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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 109 records · Page 6Linked to original sources

Analysis of predictive factors for recurrence after hepatectomy for colorectal liver metastases.

Hepatectomy for liver metastases from colorectal cancer has recently received general acceptance as a safe, potentially curative treatment. Most patients, however, die of recurrent disease after hepatectomy. The predictive factors for recurrence after first resection of liver metastases have not yet been clarified. The authors aimed to determine the factors that can predict recurrence, especially hepatic-only recurrence after hepatectomy for colorectal liver metastases. Seventy-six patients who underwent liver resection of colorectal metastases were studied retrospectively. Forty-seven (61.8%) of the patients had a recurrence. The patients' disease-free survival after first hepatectomy and the second recurrence sites were univariately and multivariately analyzed using 16 clinicopathologic variables. Wall invasion, lymph node metastases, lymphatic invasion, venous invasion of the primary tumor, 24 months or longer disease-free interval after resection of the primary colorectal cancer, and bilateral liver metastases significantly influenced the disease-free survival (log-rank test: p < 0.05). The multivariate analysis revealed that venous invasion of the primary tumor and bilateral hepatic metastases were independent risk factors for recurrence after hepatectomy. The liver was the only site of second recurrence in 23 patients. Patients with lymph node metastases and venous invasion of the primary tumor had a significant difference between hepatic-only and extrahepatic recurrence after first hepatectomy (chi-square test or Fishers' exact test: p < 0.05). Recurrence after hepatectomy was influenced more by factors associated with the primary colorectal cancer than factors surrounding the first liver metastases. Venous invasion of the primary colorectal cancer was the most important predictable factor for hepatic-only second recurrence.

Adult↗

Computational analysis of full-length mouse cDNAs compared with human genome sequences.

Although the sequencing of the human genome is complete, identification of encoded genes and determination of their structures remain a major challenge. In this report, we introduce a method that effectively uses full-length mouse cDNAs to complement efforts in carrying out these difficult tasks. A total of 61,227 RIKEN mouse cDNAs (21,076 full-length and 40,151 EST sequences containing certain redundancies) were aligned with the draft human sequences. We found 35,141 non-redundant genomic regions that showed a significant alignment with the mouse cDNAs. We analyzed the structures and compositional properties of the regions detected by the full-length cDNAs, including cross-species comparisons, and noted a systematic bias of GENSCAN against exons of small size and/or low GC-content. Of the cDNAs locating the 35,141 genomic regions, 3,217 did not match any sequences of the known human genes or ESTs. Among those 3,217 cDNAs, 1,141 did not show any significant similarity to any protein sequence in the GenBank non-redundant protein database and thus are candidates for novel genes.

Algorithms↗

Five-year survivors after aggressive surgery for stage IV gallbladder cancer.

PURPOSE: To describe 5-year survivors after radical surgery for stage IV gallbladder cancer and to determine the characteristics leading to potential long-term survival. METHODS: Of 59 patients undergoing radical resection for stage IV disease between 1979 and 1994, 6 patients who have survived for more than 5 years were followed up. RESULTS: Three patients had developed obstructive jaundice due to involvement of the hepatic hilum, but the other three had not. The jaundiced patients had remarkable tumor spread over the bile duct and right hepatic artery within the hepatoduodenal ligament. However, the proper and left hepatic arteries and the portal trunk and its left branch were free from tumor involvement. The nonjaundiced patients had N1 or N2 lymph node metastasis. However, none underwent bile duct resection or pancreatoduodenectomy to establish radical lymphadenectomy. CONCLUSIONS: Selected patients with stage IV gallbladder cancer may be candidates for 5-year survival when the primary tumor is fairly localized even if it forms a large mass and involves neighboring organs including the hepatic duct, lymph node metastasis is limited to N1 and N2 except for the celiac and superior mesenteric nodes and is less infiltrative, and distant metastasis including that in the paraaortic area is absent.

Adult↗

Portal venous dilatation and stenting for bleeding jejunal varices: report of two cases.

