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Biomedical subjects

Y Takemoto

Publications and source records attributed to Y Takemoto.

At least 181 records · Page 10Linked to original sources

Preferential hindquarter vasodilation in the hypotension induced by GABA injection into the cisterna magna of conscious rats.

Injection of GABA into the cisterna magna of conscious rats induced a vasodilation in the hindquarter without significant change in the renal and superior mesenteric areas, when arterial pressure and heart rate markedly decreased. This circulatory change indicates that GABA decreased arterial pressure as an effect on the CNS, in particular, through a hindquarter resistance reduction, along with a bradycardia.

Animals↗

[An evaluation of a therapy with antibacterial and antifungal agents infections with hematological disorders].

The primary objective of this study is to confirm the efficacy and safety of combination therapy with antibacterial and antifungal drugs for patients with hematological disorders complicated with infections of unknown causative organisms. The subjects consisted of 55 patients with hematological disorders, 28 males and 27 females, ranging from 1 to 78 years of age, with an average age of 34 years. The breakdown of the patients by disease was: 41 leukemias, 10 malignant lymphomas, 3 myelodysplastic syndromes and an aplastic anemia. All patients were treated with sulbactam/cefoperazone (SBT/CPZ) and aminoglycoside (AG) plus fluconazole (FLCZ) as an empiric therapy. Overall efficacy rate was 54.5% for all the patients: 57.7% for patients with suspected sepsis and 0% for those with pneumonia from which unknown organisms were detected. The efficacy rate was 59.4% for patient who had been previously treated with other antibiotics and 47.8% for those who had not previously been treated. The above results suggested that this combination therapy might be effective for severe infections of unknown causative organisms associated with hematological disorders.

Adolescent↗

Hematopoietic recovery from host progenitors with normal karyotype devoid of Philadelphia chromosome in a patient with CML after allogeneic BMT.

A male patient with CML received a BMT from his sister and developed chronic GVHD. The host-origin normal karyotype (46,XY) was identified for the first time in the 60th month after BMT. Detection of Y-chromosome-specific DNA in BM and peripheral blood (PB) showed that all BM samples obtained 6 months from BMT were positive for Y-specific DNA, while PB became positive in the 60th month after BMT. The BCR-ABL mRNA derived from leukemic cells was detected in the 36th month post-BMT, but not in the 60th month or thereafter. Fluorescence in situ hybridization revealed that 1.5% and 0.6% in BM and PB cells were Y-positive in the 70th month post-BMT, respectively. DNA analysis of hematopoietic progenitor colonies revealed 1 of 42 erythroid colonies to be host derived. These results indicate that host-origin hematopoietic cells survive chronic GVHD, while the Ph1 clone was eliminated.

Adult↗

Liver resection in the aged (seventy years or older) with hepatocellular carcinoma.

BACKGROUND: Thirty-two patients who were 70 years of age or older underwent hepatic resection in the treatment of hepatocellular carcinoma. There were 25 men and 7 women. Age ranged from 70 to 84 years, averaging 74 +/- 3 years (mean +/- SD). Underlying liver diseases were associated in all patients but one, cirrhosis of the liver in 22, and chronic hepatitis in nine. METHODS AND RESULTS: The operative mortality rate within 1 month was 12.5%, and the overall in-hospital death rate was 18.8%. The 5-year survival rate was 17.6% for all patients and 24.3% when six hospital deaths were excluded. The Child's grade was a good predictor for early and late morbidity and death, the 5-year survival rate of patients with Child's class A disease being 30%. Retrospective comparisons were conducted between the current patients and patients younger than 50 years old who had been operated on during the same period: resectability rate, 61.5% versus 57.8%; hospital mortality rate, 18.8% versus 11.6%; and 5-year survival rate, 24.3% versus 48.6%, respectively. CONCLUSIONS: These results seem to indicate that the treatment policy of hepatocellular carcinoma in the aged should be identical to that in young people.

