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Biomedical subjects

K Tokunaga

Publications and source records attributed to K Tokunaga.

At least 343 records · Page 19Linked to original sources
PubMed1993

Increased anti-HIV-1 activity of CD4 CDR3-related synthetic peptides by scrambling and further structural modifications, including D-isomerization and dimerization.

We recently showed that S1, a sequence-scrambled form of CD4 CDR3-related synthetic peptide, has more potent inhibitory activities on HIV-1 replication and HIV-1-induced syncytium formation than the original form. In this study, a series of derivatives of S1 were synthesized and their anti-HIV-1 activities were evaluated. A D-isomer was as potent as S1, and a homodimer was 10- to 18-fold more potent than S1. The increased antiviral activity of the dimer peptide was related to alpha-helix formation, as detected by circular dichroism.

Amino Acid Sequence↗
PubMed1993

Extralysosomal degradation of high-density lipoproteins in a human hepatoma cell line, Mahlavu.

Lipoprotein metabolism has been investigated in a novel human hepatoma cell line, Mahlavu, which has been reported to possess the characteristics of hepatocytes. Low-density lipoprotein (LDL) was degraded by Mahlavu cells. LDL taken up by the cells suppressed intracellular cholesterol biosynthesis and promoted cholesterol esterification in a manner similar to that of HepG2 cells. High-density lipoprotein (HDL) was also degraded by Mahlavu cells, whereas it was not degraded by fibroblasts. We compared the mode of intracellular metabolism of HDL to that of LDL. In contrast to the LDL receptor pathway, the degradation of HDL was not inhibited by 100 microM chloroquine added to the medium, indicating that the degradation may not occur in lysosomes. Cholesterol taken up as HDL-cholesterol by the Mahlavu cells had no effect on the intracellular biosynthesis of cholesterol nor on cholesterol esterification. The conditioned media in which Mahlavu cells had been cultured did not promote the degradation of HDL, suggesting that HDL is degraded intracellularly. These data suggest that HDL is taken up and degraded by the liver cells in contrast to extrahepatic peripheral cells such as fibroblasts and macrophages in which the degradation of HDL does not occur. The results indicate that HDL-associated cholesterol may be processed via a pathway different from that of LDL metabolism and that the degradation of HDL occurs extralysosomally.

Carcinoma, Hepatocellular↗
PubMed1993

Revised technique of cardiopulmonary bypass in one-stage repair of interrupted aortic arch complex.

Twenty infants with interrupted aortic arch associated with various intracardiac anomalies underwent primary complete repair using pulsatile high-flow cardiopulmonary bypass with a short period of circulatory arrest. Age at repair ranged from 11 to 126 days (mean age, 43 days). Weight ranged from 2.2 to 5.5 kg (mean weight, 3.4 kg). Associated cardiac lesions included ventricular septal defect (14 patients), truncus arteriosus (3), transposition of the great arteries (2), and aortopulmonary window (1 patient). Left ventricular outflow tract obstruction was relieved in 2 patients. The aortic arch was reconstructed with a polytetrafluoroethylene graft in 7 patients and by direct anastomosis in the most recent 11 patients. An arterial cannulation method has been devised to facilitate direct anastomosis between the ascending aorta and the descending aorta, to lessen circulatory arrest time, and to prevent dangerous laceration and postoperative narrowing of the thin, small ascending aorta at the cannulation site. Two patients died, a surgical mortality rate of 10%. There has been one late death, which was due to severe truncal valve insufficiency. The other patients are doing well with a mean follow-up of 3 years 6 months. Restenosis of the direct anastomosis has not been noted in any patient. However, subaortic stenosis with pressure gradients of 30 to 40 mm Hg developed in 3 patients. In conclusion, one-stage repair including direct anastomosis for the aortic arch reconstruction and repair of all coexisting intracardiac defects is thought to be the treatment of choice.

Anastomosis, Surgical↗
PubMed1993

Trans-ventricular septal defect approach for resection of accessory mitral valve tissue.