We present two patients who underwent a portal stent placement for bleeding jejunal varices of the afferent loop caused by extrahepatic portal venous stenosis. Case 1 involved a 66-year-old woman who developed bleeding jejunal varices due to extrahepatic portal venous stenosis 1 year after a pancreaticoduodenectomy with intraoperative radiation therapy. Percutaneous transhepatic balloon dilatation and stent placement were performed. Since undergoing the procedure, no bleeding has occurred. Case 2 concerned a 44-year-old woman who had a rupture and bleeding of jejunal varices 16 years after a choledocojejunostomy. Stenosis was observed from the right and left branches of the portal vein to its intrahepatic branches. Both balloon dilatation and stent placement were attempted. However, the stent could not be fully inserted into the intrahepatic portal vein. Portal stent placement is less invasive and radical, and therefore should be attempted for the treatment of extrahepatic portal venous stenosis. However, there are limits to its application if the stenosis extends to the intrahepatic branches of the portal vein.

Adult↗

Thymic carcinoid in a patient with multiple endocrine neoplasia type 1: report of a case.

We report herein the rare case of a 33-year-old man found to have a multiple endocrine neoplasia type 1 (MEN1)-associated carcinoid tumor in the thymus. A chest roentgenogram demonstrated an asymptomatic anterior mediastinal mass, 7 cm in diameter, and ultrasound-guided percutaneous Tru-Cut biopsy revealed a carcinoid tumor of the thymus. An extended thymectomy was performed through a median sternotomy and pathological examination confirmed the diagnosis of a thymic carcinoid tumor, which was mainly encapsulated with locally invasive growth into the pleura. Despite the absence of a family history of MEN1, he was treated for two pancreatic islet cell tumors, hyperparathyroidism, an adrenal tumor, and a retroperitoneal lipoma. MEN1 mutations were detected both in blood samples and pancreatic tumor tissues. He is now well without any evidence of tumor recurrence 27 months after the operation for the thymic carcinoid. MEN1 mutations were screened by direct nucleotide sequencing of all protein-coding regions of exons 2-10 of the MEN1 gene. Heterozygous germline mutation was detected in the blood sample analyses. Moreover, fresh-frozen pancreatic tumor tissues showed a loss of heterozygosity in the MEN1 region.

Adult↗

High tibial osteotomy for varus gonarthrosis: a 10- to 24-year follow-up study.

From January 1976 to December 1990, 66 high tibial osteotomies for medial gonarthrosis were performed in 59 patients. Thirty knees of 26 patients (18 women and 8 men) were reviewed after a mean follow-up period of 15.3 years (range, 10-24 years). The mean age of these 26 patients was 59 years at the time of operation and 75.5 years at the latest follow-up. The average femoro-tibial angle changed, from 187 degrees before surgery to 170 degrees after surgery, and to 174 degrees at the latest follow-up. Progression of osteoarthritic changes was observed in 87% for the medial and in 90% for the lateral compartment of the knee. Clinical results, assessed according to the Japanese Orthopaedic Association (JOA) knee score, showed improvement with a score of 65 points before surgery, and a score of 81 points at the latest follow-up. The overall clinical results were satisfactory for 60% of the knees. The results of this long-term follow-up study show that high tibial osteotomy for medial compartment osteoarthritis can be effective for as long as 15 years.

Aged↗

Differences between squamous cell carcinoma and keratoacanthoma in angiotensin type-1 receptor expression.

Angiotensin II receptors are the specific receptors of angiotensin II of the renin-angiotensin system. The existence and role of the receptors in the skin have not been determined. We immunohistochemically studied the expression of angiotensin receptors in the human skin. The results demonstrated the expression of angiotensin type 1 receptor (AT1) in the normal human suprabasal epidermis. The expression pattern suggests the role of AT1 in association with differentiation. In addition, we studied the expression of AT1 in squamous cell carcinoma (SCC) of the skin, SCC of the lip, and keratoacanthoma (KA). Our experiments showed that high, intermediate, and low levels of AT1 were observed in 37 (74.0%), 7 (14.0%), and 2 (4.0%) of 50 cases of SCC of the skin, respectively, and the negative periphery pattern was observed in 17 (77.3%) of 22 cases of KA. These observations suggest that the immunohistochemical study of AT1 is useful to distinguish SCC from KA. Studying the role and distribution of AT1 may help in understanding the pathophysiology of the skin.

