Biomedical subjects

J Sato

Publications and source records attributed to J Sato.

At least 289 records · Page 16Linked to original sources

PubMed1992

Strong heat stimulation sensitizes the heat response as well as the bradykinin response of visceral polymodal receptors.

1. Hyperalgesia after thermal injury is a common phenomenon, but its mechanism is poorly understood. As a step toward understanding the mechanism for heat sensitization, we searched conditions that would induce sensitization consistently and studied changes in polymodal receptors in their responses to heat (45 and 48 degrees C) and to bradykinin. Experiments were conducted in vitro, with the use of testis-superior spermatic nerve preparations excised from anesthetized dogs. 2. Stimulation at 55 degrees C for 30 s induced clear augmentation of the responses to stimulations at 45 and 48 degrees C when tested within 10 min in 22 out of 24 testicular polymodal units. In the remaining two units, weak or delayed augmenting tendencies were observed. The response to stimulation at 45 degrees C increased from 0.28 +/- 0.08 to 2.99 +/- 0.46 (SE) imp/s, whereas at 48 degrees C it increased from 1.08 +/- 0.16 to 4.60 +/- 0.63 imp/s (P < 0.001, n = 24). A low-level ongoing discharge appeared in about one-half of the units studied. 3. Despite frequent rinsing of the receptive field, augmentation of the heat response observed after stimulation at 55 degrees C continued for up to approximately 3 h. 4. The response to bradykinin (94 nM) was also potentiated: the net mean discharge rate (NMDR) during a 1-min application period of bradykinin as well as the total number of impulses induced by one bradykinin application significantly increased from 0.91 +/- 0.27 to 1.97 +/- 0.32 imp/s and from 213.9 +/- 42.3 to 433.5 +/- 58.7 impulses, respectively (P < 0.001, n = 15).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Phase I/II trial and pharmacokinetics of intrathecal diaziquone in refractory meningeal malignancies.

PURPOSE: Because there is a compelling need to develop new agents for intrathecal use, we investigated the safety, efficacy, and CSF pharmacokinetics of diaziquone (AZQ) following intrathecal administration in patients with refractory meningeal malignancies. PATIENTS AND METHODS: Thirty-nine patients received 45 courses of intrathecal AZQ. Two schedules were studied; twice-weekly administration of a 1- or 2-mg dose and "concentration times time" (C x T) administration of 0.5 mg every 6 hours for three doses, administered once weekly. RESULTS: Dose-limiting toxicity consisting of headache, nausea, or vomiting occurred in only three patients and only at the 2-mg, twice weekly dose. The schedules of 1 mg twice-weekly and 0.5 mg every 6 hours for three doses were well tolerated. Thirty-seven courses were assessable for response. The overall response rate was 62%. Complete responses (CRs) occurred in 14 of 37 courses (38%) and partial responses (PRs) occurred in nine of 37 courses (24%). Among patients with meningeal leukemia, CRs were observed in 11 of 26 courses (42%) and PRs in nine of 26 courses (35%). There was no difference in response rate related to dose or schedule. The pharmacokinetic behavior of intrathecally administered AZQ was characterized by biexponential disappearance from ventricular CSF, with mean half-lives of 18.2 and 78.6 minutes. The mean clearance rate was 0.37 mL/min. CONCLUSION: Intrathecal AZQ is safe, well tolerated, and highly active against refractory meningeal malignancies.

Adolescent↗

PubMed1992

Single-dose kinetics of primidone in human subjects: effect of phenytoin on formation and elimination of active metabolites of primidone, phenobarbital and phenylethylmalonamide.

