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Biomedical subjects

T Kiyama

Publications and source records attributed to T Kiyama.

At least 19 recordsLinked to original sources

A genomic view of the sea urchin nervous system.

The sequencing of the Strongylocentrotus purpuratus genome provides a unique opportunity to investigate the function and evolution of neural genes. The neurobiology of sea urchins is of particular interest because they have a close phylogenetic relationship with chordates, yet a distinctive pentaradiate body plan and unusual neural organization. Orthologues of transcription factors that regulate neurogenesis in other animals have been identified and several are expressed in neurogenic domains before gastrulation indicating that they may operate near the top of a conserved neural gene regulatory network. A family of genes encoding voltage-gated ion channels is present but, surprisingly, genes encoding gap junction proteins (connexins and pannexins) appear to be absent. Genes required for synapse formation and function have been identified and genes for synthesis and transport of neurotransmitters are present. There is a large family of G-protein-coupled receptors, including 874 rhodopsin-type receptors, 28 metabotropic glutamate-like receptors and a remarkably expanded group of 161 secretin receptor-like proteins. Absence of cannabinoid, lysophospholipid and melanocortin receptors indicates that this group may be unique to chordates. There are at least 37 putative G-protein-coupled peptide receptors and precursors for several neuropeptides and peptide hormones have been identified, including SALMFamides, NGFFFamide, a vasotocin-like peptide, glycoprotein hormones and insulin/insulin-like growth factors. Identification of a neurotrophin-like gene and Trk receptor in sea urchin indicates that this neural signaling system is not unique to chordates. Several hundred chemoreceptor genes have been predicted using several approaches, a number similar to that for other animals. Intriguingly, genes encoding homologues of rhodopsin, Pax6 and several other key mammalian retinal transcription factors are expressed in tube feet, suggesting tube feet function as photosensory organs. Analysis of the sea urchin genome presents a unique perspective on the evolutionary history of deuterostome nervous systems and reveals new approaches to investigate the development and neurobiology of sea urchins.

Animals↗

Nitric oxide enhances experimental wound healing in diabetes.

BACKGROUND: Diabetes is characterized by a nitric oxide deficiency at the wound site. This study investigated whether exogenous nitric oxide supplementation with the nitric oxide donor molsidomine (N-ethoxycarbomyl-3-morpholinyl-sidnonimine) could reverse the impaired healing in diabetes. METHODS: Wound healing was studied by creating a dorsal skin incision with subcutaneous polyvinyl alcohol sponge implantation in diabetic and non-diabetic rats. Half of each group was treated with molsidomine. Collagen metabolism was assessed by wound breaking strength, hydroxyproline (OHP) content, RNA expression for collagen type I and III, and matrix metalloproteinase (MMP) 2 activity in wound sponges. Wound fluid, plasma and urinary nitric oxide metabolite levels, and the number of inflammatory cells were assessed. RESULTS: OHP content and wound breaking strength were significantly increased by molsidomine. MMP-2 activity in wound fluid was decreased in diabetes and upregulated by nitric oxide donors. The impaired inflammatory reaction in diabetes was unaffected by nitric oxide donor treatment and ex vivo nitric oxide synthesis was no different between wound macrophages from control and diabetic animals, suggesting that the nitric oxide deficiency in the wound is due to a smaller inflammatory reaction in diabetes. CONCLUSION: The nitric oxide donor molsidomine can at least partially reverse impaired healing associated with diabetes.

Animals↗

Primary adenocarcinoma of the duodenum demonstrated by ultrasonography.

A 57 year-old man presented with abdominal discomfort and melena. Abdominal ultrasonography clearly revealed a duodenal tumor as a hypoechoic mass in the transverse segment of the duodenum. The lesion was a 4 x 4-cm oval mass with partial concavity, an irregular surface, high-level central echoes, and a hypoechoic periphery. After confirmation of the diagnosis of duodenal carcinoma, a pylorus-preserving pancreatoduodenectomy was performed curatively. Pathological examination revealed moderately differentiated tubular adenocarcinoma partially invading the pancreatic parenchyma. Ultrasonography can be used to detect lesions of the transverse segment of the duodenum as the first imaging procedure.

Adenocarcinoma↗

Trauma and wound healing: role of the route of nutritional support.

