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Biomedical subjects

Y Takemoto

Publications and source records attributed to Y Takemoto.

At least 145 records · Page 8Linked to original sources

[Urgent allogeneic bone marrow transplantation using a preparative regimen of cyclophosphamide anti-human thymocytes rabbit globulin in a patient with severe aplastic anemia with pneumonia].

A 16-year-old girl was diagnosed as having severe aplastic anemia (SAA) had received emergency complicated by sever pneumonia. She had an HLA-identical younger brother and been urgently transplantation with her brother's marrow following a preparative regimen of CY+rabbit antithymocyte globulin (ATG). Granulocyte transfusions carried out before and after the transplant prevented exacerbation of the pneumonia. The pneumonia was cured in association with the hematopoietic recovery after BMT. No signs or symptoms of acute or chronic graft-versus-host disease were recognized and her hematological data are normal. The rabbit ATG was thought to be effective in preventing rejection and could be used in the preparative regimen instead of total body irradiation.

Adolescent↗

Rationale of lymph node dissection for breast cancer--from the viewpoint of analysis of axillary lymphatic flow using activated carbon particle CH40.

In order to rationalize lymph node dissection for breast cancer, we reviewed regional lymphatic flow from the mesial and outer half of the breast using intra-tumoral injection of activated carbon particles (CH40). Seventy patients with breast cancer were included in this study. Cancers were located in the mesial half of the breast in 25 cases and in its outer half in 41 cases. Since regional lymph nodes were blackened by CH40, lymph node dissection was performed easily and small lymph nodes could be readily examined. The average number of resected nodes in each case was 29.4. When CH40 was injected into the mesial half of the breast, the rates of blackened nodes (number of macroscopically blackened lymph nodes/number of total removed lymph nodes) in the stations were 46.6% (No. 1a), 41.4% (No. 1b), 62.1% (No. 1c), 61.8% (No. 2), 69.2.% (No. 2h), and 65.6% (No. 3). When CH40 was injected into outer half of the breast, those were 62.0% (No. 1a), 64.3% (No. 1b), 68.7% (No. 1c), 75.3% (No. 2), and 67.8% (No. 2h). Regardless of tumor location, the rates of blackened nodes were high in each station. In conclusion, regardless of tumor location it is impossible to determine the level of axillary dissection for breast cancer. It should be all or nothing.

Axilla↗

Ki-67 and p53 immunoreactive stain and early colorectal neoplasms.

The aim of this work was to conduct a histopathological study of the different pathways of colorectal tumorigenesis by using Ki-67 and p53 immunoreactive stains. Between 1987 and 1993, 14,023 patients were investigated by colonoscopy at Akita Red Cross Hospital and several affiliated hospitals. Five hundred and sixty-five cases of early colorectal neoplasms identified in this population were used in the present study. Specimens were cut in half: one half was cut along the vertical axis, the other half along the horizontal axis to analyze the structure of glands which opened to the surface. They were stained with hematoxylin-eosin, Ki-67 and p53 immunoreactive stains. macroscopically, early colorectal neoplasms were classified into two types: protruding type and depressed type. The protruding type was mainly composed of branching glands. In contrast, the depressed type was almost completely composed of straight glands which opened to the surface. The Ki-67 positive ratio was almost equal. However, the p53 positive ratio was significantly different in the protruding type and the depressed type. The results suggest the existence of at least two pathways of colorectal tumorigenesis: one with the process of branching structure and one without the process of branching structure. Furthermore, there were clinical and immunohistochemical indications that the depressed type invades into deeper layers more rapidly than does the protruding type.

Adolescent↗

LckBP1, a proline-rich protein expressed in haematopoietic lineage cells, directly associates with the SH3 domain of protein tyrosine kinase p56lck.