Age Factors↗

[Bone marrow transplantation for refractory anemia].

Each nineteen patients with severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) have been treated by allogeneic bone marrow transplantation (BMT) at Hyogo College of Medicine between 1980 and 1991. Rejection was one of the major problems for SAA patients. Conditioning regimen including irradiation reduced the rejection rate, but secondary cancers may develop as the dose of irradiation increased. It is practically important to determine the indication of BMT for MDS-refractory anemia (RA). We considered the indication of BMT for those who have abnormal karyotypes and/or life threatening complications. Five out of nine patients with MDS-RA are surviving after BMT. Four out of ten cases with MDS RAEB-T and overt leukemia are alive. BMT should be recommended for patients with MDS who satisfy the above conditions, if suitable donors are available. However, it remains to be determined whether the patients with RAEB or MDS overt leukemia should be treated with chemotherapy prior to the preconditioning for BMT.

Adolescent↗

High serum IL-6 level reflects susceptible status of the host to endotoxin and IL-1/tumor necrosis factor.

Patients with high level of serum endotoxin did not necessarily develop into lethal shock, whereas some patients died of septic shock even when their serum endotoxin levels were low. These results indicate that limiting factor which determines the host to be endotoxin shock principally depends on the host susceptibility to endotoxin instead of serum endotoxin level. To understand this susceptible status of the host to endotoxin, we used Propionibacterium acnes primed mouse endotoxin shock model. We found that P. acnes-primed mice responded to low dose of LPS by enhanced production of IL-1 and TNF. And such mice were highly susceptible to the lethal shock inducing effect of IL-1 and/or TNF, which also induced high level of serum IL-6 in these mice. Therefore, measurement of serum IL-6 level provides us with the information of the preceding exposure of the host to either LPS or IL-1 and/or TNF and the highly susceptible status of the host to these stimuli. Based on these results obtained from animal model, we investigated the relationship between serum IL-6 levels and serum endotoxin levels in the patients with malignant hematologic disorders. We found that these patients fell into two groups; an endotoxin susceptible group, equivalent to P. acnes-primed mice, showing high level of serum IL-6 with low level of serum endotoxin, and a nonendotoxin susceptible group, equivalent to P. acnes-nonprimed mice, showing low or undetectable level of serum IL-6 with high level of serum endotoxin. We propose that the measurement of serum IL-6 level in the patients positive for endotoxin is a useful tool in evaluating diagnosis and prognosis of endotoxin shock.

Adolescent↗

Comparison between diploid and aneuploid hepatocellular carcinomas: a flow cytometric study.

Nuclear DNA content of hepatocellular carcinoma (HCC) was estimated by flow cytometry after hepatic resection in 91 patients during the past 5 years. There were 53 diploid and 38 aneuploid tumours. Clinicopathological features were compared retrospectively between the patients with diploid and those with aneuploid HCC. DNA ploidy did not show any correlation with age, sex, alcohol abuse, hepatitis B virus, serum alpha-fetoprotein level or underlying liver disease. Histopathologically, the incidence of HCC less than 2 cm in diameter tended to be higher in the diploid group but no difference was seen for large tumours (greater than 5 cm). The grade of tumour differentiation also tended to be higher in this group of small HCC. The ploidy pattern did not influence the rate of capsule or daughter nodule formation, or venous invasion. There were no significant differences in survival rate or in the incidence and time of intrahepatic tumour recurrence between the two groups. This study may indicate that nuclear DNA ploidy is not a particularly predictive factor for the surgical treatment of HCC.

Aneuploidy↗

Serum thymidine kinase, a possible marker for monitoring the effect of bone marrow transplant treatment in early recovery phase.

