Search PubMed⌕ Search

Biomedical subjects

J Satoh

Publications and source records attributed to J Satoh.

At least 145 records · Page 8Linked to original sources

Quantitative assay of lentinan in human blood with the limulus colorimetric test.

A conventional limulus test detects not only endotoxin but also beta (1----3) glucan. Therefore, using a quantitative limulus test (the limulus colorimetric test) we studied the pharmacokinetics of lentinan, an antitumor beta (1----3) glucan, in the blood of 10 health volunteers and three patients with advanced gastric cancer. The calibration curve of lentinan in the human plasma was linear in the range of 0 to 100 ng/ml. When incubated with human plasma at 37 degrees C in vitro, lentinan had the recovery of almost 100% as compared to the initial concentration even after 60-min incubation, indicating the stability of lentinan in human plasma. When 1 mg of lentinan was intravenously administered over a 2 hr period, lentinan concentration reached the maximum levels (50-80 ng/ml) at the end of the drip infusion and decreased gradually thereafter. In the near future, the more appropriate modes of lentinan administration will be determined by further investigation of its kinetics in the human body.

Colorimetry↗

Quantitative analysis of the effect of colony-stimulating factors on human marrow progenitor growth in liquid-suspension cultures: application of limiting dilution assay.

Proliferation of human marrow progenitors in liquid cultures can be quantitated by limiting dilution clonal analysis (LDA) of progenitors in microwells. In this study, we have used LDA to study the effect of purified native or recombinant granulocyte colony-stimulating factors (G-CSFs) and recombinant granulocyte-macrophage CSF (GM-CSF) on progenitor growth. These results were compared to those of simultaneous cultures in methylcellulose. In LDA, single-hit kinetics were obtained with up to 500 U/ml of the recombinant preparation. In LDA with recombinant GM-CSF, progenitor growth conformed to single-hit kinetics from 100 to 2000 U/ml with maximum progenitor frequency at 500 U/ml. In simultaneous methylcellulose cultures with recombinant GM-CSF, colony formation reached a plateau at 100 U/ml. In LDA, purified native G-CSF was shown to support progenitor growth with single-hit kinetics at 100 U/ml, but at greater concentrations (greater than 150 U/ml), it suppressed progenitor growth with almost complete inhibition at a concentration of 200 U/ml. However, this dose-response effect was not observed in either simultaneous methylcellulose culture with G-CSF or in LDA with a purified recombinant preparation of the corresponding G-CSF. In methylcellulose cultures, colony formation reached a maximum at 100 U/ml and maintained a plateau up to 1000 U/ml. Hence, liquid culture allowed detection of contaminating suppressive activity in the G-CSF preparation that was not detected by methylcellulose assay. LDA may be more sensitive than methylcellulose culture for screening factors regulating human hematopoietic cell growth.

Bone Marrow↗

[Randomized-controlled study of treatment with UFT-MMC or UFT-ACR in advanced gastric cancer. Tohoku Study Group of Cancer Treatment for the Digestive Organs].

The effect of UFT-MMC- or UFT-ACR-therapy on the unresectable or recurrent gastric cancer was studied by a multicenter, randomized-controlled trial. All the patients who were randomly divided into the two groups were administered orally with 400 or 600 mg/day of UFT everyday. In addition, the UFT-MMC group was intravenously injected weekly for three weeks and then triweekly after six weeks with 6 or 8 mg/body of MMC, while the UFT-ACR group was intravenously injected with 20 mg/body of ACR for 5 serial-days every three weeks. Out of 88 cases registered, 75 (85.2%) were evaluable, consisting of 40 (31 complete cases) in UFT-MMC and 35 (27 complete cases) in UFT-ACR. There was no difference in various background factors between the two groups. PR, NC and PD was 10/31, 15/31 and 6/31 in the UFT-MMC group, whereas 0/27, 22/27 and 5/27 in the UFT-ACR group, respectively. The efficacy in the former group was higher, though not significant (U-test, p = 0.052), than that in the latter group. However, there was no difference in the 50% survival time (4.9 months in UFT-MMC vs. 5.4 months in UFT-ACR) of the either group.

Aclarubicin↗

[Recovery kinetics of hematopoiesis after peripheral blood stem cell autotransplantation].

