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Biomedical subjects

K Imamura

Publications and source records attributed to K Imamura.

At least 217 records · Page 12Linked to original sources

Valvular heart disease in Kawasaki syndrome: incidence and natural history.

To elucidate the incidence and natural history of valvular heart disease in Kawasaki syndrome, we analyzed patients who were found to have a new heart murmur after the onset of the disease. Among 1215 patients we found 13 (1.1%) with valvular disease (12 with mitral regurgitation and one with aortic regurgitation). We compared these patients with 30 who did not have valvular lesions. The duration of fever was longer and the incidence of coronary artery lesions significantly higher than in those without valvular disease. Heart murmurs disappeared within 2 months after the onset of valvular heart disease in five patients, whereas in another six, all involving valve prolapse, they persisted for 2 years or more. We postulate that two different mechanisms may be responsible for the variation in the duration of valvular heart disease: one, which disappeared spontaneously, was attributed to pancarditis; the other, which persisted, was due to dysfunction in valve and papillary muscles as a result of ischemia.

Angiography↗

Measurement of inhibin concentrations in men: study of changes after castration and comparison with androgen levels in testicular tissue, spermatic venous blood, and peripheral venous blood.

We measured serum inhibin levels in eight untreated patients with prostatic cancer undergoing castration by RIA using an antiserum against 31-kDa bovine follicular fluid inhibin. The inhibin concentrations in testicular tissue and spermatic venous blood were also measured in six of these patients. Serum inhibin levels (mean +/- SD, 377.8 +/- 212.1 U/L), declined rapidly after castration (15 min after, 233 +/- 171.4; 30 min, 224.6 +/- 156.6; 1 h, 181.5 +/- 95.9; 2 h, 174.3 +/- 69.4; 4 h, 122 +/- 6.4; 6 h, less than 120). High concentrations of inhibin were detected in testicular tissue (31,360 +/- 15,180 U/kg), and the levels in spermatic venous blood (3,178.3 +/- 1,386.8 U/L) were approximately 10 times greater than those in peripheral blood (385.5 +/- 233.1 U/L). Testosterone levels were 1,968.2 +/- 992.3 nmol/kg in testicular tissue and approximately 100 times greater in spermatic venous blood (1,631.6 +/- 389.7 nmol/L) than in peripheral blood (18.0 +/- 4.4 nmol/L). These results suggest that circulating inhibin in men mainly originates from testis and that one of the routes of secretion is via the bloodstream.

Aged↗

[Clinical study of tumor markers in prostatic cancer].

We measured prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostatic specific antigen (PSA) levels simultaneously in the serum of 52 patients with untreated prostatic cancer and 44 patients with benign prostatic hypertrophy to assess the clinical usefulness of these tumor markers. PAP and PSA were measured by radioimmunoassay and gamma-Sm by enzyme immunoassay. The positive rates of PAP, gamma-Sm and PSA in patients with prostatic cancer were 50.0, 61.5 and 69.2%, respectively, and those in patients with benign prostatic hypertrophy were 11.4, 13.6 and 13.6%, respectively. In patients with early stage prostatic cancer (stage A and B), the positive rates of PAP, gamma-Sm and PSA were 20.8, 41.7 and 54.2%. The efficiency of PSA was the highest among the three markers. The positive rate of the combination assay of PAP and PSA, that of gamma-Sm and PSA and that of PAP, gamma-Sm and PSA were slightly higher than that of the PSA assay alone. However, the efficiency of the PSA assay alone was higher than that of any combination. No significant correlation was found between histopathological grade and the level of each tumor marker. A significant correlation was found between PAP and gamma-Sm (r = 0.68, P less than 0.001), and between PAP and PSA (r = 0.61, P less than 0.001), but there was no correlation between gamma-Sm and PSA. These results suggest that PSA is the most useful marker and the combination assay of multiple markers is not so advantageous, at least for screening of prostatic cancer.

Acid Phosphatase↗

Controlled trial comparing an elemental diet with prednisolone in the treatment of active Crohn's disease.

