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Biomedical subjects

H Kinoshita

Publications and source records attributed to H Kinoshita.

At least 73 records · Page 4Linked to original sources
PubMed2001

Mild alkalinization and acidification differentially modify the effects of lidocaine or mexiletine on vasorelaxation mediated by ATP-sensitive K+ channels.

BACKGROUND: The previous study by the authors showed that the class Ib antiarrhythmic drug lidocaine impairs but mexiletine augments vasorelaxation mediated by adenosine triphosphate-sensitive K+ channels. Lidocaine and mexiletine have different values of the negative logarithm of the drug-proton dissociation constant, indicating that the ion channel-blocking effects of these drugs under different pH levels may vary. However, the role of pH in the effects of lidocaine and mexiletine on vasodilation mediated by K+ channels has not been studied. Therefore, the current study was designed to examine whether the inhibition and augmentation of vasorelaxation in response to an adenosine triphosphate-sensitive K+ channel opener, levcromakalim, by the clinically relevant concentrations of lidocaine or mexiletine are modified by mild alkalinization or acidification in the isolated rat aorta. METHODS: Rings of the rat aorta without endothelium were suspended for isometric force recording. Three types of modified Krebs-Ringer solutions (pH 7.2, 7.4, and 7.6) were prepared by changing the composition of NaCl and NaHCO3. During contractions in response to phenylephrine (3 x 10(-7) M), relaxations in response to levcromakalim (10(-8) to 10(-5) M) were obtained. Lidocaine (10(-5) to 10(-4) M), mexiletine (10(-5) to 10(-4) M), or glibenclamide (10(-5) M) was applied 15 min before addition of phenylephrine. RESULTS: Relaxations in response to levcromakalim, which are abolished by the selective adenosine triphosphate-sensitive K+ channel antagonist glibenclamide (10(-5) M), were not different among the three pH groups. In the normal Krebs-Ringer solution of pH 7.4, lidocaine significantly reduced these relaxations in a concentration-dependent fashion. Alkalinization of pH 7.6 augmented the inhibitory effect of lidocaine on these relaxations, whereas acidification of pH 7.2 substantially abolished this effect. In contrast, mexiletine pH independently augmented relaxations in response to levcromakalim. Glibenclamide (10(-5) M) abolished these relaxations in arteries treated with mexiletine (10(-4) M) in any pH group. CONCLUSIONS: These results suggest that even under conditions of such mild alkalosis or acidosis, vasorelaxation via adenosine triphosphate-sensitive K+ channels is dependent on pH in the presence of clinically relevant concentrations of lidocaine but not mexiletine.

ATP-Binding Cassette Transporters↗
PubMed2001

Reactivation of viral replication after liver resection in patients infected with hepatitis B virus.

OBJECTIVE: To investigate the mechanisms and risk factors underlying postoperative reactivation of hepatitis after liver resection for hepatitis B virus-related hepatocellular carcinoma. SUMMARY BACKGROUND DATA: Although risk factors for acute hepatic failure after liver resection have been reported in patients with chronic liver disease, the issue of reactivation of hepatitis B virus replication after liver resection is unresolved. METHODS: Fifty-five patients with hepatocellular carcinoma and hepatitis B surface antigen underwent liver resection. In 25 of these 55 patients, serum levels of hepatitis B virus DNA and the type of hepatitis B virus were determined before and after surgery. RESULTS: Postoperative hepatitis occurred in 13 of the 55 patients (24%). Reactivation of viral replication occurred after liver resection in 7 of the 25 patients tested, and alanine aminotransferase activity increased in 6 of these 7 patients. High preoperative alanine aminotransferase activity, high levels of hepatitis B virus DNA, presence of wild-type DNA, and detection of hepatitis B core antigen in hepatocytes, all features of the immune clearance phase in the natural course of hepatitis B virus infection with no surgery, were more likely to be found in patients with reactivation than in patients without reactivation. CONCLUSIONS: During the immune clearance phase of hepatitis B virus infection, especially the period of acute exacerbation, changes in serum hepatitis B virus DNA level should be monitored for early warnings of reactivation of viral replication, likely to cause severe postoperative hepatitis and acute hepatic failure.

Adult↗
PubMed2001

Influence of previous interferon therapy on recurrence after resection of hepatitis c virus-related hepatocellular carcinoma.

