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Biomedical subjects

K Katayama

Publications and source records attributed to K Katayama.

At least 271 records · Page 15Linked to original sources

Low prevalence of hepatitis C virus antibodies in chronic liver disease in northwest China.

To evaluate the prevalence of hepatitis C virus infection in northwest China, 179 chronic liver disease patients in this area were examined for antibody to hepatitis C virus core protein (anti-HCVcore). This antibody was found in only 5 (14 percent) of 37 chronic non-A, non-B liver disease patients, in 11 (16%) of 67 asymptomatic hepatitis B virus carriers, and in 20 (27%) of 75 chronic hepatitis B patients. High titers of anti-HCVcore (cut off index > 2) were observed in 3 (60%), 5 (45%), and 9 (45%) of the anti-HCVcore-positive cases of these groups, respectively. We further investigated the seroprevalence of antibodies to hepatitis B virus in the 37 chronic non-A, non-B liver disease patients. All 5 anti-HCVcore-positive cases were positive for a hepatitis B virus marker, with only 44% (14/32) of the anti-HCVcore-negative patients (P < 0.05). Based on these findings, it is concluded that the prevalence of hepatitis C virus infection in chronic non-A, non-B liver disease is unexpectedly low in northwest China and that hepatitis B and C viruses seem to have a similar mode of infection in that area.

Adult↗

Kinetics of combined drug action.

For the purpose of obtaining quantitative concentration-effect relationship for combined drugs, rationales of the Hill equation were inferred and five models, i.e., normal distribution (NRD), derivative of R (DRV), vacancy-dependent binding (VDB), equiresponse (EQR), and independence (IND), were proposed to estimate the intensity of the combined drug action. In conclusion, we could not come up to the unique concentration-effect relationship. Among the five models, the EQR, NRD, and VDB models gave almost identical response intensity. Discrimination of these three models is not of great importance. The DRV model gave a characteristic concave isobologram (overadditive), for a given ratio of Hill constants and independent of pharmacologic effect. In contrast, the IND model was able to cope with convex isobolograms (underadditive).

Animals↗

Effects of cytokines on HLA class I antigen expression on Huh6 and HB611 cells.

This study investigated the expression of HLA class I antigens on Huh6 and HB611 cells induced by interferon (IFN)-alpha, IFN-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta. All of these cytokines induced the antigens on both cells in a dose-dependent manner, with IFNs inducing much more expression than TNF-alpha or IL-1 beta. We have already reported that protein kinase C (PKC) is involved in the antigen expression induced by IFN-gamma on Huh6 cells. The antigen expression induced by IFN-alpha was also blocked by a PKC inhibitor, H-7. However, the antigen expression by TNF-alpha or IL-1 beta was not inhibited by H-7, by a protein kinase A inhibitor, HA1004, nor by a calmodulin antagonist, W-7. These results suggested that PKC, Ca(2+)-calmodulin, and cAMP are not involved in the induction of HLA class I antigens on both cells by TNF-alpha and IL-1 beta. We concluded that TNF-alpha and IL-1 beta induced much less expression of HLA class I antigens on both cells than IFNs and that this might be because the signaling pathway by TNF-alpha and IL-1 beta differed from that by IFNs.

Carcinoma, Hepatocellular↗

Alpha-interferon enhances gamma-interferon production of peripheral blood mononuclear cells pre-activated with phytohemagglutinin.

The question of whether the state of T cell activation is responsible for gamma-interferon production in response to alpha-interferon was determined. When peripheral blood mononuclear cells were pre-incubated with phytohemagglutinin for 3 days, their gamma-interferon production was found to be augmented by alpha-interferon, accompanied by an increased proportion of DR-positive T cells. This did not occur with fresh cells. The effect was dose-dependent and inhibited by anti-alpha-interferon antibody. Therefore, alpha-interferon was considered to enhance the production of gamma-interferon of pre-activated peripheral blood mononuclear cells but not of resting ones. In conclusion, alpha-interferon augmented the production of gamma-interferon of peripheral blood mononuclear cells only when they had already been activated, suggesting a role of alpha-interferon as a modulator of the cellular immune response.

