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Biomedical subjects

T Aikawa

Publications and source records attributed to T Aikawa.

At least 55 records · Page 3Linked to original sources

Interferon-alpha 2a for chronic hepatitis B with e antigen or antibody:comparable antiviral effects on wild-type virus and precore mutant.

Recombinant interferon-alpha 2a (IFN-alpha 2a) in a total dose of 702 MU was given to 31 patients: nine with wild-type hepatitis B virus (HBV) and hepatitis B e antigen (HBeAg) (A); four with HBeAg and a mixed infection with wild-type HB and precore mutants (B); 11 with antibody to HBeAg (HBeAb) and a mixed infection (C); and seven with HBeAb and precore mutants alone (D). HBV DNA was not cleared in any patient in groups A and B. By contrast, in patients with HBeAb, HBV DNA was ultimately lost in four patients in group C, as well as in 10 patients in group D. Thus, patients with HBeAb and infected with precore mutants alone (D) lost serum HBV DNA more often than those with HBeAg and wild-type HBV (A). Patients with low pretreatment levels of HBV DNA cleared virus more frequently, and the response of precore mutant to IFN was comparable with that of wild-type HBV in patients who had a mixed infection. Based on these results, precore mutants do respond to IFN, and therefore, IFN is indicated in patients with HBeAb, especially those with low serum HBV DNA levels.

Adult↗

Clearance of serum hepatitis C virus RNA after interferon therapy in relation to virus genotype.

The effect of recombinant interferon-alfa on serum HCV RNA levels in Japanese patients with chronic hepatitis C was investigated. At 24 weeks of treatment, 41 (32.5%) of 126 patients lost HCV RNA from serum, and aminotransferases were normalized in 31 (75.6%) of these 41 cases. HCV genotypes were categorized into four types (Type I, II, III, IV); the frequencies among the patients were: Type I: 0%, Type II: 70.6%, Type III: 20.6%, and Type IV: 6.3%. At the end of the 24-week treatment, HCV RNA levels were remarkably decreased in Type III patients and became undetectable in 18 (69.2%) of 26. In contrast, only 18 (20.2%) of 89 patients with Type II and two of eight with Type IV lost HCV RNA from sera. The relation between HCV genotype (Type III) and response to IFN therapy was also confirmed using a logistic regression model. HCV genotype seems to be an important factor in determining the response to IFN in patients with chronic hepatitis C.

Alanine Transaminase↗

Conditioned enhancement of cough response in awake guinea pigs.

To determine whether psychological factors affect the cough response, we employed a classical conditioning procedure in which capsaicin challenge was paired with the presentation of an odor in awake guinea pigs. On days 1-4, animals received combined administrations of the unconditioning stimulus, capsaicin aerosols, and the conditioning stimulus, camphor aerosols (group 1), capsaicin and saline aerosols (group 2), and camphor and saline aerosols (group 3), and the number of coughs was counted. On day 5, all groups received camphor and saline aerosols. A significant number of coughs (p < 0.01) was observed only in group 1 when the animals were exposed to the odor alone on day 5. This suggests that associative learning enhances the cough response.

Aerosols↗

[A case of spontaneous rupture of renal cell carcinoma].

There have been a few reports on the spontaneous rupture of renal cell carcinoma. A 67-year-old female patient complaining of vomiting and severe abdominal pain was referred to our hospital. Plain computerized tomography demonstrated large heterogenous mass in the right retroperitoneum. We suspected the hemorrhagic shock because of the rupture of the right kidney and therefore emergent laparotomy was performed. Simple nephrectomy for the right kidney was performed. A pathological report revealed renal cell carcinoma, granular cell subtype, grade 1, pT3a. The patient has been followed for one year and five months after the operation, there has been no evidence of local recurrence or distant metastasis of cancer. Thirteen cases of spontaneous rupture of renal cell carcinoma in the Japanese literature are reviewed.

Aged↗

Biochemical and histological changes after more than four years of treatment of ursodeoxycholic acid in primary biliary cirrhosis.

We report on three patients with symptomatic, anicteric, and noncirrhotic primary biliary cirrhosis (Ludwig histological stage III at first liver biopsy) who were treated orally with 600 mg/day of ursodeoxycholic acid (UDCA) for more than 4 years. Follow-up liver biopsy was performed twice (at 1-3 and 4-6 years) during treatment. In all cases, during the whole period of up to 4-6 years of UDCA treatment, transaminase, alkaline phosphatase, and gamma-glutamyltranspeptidase levels improved, remaining at subnormal levels compared with pretreatment levels. Moreover, histological stage did not change throughout the UDCA treatment of up to 6 years. The second liver biopsy (at 1-3 years) revealed decreased lymphocytic infiltration in all cases, and bridging fibrosis was decreased in two cases. However, in the third biopsy at 4-6 years, portal inflammation was increased in one case without fibrotic progression; in the other two cases, bridging fibrosis was slightly worsened without portal inflammatory progression. In summary, these three cases show that liver histology was found to be improved, as were blood chemistry and pruritus, during short-term UDCA treatment, but histology results were slightly worse after long-term treatment despite the sustained improvement in biochemistry and pruritus.