The Lck tyrosine kinase molecule plays an essential role in T cell activation and T cell development. Using the expression cloning technique, we have isolated a gene that encodes a molecule, LckBP1, able to associate with murine Lck. Analysis of full-length LckBP1 cDNA indicates at least four potentially important segments: a four tandem 37 amino acid repeat motif with a potential helix-turn-helix DNA binding motif; a proline-rich region; a proline-glutamate repeat; and an SH3 domain. These four regions are very similar to the human haematopoietic-specific protein 1 (HS1). Deletion mutant analysis of LckBP1 revealed two proline-rich regions that permit association with Lck SH3. One region contains prolines conserved among HS1 and cortactin, and the other region contains a potential MAP kinase recognition site. In vivo association between Lck and LckBP1 was confirmed by immunoprecipitation of lysates from a pre-T cell line and adult thymocytes using antibodies specific for Lck and LckBP1. LckBP1 is tyrosine phosphorylated after T-cell receptor stimulation. The SH3 domain and the potential helix-turn-helix motif in LckBP1 suggest that this molecule may associate with various molecules and function as a DNA binding molecule. The data also suggest that LckBP1 mediates intracellular signalling through Lck in T cells.

3T3 Cells↗

Cell type-specific trans-activation by the B-myb gene product: requirement of the putative cofactor binding to the C-terminal conserved domain.

The myb gene family has three members, c-myb, A-myb and B-myb. We have examined the trans-activating capacity of the B-myb gene product (B-Myb) in various types of cells. B-Myb functions as a transcriptional activator in CV-1 and HeLa cells, but not in NIH3T3 cells, indicating that B-Myb is a cell type-specific transcriptional activator. Deletion analyses of B-Myb have demonstrated that the region conserved between three members of the myb gene family (CR for conserved region) is necessary for trans-activation by B-Myb. An in vivo competition assay suggests that regulatory factor(s) that binds to the CR of B-Myb is required for transactivation. Analyses using an affinity resin show that multiple proteins bind to the CR of B-Myb and that the CR-binding proteins in CV-1 and HeLa cells are different from those in NIH3T3 cells. These results suggest that the CR-binding cofactor(s) is critical for the cell type-specific trans-activation by B-Myb.

3T3 Cells↗

All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Japan Adult Leukemia Study Group.

We conducted a multicenter trial of treatment with all-trans retinoic acid (ATRA) for newly diagnosed acute promyelocytic leukemia (APL) in the AML-92 study and compared it with our previous study with standard intensive chemotherapy, the AML-89 study, in the view of complete remission (CR) rate, incidence of early death, and event-free survival (EFS). Patients were scheduled to receive oral ATRA 45 mg/m2 daily until CR. If patients had leukocyte counts above 3 x 10(9)/L at the start of therapy, they received daunorubicine (DNR) 40 mg/m2 for 3 days and behenoyl cytosine arabinoside (BHAC) 200 mg/m2 for 5 days in addition to ATRA. During the ATRA therapy, if patients showed myeloblast plus promyelocyte counts higher than 1 x 10(9)/L in the peripheral blood, they received additional DNR and BHAC in the same schedule, as well. A total of 110 patients were entered into the study. Median age was 43 years (range, 16 to 74). Twenty-eight (26%) of 109 patients (one died before the start of therapy) received ATRA alone. Ninety-seven patients (89%) achieved CR; 48 of 49 (98%) aged less than 40 years, 44 of 52 (84%) aged between 40 and 69, and 5 of 8 (63%) aged above 70 achieved CR, respectively; 25 of 28 (89%) with ATRA alone, 46 of 51 (90%) with ATRA plus initial chemotherapy and 26 of 30 (87%) with ATRA plus later chemotherapy attained CR, respectively. Nine (8%) patients died within 28 days after the start of therapy. In contrast, 44 of 62 patients (71%) attained CR, and 13 (21%) died within 28 days in the AML-89 study with the combination of DNR, BHAC, 6-mercaptopurine and prednisolone. Seven developed retinoic acid syndrome and one died of it in the present study. Other toxicities associated with this drug included cheilitis, desquamation, muscle pain, and hypertriglyceridemia. Predicted 23 months EFS for all ATRA-treated patients and disease-free survival (DFS) in the CR cases were 75% and 81%, respectively, in a median follow-up period of 21 months. Compared to the AML-89 study, there was a highly significant difference in remission rate (P = .004), EFS (P = .0007), and also early mortality rate (P = .02). Present results demonstrated that ATRA with or without chemotherapy gives a statistical improvement in CR rate and early mortality rate, as well as superior survival in newly diagnosed APL.