Effect of repetitive administration of phenytoin (PHT) on the single-dose pharmacokinetics of primidone (PRM) was investigated in 3 healthy male subjects. The peak concentration of unchanged PRM was achieved at 12 and 8 h after the administration of PRM in the absence and the presence of PHT, respectively. The elimination half-life of PRM was decreased from 19.4 +/- 2.2 (mean +/- S.E.) to 10.2 +/- 5.1 h (p < 0.05) and the total body clearance was increased from 24.6 +/- 3.1 to 45.1 +/- 5.1 ml/h/kg (p < 0.01) in the presence of PHT. No significant change was observed for the apparent volume of distribution between the two treatments. In the absence of PHT, the measurable amount (> or = 0.1 mumol/l) of phenobarbital (PB) and phenylethylmalonamide (PEMA) did not appear in the serum until 5.3 and 1.3 h after the PRM administration, and the peak concentrations of PB and PEMA were achieved at 52 and 36 h, but the concentrations of both metabolites were very low (PB 1.3 mumol/l; PEMA 1.7 mumol/l). In the presence of PHT, within 0.8 and 0.5 h after the administration of PRM, the derived PB and PEMA appeared in the serum. About a 6-fold increase in the peak concentrations of both the metabolites were observed (PB 8.2 mumol/l; PEMA 11.0 mumol/l). No significant changes were observed for the elimination half-lives of both PB and PEMA in the absence and presence of PHT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

An endoscopic study of antibiotic-associated hemorrhagic colitis.

Colonoscopy was performed on acute stage within 72 hours from onset in 48 patients with antibiotic-associated hemorrhagic colitis (AAHC). From our observations we have developed a new endoscopic classification of AAHC and investigated the incidence of each finding in further detail. We have classified in principle the endoscopic findings of the 48 subjects into two groups: major and minor ones respectively. Category of major findings were: 1) diffuse mucosal hemorrhage (100%); 2) spotty mucosal hemorrhage (100%), and 3) linear mucosal hemorrhage (22.9%), while minor findings were: 1) irregular ulcers in 10.4%; 2) aphthoid ulcers in 6.3%, and 3) linear erosions or ulcers in 4%. Minor findings were ulcers or erosions present over the hemorrhagic mucosa associated with the moderate degree of inflammation. A histopathologic study of colon biopsy specimens from 24 patients with AAHC showed hemorrhage and inflammatory cell infiltration in the lamina propria mucosae varying from mild to moderate in extent. It was concluded that AAHC was a colonic mucosal hemorrhagic disease caused by the destruction of mucosal vessels from unknown causes and in this disease mild to moderate inflammation was partially followed by ulceration over the edematous and hemorrhagic mucosa of the colon.

Adolescent↗

PubMed1992

Chemotherapy in small cell lung cancer--from view point of dose intensity.

Results of chemotherapy trials for small cell lung cancer carried out for the past 5 years were analyzed from view point of dose intensity. Early study of CDDP+EP+ADM (1985 to 1987) showed moderate response rate (RR) of 72% with MST of 369 days. Succeeding alternative protocol of CDDP+EP+VCR/CPM+ADM+MTX (1989-1990) showed improved RR of 88% and MST of 13 months. Actual dose and interval for the alternating regimen was superior to the single arm regimen. Projected relative dose intensity against MAOP protocol including 6 drugs common to our regimen was 0.86 and delivered RDI was 0.61 with comparable RR and MST. The results may indicate that change of dose intensity within the conventional range does not result in major advantage or disadvantage for substantial prolongation of the survival in SCLC patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

[Recovery of hematopoiesis after high-dose chemotherapy and peripheral blood stem cell autografts in children].

Hematopoietic recovery kinetics were evaluated in 34 children with therapy-refractory malignant tumors who underwent a total of 35 peripheral blood stem cell autografts (PBSCT) after marrow-ablative chemotherapy without total body irradiation. A negative correlation was found between the numbers of colony-forming units of granulocyte-macrophage (CFU-GM) infused per kilogram of the patients' body weight and the time of achieving an absolute granulocyte count (AGC) of 0.5 x 10(9)/l or a platelet count of 50 x 10(9)/l (granulocyte: r = -0.631, p less than 0.001, platelet: r = -0.590, p less than 0.001). The patients were classified into three groups; 14 patients who received less than 1 x 10(5) CFU-GM/kg (group A), 7 patients who received 1-3 x 10(5) CFU-GM/kg (group B), and 14 patients who received greater than or equal to 3 x 10(5) CFU-GM/kg (group C). The AGC recovered to 0.5 x 10(9)/l by 21 day in group A, 14 day in group B, and 10 day in group C. The platelet count recovered to 50 x 10(9)/l 102 in group A, 23 in group B, and 16 day in group C patients. The final platelet infusion was on day 60 in group A, day 12 in group B, and day 12 in group C. Transient decrease in the blood cell count developed in all patients 3 to 7 weeks after transplantation, and two cases developed reversible ITP. In the remaining patients, the recovered hematopoietic function was sustained for 1-48 months after transplant action.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Experience with peripheral blood stem cell collection for autografts in children with active cancer.

