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Biomedical subjects

A Kobayashi

Publications and source records attributed to A Kobayashi.

At least 217 records · Page 12Linked to original sources

Capsaicin activates heat loss and heat production simultaneously and independently in rats.

Subcutaneous administration of capsaicin (5 mg/kg) immediately increased the temperature of the tail skin (Tsk) for 2 h in urethan-anesthetized rats, suggesting an increase in heat loss. O2 consumption, an index of heat production, also immediately increased after the capsaicin injection, and this increase lasted for >10 h. Colonic temperature (Tco) decreased within 1 h after the injection, and this decrease was followed by a long-lasting hyperthermic period. Adrenal demedullation largely attenuated the capsaicin-induced increase in O2 consumption, and sympathetic denervation of the interscapular brown adipose tissue partly attenuated the increase in O2 consumption. However, capsaicin-induced heat loss was normal in these rats. In rats with cutaneous vasodilation maximized by warming and administration of hexamethonium, capsaicin did not further increase Tsk but normally induced heat production, and Tco gradually rose without a hypothermic period. Thus capsaicin simultaneously increased heat loss and heat production, and inhibition of one response did not affect the other. These findings suggest that capsaicin simultaneously activates independent networks for heat loss and heat production.

Adipose Tissue, Brown↗

Surgical treatment for biliary carcinoma arising after pancreatoduodenectomy.

The clinicopathological features and surgical treatment of biliary carcinoma around the major hepatic duct confluence arising after pancreatoduodenectomy (PD) due to initial bile duct carcinoma are described in three patients. Occurrence of biliary carcinoma more than 12 years after initial surgery and a histological finding of cholangiocellular carcinoma mixed with hepatocellular carcinoma suggested metachronous incidence of biliary carcinoma after PD. Extended right hemihepatectomy with complete removal of the residual extrahepatic bile duct and segmental resection of the jejunal loop were carried out safely without operative death or severe postoperative complications. Two patients died of tumor recurrence 6 months after surgery, and the remaining patient is currently living a normal life without evidence of recurrence 17 months after surgery. These surgical procedures are a therapeutic option in patients with biliary carcinoma around the major hepatic duct confluence arising after PD.

Aged↗

Relationship between doubling time of liver metastases from colorectal carcinoma and residual primary cancer.

BACKGROUND: The doubling times of liver metastases were calculated in order to clarify their usefulness in predicting the presence of residual cancer in the abdominal cavity in patients who had undergone curative resection of primary colorectal cancer. PATIENTS AND METHODS: Tumor doubling times were calculated retrospectively in 22 patients by serial measurement of the size of their liver metastases. RESULTS: Patients with a tumor doubling time of less than 92.4 days had a significantly poorer prognosis than those with a doubling time more than or equal to 92.4 days (p < 0.05). Local recurrence or peritoneal dissemination was significantly more likely to occur when the tumor doubling time was less than 92.4 days than when it was more than or equal to 92.4 days (p < 0.01). CONCLUSION: The doubling time of hepatic metastases in patients with colorectal carcinoma may be a useful prognostic indicator, with patients who have a shorter tumor doubling time carrying a greater risk of residual primary cancer in the abdominal cavity.

Cell Division↗

Selective inhibition of Src protein tyrosine kinase by analogues of 5-S-glutathionyl-beta-alanyl-L-dopa.

Twelve analogues of the antibacterial phenolic peptide 5-S-glutathionyl-beta-alanyl-L-dopa (5-S-GA-L-D: 1) were synthesized via orthoquinones using tyrosinase. Several synthesized compounds inhibited the v-Src autophosphorylation tyrosine kinase reaction with an IC50 value comparable to that of herbimycin. The inhibition of c-Src substrate phosphorylation was much less active than v-Src autophosphorylation inhibition. The analogues showed no effects on substrate phosphorylation by epidermal growth factor receptor (EGFR), and this selectivity is the most characteristic feature of the analogues (1-12).

