PubMed HealthSearch

Biomedical subjects

T Takino

Publications and source records attributed to T Takino.

At least 19 recordsLinked to original sources

Hepatic disposition characteristics of electrically charged macromolecules in rat in vivo and in the perfused liver.

The effect of electric charge on the hepatic disposition of macromolecules was studied in the rat. Charged derivatives of dextran (T-70) and bovine serum albumin (BSA), mitomycin C-dextran conjugates (MMC-D), and lactosaminated BSA (Lac-BSA) were employed as model macromolecules. After intravenous injection, cationic macromolecules were rapidly eliminated from plasma because of their extensive hepatic uptake, while anionic and neutral macromolecules were slowly eliminated. Cationic macromolecules were recovered from parenchymal and nonparenchymal hepatic cells at a cellular uptake (per unit cell number) ratio of 1.4-3.2, while that of Lac-BSA was 14. During liver perfusion using a single-pass constant infusion mode, cationic macromolecules were continuously extracted by the liver, with extraction ratios at steady-state (Ess) ranging between 0.03 and 0.54, whereas anionic and neutral macromolecules were almost completely recovered in the outflow at steady state. The Ess for cationized BSA (Cat-BSA) and cationic MMC-Dcat were concentration dependent and decreased at low temperatures and in the presence of colchicine and cytochalasin B. The possible participation of the internalization process in the uptake of cationic macromolecules by hepatocytes was suggested.

Animals

Hepatic disposition characteristics of 111In-labeled lactosaminated bovine serum albumin in rats.

The hepatic disposition of lactosaminated bovine serum albumin (Lac-BSA) in rats was studied at the whole body, isolated liver, and isolated parenchymal cell levels. After intravenous injection, 111In-Lac-BSA (1 mg/kg) was rapidly eliminated from the plasma due to extensive uptake by liver parenchymal cells; however, a significant decrease in hepatic clearance was observed at high dose (50 mg/kg). In a single-pass, constant infusion experiment in the isolated liver, 111In-Lac-BSA was continuously extracted. The extraction ratio at steady state (Ess) for 111In-Lac-BSA was significantly decreased by coadministrating galactose, NH4Cl, or chloroquine, and at low temperature, suggesting that hepatic uptake of Lac-BSA proceeds via receptor-mediated endocytosis for asialoglycoprotein. Kinetic analysis of 111In-Lac-BSA binding with isolated parenchymal cells at 4 degrees C yielded a dissociation constant (Kd) of 2.5 x 10(-8) M and a value of 3.5 x 10(5) maximal binding sites/cell (Bmax). The internalization rate constant (kint) for 111In-Lac-BSA was calculated to be 0.46 min-1 in liver perfusion experiments using the EDTA-wash method.

Animals

Effect of endoscopic sclerotherapy and propranolol on the blood flow of esophageal varices.

The blood flow in esophageal varices was measured by endoscopic laser Doppler velocimetry (LDV) in 27 patients histologically or clinically diagnosed as having liver cirrhosis. The effect of endoscopic injection sclerotherapy (EIS), and of intravenous oral administration of propranolol, on the output signal of LDV was evaluated. EIS was performed intravariceally after the measurement, with a 50% glucose solution, human thrombin (1000 U), and Aethoxysclerol as sclerosants.

Adult

Correlation of chromosome abnormalities with clinical characteristics in thyroid lymphoma.

Karyotypes from seven patients with thyroid lymphoma were studied before treatment. When the cytogenetic results were correlated with the clinical data, it became evident that there are two distinct groups of patients with thyroid lymphoma. In a group of patients with solely numerical abnormalities the disease is associated with a rather long duration from the onset of goiter to the time of operation for lymphoma, with abnormal thyroid function, and with positive tests for antithyroid autoantibodies. Two of four patients in this group showed trisomy 22; the remaining two showed a loss of a sex chromosome. The other group of patients with solely structural abnormalities is associated with a short duration from the onset of goiter to the time of operation, with normal thyroid function, and with the trend of negative tests for autoantibodies. Two of three patients in this group showed a 14q+ abnormality. These results indicate that there are two distinct type of thyroid lymphoma, chromosomal changes of which are implicated as pathogenetic factors in lymphomagenesis of different mechanisms.

Aged

Elevated levels of 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum during acute exacerbation of chronic hepatitis B.