Hematopoietic recovery kinetics was evaluated in five children with therapy-refractory cancers who received peripheral blood stem cell autotransplantation (PBSCT) following marrow-ablative chemotherapy. Four children received graft containing more than 1.5 X 10(4) CFU-GM/kg and days required to achieve granulocyte counts of greater than 0.5 X 10(9)/l were 6, 10, 13, and 18, respectively. One patient received 0.9 X 10(4) CFU-GM/kg, but, recovery of granulopoiesis was retarded (greater than 30 days). The days required to achieve platelet count of greater than 50 X 10(9)/l were 12, 15, 16, 195, and greater than 240, respectively. Transient decrease of blood cell counts developed 3 to 5 weeks after transplantation and thereafter, the recovery of hematopoiesis became stable. With the use of a large number of progenitors, PBSCT seems to be safe and effective new type of stem cell rescue operation as an alternative to bone marrow transplantation.

Acute Disease↗

[Rapid and complete hematopoietic reconstitution following peripheral blood stem cell autotransplantation in a child with T cell acute lymphoblastic leukemia].

Rapid and complete hematopoietic reconstitution was achieved in a child with T cell acute lymphoblastic leukemia who was autografted with peripheral blood stem cells (PBSC). A large number of PBSC was collected by two courses of 3-4 hour-lasting lymphopheresis during early remission induced by the second-line chemotherapy and then cryopreserved in liquid nitrogen. A myeloid progenitor cell dose of 203 X 10(4) CFU-GM/kg body weight was reinfused to the patient following marrow-ablative chemotherapy (MCNU 600 mg/m2, cytosine arabinoside 6 g/m2, etoposide 300 mg/m2, cyclophosphamide 160 mg/kg). Neutrophil count reached 0.5 X 10(9)/l by day + 7 and platelet count reached 20 X 10(9)/l by day + 9. Thereafter, white blood cell count continued to increase and reached a maximum of 38 X 10(9)/l on day + 14. Thus, the rapid recovery of hematopoiesis minimised marrow aplasia-related risks. This approach of stem cell rescue operation can be applied to the treatment of children with cancer, who otherwise have no hope to be cured, as an alternative to bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗

Isolation and storage of peripheral blood hematopoietic stem cells for autotransplantation into children with cancer.

Peripheral blood stem cells (PBSC) were collected for autotransplantation by a total of 46 continuous-flow leukaphereses in 17 children with various types of cancer in whom the stem-cell pool had been expanded by chemotherapy. As the cells collected by leukapheresis were contaminated with many visible cell clumps, platelets, and erythrocytes, they were separated from the platelet-rich plasma (PRP) by slow-speed centrifugation and fractionated on a discontinuous gradient of Percoll. All the hematopoietic progenitors (CFU-GM, CFU-GEMM) in the starting samples were recovered at the interface of 40% and 60% Percoll solutions largely free of other cellular components and with a substantial reduction in volume. The separation and freezing procedures could be completed within three hours after obtaining cells by leukapheresis. After their fractionation and storage, these PBSC were shown to be able to reconstitute normal hematopoiesis in ten children with poor prognosis leukemia or neuroblastoma for whom no HLA-compatible marrow donors were available and who had been subjected to marrow-ablative therapy. This separation procedure is simple, efficient, and readily available and can be used for children as a routine procedure for PBSC autotransplantation.

Adolescent↗

[Idiopathic hypokalemic periodic paralysis presenting peculiar insulin secretion].

A 24-year-old male was admitted to our hospital because of the paralytic attack. He was well until he went to bed the day before, and he found his limbs unmovable in the morning. The initial attack occurred at age 11 and subsequently he had two episodes of the reversible generalized weakness which always appeared in the morning and continued for about one day at age 14 and 21, respectively. The provocative factors were uncertain. There was no family history of paralytic attacks nor thyroid diseases. On the neurologic examination he presented flaccid tetraparesis without the facial and respiratory involvements. The laboratory studies showed that the serum potassium was 2.4 mEq/l and the thyroid function was normal. The oral and intravenous potassium chloride was given and within two days the serum potassium turned back to the normal level, and he has recovered completely from the paralysis. An oral 75g glucose load was performed. The serum immunoreactive insulin (IRI) was elevated from the basal level to 289 microU/l, showing the prominent peak response at 30 min after the load, and both the serum potassium and the grasping power decreased significantly, although the blood glucose fluctuated within the normal level. After the prophylactic treatment with acetazolamide 2,000 mg daily for 7 days, this markedly elevated initial insulin response has disappeared and moreover the weakness of grip was milder, however, the serum potassium decreased notedly. This case revealed that in the idiopathic hypokalemic periodic paralysis the attack was possibly induced by the extraordinarily secreted insulin which was supported by the acetazolamide treatment.

Acetazolamide↗

[Change of blood lentinan level in patients with advanced cancers].

