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Biomedical subjects

S Kageyama

Publications and source records attributed to S Kageyama.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Treatment of acute promyelocytic leukemia with all-trans retinoic acid and chemotherapy--multicenter trial of the Japan Adult Leukemia Study Group (JALSG)].

We report herein the clinical results of a multicenter trial of the Japan Adult Leukemia Study Group for cases of newly diagnosed acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and chemotherapy (JALSG AML-92 study). Of 196 evaluable patients, 173 (88%) achieved complete remission (CR). Multivariate analysis showed that no or minor purpura at diagnosis and age less than 30 years were favorable factors for achievement of CR. There was a significant difference in the 4-year event-free survival between the AML-92 study (54%) and both the AML-87 (32%) and AML-89 (32%) studies which consisted of intensive chemotherapy. Since prognosis in patients with APL largely depends on chemotherapy, it is important to consider more effective chemotherapy during induction and consolidation therapy.

Aclarubicin↗
PubMed2000

Multicenter prospective study of interferon-alpha and conventional chemotherapy versus bone marrow transplantation for newly diagnosed patients with chronic myelogenous leukemia. Kouseisho Leukemia Study Group.

We compared interferon-alpha (IFN-alpha therapy with bone marrow transplantation (BMT) after initial conventional chemotherapy in patients with chronic myelogenous leukemia (CML) in a multicenter prospective study. Ninety patients with Philadelphia chromosome-positive CML in chronic phase were enrolled between 1991 and 1994. Sixty-six of 89 evaluable patients received IFN-alpha after conventional chemotherapy with hydroxyurea or busulfan (IFN-alpha group). Twenty-three patients received allogeneic BMT (BMT group). Fifteen of them received transplants from HLA-identical family donors and 8 from HLA-matched unrelated donors. Forty-seven of 66 patients (71%) in the IFN-alpha group and 17 of 23 patients (74%) in the BMT group achieved complete hematologic response, and 12% in the IFN-alpha group and 13% in the BMT group achieved partial hematologic response. Complete cytogenetic response was induced in 5 (8%), partial cytogenetic response in 8 (12%), and minor cytogenetic response in 12 (18%) in the IFN-alpha group. At a median follow-up of 54 months (range, 30-76 months), in the IFN-alpha group, the predicted 6-year survival rate was 54.5% and the predicted 6-year rate of those remaining in chronic phase was 45.7%. Compared with patients with no cytogenetic response, the patients with some cytogenetic response after IFN-alpha treatment had significantly superior survival and duration of the chronic phase even after correction for the time to response using landmark analysis (P < .05). In the BMT group, the predicted 5-year survival rate was 93.3% for family-donor BMT and 21.9% for unrelated-donor BMT Acute graft-versus-host disease of grade III or IV was observed in 1 of 15 patients who received family-donor BMT and 3 of 8 patients who received unrelated donor BMT. Prior treatment with conventional cytotoxic drugs induced early hematologic response and did not reduce the effect of IFN-alpha on CML. Unrelated-donor transplantation should be offered to some patients according to patient age, HLA-matching status, time from diagnosis to BMT, and risk factors.

Adolescent↗
PubMed1999

Chromosomal diagnosis in each individual blastomere of 5- to 10-cell bovine embryos derived from in vitro fertilization.

Chromosomal normality and sex were diagnosed in each blastomere of bovine embryos derived from in vitro fertilization (IVF). Bovine embryos developing to the 5- to 10-cell stage were separated into individual blastomeres with 0.5% protease. After treatment with 100 ng/mL vinblastine sulfate for 8 to 10 h, they were prepared for chromosome samples. In total, 33 bovine embryos and 185 blastomeres were examined. Chromosomal normality was analyzed in 43.8% (81/185) of the blastomeres and 60.6% (20/33) of the embryos; while chromosomal anomalies were found in 16 (80%, 16/20) of the embryos, 5 haploid embryos and 11 mosaic (n/2n) embryos. Mosaicism characteristic of the opposite sex in X-and Y-chromosomes was found in 2 haploid embryos, and that of a Y-chromosome and of XX chromosomes in 1 n/2n embryo. Various sex-chromosome compositions were also observed in the other 10 chromosomal mosaic n/2n embryos.

