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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 325 records · Page 18Linked to original sources

[The clinicopathological features and operative results in a cancer of the remnant stomach--risk and prevention of cancer after partial gastrectomy].

The clinicopathological features and operative results were analyzed in 21 patients undergoing an operation for cancer of the remnant stomach between 1979 and 1997. The twenty-one patients were divided into two groups: Group A; n = 9: who had undergone a gastrectomy for benign gastric disease, Group B; n = 12: who had undergone the same operation for gastric cancer. In Group A, the interval between the first gastrectomy and the second was longer than in Group B. In both groups, a large number of advanced cancers (n = 16, 76.2%) and undifferentiated carcinomas (n = 15, 71.4%) were seen. Five-year-survival rates in Group A and Group B were 23.7%, 19.0%, respectively. The incidence of gastric stump cancer following partial gastrectomy was 80% in the patients on whom Billroth II reconstruction had been performed after gastrectomy. It is suggested that the residual stomach in the Billroth II reconstruction patients is susceptible to cancer development. Consideration of the reconstruction method and a systemic follow-up is needed to improve a prognosis.

Aged↗

The Fas-deficient SCID mouse exhibits the development of T cells in the thymus.

The Fas Ag is a cell surface protein that mediates apoptosis and is highly expressed on thymocytes. However, the role of the Fas system in the thymus is unclear. To study the role of the Fas system in the thymus, we established a novel SCID mouse bearing the lpr (lymphoproliferation) mutation. Thymocytes from these mice differentiated into CD4+ CD8+ T cells and then underwent further differentiation into CD4+ CD8- or CD4- CD8+ single-positive T cells with a low surface expression of CD3, whereas B cell development remained unrescued. These TCR-positive T cells can proliferate in response to stimulation with PMA plus ionomycin, but not with third-party spleen cells. Furthermore, thymocytes from scid/lpr mice had a great variety of TCR Vbeta repertoires. These results suggest that the Fas system plays an essential role in regulating the development of intrathymic T cells as well as peripheral T cells.

Animals↗

Stent placement in surgically reimplanted left main coronary artery in patient with anomalous origin of left main coronary artery from pulmonary artery.

Surgical repair of a 29-year-old woman's left coronary artery with an anomalous origin from the pulmonary artery was performed by reimplantation of the left main artery into the aorta, together with coronary artery bypass grafting. Subsequent stenosis of the reimplanted left main artery was treated with successful Palmaz-Schatz stent placement.

Adult↗

Effect of sialic acid residues of human alpha 1-acid glycoprotein on stereoselectivity in basic drug-protein binding.

The function of sialic acid groups at the terminal of sugar chains of human alpha 1-acid glycoprotein (AGP) was investigated with respect to chiral discrimination between optical isomers of basic drugs, using high-performance capillary electrophoresis/frontal analysis (HPCE/FA), a novel analytical method developed for the determination of unbound drug concentration with ultramicrosample volume (100-200 nl). Native human AGP and desialylated AGP were used as test proteins, and propranolol (PRO) and verapamil (VER) were used as model drugs. The unbound concentration of (S)-VER was 1.31 times higher than that of (R)-VER in native AGP solution. This selectivity was not affected by desialylation. Further, enzymatic elimination of galactose residues, which neighbored sialic acid groups, did not change the binding of either isomer of VER. On the other hand, the unbound concentration of (R)-PRO was 1.27 times higher than that of (S)-PRO in native AGP solution. Desialylation caused the unbound concentration of (S)-PRO to rise to the same level of (R)-PRO, resulting in loss of enantioselectivity. Thus, it follows that sialic acid groups of AGP, as a whole, are not responsible for chiral recognition between enantiomers of VER but are involved in enantioselectivity toward the isomers of PRO.

Adrenergic beta-Antagonists↗

Evaluation of a cytokine combination including thrombopoietin for improved transduction of a retroviral gene into G-CSF-mobilized CD34+ human blood cells.