To determine whether an elemental diet or prednisolone would be more effective for treating acute Crohn's disease, a controlled trial was conducted on 20 patients with acute Crohn's disease who had never received specific treatment. The first ten patients were put on an elemental diet and the remaining ten were prescribed prednisolone for six weeks at an initial dose of 0.7 mg/kg/day. Patients were assessed using the simple activity index, body weight, erythrocyte sedimentation rate, C-reactive protein and alpha 2 globulin, serum albumin, and radiographic findings of bowel lesions. At six weeks, the patients on the elemental diet showed a significantly greater improvement in the activity index, inflammatory signs such as C-reactive protein and alpha 2 globulin, and radiographic findings of bowel lesions than did those on the steroid. Patients who were given steroids for six weeks and then treated with the elemental diet for four weeks showed improvement in the radiographic findings of bowel lesions and inflammation. The present study strongly suggests that elemental diet is superior to steroids for treating active Crohn's disease.

Adult↗

[Effect of epidural anesthesia on the function of hormonal regulation in the hypothalamic-pituitary-testicular axis].

To evaluate the effects of epidural anesthesia on the hypothalamic-pituitary-testicular axis, we examined the concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T). The effects of epidural anesthesia on plasma levels of LH, FSH and T were investigated in 8 men aged from 64 to 87 years, suffering from untreated prostate cancer. There were no significant differences in plasma levels of LH, FSH or T between patients under epidural anesthesia and patients under no anesthesia. The effects of epidural anesthesia on plasma levels of LH, FSH and T after LH releasing hormone (LH-RH) administration were studied in 10 men between 65 and 84 years with diagnoses of untreated prostate cancer. Plasma LH and FSH levels increased significantly after LH-RH administration under epidural anesthesia or no anesthesia. Plasma LH and FSH were lower under epidural anesthesia than under no anesthesia. No change in plasma T level was observed after LH-RH administration under epidural anesthesia. We conclude that there is no effect of epidural anesthesia on the hypothalamic-pituitary-testicular axis.

Aged↗

Generation and characterization of monoclonal antibodies against rat microglia and ontogenic distribution of positive cells.

We have generated two mouse IgM monoclonal antibodies against rat microglia. The RMG-1 antibody recognized a 46-kilodalton cell-membrane antigen of ameboid microglia and cross-reacted with perivascular cells, monocytes/macrophages, and capillary endothelial cells of various organs but not with ramified microglia. In the normal brain, RMG-1-positive cells were found in the choroid plexus, periventricular area, corpus callosum, subarachnoid space and white matter of the cerebrum. The RMG-2 antibody recognized a 78-kilodalton cytoplasmic and cell-membrane antigen of ameboid and ramified microglia and cross-reacted with perivascular cells and monocytes/macrophages of various organs but not with endothelial cells. A small number of RMG-2-positive cells were found in the choroid plexus and subarachnoid space on embryonic day 17. On postnatal day 1, RMG-2-positive cells appeared in the periventricular area and corpus callosum and then migrated to the internal capsule and thalamic nucleus. Thereafter, the number of RMG-2-positive cells increased, reaching a maximum on postnatal day 10 to 14, and gradually decreasing by postnatal day 28. These observations show that microglia are cells of monocytic lineage that enter the brain parenchyma late in embryogenesis or early in the postnatal period and lose at least some monocytic antigens to differentiate into ramified microglia. These monoclonal antibodies will provide useful tools to investigate the relation between microglia, perivascular cells, and endothelial cells in the brain and the kinetics of these cells in normal or pathologic conditions.

Aging↗

[Curability of multidisciplinary treatment including combined hyperthermia, radiotherapy and chemotherapy].