This report examines laboratory and clinical experience with peripheral blood stem/progenitor cell harvest for autografts in 71 consecutively referred children with various types of cancer from one institution. The age of the patients ranged from 7 months to 17 years with a median of 8 years. Ten of the 71 referred children were removed from the collection procedure because of failure to induce clinical remission (nine) or deteriorating chemotherapy-induced liver failure (one). A total of 215 aphereses were performed on a CS 3000 cell separator in 61 patients, including 18 children aged 4 years or less. The methylcellulose progenitor assay was used as an index of stem cell collection. A minimum of greater than or equal to 3 x 10(5) colony-forming units-granulocyte/macrophage (CFU-GM)/kg body weight were collected in 31 of 71 children (44%) with a mean of 3.1 (range, 1-5) aphereses, and greater than or equal to 1 x 10(5) CFU-GM/kg in 46 children (65%). The incidence of serious morbidity was low. When apheresis or chemotherapy was repeated, the progenitor yields decreased rapidly. By multivariate analysis, the age of the patients was the only significant predictor of CFU-GM yield (p = 0.009). In our experience with 12 children with acute leukemia or non-Hodgkin's lymphoma, regimens containing high-dose cytarabine (2.0 g/m2 x 10) were effective for mobilization. Our results extend the earlier findings that harvesting PBSCs for autografts in children with active cancer is a safe and reliable procedure with a low incidence of serious morbidity.

Adolescent↗

PubMed1992

[Varicella-zoster virus infection after peripheral blood stem cell autografts in children with leukemia or non-Hodgkin's lymphoma].

Thirty-two patients with leukemia or non-Hodgkin's lymphoma (NHL) who underwent high-dose chemotherapy without total body irradiation (TBI) and peripheral blood stem cell autografts (PBSCT) were evaluated for the occurrence of clinically manifested varicella-zoster virus infection (VZV). In a minimum follow-up of 3 mo, there were 14 cases with VZV; 12 patients were treated with intravenous acyclovir and 2 patients received additional intravenous VZV hyperimmune immunoglobulin preparations. History of previous varicella-zoster at some time before PBSCT was the only significant risk factor for the development of VZV. Furthermore, a significant association between VZV and higher disease-free survival rate after PBSCT was proved. Development of minor and reversible VZV is rather common event after high-dose chemotherapy without TBI and PBSCT. VZV appears to be one of the factors which reflects basic physiologic mechanism preventing relapse of leukemias or NHL after PBSCT.

Adolescent↗

PubMed1992

[Clinical significance of respiratory infections associated with lung cancer patients].

An attempt was made to interpret the clinical significance of secondary infections associated with lung cancer. The incidence of secondary infections was 51.4% in 214 in-patients with lung cancer in our institution in 1988 and 1989, and almost all of them had respiratory infections caused by commonly encountered bacteria. The incidence of infection was high in lung cancer of cell types other than adenocarcinoma, and in those with hypoalbuminemia, impaired cellular immunity and obstruction of the airway. The prognosis in patients with infection was much poorer than that in patients without infection. Major pathogens responsible for infection were Staphylococcus aureus including methicillin-resistant S. aureus (MRSA), Haemophilus influenzae, Klebsiella spp. and Pseudomonas aeruginosa. These pathogens, except for H. influenzae, were isolated in the terminal stage in cases with airway obstruction and post cancer chemotherapy. The efficacy rate of 194 therapeutic regimens against infection was 57.7%. It was thus found that the efficacy rate in 1988 and 1989 exceeded that in the 1970s. The effectiveness was very poor for infections caused by S. aureus and P. aeruginosa, and for cases with airway obstruction and marked impairment of pulmonary blood flow. The efficacy rate of single-drug regimens was 57.1% (80/140) and that of combined regimens was 59.3% (32/54). The above results indicate that a new combined therapy which includes a beta-lactam antibiotic as well as measures to improve the general health of compromised hosts are required in the treatment of secondary infections in these patients.