We measured 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum of 14 HBsAg- and HBeAg-positive patients with chronic hepatitis B with or without acute exacerbation. Elevated levels of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells and serum were found in seven chronic hepatitis B patients with acute exacerbation, whereas in the remaining seven chronic hepatitis B patients without acute exacerbation, both levels were similar to those of normal subjects despite active hepatitis B virus multiplication. 2',5'-Oligoadenylate synthetase levels in peripheral blood mononuclear cells and serum, which were not statistically different from those of normal subjects prior to acute exacerbation, increased during acute exacerbation from 3- to 23-fold over initial levels following elevations in ALT activity. 2',5'-Oligoadenylate synthetase levels fluctuated over a normal range while ALT levels were elevated, and they returned to a baseline with ALT normalization. This suggests that the in vivo interferon system may be activated during acute exacerbation, and that this activation may not be a result of hepatitis B virus multiplication alone, but also of a host-immune response to hepatitis B virus multiplication. Three patients were treated with interferon during acute exacerbation. All three had elevated levels of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells and serum just before treatment. 2',5'-Oligoadenylate synthetase levels increased only 1.1- to 2.2-fold over initial levels during treatment, with none of the patients clearing HBeAg during and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase

Acute nonlymphocytic leukemia (M2) with chromosome abnormality trisomy 4 developing eight years after radiation therapy for breast cancer.

We report here the development, 8 years after radiation therapy for breast cancer, of acute nonlymphocytic leukemia (ANLL), type M2 of the FAB classification, in which trisomy 4 was detected as the only chromosomal abnormality. Simultaneous observation of cytologic and cytogenetic features of individual colonies derived from leukemic progenitor (L-CFU) and early progenitor (CFU mix) cultures in this patient revealed that all colonies examined had a normal karyotype, although the clone with trisomy 4 was predominant in the direct bone-marrow culture. These findings suggest that progenitor cells with trisomy 4 were less predominant in colony growth when stimulated by colony-stimulating factors (CSFs) than were stem cells with a normal karyotype.

Breast Neoplasms

Mechanisms of alpha-fetoprotein synthesis in hepatoma cells. Combined electron microscopic immunocytochemistry and autoradiography.

Immunoreaction of alpha-fetoprotein (AFP) was detected not only in well-differentiated hepatocellular carcinoma but also in hepatocytes forming foci in livers with hyperplastic nodules during 3'-methyl-4-dimethylaminoazobenzene hepatocarcinogenesis. The subcellular location of AFP in hepatoma cells was in the rough endoplasmic reticulum, perinuclear space and well-developed Golgi apparatus around the nucleus. In livers with hyperplastic nodules it was also in some parts of the smooth endoplasmic reticulum and Golgi regions in hepatocytes in the vicinity of submembranous areas or bile canaliculi. These findings suggest that the Golgi apparatus in hepatoma cells acts mainly as an organelle for glycosylation of AFP and that the Golgi complexes in the hepatocytes in livers with hyperplastic nodules are organelles for secretion of AFP. Combined light microscopic immunoperoxidase study and autoradiography with 3H-thymidine revealed a higher cumulative labeling index in AFP-positive hepatoma cells than in non-tumorous areas. Combined electron microscopic immunoperoxidase study and autoradiography showed that hepatoma cells with AFP immunoreactivity only in the rough endoplasmic reticulum had a significantly higher labeling index than did cells with AFP immunoreactivity in both rough endoplasmic reticulum and Golgi apparatus. These findings suggest that AFP is synthesized in hepatoma cells before or during the stage of their DNA synthesis and is then transported to the Golgi apparatus.

Animals

Two different types of antimitochondrial antibodies (anti-M2 and anti-M4) may not differentiate primary biliary cirrhosis (PBC) with prominent piecemeal necrosis from classical PBC.

Clinical and morphological features in 13 patients with primary biliary cirrhosis (PBC) who had two different types of antimitochondrial antibodies (PBC-specific, anti-M2 and mixed-form, anti-M4) in serum tested, were studied. Patients were allocated to two groups purely on the basis of the presence or absence of prominent piecemeal necrosis (PN) to elucidate the clinical significance of PN for differentiating mixed forms of chronic active hepatitis and PBC from classical PBC. Histological staging showed 10 stage I and 3 stage II. All cases had histological features of chronic non-suppurative destructive cholangitis. Prominent PN was encountered in 8 and bridging hepatic necrosis in 6. Granulomas were present in all cases without PN, but only in 3 of 8 cases with PN. Antimitochondrial antibody (AMA) was positive in all cases and anti-M2 was also positive in all but one. On the contrary, anti-M4 was positive in 2. Both anti-M2 and anti-M4 were simultaneously positive in 2, of which PN was present in only one. Therefore, anti-M4 did not relate to the presence or morphological severity of PN in PBC. Simultaneous increases in IgG and IgM were prominent features in PBC with PN.