Flow Cytometry↗

Differentiation of mumps vaccine strains from wild viruses by single-strand conformation polymorphism of the P gene.

The DNA fragments amplified through the polymerase chain reaction from part of the P gene of four mumps vaccine strains (Urabe, Torii, Hoshino and Miyahara) were subjected to single-strand conformation polymorphism (SSCP) analysis. These four vaccine strains were differentiated from each other. Furthermore, twelve wild viruses and a laboratory strain (Enders strain) were also distinguished by this method. Viruses isolated from patients who developed aseptic meningitis 4 to 6 weeks after measles-mumps-rubella vaccination showed identical SSCP patterns with the vaccine strain used for immunization. These results were well correlated with sequence analysis of P-gene segments, indicating high applicability of the SSCP analysis for differentiation of mumps vaccine strains not only from each other but from wild viruses.

DNA, Single-Stranded↗

Inhibition of IgE-mediated leukotriene generation and bronchoconstriction in primates with a new 5-lipoxygenase inhibitor, E6080.

The inhibitory effects of a novel compound, 6-hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le hydrochloride (E6080) on IgE-mediated reactions in vitro and in vivo were determined in rhesus monkeys. E6080 inhibited both antigen- and anti-human IgE-induced leukotriene C4 generations from lung fragments at similar concentrations: the IC50s of E6080 were 1.11 and 0.96 microM, respectively. AA861 also inhibited both leukotriene C4 generations with IC50s of 0.79 and 0.76 microM, respectively. All 9 monkeys demonstrating positive cutaneous reactivity against Ascaris antigen at < 10(-7) g protein/0.1 ml showed reproducible bronchoconstriction upon aerosolized antigen challenge, but 5 monkeys demonstrating weak or no reactivity to the antigen at levels > 10(-5) g protein/0.1 ml showed no significant bronchoconstriction. The high responder monkeys showed a marked increase in lung resistance (RL 335.3 +/- 85.3%, n = 11) and a decrease in dynamic lung compliance (67.7 +/- 4.2%, n = 11) after antigen challenge following pretreatment with diphenhydramine. These pulmonary changes lasted for more than 30 min. E6080 at oral doses of 3 and 10 mg/kg showed dose-dependent inhibition of both pulmonary changes. Ten milligrams per kilogram of E6080, administered 1.5 h prior to antigen challenge, significantly inhibited the changes in both parameters, while 3 mg/kg showed significant inhibition of only the RL change. These results demonstrate that E6080 inhibited immunologically stimulated leukotriene production in the lung, resulting in inhibition of the antigen-induced airway response in primates.

Animals↗

Two-layer membrane model for iontophoretic drug transport through excised rat skin.

Iontophoretic and passive transport of an ionized drug (sulfisoxazole) across excised rat skin was studied using a two-chamber cell with four electrodes under successive experimental conditions: without electrical current (stage-I) and with electrical current (stage-II). Two iontophoretic/diffusion models, i.e. a one-layer membrane model and a two-layer membrane model, in which a difference in the electrical potential gradient was taken into account between the stratum corneum and epidermis/dermis layer, were constructed to describe the non-steady-state drug permeation process during ionotrophoresis. The observed iontophoretic lag-time was two times greater than the calculated value based on the one-layer membrane model. According to the two-layer membrane model, the calculated ionotophoretic lag-time agreed with the observed value. It was revealed by model adaptation to the observed data that the stratum corneum fraction of the electro-chemical potential difference across the whole skin caused by the iontophoresis was around 90%. This result was consistent with the observation that the direct current resistance of whole skin was seven times greater than that of stripped skin.

Animals↗

Altered expression of insulin and insulin-like growth factor-I receptors in follicular and stromal compartments of polycystic ovaries.