Adult↗

Effects of 2-buten-4-olide, an endogenous satiety substance, on plasma glucose, corticosterone, and catecholamines.

Effects of 2-buten-4-olide (2-B4O), an endogenous satiety substance, on levels of plasma glucose, corticosterone, and catecholamines were examined in fed, conscious, and unrestrained rats. A vascular indwelling catheter was inserted into the right atrium of the animal from the jugular vein 1 wk before the experiment. Injection of 2-B4O and blood sampling were performed through the catheter in an unanesthetized condition. The levels of plasma glucose, corticosterone, epinephrine, and norepinephrine increased significantly for 2 h after the start of intravenous injection of 2-B4O in a dose-dependent manner. The increases in glucose and catecholamines induced by 2-B4O injection were abolished by bilateral splanchnicotomy (SPX) but not by pretreatment with anti-corticotropin-releasing factor (CRF) antibody. The increase in corticosterone was abolished not by the SPX but by pretreatment with anti-CRF antibody. These findings suggest that 2-B4O, endogenously produced during food deprivation, may facilitate sympathoadrenal and hypothalamopituitary-adrenal functions through the central nervous system.

4-Butyrolactone↗

[HCV-serotype and IFN response].

The relation between HCV-serotypes and response to interferon (IFN) in 114 cases with chronic hepatitis C treated with IFN-alpha were studied. HCV-serotypes; two distinct subgroups (serotype 1 and 2) of hepatitis C virus defined by antibodies directed to the putative core protein, were examined by ELISA developed by Machida et al. 1) Of 33 cases with serotype 2, 20 were responders, whereas, only 5 of 35 cases with serotype 1 responded to IFN therapy. 2) Of 23 cases with HCV-genotype III, 18 (78.3%) responded to IFN. Moreover, 12 (85.7%) of 14 cases who had serotype 2 were responders. On the other hand, only 17 (21.0%) cases with genotype II and 4 (12.1%) cases with serotype 1 responded to IFN. HCV-serotyping as well as HCV-genotyping in cases with chronic hepatitis C seems to be important in predicting the response to IFN therapy.

Adult↗

[Malignant rheumatoid arthritis].

Malignant rheumatoid arthritis (MRA) is designated as rheumatoid arthritis with vasculitis, but MRA is commonly called rheumatoid vasculitis in western countries. Patients with MRA show a variety of symptoms and signs based on vasculitis. The clinical features include subcutaneous nodule, skin ulcer, pericarditis, myocarditis, pleuritis, pneumonitis, intestinal infarction, mononeuritis multiplex and other involvements. The cause of the various vascular lesions in MRA has not been clearly defined, but a number of observations suggest that they result from injury induced by immune complexes, especially, those containing rheumatoid factor (RF). The theory of self-associated IgG RF has been proposed. MRA is usually treated with steroid, and steroid pulse therapy and immunosuppressants are highly useful for severe MRA.

Arthritis, Rheumatoid↗

Neoadjuvant intra-arterial chemotherapy in locally advanced breast cancer: a prospective randomized study. Osaka Breast Cancer Study Group.

A prospective randomized study of neoadjuvant chemotherapy was carried out on 73 patients with locally advanced breast cancer. Group A (n 26) received no neoadjuvant therapy, group B (n22) received intra-arterial infusions of epirubicin and group C (n25) received intravenous epirubicin. The regression of the primary tumor was significantly higher in group B than in group C (68.2 vs 36.0%, P < 0.05). The post-operative survival of responders to neoadjuvant therapy was better than that of non-responders. Side effects were milder in group B than in group C. There was, however, no difference among the three groups in terms of overall and disease-free survivals. Thus, neoadjuvant intra-arterial chemotherapy was effective for achieving loco-regional control of locally advanced breast cancer with a low toxicity, but could not improve survival.

Aged↗

Pharmacokinetic profiles of glycyrrhizin in patients with chronic hepatitis.

