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Biomedical subjects

K Hamada

Publications and source records attributed to K Hamada.

At least 55 records · Page 3Linked to original sources
PubMed2001

Long-term follow-up study of sustained biochemical responders with interferon therapy.

A proportion of chronic hepatitis C patients who were treated with interferon have a sustained normalization of transaminase levels after interferon therapy without hepatitis C virus (HCV)-RNA clearance. We determined their clinical characteristics and long-term outcome in relation to progression to liver cirrhosis (LC) and the development of hepatocellular carcinoma (HCC). A total of 250 patients with chronic hepatitis C who were treated with interferon were studied for 8 to 11 years' posttherapy. Sixty-seven patients (27%) were complete responders with clearance of HCV RNA. Twenty-six (10%) were biochemical responders who had sustained normal alanine transaminase (ALT) levels without viral clearance. The remaining patients were short-term responders (n = 70) and nonresponders (n = 87). Biochemical responders were older, had higher levels of pretreatment HCV RNA in serum than complete responders, and had less advanced liver histology than nonresponders. Histologic grading scores decreased significantly at the end of therapy, while the staging scores did not change significantly. The annual incidence of cirrhosis was 0% in biochemical and complete responders, which was significantly lower than nonresponders and the controls (P = .0001). The annual incidence of HCC was 0.37% in complete responders and 0.50% in biochemical responders, which was significantly lower than nonresponders (P = .0001 for both). Our findings suggest that biochemical responders had high pretreatment viral levels with less advanced liver histology, and their long-term outcome appeared to be good irrespective of the persistence of the virus.

Adult↗
PubMed2001

Gene therapy for bladder cancer using adenoviral vector.

BACKGROUND AND PURPOSE: Bladder cancer is common. Current treatment for patients with superficial bladder cancer involves transurethral resection followed by adjuvant bacillus Calmette-Guérin (BCG) administration. Adjuvant BCG has been reported to be effective in 38% to 68% of patients; however, more than 30% of patients do not respond. Because p53 mutations are common among superficial bladder cancers, we tested the feasibility of using p53 as a gene therapy agent for targeting superficial tumors, which are easily accessible using an intravesical approach. MATERIALS AND METHODS: Wild-type p53 was transduced into various human and murine bladder cancer cell lines (HTB9, KU-1, and MBT-2) using a recombinant adenoviral vector (Ad5CMV-p53) in vitro. Also, subcutaneous tumors were established and then treated with intratumoral injection of Ad5CMV-p53 or control viruses. RESULTS: In vitro assays revealed significant growth suppression of target cells by Ad5CMV-p53 in comparison with those receiving the control Ad5-CMV-PA vector or untreated control cells. In vivo studies using subcutaneous bladder tumor models established in syngeneic mice demonstrated that the rate of tumor growth and volume was reduced to a greater extent by 14 days of intratumoral injection of Ad5CMV-p53 rather than Ad5CMV-PA. Furthermore, the survival of host animals bearing tumors that were infected with Ad5CMV-p53 was significantly longer than that of the control group treated with Ad5CMV-PA (P < 0.01). CONCLUSION: Our data suggest that Ad5CMV-p53 is effective in suppressing bladder cancer growth and improving host survival.

Adenoviridae↗
PubMed2001

Interleukin-1-induced subacromial synovitis and shoulder pain in rotator cuff diseases.

OBJECTIVE: To determine the relationship between the expression of interleukin-1beta (IL-1beta) and IL-1 receptor antagonists (IL-1ra) in the subacromial bursa and shoulder pain in rotator cuff diseases. METHODS: Synovial specimens were analysed using various methods including reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry and in situ RT-PCR. Thirty-nine patients with rotator cuff diseases were candidates. The degree of their shoulder pain was evaluated using a visual analogue scale. RESULTS: The mRNA expression levels of the cytokines were significantly correlated with the degree of pain [IL-1beta: r=0.782; secreted IL-1ra (sIL-1ra): r=0.756; intracellular IL-1ra (icIL-1ra): r=0.806, P<0.001, respectively]. The combined results of immunohistochemistry and in situ RT-PCR analysis indicated that both synovial lining and sublining cells produce IL-1beta, while synovial lining cells predominantly produce icIL-1ra and sublining cells secrete sIL-1ra. CONCLUSIONS: The differential regulation of the two forms of IL-1ra mRNAs may play an important role in shoulder pain in rotator cuff diseases, regulating IL-1-induced subacromial synovitis.

Adult↗
PubMed2001

Heterogeneity of pulmonary fibrosis: interstitial pneumonias and sarcoidosis.

This review focuses on two representatives of pulmonary fibrosis. One is usual interstitial pneumonia lesion, typically seen in patients with idiopathic pulmonary fibrosis. The other is parenchymal fibrosis along the bronchovascular bundles, observed in patients with sarcoidosis. Both are intractable fibrosis amenable only to lung transplantation. The authors trace the historical classification of idiopathic interstitial pneumonia, discuss interstitial pneumonia associated with collagen vascular diseases and occupational exposure, and review the most important issues to clarify both types of pulmonary fibrosis.

