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Biomedical subjects

J Takeda

Publications and source records attributed to J Takeda.

At least 271 records · Page 15Linked to original sources

Para-aortic lymph node dissection for the treatment of advanced gastric cancer.

Para-aortic lymph node (No. 16) metastasis has been accepted as a factor responsible for non-curability in gastric cancer surgery. Recently in Japan, after detailed experimental and clinical studies of the lymph flows from the stomach and/or perigastric nodes to these No. 16 nodes, it is now considered to be curable. From 5 autopsy cases, the mean number of No. 16 nodes has been determined to be 43. The frequency of positive No. 16 metastasis (No. 16(+)) was found to be 24%, occurring in 35 of 144 cases with advanced gastric cancer following R3 gastrectomy plus No. 16 dissection. The 5 year-survival rate of R3+ No. 16 dissection was 70.1% in n1(+), 49.8% in n2(+) and 24.3% in n3(+) and had better prognoses (by Kaplan-Meier statistics) than those without dissection of the No. 16 nodes. Only 37 patients in the Japanese literature have had No. 16 dissections, and were confirmed histologically to have had No. 16(+) and subsequently survived more than 5 years. The number of those surviving No. 16(+) can be expected to increase in the near future with the adoption of R3 gastrectomy plus No. 16 dissection.

Aorta, Abdominal↗

Early gastric cancer associated with synchronous multiple liver metastasis--two rare cases.

From 1976 to 1991, 1,640 cases of gastric cancer were resected in our department. Of these, 659 (40.2%) cases were early gastric cancer (EGC). The prognosis after resection of an EGC is generally good, with a 5-year survival rate of 95%. The incidence of an EGC with synchronous liver metastasis is very rare. To our knowledge, only 15 cases of an EGC with synchronous liver metastasis have been reported in the Japanese literature. From 10 cases adequately described the EGC with synchronous liver metastasis derived only from sm-cancers (cancers confined to the submucosa) of medullary type, histologically, more commonly occurring in males than EGC generally, (of elevated type) and with positive lymph node metastasis. Here we report two additional rare cases of EGC with liver metastasis.

Aged↗

Early gastric cancer with juxta lymph node (n3) metastasis.

From 1976 to 1992, a total of 714 cases of early gastric cancer (EGC) were treated by resection in the First Department of Surgery, Kurume University Hospital. For EGC, the overall lymph node metastasis rate is generally 10%, with the lymph node metastasis observed mainly in the Group 1 perigastric nodes in both mucosal cancer and submucosal cancer. Three rare cases of an early gastric cancer with Group 3 juxta regional lymph node metastasis are described because Group 3 lymph nodes are rarely discovered. To our knowledge, only 14 other cases of EGC with juxta regional lymph node metastasis have been reported in the Japanese literature.

Aged↗

Retrospective studies of synchronous double early gastric cancer.

From 1984 to 1990, 922 cases of gastric cancer underwent resection in the First Department of Surgery, at Kurume University Hospital. Of these, 381 (41.3%) cases were early gastric cancer (EGC). Among these EGC, synchronous double early gastric cancer (double EGC), according to the diagnostic criteria of Moertel, was found in 49 (12.9%) cases involving 98 foci. In cases of a double EGC, the primary and secondary foci can be distinguished. Double EGC occurred more frequently in males than females (7.1:1). In the elderly, the incidence of a double EGC was higher than the incidence of a single EGC. Double EGC occurred more frequently in the lower third of the stomach than a single EGC. And a macroscopically elevated and histologically differentiated type primary focus was more frequently found in double EGC than in single EGC. Of the 49 secondary foci in the double EGC, 12 (24.5%) foci were a microcarcinoma of less than 5 mm in greatest diameter, and 48 (98%) were limited to the mucosa (m-cancer). Therefore, a preoperative detailed examination of the whole stomach by endoscopy and an intraoperative careful search under gastrotomy must be made in the remnant of the stomach in cases of distal or proximal partial gastrectomy to ensure adequate excision.