Reported are the results in 311 patients who received a multidisciplinary treatment for their cancers, said treatment combining hyperthermia, radiotherapy, and chemtherapy. Of his number, 266 patients were in the advance stage of their disease while another 42 still had localized cancers. According to the criteria of Koyama and Saitoh for evaluating solid tumors that had received chemotherapy, of 298 evaluable patients, 64 showed a complete response (CR), 94 showed a partial response (PR), 89 showed no change (NC), and 57 showed a progressive disease (PD), for an overall response of 53.0% (158 cases). A multidisciplinary treatment combining radiotherapy and hyperthermochemotherapy was used for cases involving localized tumors of the vulva, the skin, the thyroid gland, the prostate gland, the uterus, the rectum, the soft tissue bone, and the ovary, though our treatment regimen could not be continued in cases of tumors involving the stomach, the esophagus, the lung, the mediastinum, the liver, and the pancreas. Our data has shown that a high overall rate of curability was achieved in cases involving the stomach, the bladder, the blood, the skin, the head, and neck, and the esophagus.

Adult↗

[Changes in immunoparameters following cryosurgery in prostate cancer].

To determine the effect on immunoparameters of cryosurgery in cases of stage B prostatic cancer and to determine whether such changes were specifically related to the cryosurgery technique, immunoparameters were measured and compared with cases of prostatic hyperplasia treated by transurethral resection (TUR-P). A decrease in immunoparameters was recognized in the cryosurgery group at 1-3 days postoperatively (increase in IAP, decrease in NK cell activity, decrease in lymphocyte blastogenesis reaction to PHA). The protein histograms, immunoglobulin and IAP changed similarly after the two above procedures. These changes were thought to be due to the invasive nature of the procedures. However, some difference was seen between the cryosurgery group and the TUR-P group in terms of rate of lymphocyte blastogenesis reaction to PHA and Con A, IgG, complement and NK cell activity which might indicate a specific effect of cryosurgery different from TUR-P.

Aged↗

Interaction of noradrenergic and cholinergic systems in regulation of ocular dominance plasticity.

We studied interactions among the noradrenergic (NA) and the muscarinic cholinergic (ACh) systems in the regulation of ocular dominance plasticity in kitten visual cortex. The cortex was bilaterally infused with 6-hydroxydopamine (6-OHDA) for a week. Upon termination of the 6-OHDA infusion, one hemisphere was infused with a muscarinic ACh agonist, bethanechol, through the same, chronically implanted cannula for the second week together with monocular lid suture. The other hemisphere received an infusion of the vehicle solution alone. (1) Only in the hemisphere infused with bethanechol at relatively high concentrations did we obtain a clear shift in ocular dominance. We also found that the effect of bethanechol was concentration-dependent. (2) By comparing necessary concentrations of bethanechol and NA for the respective maximal effects, we noted that the former was at least 100-fold less effective than the latter in restoring the plasticity. (3) The cortical infusion of bethanechol did not restore the plasticity to the propranolol-pretreated cortex; the ocular dominance distribution remained virtually unchanged. This result was interpreted as suggesting that functioning beta-adrenoreceptors are needed for the cortical effect of activating the muscarinic ACh receptors to become detectable. (4) The expected shift in ocular dominance following monocular deprivation was partially suppressed, when highly concentrated scopolamine, a muscarinic ACh antagonist, was used, indicating that the involvement of the ACh system in this matter was indirect. The concentration of scopolamine needed for the half-maximum effect was 172-fold higher than that of propranolol. We thus conclude that the involvement of the muscarinic ACh system in ocular dominance plasticity is secondary to that of the NA-beta-adrenoreceptor system.

Aging↗

[A comparative study between cefodizime (CDZM) and cefotaxime (CTX) in respiratory tract infections].