Interferon (IFN) therapy decreases the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV). One hundred and fifty-nine consecutive patients who underwent liver resection for HCV-related HCC were studied. In 17 (group 1) of the 159 patients, HCC was detected during or after IFN therapy. The incidences of recurrence after surgery in the group 1 patients and the other 142 patients (group 2) were compared. Eight patients had a complete response to IFN, 4 had a partial response, and 5 had no response. The proportion of patients without HCV viremia was significantly higher in the group 1 patients (P < 0.0001). The tumor-free survival rate was significantly higher in the group 1 patients (P = 0.0010). By multivariate analysis of various risk factors for recurrence, no previous IFN was a significant independent risk factor for recurrence (risk ratio = 6.336; 95%CI, 1.512 - 26.50). The patients with HCC who underwent IFN therapy previously are good candidates for liver resection because recurrence after the operation was rarely observed.

Aged↗
PubMed2001

Relationship of the microvascular type to the tumor size, arterialization and dedifferentiation of human hepatocellular carcinoma.

Unlike normal liver with the sinusoids, hepatocellular carcinomas (HCCs) possess capillaries. Whether these capillaries derive from the sinusoids remains unclear in human HCCs. This study aimed to examine sinusoidal capillarization in human HCCs and its relationship to the tumor size, arterialization and dedifferentiation. Thirty-eight HCCs with a diameter of 10 - 140 mm were pathologically and angiographically examined. By electron microscopy, the microvasculature of tumors was classified into sinusoidal, intermediate and capillary types, which were all negative, partially positive and all positive, respectively, for four parameters, i.e., endothelial defenestration, continuous basement membrane, lack of Kupffer cells, and lack of lipid-containing hepatic stellate cells. Well-, moderately and poorly differentiated HCCs displayed sinusoidal / intermediate / capillary types, intermediate / capillary types and only capillary type, respectively, suggesting the transition from the sinusoids to capillaries in well-differentiated (and probably moderately differentiated) HCCs. Furthermore, well-differentiated HCCs with a diameter of less than 30 mm often received preferential portal venous blood, while moderately and poorly differentiated ones were all supplied with arterial blood, indicating a relationship between dedifferentiation and arterialization. In contrast, the microvascular type displayed no significant relationship with tumor size or arterialization in well-differentiated HCCs. The present study has demonstrated that sinusoidal capillarization occurs in human well-differentiated HCCs and seems to be related to dedifferentiation of parenchymal tumor cells, but not to tumor size or arterialization.

Adult↗
PubMed2001

Effects of renal function on pharmacokinetics of recombinant human granulocyte colony-stimulating factor in lung cancer patients.

Animal studies suggest that the kidney is involved in the elimination of recombinant human granulocyte colony-stimulating factor (rhG-CSF), which is used for patients with neutropenia during cancer chemotherapy. Since anticancer drugs induce nephrotoxicity, it is important to clarify the role of the kidney in the pharmacokinetics of rhG-CSF in cancer patients. Our study was designed to evaluate the relationship between the pharmacokinetics of rhG-CSF and renal function in lung cancer patients compared to the absolute neutrophil count (ANC). The pharmacokinetic studies were conducted with 25 lung cancer patients. Following chemotherapy using platinum-based compounds, a bolus 5 microg of rhG-CSF/kg of body weight was intravenously injected from the first day of leukopenia or neutropenia. Pharmacokinetic parameters were estimated by fitting the concentration in serum-time data to a two-compartment model according to the population pharmacokinetics and the Bayesian method. Creatinine clearance (CL(CR)) was predicted by the Cockcroft-Gault formula. rhG-CSF clearance (CL(G-CSF)) correlated significantly with the ANC (r = 0.613; P < 0.001) and CL(CR) (r = 0.632; P < 0.001). Multiple linear regression analysis showed that the combination of the ANC and CL(CR) accounted for 57.4% of the variation of CL(G-CSF). In patients with an ANC of <1,000/microl, CL(CR) accounted for 72.9% of the variation of CL(G-CSF) (P < 0.001). Our findings suggest that renal function and neutrophil counts correlate with CL(G-CSF) and that the role of renal function in eliminating rhG-CSF is important in lung cancer patients with neutropenia.

Adult↗
PubMed2001

Identification of the varR gene as a transcriptional regulator of virginiamycin S resistance in Streptomyces virginiae.