Accessory mitral valve tissue is a rare cause of left ventricular outflow tract obstruction, which can be difficult to recognize. Surgical resection by the conventional transaortic approach with or without left atriotomy is extremely difficult in infants with a small aorta. When a ventricular septal defect is present, it may be the best way to approach the accessory mitral valve tissue, because the ventricular septal defect is located just in front of it. Five infants underwent resection of accessory mitral valve tissue together with repair of other intracardiac malformations. In 3 infants, resection of accessory mitral valve tissue was easily performed through the ventricular septal defect, which required enlargement in 2 patients.

Female↗
PubMed1993

Frequency of intron 14 splicing defect of cholesteryl ester transfer protein gene in the Japanese general population--relation between the mutation and hyperalphalipoproteinemia.

Cholesteryl ester transfer protein (CETP) deficiency, which has been found only in Japan, is characterized by marked hyperalphalipoproteinemia (HALP) and abnormalities of both low density and high density lipoproteins. We have reported that this deficiency is commonly associated with a G-->A mutation at the intron 14 splice donor site of the CETP gene (Yamashita et al., Biochem. Biophys. Res. Commun., 170 (1990) 1346-1351). In the current study, we determined the frequency of this mutation in Japanese subjects by using polymerase chain reaction. A single primer-template mismatch of one base pair from the CETP gene mutation permitted the introduction of a cleavage site for Nde I in mutant alleles but not in normal ones. Out of 171 patients with marked HALP whose serum HDL-cholesterol was more than 100 mg/dl, 6 (3.5%) subjects were homozygous and 48 (28.1%) were heterozygous for this mutation. Furthermore, in unrelated 512 healthy Japanese subjects, 5 (0.98%) were identified as heterozygotes. Relative allelic frequency of A at the intron 14 splice donor site was 0.0049 and the frequency of homozygous CETP deficiency was estimated to be approximately 1/42,000. These results demonstrate that this common mutation may be frequent in the Japanese population. Although HALP is very heterogenous, this mutation could be one of the major causes of marked HALP.

Alleles↗
PubMed1993

Genotyping and association analysis of HLA-B61 in Japanese.

The distribution of HLA-B61-related alleles, B*4002-B*4006, was examined in the Japanese population by using PCR-SSO and PCR-RFLP methods. About half of the B61-positive individuals possessed B*4002 and the remaining half possessed B*4006. In addition, these two major B61 alleles were separately associated with different HLA-C alleles: B*4002 exhibited a strong linkage disequilibrium with Cw10, whereas B*4006 was strongly associated with C blank and DR9. Amino acid residues that contribute to the serologic epitopes of the B61 group and their relationships with other HLA-B locus antigens are discussed.

Alleles↗
PubMed1993

Expression of human immunodeficiency virus type 1 Nef antigen on the surface of acutely and persistently infected human T cells.

The authors have previously shown the role of human immunodeficiency virus type 1 (HIV-1) Nef protein as a growth inhibitor to CD4+ T lymphocytes. We now report that the Nef antigen is partly expressed on both acutely and persistently infected human T cells. To investigate the cell surface expression of the Nef antigen, murine monoclonal antibodies (mAbs) were prepared by immunization with a recombinant Nef protein. The recombinant Nef was expressed by a baculovirus expression system as a truncated Nef protein with 22 kDa containing the middle to the C-terminus. Three clones were found to produce mAbs with IgM isotype against Nef protein by ELISA with the same truncated Nef. All these mAbs reacted on immunoblotting with two forms of Nef, 25 kDa and 27 kDa, in an HIV-1-infected human T-cell line and with the 27 kDa Nef in retroviral vector-infected mouse fibroblasts expressing a full-length Nef protein. Membrane immunofluorescence and flow cytometry with these mAbs revealed the Nef antigen to be expressed, at least in part, on the surface of these cells. Thus, the cell-surface form of Nef might play an important role in the selective depletion of CD4+ cells in HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Improved yield of obese rats using a double coordinate system to locate the ventromedial or paraventricular nucleus.