Aged↗

[Appropriate administration of granulocyte colony stimulating factor for malignant lymphoma of the head and neck].

The effects of granulocyte colony stimulating factor (G-CSF) were evaluated in 9 patients with malignant lymphoma of the head and neck. The effects of 31 cycles of cytotoxic chemotherapy were treated with G-CSF. G-CSF was given by one of the following three routes: 1) administration before or with cytotoxic chemotherapy, 2) administration after cytotoxic chemotherapy with leukocyte counts of more than 2000/mm3, and 3) administration after leukocyte counts had dropped to less than 2000/mm3. The first group consisted of one cycle of CHOP therapy and 2 cycles of VAMA therapy. The second group consisted of 10 cycles of CHOP therapy. The third group consisted of 13 cycles of CHOP therapy and 5 cycles of VAMA therapy. Leukocyte nadirs occurred on around day 14 for CHOP therapy and around day 21 for VAMA therapy without G-CSF treatment. In the first group, the leukocyte nadirs occurred earlier with G-CSF treatment. Additional G-CSF treatments were given in two of the three cycles. In the second group, the leukocyte counts did not drop below 2000/mm3 in three of the ten cycles. Additional G-CSF treatments were given in five of the remaining seven cycles. The two other cycles went without additional treatment. The mean volume of G-CSF was 305 +/- 86 micrograms. In the third group, the leukocyte counts increased to more than 2000/mm3 immediately after G-CSF administration in CHOP therapy. The mean volume was 227 +/- 78 micrograms, significantly less than that of the second group. The leukocyte counts also exceeded 2000/mm3 3-5 days after G-CSF administration in 5 cycles of VAMA therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

[Expression of the growth factors (EGF, EGFR, and TGF alpha) and PCNA in superspreading and penetrating types of gastric carcinomas].

Expression of EGF, EGFR, TGF alpha, and PCNA in resected gastric carcinomas (15 cases of superspreading type and 25 cases of penetrating type) was immunohistochemically studied to understand biological features of these two types of gastric carcinomas. EGF, EGFR, and TGF alpha positive cases were preferentially found in the penetrating type rather than in the superspreading type (p < 0.05). Incidence of PCNA high expression cases in the penetrating type was significantly higher than that in superspreading type. Nineteen cases (76%) of the penetrating type and 1 case of the superspreading type (6.7%) were diffusely PCNA (+), and the incidence of in the former type was significantly higher than that of the latter type (p < 0.001). One case of the superspreading type and 13 cases of the penetrating type were either EGF (+) or TGF alpha (+), and EGFR (+), and the incidence in the latter type was significantly higher than that in the former type (p < 0.05), suggesting that growth and invasion of carcinoma cells, especially in the penetrating type, may depend on "autocrine mechanism". Incidence of the growth factors (+) and PCNA (+) cells in classical type of signet ring cells was lower than that in other types of singnet ring cells.

Carcinoma, Signet Ring Cell↗

Splice variant of the somatostatin receptor 2 subtype, somatostatin receptor 2B, couples to adenylyl cyclase.

The diverse biological actions of somatostatin (SRIF) are mediated by a family of receptors, of which five have been cloned and characterized. One of the SRIF receptor subtypes, SSTR2, has been shown to exist in two forms. SSTR2A and SSTR2B are 369 and 346 amino acids in size, respectively, and differ in length and amino acid sequence in their intracellularly located carboxyl termini. SSTR2A and SSTR2B are generated by alternative splicing of SSTR2 mRNA. We previously characterized mouse SSTR2A and showed that it could be distinguished from other cloned SRIF receptor subtypes by its high affinity for MK-678 and its lack of coupling to adenylyl cyclase. To determine whether the properties of mouse SSTR2A and SSTR2B differ, we have expressed both in COS-7 cells and characterized their ligand-binding properties and ability to couple to adenylyl cyclase. The two receptors exhibited similar affinities for a number of SSTR2-selective agonists such as MK-678. Pretreatment with SRIF of COS-7 cells expressing each receptor reduced high affinity agonist binding to both SSTR2A and SSTR2B, indicating that both receptors can be regulated. Furthermore, agonist binding to both receptors was reduced by GTP analogs and Na+, indicating that they both associate with G proteins. As shown previously, SSTR2A could not mediate SRIF inhibition of forskolin-stimulated cAMP formation. In contrast, SSTR2B was coupled to adenylyl cyclase and was able to mediate SRIF inhibition of forskolin-stimulated cAMP formation. Thus, SSTR2A and SSTR2B differ in their ability to couple to adenylyl cyclase. Because SSTR2A and SSTR2B differ only in the length and amino acid sequence of their carboxyl termini, these findings imply that the carboxyl-terminal 15 residues of SSTR2B may be involved in coupling this receptor to adenylyl cyclase.