A gene designated varR (for virginiae antibiotic resistance regulator) was identified in Streptomyces virginiae 89 bp downstream of a varS gene encoding a virginiamycin S (VS)-specific transporter. The deduced varR product showed high homology to repressors of the TetR family with a conserved helix-turn-helix DNA binding motif. Purified recombinant VarR protein was present as a dimer in vitro and showed clear DNA binding activity toward the varS promoter region. This binding was abolished by the presence of VS, suggesting that VarR regulates transcription of varS in a VS-dependent manner. Northern blot analysis revealed that varR was cotranscribed with upstream varS as a 2.4-kb transcript and that VS acted as an inducer of bicistronic transcription. Deletion analysis of the varS promoter region clarified two adjacent VarR binding sites in the varS promoter.

Amino Acid Sequence↗
PubMed2001

Lewis and Secretor gene effects on Lewis antigen and postnatal development of Lewis blood type.

Lewis (Le) and Secretor (Se) gene effects on postnatal change in Lewis antigens are described based on the quantitative analysis of Lewis antigens in blood. Genuine Lewis blood types were determined by Le and Se genotyping in DNA samples obtained from umbilical cord blood and infant blood. Lewis(a) (Le(a)) and Lewis(b) (Le(b)) antigen levels were measured by a time-resolved fluoroimmunoassay. We found that Lewis phenotypes in infants over 9 months of age agreed with the genuine types. In cord blood, the dosage effect of the Se gene on antigen levels was observed, but the Le gene effect was not observed. Both Se and Le gene effects were observed in newborn babies' blood 3-6 days after birth.

Aging↗
PubMed2001

Virologic and biochemical changes and prognosis after liver resection for hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND/AIMS: During the natural course of hepatitis B virus (HBV) infection, clearance of HB e antigen (HBeAg) and HB surface antigen (HBsAg) occurs with remission of liver disease. We investigated the effects of postoperative changes in virologic and biochemical parameters on the prognosis after liver resection for HBV-related hepatocellular carcinoma (HCC). METHODS: We investigated the relationship between postoperative changes in virologic and biochemical parameters and the incidence of intrahepatic recurrence and the outcome during a 3-year period following surgery in 30 HCC patients with HBsAg. RESULTS: The incidence of intrahepatic recurrence of HCC was significantly higher in patients with acute postoperative exacerbation of hepatitis (p = 0.0084), a sustained high serum concentration of HBV DNA (> or = 5.0 mEq/ml, p = 0.001), and sustained expression of HBsAg after surgery (p = 0.0421). A high serum concentration of HBV DNA was significantly associated with a shorter survival time (p = 0.0447) and the cause of death was recurrence of HCC. CONCLUSION: Patients with acute postoperative exacerbation of hepatitis, sustained HBsAg expression, and sustained high serum concentrations of HBV DNA after surgery may require more intensive postoperative monitoring for HCC recurrence.

Adult↗
PubMed2001

Successful treatment of dissemination of hepatocellular carcinoma to the pleura and diaphragm after percutaneous liver biopsy.

BACKGROUND/AIM: Treatment for dissemination of hepatocellular carcinoma to the pleura and diaphragm following percutaneous needle biopsy has not been established. METHODS: The case of a 57-year-old man who underwent percutaneous needle biopsy for liver tumor is presented. RESULTS: Ten months after resection of the tumor (moderately differentiated hepatocellular carcinoma), masses in the right pleural cavity and on the diaphragm were detected by computed tomography. Resections of the masses with surrounding tissue and the diaphragm and wedge resection of the right lung were performed. A wide range of the pleura and the diaphragm was coagulated with an argon beam coagulator. The patient is in good health without recurrence 4 years after the operation. CONCLUSION: Aggressive surgical treatment should be considered for patients with dissemination of hepatocellular carcinoma by needle biopsy when the lesions are limited.

Biopsy, Needle↗
PubMed2001

Treatment of adrenal metastases after hepatic resection of a hepatocellular carcinoma.

BACKGROUND: The adrenal gland is a common site of extrahepatic metastases from a hepatocellular carcinoma (HCC). However, treatment of adrenal metastases has not been well characterized. METHODS: Of 562 patients who underwent hepatic resection for a HCC, 91 developed extrahepatic metastases. We reviewed the medical records of 10 patients with adrenal metastases (9 males and 1 female; mean age 63 years at the time of hepatic resection). RESULTS: The mean diameter of the primary tumors was 5 cm, and all were located in the right lobe of the liver. The mean interval from hepatic resection to recurrence was 18 months. Seven patients underwent treatment of intrahepatic recurrence. To treat the adrenal metastases, surgical resection was performed in 4 patients, and transcatheter arterial embolization was performed in 1 patient. The patients treated had no other extrahepatic metastases. The mean diameter of the resected adrenal tumors was 6 cm. There was no hospital mortality. With surgical resection, 1 patient has been alive 63 months after recurrence. CONCLUSIONS: Adrenal metastases from a HCC were often large at the time of diagnosis. Since surgical resection was a safe procedure, and some patients could be alive for a long time, it should be performed whenever possible.