Adult↗

PubMed1992

Production of interleukin 3 and granulocyte-macrophage colony-stimulating factor from stimulated blood mononuclear cells in patients with aplastic anemia.

Blood cells from patients with aplastic anemia (AA) were evaluated for the ability to produce interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on stimulation with phytohemagglutinin (PHA) or antilymphocyte globulin (ALG) by the use of an IL-3-dependent cell-line, TF-1, and the GM-CSF-IRMA kit. The IL-3 levels in patients with active AA were significantly lower, both in PHA-stimulated conditioned medium (CM) and in ALG-CM, than those of normal healthy donors (HD; p < 0.01). The degree of reduced IL-3 production in AA patients correlated well with the severity of neutropenia; the level of IL-3 returned to normal after successful treatment with ALG plus methylprednisolone (ALG therapy). On the other hand, GM-CSF production in AA patients varied widely and was only significant in remission patients in PHA-CM; in this case production was higher than that in active AA patients (p < 0.05) or in HD (p < 0.01). Sensitivity to PHA or ALG stimulation was evaluated by the ratio of IL-3 concentrations in ALG-CM versus PHA-CM (ALG/PHA index). The index varied widely from < 0.1 to > 10 in AA patients, contrasting to the clustered values in HD. Seven of the eight patients who had an ALG/PHA index of > 1.0 showed a good clinical response to ALG therapy. However, 12 of the 14 patients who had a lower index (< 1.0) failed to respond. The ALG/PHA index might have an ability to predict the response to ALG therapy.

Adolescent↗

PubMed1992

Analysis of growth failure in children treated for acute lymphoblastic leukemia.

Growth patterns were surveyed in 303 children with acute lymphoblastic leukemia who had remained in continuous first complete remission for a minimum of 1 year (median 3 years). Chemotherapy was given for 3 years, and central nervous system prophylaxis consisted of cranial irradiation at a total dose of 18 Gy or intravenous high-dose methotrexate (1.5-6 g/m2 for three to six doses). Intensive chemotherapy, including cyclophosphamide, doxorubicin, and cytosine arabinoside was given to children with high-risk features. Two of 205 children with low- or intermediate-risk features and 13 of 98 children with high-risk features showed a decrease in the growth rate of less than -2 SD. In 14 of these 15 patients, the age at onset was over 9 years and growth failure became most predominant in the prepubertal period: ten of these children showed a tendency toward delayed pubertal development, but eight showed later catch-up growth with pubertal maturation after completion of chemotherapy. Thus, chemotherapy appeared to contribute temporarily to the growth failure and gonadal impairment that occurred in the prepubertal period. No obvious correlation between the administered cranial irradiation and growth failure was found, but further study with a longer follow-up will be necessary to determine the long-term effects of irradiation on subsequent growth patterns in children.

Adolescent↗

PubMed1992

[Clinical toxicity at the infusion of cryopreserved and thawed peripheral blood stem cell grafts in children].

To test the safety of infusing cryopreserved and thawed peripheral blood stem cells (PBSC) in children, toxicity assessment was made at 36 infusions in 33 children with various types of cancer. The mean volume of PBSC graft infused was 224 ml (range, 46-500 ml) or 8.0 ml/kg (1.7-23.8 ml/kg), in containing 10% dimethylsulfoxide (DMSO). Vomiting was the only toxic feature related to the amount of DMSO. However, eight patients developed transient shock, but recovered shortly afterward with or without supportive therapy. Attention should be drawn to increased risk in children receiving thawed blood cell grafts.