Adenylyl Cyclases↗

[A case of massive hemorrhage associated with the removal of longstanding intrabronchial foreign body].

A 46 year old male patient was admitted with fever and cough. A chest X-ray film revealed a foreign body shadow of a denture fragment in the right intermediate bronchus that he had swallowed one year and half ago. Rigid bronchoscopy was used to remove the foreign body under general anesthesia. During the procedure, massive hemorrhage occurred from bronchus, and the foreign body was not removed successfully and the patient sustained near cardiac arrest. Postoperatively, he recovered from the near fatal condition with support of mechanical ventilation in ICU for several days. After one month, pulmonary angiography was performed and it revealed the transfiguration of pulmonary artery and other vessels close to the foreign body. Granular tissue around the foreign body was observed by preoperative bronchoscopy. Disruption of such vessels and granular tissue by rigid and forced fiberscopy was suspected to have caused the massive bleeding. Later, the denture fragment was successfully removed by right thoracotomy. We should take this complication into consideration and preoperative fiberoptic bronchoscopy and pulmonary angiography may be beneficial to the anesthetic management of such patients.

Anesthesia, General↗

[Changes of peripheral airways through mechanical ventilation in acute respiratory failure].

To evaluate the morphologic changes in the peripheral airways associated with positive pressure ventilation, fine fiberoptic bronchoscopy (1.8 mm outer diameter) was performed in 12 patients who had no history of prior pulmonary failure. In 19 examinations, the main morphologic findings were paleness and bronchial dilatation in the peripheral airways where increased secretions, pigmentation and stenosis or collapse were also observed. Patients with bronchial dilatation had longer periods of mechanical ventilation (17 +/- 8 days) compared to those without dilation (10 +/- 5 days). The structural destruction in the peripheral airways observed in patients on prolonged positive pressure mechanical ventilation suggests that barotrauma may be more widespread than previously recognized.

Acute Disease↗

[The effects of anesthetic techniques and insufflating gases on ventilation during laparoscopy].

The present study was performed to clarify the influences of anesthetic methods and insufflating gases on arterial blood gas and ventilation during laparoscopy. Forty five women undergoing laparoscopy for gynecological procedure were studied after dividing into four groups; general anesthesia with control ventilation or epidural anesthesia with spontaneous breathing, plus insufflation with carbon dioxide (CO2) or nitrous oxide (N2O). After CO2 insufflation, PaCO2 increased significantly in the patients who were mechanically ventilated, but not in the patients breathing spontaneously. After N2O insufflation, the decrease in tidal volume (VT) and the increase in VD/VT were significant, but minute ventilation was well maintained by the compensatory increase in respiratory frequency during spontaneous breathing. On the other hand, after CO2 insufflation VE and VD/VT increased significantly without any change in VT. PaO2 decreased significantly after both insufflation and Trendelenburg tilt in all groups, probably secondary to the decrease in functional residual capacity. These findings suggest that during laparoscopy, ventilation could be well maintained by spontaneous breathing, although the increase in VD/VT and costal breathing indicate the increase in respiratory work load. We recommend that ventilation and oxygenation should be closely monitored during laparoscopy to avoid hypercapnia and hypoxia.