Animals↗
PubMed1999

Emergence of resistance to acyclovir and penciclovir in varicella-zoster virus and genetic analysis of acyclovir-resistant variants.

We have characterized the differential actions of acyclovir and penciclovir against varicella-zoster virus (VZV) in cell culture by comparing the frequency of appearance of resistant viruses followed by their characterization. Cells were infected with cell-free virus and the cultures were successively treated with increasing concentrations of acyclovir or penciclovir. Drug-resistant viruses were selected in the presence of 6 microg/ml of acyclovir or penciclovir. The emergence frequency of resistant viruses was significantly higher following acyclovir exposure than following penciclovir exposure (Fisher's exact test, P<0.0001), possibly reflecting virus growth differences under these experimental conditions. Based on antiviral drug susceptibility and thymidine kinase (TK) activity assays, 11 acyclovir-resistant variants from seven experiments using three virus strains (Kawaguchi strain, Oka varicella vaccine strain and a clinical isolate from a zoster patient) were found to be TK-deficient. Sequence analysis of TK-deficient variants of the Kawaguchi strain revealed deletions that caused frameshifts, resulting in premature termination in the TK gene.

Acyclovir↗
PubMed1999

Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human bladder cancer.

We investigated the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) in primary bladder cancer, its association with clinicopathologic findings, and their prognostic value. mRNA was extracted from 20 bladder cancer specimens and 6 normal bladder mucosal tissues. Relative amounts of PD-ECGF/TP mRNA were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and compared with the level of glyceraldehyde-3-phosphate dehydrogenase mRNA (used as an internal standard). PD-ECGF/TP expression was examined by immunohistochemistry in 85 patients who underwent cystectomy for bladder cancer. Serum PD-ECGF/TP levels were measured in 23 patients using a sandwich-type enzyme-linked immunosorbent assay. By RT-PCR analysis, expression of PD-ECGF/TP was found to be 7-fold higher in invasive tumors than in superficial tumors (P<0.01) and 9-fold higher than in normal bladder (P<0.01). Out of 85 transitional cell carcinoma tissue samples, 69 (81%) were evaluated as PD-ECGF/TP-positive by immunohistochemical staining. PD-ECGF/TP expression correlated significantly with tumor grade (P = 0.001), depth of invasion (P = 0.012), and lymphatic invasion (P = 0.01). No correlation was found between expression of PD-ECGF/TP and the number of tumors, tumor configuration, lymph node involvement, venous invasion, c-erbB-2 expression, or overall survival. We could not detect a significant serum level of PD-ECGF/TP in any patient. The results suggest that PD-ECGF/TP might give valuable information for bladder cancer management, though it may not be a good new tumor marker for bladder cancer.

Adult↗
PubMed1999

Complications of laparoscopic adrenalectomy in 75 patients treated by the same surgeon.

OBJECTIVE: We analyzed the complications of endoscopic adrenalectomy. METHODS: We retrospectively reviewed the operative and postoperative complications among 75 patients with adrenal tumors who underwent endoscopic adrenalectomy by the same surgeon. RESULTS: Five patients (6.7%) were converted to open surgery. Of these, there were 2 with metastatic adrenal carcinoma, and 1 with adrenal tuberculosis. A total of 21 patients (28%) had 24 complications (32%). There was no mortality. As for access and pneumoperitoneum-related complications, 5 cases of subcutaneous emphysema and 3 of radiating shoulder pain occurred. Intraoperative complications included 2 cases of vascular injury, 2 of organ injury, and 4 of massive bleeding (>500 ml). Postoperative complications included 2 cases of mild paralytic ileus, 2 asthma, and 1 each of angina, wound infection, retroperitoneal hematoma, and contralateral atelectasis. Except for the patients with adrenal malignancy and adrenal tuberculosis, 71% of the complications occurred among the initial 25 patients with laparoscopic adrenalectomy and 80% occurred in the initial 10 retroperitoneoscopic patients. CONCLUSION: Although endoscopic adrenalectomy is a valuable alternative to open surgery, it should be done by a skilled laparoscopist in patients with adrenal inflammatory lesions or malignancy. Careful patient selection and correct choice of surgical approach according to the tumor size and the patient's condition are the most important points for avoiding the complications of laparoscopic adrenalectomy.