We examined cell culture conditions with various combinations of cytokines including thrombopoietin (TPO) to obtain the most efficient transduction of recombinant retrovirus vectors into G-CSF-mobilized blood CD34+ cells which were obtained from children and purified with an Isolex 50 system (Baxter; Deerfield, IL). Three different 4-day culture conditions for the stimulation of CD34+ cells were compared in terms of a cell-cycle analysis by fluorometry and gene transduction efficiency as determined by resistance to G418 and NeoR polymerase chain reaction (PCR) for individual colony-forming unit-granulocyte/macrophage (CFU-GM) grown in a methylcellulose culture system. The cytokines tested were: A) interleukin (IL)-6 + stem cell factor (SCF); B) IL-3 + IL-6 + SCF, and C) IL-3 + IL-6 + SCF + TPO. Without a cell culture, the percentage of CD34+ cells in the cell cycle (the percentage of cells in phases S and G2/M) was 4.6%. After a four-day culture (n = 5), this value increased with the addition of IL-3 (22%) or IL-3 + TPO (27%, p < 0.05) as compared to that with the baseline cocktail of IL-6 + SCF (15%). The cell number uniformly increased approximately 10-fold in each culture condition. The average efficiency of gene transfer into incubated CD34+ cells with the corresponding combinations of cytokines was, respectively, 57%, 47%, and 30% for G418-screened CFU-GM and 72%, 68%, and 51% for polymerase chain reaction-positive CFU-GM. A statistically significant difference (p < 0.01) was found for G418/CFU-GM with IL-3 + IL-6 + SCF (57%) versus IL-3 + IL-6 + SCF + TPO (30%). Hence, it is likely that the increased cell proliferation produced by the addition of TPO was not necessarily translated into an increased rate of retroviral-mediated gene transduction, possibly because TPO preferentially induced the differentiation of stem cells into mature progenitors in these culture systems.

Anti-Bacterial Agents↗

Aberrant immunity in the central nervous system in relation to disease progression in HAM/TSP.

The immunological status of the central nervous systems of 19 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was distinct from that of 6 asymptomatic HTLV-I carriers. Cross-sectional analysis of the time course of disease-related abnormalities in the cerebrospinal fluid (CSF) showed that activated B cell function was a feature in relatively early HAM/TSP patients in whom duration of the disease was less than 5 to 6 years. During this period many patients experienced notable neurological deterioration. By contrast, an increase in CD8+CD11a+ cytotoxic T lymphocytes along with elevated beta 2-microglobulin levels in the CSF was a consistent finding in early as well as late patients with more than a 10-year history of the illness. In light of the generally progressive course of this disorder, the mode of immunity related to the pathogenesis of HAM/TSP may be different according to the stages of the disease.

Adult↗

Primary leiomyosarcoma arising in the lesser sac: report of a case.

We describe herein a very rare case of leiomyosarcoma arising in the lesser sac. A 58-year-old man with a psychiatric disorder was admitted to our department for the investigation of epigastralgia and nausea which he had been suffering since the previous month. A laparotomy revealed that the abdominal mass, found on physical examination, was a primary lesser omental tumor, histological examinations of which confirmed a diagnosis of leiomyosarcoma. The tumor cells showed a DNA diploid pattern. Leiomyosarcoma of the lesser sac is extremely unusual and it is important that it be distinguished from an extraluminal tumor of the abdomen.

DNA, Neoplasm↗

Hepatocellular carcinoma presenting as extrahepatic mass on computed tomography.

The authors describe an extremely rare case of extrahepatic hepatocellular carcinoma. The patient was a 70-year-old man who was examined by a local doctor because of abdominal discomfort. Barium meal examination demonstrated a defect occupying the lesser curvature of the stomach from the middle of the corpus to the fornix. On an abdominal computed tomography (CT) scan, the lesion, 10 cm in diameter, touched the lower surface of the caudate lobe of the liver. Under laparotomy, the tumor was found between the caudate lobe of the liver and posterior wall of the gastric corpus. As the tumor appeared to be connected with the caudate lobe by a pedicle, only the tumor was resected. Histological examination showed the tumor to be hepatocellular carcinoma of Edmondson's grade III-IV, pedunculated type.

Aged↗

Peripancreatic fluid cytology: detection of early rejection versus graft pancreatitis after canine pancreatic transplantation.

