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Biomedical subjects

S Takao

Publications and source records attributed to S Takao.

At least 109 records · Page 6Linked to original sources

[A family of autosomal dominant facio-limb-girdle muscular dystrophy].

A family of autosomal dominant facio-limb-girdle muscular dystrophy was reported. The proband was a 28-year-old male. His father and sister suffered from a similar disease. All patients developed weakness of lower limbs and atrophy of thigh at second to fourth decades. All showed mild facial and neck flexor weakness as well as proximal dominant weakness and atrophy of four limbs. Limb muscle involvement was more severe in lower limbs than in upper limbs in all cases. Interestingly, all showed limitation of ankle dorsiflexion (tight heel cord), although distal muscles of lower limbs were not involved or only mildly involved clinically. On laboratory examination, serum CK increased slightly. Needle EMG revealed low amplitude, polyphasic MUP in limb muscles in all cases. Biopsied muscles taken from the proband showed non-specific myogenic changes. Rimmed vacuoles were not observed. Our cases were different from Bethlem myopathy, because the age of onset was late and joint contractures were mild in our cases, as compared with Bethlem myopathy. Clinical manifestations of our family showed a strong resemblance to the family reported by Girchlist et al, but similar cases were not reported in Japan.

Adult↗

Evidence that portal vein decompression improves survival of canine quarter orthotopic liver transplantation.

The minimum graft volume still remains unclear in reduced-size liver transplantation (RLT). This study reports the improved survival of canine RLT using a quarter graft with the aid of a portahepatic vein shunt (PHVS). In beagles, the donor liver was reduced to the right lateral and caudate lobes (quarter graft) with or without provision of PHVS, and transplanted orthotopically in the recipient. The PHVS was established by an end-to-end anastomosis of the portal vein branch and the hepatic vein in the resected left lateral lobe. Liver chemistries including arterial blood ketone body ratio (AKBR) were serially measured during and after surgery. All seven animals with PHVS survived more than 3 days (mean +/- SD; 5.3 +/- 1.7 days), whereas all six without PHVS died within 3 days (1.8 +/- 0.8 days, P < 0.01). Portal vein pressures immediately after recirculation in animals with and without PHVS were 8.5 +/- 1.2 mmHg and 16.9 +/- 3.1 mmHg, respectively (P < 0.01). Regardless of the presence or absence of PHVS, AKBR dropped to a level lower than 0.7 during the anhepatic period and returned promptly to above 1.0 as early as 30 min after recirculation. Thereafter, the AKBR values in animals with PHVS remained higher than 1.0, whereas those in animals without PHVS showed a progressive decrease, showing a statistically significant difference between the two groups after 12 hr (P < 0.05). Graft function, as assessed by AKBR, was well correlated with survival and other liver chemistries. These results indicate that, in an extreme RLT, portal hypertension is a risk factor predisposing to graft failure, most likely by increasing microvascular injury after recirculation.

Animals↗

Flow cytometric analysis of DNA heterogeneity in superficial carcinoma of the esophagus.

BACKGROUND: There are few studies of flow cytometric analysis for DNA heterogeneity of patients with superficial carcinoma of the esophagus limited to the epithelium or superficially invading the lamina propria or submucosa. METHODS: Flow cytometric analysis of cellular DNA content was performed on superficial carcinomas of the esophagus using paraffin embedded blocks of the surgically resected specimens from 56 patients. To evaluate the intratumoral DNA heterogeneity, a total of 141 samples of the 56 tumors were analyzed, depending upon the tumor size. RESULTS: One or two of the samples was available from 18 of 19 patients with tumors 2 cm or less in greatest dimension, whereas more than three of the samples were available from 22 of 37 patients with tumors 2.1 cm or greater in dimension (P < 0.003). Of 56 tumors, 40 (71.4%) exhibited DNA aneuploidy; DNA heterogeneity was found in 26 tumors (46.4%). The remaining 16 tumors exhibited DNA diploidy. Two of the five tumors that were limited to the epithelium had DNA heterogeneity. The mean dimension of the tumors with DNA heterogeneity was significantly greater (5.8 +/- 2.8 cm) than those exhibiting DNA diploidy (2.3 +/- 1.1 cm) and DNA aneuploidy without heterogeneity (2.9 +/- 2.4 cm). Recurrences after esophagectomy were detected in 6 of the 56 patients; the DNA ploidy pattern of these six patients exhibited DNA heterogeneity. CONCLUSION: The incidence of DNA heterogeneity increases as tumor size increases and is associated with an increased risk of tumor recurrence after esophagectomy in patients with superficial carcinoma of the esophagus.