Adrenal Gland Diseases↗
PubMed1999

Acyclovir treatment of skin lesions results in immune deviation in mice infected cutaneously with herpes simplex virus.

Clinical observations indicate that the antibody response to herpes simplex virus (HSV) in patients undergoing acyclovir treatment is reduced and, although the exact mechanism is not clear, some authors interpret it as immunosuppression. In order to clarify the mechanism, we cutaneously infected mice with HSV-1 and treated the resulting skin lesions with acyclovir. The immune response to infection and treatment in these mice was then analysed. Acyclovir treatment was given orally (20 mg/kg, three times daily), starting on day 0 (D0), 2 (D2) or 4 (D4) after infection and continuing until day 10. The serum antibody titre and the severity of skin lesions were significantly higher in the shortest treatment group (D4) than in the longer treatment groups (D0 and D2). In contrast, a skin test analysing delayed-type hypersensitivity (DTH) to HSV antigen showed that the D0 and D2 groups exhibited stronger DTH than the D4 group. Acyclovir treatment failed to cause a dissociation between DTH and antibody production in mice immunized with inactivated HSV antigen. However, acyclovir treatment in infected mice suppressed the development of skin lesions and resulted in a dissociation between DTH response and antibody production, indicating a typical immune deviation. This was supported by a change in the ratio of the isotype antibody IgG2a to IgG1. The treatment of skin lesions with acyclovir reduced the level of antibody response, as observed clinically. This indicates that the reduced antibody response in patients treated with acyclovir may be, at least in part, due to immune deviation and not immunosuppression.

Acyclovir↗
PubMed1999

Insulin resistance and angiotensin converting enzyme polymorphism in Japanese hypertensive subjects.

Renin-angiotensin system activity has been shown to affect insulin sensitivity. However, the relationship between I/D polymorphism and insulin resistance is controversial. Therefore, we examined the relationship between the ACE genotype and insulin sensitivity in 51 Japanese hypertensive patients using the glucose clamp technique. The ACE genotype distribution in the hypertensive subjects was: 7 subjects with DD, 20 subjects with ID, and 24 subjects with II. Insulin sensitivity in terms of the glucose disposal rate was not significantly different among the three ACE genotypes, although there was a tendency for insulin sensitivity to decrease in the order of II, ID and DD, DD being the lowest. These findings are contrary to previous reports that insulin sensitivity was increased in normotensive subjects with the DD genotype who were Caucasian or African-American. There might be a difference due to race and whether the subjects are hypertensive or obese. We concluded that insulin sensitivity was not different among the ACE genotypes in the Japanese hypertensive subjects, supporting a previous report on the Chinese population. To date, insulin sensitivity has not been found to differ with ACE genotypes in the oriental population.

Adult↗
PubMed1999

No beneficial effect from addition of etoposide to daunorubicin, cytarabine, and 6-mercaptopurine in individualized induction therapy of adult acute myeloid leukemia: the JALSG-AML92 study. Japan Adult Leukemia Study Group.