Enzyme Inhibitors↗

Production of ethyl (R)-2-hydroxy-4-phenylbutanoate via reduction of ethyl 2-oxo-4-phenylbutanoate in an interface bioreactor.

Ethyl (R)-2-hydroxy-4-phenylbutanoate [(R)-EHPB], a useful intermediate for the synthesis of various anti-hypertension drugs, was produced via microbial reduction of ethyl 2-oxo-4-phenylbutanoate [EOPB] in an interface bioreactor. Rhodotorula minuta IFO 0920 and Candida holmii KPY 12402 were selected as the best type culture and isolated yeasts, respectively. The highest enantiomeric excess of (R)-EHPB produced by R. minuta and C. holmii were 95 and 94%, respectively. C. holmii was used for the reduction of EOPB in a pad-packed interface bioreactor (inner volume, 3 liter). After incubation for 4 days, 4.4 g of (R)-EHPB was obtained via extraction with methanol followed by column chromatography. The overall yield, chemical purity, and enantiomeric excess of (R)-EHPB were 58%, 99.1%, and 90%, respectively.

Agar↗

Expression of inducible nitric oxide synthase and inflammatory cytokines in alveolar macrophages of ARDS following sepsis.

STUDY OBJECTIVE: The objective of this study was to evaluate the role of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines in alveolar macrophages (AMs) in the pathogenesis of ARDS following sepsis. SETTING: ICU in a university hospital. DESIGN: Prospective exploratory, open-labeled study was carried out. PATIENTS: A total of 24 patients were investigated: 8 patients diagnosed as having ARDS following sepsis (ARDS group); 8 patients under general anesthesia in the operating room whose lung functions were normal (control group); and 8 patients who were intubated and artificially ventilated for 1 week in the ICU whose lung functions were not deteriorated without fulfilling the ARDS criteria and whose general state fulfilled the sepsis criteria (long-term ventilation group, or LTV group). MEASUREMENTS AND RESULTS: The expression of iNOS, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) in AMs obtained from BAL fluid (BALF) was determined by the immunofluorescent technique. We observed the significant expression of iNOS, IL-6, and IL-8 only in the ARDS group. Meanwhile, NOx (the sum of NO2- + NO3-) was elevated in the BALF supernatant, and IL-6 and IL-8 levels in both the BALF supernatant and the serum were also elevated in the ARDS group. No significant expressions were detected in the control and the LTV group. CONCLUSIONS: The result that iNOS was detected only in ARDS patients following sepsis suggests that iNOS together with proinflammatory cytokines produced by AMs might play a pivotal role in the pathogenesis of acute lung injury and be useful for monitoring disorders in the lung in such conditions.

Adult↗

Vitamin D receptor genotype is associated with cortical bone loss in Japanese patients with primary hyperparathyroidism.

Vitamin D receptor (VDR) genotype was determined in 66 Japanese patients with primary hyperparathyroidism (pHPT). In contrast to previous report showing an association between VDR genotype bb and the development of pHPT in a Swedish population, we did not find any differences in the frequencies of the VDR genotypes between pHPT and the control. The bone mineral density in the radius was significantly lower (Z score, -1.723 +/- 1.819) in bb genotype than in BB/Bb genotype (+0.255 +/- 2.344) in pHPT patients. Based on the fact that PTH requires vitamin D3 to take effect on calcium mobilization from bone, it is possible that VDR polymorphism may influence the PTH action on bone.

Adult↗

[A case of cardiac rupture which occurred 34 years after mastectomy].

We experienced a case of cardiac rupture associated with mastectomy. A 78-year-old woman, who underwent left mastectomy 34 years before, complained of bleeding from a chest tumor located on the operative scar of the left mastectomy and postoperative irradiation. The tumor was noticed 10 months prior and became larger and repeated bleeding. It was first diagnosed as hemangioma by nearby practitioner. She was referred to the university hospital because of uncontrollable bleeding from the tumor. Without definite diagnosis, the tumor ruptured suddenly 52 days after the admission and the patient lapsed into the state of hemorrhagic shock and cardiopulmonary resuscitation was performed. Following emergency operation was performed on stand-by of cardiopulmonary bypass (CPB). The operation was successful with the aid of partial CPB and the final diagnosis of cardiac rupture was determined during the surgery. A case of cardiac rupture after mastectomy and radiation is rare, and this is the first report in the Japanese literature to date. The patient could be saved because the operation was performed on stand-by CPB.