Adolescent↗

[A case of advanced gastric cancer with liver and lung metastasis effectively treated by combined chemo-immunotherapy of MMC, 5'-DFUR, OK-432].

A sixty-eight-year-old male patient was diagnosed as having inoperable advanced gastric cancer with liver and lung metastasis. The patient was treated by combined chemo-immunotherapy of MMC 10 mg/M, 5'-DFUR 800 mg/day and OK-432 5 KE/2 W. Six months after commencing chemotherapy, CT-scan and upper GI series revealed that metasized liver tumors and stomach lesion were remarkably decreased in size and no cancer cell was confirmed by endoscopic biopsy. Further, the metastatic lung tumor has disappeared on chest X-ray. The patient had been well without any evidence of tumor re-progression for over one year, but from July the liver tumor began to metastasize again and the patient eventually died of liver metastasis on Jan. 1, 1993.

Adenocarcinoma↗

[Blood gas changes during hypotensive anesthesia induced by prostaglandin E1].

The influence of prostaglandin E1 (PGE1) on PaO2 at doses that produced slight hypotension was evaluated in 176 patients scheduled for surgery. When systolic blood pressure was stabilized after induction of anesthesia, PGE1 infusion was started until 20% reduction of systolic blood pressure was achieved. Arterial blood gases were analyzed before infusion of PGE1 and 30 min after the completion of this hypotensive level respectively. The reductions in both PaO2 [from 177 +/- 64 mmHg to 164 +/- 65 mmHg (mean +/- SD) (P < 0.01)] and PaO2/FIO2 [from 486.5 +/- 144.4 to 437.6 +/- 121.6 (P < 0.01)] were observed with PGE1 infusion of 0.079 +/- 0.068 micrograms.kg-1.min-1. The results of this study show that PaO2 decreases during induced hypotension with PGE1 infusion, but this decrease is not clinically significant.

Adult↗

Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues.

Transcription factors containing the POU-domain have been shown to be important regulators of tissue-specific gene expression in the pituitary and lymphoid cells. Using a polymerase chain reaction (PCR)-based strategy, we have searched for similar factors that may be expressed in adult human pancreatic islets. This approach resulted in the amplification of sequences encoding the octamer binding proteins Oct1 and Oct3 (also called Oct4). The isolation of cDNAs encoding Oct3 revealed the expression of two isoforms of this transcription factor termed Oct3A and Oct3B that are generated by alternative splicing. Human Oct3A and Oct3B are composed of 360 and 265 amino acids, respectively, of which the 225 amino acids at the COOH-termini are identical. The sequence of human Oct3A shows 87% amino acid identity with mouse Oct3. Reverse-transcriptase PCR showed low levels of expression of both Oct3A and Oct3B mRNA in all adult human tissues examined. We also isolated and characterized the human Oct3 gene (OTF3) and a related gene, OTF3C. The human Oct3 gene, localized to human chromosome 6 in the region of the MHC complex, spans about 7 kb and consists of five exons. The Oct3-related gene, OTF3C, is a retroposon and has been localized to human chromosome 8. Southern blotting and PCR amplification of human DNA indicated the presence of other OTF3-related genes as has been previously noted in the mouse. Two polymorphisms which can be typed using PCR were identified in OTF3 which will facilitate genetic studies of this gene.

Amino Acid Sequence↗

Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus.

DNA polymorphisms in the glucokinase gene have recently been shown to be tightly linked to early-onset non-insulin-dependent diabetes mellitus in approximately 80% of French families with this form of diabetes. We previously identified a nonsense mutation in exon 7 in one of these families and showed that it was the likely cause of glucose intolerance in this dominantly inherited disorder. Here we report the isolation and partial sequence of the human glucokinase gene and the identification of two missense mutations in exon 7, Thr-228----Met and Gly-261----Arg, that cosegregate with early-onset non-insulin-dependent diabetes mellitus. To assess the molecular mechanism by which mutations at these two sites may affect glucokinase activity, the crystal structure of the related yeast hexokinase B was used as a simple model for human beta-cell glucokinase. Computer-assisted modeling suggests that mutation of Thr-228 affects affinity for ATP and mutation of Gly-261 may alter glucose binding. The identification of mutations in glucokinase, a protein that plays an important role in hepatic and beta-cell glucose metabolism, indicates that early-onset non-insulin-dependent diabetes mellitus may be primarily a disorder of carbohydrate metabolism.

