, serum nutritional parameters, and emptying time of the gastric substitute were evaluated. RESULTS: The PR group showed significantly greater food intake in a single meal than the RY and PI groups, and greater weight recovery than the PI group. A gastric emptying test also revealed satisfactory retention capacity and emptying time of the gastric substitute in the PR group. CONCLUSIONS: Pouch and Roux-en-Y reconstruction is the most useful of the three procedures for improving the postoperative quality of life. In patients with pouch and interposition reconstruction, the clinical assessment was quite poor, even though it is a physiologic route.

Adult↗

Sedative effect of medetomidine and its reversal by atipamezole in house musk shrews (Suncus murinus).

This study was undertaken to evaluate the sedative effect of medetomidine, an alpha 2-adrenoceptor agonist, and the counteractive effect of atipamezole, an antagonist to medetomidine, in house musk shrews (Suncus murinus). Two hundred, 300, 400, or 600 micrograms/kg of medetomidine was intraperitoneal injected into 89 house musk shrews. A sedative effect was produced in one to two minutes after injection. The dose-dependent prolongation of the sedative duration and the dose-dependent appearance of a hypothermic effect were demonstrated. With 200 micrograms/kg of medetomidine, the sedative effect obtained was not adequate in some of the animals. With 300 micrograms/kg and above, a stable sedative state was induced in all the animals. The duration of sedation in the house musk shrews was much longer (p < 0.01) in males than in females. This suggested the higher susceptibility of male house musk shrews to this drug. The sedative effect and hypothermia obtained with 400 micrograms/kg of medetomidine were completely counteracted by more than 2.0 mg/kg of atipamezole. With 0.5 and 1.0 mg/kg of atipamezole, only a partial antagonistic action was produced. Transient vomiting appeared in 4.5% of the house musk shrews at approximately one minute after injection of medetomidine. This side-effect had occurred before the sedative effect was obtained, and was not serious enough to be a problem. None of the 89 house musk shrews died in this experiment. The above results show that the combination of medetomidine and atipamezole is a highly effective and safe anesthetic treatment which permits easy handling of house musk shrews.

Adrenergic alpha-Antagonists↗