Aged↗

Wear and osteolysis in total joint replacements.

UNLABELLED: This presentation summarizes the results of our recent studies on the pathogenesis of osteolysis around total joint arthroplasties. First, interface tissues with adjacent bone were retrieved and histopathologically investigated with reference to the cells on the bone surface. Secondly, polyethylene particles were extracted with the tissue digestion method and characterized with scanning electron microscopy. Finally, an animal model for osteolysis was created and various interface conditions were compared concerning their resistance to particle migration. Histopathological examinations demonstrated that active bone formation, regarded as a repair process, was the commonest feature, even in revised cases. They also highlighted the role played by macrophages, not as cells producing inflammatory mediators which could activate osteoclasts, but as cells primarily responsible for the bone loss in osteolytic lesions. Among the particle species present, only polyethylene particles were shown to play a significant role in macrophage recruitment and subsequent osteolysis. A quantitative extraction of polyethylene particles showed a significant difference in the "number" of particles between osteolysis positive and negative cases whereas the "sizes" of particles were similar in these two groups. The critical number of particles for osteolysis was around 1 x 10(10) particles/g tissue and the cellular reaction against phagocytosable particles accumulated over this concentration may be the prerequisite for progression of osteolysis. The animal model for osteolysis indicated that the progression of osteolysis depends on the integrity of the bone-implant interface. We suggest that the solid fixation of the prosthesis performed by current techniques (e.g., improved cementing technique, hydroxyapatite coating) is beneficial for preventing particle migration and subsequent osteolysis. CLINICAL RELEVANCE: Osteolysis induced by particulate wear debris from implant materials has been recognized as the major cause of long-term failure in total joint replacements. However, the development of preventive measures for this phenomenon has not been successful because the mechanism in which wear particles cause osteolysis is not quite clear. On the basis of results obtained in this study, we believe that the basic strategy for addressing the problem of osteolysis is to reduce the "number" of accumulated wear particles in the interface tissues. This could be achieved either by improving the materials or the geometry of the articulating counterface. Another possibility is to increase the integrity of the bone-implant interface to prevent particle migration. It is important to note that pre-clinical testing of materials and prosthetic designs should include an analysis of the characteristics of the particle generated (e.g., size and number). The widespread bone formation, even in revised cases, is encouraging in view of "conservative treatment" of aseptic loosening. Assuming that bone loss in aseptic loosening is not a remorseless process, some form of intervention, whether mechanical or pharmacological, might be possible to tip the balance more in favour of bone formation than resorption. A comprehensive understanding of the bone reactions in osteolysis, including the basic mechanisms of bone loss, shown in this study, are decisive for the development of preventive measures that may minimize the clinical impact of this phenomenon.

Animals↗

Staged hepatectomy after emergency transcatheter arterial embolization for ruptured hepatocellular carcinoma.

BACKGROUND: Staged hepatectomy after emergency transcatheter arterial embolization (TAE) has been advocated in ruptured hepatocellular carcinoma (HCC). However, there have been no reports of clinical series of this strategy. The purpose of this study was to evaluate the protocol of this therapeutic strategy. METHODS: Sixteen patients with suspected rupture of HCC were included in the study. After emergency TAE, tumor resectability was assessed, followed by staged hepatectomy or repeated TAE. The patients were reevaluated with regard to rupture of HCCs. RESULTS: Primary hemostasis was achieved successfully in all patients. Eleven patients were finally judged to have experienced HCC rupture. Seven of them underwent staged hepatectomy; the other four underwent repeated TAE because their tumors were considered unresectable. Survival time tended to be longer, but not to a significant extent, in patients who underwent hepatectomy (range, 139 to 1527 days; median, 375 days) than in those treated by TAE alone (range, 43 to 1317 days; median, 158 days). CONCLUSIONS: Staged hepatectomy after TAE is a rational treatment for patients with ruptured HCC. Although TAE is highly effective for initial hemostasis, hepatectomy appears to provide better long-term survival.