We measured serum thymidine kinase (TK) activity with a radioenzyme assay system employing [I-125]-iododeoxyuridine as the tracer on serial specimens from five bone marrow transplant (BMT) patients before and after transplantation. The serum level of TK activity in the 4 patients with effective BMT treatment ranged from 3.0 to 16.9 U/L (mean, 7.80 U/L) before transplantation and from 27.3 to 236.1 U/L (mean, 82.95 U/L) after the BMT treatment. Mean serum TK activity increased 13.17-fold (range, 1.68 to 29.14-fold). In contrast, the activity in the patient with ineffective BMT treatment was not significantly different during, before, or after BMT treatment. In addition, serum TK activity in BMT patients was well correlated with the change in the number of leukocytes before and after BMT treatment [r = +0.709 (p less than 0.01), y = 0.012 x +0.87]. We conclude that the determination of serum TK activity in BMT patients is very useful in monitoring the course of bone marrow transplantation in the early recovery phase.

Adolescent↗

DNA ploidy pattern in synchronous and metachronous hepatocellular carcinomas.

DNA ploidy of hepatocellular carcinoma (HCC) was studied in 28 patients using a flow cytometric method. Fourteen patients had two HCCs synchronously, and the remaining 14 had tumor recurrence in the remnant liver 3-41 months after curative resection of primary HCCs. DNA ploidy pattern and histopathologic parameters were compared between the synchronous and metachronous HCCs. Among those with synchronous HCCs, both tumors were diploid in 7 cases and aneuploid in 2 instances. Five patients had HCCs of different DNA ploidy pattern. On the other hand, 5 of 14 patients with metachronous HCCs had a consistent DNA ploidy between primary and recurrent tumors. In 4 cases, the first tumor was diploid whereas the recurrent HCC was aneuploid or tetraploid. In the remaining 5 cases, the primary HCC was aneuploid, but the recurrent tumor was diploid. Assuming that the difference in DNA ploidy pattern indicates a different clonal origin, the current results indicate that at least 36% of synchronous HCCs and 64% of recurrent HCCs develop in a multicentric fashion.

Adult↗

The salutary effect of FK506 in ischemia-reperfusion injury of the canine liver.

The present study was designed to elucidate the effect of FK506 on 90 min of warm ischemia of the liver and reperfusion in 30 dogs. Three groups of animals were studied. Group 1 animals received FK (0.15 mg/kg/day) for three days prior to the ischemia and group 2 animals got 2 ml of saline solution for three days instead of FK and were considered controls. In group 3 FK (0.15 mg/kg/day) was injected immediately upon reperfusion and two days thereafter. Evaluation of the effectiveness of the drug was monitored by measuring the serum activities of AST, ALT, LDH, serum total bilirubin, malondialdehyde, and by histopathological examinations of the liver specimens and survival of the animals for 7 days after reperfusion. The 7 day survival of the animals in group 1 (80%) was significantly (P < 0.05) improved compared with those in group 2 (30%) and group 3 (20%). The serum activities of AST, ALT, and LDH and total bilirubin were significantly lower in group 1 than in group 2 and group 3. FK pretreatment significantly prevented hepatocellular necrosis and neutrophilic infiltration in group 1 in comparison with those in group 2 and group 3. Although the malondialdehyde level in hepatic venous blood was relatively lower in group 1, this difference was not statistically significant. Three days FK pretreatment prevented hepatocellular injury and enzyme leakage after 90 min of hepatic ischemia, whereas FK treatment immediately upon reperfusion failed to do so. In conclusion, donor organ pretreatment with FK may become a promising strategy for improved allograft survival in liver transplantation.

Animals↗

Comparison of the survivals between bone marrow transplantation and chemotherapy for acute leukemia in first remission--a Japanese single institution study.