Animals↗
PubMed2001

Anti-cachectic effect of clarithromycin for patients with unresectable non-small cell lung cancer.

We have previously reported that long-term treatment with clarithromycin (CAM) increased the median survival of patients with non-small cell lung cancer, and improved various clinical parameters in these patients. In the present study, CAM was administered to 33 patients with unresectable primary non-small cell lung cancer, who had received chemotherapy, radiotherapy or both (basic cancer therapy). Patients with clinical backgrounds matched to the CAM group, who did not receive CAM treatment, were included into this study as a control group (non-CAM group). CAM treatment was initiated 4 weeks after the basic cancer therapy. The non-CAM group did not receive a placebo. Before and after the 3-month treatment with CAM, body weight, serum levels of interleukin-6 (IL-6, a cytokine which, together with TNF-alpha, plays a crucial role in the development of cancer cachexia), total protein, albumin, cholinesterase and hemoglobin were measured for the evaluation of the patients' clinical status. There were no statistically significant differences in serum levels of IL-6 between the CAM group before the treatment and the non-CAM group. After 3 months of CAM treatment, serum levels of IL-6 significantly decreased. In contrast, body weight, cholinesterase, and hemoglobin increased to a significant extent. Among these four parameters, however, the decrease in serum IL-6 levels was only statistically correlated with the increase in body weight, but not with that in other parameters. Furthermore, CAM-treated patients whose serum IL-6 levels were decreased after 3 months of treatment survived longer: there was a statistically significant correlation between the decrease in serum IL-6 and survival time. In contrast, in the non-CAM group, these parameters did not change significantly during the study. These results suggest that CAM may reduce the progression of cancer-associated cachexia.

Aged↗
PubMed2001

Effect of roxithromycin on eotaxin-primed reactive oxygen species from eosinophils.

BACKGROUND: The CC chemokine eotaxin not only attracts eosinophils to inflamed sites but also promotes adhesion, degranulation and reactive oxygen species production of eosinophils. Reactive oxygen species released from eosinophils are believed to injure epithelial cells at inflamed sites, resulting in airway hyperresponsiveness. Roxithromycin has been reported to have antiasthmatic effects, although its mechanism of action is not thoroughly understood. Therefore, the effect of roxithromycin on eotaxin-primed reactive oxygen species production from eosinophils was studied. METHODS: Reactive oxygen species production by eosinophils cultured with or without roxithromycin was evaluated using luminol-dependent chemiluminescence. RESULTS: Roxithromycin inhibited the release of reactive oxygen species from eosinophils evoked with the calcium ionophore A23187, regardless of pretreatment with or without eotaxin. CONCLUSION: Roxithromycin may protect epithelial cells at inflamed sites, at least partly by inhibiting the release of reactive oxygen species from eosinophils.

Adolescent↗
PubMed2001

Diltiazem ameliorates contractile dysfunction without shortening of action potential duration in ischemic heart of anesthetized dogs.

The purpose of the following experiment was to determine whether amelioration of myocardial contractile dysfunction by diltiazem is mediated by shortening of monophasic action potential duration (MAPD) during myocardial ischemia in anesthetized dogs. Diltiazem improved regional contraction during reperfusion after 10-min occlusion. The shortening of MAPD and increase in [K+]e were blunted by treatment with diltiazem. These results suggest that shortening of action potential duration during myocardial ischemia is unlikely to be a reason for the amelioration of contractile dysfunction.

Action Potentials↗
PubMed2001

Nitric oxide buffers renal medullary vasoconstriction induced by prostaglandins synthesis blockade.

The aim of this study was to examine whether nitric oxide (NO) buffers the renal medullary vasoconstriction induced by a prostaglandins (PG) synthesis inhibitor. Daily blood pressure measurements were made with implanted catheters and changes in cortical blood flow (CBF) and medullary blood flow (MBF) were determined by implanted optical fibers and laser-Doppler flow measurement techniques in conscious rats. Sodium and water balance were also determined. Infusion of meclofenamate, a nonisozyme-specific cyclooxygenase (COX) inhibitor, at 5 microg/kg/min over 4 consecutive days (n=12 rats) elicited a transitory increase (p<0.05) in mean arterial pressure (MAP) and a transitory decrease (p<0.05) in MBF and sodium excretion without altering CBF. In contrast, the simultaneous infusion of meclofenamate and N(G)-nitro-L-arginine methyl ester (L-NAME, 0.8 microg/kg/min), a NO synthesis inhibitor, over 4 consecutive days (n=12) produced a continuous increase (p<0.01) in MAP and a continuous decrease (p<0.05) in MBF and sodium excretion without altering CBF. The results of this study suggest that the renal medullary vasoconstrictor effects and sodium retention induced by meclofenamate are enhanced by a subpressor dose of L-NAME, and that NO may buffer the renal medullary vasoconstriction induced by the blockade of PG synthesis in conscious rats.