To assess the efficacy of etoposide added to the standard remission induction therapy for acute myeloid leukemia (AML), newly diagnosed adult AML patients were randomized to receive either daunorubicin (40 mg/m2/day x 4 or more), behenoyl cytarabine (200 mg/m2/day x 10 or more), and 6-mercaptopurine (70 mg/m2/day x 10 or more) (BHAC-DM), or the same three drugs plus etoposide (100 mg/m2/day x 5) (BHAC-EDM) for response-oriented individualized induction therapy. The patients achieving complete remission (CR) received the same 3 courses of consolidation therapy followed by 6 courses of maintenance/intensification therapy. M3 patients were excluded because all-trans retinoic acid was used. Of 667 patients registered, 655 were evaluable. The median age was 49 (range 15 to 85). CR rates were 77% in the BHAC-DM group and 75% in the BHAC-EDM group. In 173 M4 patients, CR rates were 86% and 69% (P = 0.009), and in 32 M5 patients, 80% and 77% (P = 0.810) in the BHAC-DM and the BHAC-EDM groups, respectively. The predicted 6-year overall survival rates were 30% and 38% (P = 0.925) for the BHAC-DM and BHAC-EDM groups, and the disease-free survival rates of CR patients were 25% and 35% (P = 0.352), respectively. Nonhematological toxicities after the first course of induction therapy were almost equal among the two groups, with the exception of a greater loss of hair (P = 0.024) and more frequent diarrhea (P = 0.013) in the BHAC-EDM group. We concluded that in the present study, the addition of etoposide to the standard individualized induction therapy showed no advantage in adult AML, even among M4 and M5 patients.

Acute Disease↗
PubMed1999

Infectious complications during remission induction therapy in 577 patients with acute myeloid leukemia in the Japan Adult Leukemia Study Group studies between 1987 and 1991.

The Japan Adult Leukemia Study Group analyzed infectious episodes in 577 patients with acute myeloid leukemia during remission induction therapy between 1987 and 1991. 542 patients (93.9%) experienced at least one infectious episode, 121 (21.0%) had microbiologically documented infection; there was clinically documented infection in 184 (31.9%) and unexplained fever in 237 (41.1%). Among 121 microbiologically documented infections, bacteremia/fungemia was observed in 68, pneumonia in 33, and other types of infections in 20. Among the bacteremia/fungemia, gram-negative bacteria accounted for 41.2% (Pseudomonas aeruginosa was the most common), gram-positive bacteria for 39.7%, fungi for 16.2% (Candida spp. being most frequent), and polymicrobial for 2.9%. The most frequent isolates among pneumonia were Pseudomonas aeruginosa and Aspergillus. A total of 70 patients (12.1%) died during remission induction. Mortality of 68 patients with bacteremia/fungemia was 26.5%; in these patients, mortality with concomitant pneumonia increased to 41.4%; without pneumonia, mortality was 15.4% (P < 0.05). Mortality according to the isolated microbes was 17.2% for gram-negative bacteria, 25% for gram-positive bacteria, and 54.5% for fungi. Mortality of 113 patients with pneumonia (33 microbiologically documented and 80 clinically documented), 20 with other microbiologically documented infections, 104 with other clinically documented infections, and 237 with unexplained fever was 25.7%, 5.0%, 5.8%, and 5.1%, respectively.

Acute Disease↗
PubMed1999

[Evaluation of serum lipid levels in clinical benign prostatic hyperplasia patients with terazosin monotherapy].

Nine clinical benign prostatic hyperplasia (BPH) patients were treated with oral terazoin monotherapy (2 mg daily) for 12 weeks. Serum lipid levels (total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, apoproteins) were estimated prior to and every 4 weeks during treatment in 5 patients. International Prostate Symptom Score (IPSS) and pressure-flow study were evaluated before and 12 weeks after treatment in 4 patients. The total cholesterol level decreased from a baseline of 210 +/- 36.6 mg/dl by 6.6% at the 12th week. This result was not significant but suggested a favorable effect of terazosin on diminishing the risk of coronary heart disease. This effect was marked especially in patients with a total cholesterol level over 200 mg/dl. On the other hand, IPSS improved in all cases. The mean change ranged from 19.5 to 10.0 and the mean peak flow rate from 9.0 to 15.7 ml/s. On Shäffer's nomogram, 1 patient showed improvement of obstruction and the other 3 patients were diagnosed as having week detrusor without obstruction. Clinical BPH patients with hyperlipidemia may markedly benefit from terazosin, which is a safe and useful initial treatment for BPH.

Aged↗
PubMed1998

A live non-neurovirulent herpes simplex virus vector expresses beta-galactosidase in the nervous system of the Wistar and Sprague-Dawley strain rat for a prolonged period.