A conventional limulus test can detect not only endotoxin but also beta(1----3) glucan. Therefore, with a quantitative limulus test, the limulus colorimetric test, we studied the pharmacokinetics of lentinan, an antitumor beta(1----3) glucan preparation, in the blood of 10 healthy volunteers and 20 patients with advanced cancers. The calibration curve of lentinan in the human plasma was linear in the range of 0 to 100 ng/ml. Two mg of lentinan was administered once a week and blood samplings for the measurement were done immediately before the next lentinan administration to document trough-levels serially at a week interval. Trough-levels tended to rise gradually and showed a rapid elevation between 4 and 8 weeks after beginning of administration. This phenomenon may correlate closely with the antitumor effect of lentinan and, therefore, deserves further investigations.

Antineoplastic Agents↗

[Hanging survivor showing alpha coma--a case report].

A case of a survivor who showed alpha coma after an attempted suicide by hanging was reported. A 19 years old woman was admitted to the hospital because of respiratory arrest following a hanging attempt on October 10, 1987. She was found pendent completely. On admission she was comatose and the pupils were not reactive to light. The systolic blood pressure was 60 mmHg and immediately an endotracheal intubation was instituted. After six hours from the onset, the spontaneous respiration was restored and the pupils reacted briskly to light. At 48 hours later she was still comatose, presenting flaccid quadriplegia with no responses to stimulations. An EEG showed a moderate amount of regular, 8 approximately 10 Hz, 10 approximately 50 microV potentials distributed predominantly on the centro-parieto-occipital regions. This alpha rhythm had persisted until 72 hours from the onset, and subsequently diffuse 5 approximately 7Hz, 10 approximately 40 microV slow activity replaced the alpha frequency at 120 hours after the attempt. On the 5th hospital day the hyperbaric oxygen therapy was given and on the 7th day she had become conscious, but showed the apallic syndrome. The both auditory and somatosensory evoked potentials were normal. On the 45th day the brain MRI revealed diffuse cerebral cortical atrophy, although no lesions were visualized in the brain stem. She showed gradual progress towards neurologic recovery. This is the first presentation of a survivor from alpha coma caused by anoxic encephalopathy following a hanging attempt.

Adult↗

TaqI polymorphism in the LDL receptor gene and a TaqI 1.5-kb band associated with familial hypercholesterolemia.

The low density lipoprotein (LDL) receptor gene was analyzed in 67 unrelated healthy Japanese and 38 members of six consecutive families with familial hypercholesterolemia (FH) by Southern blot hybridization with TaqI, an LDL receptor cDNA fragment containing exons 1 to 8 being used as a probe. A new TaqI RFLP at the LDL receptor locus was detected with allele frequencies of 0.67 and 0.33. The data obtained with smaller cDNA subfragment probes revealed that the TaqI RFLP site is located within 1.1 kb of the 5' side of the EcoRI site of exon 5. The TaqI RFLP was in linkage disequilibrium with the PstI RFLP but showed no significant linkage disequilibrium with the RFLPs for AvaII, ApaLI/I15, PvuII, NcoI, and ApaLI/3'. Among the seven RFLPs at the LDL receptor locus, the TaqI RFLP was the only useful genetic marker in one of the six families with FH. Furthermore, the association of an additional TaqI 1.5-kb band with a mutant LDL receptor gene was observed in another family with FH in which the proband was homozygous for all of the seven RFLPs. The data obtained with various restriction enzymes and smaller cDNA subfragments probes suggested that a minor change in nucleotide sequences in the region including exons 5 to 8 is present in the mutant gene. These data suggest that the TaqI RFLP is a useful genetic marker at the LDL receptor locus and that TaqI serves for the analysis of some mutant LDL receptor genes, when used with small LDL receptor cDNA probes.

DNA Restriction Enzymes↗

Immunohistochemical study of chromogranin in 100 cases of pheochromocytoma, carotid body tumour, medullary thyroid carcinoma and carcinoid tumour.

Neuroendocrine cells have histologically common features represented by argyrophilic cytoplasm containing neuroendocrine granules. Neuroendocrine granules are composed of various kinds of peptide hormones, amines, carrier proteins and ATP. Although various kinds of peptide hormones have been detected in neuroendocrine tumours, a peptide hormone has not been required as a standard marker for these tumours. Chromogranin is a purified protein which binds catecholamines specifically and is recognized as a carrier protein. We carried out an immunohistochemical study of chromogranin immunoreactivity in 100 neuroendocrine tumours including pheochromocytomas, carotid body tumours, medullary thyroid carcinomas and carcinoid tumours. Marked immunoreactivity was observed in 85% of carcinoid tumours and 100% of the other tumour types. A non-functioning paraganglioma and a malignant carcinoid tumour without any other detectable marker also showed strong immunoreactivity to chromogranin. Chromogranin immunoreactivity is a useful tool for neuroendocrine tumours.