It is particularly difficult to distinguish between early rejection and graft pancreatitis when early rejection produces an elevated serum amylase level. In this study we determined whether peripancreatic fluid cytology (PFC) can differentiate early acute rejection and graft pancreatitis as an alternative diagnostic tool to graft biopsy that has the potential of pancreatic fistula and hemorrhage. Sixty-two dogs received either a segmental pancreas allograft (n = 25) or autograft (n = 37) heterotopically in the neck. This study included five groups: allografts without immunosuppression (group A, n = 12), allografts with immunosuppression (group B, n = 13), autografts without immunosuppression (group C, n = 11), autografts with immunosuppression (group D, n = 12), and autografts treated by 45 minutes of pretransplant warm ischemia to induce acute graft pancreatitis (group E, n = 14). A closed suction drainage catheter was placed next to the graft to collect peripancreatic fluid daily after the transplant. PFC was performed using May-Gruenwald-Giemsa double-staining technique and compared to the corresponding histology through the observation period. In analyses of 50 functioning grafts, PFC performed on day 1 showed similar neutrophil accumulations in all groups. In sharp contrast, on days 3 and 6, group A had dramatically increased mononuclear cell concentrations in PFC, whereas groups B, C, and D showed significantly lower concentrations, the percent of mononuclear cells among total leukocytes being 47.3 +/- 23.4%, 11.8 +/- 4.9%, 4.3 +/- 1.8%, and 6.4 +/- 2.4% (day 3); and 32.7 +/- 9.8%, 10.5 +/- 4.8%, 7.2 +/- 4.2%, and 8.6 +/- 6.4% (day 6) in groups A, B, C, and D, respectively. On the other hand, in group E numerous degenerating neutrophils with a marked to moderate increase in necrotic tissue fragments were observed by PFC on days 3 and 6. In terms of graft histology on days 3 and 6, group A showed interstitial mononuclear cell infiltration indicating an acute rejection process, whereas groups B, C, and D had minimal inflammatory cell infiltration. In group E graft pancreatitis was histologically confirmed on days 3 and 6. These results suggest that PFC after pancreas transplantation could be a safe, simple, useful diagnostic tool for discriminating early graft rejection from graft pancreatitis.

Animals↗

Pharmacokinetics of adriamycin and cisplatin for anhepatic chemotherapy during liver transplantation.

We investigated the pharmacokinetics of cytotoxic anticancer agents administered under anhepatic conditions. Beagle dogs underwent either a sham operation consisting of laparotomy only (control group, n = 11) or a laparotomy and total hepatectomy under venovenous bypass (anhepatic group, n = 12). Each dog received a bolus intravenous injection of either Adriamycin (1 mg/kg) or cisplatin (1 mg/kg). The plasma and urine concentrations of each drug were measured at intervals for up to 2 h after drug injection. The dogs given Adriamycin were then sacrificed to determine tissue drug concentrations in the liver (controls only), spleen, kidney, heart, lung, skeletal muscle and small intestine. The control and anhepatic groups showed similar Adriamycin profiles during the initial 5 min after drug injection. However, subsequently, the plasma Adriamycin concentrations remained persistently higher in the anhepatic dogs than in the controls, yielding a two-fold elevation of the mean area under the concentration-time curve in the anhepatic group (P < 0.01 vs controls). The renal clearance values did not significantly differ between the two groups. The tissue Adriamycin concentrations in all measured organs, excluding the liver, were higher in the anhepatic group than in the controls. In a second set of experiments with cisplatin, the plasma platinum concentrations did not significantly differ between the two groups throughout the time course. However, the renal clearance of platinum in the anhepatic dogs showed a fourfold increase compared with that in the controls (P < 0.01). These pharmacokinetic data suggest that Adriamycin carries the risk of increased systemic toxicities, while cisplatin may be associated with increased renal toxicity when administered during the anhepatic period of liver transplantation.

Animals↗

Fine structure of the semicompact formation of the nucleus ambiguus of the rat.