The outcome of sixty-four patients with acute leukemia in first remission who had been treated with either bone marrow transplantation (BMT) or conventional chemotherapy was retrospectively evaluated (a median follow-up of 37 months). Among them, 26 patients (age range; 14-42 years) received allogeneic BMT from HLA-identical siblings and 38 patients (age range; 13-43 years) who had no HLA-identical donors undertook the continued combination chemotherapy. Kaplan-Meier product-limit estimate of actuarial survival of acute myelogenous leukemia (AML) patients was 48.9% for the BMT group and 15.7% for the chemotherapy group (p = not significant, NS). For acute lymphoblastic leukemia (ALL) patients, the survival following BMT was 80.2% and was significantly higher than that of the chemotherapy group of 33.3% (p < 0.05). The disease-free survival of AML and ALL for the BMT group was 34.3% and 36.5%, respectively, which was higher than that of the chemotherapy group (16.7% and 23.4%, respectively (p = NS)). These findings in our Japanese single institution study suggested that BMT may be the treatment of choice for adult patients with acute leukemia in first remission if they had suitable donors and that more effective therapeutic regimens were necessary for patients without compatible donors in order to obtain the longer remission duration.

Acute Disease↗

[Measurement of busulfan concentration in plasma and spinal fluid from transplant patients pretreated with busulfan and cyclophosphamide].

Busulfan (BU) concentrations in the blood and spinal fluid of 7 patients pretreated with BU for bone marrow transplantation (BMT) were measured using gas chromatography. The data from these periodically obtained samples were used to study the relationship between the BU concentration and complications (e.g. vomiting), indicating that vomiting leads to a lower maximum BU level. The trough level of BU concentration at 6 hours after administration was stable at around 500 ng/ml, not showing little effect of vomiting. The BU concentrations in the spinal fluid were virtually the same as those in plasma collected at the same time and the spinal fluid/plasma ratio of the BU concentration averaged 1.06. No veno-occlusive disease (VOD) was noted. Failure of engraftment occurred in one case of myelofibrosis, however, as the plasma BU concentration in this case was not lower than the others, the graft failure was not considered to be due to the preconditioning regimen including BU.

Adolescent↗

[Interleukin-6 in hematological diseases with septic shock].

The authors measured the level of interleukin-6 (IL-6), endotoxin and CRP from 7 patients of documented sepsis with hematological disorders. IL-6 was higher in patients who developed septic shock, compared with patients who had only sepsis. These data revealed the importance in the level of IL-6, rather than endotoxin and CRP, in managing the patients with septic shock.

Hematologic Diseases↗

[Primary myelofibrosis successfully treated with allogeneic bone marrow transplantation].

A 31-year-old man with primary myelofibrosis initially received low dose Ara C. Splenomegaly decreased but pancytopenia continued. Allogeneic bone marrow transplantation from his sister was then performed. Busulfan and cyclophosphamide were used as a preconditioning regimen, which included neither irradiation nor splenectomy. As the bone marrow was hypoplastic after transplantation, G-CSF was given. It was useful for systemic infection. After transplantation, leukoerythroblastosis and tear drop poikilocytosis disappeared in peripheral blood. Finally, bone marrow fibrosis disappeared and hemopoiesis to normal limits recovered 17 months later. These results demonstrate that bone marrow transplantation is effective for primary myelofibrosis for which there is no otherwise curative therapy.

Adult↗

Peptidyl antithrombogenic agents for extracorporeal blood circulation.

The reduction of platelet aggregation and adhesion is essential for preventing thrombus formation during extracorporeal circulation. This report addresses some performances of peptidyl antithrombogenic agents which bind to the adhesive site of fibrinogen. This was based on the recent finding that the sequence of the binding domain of the platelet membrane receptor to fibrinogen was identified as TDVNGDGRHDL (one-letter amino acid code; Thr-Asp-Val-Asn-Gly-Asp-Gly-Arg-His-Asp-Leu), entitled B12. The addition of B12 and shorter-chain analogue peptides dose-dependently suppressed platelet aggregation and adhesion onto a fibrinogen-coated surface. The shorter the amino acid sequence, the less effective was inhibition. The inhibitory effect on platelet adhesion in vivo was significant under continuous infusion of B12. These inhibitory effects were compared with those by a receptor-binding RGD (Arg-Gly-Asp) peptide, which is the common active site to adhesive proteins.

Amino Acid Sequence↗