Adolescent↗

A simple method for collecting eggs of taeniid cestodes from fresh, frozen or ethanol-fixed segments.

A simple method was devised for collecting eggs of Taenia taeniaeformis and T. saginata. All gravid segments, either fresh or frozen or 70% ethanol-fixed, were gently scraped using a pestle on a 150 mesh stainless steel sieve. Eggs and tissue debris were washed out all together with mouse tonicity phosphate buffered saline (MTPBS) through the 150 mesh sieve into a glass beaker. Egg suspension with a huge amount of tissue debris in MTPBS was centrifuged 5 min at 3000 r.p.m. (x 1600 g) and the pellet of eggs and tissue debris was resuspended with 1 vol. of MTPBS and 2 vol. of Percoll (Pharmacia) and centrifuged 60 min at 3000 r.p.m. More than 90% of eggs sedimented in the pellet. The supernatant covered with tissue debris was decanted, and the egg pellet was resuspended and centrifuged several times with MTPBS to remove Percoll. It is suggested that this simple method may prove useful for preparation of eggs of biohazardous taeniid cestodes, such as Taenia solium and Echinococcus spp.

Animals↗

Effect of tauroursodeoxycholic acid on bile flow and calcium excretion in ischemia-reperfusion injury of rat livers.

BACKGROUND/AIMS: Tauroursodeoxycholic acid is known to have a hepatoprotective action in cholestatic disorders. We evaluated whether oral pretreatment with tauroursodeoxycholic acid could protect the liver from ischemia-reperfusion injury, with particular regard to its effect on bile flow and biliary calcium excretion. METHODS: A 1-hour in vivo ischemia-reperfusion model of 70% of the lobes of rat liver was used. Animals were divided into six groups (each group; n = 8); a non-ischemia sham group (CS), a control group without bile acids (CON), and 4 bile acid groups; 10 mg/kg and 50 mg/kg (U10, U50), taurocholic acid 10 mg/kg (CA10) and tauroursodeoxycholic acid 10 mg/kg (CD10). Bile acids were given orally for 7 days before operation. RESULTS: Three hours after reperfusion, oral bile acid pretreatment failed to reduce the hepatic ischemia-reperfusion injury biochemically, but histological improvement was observed in the tauroursodeoxycholic acid groups. After reperfusion, tauroursodeoxycholic acid significantly increased bile flow from the ischemic liver, and also significantly increased serum calcium concentration. Although tauroursodeoxycholic acid did not change biliary calcium concentration, it significantly enhanced total biliary calcium output during reperfusion. CONCLUSION: Thus, tauroursodeoxycholic acid inhibited tissue calcium accumulation and enhanced sinusoidal and biliary calcium output during hepatic ischemia-reperfusion. However, it is still unclear if calcium mobilization is part of the protective mechanisms of tauroursodeoxycholic acid in ischemia-reperfusion injury of the liver.

Analysis of Variance↗

p53 immunoreactive stain and early colorectal adenocarcinomas.

565 cases of early colorectal adenocarcinomas were used in this study to examine mechanisms of carcinogenesis. Specimens were paraffin embedded and histological sections were stained with haematoxylin-eosin and p53. Macroscopically, early colorectal adenocarcinomas could be classified into two types: protruding and depressed. The former were composed of branching glands, while the latter were composed of straight glands which opened to the surface. The p53 positive ratio was similar for protruding tumours but was higher in depressed submucosal invasive adenocarcinomas than in depressed intramucosal adenocarcinomas. These results raise the possibility of at least two pathways for colorectal carcinogenesis, adenoma-carcinoma lesions and de novo carcinoma lesions.