Following severe trauma and surgical injury, nutritional support via the enteral route has been shown to lead to increased survival and decreased complications when compared to the parenteral route. We hypothesized that the route of nutrient delivery may affect cutaneous wound healing following severe traumatic insult. Forty-six Sprague Dawley rats underwent bilateral closed femoral fractures, central venous catheterization, gastrostomy placement and dorsal skin incision with placement of polyvinyl alcohol sponges into subcutaneous pockets. Identical nutritional infusates of 25% dextrose, 4.25% amino acids, and vitamins were given, half the animals receiving the infusion via the gastrostomy (ENT) and the other half via the venous catheter (TPN). Animals were sacrificed on post-operative days 5, 7, or 10. Wound breaking strength (WBS, g) and sponge granuloma hydroxyproline content (OHP- a measure of wound collagen deposition, microg/ 100mg sponge) were measured. There were no significant nutritional differences between the two feeding groups. On days 5 and 7, WBS was significantly higher in the ENT group (58.0 +/- 3.1 g vs 48.9 +/- 2.6 g, p < 0.05, and 123 +/- 19 g vs 87.6 +/- 4.2 g, p < 0.05 vs TPN respectively). Sponge OHP content on day 5 was significantly higher in the ENT group (101 +/- 3 vs 86.7+/-5.8 microg/100 sponge, p < 0.05). These data demonstrate that the enteral feeding route imparts a benefit to early post-traumatic wound healing s compared to parenteral feeding.

Analysis of Variance↗

Effect of early postoperative feeding on the healing of colonic anastomoses in the presence of intra-abdominal sepsis in rats.

PURPOSE: Intra-abdominal infection is generally considered a major risk factor for dehiscence of primary colon anastomosis. To elucidate the indications for nutritional support during intra-abdominal sepsis, we investigated the healing of anastomoses in an animal model. METHODS: Twenty male Sprague-Dawley rats (280-320 g) underwent cecal ligation and single puncture. After 24 hours the perforated cecum was removed, and the left colon was transected and anastomosed in a single-layer inverted fashion. Animals were randomly assigned to receive both chow and water (early-fed group; n = 10) or water alone for the first 72 hours and chow thereafter (late-fed group; n = 10). Colon-bursting pressure was measured five days after the anastomosis, at which time the anastomosis was excised. RESULTS: The survival rate after cecal ligation and single puncture was 100 percent, and blood cultures were positive in 20 percent of animals five days after surgery. All data are expressed as means +/- standard error of the mean. Body weight increased more in the early-fed group than in the late-fed group (15.6+/-3 vs. -6.3+/-2.8 g; P < 0.001). Early feeding resulted in increased anastomotic bursting pressure (200+/-11 vs. 161+/-12 mmHg; P < 0.05) and total collagen concentration at the site of anastomosis (2.36+/-0.09 vs. 2.01+/-0.07 microg/mg wet tissue; P < 0.01) compared with the late-fed group. CONCLUSION: Early feeding has a positive effect on anastomotic healing in the presence of intraabdominal sepsis. The mechanism by which early feeding enhances the colonic anastomotic healing is unclear, although preservation of colonic collagen seems to play a significant role.

Anastomosis, Surgical↗

CAAT sites are required for the activation of the H. pulcherrimus Ars gene by Otx.

A product of sea urchin homologues of the Drosophila orthodenticle gene, HpOtxL has been implicated as a transcription activator of the aboral ectoderm-specific arylsulfatase (Ars) gene during early development of the sea urchin embryo. Using an in vivo transactivation system, we present evidence that HpOtxL activates the target gene by interacting with co-factors. Otx binding sites alone have little effect on the activity of an Ars promoter, but when both Otx binding sites and CAAT sequences are present in the enhancer region of Ars, the fragment shows a high enhancer activity. A gel mobility shift assay reveals that a nuclear protein binds to the CAAT sequences present near the Otx binding sites in the enhancer region of Ars. The activation domain of HpOtxL resides in the C terminal region between amino acids 218 and 238. The N-terminal region is responsible for the enhancement of transactivation of the Ars promoter, although the region itself does not function as an activation domain. HpOtxE, which possesses an N-terminal region different from HpOtxL, does not activate the Ars promoter even in the presence of CAAT sequences. Together with previous findings, our results suggest that Otx regulates different genes by interacting with different co-factors in sea urchin development.

Animals↗

Eosinophilic lung diseases: diagnostic accuracy of thin-section CT in 111 patients.

