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Biomedical subjects

T Sano

Publications and source records attributed to T Sano.

At least 289 records · Page 16Linked to original sources

Surgical treatment for gastric leiomyosarcoma.

BACKGROUND: Gastric leiomyosarcoma is an uncommon disease, and the optimal treatment has not been established. In order to better define the optimal surgical treatment, we retrospectively analyzed our experience with these tumors. METHODS: Records of 103 patients, who underwent surgery between 1972 and 1997 were reviewed. RESULTS: The upper third of stomach was the most frequent site of disease (66 cases). Seventy one tumors were smaller than 50 mm. Forty patients had ulcerated tumors. Twenty nine of 33 tumors had an inhomogeneous pattern on endoscopic ultrasonography. Nodal involvement was not observed in our series. The most common surgery was wedge resection, performed in 68 patients. The 5-year disease-specific survival rate after curative resection was 93.0% overall, 87.5% after gastrectomy, and 95.0% after wedge resection. 5 year survival rate was worse in patients with ulcer than those without ulcer (87.1% vs. 96.3%, p < 0.01). No patient with a tumor smaller than 3 cm died from the disease. The dominant mode of recurrence was liver and peritoneal metastasis. No lymph node recurrence was observed. CONCLUSIONS: Surgery is indicated for tumors larger than 3 cm, with rapid growth, with inhomogeneous US pattern, or with ulceration. Wedge resection is the preferred treatment.

Disease-Free Survival↗

Another critical region for deletion of 22q11: a study of 100 patients.

Deletions at 22q11.1-q11.2 present with variable manifestations usually referred to as DiGeorge or velo-cardio-facial syndrome. We previously reported that deletions observed in patients with the syndrome can be subgrouped into three types (common large deletion, proximal deletion, and distal deletion) and demonstrated the presence of a second critical region for the syndrome. In order to characterize further the second critical region, a 22q11 deletion map was constructed from the data of 100 patients, using 12 DNA markers scattered in the common large deletion, and then a phenotype-genotype correlation was analyzed. The second critical region was found to correspond to the distal deletion encompassing the HCF2, cHKAD26, and D22S935 loci, and the proximal and distal deletions do not overlap each other. Although it seems that this condition is a contiguous gene syndrome, the phenotype of patients with these two types of deletion was indistinguishable from that of patients with the common large deletion. Thus, it is plausible that several genes located in the two segments corresponding to the two deleted regions are involved in the same developmental pathway or in an extremely long-range position effect.

Chromosome Deletion↗

A domain for G protein coupling in carboxyl-terminal tail of rat angiotensin II receptor type 1A.

To delineate domains essential for Gq protein coupling in the C-terminal region (C-tail) of rat angiotensin II (Ang II) receptor type 1A (AT1A), we modified the putative cytosolic regions of the receptor by truncation or alanine substitution and determined resultant changes in the guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) effect on Ang II binding and inositol trisphosphate production by the agonist. Independently, we studied the effect of synthetic C-tail peptides (P-5) and its alanine substitution analogs on [35S]GTPgammaS binding to Gq. Effects of GTPgammaS on Ang II binding (shift to a low affinity form) and inositol trisphosphate production in the deletional mutant receptor 1-317 AT1A was similar to wild type AT1A, whereas in shorter C-terminal deletion mutants 1-309, 1-311, 1-312, 1-313 AT1A, and substitutional mutants Y312A, F313A, and L314A these activities were markedly reduced. The binding of [35S]GTPgammaS to Gq was promoted by the synthetic C-terminal peptide P-5 but not when mutated at Tyr312, Phe313, or Leu314. Results indicate that Tyr312, Phe313, and Leu314 in cytosolic carboxyl-terminal region of rat AT1A are essential for coupling and activation of Gq.

Amino Acid Sequence↗

Induction of transplantation tolerance in adult rats by vascularized spleen transplantation.