This article describes a highly efficient method for making VMH and PVN-lesioned obese rats by using a newly developed coordinate system. In previous methods, the coordinates for creating VMH and PVN lesions were determined from single point, either the interaural line or the bregma. Because skull size varies, the use of two reference points resulted in greater consistency. We therefore developed a system for making VMH- and PVN-lesioned obese rats using both the interaural line and the bregma. With this new double coordinate system the success rate for producing obese rats varied from 52% to 92% for VMH lesions and from 36% to 61% for PVN lesions.

Animals↗
PubMed1993

Marked reduction of acyl-CoA synthetase activity and mRNA in intra-abdominal visceral fat by physical exercise.

Several reports have suggested that the reduction of intra-abdominal visceral fat after physical exercise is more prominent than that of subcutaneous fat. We compared some parameters in mesenteric and subcutaneous fats between sedentary and exercised rats (treadmill running; 10-20 m/min, 60 min/day, 7 days). Tissue weight and cell volume were decreased in mesenteric fat by the exercise. The exercise reduced activity and mRNA levels of acyl-CoA synthetase (ACS; 67 and 26% of those of the sedentary group, respectively), mRNA levels of lipoprotein lipase (LPL; 49% of those of the sedentary group), and GLUT-4 (38% of those of the sedentary group) in the mesenteric fat. In contrast, all of these parameters did not change significantly in the subcutaneous fat. Gastrocnemius muscle was heavier in exercised rats. ACS activity was elevated in the gastrocnemius muscle of the exercised rats (137% of those of sedentary group), although mRNA levels of ACS, LPL, and GLUT-4 did not change in the muscle by the exercise. These observations suggest that mesenteric fat may contribute to switching of distribution of plasma energy flux, including lipid and glucose, from fat tissue to muscle in physical exercise.

Abdomen↗
PubMed1993

Involvement of epidermal growth factor in inducing obesity in ovariectomized mice.

Ovariectomy (Ovx) of mice significantly increases the epidermal growth factor (EGF) concentration in the submandibular gland. To elucidate the role of this elevated EGF in obesity of Ovx mice, we examined the effects of sialoadenectomy (Sx) and anti-EGF rabbit antiserum administration on the body weight (BW) gain and carcass fat deposition in Ovx animals. Studies were performed in four groups of mice consisting of control, Ovx, Ovx+Sx, and Ovx+anti-EGF groups. Ovx increased the BW gain compared with the control animals, whereas Sx and anti-EGF significantly reduced it. Although the relative weights (weight ratio to BW) of the liver and kidney were not significantly changed by Ovx, Sx, or anti-EGF treatment of Ovx mice, the relative weights of mesenteric, parametrial, and subcutaneous fat tissues were increased in Ovx mice, and this increase was significantly reduced by Sx or anti-EGF administration. Ovx induced adipocyte hypertrophy, and this effect was eliminated by Sx and anti-EGF. Moreover, acyl-CoA synthetase mRNA level was increased by Ovx, and this increase was reduced by Sx and anti-EGF in mesenteric fat tissue. These findings suggest that elevation of EGF may play a role in the induction of obesity in Ovx mice.

Acetate-CoA Ligase↗
PubMed1993

Chronic neutropenia associated with C2 and C9 deficiency.

A Japanese male with a deficiency of the second and ninth components of complement associated with chronic idiopathic neutropenia is presented. In this case the second component of complement is totally deficient while the ninth component is approximately half that of normal control. Neutrophil granulocytes are constantly few, but this case shows no evidence of susceptibility to either viral or bacterial infections. His HLA type is different from that of Caucasians, suggesting that the genetic abnormality responsible for the complement deficiency of this Japanese case is different from that seen in Caucasian patients.

Adult↗
PubMed1993

Invasive development of right atrial myxoma--a case report.