Animals↗
PubMed2001

Sarcoidosis with granulomatous interstitial nephritis: report of three cases.

Three cases of sarcoidosis with granulomatous interstitial nephritis are reported. Patients were all male and over 50 years of age. They simultaneously had evidence of multiorgan involvement of sarcoidosis including lung and skin and/or eye. In addition, distinct features were found in each case: a granulomatous infiltration mimicking unilateral renal tumor (case 1); renal insufficiency solely due to granulomatous interstitial nephritis (case 2); and renal insufficiency with calcemic nephropathy and granulomatous interstitial nephritis (case 3). Prednisolone therapy resulted in disappearance of the pseudotumor in case 1 and partial improvement of renal function in cases 2 and 3. In cases 2 and 3, however, plasma creatinine did not return to normal values and a second renal biopsy in case 2 demonstrated residual interstitial fibrosis and few granulomas, suggesting that steroid therapy did not achieve complete reversal of changes.

Aged↗
PubMed2001

[Renal hemodynamic effect of angiotensin II type 2 receptor].

In the present study, the role of the angiotensin II type 2 receptor in the regulation of medullary blood flow in conscious Spontaneous Hypertensive Rats(SHR) was investigated. We tested the hypothesis that AT2 receptor activation may exert the opposite effects of AT1 receptors in terms of renal hemodynamics. Mean arterial pressure(MAP), daily sodium balance, cortical blood flow(CBF), and medullary blood flow(MBF) were measured over a 10-day protocol in several groups of rats in which optical fibers for laser-Doppler flowmetry had been implanted and which received the following drug combinations: the AT1 receptor antagonist CV11976(CV) alone and CV plus AT2 receptor antagonist PD123319 (PD). In the CV alone group, the renal interstitial administration of CV decreased MAP, caused sodium diuresis, and increased MBF significantly. In the CV plus PD group, the renal interstitial administration of PD prevented sustained hypotension, sodium diuresis, and increased medullary blood flow during CV administration. These data indicated that AT2 receptor activation leads to vasodilation in the renal medulla and an antihypertensive effect in SHR. AT2 receptors play an important role in the renal medullary blood flow.

Animals↗
PubMed2001

Mutational analysis of the Smad6 and Smad7 genes in hepatocellular carcinoma.

Resistance to the transforming growth factor-beta (TGF-beta) is a frequently found phenotype in human malignancies. The recent identification of Smad6 and Smad7, both anti-Smads which inhibit TGF-beta signaling, raises a possibility that constitutive activation of the anti-Smads by a somatic mutation may impair the TGF-beta signaling pathway. We tested this hypothesis by screening the entire coding sequences of these anti-Smads for mutations in 52 hepatocellular carcinoma (HCC) samples using polymerase chain reaction - single strand conformation polymorphism analysis. We detected no mutations, but found 3 single nucleotide polymorphisms (SNPs) in the Smad6 gene and 2 SNPs in the Smad7 gene. These results suggest that mutations of the Smad6 and Smad7 genes are not the main cause of the TGF-beta resistance in human HCC.

Alleles↗
PubMed2001

Significance of increase in lipocortin-1 gene transcripts in the blood monocytes of patients with pulmonary sarcoidosis.

BACKGROUND AND AIM OF THE WORK: Lipocortin-1 (also known as annexin-1) is upregulated by corticosteroids and plays a prominent part in many of their anti-inflammatory actions. In our previou investigation, lipocortin-1 gene expression in blood monocytes was higher in sarcoidosis patients tha in healthy subjects or IPF patients. In this study, we examined the amounts of lipocortin-1 gene tran scripts [at baseline and after stimulation by synthetic adrenocorticotrophic hormone (ACTH)] in the blood monocytes of sarcoidosis patients, and then we analyzed the relationships between these amount and several clinical indexes. METHODS: Serum and blood monocyte samples were prepared from 21 sar coidosis patients before and after ACTH stimulation. The amounts of lipocortin-1 and beta-actin gene tran scripts obtained from monocytes were quantified by RT-PCR. The patients were prospectively followe for at least 2.5 years. RESULTS: 1. Serum cortisol was increased in all patients after synthetic ACTH in jection. 2. Lipocortin-1 gene transcripts tended to increase in parallel with increases in serum cortisol but the relationship was not significant. 3. The amounts of lipocortin-1 gene transcripts induced by syn thetic ACTH were related to two indexes of disease activity/extension: the presence of parenchymal lesions (p = 0.018), and the presence of extrathoracic lesions (p = 0.043). 4. After 3 years of follow-up the patients with higher basal amounts of lipocortin-1 gene transcripts in monocytes showed improve ment of sACE activity and FEV1/FVC%. CONCLUSION: The amounts of lipocortin-1 gene transcripts induced by synthetic ACTH were related to the presence of parenchymal lesions, while their basa amounts correlated with either improvement of sACE activity or stabilization of FEV1/FVC%.

Adrenocorticotropic Hormone↗