It was demonstrated by Bitter-Seurmann et al. that tolerance to subsequent skin allografts can be brought about, in some rat strain combinations, by heterotopic spleen allografts. We report here that in adult rats, tolerance can be also induced by vascularized spleen allografts using various strain combinations. DA (RT1av1) rats always accepted major histocompatible complex (MHC)-compatible but minor histocompatibility antigen (miH)-incompatible ACI (RT1av1) spleen grafts spontaneously, and further that those DA rats bearing ACI spleen grafts accepted subsequent ACI skin grafts indefinitely. In contrast, Fischer 344 (RT1lvl) rats always accepted not only the "weak" MHC-incompatible Lewis (RT1l) spleen grafts but also subsequent Lewis skin grafts indefinitely, when recipients were administered a short course of FK506 only at the time of primary spleen transplantation. Furthermore, in a number of MHC- and miH-incompatible strain combinations, recipients always accepted primary spleen grafts indefinitely when given a short course of FK506, but those recipients bearing donor spleens revealed split tolerance, that is, rejected subsequent donor-specific skin grafts but accepted heart grafts indefinitely. We conclude that the spleen seems to be a possible organ to induce transplantation tolerance, and that even if the MHC and miH are mismatched, unresponsiveness to at least heart grafts can be achieved by the administration of additional FK506 at the time of spleen transplantation.

Animals↗

Anatomic features and surgical strategies in double-outlet right ventricle.

BACKGROUND: The objective of this study was to review anatomic features and surgical strategies in children with double-outlet right ventricle (DORV) and to assess risk factors for early mortality. METHODS AND RESULTS: Records were reviewed of all children with DORV undergoing surgery between 1978 and 1993. Noncomplex patients (group 1) had atrioventricular (AV) concordance, a single ventricular septal defect (VSD), balanced ventricles, no straddling AV valves, and no major pulmonary artery anomaly. Group 2 (complex) comprised all remaining patients. Independent risk factors analyzed included location of the main VSD, presence of additional VSDs, coarctation, ventricular outflow obstruction, ventricular hypoplasia, age at operation, operation before 1985, previous palliation, and type of definitive operation. Of 193 patients, 117 were in group 1 and 76 in group 2. In 148 patients, biventricular repair was undertaken, including 111 of 117 group 1 patients and 37 of 76 group 2 patients. Early mortality was higher among group 2 patients undergoing biventricular repair than among group 1 patients (8 of 37 versus 4 of 111, P<.005) and higher than group 2 patients undergoing a Fontan procedure (none of 29, P<.01). Aortic arch obstruction, operation before 1985, and multiple VSDs were significant risk factors for mortality. Age <1 month (P<.05) and multiple VSDs (P<.005) were independent risk factors after definitive repair. Up-to-date follow-up is available on 144 surviving patients, with 127 (88%) in New York Heart Association class I and the remaining 17 in class II. Overall 10-year survival probability was 81%, whereas probability of survival, free from reoperation (after definitive surgery), was 65% at 10 years. CONCLUSIONS: Biventricular repair can be achieved in most patients with DORV with low risk. In complex DORV, a Fontan procedure is associated with a lower surgical mortality.

Adolescent↗

Engineering subunit association of multisubunit proteins: a dimeric streptavidin.

A dimeric streptavidin has been designed by molecular modeling using effective binding free energy calculations that decompose the binding free energy into electrostatic, desolvation, and side chain entropy loss terms. A histidine-127 --> aspartic acid (H127D) mutation was sufficient to introduce electrostatic repulsion between subunits that prevents the formation of the natural tetramer. However, the high hydrophobicity of the dimer-dimer interface, which would be exposed to solvent in a dimeric streptavidin, suggests that the resulting molecule would have very low solubility in aqueous media. In agreement with the calculations, a streptavidin containing the H127D mutation formed insoluble aggregates. Thus, the major design goal was to reduce the hydrophobicity of the dimer-dimer interface while maintaining the fundamental structure. Free energy calculations suggested that the hydrophobicity of the dimer-dimer interface could be reduced significantly by deleting a loop from G113 through W120 that should have no apparent contact with biotin in a dimeric molecule. The resulting protein, containing both the H127D mutation and the loop deletion, formed a soluble dimeric streptavidin in the presence of biotin.

Aspartic Acid↗

A new approach for containment of microorganisms: dual control of streptavidin expression by antisense RNA and the T7 transcription system.