PURPOSE: To determine whether various eosinophilic lung diseases can be differentiated by means of thin-section computed tomography (CT). MATERIALS AND METHODS: Thin-section CT scans in 111 patients with eosinophilic lung diseases-40 with chronic eosinophilic pneumonia, 16 with Churg-Strauss syndrome, 16 with allergic bronchopulmonary aspergillosis (ABPA), 13 with acute eosinophilic pneumonia, 12 with simple pulmonary eosinophilia, 11 with drug-induced eosinophilic pneumonia, and three with hypereosinophilic syndrome-were assessed independently by two observers. The observers recorded the abnormalities, diagnosis, and degree of confidence in the diagnosis. RESULTS: The two observers made a correct first-choice diagnosis on average in 61% of readings. The correct diagnosis was made in 78% of cases of chronic eosinophilic pneumonia; 81%, acute eosinophilic pneumonia; 44%, Churg-Strauss syndrome; 84%, ABPA; 17%, simple pulmonary eosinophilia; 27%, drug-induced eosinophilic pneumonia; and 33%, hypereosinophilic syndrome. The two observers made a correct diagnosis with a high degree of confidence in 36% of readings. There was moderate agreement between the observers for the correct diagnosis (kappa, 0.47) and for the correct diagnosis with a high degree of confidence (kappa, 0.59). CONCLUSION: Although eosinophilic lung diseases often can be differentiated by means of thin-section CT, correlation between CT findings and careful clinical evaluation are required for a definitive diagnosis.

Adolescent↗

Spontaneous gastrointestinal perforation in patients with lymphoma receiving chemotherapy and steroids. Report of three cases.

Spontaneous gastrointestinal perforations in three patients with lymphoma were considered to be treatment-related conditions. All three were diagnosed as having malignant lymphoma by histological examination, and treated with chemotherapy and steroids. Four to 14 days after the start of chemotherapy, they complained of abdominal pain and plain roentgenograms revealed pneumoperitoneum. The interval between the onset of peritonitis and operation was almost 24 h. Emergency operations were carried out; one patient with a jejunal perforation underwent resection of the jejunum, another with a gastric perforation received a simple closure with omental patch, and the third with a gastric perforation underwent gastrectomy. Two patients recovered from the surgery, while the gastrectomy patient died due to sepsis. The favorable outcome of the surgical intervention is attributed to early diagnosis, prompt exploration, and selective operative procedures. We recommended a simple closure with omental patch for gastroduodenal perforation. Resection and primary anastomosis are possible only in the small bowel.

Adult↗

[Effects of intravenous and oral administration of ondansetron hydrochloride on chemotherapy-induced nausea and vomiting in patients with esophageal cancer].

The effects of ondansetron hydrochloride (OND) were studied through 11 courses of chemotherapy, including 70 mg/m2 of cisplatin, in 9 patients with advanced esophageal cancer. During the observation period of 5 days, 4 mg of OND was given intravenously on the day of cisplatin infusion and orally for consecutive 4 days, and nausea was controlled by over 70%. Vomiting was controlled by over 80%. The inhibitory effect of OND on nausea and vomiting was found in 72.7% on the day of cisplatin injection and 88.9% overall. No other side effects of OND except slight increases in total bilirubin and LDH were found in any patient. These findings suggest that intravenous and oral administration of OND may inhibit chemotherapy-induced nausea and vomiting in patients with advanced esophageal cancer.

Administration, Oral↗

[Primary Sjögren's syndrome with lymphocytic interstitial pneumonia and pulmonary multiple cystic lesions].

We report a case of primary Sjögren's syndrome with lymphocytic interstitial pneumonia and multiple cystic lesions. The patient was a 64-year-old woman. Abnormal chest shadows were detected by x-ray and computed tomographic (CT) examinations. The patient had no family history of disease and had never smoked. She had complained of dryness in the eyes and mouth for about 10 years. Laboratory tests were positive for anti-nuclear antigen, anti-SS-A antigen, and anti-SS-B antigen. Sialography revealed marked destruction of the salivary glands, yielding a diagnosis of Sjögren's syndrome. Chest X-ray films and CT scans showed multiple cystic lesions in both lungs, measuring from a few mm to 3 cm in diameter, as well as fine centrilobular nodules. Slight anemia and hyper gamma globlinemia were also detected. Pulmonary function tests showed mild obstructive disturbance. Bronchoalveolar lavage analysis disclosed an elevated lymphocytic fraction (28.6%), but transbronchial lung biopsy provided no adequate specimens for diagnosis. Thoracoscopic lung biopsy specimens demonstrated marked infiltration of lymphocytes and histiocytes through the interstitium of alveolar walls and peri-bronchovascular sheath, with some lymphoid follicles. The overall appearance was compatible with lymphocytic interstitial pneumonia. The cysts themselves were nonspecific, and no cellular infiltration was noted in the cyst walls. Because of the predominantly peribronchial distribution of the lesions, we suspected that the cysts were formed by the check valve mechanism. However, no definitive evidence was obtained.

Cysts↗

Structure and function of a sea urchin orthodenticle-related gene (HpOtx).