Adult↗

Chemical stimulation of the nucleus tractus solitarii decreases spinal cord blood flow in anesthetized rats.

L-Glutamate was microinjected into the nucleus tractus solitarii (NTS) in anesthetized (chloralose and urethane), paralyzed and artificially ventilated rats, and spinal cord blood flow (SCBF) was determined using a combination of labeled microspheres. Unilateral chemical stimulation of the NTS (n = 13) significantly decreased SCBF in the cervical cord from 43 +/- 6 (mean +/- SEM) to 28 +/- 4 (P < 0.05), in the thoracic cord from 35 +/- 3 to 24 +/- 4 (P < 0.01), and in the lumbar cord from 49 +/- 3 to 40 +/- 3 ml min-1 (100 g)-1 (P < 0.05). The decrease in SCBF was not due to the decrease in arterial blood pressure (ABP) because the SCBF during the chemical stimulation of the NTS was significantly smaller (P < 0.05) than the SCBF during controlled hemorrhagic hypotension (n = 11). Chemical stimulation of the NTS did not affect the reactivity of the spinal cord vessels to hypercapnia (n = 5). Microinjection of the vehicle solution into the NTS had no effects on spinal cord circulation (n = 9). These results suggest that the cell bodies within the NTS may play a role in the control of spinal cord circulation.

Animals↗

Lymph node metastasis of early stage carcinoma of the esophagus and of the stomach.

We undertook a comparative histologic study of early stage carcinoma of the esophagus and stomach, with tumor invasion limited to the submucosa. Here we analyze lymph node metastasis, lymphatic invasion, and vascular invasion. Our study is based on a retrospective review of 77 patients with early stage carcinoma of the esophagus and 192 patients with early stage carcinoma of the stomach treated during the period from 1973 through 1991. The incidence of lymph node metastasis and lymphatic invasion was significantly higher in intramucosal or submucosal esophageal cancer than in intramucosal or submucosal gastric cancer. However, there was no significant difference between intramucosal esophageal cancer and submucosal gastric cancer. The metastatic site of lymph nodes in esophageal cancer tended to be distant from the location of primary tumor compared with lymph nodes invaded by gastric cancer. Lymphatic invasion and vessel invasion between submucosal esophageal cancer and submucosal gastric cancer was statistically significant. From these results, we conclude that intraepithelial or intramucosal esophageal cancer is comparable to early stage carcinoma of the stomach, whereas submucosal esophageal cancer is actually an advanced lesion.

Adenocarcinoma↗

Increased midkine gene expression in human gastrointestinal cancers.

Midkine (MK) is a product of a retinoic acid-responsive gene, and is a novel growth differentiation factor. We examined the expression of the MK gene in specimens of 47 surgically removed human carcinomas of the gastrointestinal organs, namely, gastric, colorectal, hepatocellular, pancreatic, esophageal, ampullary duodenal and bile duct carcinomas. In most cases, the MK mRNA level was higher in cancer specimens than in the corresponding non-cancerous tissues. Furthermore, MK mRNA was more highly expressed in the colon adenocarcinoma lesion than in the adenoma lesions, in the two familial polyposis cases. While MK mRNA was not detected in the normal liver, it became detectable in cirrhotic tissues in 2 of 4 cases, and its expression was increased in the cancerous tissues. Thus, the increase of MK mRNA level is a phenomenon seen in many human gastrointestinal carcinomas. The increased expression of the MK gene in gastric carcinoma was significantly more prominent in well and moderately differentiated adenocarcinomas than in poorly differentiated adenocarcinomas and signet ring cell carcinomas.