Adult↗

The immunohistochemical localization of Bax and Bcl-2 and their relation to apoptosis during amelogenesis in developing rat molars.

Bax and Bcl-2 are members of a family of intracellular, membrane-associated proteins that regulate programmed cell death. It has been suggested that, when Bax predominates, programmed cell death is accelerated and the apoptosis inhibitory activity of Bcl-2 is suppressed. The present study was undertaken to immunohistochemically (IHC) localize Bax and Bcl-2 in the cells of the enamel organ during amelogenesis in rat molars. Also, apoptotic cells were detected by TUNEL staining. The IHC intense localization of Bcl-2 and light staining for Bax in the pre-ameloblasts suggest that apoptosis is inhibited in the proliferating pre-ameloblasts. This is consistent with an absence of TUNEL staining for apoptosis in these cells. However, in the late secretory and transition ameloblasts, and adjacent stratum intermedium, evidence of apoptosis of the ameloblasts was observed. Bax and Bcl-2 were co-localized in the proximal ends of late secretory, transition and early maturation-stage ameloblasts, but immunoreactivity for Bax markedly increased in the proximal ends of late secretory and transition ameloblasts, while the Bcl-2 staining appeared to be lighter. This suggests that Bax antagonized Bcl-2 function, limiting the ability of Bcl-2 to prolong cell survival. In the early maturation stage, Bax staining faded while the immunoreactivity for Bcl-2 increased. Evidence of distinct apoptosis was reduced in the early maturation stage ameloblasts. When related to the occurrence of apoptosis during amelogenesis, the relative intensity of expression of Bax and Bcl-2 changed in a pattern consistent with that observed in other cell lines. This indicates that these proteins play essential roles in the process of amelogenesis, as predicted by their proposed mechanisms of action in the control of apoptosis.

Age Factors↗

A role of jumonji gene in proliferation but not differentiation of megakaryocyte lineage cells.

In this study, megakaryocytopoiesis was investigated in the recessive mutant mouse, jumonji, obtained by a gene-trap strategy. We investigated the number of megakaryocyte progenitors in the fetal liver, yolk sac, and peripheral blood of jumonji homozygous embryos by in vitro colony forming assay and monitored colony formation from single megakaryocyte progenitors. We also investigated the differentiation of jumonji-deficient megakaryocytes in terms of the expression of megakaryocyte differentiation markers PF4, CD62P, and GATA-1, proplatelet formation, cytoplasmic maturation, and endomitosis. We found that the population of megakaryocyte progenitors in the fetal liver, yolk sac, and peripheral blood of jumonji homozygotes increased. A fraction of megakaryocyte progenitors derived from the fetal liver of jumonji homozygotes formed larger colonies in vitro when compared with controls. This abnormality is caused by delayed growth arrest in the progeny. Immature megakaryocyte progenitors showed this abnormality. The megakaryocytes of jumonji homozygotes expressed PF4, CD62P, and GATA-1, obtained cytoplasmic maturation, extended proplatelet-like processes, and underwent endomitosis. The loss of the jumonji gene causes an increase in the number of megakaryocyte lineage cells. Our data suggest that the jumonji gene regulates proliferation but not differentiation of megakaryocyte lineage cells.

Animals↗

Slow synchronized bursts of inhibitory postsynaptic currents (0.1-0.3 Hz) by cholinergic stimulation in the rat frontal cortex in vitro.