Acute Disease

A case of endoscopic injection sclerotherapy for a bleeding duodenal varix.

A case of bleeding duodenal varix which was treated successfully with endoscopic injection sclerotherapy (EIS) is reported. The patient developed a hemorrhage from a varix in the descending portion of the duodenum two months after EIS for esophageal varices, and hemostasis was achieved using EIS with an intravericeal injection of 1% polidocanol. The duodenal varix decreased in size after EIS. Two months after EIS, a splenectomy was performed. During a 14-month follow up period after the EIS for the duodenal varix, there was no recurrent bleeding.

Adult

Simultaneous existence of double minute chromosomes and a homogeneously staining region in a retinoblastoma cell line (Y79) and amplification of N-myc at HSR.

We observed double minute chromosomes (dmin) and a homogeneously staining region (HSR) in the same metaphase cells obtained from a retinoblastoma cell line, Y79. All of the 132 metaphases examined contained an HSR on the short arm of chromosome 1(1pHSR) and five cells (3.8%) had two to four dmin. To determine whether 1pHSR and dmin carried amplified N-myc sequences, we performed an in situ hybridization using an N-myc probe. Silver grains clustered on and along the 1pHSR, but not on the dmin. These findings indicate that the HSR on chromosome 1 is associated with amplification of N-myc in Y79 cells.

Chromosome Aberrations

Myelodysplastic syndrome preceding acute myelomonocytic leukemia with dysplastic marrow eosinophilia and inv(16).

A 44-year-old Japanese male having refractory anemia with excess of blasts (RAEB) preceding acute myelomonocytic leukemia (AMMoL) with dysplastic marrow eosinophilia (M4Eo in the FAB classification) is reported. Sequential cytogenetic studies revealed a specific chromosomal abnormality, inv(16) (p13q22), when RAEB was first diagnosed and again when overt leukemic transformation compatible with M4Eo was manifested. However, during the interval between the RAEB and AMMoL, an unrelated abnormal karyotype without inv(16), 47,XY,+9, was seen, when hematological data revealed remission after a low dose of cytosine arabinoside was administered. In this patient eosinophils in the marrow were involved in the leukemic process cytogenetically, because a few metaphases overlaid with eosinophilic granules had the inv(16) with other numerical abnormalities.

Adult

[Evaluation of plasma PIVKA-II as a new marker for hepatocellular carcinoma].

We have measured the plasma PIVKA-II levels in 188 cases of various liver disease with HCC and malignant diseases in other organs by an EIA, using a monoclonal antibody (E-1023 kit, Eisai), and also have measured the plasma vitamin K levels in cases of HCC and cholestasis by an HPLC. Plasma PIVKA-II was detected in many cases of HCC (67%, 35 of 52 cases) and cholestasis (60%, 6 of 10 cases). In contrast, the positivities of PIVKA-II in the other diseases including benign liver diseases were very low. Combination assays of PIVKA-II and vitamin K revealed that PIVKA-II correlates with vitamin K in cholestasis but not in HCC, suggesting that PIVKA-II in HCC does not depend on a systemic deficiency of vitamin K. From these results, it was concluded that PIVKA-II is a reliable marker which can reflect the clinical course of HCC.

Adult

Clinical and cytogenetic features in six patients with chronic myelogenous leukemia and a complex Philadelphia translocation.

Six patients with chronic myelogenous leukemia and a complex Philadelphia (Ph1) translocation are described. The complex Ph1 translocations were a three-way translocation in five patients and a five-way translocation in one. Additional chromosomal aberrations were detected in four of five patients when the blastic crisis supervened. The median survival time was 42 months. The remaining patient died of acute myocardial infarction 23.5 months after the diagnosis of CML was made. There seems no difference between these six patients and those with the standard Ph1 with respect to clinical, hematologic and cytogenetic findings.

Adolescent

[Clinical evaluation of a combination treatment with cefbuperazone and amikacin in infections complicating with hematological disorders].

