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Biomedical subjects

S Kageyama

Publications and source records attributed to S Kageyama.

At least 19 recordsLinked to original sources

[Role of growth hormone in the pathogenesis of dawn phenomenon in IDDM].

The early morning hyperglycemia of diabetic patients has been commonly referred to as the "dawn phenomenon". Recently the nocturnal surges of growth hormone (GH) have been suggested as an important factor in the pathogenesis of the dawn phenomenon. In order to reassess the role of the nocturnal GH secretion in the dawn phenomenon, seven C-peptide negative diabetic patients were studied during 48hr-feedback control using a closed-loop insulin infusion device (Biostator). They received oral sleeping medication only on the first night (control) and sleeping medication with anticholinergic agent (pirenzepine 75mg) on the second night, and blood glucose, insulin requirements, GH and cortisol concentrations during 0000hr and 0700hr were measured. The peak of sleep-induced GH secretions was markedly suppressed by pirenzepine in comparison with the control night (19.8 +/- 3.7 vs. 3.0 +/- 1.2ng/ml; p less than 0.05). Insulin requirements during 0500hr and 0700hr were suppressed significantly by pirenzepine (3.0 +/- 0.2 vs. 2.0 +/- 0.2U/2hr; p less than 0.05). Insulin infusion ratio, i.e. insulin requirements during 0500hr and 0700hr divided by those during 0000hr and 0200hr, was decreased by pirenzepine (2.2 +/- 0.3 vs. 1.5 +/- 0.2; p less than 0.05). There were no significant differences in blood glucose and cortisol concentrations whether or not the anticholinergic agent was given. In conclusion, these results have shown that an anticholinergic agent may be useful in the management of insulin-treated patients with marked dawn phenomenon.

Adult

Plasma HIV-1 viremia in HIV-1 infected individuals assessed by polymerase chain reaction.

We established a method to estimate the amounts of HIV-1 particles in plasma from patients with HIV-1 infection by using polymerase chain reaction (PCR) following reverse transcription (RT) of viral RNA (RNA-PCR) and assessed the potential usefulness of this approach to monitor the changes of viral load in patients with AIDS or AIDS-related complex (ARC) receiving 2',3'-dideoxyinosine (ddI). Plasma samples were obtained from 77 patients with HIV-1 infection (49 AIDS/ARC and 28 asymptomatic seropositives). Following ultracentrifugation of plasma, RNA was extracted from the pelleted virus and subjected to RT and PCR. The number of HIV-1 virus particles in each sample was determined using known amounts of HIV-1 DNA as reference control for PCR. The current plasma RNA-PCR technique quantitatively detected HIV-1 particles in plasma from 76 of 77 (98.7%) HIV-1-infected individuals examined. The numbers of HIV-1 particles in plasma from patients with AIDS or ARC were markedly higher than those in plasma from asymptomatic seropositive individuals (p less than 0.0001). Higher levels of plasma HIV-1 particle numbers were detected in individuals with lower CD4+ T cell counts. Patients (n = 10) who received oral ddI at doses greater than or equal to 6.4 mg/kg/day for 8 to 14 weeks had a profound decrease in plasma HIV-1 particle numbers (p = 0.0051). Patients (n = 7) receiving ddI for 45 to 71 weeks also had a decrease (p = 0.018). It should be noted, however, that more research is required to evaluate the usefulness of this technique in assessing the disease status and monitoring the activity of antiretroviral therapy.

Base Sequence

In vitro inhibition of human immunodeficiency virus (HIV) type 1 replication by C2 symmetry-based HIV protease inhibitors as single agents or in combinations.

C2 symmetry-based human immunodeficiency virus (HIV) protease inhibitors were examined in vitro as single agents or in combination with 3'-azido-2',3'-dideoxythymidine (AZT) or 2',3'-dideoxyinosine for activity against HIV type 1 (HIV-1). Ten C2 symmetry-based or pseudo-C2 symmetry-based HIV protease inhibitors were active against a laboratory strain (HIV-1IIIB) in the HIV-1 cytopathic effect inhibition assay. Three inhibitors, A75925, A76928, and A77003, selected to represent a range of aqueous solubility and antiviral activity, were active against four different HIV-1 strains tested. These three inhibitors exhibited a significant inhibition of the cytopathic effect of HIV-1 against the CD4+ ATH8 cell line, with 90% inhibitory concentrations ranging from 0.1 to 4 microM. Cellular toxicity was negligible at up to 20 microM. Furthermore, they completely inhibited the replication of monocytotropic strain HIV-1Ba-L in purified monocytes and macrophages at 0.75 to 2 microM. Potent inhibitory activity against a primary HIV-1 isolate and an AZT-resistant HIV-1 variant was also observed for all three inhibitors in phytohemagglutinin-activated peripheral blood mononuclear cells. When these three HIV protease inhibitors and AZT or 2',3'-dideoxyinosine were used in combinations against a primary HIV isolate in phytohemagglutinin-activated peripheral blood mononuclear cells and the results were analyzed with the COMBO program package, their antiviral activities were identified to be synergistic in some cases and additive in others. The present data warrant further investigations of these compounds as potential antiviral agents for the therapy of HIV infections.