Adult↗

[Effect of combination chemotherapy of low-dose CDDP. Continuous infusion of 5-FU, and intermittent CPT-11 administration for 2 advanced pancreatic cancer cases with liver metastasis].

For advanced pancreatic cancer, there is no typical chemotherapy regimen non single chemotherapeutic agent. For example, 5-FU, Doxorubicin, MMC and Epirubicin obtained only 15-24% efficacy, and general combination chemotherapy was FAM, 5-FU+CDDP and 5-FU+Leucovorin for pancreatic cancer. Generally, in pancreatic cancer cases the performance status was poor, and most could not endure the chemotherapy regimen. 5-FU continuous infusion and low-dose CDDP regimen were effective and showed fewer side effects for pancreatic cancer. Then, for 2 cases of advanced pancreatic cancer with liver metastasis, 5-FU continuous infusion + low-dose CDDP + intermittent CPT-11 administration (5-FU 500 mg/body/24 hr + CDDP 5mg x 5 days-6 courses + CPT-11 100 mg-125 mg-150 mg, bolus i.v. intermittently) was effective. Thus, this regimen could well be effective for advanced pancreatic carcinoma.

Adenocarcinoma↗

[Bioelectrical impedance analysis of body composition in patients with pulmonary emphysema].

In this study we utilized bioelectrical impedance analysis (BIA) to compare the body composition of 36 stable pulmonary emphysema (PE) patients with 19 healthy controls. We compared the PE patients and healthy controls in terms of fat-free mass (FFM) and body fat (BF) as percentages of ideal body weight (FFM/IBW, BF/IBW). FFM/IBW and BF/IBW were significantly lower in the PE patients than in the controls (75.0 +/- 9.8% vs. 85.2 +/- 7.3%, p < 0.001 and 11.8 +/- 6.4% vs. 16.7 +/- 7.7%, p < 0.05, respectively). We divided the PE patients into two subgroups according to FFM, then investigated the relationships between FFM and skeletal muscle strength, and between FFM and respiratory muscle strength. In patients with reduced FFM (FFM < 43.5 kg) grip strength as an index of skeletal muscle strength was significantly lower than in patients without reduced FFM (FFM > or = 43.5 kg) (25.7 +/- 7.8 kg vs. 36.2 +/- 7.2 kg, p < 0.005). As indexes of respiratory muscle strength, maximal expiratory pressure (PEmax) and maximal inspiratory pressure (PImax) were lower in the patients with reduced of FFM, but not to a statistically significant degree (49.6 +/- 20.8 cm H2O vs. 58.7 +/- 23.9 cm H2O and 40.5 +/- 19.2 cm H2O vs. 50.2 +/- 22.1 cm H2O, respectively). In the PE patients, FFM correlated closely with vital capacity (r = 0.528, p < 0.001), forced vital capacity (FVC) (r = 0.531, p < 0.001), FEV1.0 (r = 0.554, p < 0.001), FEV1.0/FVC (r = 0.467, p < 0.005), RV/TLC (r = -0.395, p < 0.05), DLco (r = 0.770, p < 0.001), and DLco/VA (r = 0.622, p < 0.001). However no correlation was observed between BF and any of the measures of lung function. The findings of our study suggest that FFM correlates with skeletal muscle strength, respiratory muscle strength and some measures of lung function in patients with PE, and that assessments of body composition are valuable to their clinical management.

Aged↗

[Thoracoscopic lung volume reduction surgery for emphysema].