The efficacy and the safety of a combination regimen using cefbuperazone (CBPZ) and amikacin (AMK) were evaluated in severe infections in patients with hematological diseases. Twenty two patients were subjected to this combination therapy; among these, 18 patients were evaluable for the effectiveness. They included 9 cases of leukemia, 5 cases of malignant lymphoma, 2 cases of aplastic anemia, and 2 cases of angio-immunoblastic lymphadenopathy with dysproteinemia. Excellent responses were obtained in 5 patients and good responses in 5 patients, with a total effectiveness of 55.6%. Efficacy rates for individual types of infections were; 2/2 in sepsis, 6/14, or 42.9% in suspected sepsis, 1/1 in urinary tract infection, and and 1/1 in upper respiratory infection. The combination treatment was also effective in 4 of 6 cases in which neutrophil counts were less than 500/mm3 prior to therapy. Side effects were observed in only one patient. Mild proteinuria occurred in a 80-year-old male in 6 days after the regimen was started, but was not serious. These results indicate that a combination of CBPZ and AMK is safe and effective for the treatment of infections even in patients with compromised immunodefenses.

Adolescent

[Clinical evaluation of cefpiramide for infections in leukemia and related disorders].

Forty one patients with infections associated with leukemia and related disorders were treated with cefpiramide (CPM). In 26 patients among them, we were able to evaluate the effectiveness of CPM against infections. Fifteen patients were not evaluated, because 6 patients were subjected to additional therapy such as gamma-globulin and other antibiotics, 5 were prophylactically treated, 2 had fever episode which were retrospectively reviewed to be originated from tumor mass, 1 received too short a duration of administration of CPM (2 days) to evaluate its effectiveness, and 1 with whom no precise data were recorded. Excellent responses were observed in 10 patients (38.5%) and good responses in 6 (23.1%) among these 26, with a total efficacy rate of 61.5%. Whereas, we found only one patient who showed an unfavorable side effect out of 31 patients including the 26 and 5 other patients who were prophylactically treated. The side effect observed was a mild bleeding tendency occurred in 77 years old female at 11 days after CPM was administrated. The bleeding tendency was easily diminished with the cessation of CPM treatment and a parenteral use of vitamin K. These results suggest that CPM is an effective and safe antibiotic for the treatment of infections in patients with leukemia and related disorders.

Adolescent

Autoradiographic study on healing process of cysteamine-induced duodenal ulcer in rat. Possible importance of Brunner's glands in ulcer healing.

The healing process of cysteamine-induced duodenal ulcer was studied by [3H]thymidine autoradiography. After the development of ulcer in the duodenum, cell proliferation was markedly activated not only in the crypts but also in the Brunner's glands near the ulcer. In the initial stages of ulcer healing, they both contributed to form the surface covering regenerating epithelium. Granulation tissue also proliferated at the base of the ulcer. In later stages of ulcer healing, new crypts were formed in the floor of the ulcer. New villi regenerated from these crypts and Brunner's glands regenerated by proliferation in situ. The ulcer base then was completely covered with new villi and granulation tissue was replaced by dense fibrous connective tissue. The present study suggested that the Brunner's glands, together with the crypts of Lieberkühn, play an important role in the healing process of cysteamine-induced duodenal ulcer.

Animals

Immunocytochemical investigation of hepatitis B virus-associated antigens in cases of liver cirrhosis and HBsAg antigenemia and their relationship to development of hepatocellular carcinoma.

Using light and ultrastructural immunoperoxidase techniques, we examined the distribution of hepatitis B virus (HBV)-associated antigens and the subcellular localization of hepatitis B surface antigen (HBsAg) in liver biopsies of HBsAg-positive patients with cirrhosis. The localization patterns of HBsAg in hepatocytes were membranous, cytoplasmic, festoon and inclusion body types. Cytoplasmic and festoon types were seen more often than the membranous type in pseudolobules, and hepatitis B core antigen (HBcAg)-positive cells with cytoplasmic type were distributed in the periphery of pseudolobules with active inflammation. Immunoelectron microscopy in the cytoplasmic or festoon type of HBsAg showed immunoreaction in the cisternae and on virus-like particles in the cisternae in patients with hepatitis B e antigen (HBeAg) antigenemia. Simultaneous staining of HBsAg and HBcAg revealed that hepatocytes with cytoplasmic or festoon type of HBsAg contained HBcAg-immunoreactivity. The inclusion body type of HBsAg was characteristic of liver cirrhosis with hepatocellular carcinoma (HCC); the subcellular localization of HBsAg was seen in clusters of the endoplasmic reticulum around the nucleus, and HBsAg-immunoreactivity was observed on many virus-like particles in most of the cisternae in those with HBeAg antigenemia. These findings suggest that the synthesis of HBsAg is active in patients with liver cirrhosis and that the formation of HBV is also active in those with HBeAg antigenemia and that HBV may be retained more in cirrhotic livers with hepatocellular carcinoma after proliferation than in those without it.

Antigens, Viral