Adenocarcinoma↗

Effects of gamma-aminobutyric acid on regional vascular resistances of conscious spontaneously hypertensive rats.

1. The regional vascular effects of a central injection of gamma-aminobutyric acid (GABA) in conscious spontaneously hypertensive rats (SHR) were compared with normotensive control rats (NCR), including Wistar-Kyoto rats (male, 10-20 weeks of age). One week or more after insertion of a cannula into the cisterna magna, an electromagnetic flow probe was implanted around one of five arteries, and a catheter for measurement of blood pressure and heart rate was inserted into the terminal aorta or common carotid artery. Cardiovascular changes were observed in the conscious animal after recovery from the surgery. Peripheral resistance was calculated as pressure divided by flow. 2. Ten min following intracisternal injection of 10 mu mol of GABA, mean arterial pressure and heart rate were significantly lowered (P < 0.05; t-test): - 29 and -16% (70 d.f.) in SHR versus -23 (116 d.f.) and -19% (112 d.f.) in NCR. Hindquarters, carotid, superior mesenteric and renal, but not coeliac, vascular resistances were significantly lowered (P < 0.05; t-test, 21, 9, 18 d.f.) in SHR. However, when comparing the effect of GABA injection in SHR and NCR, there were no significant differences in coeliac, carotid and hindquarters vascular resistances, but there were significant decreases in superior mesenteric and renal vascular resistances in SHR. 3. These results indicate that: (i) a cisternal injection of GABA in SHR decreases both peripheral vascular resistance and heart rate, and thereby lowers blood pressure; (ii) the vascular resistance of the superior mesenteric and renal vascular beds was more decreased in SHR than in NCR. This suggests that the GABAergic control of regional vascular resistance differs in the SHR and the NCR.

Animals↗

Repeated hepatic dearterialization for unresectable liver metastases from gastric cancer: review of five cases.

A novel method of repeated hepatic dearterialization was evaluated in five patients with multiple metastases from gastric cancer in both hepatic lobes. After gastrectomy with extensive lymph node dissection (R2/3), all patients underwent implantation of a vascular occluder around the hepatic artery. Cannulation of the hepatic artery was added for later chemotherapy. The hepatic artery was occluded repeatedly for 1 hour twice daily in combination with intrahepatic infusion of anticancer drugs for as long as possible. Three of five patients demonstrated marked tumour regression with unexpectedly long survival (16 months in two patients and one still alive at 15 months). Carcinoembryonic antigen (CEA) levels decreased to almost normal in four patients who had initially high levels. The present experiences seems to indicate that long survival can be hoped for in patients with advanced gastric cancer with unresectable liver metastases.

Aged↗

Serum hepatocyte growth factor levels in patients with chronic renal failure.

The serum levels of hepatocyte growth factor (HGF) were determined in chronic renal failure (CRF) patients. Nondialysis patients with renal insufficiency had significantly higher serum HGF than normal subjects (0.34 +/- 0.10 ng/ml, n = 21 vs. 0.19 +/- 0.05 ng/ml, n = 15; p < 0.001), and the elevated serum HGF correlated with their serum creatinine levels. Hemodialysis (HD) patients treated for 5-10 years showed higher serum HGF than those receiving HD for 1 year or less (0.45 +/- 0.14 ng/ml, n = 8 vs. 0.33 +/- 0.11 ng/ml, n = 9; p < 0.05). Continuous ambulatory peritoneal dialysis patients also showed elevated serum HGF levels comparable to those of HD patients. There was no difference in serum HGF levels in HD patients with or without acquired cystic disease of kidney. Consequently, serum HGF is elevated in CRF, which may be attributed to the increased production of HGF in response to the chronic renal injury, the effect of heparin, or reduced removal of serum HGF in CRF patients.

Adult↗

Leukemia developing after 131I treatment for thyroid cancer in a patient with Werner's syndrome: molecular and cytogenetic studies.