We investigated the fine structure of the semicompact formation of the nucleus ambiguus (AmS), which was identified by retrogradely labeled pharyngeal (PH) motoneurons. When cholera toxin subunit B-conjugated horseradish peroxidase was injected into the lower pharyngeal muscle, many retrogradely labeled PH neurons were found throughout the AmS. Besides the PH neurons, two types of neurons were recognized in the AmS: unlabeled medium-sized neurons and unlabeled small neurons. The PH neuron was large (27.6 x 44.1 microm) and polygonal, and contained many Nissl bodies and well-developed cell organelles with a prominent spherical nucleus. The medium-sized neuron was dark and oval (19.3 x 33.2 microm), and contained many free ribosomes and much swollen rough endoplasmic reticulum with a distorted oval nucleus. The small neuron was spindle-shaped (12.3 x 20.2 microm), and had poorly developed cell organelles with an irregularly shaped nucleus. The average number of axosomatic terminals in a sectional plane was largest in the PH neurons (32.8), smaller in the medium-sized neurons (23.1), and smallest in the small neurons (6.3). The number of axo-somatic terminals containing round vesicles (Gray's type I) was almost equal to that of terminals containing pleomorphic vesicles (Gray's type II) in the PH neuron, and slightly smaller in the small and the medium-sized neurons. About 60% of the axodendritic terminals were Gray's type I, and 40% were type II. These results indicate that there are two different types of interneurons besides the PH motoneurons in the AmS.

Animals↗

Tendency toward atopy in Kawasaki disease.

UNLABELLED: To evaluate the possible trend towards developing allergic disease in children who had suffered from Kawasaki disease (KD), we evaluated data related to allergy that were collected by parental questionnaire on 1,165 children who had suffered from KD. Comparisons were made with 5,825 sex- and age-matched control children. The incidence of household pets and of cigarette smoking in the family were significantly lower in the children with a history of KD than in those of control children. A family history of allergy was significantly more common in the children with a history of KD (71%) versus the controls (56%) (P < 0.001). The incidence of atopic dermatitis and of allergic rhinitis was significantly higher (by approximately 1.7 times) in the KD children versus the control group (P < 0.01), even in subgroups with no family history of allergy. CONCLUSION: We suggest that a genetic predisposition to atopy may be associated with a susceptibility to KD. Patients with KD tended to develop atopic dermatitis and allergic rhinitis.

Case-Control Studies↗

Efficacy of interferons in treating children with chronic hepatitis C.

UNLABELLED: Twenty-two children with chronic hepatitis serologically positive for hepatitis C virus (HCV) were treated with interferon-alpha (IFN-alpha). Liver biopsy showed chronic active hepatitis in 13 and chronic persistent hepatitis in 9 patients. A sustained clearance of HCV was observed in 8/22 children 12 months after the administration of IFN-alpha for 26 weeks, associated with normalization of HCV core antibody. Of these eight patients six had HCV genotype III and two HCV genotype II or IV. Hepatitis relapsed in seven other patients after completion of IFN-alpha with an increase in HCV core antibody titre, five with HCV genotype II, and two with HCV genotype III or IV. A second course of IFN-alpha suppressed the reactivation of HCV in all seven patients. Three of seven responders who relapsed after the first course remained negative for HCV RNA 12 months after their second course of IFN-alpha. However, the remaining four patients with HCV genotype II again relapsed after completing their second course of IFN-alpha. Seven children with the HCV genotype II resistant to IFN, including 8 weeks of IFN-beta administration, and showed no significant reduction in HCV core antibody titre. CONCLUSION: The genotype of HCV (III) and a reduction in the core antibody titre appear to be useful parameters for predicting the response to IFN-alpha therapy.

Adolescent↗

Single catheter technique of hepatic venous isolation and extracorporeal charcoal hemoperfusion for malignant liver tumors.