Blood Preservation↗

PubMed1992

Absorption, plasma concentration, and excretion after single administration of 14C-(+-)-3-(benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5- nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate hydrochloride in rats and dogs.

The absorption, plasma concentrations, and excretion of a newly synthesized calcium antagonist, TC-81 ((+-)-3-(benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate hydrochloride, CAS 96515-74-1) were studied following a single oral or intravenous administration of 14C-labelled compound. After oral administration, 14C-TC-81 was rapidly and well absorbed from the gastrointestinal tract. The peak plasma concentrations of radioactivity were observed at 0.5-1 h (rats) and 1-2 h (dogs) h after dosing. The elimination of the radioactivity in plasma was biphasic with a half-life of 3.8-5.2 h (a phase) and 42.9-56.2 h (beta phase) in the rats or 3.2 h (a phase) and 61.5 h (beta phase) in dogs. Maximum plasma concentrations of unchanged drug after oral administration of TC-81 to male rats at the doses of 0.5, 1.0, and 3.0 mg/kg were 1.7, 7.3 and 15.6 ng/ml, respectively. They were attained at 0.5 h after dosing in every dose examined. Plasma levels of unchanged drug declined with a half-life of 0.39-1.15 h. When TC-81 was orally administered to male dogs at the doses of 0.1, 0.2 and 0.5 mg/kg, plasma concentrations of unchanged drug reached the maximum level at 0.5 h after dosing and the values were 0.8, 3.3 and 9.6 ng/ml, respectively. They were eliminated with a half-life of 2.4-2.8 h. The absolute bioavailability of unchanged drug was estimated to be 2.6-7.0% (rats) and 5.3-15.5% (dogs) of the dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1992

Distribution to and elimination from tissues following a single or repeated administration of 14C-(+-)-3-(benzyl-methylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedica rbo xylate hydrochloride in rats.

A newly synthesized calcium antagonist, TC-81((+-)-3-benzylmethylamino)-2,2-dimethylpropyl methyl-4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate hydrochloride, CAS 96515-74-1) was administered to adult male rats, pregnant and lactating rats with a single oral dose or with repeated doses of 0.3 mg/kg for 2 weeks. The distribution to tissues, placental transfer and secretion of the radioactive drug into milk was studied using whole body autoradiography methods and quantitative determination of total radioactivity after autopsy. 14C-TC-81 was distributed rapidly but disproportionately to the tissues after single administration. The highest concentration of radioactivity was observed in the liver. The radioactivity in the various tissues declined slowly comparing to the plasma but at 96 h after dosing the radioactivity was detected only in the liver. The radioactivity penetrated the blood-placental barrier to a low extent after oral administration of 14C-TC-81 to pregnant rats. When 14C-TC-81 was administered to lactating rats, the radioactivity was secreted into the milk with the maximum concentration of radioactivity, 86% of the corresponding plasma concentration. Following 14-day oral treatments of male rats the equivalent concentration in the plasma was increased 1.5 fold as compared to the single treatment. In all tissues, the AUC0-24 h after 1, 7, and 14 days treatment were gradually increased, but these increases were almost the same as or even less than the rise observed in the plasma. After the last dosing, the radioactivity declined slowly with time in most of the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Candida albicans serotype A strains grow in yeast extract-added Sabouraud liquid medium at pH 2.0, elaborating mannans without beta-1,2 linkage and phosphate group.

Cultivation of three Candida albicans strains, NIH A-207, J-1012, and NIH B-792, abbreviated as A-, J-, and B-strains, respectively, in yeast extract-enrich Sabouraud liquid medium at pH 2.0 provided the following findings, i.e., the two former strains belonging to serotype A were able to grow in this medium in almost the same rates as those in the same medium of pH 5.9, while B-strain cells did not proliferate under the former condition. The cells of A- and J-strains cultivated at pH 2.0 did not undergo agglutination with the factor serum 6 in a commercially available factor serum kit, Candida Check, corresponding to C. albicans serotype A-specific epitope. It was also revealed by 1H-13C correlation spectra of the mannans isolated from the cells of A- and J-strains contained neither phosphate group nor beta-1,2-linked mannopyranose unit, although these mannans retained non-reducing terminal alpha-1,3 linked mannopyranose units, providing a substantiating evidence that the serotype A-specific epitope contains a non-reducing terminal beta-1,2-linked mannopyranose unit.

