[Functions of human immunodeficiency virus regulatory genes].
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Gene Expression Regulation, Viral↗
Biomedical subjects
K Tokunaga
Publications and source records attributed to K Tokunaga.
[A case of post-biopsy arterio-venous fistula in a renal allograft].
We report here a case of post-biopsy arterio-venous fistula in a renal allograft which was successfully embolized. Percutaneous needle biopsy of renal allograft is performed when the cause of deteriorating renal function is clinically difficult to diagnose, and the pathological diagnosis obtained by it determines the therapy. An easy and safe biopsy encourages the clinician, but some complications occur after the procedure. Arterio-venous fistula is one of the complications after percutaneous needle biopsy of renal allograft. Color-coded ultrasonography is effective to find it, and transarterial embolization should be tried first to treat it.
Adult↗
[A controlled study of AO-90, a methionine-free intravenous amino acid solution, in combination with 5-fluorouracil and mitomycin C in advanced gastric cancer patients (internal medicine group evaluation)].
The results of recent preclinical and clinical studies suggest that AO-90, a methionine-free intravenous amino acid solution (7.43%), potentiates the antitumor effect of 5-fluorouracil (5-FU). In the present multi-center, randomized, controlled study conducted at the internal medicine departments of 24 institutions between July 1991 and May 1993, patients with advanced gastric cancer were randomly allocated to receive either AO-90 (500-750 mL/day, AO/MF group) or Amiparen, a commercial intravenous amino acid solution (600-800 mL/day, C/MF group) by total parenteral nutrition for 14 days. Both groups received MF therapy which consisted of a continuous infusion of 5-FU at 350 mg/m2/day for 14 days and an i.v. push of mitomycin C 7 mg/m2 on days 7 and 14 (one course). Additional treatment courses were initiated after a withdrawal period when appropriate. Of the 53 subjects enrolled, 52 (98.1%) were eligible and 47 (88.7%) completed the scheduled treatment (AO/MF group: 23, C/MF group: 24). Although there were significant differences for age and sex between the groups, the Mantel-Haenszel test showed that these unevenly distributed characteristics did not affect the study results. The overall clinical response rates in the completed cases were 30.4% (7/23) in the AO/MF group and 16.7% (4/24) in the C/MF group. In particular, the response rate in the inoperable advanced cases with liver metastases, ascites or distant metastases was 45.5% (5/11) in the AO/MF group versus 16.7% (2/12) in the C/MF group. The treatment-related adverse reactions observed were mainly hematologic and subjective/objective symptoms, such as decreased leukocyte count, hemoglobin level and platelet count, nausea/vomiting, diarrhea, stomatitis, and fever. The differences in the incidence were not significant between the groups. These results show that AO-90 in combination with MF therapy is efficacious in the treatment of patients with gastric cancer.
Adolescent↗
A simple method for detecting single base substitutions and its application to HLA-DPB1 typing.
We have developed a simple and reliable method, PCR-PHFA (polymerase chain reaction dependent preferential homoduplex formation assay), for detection of single base substitutions within PCR amplicons. This technique is based upon strand competition during hybridization between a double labeled amplicon, prepared from biotin and DNP labeled primers, and an unlabeled amplicon. Under the precisely controlled temperature gradient, the preferential formation of a homoduplex over a heteroduplex occurs. After annealing, the identical sequence of the double labeled and unlabeled amplicon resulted in a low population of regenerated double labeled dsDNA due to strand exchange between them. Even when the two differed by only a single base substitution, double labeled molecule was regenerated efficiently because of preferential homoduplex formation. The regenerated double labeled molecule was captured onto a streptavidin coated microtiter plate and quantified enzymatically with a chromogenic substrate. The technique has been successfully applied in HLA-DPB1 typing. Furthermore, we detected a mutated gene even in the presence of a large excess of the corresponding normal gene.
Base Sequence↗
Brief report: polymorphic microsatellite markers for the diagnosis of graft-versus-host disease.
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Alleles↗
The risks of reoperation for prosthetic valve dysfunction.
A retrospective study was conducted on 124 patients who underwent re-replacement of previously implanted prosthetic heart valves for structural valve failure, prosthetic valve endocarditis, periprosthetic leak, a thrombosed valve, hemolysis, or prophylactic removal. In total, 85% of the explanted valves were bioprostheses, and 70% of the newly implanted valves were mechanical valves. The overall operative mortality rate was 8.1%, being 3.2% of 95 single valve recipients and 25.0% of 28 double valve recipients (P < 0.001). The overall mortality rate dropped from 13.6% of 66 patients before 1988, to 1.7% of 58 patients encountered in the last 3 years (P < 0.02). Since 1988, a third of the patients have undergone reoperation without homologous blood transfusion. A univariate analysis revealed eight operative risk factors, namely: higher values of preoperative blood urea nitrogen or total bilirubin, double valve replacement at the redo operation, NYHA class IV, urgency of reoperation, a duration of implantation of less than 3 months, reoperation in the earlier period of this study, and reexploration for bleeding or cardiac tamponade after re-replacement surgery. A multivariate statistical analysis demonstrated that preoperative blood urea nitrogen, urgency of reoperation, double valve replacement, and the duration of implantation were independent risk factors. Thus, we recommend that surgery be performed early, before the occurrence of other organ failure induced by congestive heart failure due to any form of valve dysfunction.