The pharmacokinetics of glycyrrhizin (G) in eight patients with chronic hepatitis receiving chronically i.v. administration of 120 mg dose of G was investigated. The plasma concentration of G in the patients after dosing declined in a monophasic manner. However, the pharmacokinetic profiles varied among patients. The mean elimination half-life (t1/2) and the total body clearance (CLtot) were 6.0 h (range 4.3-10.7 h) and 7.9 ml h-1 kg-1 (4.5-12.7 ml h-1 kg-1), respectively. The variation of the CLtot for G was closely related to that of aspartate aminotransferase (r = -0.739, p < 0.05) and alanine aminotransferase (r = -0.783, p < 0.05) activities in the plasma.

Adult↗

High prevalence of hepatitis B and C viral markers in Japanese patients with hepatocellular carcinoma.

In order to assess the etiologic role of hepatitis C virus (HCV) as well as hepatitis B virus (HBV) in the etiology of HCC, we compared the prevalence of HCV-related antibodies (anti-C100-3, anti-CP9, anti-CP10) and HBV-related markers (HBsAg, anti-HBs, anti-HBc) in sera of patients with liver cirrhosis (LC) with (n = 62) and without (n = 54) hepatocellular carcinoma (HCC). In HBsAg-negative cases, at least one HCV-related marker (including HCV RNA) was detected in 92.3% (48/52) of HCC cases and in all of the 44 LC cases without HCC, with no significant difference between these two groups. In HBsAg-positive cases, the prevalence of either one of these HCV-related markers was 40.0% (4/10) both in patients with and without HCC, and there was no significant difference between these two groups. Moreover, in HBsAg-negative cases and 11 cases of positive HCV-related markers, the prevalence of anti-HBs and/or anti-HBc was significantly higher in LC patients with HCC (85.4%) than those without HCC (43.2%, P < 0.001). These results show a high prevalence of hepatitis B and C viral markers in Japanese patients with HCC and further indicate that previous HBV infection is a risk factor in the occurrence of HCC in HBsAg-negative LC and LC with positive HCV-related markers.

Carcinoma, Hepatocellular↗

Overexpression of PRAD1 in a mantle zone lymphoma patient with a t(11;22)(q13;q11) translocation.

The PRAD1 gene identified from the chromosome band 11q13 region was previously demonstrated to be overexpressed in cell lines with t(11;14)(q13;q32) translocation and was suggested to be a candidate BCL-1 gene. We report here one case of mantle zone lymphoma with a t(11;22)(q13;q11), a variant translocation at the BCL-1 locus, having the PRAD1 overexpression. By analogy with the c-myc gene in Burkitt's lymphoma and the BCL-2 gene in follicular lymphoma, this case supports strongly the idea that the PRAD1 is the candidate BCL-1 gene.

Aged↗

Characterization of growth and differentiation of normal human submandibular gland epithelial cells in a serum-free medium.

Parenchymal tissue of human submandibular glands was cultured in a serum-free medium consisting of a 1:9 mixture of Dulbecco's modified Eagle's medium and MCDB 153 supplemented with 10 ng/ml epidermal growth factor, 10 microM dexamethasone and 1 microgram/ml insulin. Cultivation of the tissue in this medium resulted in propagation of loosely arranged epithelioid cells on plastic, without the necessity of a matrix. Epidermal growth factor significantly enhanced mitogenesis of cultured cells, which expressed specific high- and low-affinity receptors for epidermal growth factor. The epithelioid cells were found to represent the undifferentiated ultrastructure of ductal cells. Immunocytochemically, cultured epithelioid cells expressed antigens specific to basal cells of the intra- and interlobular ducts in situ, including cytokeratins 3 and 6 and cytokeratins 13 and 16, vimentin, and alpha-smooth muscle actin. Moreover, cytoplasm of the cells was immunostained using antibody against the basement membrane component, type IV collagen. These results suggested that cultured epithelioid cells are undifferentiated ductal cells, which have the characteristics of basal cells of the intra- and/or interlobular ducts. Cultured epithelioid cells maintained the characteristics for serial passage until the time that the cultures were confluent. On the other hand, several stratified foci developed on the confluent monolayer. The stratified cells were strongly positive for cytokeratins 3 and 6, but negative for vimentin, alpha-smooth muscle actin and type IV collagen. Moreover, the stratified cells were strongly stained with the antibody against epithelial membrane antigen. This antibody stained the luminal membrane domain of salivary epithelial cells. Electron micrograph of the vertical section through the foci revealed stratified cell layers with a gradual transition from basal cells to squamous epidermoid cells. This result suggests that cultured epithelioid cells, which have the characteristics of basal cells of the intra- and/or interlobular duct, have the potential to differentiate into luminal duct cells.