Adrenal Gland Neoplasms↗
PubMed2001

Expression of ovarian prolactin receptor in relation to hormonal changes during induction of ovulation in the rat.

We examined the relationships between the expression of the short and long forms of the prolactin (PRL) receptor (PRLR) mRNA in the ovary and changes in the levels of serum hormones such as sex steroid hormones and PRL during induction of ovulation in the rat. The expression of both forms of PRLR mRNA in the ovary was examined by Northern blot analysis in immature female rats treated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Ovarian tissues and blood samples were obtained before treatment, 24 and 48 h after PMSG injection and 4, 6, 8, 12, 24 and 48 h after hCG treatment. Serum levels of 17beta-estradiol, progesterone and PRL were determined by radioimmunoassay. Serum levels of 17beta-estradiol rapidly increased to a maximal level 48 h after PMSG injection and then rapidly declined until 4 h after hCG injection. Serum levels of progesterone gradually increased after PMSG treatment, markedly increased to 114.2 nmol/l 8 h after hCG treatment and remained high until 48 h after hCG treatment. The serum level of PRL peaked at 66.2 microg/l (p < 0.01) 48 h after PMSG injection, and a temporary decrease after hCG treatment was followed by a continuously high level from 8 to 48 h. The expression of the long form of PRLR mRNA increased significantly (p < 0.01) to 688% of the control level after PMSG treatment, while that of the short form increased to only 184% of the control level. The expression of the long form of PRLR-mRNA rapidly declined until 6 h and then gradually increased until 48 h after hCG treatment. On the other hand, the expression of the short form of PRLR mRNA decreased to a nadir 12 h after hCG injection and then increased significantly (p < 0.01) to 142% of the control level. Our results showed that the changes in the short and long forms of PRLR mRNA differed in a time-specific manner and that these two forms are involved in different functions in the rat ovary during induction of ovulation. It is thought that the long form of PRLR mRNA is involved in folliculogenesis, while the short form of PRLR mRNA may play an important role in the formation and maintenance of the corpus luteum in the rat ovulatory cycle.

Animals↗
PubMed2001

Efficacy of every-other-day administration of conjugated equine estrogen and medroxyprogesterone acetate on gonadotropin-releasing hormone agonists treatment in women with endometriosis.

We performed a randomized controlled study to determine the efficacy of add-backed therapy by every-other-day administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) on GnRH agonists (GnRH-a) treatment in Japanese women with symptomatic endometriosis. At the end of treatment, serum estrone and estradiol levels in the add-back group (n = 11) were significantly higher than those in the control group (n = 10). The assessment of Beecham classification by bimanual examination, serum CA-125 levels, and the frequency of genital bleeding revealed no significant differences between the two groups. The add-back group showed reduced Kupperman indices relative to those of the control group, and could prevent the loss of bone density. These findings led to a conclusion that GnRH-a therapy added back by every-other-day administration of 0.625 mg CEE and 2.5 mg MPA was a safe and effective treatment for Japanese women with endometriosis.

Adult↗
PubMed2001

The role of oxygen-derived free radicals in augmented relaxations to levcromakalim in the aorta from hypertensive rats.

Hydrogen peroxide and peroxynitrite induce relaxations via ATP-sensitive K+ channels, indicating that oxygen-derived free radicals may activate these channels. Levels of free radicals are increased throughout the arterial wall in animal models of atherosclerosis, and therefore, vasorelaxation via ATP-sensitive K+ channels may be augmented in chronic hypertension. The present study was designed to determine whether relaxations to an ATP-sensitive K+ channel opener, levcromakalim, are increased in the aorta from spontaneously hypertensive rats (SHR) and whether free radical scavengers reduce these relaxations. Rings of aortas without endothelium taken from age-matched Wistar-Kyoto rats (WKY) and SHR were suspended for isometric force recording. Relaxations to levcromakalim (10(-8) to 10(-5) M), which are abolished by glibenclamide (10(-5) M), were augmented in the aorta from SHR, compared to those in the aorta from WKY. In the aorta from SHR, catalase (1200 U/ml), but neither superoxide dismutase (150 U/ml) nor deferoxamine (10(-4) M), reduced relaxations to levcromakalim, whereas in the aorta from WKY, the free radical scavengers did not affect these relaxations. These results suggest that in chronic hypertension, vasorelaxation to an ATP-sensitive K+ channel opener is augmented and that hydrogen peroxide produced in smooth muscle cells may partly contribute to these relaxations.