Two distinct types of orthodenticle-related proteins (HpOtxE/L) have been implicated as transcription activators of the aboral ectoderm-specific arylsulfatase (Ars) gene. Here, we describe the structure of HpOtx gene and present evidence that mRNAs of HpOtxE/L are transcribed from a single HpOtx gene by altering the transcription start site and by alternative splicing. By transactivation experiments, we have also demonstrated that HpOtxL activates the Ars promoter in the gastrula-stage embryo.

Animals↗

[Successful treatment of hepatic metastasis of gastric cancer with 5'-DFUR and Lentinan].

Satisfactory therapeutic effects are rarely obtained with oral chemotherapy for gastric cancer. We have experienced successful treatment for synchronous hepatic metastasis of gastric cancer with 5'-DFUR and Lentinan. The patient was a 78-year-old female, diagnosed as having gastric cancer with multiple hepatic metastases, who underwent gastrectomy. Immunohistochemistry of the resected specimens with anti-thymidine phosphorylase (dThdPase) antibody yielded positive results for dThdPase in the primary tumor as well as the hepatic metastases. Two months after surgery, administration of 400 mg of 5'-DFUR per day and 2 mg i.v. of Lentinan every other week was started. Four months after discharge, carcinoembryonic antigen (CEA) in plasma showed an abrupt logarithmic decline. Furthermore, a 99% reduction in hepatic metastases was demonstrated by abdominal CT. At present, 22 months after surgery, the patient is managed on an outpatient basis with no complaints of any side effects. Immunochemotherapy using 5'-DFUR and Lentinan may be effective against gastric malignancies expressing dThdPase activity.

Adenocarcinoma↗

[Evaluation of peritoneal lavage smears and intraperitoneal administration of anti-neoplastic agents in stage III and IV gastric cancer].

Examinations of peritoneal lavage smears (cy) in gastric cancer surgical stages III and IV are very important for determining the disease stage. We have been carrying out these examinations for 8 years. One hundred sixty patients with gastric cancer were examined. The incidence of cy positivity was higher in T4 than in T3, and higher in P1,2,3 than in P0. We performed intraperitoneal administration of CDDP in 10 patients with gastric cancer using a reservoir (Infuse-A-Port) implanted in the abdominal wall once a week. No difference in survival was observed between patients who received chemotherapy via i.p. and those who received it i.v.

Adenocarcinoma↗

Metalloproteinase inhibitors and wound healing: a novel enhancer of wound strength.

BACKGROUND: Wound strength is a balance between collagen synthesis and degradation. The role of collagen breakdown in wound healing is still not well understood. We investigated the role of collagenases (metalloproteinases [MMPs]) in wound healing in using GM6001, a novel inhibitor of MMPs. METHODS: We used the dorsal skin incision model with implantation of polyvinyl alcohol sponges. Twenty male Sprague-Dawley rats were randomly assigned to receive either GM6001 (10 mg/kg body weight) or 2 mL saline subcutaneously. Ten days after operation the animals were killed and fresh wound breaking strength, scar and sponge hydroxyproline content, and collagen type I gene expression in sponges were assayed. In addition, the inflammatory response and the wound fluid cytokine (tumor necrosis factor-alpha [TNF-alpha] and transforming growth factor-beta 1 [TGF-beta 1]) profile were studied. RESULTS: GM6001 significantly increased wound strength (422 +/- 59 vs 302 +/- 33 g, P < .05), whereas scar collagen content did not differ. In the sponge granulomas the inflammatory infiltrate, the collagen content, and the collagen type I gene expression were all significantly decreased by GM6001. CONCLUSIONS: Inhibition of MMP activity during acute wound healing enhances wound strength even though new collagen synthesis and the inflammatory response are significantly decreased. This could be achieved by decreasing collagen turnover or increasing collagen maturation and crosslinking, or both.

Animals↗

[Role of peritoneal lavage smears and gastric wall brushing smears in gastric cancer surgery].

Examinations of peritoneal lavage smears (LC) and gastric wall brushing smear cytology (BC) appear to be important for determining accurately the stage of gastric cancer. We have been carrying out such examinations during gastric cancer surgery for 7 years. In the present study, we evaluated the results obtained from 287 patients with gastric cancer. Tumor invasion and peritoneal dissemination were correlated with a positive incidence of cancer cells in LC and/or BC. Gastric cancer showing serosal invasion was classified into positive for LC and/or BC and negative for LC and/or BC. Patients positive for LC and/or BC had a poorer prognosis. For future gastric cancer treatment, patients positive for peritoneal cytology are expected to be targeted for intensive treatment during or before surgery.

Adenocarcinoma↗