Cell Differentiation↗

Late asthmatic response causes peripheral airway hyperresponsiveness in dogs treated with metopirone.

To determine if late asthmatic response (LAR) is associated with hyperresponsiveness of airway smooth muscle itself, we performed antigen challenge in dogs treated with Metopirone. We studied the contractile response to acetylcholine (ACh) in isolated bronchial and bronchiolar segments 8 h after either saline inhalation (the control group) or antigen challenge in dogs demonstrating immediate asthmatic response (IAR) alone and in dogs demonstrating both IAR and LAR. Airway responses to Ascaris suum antigen were assessed by changes in respiratory resistance measured with the forced oscillation technique at 3 Hz. Concentration-response curves of bronchial preparations to ACh did not differ significantly among three groups consisting of the control, IAR and LAR. However, the contractile response of bronchiolar preparations to ACh was significantly greater in the LAR group when compared to the control and IAR groups at the concentrations of ACh ranging from 10(-6) to 3 x 10(-4) M (p < 0.01). SQ 29548, a receptor antagonist of thromboxane A2 and prostaglandin D2 (PGD2), inhibited LAR-induced hyperresponsiveness to ACh in a concentration-dependent fashion. The bronchiolar preparations obtained from dogs showing LAR contained a significantly higher amount of PGD2 than those obtained from dogs showing IAR alone (p < 0.01, n = 6). These results suggest that LAR is associated with hyperresponsiveness of peripheral airway smooth muscle to ACh, and this augmented response to ACh mediates via PGD2 released during LAR.

Acetylcholine↗

Evidence for substance P as an endogenous substance causing cough in guinea pigs.

We examined an endogenous substance causing cough in awake guinea pigs. An intraperitoneal injection of phosphoramidon, a selective inhibitor of neutral endopeptidase (E.C. 3.4.24.11), caused cough in a dose-dependent fashion for approximately 40 min. At a dose of 3 x 10(-3) mol/kg, phosphoramidon caused a total of 11.6 +/- 1.4 coughs in 40 min. Phosphoramidon (3 x 10(-3) mol/kg)-induced cough was significantly inhibited by systemic pretreatment with capsaicin (p < 0.01). Aerosols of FK 888 (1 min), a specific inhibitor of substance P (NK1) receptor, inhibited phosphoramidon (3 x 10(-3) mol/kg)-induced cough in a dose-dependent fashion with complete inhibition at a dose of 10(-5) M. Likewise, aerosols of FK 224 (10(-5) M; 1 min), another inhibitor of NK1 and NK2 receptors, or lidocaine (4%, 1 min) significantly inhibited phosphoramidon (3 x 10(-3) mol/kg)-induced cough (p < 0.01). Furthermore, aerosols of FK 888 (10(-5) M; 1 min) significantly inhibited cough induced by cigarette smoke in awake guinea pigs (p < 0.01). These results suggest that substance P released from sensory nerves in the airway may be an endogenous substance causing cough and the substance P antagonist may be the drug for treatment of cough in respiratory disease.

Aerosols↗

Evidence that an atypical beta-adrenoceptor mediates the prejunctional inhibition of non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

We investigated the effect of the putative beta 3 agonist BRL 35135 on non-adrenergic non-cholinergic (NANC) contractions in guinea-pig bronchial strips. BRL 35135 (10(-9) to 10(-6) M) did not alter the baseline tension but reduced NANC contractions induced by electrical field stimulation (EFS) in a concentration-dependent fashion without having a significant effect on the contraction induced by substance P (10(-6) M). BRL 35135 (10(-6) M) also reduced the contraction induced by capsaicin (10(-7) M). Likewise, BRL 37344 (10(-9) to 10(-6) M) reduced NANC contractions induced by EFS in a concentration-dependent fashion. While BRL 37344 up to concentrations of 10(-8) M did not alter the contraction induced by SP (10(-6) M), BRL 37344 (10(-8) M) significantly inhibited NANC contractions induced by EFS and capsaicin (10(-7) M), (P less than 0.01). The inhibitory effect of BRL 35135 (10(-6) M) on NANC contractions induced by EFS was not significantly altered by the non-selective beta-adrenoceptor antagonists, propranolol and pindolol (P greater than 0.10), by the beta 1-selective antagonists, atenolol and metoprolol (P greater than 0.20) (10(-8) to 10(-6) M), or by the alpha-adrenoceptor antagonist, phentolamine (10(-7) to 10(-5) M) (P greater than 0.50). These results suggest that beta 3 agonists exert a prejunctional inhibitory action on NANC contractions.

Animals↗