Cholinergic inputs from the basal forebrain to cortex exert profound effects on cortical activities, such as a rhythmic synchronization. For these modulatory effects inhibitory interneurons could play crucial roles within the cortical circuitry. To study cholinergic modulation of GABA-mediated inhibition, we recorded inhibitory postsynaptic current (IPSC) during application of cholinergic agonists in the rat frontal cortex in vitro. Both carbachol and muscarine caused two temporally different patterns of IPSC modulation in both pyramidal cells and inhibitory interneurons: tonic or periodic increase of GABA-A receptor-mediated inhibition. The tonic pattern showed a continuous increase of IPSC frequency, while the periodic increase manifested itself as rhythmic (0.1-0.3 Hz, mean 0.2 Hz) bursts of IPSC (frequency: 6-69 Hz, mean 24 Hz; burst duration: 1.2-4.3 s, mean 2.2 s). Both types of increase were suppressed by atropine or pirenzepine, muscarinic-receptor antagonists. The periodical IPSC bursts were not affected by antagonists for ionotropic glutamate receptors. Following cholinergic stimulation, periodic IPSC bursts in nearby cells were synchronized as a whole, but individual inhibitory events within the bursts were not always temporally correlated, suggesting synchronized depolarizations of several presynaptic interneurons. It has been revealed that slow rhythmic depolarizations accompanying spike firing can be generated within the cortex. In addition to this periodic excitation of cortical circuits, these results indicate that cortical inhibitory interneurons have their own acetylcholine-dependent mechanism generating the slow rhythm independent of the excitatory circuits.

Acetylcholine↗

Cytokine regulation of cartilage-derived retinoic acid-sensitive protein (CD-RAP) in primary articular chondrocytes: suppression by IL-1, bfGF, TGFbeta and stimulation by IGF-1.

Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a secreted protein identified in our laboratory by RT-PCR and differential display [U.H. Dietz, L.J. Sandell. Cloning of a retinoic acid-sensitive mDNA expressed in cartilage and during chondrogenesis. J. Biol. Chem. 271 (1996) 3311-3316]. It is synthesized by chondrocytes throughout development and down-regulated by retinoic acid in coordination with type II collagen gene expression. To further explore the regulation CD-RAP in primary articular chondrocytes, we examined effects of selected cytokines on CD-RAP gene expression compared to their effects on type II collagen expression. Northern blot analysis showed that expression of CD-RAP mRNA was suppressed by bFGF, IL-1beta and retinoic acid in coordination with type II collagen mRNA. TGF-beta decreased CD-RAP expression while increasing type II collagen mRNA whereas both mRNAs were up-regulated by IGF-1. In chondrocytes dedifferentiated with retinoic acid, IGF-1 induced re-expression of both CD-RAP and type II collagen mRNAs. The mechanism of stimulation of CD-RAP by IGF-1 was further investigated. An mRNA stability assay revealed that IGF-1 had no effect on CD-RAP or type II collagen mRNA half life, suggesting that the enhancement by IGF-1 is due to increased gene transcription. To study the transcriptional mechanism, we used the 5'-flanking region of the CD-RAP gene fused to a promoter-less reporter plasmid encoding luciferase. Deletion analysis of the CD-RAP promoter indicated that an IGF-1-responsive element is present between nucleotides -475 and -458. These data indicate that CD-RAP expression can be regulated by cytokines known to influence chondrocyte metabolism and that IGF-1 up-regulates CD-RAP gene expression through a transcriptional mechanism.

Animals↗

Novel mode of processing and secretion of connective tissue growth factor/ecogenin (CTGF/Hcs24) in chondrocytic HCS-2/8 cells.

The synthesis, processing, and secretion of human connective tissue growth factor (CTGF/Hcs24) in a human chondrocytic cell line, HCS-2/8, were analyzed immunochemically. By metabolic pulse-labeling, chasing, and subsequent immunoprecipitation analyses, active synthesis of CTGF was observed not only in growing HCS-2/8 cells, but also in confluent cells. However, secretion and processing of CTGF were found to be regulated differentially, depending upon the growth status. During phases of growth, HCS-2/8 cells released CTGF molecules immediately without sequestering them within the cell layer. In contrast, after the cells reached confluence, the secretion slowed, resulting in an accumulation of CTGF in the cells or extracellular matrices (ECMs). Also, in confluent cell layers, a 10 kDa protein that was reactive to an anti-CTGF serum was observed. This CTGF-related small protein was not detected immediately after labeling, but gradually appeared within 6 h after chase, which suggests its entity as a processed subfragment of CTGF. Surprisingly, the 10 kDa protein was stable even 48 h after synthesis, and was not released by ECM digestion, suggesting an intracellular maintenance and function. Taken together, the behavior of CTGF in HCS-2/8 cells is remarkably different from that reported in fibroblasts, which may represent unique roles for CTGF in the growth and differentiation of chondrocytes.