Animals↗
PubMed2001

Haemorrhagic hepatic cyst: a differential diagnosis of cystic tumour.

A 63-year-old man was found on ultrasound examination to have a hepatic cystic mass with a mural nodule, which was mildly enhanced on contrast enhanced CT and MRI. At surgery, the cystic fluid was haemorrhagic and histological examination of the mural nodule demonstrated an organized haematoma. This case is of interest in that an apparent mural nodule was present in a non-neoplastic cyst. Haemorrhagic hepatic cyst with an organized haematoma should be included in the differential diagnosis of cystic neoplasms.

Cysts↗
PubMed2001

Competitive amino acid transport between L-tryptophan and other amino acids in Schizophyllum commune.

In our study on nutritional requirement for the hyphal growth of Schizophyllum commune, we found that a Trp- mutant could not grow in the L-Trp-supplied medium in the presence of L-Ser. Further growth studies showed that not only L-Ser but also as many as 11 kinds of amino acid including L-Ala, L-Arg, L-Asn, L-His, L-Leu, L-Met, L-Phe, L-Ser, L-Thr, L-Tyr and L-Val inhibited the growth of the Trp- mutant in the L-Trp-supplied medium. However, these amino acids did not inhibit the growth of a Trp+ strain. The inhibition of growth of Trp+ strain induced by a Trp analogue of 5-fluoro-DL-tryptophan (5FT), which was usually recovered by L-Trp, was rescued by the same amino acids mentioned above. The exceptions were Gly and L-Ile, which also recovered the growth inhibition induced by 5FT. These results indicate that the permease responsible for the Trp transport in S. commune might also be active to other amino acids. However, it is considered that the permease shows high affinity to L-Trp and low affinity to other amino acids. As a result, the transport of L-Trp and 5FT may be counteracted by other amino acids.

Journal Article↗
PubMed2001

Concentration of docosahexaenoic acid from fish oils using Geotrichum sp. FO347-2.

Geotrichum sp. FO347-2 could use refined sardine oil as a sole carbon source. Dry cell mass reached a maximum of 0.788 g per g of the oil added for 72 h. Total weight of the cellular lipids was largest around 24 h, when the contents of triglyceride and free fatty acid were 63.6 and 22.2%, respectively. Docosahexaenoic acid (DHA) was incorporated and concentrated in the cellular lipids, and the content reached 25.9% for 24 h, adding sardine oil containing 12.3% DHA. DHA and eicosapentaenoic acid were also concentrated in residual lipids outside the cells. Using tuna head oil containing 26.8% DHA, FO347-2 was compared with Candida guilliermondii FO726A with respect to DHA incorporation. FO347-2 and FO726A accumulated similar amounts of DHA, i.e. 53 and 55 mg, respectively, in 1 g of freeze-dried cells after 24-h cultivation at 30 degrees C. The recovery rates of DHA from the tuna oil for FO347-2 and FO726A were 19.4 and 19.7%, respectively.

Culture Media↗
PubMed2001

Adenosquamous carcinoma of the pancreas: successful treatment with extended radical surgery, intraoperative radiation therapy, and locoregional chemotherapy.

BACKGROUND: Adenosquamous carcinoma of the pancreas is a rare tumor with an extremely poor survival rate. No obvious evidence that multidisciplinary treatments improves the prognosis and survival has been reported. PATIENT AND RESULTS: A 63-yr-old female with adenosquamous carcinoma of the pancreas underwent extended radical surgery, intraoperative radiation therapy, postoperative intraarterial chemotherapy, and external beam radiation therapy. The patient is alive at 40 mo after surgery with no recurrence. CONCLUSIONS: Multidisciplinary treatments including aggressive surgery, intraoperative radiation therapy, and locoregional chemotherapy might improve the survival of patients with adenosquamous carcinoma of the pancreas to inhibit liver metastasis and local recurrence.

Antineoplastic Agents↗