Adult↗

[Molecular biological mechanism of cancer metastasis and the prediction of metastasis in clinical cases].

An outline of the mechanism of cancer metastasis is presented from a molecular biological point of view, and the present state and future possibility of prediction about cancer metastasis in clinical cases is described. Cancer metastasis is developed through multiple steps. With the progress of studies on the mechanism of metastasis, the effort to predict cancer metastasis in clinical cases has progressed. Metastasis is formed in concern with many factors, so it may be highly difficult to explain clinical metastasis by a single factor. It will be important to comprehensively put many factors into consideration. For the preoperative diagnosis of the potential of metastasis, examination of specimens from endoscopic biopsy or blood serum will become more important.

Cell Adhesion Molecules↗

A modified invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay for quantitating tumor cell invasion.

Reconstituted basement membrane matrix (Matrigel) has been utilized for in vitro assay of tumor cell invasion in recent years. In the conventional chamber for the invasion assay, however, a large number of cells passed easily through the center of the Matrigel-coated filter because the Matrigel layer could not be completely uniform by the meniscus formation. To prevent the meniscus phenomenon of the Matrigel layer, we devised a water-repellent treatment of the inside wall of the assay chamber with paraffin. Consequently, very few erythrocytes passed through the Matrigel-coated filter of this modified chamber with the erythrocyte assay, which was used to demonstrate the evenness and uniformity of the Matrigel layer on the filter. For quantitating a small number of cells which invaded through the Matrigel-coated filter by the invasion assay, a tetrazolium-based colorimetric 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) assay was used. The invasive abilities of the eight different cells were determined by this invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium+ ++ bromide assay using the modified chamber with a filter coated with 70 microliters of the 0.2-mg/ml Matrigel. After 72 h of incubation, the malignant cell lines significantly exceeded the normal cell lines in the percentage of invasion (P < 0.01). Therefore, the modified invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium+ ++ bromide assay provides a simple, easily reproducible in vitro assay for quantitating tumor cell invasion.

Animals↗

Caudal ventrolateral medullary depressor area controls cerebral circulation via rostral ventrolateral medullary pressor area.

The cerebral blood flow (CBF) was determined by radiolabeled microsphere technique in urethane (1.1-1.5 g.kg-1, i.p.) anesthetized Wistar rats. Microinjection of L-glutamate (1.7 nmol) into the ventrolateral medullary depressor area (VLDA) produced a significant (P < 0.01) decrease in CBF from 64 +/- 9 (mean +/- S.E.M.) to 48 +/- 9 ml.min-1.(100g)-1 and a significant (P < 0.01) increase in cerebrovascular resistance (CVR) from 1.7 +/- 0.2 to 2.4 +/- 0.4 mmHg per [ml.min-1.(100g)-1] in the cerebral cortex ipsilateral to the stimulated VLDA side but not in other structures such as brain stem and cerebellum (n = 9). Cervical sympathectomy blocked the decrease in CBF and increase in CVR elicited by chemical stimulation of the VLDA (n = 10). Depression of the ventrolateral medullary pressor area (VLPA) neurons induced by microinjection of muscimol into the VLPA blocked the CBF decrease and CVR increase following chemical stimulation of the VLDA (n = 11). Microinjection of the vehicle solution into the VLDA had no effects on systemic and cerebral circulation (n = 7). These results suggest that a vasoconstrictor pathway to control cerebral vessels involves an excitatory projection from the VLDA to the VLPA and the changes in cerebral circulation are mediated by the cervical sympathetic nerves.