Amino Acid Sequence↗

Molecular epidemiologic analysis of Vibrio cholerae O1 isolated during the 1997-8 cholera epidemic in southern Thailand.

An unusually high incidence of Vibrio cholerae O1 infection was observed in southern Thailand between late December 1997 and March 1998. Fifty-seven V. cholerae O1 strains were isolated in five provinces during this epidemic and were examined. They were El Tor Ogawa strains exhibiting similar antibiograms. All strains were resistant to tetracycline, which had not been reported in Thailand since 1993. The ribotypes. hybridization patterns with ctx and zot gene probes, arbitrarily primed PCR profiles, and pulsed-field gel electrophoresis profiles of the representative strains were compared with the clinical strains isolated from patients in India and Bangladesh in 1997 and 1998 and from international travellers originating from various Asian countries during the 1992-8 period. All southern Thailand strains and the 1998 international traveller strain of Thai origin showed indistinguishable genetic fingerprinting patterns that were distinct from those of other test strains. The results suggest that a tetracycline-resistant clone newly emerged in late December 1997 caused the large epidemic in southern Thailand and that the variants with a slightly different antibiogram appeared during the course of the spreading epidemic.

Cholera↗

Treatment of bladder cancer cells in vitro and in vivo with 2-5A antisense telomerase RNA.

Bladder cancer is the most common malignant tumor of the urinary tract. Novel treatment approaches are essential because of the failure of current treatment options to cure a high percentage of patients. Telomerase, a ribonucleoprotein, is detected in almost all bladder cancer, but not in normal bladder tissues. Therefore, telomerase is expected to be a very promising candidate for targeted therapy of bladder cancer. In this study, we synthesized a 19-mer antisense oligonucleotide against the RNA component of human telomerase (hTR) linked to a 2-5A molecule (2-5A-anti-hTR) and investigated its antitumor effect against bladder cancer cells. The 2-5A antisense strategy relies on the recruitment and activation of RNase L at the site of targeted RNA sequence. Here we demonstrate that treatment with 2-5A-anti-hTR reduced the viability of seven bladder cancer cell lines (UM-UC-2, UM-UC-3, UM-UC-6, UM-UC-9, UM-UC-14, RT4 and T24) expressing telomerase activity to 21-55% within 4 days. The cytotoxicity was mainly due to induction of caspase-dependent apoptosis. In contrast, normal fibroblast WI38 cells lacking telomerase activity were resistant to the treatment. Furthermore, treatment of subcutaneous UM-UC-2 tumors in nude mice with 2-5A-anti-hTR significantly suppressed the tumor growth through induction of apoptosis (P < 0.001). These findings may offer a strong support to the feasibility of the 2-5A-anti-hTR treatment for human bladder cancer.

Animals↗

Immunohistochemical study of angiotensin receptors in normal human sweat glands and eccrine poroma.

BACKGROUND: Angiotensin II exerts its actions through its specific receptors. However, expression of these receptors has not been determined in sweat glands. OBJECTIVES: To clarify the expression and localization of the angiotensin receptors in normal human sweat glands and eccrine poroma. METHODS: Expression of angiotensin type 1 (AT1) and type 2 (AT2) receptors in normal human eccrine and apocrine sweat glands and 12 cases of eccrine poroma was studied using immunohistochemistry. RESULTS: In eccrine sweat glands, the acrosyringium and the inner surfaces and luminal cells of the intradermal duct showed positive staining with AT1. In apocrine sweat glands, the intraepithelial duct and luminal cells of the intradermal duct showed positive staining with AT1. In 12 cases of eccrine poroma, some of the tumour cells in the tumour strands and cells surrounding the luminal structures stained positively. There were no positive findings with AT2. CONCLUSIONS: Studying AT1 distribution may be useful in understanding the pathophysiology of sweat glands and sweat gland tumours.

Acrospiroma↗