In the ovary, insulin and insulin-like growth factor-I (IGF-I) act synergistically with FSH to augment estrogen production by granulosa cells and with LH to augment androgen production by thecal stromal cells. It is also evident that insulin resistance is common in patients with polycystic ovary syndrome (PCO). Thus, in the present study we investigated the expression of insulin and IGF-I receptors in PCO ovaries and compared them with those in normal ovaries. Ovarian tissues were obtained from four PCO patients undergoing wedge resection, and from six patients who underwent radical hysterectomy. Immunohistochemical staining for insulin and IGF-I receptors was performed by avidin/biotin immunoperoxidase techniques. In normal ovaries, the expression of insulin and IGF-I receptors in follicular compartment became apparent in the preantral follicle stage and augmented with the follicular growth, while the stromal cells, regardless of the follicle stage, possessed insulin and IGF-I receptors. In PCO ovaries associated with hyperinsulinemia, no expression of insulin receptors was detected in granulosa or thecal stromal cells, while IGF-I receptor expression increased in thecal stromal cells but decreased in granulosa cells compared to those in normal ovaries. However, in PCO ovaries from patients without hyperinsulinemia, insulin receptor expression was apparent in both granulosa and thecal stromal cells, with a similar intensity to that observed in normal ovaries, while IGF-I receptor expression was negligible in granulosa cells but sustained in thecal stromal cells. These findings suggest that decreased expression of insulin receptors in PCO ovaries associated with hyperinsulinemia may be secondary to receptor down regulation, whereas defective expression in granulosa cells along with elevated or persisted expression in thecal stromal cells of IGF-I receptors may be common in PCO ovaries and contribute to the endocrine profiles of PCO in which varying degrees of hyperandrogenism is a predominant feature.

Adult↗

Changes in antibodies to specific hepatitis C virus antigens with interferon-alpha therapy: analysis by recombinant immunoblot assay.

Antibodies to hepatitis C virus NS3 (C33C), NS4 (5-1-1 and C100-3), and core (C22-3) proteins were tested for by a second-generation recombinant immunoblot assay of serum samples from 42 chronic hepatitis C patients treated with interferon-alpha. Antibodies to 5-1-1 and C100-3 were found in 83% (35/42) before therapy, and those to C22-3 and C33C in all patients. At 6 months after therapy withdrawal in patients with sustained virus clearance, only antibodies to 5-1-1 and C100-3 showed significant decreases (p < 0.05) (5/5 and 7/7, respectively). Antibodies to C22-3 and C33C decreased less frequently in only 11% (1/9) (p < 0.01) and 44% (4/9) (p < 0.05), respectively. Thus, antibodies to 5-1-1 and C100-3 are prone to decrease following a decline in viremia. The antibody to the C22-3 (core) protein was least likely to decrease and may serve as a reliable marker of exposure to the virus.

Adult↗

Quantitative analysis of antibodies to hepatitis C virus during interferon-alpha therapy.

We quantified IgG antibodies to structural (core) and nonstructural (C100-3) hepatitis C virus proteins in 42 patients with chronic hepatitis C treated with a 6-mo course of interferon-alpha. Sera were drawn before and at the end of therapy and also 6 mo after therapy withdrawal; they were stored for later analysis of antibodies and serum hepatitis C virus RNA. Sustained virus clearance was observed at the end of therapy and 6 mo after therapy withdrawal in nine cases; it was accompanied with sustained reductions of antibody to hepatitis C virus core protein and antibody to C100-3 protein. A sustained reduction of antibody to hepatitis C virus core protein was specific to sustained virus clearance, although that of antibody to C100-3 protein was not. None of the patients who did not show reductions of levels of both antibodies at the end of therapy displayed sustained virus clearance. Five patients showed hepatitis C virus RNA negativity and normal aminotransferase levels at the end of therapy without reduction of antibody to hepatitis C virus core protein levels. Of these five patients, relapse of hepatitis occurred in four, and viremia was present 6 mo after therapy withdrawal in all cases. These results demonstrate that testing for antibody titers may add information for evaluating virus clearance after interferon therapy.