A thirty-nine-year-old man was admitted to the authors' department complaining of exertional dyspnea and high fever. An echocardiogram showed a mass in the right atrium, which was observed to move to the right atrium during the systolic phase and to the right ventricle during the diastolic phase. Magnetic resonance imaging showed that the mass developed from the right atrium to the superior vena cava. Intravenous digital subtraction angiography also showed a partial defect of the right atrium as well as obstructions of both the superior vena cava and the bilateral innominate veins. A pulmonary hemodynamic scintigram showed multiple defects at the mid and inferior areas of each lung, suggesting multiple pulmonary infarctions. The right atrial tumor was surgically removed. The superior vena cava and the innominate veins were found to be obstructed by organized thrombi, and the tumor had invasively grown into the right atrial wall. Histologic findings demonstrated that most of the tumor was composed of organized thrombi with scattered myxomatous tissue and was diagnosed as cardiac myxoma. These histologic findings suggest that the histogenesis of this right atrial myxoma might be thrombogenic.

Adult↗
PubMed1993

Patients with Graves' disease who developed insulin autoimmune syndrome (Hirata disease) possess HLA-Bw62/Cw4/DR4 carrying DRB1*0406.

The insulin autoimmune syndrome (IAS) is characterized by the following diagnostic criteria: severe spontaneous hypoglycemia without evidence of exogenous insulin administration, high levels of total serum immunoreactive insulin, and the presence of a high titer of antiinsulin antibody. Just before the onset of IAS, 13 of the 35 (37%) patients with IAS examined in this study had taken methimazole for the treatment of Graves' disease. To investigate the difference between the Graves' disease patients treated with methimazole who developed IAS and other IAS patients, HLA class II genes in both groups were analyzed by serological and DNA typing methods. All 13 patients with Graves' disease who developed IAS possessed a specific allelic combination, Bw62/Cw4/DR4 carrying DRB1*0406, whereas only 1 of 50 Graves' disease patients without IAS had Bw62/Cw4/DR4 (odds ratio, 891; P < 1 x 10(-10)) and carried not DRB1*0406 (odds ratio, 2727; P < 1 x 10(-10)), but DRB1*0405. Of the 22 IAS patients without Graves' disease, 13 had the combination Bw62/Cw4/DR4 carrying DRB1*0406 (odds ratio, 19.0; P < 0.07). Thus, it is highly likely that patients with Graves' disease develop IAS via treatment with methimazole when their Bw62/Cw4/DR4 carry DRB1*0406.

Adolescent↗
PubMed1993

Effects of preserving mitral apparatus on ventricular systolic function in mitral valve operations in dogs.

The mitral apparatus can affect left ventricular function through various mechanisms, such as the direct mechanical coupling between the mitral anulus and papillary muscle and the mitral annular contraction. To evaluate the relative contribution of these mechanisms, we investigated in five groups of 35 dogs that underwent open chest operations how preservation of the mitral apparatus affects left ventricular systolic function. We performed atriotomy in the first group. We sutured a prosthetic rigid ring around the mitral anulus in the second group. We replaced the mitral valve and preserved the anterior chordae in the third group, the posterior chordae in the fourth group, and no chordae in the fifth group. The postoperative percentage of recovery of ventricular function (as assessed by the slope of the end-systolic pressure-volume relation) from preoperative control values were 92.2% +/- 4.8%, 89.5% +/- 12.8%, 85.7% +/- 9.5%, 75.1% +/- 12.9%, and 61.3% +/- 8.0%, respectively. Preservation of the mitral apparatus significantly improved left ventricular function compared with that of conventional mitral valve replacement. The average relative contribution of the ventricular muscle to left ventricular function, the mitral anulus-papillary muscle continuity, and the mitral annular contraction were 66.5%, 30.6%, and 2.9%, respectively. We conclude that it is more beneficial to preserve the mitral apparatus in mitral valve replacement. The prosthetic ring does not detract from the functional benefit of the preservation of the mitral apparatus.

Animals↗