The clinical efficacy and safety of Cefodizime (CDZM), a new cephem antibiotic, was objectively compared with that of Cefotaxime (CTX) in patients with respiratory infections under a well-controlled comparative study. Patients were administered CDZM or CTX by drip infusion b.i.d. for 14 days in principle at a daily dose of two grams. The parameters assessed were clinical efficacy, safety and clinical usefulness. The following results were obtained: 1. On the basis of committee judgement the clinical efficacy rate was 78.1% (125/160) for the CDZM group, 82.7% (124/150) for the CTX group, and no significant difference was observed between the two drug groups. On the other hand, on the basis of judgement by physicians in charge, the clinical efficacy rate was 83.1% (133/160) for the CDZM group, 83.9% (125/149) for the CTX group, and no significant difference was observed between the two groups. 2. The corresponding figures for patients with pneumonia and pulmonary suppuration were 82.4% (70/85) for the CDZM group, 79.7% (59/74) for the CTX group and no significant difference was observed according to the committee judgement. The judgement by physicians in charge also revealed 83.5% (71/85) for the CDZM group and 82.2% (60/73) for the CTX group. No significant difference was noted between the two groups. While, the committee judgement for the clinical efficacy in patients with chronic respiratory tract infections showed 73.3% (55/75) for the CDZM group, 85.5% (65/76) for the CTX group, and no significant difference was observed between the two drug groups. The corresponding figures were 82.7% (62/75) for the CDZM group, 85.5% (65/76) for the CTX group, and no significant difference was observed between the two drug groups on the judgement by physicians in charge. Furthermore, the clinical efficacy of both drugs on chronic respiratory tract infections was assessed according to "Criteria for Evaluation of Clinical Efficacy of Chemotherapeutics on Chronic Respiratory Tract Infection". It was 76.8% (53/69) for the CDZM group, 76.3% (58/76) for the CTX group, and no significant difference was observed between the two groups. 3. The bacteriological eradication rate of causative pathogens was 92.4% out of 66 patients treated with CDZM and 95.5% out of 67 patients treated with CTX in whom judgement was possible. No significant difference was observed between the two drug groups. 4. The adverse reactions occurred in 4 (2.2%) patients for the CDZM group and 8 (4.5%) patients for the CTX group respectively, with no significant inter-group difference in frequency of these reactions for all cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester.

The treatment of human HL-60 promyelocytic leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcript. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNF mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase A2 blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B4. In contrast, the cyclooxygenase metabolite prostaglandin E2 inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B4 and prostaglandin E2.

Arachidonic Acid↗

Effects of botulinum toxin type D on secretion of tumor necrosis factor from human monocytes.

Botulinum toxins are potent neurotoxins which block the release of neurotransmitters. The effects of these toxins on hematopoietic cells, however, are unknown. Monocytes secrete a variety of polypeptide growth factors, including tumor necrosis factor (TNF). In the study reported here, the effects of botulinum toxin type D on the secretion of TNF from human monocytes were examined. The results demonstrate that botulinum toxin type D inhibits the release of TNF from monocytes activated by lipopolysaccharide (LPS) but not by 12-O-tetradecanoylphorbol-13-acetate. Botulinum toxin type D had no detectable effect on intracellular TNF levels in LPS-treated monocytes, indicating that the effects of this toxin involve the secretory process. This inhibitory effect of botulinum toxin type D on TNF secretion from LPS-treated monocytes was partially reversed by treatment with 12-O-tetradecanoylphorbol-13-acetate or introduction of guanosine 5'-[gamma-thio]triphosphate into these cells. The results demonstrate that TNF secretion is regulated by at least two distinct guanine nucleotide-binding proteins, one responsible for the activation of phospholipase C and another which acts as a substrate for botulinum toxin type D. ADP-ribosylation of monocyte membranes by botulinum toxin type D demonstrated the presence of three substrates with Mrs of 45,000, 21,000, and 17,000. While the role of these substrates in exocytosis is unknown, the results suggest that the Mr 21,000 substrate is involved in a process other than TNF secretion.

Binding Sites↗

A phase I trial of recombinant human tumor necrosis factor and interferon-gamma: effects of combination cytokine administration in vivo.