We have constructed a live non-neurovirulent herpes simplex virus vector expressing beta-galactosidase under the control of the latency associated transcript promoter without inducing inflammation. Pathogenicity of the recombinant virus (betaH1) was not observed in the cutaneous, intravenous and intracerebral infection in mice. When betaH1 was inoculated at the caudate putamen of rats, beta-galactosidase activity was observed in neurons at the inoculation site and its projecting frontal cortex. Expression of beta-galactosidase was observed in the neurons of the innervating dorsal root ganglia 45 days after inoculation of betaH1 into the hind paws of the rats. Neither inflammation nor tissue destruction was observed in both neural tissues in this study. Thus this non-neurovirulent recombinant virus is a suitable vector for expressing the foreign genes in the nervous system for the prolonged period.

Animals↗
PubMed1998

Slight difference in primary amino acid sequence of p17 matrix protein of HIV-1 exerts profound influence on its antigenicity.

HIV-1 p17 antigen has been studied for its biological significance in vitro as well as its immunological roles in vivo. By immunological approach of antibody-binding to HIV-1 p17 antigens of several subtypes in combination with computerized analysis of those tertial structures, it became evident that, irrelevant of similarity of linear amino acid sequence of different HIV-1 subtypes, a few amino acid substitutions close to or distant from specified epitope(s) affected their tertial structure resulting in change in ability of its binding to selected antibody. ELISA employing two monoclonal antibodies, A144 and C415, could detect p17 of subtypes A and B, but not of subtypes C, D, and E. Since the epitope site corresponding to A144 has been reported to be important for biological activity of p17 of HIV-1, change in tertial structure around this epitope may explain some difference in biology of HIV-1, such as infectivity of subtypes B and E.

Amino Acid Sequence↗
PubMed1998

Caffeine inhibits paresthesia induced by herpes simplex virus through action on primary sensory neurons in rats.

Herpetic infection causes paresthesia, including hypoalgesia, in humans and hypoalgesia in rats. This study was conducted to examine the effect of caffeine, which inhibits replication of herpes simplex virus type-1 (HSV) and affects several neuronal functions, on HSV-induced paresthesia in rats. HSV-induced hypoalgesia was suppressed by repeated treatment of unilateral hindpaw with 10% caffeine gel regardless of when the treatment was started. Repeated treatment with acyclovir, an anti-HSV agent, suppressed HSV-induced hypoalgesia only when started before inoculation; acyclovir did not produce therapeutic effects on the HSV-induced sensory abnormality. Many dorsal root ganglion neurons were positive for HSV antigen following HSV inoculation of the hindpaw. Repeated treatment with caffeine and acyclovir markedly decreased HSV antigen-positive neurons in the dorsal root ganglia when started before, but not 2 or 4 days after, infection. These results suggest that topical caffeine inhibited HSV-induced paresthesia through direct action on sensory neurons, and that not only antiviral activity but also direct alteration of neural functions are involved in the caffeine sensory actions.

Acyclovir↗
PubMed1998

Immune response to varicella-zoster virus glycoproteins in guinea pigs infected with Oka varicella vaccine.

A varicella skin test antigen has been developed based on the induction of delayed-type hypersensitivity to varicella-zoster virus (VZV), and has been used to evaluate the immune status to VZV. The authors have purified gB, gE:gI and gH:gL and examined their cutaneous reactivity in guinea pigs infected with Oka varicella vaccine. The cutaneous reaction to each glycoprotein was observed and the maturation process of cutaneous reaction was examined in infected guinea pigs. Cutaneous reaction to gH:gL, a major target of virus-neutralizing antibody, appeared first on day 3 among three glycoprotein complexes and the reaction to gE:gI, the most abundant glycoprotein, became strongest three weeks after infection. The earliest recognition of gH:gL may contribute to minimizing the spread of viral infection. Thus, the skin test may be a suitable marker to assess the cell-mediated immunity in varicella, including vaccine recipients and zoster, in relation to the immune status of glycoproteins.

Animals↗