BACKGROUND: A single catheter technique of hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) using a 4-lumen/2-balloon (4L-2B) catheter was developed to perform high-dose intra-arterial chemotherapy of the liver. Herein we report the technique, safety, and pharmacokinetics of this system in comparison with the original double-balloon technique. PATIENTS AND METHODS: Sixteen patients with malignant liver tumors were treated by hepatic arterial infusion (HAI) with adriamycin at a dose of 100 mg/m2 under HVI-CHP. Seven patients underwent HVI-CHP by the double-balloon technique (group A), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other nine patients were treated by the single catheter technique (group B). In group B, hepatic effluent was isolated by balloon inflations and directed to filters through fenestrations of one major lumen of a 4L-2B catheter. The filtered blood was returned straight to the right atrium through the other major lumen of the catheter. RESULTS: All patients in group A had a smooth stepwise induction of HVI-CHP, whereas one of nine patients in group B developed severe hypotension requiring interruption of HVI. The hepatic venous flow rate in group B during HVI-CHP was significantly higher than that in group A (P < 0.05). Systemic adriamycin exposure, as assessed by the area under the time concentration curve in systemic serum, was significantly higher in group A compared to that in group B (P < 0.01). CONCLUSIONS: The single catheter technique is hemodynamically tolerable and feasible in the majority of patients with malignant liver tumors. In view of systemic drug exposure, the single catheter technique is superior to the original double-balloon technique.

Aged↗

Alzheimer's disease amyloid beta-protein forms Zn(2+)-sensitive, cation-selective channels across excised membrane patches from hypothalamic neurons.

We have previously shown that the 40-residue peptide termed amyloid beta-protein (A beta P[1-40]) in solution forms cation-selective channels across artificial phospholipid bilayer membranes. To determine whether A beta P[1-40] also forms channels across natural membranes, we used electrically silent excised membrane patches from a cell line derived from hypothalamic gonadotrophin-releasing hormone GnRH neurons. We found that exposing either the internal or the external side of excised membrane patches to A beta P[1-40] leads to the spontaneous formation of cation-selective channels. With Cs+ as the main cation in both the external as well as the internal saline, the amplitude of the A beta P[1-40] channel currents was found to follow the Cs+ gradient and to exhibit spontaneous conductance changes over a wide range (50-500 pS). We also found that free zinc (Zn2+), reported to bind to amyloid beta-protein in solution, can block the flow of Cs+ through the A beta P[1-40] channel. Because the Zn2+ chelator o-phenanthroline can reverse this blockade, we conclude that the underlying mechanism involves a direct interaction between the transition element Zn2+ and sites in the A beta P[1-40] channel pore. These properties of the A beta P[1-40] channel are rather similar to those observed in the artificial bilayer system. We also show here, by immunocytochemical confocal microscopy, that amyloid beta-protein molecules form deposits closely associated with the plasma membrane of a substantial fraction of the GnRH neurons. Taken together, these results suggest that the interactions between amyloid beta-protein and neuronal membranes also occur in vivo, lending further support to the idea that A beta P[1-40] channel formation might be a mechanism of amyloid beta-protein neurotoxicity.

Amyloid beta-Peptides↗

Excellence of the two-layer method (University of Wisconsin solution/perfluorochemical) in pancreas preservation before islet isolation.

BACKGROUND: In islet transplantation pancreatic preservation before islet isolation is an obstacle compromising islet yield and viability. We tested the feasibility of a two-layer method (University of Wisconsin solution [UW]/perfluorochemical) for pancreatic preservation before islet isolation. METHODS: Dog pancreases were processed into pure islets by the method of Ricordi preceded by five different preservations (groups 1-a and 1-b, the two-layer method for 3 and 24 hours; groups 2-a and 2-b, simple cold storage in UW for 3 and 24 hours; group 3, without preservation). Islet yields and functional success after autotransplantation into the liver were compared among the groups. RESULTS: Postpurification islet equivalents (IE)/gm pancreas and functional success rate were 5600 (mean), 83% in group 1-a; 4000, 56% in group 1-b; 4700, 33% in group 2-a; 1300, 0% in group 2-b; and 5000, 89% in group 3 (p < 0.05; 2b versus 1-a, 1-b, and 3), respectively. There was no statistical difference among groups 1-a, 1-b, and 3 in terms of islet yield and function (p > 0.2). CONCLUSIONS: The two-layer method is more effective than conventional simple cold storage in UW for pancreatic preservation before islet isolation. Clinical trials with the two-layer method are warranted.

Adenosine↗