Adult↗

[Lymphocyte subsets and interleukin-2 receptor in breast cancer patients].

The lymphocyte subsets and IL-2R (p55/Tac) in breast cancer patients were analyzed using monoclonal antibody and flow cytometry until 6 post-operative month. Results were as follows: 1. Lymphocyte fraction of CD3, 4, 8 was maintained from pre-operative to post-operative 6 month. 2. IL-2R value was lower in recurrence group than in breast benign disease group and it was lower. In pre-operative IL-2R in Stage III group than in Stage I and, Stage II. It was lower in DNA aneuploidy group than in DNA diploidy group. 3. At the post-operative 6 month, IL-2R was higher in Stage III group, ly-factor positive group, v-factor positive group and DNA aneuploidy group than in recurrence group. When breast cancer recurred after resection, IL-2R value returned to initial value. In conclusion, IL-2R may be possibly one of the factors of recurrence of breast cancer.

Adult↗

[HTLV-I associated myelopathy presenting with profound atrophy of unilateral lower limb].

A 63-year-old woman had suffered from progressive weakness and wasting of the right lower limb for seven years. In the lower limbs, there were profound muscular atrophy and weakness on the right, and mild weakness with spasticity on the left. Muscle strength of the upper limbs was normal. Sensory examination was normal except for paresthesias below the right knee. Anti-HTLV-I antibody titer was raised both in serum and in the CSF. Motor nerve conduction studies of the lower limbs showed small compound muscle action potentials and somewhat slow conduction velocities, more evident in the right side. F-wave was evoked only in the left tibial nerve and its latency was increased. Sensory nerve conduction studies were normal in the lower limbs. Somatosensory evoked potentials (SEPs) after tibial nerve stimulation at the ankles showed increased interpeak latencies between lumbar N20 and scalp P37. Nerve conduction studies in the upper limb were normal. Single fiber electromyography suggested anterior horn involvement not only in the lumbosacral cord but also in the cervical cord. Weakness and spasticity improved after oral administration of prednisolone. The SEPs findings and a favorable response to prednisolone excluded the possibility of amyotrophic lateral sclerosis. This case is a clinical variant of HTLV-I-associated myelopathy presenting profound atrophy of unilateral lower limb.

Female↗

[Modes of spread and surgical strategy for gallbladder carcinoma with subserosal invasion].

The mode of spread and the prognosis were investigated in 22 patients with resected gallbladder carcinoma invading the subserosal layer. By the Kaplan-Meier method, the 5-year survival rate was 68.8% in patients receiving curative or relatively noncurative resection. On the other hand, no patient survived for more than 3 years after noncurative resection. The mode of subserosal infiltration was classified according to the general rules for gastric cancer study. At least systemic lymph node dissection (R2) should be performed in patients with ss alpha cancer, because lymph node metastasis in these patients were confined to the 1st group. More extensive lymph node dissection (R2 with 9, 16) is essential for patients with ss beta and ss gamma, because lymph node metastasis to at least the 2nd group were seen in 75% of them. The surgical margin was positive for cancer in all patient with infiltration of the hepatoduodenal ligament. Therefore, it was considered that hepatoligamentectomy should be performed in these patients to obtain a cancer free surgical margin. Among patients undergoing curative or relatively noncurative resection, the recurrence rate was 43% in those with lymph node metastasis and 50% in those with DNA aneuploidy. Therefore, it appears that adjuvant chemotherapy should be given to such patients.

Aged↗

[Arterial infusion chemotherapy of 5-FU and leucovorin for patients with liver metastases from colorectal cancer].