The combination of tumor necrosis factor (TNF) and interferon-gamma has synergistic bioactivity in numerous preclinical model systems. We have tested this potential synergism in vivo by administration of both cytokines to patients with advanced cancer using overlapping 24-hour continuous intravenous (IV) infusions in a phase I trial. Thirty-six patients were treated with a fixed dose of interferon-gamma (200 micrograms/m2/d) with interpatient dose escalation of TNF (from 5 to 205 micrograms/m2/d). The dose-limiting toxicity at the maximal-tolerated dose (MTD) of TNF (205 micrograms/m2) with interferon-gamma was hypotension. Other toxicities noted included an influenza-like syndrome, transient decreases in circulating leukocyte and platelet counts, subclinical evidence of disseminated intravascular coagulation, and the sporadic occurrence of acute pulmonary toxicity. The recommended phase II dose for this combination schedule is TNF, 136 micrograms/m2, with interferon-gamma, 200 micrograms/m2. The addition of interferon-gamma to TNF resulted in a greater than three-fold increase in toxicity compared with TNF administered as a single agent, supporting the hypothesis that the combination of these cytokines may induce synergistic effects in vivo.

Adult↗

Antigenicity tests on propiverine hydrochloride in guinea pigs and mice.

Antigenicity of propiverine hydrochloride (P-4), a newly developed drug for pollakisuria, was investigated in guinea pigs and mice. 1. Two strains of mice (BALB/c and C3H/He) showed no production of antibodies against P-4 inoculated with aluminum hydroxide gel (alum) as an adjuvant, judged by the heterologous passive cutaneous anaphylaxis (PCA) test using rats. On the other hand, antibodies against P-4-ovalbumin (OVA) conjugate inoculated with alum was definitely detected. 2. In the studies with guinea pigs, both the inoculation of P-4 alone and of P-4 with Freund's complete adjuvant (FCA) as an adjuvant did not produce positive reactions in any of homologous passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA) and passive hemagglutination (PHA) tests. On the other hand, the inoculation of P-4-OVA conjugate with FCA produced positive reaction in all of PCA, ASA and PHA tests. 3. In the active cutaneous anaphylaxis (ACA) test in guinea pigs inoculated with P-4-OVA conjugate with FCA, positive reaction was produced by eliciting injection of P-4-human serum albumin (HSA). 4. In the Schultz-Dale reaction test, any animals in any groups showed no positive reaction to both eliciting antigens, P-4 and P-4-HSA. 5. These findings showed that P-4 had no antigenicity in guinea pigs and mice.

Anaphylaxis↗

The role of the sympathetic nervous system in cysteamine-induced gastric lesions in rats.

Cysteamine.HCl, when administered subcutaneously at 350 mg/kg, consistently induced severe gastric lesions in Wistar Kyoto rats (WKY), but not in spontaneously hypertensive rats (SHR). In both WKY and SHR, visible ulcers could not be induced in the duodenum in response to cysteamine. It appears that the stomach and duodenum of SHR are resistant to cysteamine due to hyperfunctioning of the sympathetic nervous system.

Animals↗

[Comparison of non-HPLC 1 alpha, 25(OH)2D assay system with the HPLC method].

Recently, a method not requiring high performance liquid chromatography (HPLC) has been developed (Amersham Inc., U.K) for the measurement of levels of 1 alpha, 25(OH)2D, which demonstrates the most potent physiological effect among the metabolites of vitamin D. Until recently, purification of 1 alpha, 25(OH)2D fraction with HPLC has been considered indispensable prior to radioreceptor assay of this metabolite. Therefore, we used the Amersham assay system to determine whether it is possible to correctly measure the level of 1 alpha, 25(OH)2D without the HPLC process. The procedures we used were to extract the serum with an organic solvent, followed by fractionation of vitamin D metabolites through an LH-20 column. The products with or without the use of HPLC were submitted to radioreceptor assay using chick embryo intestinal receptors. As a result, it was found that (1) Separation and yield were improved by changing the column size, (1) Serum values 1 alpha, 25 (OH)2D in healthy subjects obtained by HPLC and non-HPLC methods were in good agreement with the theoretical values. Although the values thus obtained in patients with chronic renal insufficiency (with or without dialysis) were somewhat lower than the theoretical values, the result was consistent because there was no significant difference between the tow sets of measured values, and the correlation coefficient was r = 0.990. (3) Variations within the assay were CV = 16.5% for HPLC group and CV = 21.4% for non-HPLC group.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