Animals↗

Occult lymph node metastasis in gastric cancer with submucosal invasion.

To evaluate more precisely the incidence of lymph node metastasis in patients with submucosally invaded (sm) gastric cancer, three additional sections were made from the remaining half of 1,794 lymph nodes taken from 57 patients, for a detailed reexamination. Lymph node metastasis was demonstrated in 19 nodes from 11 patients by the initial routine examination; however, the detailed reexamination showed cancer involvement in a further nine lymph nodes from eight patients. Of these eight patients, metastasis had not been detected in any lymph nodes by routine examination in six. Macroscopically, the lesion was of the depressed or mixed type in six of the eight patients. From the intranodal location and growth pattern of the cancer foci, lymph nodes with occult metastasis were divided into the marginal sinus type, the medullary sinus type, and the mixed type, with the marginal type being found most frequently. The overall incidence of lymph node metastasis in patients with sm gastric cancer was as high as 29.8% (17/57) in this series. Moreover, a follow-up study revealed that two patients with occult metastasis died of cancer recurrence postoperatively. Accordingly, systematic regional lymph node dissection should be carried out at the time of surgery for sm gastric cancer.

Adenocarcinoma↗

Direct hemoperfusion under infrahepatic inferior vena caval isolation for the intraarterial chemotherapy of pelvic tumors.

A new simple technique consisting of direct hemoperfusion under infrahepatic inferior vena caval isolation for intraarterial chemotherapy of pelvic tumors is herein described. The inferior vena cava is occluded at the infrahepatic level by means of balloon inflation using a balloon-tipped catheter (16F), which is placed through the right greater saphenous vein. The isolated infrahepatic vena caval blood is withdrawn by a centrifugal pump through a catheter (16F) in the contralateral greater saphenous vein and is filtered by direct hemoperfusion during intraarterial infusion of anticancer drugs. Venous reentry is provided by the central lumen of the balloon-tipped catheter. This procedure was used sequentially on two different occasions to treat a patient with an extensive pelvic tumor. Good hemodynamic stability and a reduction of the systemic drug toxicities were confirmed in both trials. Therefore, we believe that this technique is technically feasible and highly effective in reducing systemic toxicities during high-dose intraarterial chemotherapy for pelvic tumors.

Aged↗

A new family of heparin-binding growth/differentiation factors: increased midkine expression in Wilms' tumor and other human carcinomas.

Midkine (MK) and heparin-binding growth-associated molecule/pleiotrophin form a new family of heparin-binding growth/differentiation factors. We studied MK gene expression in human tumors. In normal human reference tissues, MK was highly expressed in the mucosal tissue of the small intestine, moderately in the thyroid, weakly in the tissues of the lung, colon, stomach, kidney, and spleen, and not at all in the liver. All of 6 surgically removed specimens of Wilms' tumor highly expressed MK. Also, a moderate to intense level of MK expression was noted in the majority of surgically removed hepatocellular carcinomas. The MK mRNA level was analyzed in a number of cultured and nude mice-transplanted lines of human tumors. In stomach, colon, pancreatic, lung, and esophageal carcinomas, a moderate to high level of MK expression was found in the majority of them. These results suggest an important role of MK in the development and/or biological behavior of tumors and raised a possibility to use MK as a diagnostic marker. Heparin-binding growth associated molecule/pleiotrophin mRNA was low or scarcely detectable in samples analyzed thus far except for significant levels of the expression that were observed in PA-1 teratocarcinoma cells and in some surgical specimens of Wilms' tumor.

Base Sequence↗

Deregulated c-fos modulates B cell responses to switch mediators.