Adult↗

Fructose transporter in human spermatozoa and small intestine is GLUT5.

We recently reported that the glucose transporter isoform, GLUT5, is expressed on the brush border membrane of human small intestinal enterocytes (Davidson, N. O., Hausman, A. M. L., Ifkovits, C. A., Buse, J. B., Gould, G. W., Burant, C. F., and Bell, G. I. (1992) Am. J. Physiol. 262, C795-C800). To define its role in sugar transport, human GLUT5 was expressed in Xenopus oocytes and its substrate specificity and kinetic properties determined. GLUT5 exhibits selectivity for fructose transport, as determined by inhibition studies, with a Km of 6 mM. In addition, fructose transport by GLUT5 is not inhibited by cytochalasin B, a competitive inhibitor of facilitative glucose transporters. RNA and protein blotting studies showed the presence of high levels of GLUT5 mRNA and protein in human testis and spermatozoa, and immunocytochemical studies localize GLUT5 to the plasma membrane of mature spermatids and spermatozoa. The biochemical properties and tissue distribution of GLUT5 are consistent with a physiological role for this protein as a fructose transporter.

Animals↗

Identification and analysis of the gene encoding human PC2, a prohormone convertase expressed in neuroendocrine tissues.

In recent studies we have identified PC2 and PC3, members of a family of serine proteases that are related structurally to subtilisin, and have provided evidence that these are involved in the tissue-specific processing of prohormones and neuropeptides. PC2 is expressed at high levels in the islets of Langerhans, where it participates in the processing of proinsulin to insulin (S.P.S. and D.F.S., unpublished data). To evaluate the regulated expression of the human PC2 (hPC2) gene we have analyzed its structure and characterized its promoter. A map of the gene was constructed by using 11 clones isolated from two human genomic DNA libraries. The gene spans greater than 130 kilobase pairs and consists of 12 exons. Comparison with the structure of the gene encoding human furin, another member of this superfamily, revealed a high degree of conservation of exon-intron junctions. The hPC2 gene was localized to chromosome 20, band p11.2. The 5' flanking region of the hPC2 gene is very G+C-rich and contains six potential Sp1 binding sites but no TATA or CAAT box. Expression of chloramphenicol acetyltransferase reporter fusions containing the putative promoter region was observed to occur in beta TC-3 mouse insulinoma cells but not in HepG2 human hepatoma cells, consistent with the known tissue-specific pattern of expression of the hPC2 gene. Analysis of the level of chloramphenicol acetyltransferase activity with several deletion mutants identified the region from -1100 to -539 from the translation start site as essential for hPC2 promoter activity.

Amino Acid Sequence↗

Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus.

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM) which is characterized by an early age at onset and an autosomal dominant mode of inheritance. Except for these features, the clinical characteristics of patients with MODY are similar to those with the more common late-onset form(s) of NIDDM. Previously we observed tight linkage between DNA polymorphisms in the glucokinase gene on the short arm of chromosome 7 and NIDDM in a cohort of sixteen French families having MODY. Glucokinase is an enzyme that catalyses the formation of glucose-6-phosphate from glucose and may be involved in the regulation of insulin secretion and integration of hepatic intermediary metabolism. Because the glucokinase gene was a candidate for the site of the genetic lesion in these families, we scanned this gene for mutations. Here we report the identification of a nonsense mutation in the gene encoding glucokinase and its linkage with early-onset diabetes in one family. To our knowledge, this result is the first evidence implicating a mutation in a gene involved in glucose metabolism in the pathogenesis of NIDDM.

Base Sequence↗