Didanosine

[Primary tumor of the ureteral stump following nephrectomy for non-malignant disease. A case report].

Primary tumor in the ureteral stump is rare. A 66-year-old woman visited our hospital because of microscopic hematuria. She had undergone right nephrectomy for the contracted kidney 36 years ago. Intravenous pyelography and cystoscopy showed no positive findings for hematuria. But urine cytology indicated class V. The flexible ureterorenoscopy disclosed a nonpapillary sessile tumor in the ureteral stump. We also did the biopsy of the tumor under the direct vision before open surgery. The specimen showed transitional cell carcinoma, grade 3. The ureteral stump was successfully removed. The flexible ureterorenoscopy was most useful for the diagnosis in this case.

Aged

[Idiopathic thrombocytopenic purpura associated with pregnancy].

We examined 14 patients (18 cases) with idiopathic thrombocytopenic purpura (ITP) during pregnancy at our department. ITP, which had improved, recurred during pregnancy in 4 cases while it developed for the first time during pregnancy in 10 cases. In the other 4 cases, pregnancy occurred in the course of ITP. Although a normal infant was born in 14 cases, 3 stillbirth and a premature infant was observed in 4 cases. Six deliveries had some toxemia of pregnancy. A transient decrease in neonatal platelets was observed in 4 of 14 cases and mother's platelets count was less than 40 X 10(3)/microliters in the 4 cases. Although antinuclear antibody, Coomb's test and antiphospholipid antibody were positive in some cases, these were not markedly related to clinical course or neonatal platelets count. Eleven cases were treated with glucocorticoids, high dose gamma globulin or platelets transfusion, but 11 cases were not treated. Since ITP is frequently observed during pregnancy and may be some risk factor for pregnancy, treatment of ITP is important during pregnancy.

Adult

[Plasma interleukin-6 in patients with disseminated intravascular coagulation].

Plasma Interleukin-6 (IL-6) level was measured in 60 patients with disseminated intravascular coagulation (DIC). Plasma IL-6 level was high in patients with DIC, and was particularly high in patients with multiple organ failure (MOF) or poor prognosis. Plasma IL-6 level correlated positively with C-reactive protein in patients without DIC, but not in those with DIC. The increased plasma IL-6 level observed in DIC patients suggests that activation of the immune system is involved in the progression of DIC and in the pathology of organ failure.

Adult

[Percutaneous nephrostomy versus the placement of double pigtail ureteral stent for the treatment of postrenal failure secondary to malignancies].

From August 1989 through September 1991 we performed percutaneous nephrostomy under ultrasonic guidance in 26 kidneys of 25 patients. We also indwelled double pigtail ureteral stents by endoscopy in 14 kidneys of 13 patients. No patients died because of renal failure. The survival was dependent on progression of primary disease and performance status. Neither significant nor life-threatening complications were encountered. The difference in the improvement of renal function between nephrostomy group and stent group was not statistically significant. Although the indwelling ureteral stent method requires no external drainage bag, this method has certain drawback such as occasional obstruction of stent. Especially in poor risk patients, percutaneous nephrostomy technique seems to be better than placement of double pigtail ureteral stent in the treatment of postrenal failure secondary to malignancies.

Adult

Targeted therapy of human immunodeficiency virus-related disease.

Since the discovery of human immunodeficiency virus (HIV) as a pathogenic retrovirus linked to acquired immunodeficiency syndrome (AIDS), a number of potentially useful strategies for antiretroviral therapy of AIDS and its related diseases have emerged. One such strategy involves use of the broad family of 2',3'-dideoxynucleosides, to which 3'-azido-2',3'-dideoxythymidine (AZT) belongs. AZT has been shown to reduce the replication of HIV in vivo and to confer significant clinical benefits in patients in both early and advanced stages of infection. Other members of the family, 2',3'-dideoxycytidine (ddC), 2',3'-dideoxyinosine (ddI), and 2',3'-didehydro-2',3'-dideoxythymidine (d4T), have also been reported to be active against HIV in short-term clinical trials. The armamentarium of antiretroviral agents is rapidly growing. Various nonnucleoside agents have recently been identified to be active against HIV in vitro. HIV-1 protease inhibitors are notable as possible new therapies for HIV-1-related diseases. However, we have faced several new challenges in the antiretroviral therapy in AIDS. These include long-term drug-related toxicities; emergence of drug-resistant HIV variants; and development of various cancers, particularly as effective therapies prolong survival. Progress in understanding structure-activity relations and clinical effectiveness will continue with dideoxynucleoside analogs. However, it seems certain that a variety of nonnucleoside analogs affecting multiple steps in viral replication will become available before long, and combination therapies using multiple antiretroviral drugs will be available. Such therapies will exert major effects against the moribidity and mortality caused by HIV.