The use of microorganisms in the open environment would be of less concern if they were endowed with programmed self-destruction mechanisms. Here, we propose a new genetic design to increase the effectiveness of cell suicide systems. It ensures very tight control of the derepression of cell death by the combination of the bacteriophage T7 RNA polymerase-lysozyme system and an inducible synthesis of antisense RNA and the Escherichia coli LacI repressor. Functionality of this regulatory concept was tested by applying it to containment of Gram-negative bacteria, based on the conditional expression of the lethal Streptomyces avidinii streptavidin gene. Toxicity of streptavidin is derived from its exceptionally high binding affinity for an essential prosthetic group, D-biotin. The entire construct was designed to allow the soil bacterium Pseudomonas putida to survive only in the presence of aromatic hydrocarbons and their derivatives which it can degrade. Under favorable growth conditions, clones escaping killing appeared at frequencies of only 10(-7)-10(-8) per cell per generation. The general requirement for biotin through the living world should make streptavidin-based conditional lethal designs applicable to a broad range of containment strategies.

Bacterial Proteins↗

Total gastrectomy for primary gastric lymphoma at stages IE and IIE: a prospective study of fifty cases.

BACKGROUND: Treatment of primary gastric lymphoma at Ann Arbor stage IE or IIE is controversial. Randomized trials to compare various modalities are not feasible because of the rarity of this disease. We have prospectively treated patients by means of primary surgery to achieve complete local control and accurate staging. METHODS: Between 1987 and 1995, 50 patients with stage IE or IIE gastric lymphoma were prospectively treated by total gastrectomy with systematic lymphadenectomy. When nodal metastases were histologically confirmed or the resection was noncurative, chemotherapy was added. Intragastric tumor spread, lymph node metastasis, and treatment results were examined. RESULTS: Resection was potentially curative in 48 cases. There were no operative deaths. Histologically, the middle third of the stomach was most frequently involved. Either the proximal two thirds or the entire stomach was involved in 62% of all patients. Lymph node metastasis was demonstrated in 25 patients. The deeper the tumor invasion in the gastric wall, the more frequent and distant the nodal involvement. The 5-year survival rate was 85.6%, excluding one death caused by heart disease. CONCLUSIONS: Primary surgery followed by chemotherapy in selected cases is an appropriate strategy for primary gastric lymphoma in patients in whom this regimen can be safely carried out.

Adult↗

Epithelioid angiosarcoma of bone.

Angiosarcoma of bone is a rare, high-grade sarcoma of vascular origin. This article describes an epithelioid angiosarcoma in the humerus of a 48-year-old man. A multilocular osteolytic lesion with undefined margins and destroyed cortical and medullary bone, associated with a large soft tissue mass was demonstrated radiologically in the proximal metaphysis of the right humerus. The tumor, resected by amputation, was composed mostly of proliferating malignant cells with an epithelioid morphology. It had a predominantly sheet-like growth pattern, and an occasional pseudoglandular or alveolar arrangement, mimicking an adenocarcinoma. The dilated anastomotic vascular spaces lined by epithelioid endothelial cells and the intracytoplasmic lumina/vacuoles that sometimes contained erythrocytes suggested focal endothelial differentiation. On immunohistochemical investigation, many neoplastic cells expressed cytokeratin and endothelial markers: factor-VIII related antigen, CD31, and UEA-I. The ultrastructure of the tumor was consistent with that of an angiosarcoma. Our patient died of disease shortly after the diagnosis, implying an aggressive clinical course. Awareness of the existence of skeletal epithelioid angiosarcoma, combined with the identification of intracytoplasmic lumina, or at least small vasoformative foci, and immunohistochemical positivity for endothelial markers provide the best guide for distinguishing this tumor from metastatic carcinomas.

Biomarkers, Tumor↗

Effect of hot water extract of Chlorella vulgaris on cytokine expression patterns in mice with murine acquired immunodeficiency syndrome after infection with Listeria monocytogenes.

We have previously reported that oral administration of hot water extract of Chlorella vulgaris (CVE) enhances resistance to Listeria monocytogenes through augmentation of Listeria-specific cell-mediated immunity in normal mice and mice with murine acquired immunodeficiency syndrome (MAIDS) caused by murine leukemia virus (MuLV) LP-BM5. To elucidate the mechanisms whereby CVE augments the cell-mediated immunity, we examined the expression patterns of mRNA for cytokines in normal and MAIDS mice given CVE orally after L. monocytogenes infection. The expression levels of IL-1 alpha, IL-12, GM-CSF, MIP and TNF alpha genes were significantly augmented in the peritoneal adherent cells by oral administration of CVE for 2 weeks before Listeria infection. The expression levels of gamma IFN and IL-12 mRNA were significantly higher in the spleen after Listeria infection in CVE-treated mice than in normal mice, while the expression of IL-10 mRNA in the spleen was decreased by CVE administration. In MAIDS mice, oral administration of CVE also augmented the expression of gamma IFN and IL-12 mRNA in the spleen after Listeria infection, while it rather reduced the expression of IL-10 mRNA. These results suggest that CVE may preferentially augment THI responses against Listeria via activation of macrophages to produce IL-12 and enhance host defence against Listeria infection both in normal and MAIDS mice.