A 40-year-old female patient with Werner's syndrome (WS) suffering from thyroid cancer and myelodysplastic syndrome (MDS) is reported. She had been diagnosed as having WS complicated with thyroid cancer seven years previously. Total thyroidectomy and radioactive iodine (131I, 100 mCi/year) therapy for seven years had slowed the progression of thyroid cancer. She suffered a sudden onset of MDS at the age of 40 years. After six months she died from overt leukemia. We found an additional chromosome aberration of chromosome 10 in the progression of leukemia from MDS.

Adenocarcinoma, Papillary↗

Regional hemodynamic changes and vasopressin release induced by intracisternal injection of L-proline in the conscious rat.

Electromagnetic flow probes were used to measure regional blood flow responses to central injection of L-proline in conscious rats. Ten min after intracisternal injection of 10 mumol of L-proline, arterial pressure increased from 113 +/- 1.6 (mean +/- SEM, n = 23) to 142 +/- 2.9 mmHg, while the heart rate decreased from 383 +/- 9.6 (n = 23) to 313 +/- 5.4 beats/min, vascular resistance increased an average of 239% in the superior mesenteric artery (n = 8) and 72% in the renal artery (n = 8), without change in the terminal aorta (-6%, n = 7). However, 10 mumol of D-proline induced neither blood pressure increase nor bradycardia 10 min after its injection. After sino-aortic denervation, the heart rate was not decreased by L-proline injection. Ganglionic blockade with chlorisondamine evoked significantly greater pressor action by L-proline injection than that without treatment, but intravenous injection of the vasopressin antagonist, (d(CH2)5(1), O-Me-Tyr2, Arg8)-vasopressin (10 micrograms/kg), promptly dilated the superior mesenteric vascular bed and lowered the arterial pressure. In addition, pretreatment with the vasopressin antagonist alone almost abolished the pressor and vasoconstrictor action induced by L-proline injection. These results indicate that intracisternal injection of L-proline specifically elicited an increase in arterial pressure mainly through marked vasoconstriction of the superior mesenteric artery bed, and that bradycardia was elicited via the baroreflex. Thus, vasopressin release in the blood-stream was involved in these hemodynamic actions.

Animals↗

Hindquarter vasodilation after intracisternal injection of D-arginine in the conscious rat.

The cardiovascular effects of the centrally injected D-arginine were investigated in the conscious rat chronically instrumented with cisternal, arterial, and venous cannulae, as well as an electromagnetic flow probe around the superior mesenteric artery, renal artery, or terminal aorta (hindquarter). Intracisternal injection of D-arginine (10 mumol) increased arterial blood pressure and hindquarter flow lasting for 60 min or more. Previous injection of the beta-adrenoceptor blocker, propranolol (2 mg/kg, I.V.), markedly attenuated the hindquarter vasodilation caused by D-arginine; this response suggests the release of adrenaline. Peripheral resistance, calculated as arterial pressure divided by regional flow, increased in both the superior mesenteric artery (60%) and the renal artery (45%) 5 min after intracisternal injection of D-arginine. In the hindquarter, however, peripheral resistance decreased by 35% and arterial pressure increased by 25%. The pressor effect was significantly attenuated by producing ganglionic blockade with chlorisondamine (5 mg/kg, I.V.). The total peripheral blood flow increased from 12.9 to 15.9 ml/min/100 g body weight. This response indicates that the pressor effect of D-arginine is due to an increase of cardiac output rather than of peripheral resistance. Centrally administered D-arginine appears to activate the sympatho-adrenal system, especially the release of adrenaline.

Animals↗

The central effect of L-cysteine on cardiovascular system of the conscious rat.