Fifteen patients with liver metastases from colorectal cancer were treated by arterial infusion of 5-FU and leucovorin. Two regimens were performed. One was weekly bolus infusion of leucovorin following bolus infusion of 5-FU (bolus group), the other was 5 days continuous infusion of 5-FU and leucovorin in 3 weeks (continuous group). One PR was obtained both in the bolus group and in the continuous groups. The objective response rate was 11% in the bolus group and 20% in the continuous group. The one- and 2-year survival rates for these patients were 40% and 0% in the bolus group, and 80% and 60% in the continuous group, respectively. These results suggest that continuous arterial infusion of 5-FU and leucovorin was more effective than individual bolus arterial infusion of leucovorin and 5-FU for patients with liver metastases from colorectal cancer.

Adult↗

Protective effect of E3330, a novel quinone derivative, in galactosamine-induced hepatitis in rats.

The effect of E3330 ((2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2-++ +propenoic acid), a novel quinone derivative, was studied in the galactosamine-induced hepatitis model in F344 rats, in which endogenous endotoxin is believed to play a critical pathogenetic role. Subcutaneous injection of 300 mg/kg of galactosamine into rats resulted in liver injury. Oral treatment with E3330 (10-100 mg/kg) 1 hr after galactosamine challenge attenuated the liver injury. E3330 was also effective when administered p.o. 6 or 12 hr after galactosamine challenge. Subcutaneous injection of 1000 mg/kg of galactosamine into rats resulted in more severe liver injury with endotoxemia. The plasma endotoxin was detected 24 to 48 hr after the galactosamine challenge. The time course of increase in plasma endotoxin level was in good agreement with that in plasma aminotransferase activity. E3330 (100 mg/kg) significantly attenuated the liver injury, but did not affect the endotoxin level. Exogenous administration of endotoxin enhanced the hepatotoxicity of galactosamine. Pretreatment with E3330 also protected rats from severe liver injury induced with endotoxin plus galactosamine. These results suggest that E3330 may exert its hepatoprotective effects through inhibition of an effect of endotoxin in galactosamine-induced hepatitis in rats.

Animals↗

Protective effects of E3330, a novel quinone derivative, on galactosamine/tumor necrosis factor-alpha-induced hepatitis in mice.

Oral pretreatment with E3330, a novel quinone derivative, attenuated liver injury induced with tumor necrosis factor-alpha in galactosamine-sensitized mice. Tumor necrosis factor-alpha is known to induce inflammatory mediators such as leukotrienes and prostanoids. An in vitro study showed that E3330 inhibited the generation of leukotriene B4 and thromboxane B2, but enhanced prostaglandin E2 generation from rat peritoneal exudate cells stimulated with the Ca(2+)-ionophore, A23187. These findings suggest that the protective effect of E3330 on galactosamine/tumor necrosis factor-alpha hepatitis is due at least in part to its inhibition of the generation of leukotrienes. The inhibition of thromboxane B2 generation or the enhancement of prostaglandin E2 generation by E3330 may also contribute to its hepatoprotective effect.

Animals↗

Deletion mutagenesis of stem cell factor defines the C-terminal sequences essential for its biological activity.

We constructed a series of murine stem cell factor (mSCF) cDNAs which were sequentially truncated at the 3' termini. The resultant six mutant cDNA encode N-terminal 183, 179, 162, 149, 142 and 133 amino acid residues of the mature mSCF protein fused to the heterogeneous C-terminal peptides derived from the linker sequences. Each mutant cDNA was transiently expressed in COS cells, and the cultured supernatant was assayed for its ability to support the growth of a human factor-dependent cell line, TF-1 and to enhance colony formation by murine hematopoietic progenitor cells. The results showed that as few as N-terminal 142 but not 133 amino acid residues of mSCF remained biologically active in vitro, suggesting that the region of 9 amino acids from Asp134 to Ser142 containing a Cys138-mediated disulfide bond may contribute to the C-terminal end of the active subdomain of mSCF.

Amino Acid Sequence↗