Adrenal Gland Neoplasms↗

In vivo and in vitro studies of the prevention of proteolipid apoprotein-induced murine experimental allergic encephalomyelitis by monoclonal antibody against L3T4.

The suppressive effect of anti-L3T4 monoclonal antibody (mAb) on murine experimental allergic encephalomyelitis (EAE) induced by sensitization with proteolipid apoprotein (PLP) was examined in vivo and in vitro. This mAb inhibited the antigen-specific proliferation of the encephalitogenic T cell lines but did not block the mitogen-mediated response. Serial injections of the mAb during the pre-effector phase of EAE markedly suppressed the development and relapse of the disease but this treatment initiated after appearance of clinical signs was not effective. In treated animals, L3T4+ T cells in the spleen were profoundly decreased and the antigen-specific proliferative response of spleen cells was completely suppressed. Moreover, adoptive transfer of spleen cells from the treated mice induced resistance against EAE induction in the recipients. However, no obvious evidence for antigen-specific suppressor cells was found in vitro in the L3T4- populations of spleen cells from treated mice.

Acute Disease↗

Extensive cerebral infarction due to involvement of both anterior cerebral arteries by Wegener's granulomatosis.

The central nervous system is often affected in Wegener's granulomatosis (WG), but massive cerebral infarction due to occlusion of branches of the anterior cerebral arteries (ACA) by granulomatous lesions or thrombosis, or both, has seldom been reported. A case is reported here of a 67 year old man with WG complicated by generalised necrotising vasculitis in the lung, kidney, and gastrointestinal tract, and cerebral infarction in the territory of both anterior cerebral arteries, probably caused by thrombosis and a contiguous invasion of granulomatous lesion from the nasal cavity.

Aged↗

NOD mice with high incidence of type 1 diabetes are not T lymphocytopenic.

An autoimmune pathogenesis has been indicated in insulin-dependent (type 1) diabetes mellitus (IDDM). Previously we reported that non-obese diabetic (NOD) mice as an animal model of spontaneously developing IDDM were immunologically characterized by T lymphocytopenia and impaired cellular immunities. The cumulative incidence of diabetes in the T lymphocytopenic female NOD mice was 10-20% by 24 weeks of age. On the other hand, the incidence of diabetes are 80-90% in the female NOD/Shi-Sendai (S), in whom proportion of lymophocyte subsets has not been known yet. Therefore, we examined the spleen cells of female NOD/Shi-S and female NOD/Shi with high incidence of diabetes, and of female Jcl:ICR as a control. Cell numbers, populations of T cells (Thy 1.2+, Lyt-1+ and Lyt-2+), B cells (surface-Ig+), NK cells (acialo GM1+) and responsiveness to Concanavalin A were analyzed as immunological parameters. In contrast to the T lymphocytopenic NOD, these immunological parameters were not impaired in the NOD/Shi-S and NOD/Shi in comparison to those of Jcl:ICR. The results indicate that there may be a positive association between the incidence of diabetes and T cell number and functions in female NOD mice.

Animals↗

Treatment with streptococcal preparation (OK-432) suppresses anti-islet autoimmunity and prevents diabetes in BB rats.

We have recently shown that a streptococcal preparation (OK-432) inhibits insulitis and prevents diabetes in nonobese diabetic (NOD) mice, an animal model of insulin-dependent diabetes mellitus (IDDM). We extended this study to another model of IDDM, namely BB rats. Male and female BB rats were injected weekly with 0.2 mg OK-432 i.p. starting from 5 to 6 wk and continuing through 20 or 30 wk of age. The cumulative incidence of IDDM over 20 wk in the OK-432-treated BB rats (4 of 54, 7.4%) was significantly (P less than .01) lower than that found in the nontreated BB rats (13 of 47, 27.7%). We examined some of these rats as follows. All of the OK-432-treated BB rats tested showed normal glucose levels before and after oral glucose administrations, as did the nontreated and nondiabetic BB rats. Histological examination of pancreatic sections revealed that the OK-432-treated rats retained a greater number of intact islets without infiltration of the mononuclear cells than did the nontreated BB rats. A preliminary in vitro study further demonstrated that the cytotoxic activities of spleen cells against a rat insulinoma cell line, RIN, were suppressed in the OK-432-treated rat. However, the treatment of BB rats with OK-432 showed no suppressive effects in the spleen cell number, the responsiveness of spleen cells to concanavalin A, the populations of OX19+, W3/25+, and OX8+ peripheral blood lymphocytes, or in the titers of cell surface antibody against RIN. These results suggest that a nonimmunosuppressive immunomodulator such as OK-432 may be useful as an agent for immunotherapy of IDDM.

Animals↗