We examined effects of deregulated c-fos on the proliferation and differentiation of B cells in vitro, using splenic B cells from H2-c-fos transgenic mice. When these cells were cultured with lipopolysaccharide (LPS) plus recombinant interleukin 4 (rIL-4) (10(4) U/ml), the proliferative response of the B cells was augmented with any dose of LPS used. This augmented proliferation resulted in an increase in IgG1 production in the culture, at the lower concentrations of LPS (< 2.5 micrograms/ml). However, H2-c-fos B cells did not produce IgG1 in the culture at higher concentrations of LPS (> 5 micrograms/ml) probably due to the perturbation of B cell differentiation to antibody-forming cells. These results suggest that the deregulated expression of c-fos modulates the proliferation and differentiation of B cells stimulated with LPS plus rIL-4.

Animals↗

Novel DNA polymorphism in the mouse tumor necrosis factor receptors type 1 and type 2.

The introduction of the polymerase chain reaction (PCR) provides an entirely new means of analyzing DNA polymorphism and makes practical the analysis of length variation in simple-sequence tandem repeats of dinucleotides. In the process of cloning and sequencing the mouse genomic DNA for tumor necrosis factor (TNF) receptors type 1 and type 2, we identified two simple dinucleotide repeats within the noncoding regions of TNF receptor type 1 and three such sequences within TNF receptor type 2. PCR analysis of these sequences, using genomic DNA from 21 different inbred and wild mouse strains, as demonstrated by running the amplified products on sequencing gels, showed that the repeats are highly polymorphic. We identified seven alleles of TNF receptor type 2 and five alleles of TNF receptor type 1. Using these polymorphic markers in two sets of recombinant inbred strains of mice, the chromosomal localization of Tnfr-1 was mapped to mouse chromosome 6 and Tnfr-2 was located to the distal portion of mouse chromosome 4.

Animals↗

Inflammatory pseudotumor of the spleen: report of a case.

A case of an inflammatory pseudotumor arising in the spleen of a 60-year-old Japanese male is described herein. This benign lesion is extremely rare, with only 12 cases, including our own, having been reported in the world literature. We preoperatively diagnosed the splenic tumor as a metastasis, due to the coexistance of advanced stage carcinoma in the sigmoid colon. However, after splenectomy, histopathological examination of the mass revealed an inflammatory process. Inflammatory pseudotumors often pose diagnostic difficulties because the clinical and radiologic findings are suggestive of malignancy. The clinical and pathological features of cases previously reported are reviewed following the presentation of this case.

Adenocarcinoma↗

Modified pancreaticogastrostomy following pancreaticoduodenectomy.

A modified pancreaticogastrostomy without gastrotomy was performed in 46 patients undergoing pancreaticoduodenectomy for malignant or benign disease. Postoperative complications related to the modified pancreaticogastrostomy occurred in one patient (2%). Operative mortality was 4% and was unrelated to the pancreaticogastrostomy itself. During the first postoperative year, four patients died of causes unrelated to the original disease process, and nine patients died of recurrent carcinoma. The remaining 31 patients were alive and well at a mean follow-up of 20 months. Results of postoperative gastroscopy were normal in all patients studied. A modified pancreaticogastrostomy without gastrotomy is a safe and effective procedure for pancreatic reconstruction in pancreaticoduodenectomy.

Adult↗

B cell development is perturbed in bone marrow from c-fos/v-jun doubly transgenic mice.

c-fos and c-jun gene products form a heterodimeric complex (AP-1) that regulates target gene expression by binding to a specific DNA sequence motif. In order to study a role of AP-1 (Fos/Jun) in growth and differentiation of immature B lineage cells, we have established and mated two independent transgenic mice carrying the mouse c-fos gene or the viral v-jun gene fused to the H-2K promoter. IL-7 dependent bone marrow cell culture from doubly transgenic (H2-fos/jun) mice demonstrated severe delay of early B cell development. Proliferation of pre-B cells in the fresh bone marrow from H2-fos/jun mice to IL-7 stimulation was very low. These results suggest that the deregulated production of AP-1 perturbs IL-7 mediated proliferation and differentiation of immature B cells.

Animals↗