Animals↗

Exercise training in Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus: effects on the B-cell mass, insulin content and fibrosis in the pancreas.

The effects of exercise on alterations in the amount of B-cell mass, insulin content and fibrous tissue present in the pancreas were examined for a diabetic state induced by a 70% pancreatectomy and a prediabetic state in Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model for the spontaneous development of non-insulin-dependent diabetes mellitus (NIDDM). The rats (5-weeks old) were trained either by a 6-week running program or sedentary controls, and at 6-weeks of age, received either a 70% pancreatectomy or a sham-pancreatectomy (sham). As in our previous report, persistent hyperglycemia was detected after surgery for both trained pancreatectomized (Px) and sedentary Px groups. In the nondiabetic sham rats, exercise training resulted in a significantly smaller increase in body weight and beneficial effects on the pancreas as reflected by an increase in pancreatic volume, accompanied by increases in B-cell mass and insulin content as well as less connective tissue in the pancreas compared with the sedentary nondiabetic sham rats. The effect was not sufficient to improve sustained hyperglycemia in the trained diabetic Px rats. This is probably due to a decreased capacity for B-cell proliferation in response to an increased demand for insulin. Although exercise failed to improve this inherent defect in B-cell proliferation, it ameliorated the further deterioration of the pancreas which occurred with hyperglycemia, and resulted in a higher quantity of insulin stored per milligram of B-cell mass (as function of B-cell mass) and less fibrosis in the pancreas, compared with the sedentary diabetic Px rats. The findings of the present study suggest that exercise training has a beneficial effect on the pancreas in the nondiabetic state, and also exerts some positive effects in the diabetic state in this model rat.

Animals↗

A prospective study of surgery and adjuvant chemotherapy for primary gastric lymphoma stage II.

The standard management of primary gastric lymphoma (PGL) (stage II) has not been established despite the use of various treatment modalities. The present prospective trial of combined surgery and chemotherapy for the treatment of PGL (stage II) included 25 consecutive patients treated between July 1978 and December 1993. Twenty-one patients were treated with total gastrectomy and four with partial gastrectomy; this was followed by post-operative chemotherapy with m-VEPA (vincristine, cyclophosphamide, prednisolone and doxorubicin), followed by consolidation chemotherapy with VEMP (vindesine, cyclophosphamide, methotrexate and prednisolone) or VQEP (vindesine, carbazilquinone, cyclophosphamide and prednisolone). Twenty-one of the 25 patients who completed post-operative chemotherapy were free of relapse 26-203 (median 94) months after the gastrectomy. Of the four patients who did not complete the projected chemotherapy, two relapsed and died of lymphoma. Another patient with recurrent lymphoma died in an accident, and the fourth patient was in remission at 54 months after surgery. The post-operative overall and disease-free survival rates at 10 years for the 25 evaluable patients were 81.6% and 92.0% respectively. Major surgical complications and treatment-related death after chemotherapy were not observed. PGL (stage II) appears to be curable when treated with gastrectomy and adjuvant chemotherapy.

Adult↗

Transgenic potato expressing a double-stranded RNA-specific ribonuclease is resistant to potato spindle tuber viroid.

We have produced transgenic potato lines expressing the yeast-derived double-stranded RNA-specific ribonuclease pac1. Five lines of pac1 potato (Solanum tuberosum L., cultivar Russet Burbank) challenged with potato spindle tuber viroid (PSTVd) suppressed PSTVd infection and accumulation. All of the progeny potato tubers produced by resistant plants were also free of PSTVd. Because the pac1 gene product digested PSTVd in vitro, double-stranded regions in PSTVd molecule and/or replicative intermediates may be targeted by pac1 gene product in the transgenic potato plant.

Endoribonucleases↗