Acquired Immunodeficiency Syndrome

Inhibitors of IMP dehydrogenase stimulate the phosphorylation of the anti-human immunodeficiency virus nucleosides 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine.

2',3'-Dideoxyadenosine (ddAdo) and its deamination product 2',3'-dideoxyinosine (ddIno) (didanosine) inhibit the replication and infectivity of the human immunodeficiency virus (HIV) in a number of in vitro assay systems. Early clinical studies (phase I) have indicated a role for ddIno in the treatment of patients with severe HIV infection. In the present in vitro study, the formation in human T cells (MOLT-4, ATH8, and CCRF-CEM) of the pharmacologically active metabolite of ddIno and ddAdo, 2',3'-dideoxyadenosine-5'-triphosphate (ddATP), was found to be stimulated 2-4-fold by appropriate concentrations of inosinate dehydrogenase (IMPD) inhibitors such as ribavirin, tiazofurin, and mycophenolic acid. Concomitant with this increase in ddATP formation from ddIno was an increase in anti-HIV activity of this agent when it was combined with ribavirin in the ATH8 cell assay system and with tiazofurin in the MOLT-4 assay system. No change was noted in the intracellular concentration of the corresponding physiological deoxynucleoside-5'-triphosphate, dATP; positive correlation was observed, however, between the increase in ddATP formation from ddIno and the increase in intracellular IMP occurring as a consequence of IMPD inhibition. The results support the hypothesis that the stimulation of ddATP formation seen when ddIno is combined with ribavirin or other IMPD inhibitors is a consequence of an increased concentration of IMP, the major phosphate donor for the initial phosphorylation step in the anabolism of ddIno to ddATP, i.e., ddIno----ddIMP.

Antiviral Agents

[Elevated plasma interleukin-6 in patient with idiopathic thrombocytopenic purpura].

Plasma Interleukin-6 (IL-6) level was measured in patients with idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), rheumatoid arthritis and aplastic anemia. Increase in the plasma level of IL-6 was observed in patients with ITP and SLE. The plasma IL-6 level decreased with progression of the treatment for ITP, and it showed weak negative correlations with the platelet count at the onset of ITP. The increases in the plasma IL-6 level suggest the involvement of activation of the immune system in the pathogenesis of ITP.

Adolescent

Effect of atrial natriuretic peptide on renin release in rat isolated glomeruli.

Effects of atrial natriuretic peptide (ANP) on renin release in isolated rat glomeruli were investigated. ANP suppressed renin release by 25% at 5 x 10(-8) M when glomeruli were incubated in a medium containing 1.26 mM calcium (p = 0.0019). When glomeruli were incubated in a calcium free medium containing 2 mM EGTA, ANP suppressed stimulated renin release significantly at 5 x 10(-8) and 5 x 10(-9) M by 25% (p = 0.0204, and p = 0.0101, respectively). These results indicate that ANP suppresses renin release in a dose dependent manner, probably through a calcium independent process.

Animals

DOPA decarboxylase inhibition does not influence the diuretic and natriuretic response to exogenous alpha-atrial natriuretic peptide in man.

The role of dopamine synthesis in the renal actions of human alpha-atrial natriuretic peptide (alpha ANP) was investigated in six dehydrated volunteers using the DOPA decarboxylase inhibitor carbidopa. Each subject received oral placebo or carbidopa (100 mg) followed by an infusion of alpha ANP 10 pmol.kg-1.min-1 for 1 h. The responses to placebo alone and to carbidopa alone were investigated on separate occasions. alpha ANP produced a similar increase in plasma immunoreactive alpha ANP whether placebo or carbidopa pretreatment had been given. Urinary dopamine excretion was increased by alpha ANP. Carbidopa pretreatment substantially attenuated this increase without affecting the natriuretic or water-diuretic response to alpha ANP. Carbidopa also failed to alter the change in filtration fraction produced by alpha ANP. The results suggest that increased synthesis of intrarenal dopamine is not required for the renal effects of alpha ANP in man.