The hemodynamic effects of intracisternal injection of the nonessential amino acid L-cysteine were studied in conscious chronically instrumented rats. Injections of L-cysteine (0.05-0.2 M in artificial cerebrospinal fluid, 10 microliters) into the cisterna magna dose-relatedly elicited an increase in arterial pressure but a decrease in superior mesenteric blood flow as measured by an electromagnetic flow probe. Injections of the excitatory amino acid transmitter L-glutamate at comparable doses caused much the same pressor and vasoconstrictor effects as did L-cysteine. Prior I.V. injection of vasopressin V1-receptor antagonist, (d(CH2)5(1), O-Me-Tyr2, Arg8)-vasopressin (10 micrograms/kg), markedly attenuated the effects of L-glutamate but not of L-cysteine. Ganglionic blockade with chlorisondamine (5.0 mg/kg) failed to attenuate the effects of either amino acid, whereas an additional intravenous injection of vasopressin antagonist, completely abolished the effects. These results indicate that the circulatory effects of L-cysteine are probably due to autonomic nervous activation combined with vasopressin release, unlike those of L-glutamate which acts mainly through vasopressin release. L-Cysteine may contribute to central cardiovascular control, since it induces the marked circulatory effects comparable to or greater than those of L-glutamate.

Animals↗

Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species.

The 5-hydroxytryptamine3 receptor 5-HT3R has been implicated in gut and cardiac motility and in behavioral disorders. Characteristics of 5-HT3Rs appear to be heterogeneous among species, but human 5-HT3R cDNA has not been identified. We isolated a cDNA encoding 5-HT3R from human hippocampus. The mouse 5-HT3R gene has been reported to generate two alternative splicing isoforms that differ by six amino acids. All of our isolated human clones corresponded to the shorter isoform. Amino acid identities with mouse neuroblastoma N1E-115 and rat brain 5-HT3Rs were 84% for each. Southern blot analysis of human genomic DNA suggested that our cloned transcript encoded a human counterpart for the rodent 5-HT3Rs. This gene was assigned to chromosome 11 using polymerase chain reaction analysis of a human/rodent somatic cell hybrid panel. With the use of Northern blot analysis, 5-HT3R transcripts were identified in human small intestine, colon, and brain regions including hippocampus, amygdala, and striatum. In human heart, 5-HT3R expression was not detectable even with reverse transcriptase-polymerase chain reaction analysis, although it was detectable in mouse heart. Transfection of COS-1 with human 5-HT3R cDNA induced specific binding of the 5-HT3R-selective radioligand [3H]YM060. Human 5-HT3R showed typical characteristics of the 5-HT3R, but its affinity for the 5-HT3R agonist m-chlorophenylbiguanide was much lower than that of rat 5-HT3R. When injected with human 5-HT3R cRNA, the oocytes responded to 5-HT3R agonists with a rapidly developing inward current. The potency of the agonists to induce inward current paralleled that to compete with the radioligand binding, and 2-methyl-5-hydroxytryptamine, a partial agonist for mouse 5-HT3R, was a full agonist for human 5-HT3R. Our data revealed that the 5-HT3R molecule has interspecies differences in both tissue distribution and functional profile.

Amino Acid Sequence↗

FK506 treatment of graft-versus-host disease developing or exacerbating during prophylaxis and therapy with cyclosporin and/or other immunosuppressants. Japanese FK506 BMT Study Group.

A phase II study of the efficacy and safety of FK506, a new potent immunosuppressant, has been conducted in 49 patients with GVHD after allogeneic BMT. Eighteen patients with acute GVHD and 31 with chronic GVHD entered the study. FK506 was administered at an initial dose of 0.05 mg/kg i.v. or 0.15 mg/kg orally twice a day to those whose GVHD had become uncontrollable with cyclosporin and/or other immunosuppressants. The response to FK506 was evaluated in 13 patients with acute and 26 with chronic GVHD. A marked response was observed in 5 and a good response in 2 of 13 patients with acute GVHD. For those with chronic GVHD, the response was marked in 2 patients, good in 10 and poor in 8. The most common adverse effects were renal toxicity (53.1%), followed by nausea and vomiting (30.6%) and a feeding of warmth (18.4%). There was a correlation between renal toxicity and whole blood levels of FK506. The dose should be adjusted to keep a trough level between 15 and 25 ng/ml. FK506 is promising in the treatment of both acute and chronic GVHD, even if it is intractable with other immunosuppressants, and may be most effective if administered early in the course of GVHD.

Acute Disease↗