Candida albicans↗

PubMed1991

Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury.

The mechanisms by which peripheral nerve injuries sometimes lead to causalgia, aberrant burning pain peripheral to the site of nerve damage, are uncertain, although the sympathetic nervous system is known to be involved. Whether such syndromes could be the result of the development of responsiveness by some cutaneous pain receptors (C-fiber nociceptors) to sympathetic efferent activity as a consequence of the nerve injury was tested in an animal model. After nerve damage but not in its absence, sympathetic stimulation and norepinephrine were excitatory for a subset of skin C-fiber nociceptors and enhanced the responsiveness of these nociceptors to tissue-damaging stimulation. These effects were demonstratable within days after nerve lesions, occurred at the cutaneous receptive terminal region, were manifest in sensory fibers that had not degenerated after the injury, and were mediated by alpha 2-adrenergic-like receptors.

Animals↗

PubMed1991

Comparison of the effects of prostaglandins E2 and I2 on testicular nociceptor activities studied in vitro.

Effects of exogenous prostaglandin (PG) E2 and PGI2 on testicular polymodal receptor activities were compared in in vitro recordings of single- or multi-fiber discharges from canine testis-spermatic nerve preparations. PGI2 up to 1.4 x 10(-6) mol/l (cumulative method) or 1.0 x 10(-5) mol/l (non-cumulative method) excited only weakly some of the receptors, and similar observations were made with PGE2. Both PGs applied cumulatively or non-cumulatively at concentrations above 1.4 x 10(-8) mol/l augmented the response to bradykinin (9.4 x 10(-8) mol/l) in more than half of the cases tested. The augmenting effect of PGE2 lasted longer than that of PGI2 both with the cumulative and the non-cumulative method. The degree of augmentation tended to increase dependent on concentration, but some cases showed no further increase or rather a decrease in augmentation by PGs at a ten times higher concentration, especially when PGs were applied cumulatively. A second challenge by PG after a short interval (2 min) did not induce augmentation. These phenomena were considered to be tachyphylaxis to PGs. Cross-tachyphylaxis to PGE2 and PGI2 was also observed. There was not much difference in excitatory and augmenting potencies between these two PGs, but there was a clear difference in the concentrations of the PGs necessary to induce excitation of polymodal receptors and to facilitate their response to bradykinin.

Animals↗

PubMed1991

Expression of liver-specific functions and secretion of a hepatocyte growth factor by a newly established rat hepatoma cell line growing in a chemically-defined serum-free medium.

A rat hepatoma cell line 3'-mRLh-2 was established from 3'-methyl-4-dimethylaminoazobenzene-induced hepatoma. Cells proliferated well in 5Fs-DM-160, a chemically-defined serum-free medium; population doubling time was 68.5 h, and modal chromosome number was 81 (21%). The cells were transplantable, and the transplanted tumors were histologically diagnosed as hepatocellular carcinoma. They were cytochemically positive for gamma-glutamyl transpeptidase. The cells possessed about 30% of tyrosine aminotransferase activity level in the rat liver, and showed 5.5 to 7.4-fold induction of this enzyme activity in response to dexamethasone. Also, the cells secreted alpha-fetoprotein, albumin, transferrin, alpha 1-acid glycoprotein, C-reactive protein, fibrinogen, complement component C3, and other five-serum proteins. Furthermore, the conditioned medium stimulated DNA synthesis in primary cultures of adult rat hepatocytes in a dose-dependent, saturable manner and in the absence of epidermal growth factor. These properties of the cell line 3'-mRLh-2 were compared with those of the popular rat hepatoma cell lines, such as H4-II-E-C3 from Reuber hepatoma H35 and HTC from Morris hepatoma 7288C.

Animals↗