In recent years, several institutions have been performing lung volume reduction surgery (LVRS) for emphysema, and have reported that LVRS is effective for patients with emphysema that is resistant to other forms of therapy. However, questions remain about the relationship between the extent of resection and the therapeutic benefits. In our study, 15 men with emphysema underwent thoracoscopic LVRS. We analyzed the effects of LVRS on pulmonary function, exercise performance, and subjective symptoms after both bilateral and unilateral procedures. The patients who underwent the bilateral procedure, demonstrated significantly improved pulmonary function and exercise performance and relief of their subjective symptoms. Those who underwent the unilateral procedure, demonstrated significantly improved pulmonary function and relief of their subjective symptoms. Forced expiratory volume in 1.0 second increased by an average of 51% after the bilateral procedure, and 17% after the unilateral procedure. We conclude that thoracoscopic LVRS is an effective treatment for emphysema, especially with the bilateral procedure.

Aged↗

Inhibition of protein tyrosine kinase by 5-S-GAD, a novel antibacterial substance from an insect.

The effect of N-beta-alanyl-5-S-glutathionyl-dopa (5-S-GAD), a compound originally isolated from Sarcophaga peregrina (a flesh fly) as an antibacterial substance, on protein phosphorylation was examined using v-src-transformed NIH3T3 cell lysates. 5-S-GAD was found to inhibit tyrosine phosphorylation of protein tyrosine kinase v-src, but not serine/threonine phosphorylation of protein kinase C. The potency of this compound was comparable to that of herbimycin A. Our results suggested that a substitution at position 5 of the catechol in 5-S-GAD with the sulfur of cysteine is essential for 5-S-GAD to inhibit protein tyrosine kinase v-src.

3T3 Cells↗

Monoclonal antibodies against pupa-specific surface antigens of Sarcophaga peregrina (flesh fly) hemocytes.

Monoclonal antibodies were raised against pupal hemocytes of Sarcophaga peregrina. Four of the antibodies tested bound specifically to the surface of live pupal hemocytes, and these hemocytes appeared to be granulocytes from their morphology. The antigen recognized by one of the antibodies, MAb 9C8, was considered to be a membrane protein with a molecular mass of 120-kDa. Another antibody, MAb 9F3, was found to recognize possibly the same 120-kDa protein and two cytoplasmic proteins commonly present in both pupal and larval hemocytes.

Animals↗

A point mutation responsible for defective function of the aryl-hydrocarbon-receptor nuclear translocator in mutant Hepa-1c1c7 cells.

A 3,4-benzopyrene-resistant mutant clone (c4) of the mouse hepatoma Hepa-1c1c7 cell line was examined for the mutation that causes the defective function of aryl-hydrocarbon receptor (AHR) nuclear translocator (Arnt). Arnt dimerizes with AHR and mediates the induction signal of aryl-hydrocarbon hydroxylase activity. The Arnt cDNAs of c4 cells were cloned by reverse-transcription/PCR to compare the sequences with that of wild-type Arnt cDNA. The Arnt cDNA of c4 cells was found to have a single point mutation, leading to replacement of Gly326 with Asp between two internal repeats in the highly conserved Per-Arnt-Sim (PAS) domain, PAS A and PAS B. The inability of [Asp326]Arnt/AHR heterodimers to enhance reporter gene transcription under the control of the CYP1A1 gene promoter and enhancer confirmed that the G326-->D substitution was a causative mutation. While fluorescence microscopy and coimmunoprecipitation experiments showed that this mutant form of Arnt was not changed from wild-type Arnt in terms of nuclear localization or heterodimer formation with AHR, the binding activity of the [Asp326]Arnt x AHR heterodimer to the xenobiotic-responsive element was reduced markedly. Determination of the turnover rate in COS-7 cells transfected with expression plasmids for mutant Arnt or normal Arnt showed that the mutant protein turned over with an accelerated rate compared with that of the normal. Moreover, the mutant protein displayed increased proteolytic digestibility in vitro with various proteases.

Amino Acid Sequence↗