Adult

[Therapeutic evaluation of combination therapy using C-425 and antibiotics in severe bacterial infections--a double blind group comparative study. The C-425 Research Group for Infectious Comparative Study].

Clinical usefulness of C-425, a native human immunoglobulin liquid preparation for intravenous injection, was studied in combination with antibiotics in severe bacterial infections in a double blind group comparison using an alkylated human immunoglobulin liquid preparation (Polyglobin, A.gamma G) as a reference drug. The following results were obtained: 1. C-425 or A.gamma G was administered to a total of 117 patients, of whom 89 patients, 45 in C-425 group and 44 in A.gamma G group, were included in the present analysis of efficacy and usefulness. Analysis of safety of the drugs included a total of 113 patients, 58 in C-425 group and 55 in A.gamma G group. 2. Efficacy and usefulness were graded according to a visual analog scale (VAS). 3. Mean efficacy values with standard deviations of VAS value were calculated at 52.0 +/- 34.9 for the C-425 group, and 47.2 +/- 34.8 for the A.gamma G group. The respective medians were 59.0 and 61.0. The Mann-Whitney U-test revealed no significant differences between the two groups. When those with VAS values of 50 or above were regarded as cases of effective treatment, the efficacy rates of the two groups were also practically comparable. 4. Side effects were not observed in either drug group. 5. Mean usefulness values with standard deviations were 52.3 +/- 34.9 for the C-425 group, and 47.9 +/- 35.0 for the A.gamma G group. The respective medians were 60.0 and 61.0. The Mann-Whitney U-test revealed no significant differences between the two groups. When the cases with VAS values of 50 or above were regarded as cases of useful treatment, there were no significant differences in the utility rates between the two groups. From these results, C-425 was considered to be useful for treating severe bacterial infections when used combined with antibiotics.

Adolescent

Disappearance of anti-p17 correlates with successful isolation of human immunodeficiency virus and deterioration in clinical status.

Anti-p17 was examined as a human immunodeficiency virus (HIV) marker predicting the onset of the acquired immunodeficiency syndrome (AIDS). Two different comparisons were done: (1) anti-p17 negativity and successful HIV isolation; and (2) anti-p17 negativity and clinical status, using the Centers for Disease Control classification. Anti-p17 negativity was not only significantly correlated with deterioration in clinical status (P less than 0.01), but also with successful HIV isolation (P less than 0.05). HIV isolation was affected by several drugs, e.g. zidovudine. However, the results of the antibody test were not affected. It is significant that anti-p17 can compensate for the defects of virus isolation.

Acquired Immunodeficiency Syndrome

[Aspiration biopsy of regional lymph node in bladder cancer].

Percutaneous transabdominal fine needle aspiration biopsy (FNAB) of the pelvic and retroperitoneal lymph nodes was performed in 116 patients with bladder cancer. Metastasis to the regional lymph nodes was determined by this method in 21 patients. FNAB was positive in 10 of 12 patients having unequivocally positive or highly suspicious lymphogram, and in 11 of 104 patients (11%) having normal lymphogram. The results of FNAB were compared to the finding of lymph node dissection (LND) in 51 patients. FNAB and LND were negative in 43 patients and positive in 5. Two patients were FNAB negative but LND positive, and the remaining one case was FNAB positive but LND negative. The correlation between cytological diagnosis of FNAB and histological diagnosis of LND was 94 per cent. The survival rate of the cases of FNAB positive and lymphography negative was significantly higher than that of lymphography positive (p less than 0.01). The metastatic site of 5 cases with bladder cancer who are alive now without disease after more than 3 years was under the common iliac node and the number of the involved nodes was within 3.

Aged

[Clinical evaluation of imipenem/cilastatin sodium against severe infections in patients with hematopoietic disorders].

Sixty-eight patients with severe infections associated with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS) and the efficacy and safety of this drug were evaluated. 1. Fifty-nine patients were evaluable for the efficacy. Clinical efficacies were excellent in 10 patients, good in 24, fair in 11 and poor in 14, and the overall efficacy rate was 57.6%. 2. The clinical efficacy rates were 62% against septicemia and suspected septicemia, 40% against pneumonia and 100% against urinary tract infection (1 case). 3. The clinical efficacy rates when these patients were grouped according to numbers of neutrophils after treatment were: less than 100/mm3; 44.4%, 101-500/mm3; 58.3% and over 501/mm3; 60.5%. The efficacy rate was particularly excellent, 60.0%, for patients with neutrophil counts were less than 100/mm3 both before and after treatment. 4. Sixty-eight patients were evaluable for the safety. Side effects were observed in 5 patients and abnormal laboratory test values were observed in 5 patients.

Adolescent