Adolescent↗
The efficacy of fluconazole in treating prosthetic valve endocarditis caused by Candida glabrata: report of a case.
A case of active prosthetic valve infective endocarditis (PVE) due to Candida glabrata was successfully treated by the systemic administration of fluconazole. A 66-year-old Japanese man with infective endocarditis of unknown etiology underwent aortic and mitral valve replacement to treat severe aortic and mitral regurgitation associated with multiple organ failure. Postsurgical cultures of arterial blood were repeatedly positive for C. glabrata, and therefore fluconazole was administered either intravenously or orally at a dose of 400 mg/day for 46 days. During that time the signs of inflammation including fever such as an elevated white blood cell count and the presence of C-reactive protein (CRP) all improved while the blood cultures became negative. Fluconazole is thus considered to be effective in treating PVE caused by C. glabrata. When administering this treatment, it is also important to monitor the patient's renal and liver function.
Aged↗
Simple hepatic cysts. First case report of percutaneous drainage and sclerosis with doxycycline, with a review of literature.
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Aged↗
Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men.
Associations between intra-abdominal visceral fat accumulations and coronary risk factors were studied in a sample of 29 non-obese men aged 57 +/- 10 years with coronary artery disease (CAD). Their body mass indexes (BMI) were 23.8 +/- 1.5 (range 18.7-26.3). The visceral fat area (VFA) and the subcutaneous fat area (SFA) were measured at the level of the umbilicus by computed tomography. In patients with CAD, the average VFA was significantly increased compared with that in 54 control subjects without CAD, matched for sex, age, and BMI (117.2 +/- 53.1 vs. 93.8 +/- 38.6 cm2, P < 0.05). However, their average SFA was not statistically different (111.2 +/- 33.3 vs. 106.3 +/- 35.7 cm2, N.S.). Eleven CAD patients (38%) and nine control subjects (17%) had greater than 2 S.D. higher than the mean VFA obtained from 22 healthy subjects extracted from the control subjects. Accordingly, the proportion of the subjects with high VFA was significantly higher in the CAD group. This group also had significantly higher levels of plasma glucose and insulin areas than controls determined by oral glucose tolerance tests. This may be due to insulin resistance. The proportion of the subjects with multiple risk factors including hyperlipidemia, hyperglycemia, and hypertension was significantly higher in the CAD patients with high VFA compared with the control subjects with normal VFA (CAD with high VFA 82% and control with normal VFA 33%). These findings suggest that visceral fat accumulations may play an important role in the occurrence of CAD regardless of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue↗
Allolymphocytotoxic antibodies in sera from HTLV-I-associated myelopathy/tropical spastic paraparesis patients--putative anti-HLA antibodies.
Thirty-one HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and 34 asymptomatic carriers were studied in order to investigate the presence of anti-lymphocyte antibodies in their sera. 32% of the patients produced allolymphocytotoxic antibodies reactive to peripheral blood lymphocytes (mainly T cells) as well as to B cells, which belonged to the IgM class, reacted under warm and cold conditions, and showed specificity to multiple HLA antigens, especially HLA A2, A26, A33, B7, B27, B35, B48, B61 and Cw3. Moreover, their reactivities could be absorbed by pooled platelets. Therefore, it may be suggested that either anti-HLA class I antibodies or antibodies cross-reactive to HLA were present. On Western blot analysis, the HAM/TSP cytotoxic sera reacted to the 110 kDa molecules of lymphocyte lysates. In the case of carriers, weak cytotoxic antibodies were detectable in 14% of the sera. No multispecificity to HLA class I antigens was observed and there was no reactivity to the 110 kDa band. The production of allolymphocytotoxic antibodies in HAM/TSP patients may therefore be explained by the presence of allogeneic-like stimuli in this disease. HTLV-I infected cells, expressing altered HLA antigens could possibly account for this stimulation and also contribute to the alteration of immune functions in HAM/TSP, and thus play an important role in its pathogenesis.
Adult↗
Marked reduction of pancreatic insulin content in male ventromedial hypothalamic-lesioned spontaneously non-insulin-dependent diabetic (Goto-Kakizaki) rats.
The effects of ventromedial hypothalamic (VMH) lesions were examined in male and female non-obese non-insulin-dependent diabetic (Goto-Kakizaki [GK]) rats with respect to glucose metabolism and pancreatic insulin content. VMH lesions produced hyperphagia and hyperinsulinemia in both male and female GK rats. In male rats, plasma glucose levels of VMH-lesioned GK rats (22.7 +/- 3.1 mmol/L) were significantly greater than the levels of sham-operated GK rats (10.6 +/- 1.0 mmol/L, P < .001) at 7 weeks after the operation, although there were no differences in these levels between VMH-lesioned and sham-operated groups in Wistar rats. Plasma insulin levels in male VMH-lesioned GK rats tended to be lower at 7 weeks than at 1 week. VMH lesions caused a significant decrease in the pancreatic insulin content of male GK rats (12.0 +/- 2.3 nmol/L/g pancreas) compared with male sham-operated rats (15.8 +/- 1.4 nmol/L/g pancreas, P < .05) 9 weeks postoperatively. In contrast to the results in male rats, female GK rats showed no differences in plasma glucose levels between VMH-lesioned and sham-operated groups at 7 weeks. Female VMH-lesioned GK rats also showed no difference in plasma insulin levels between 1 week and 7 weeks. The pancreatic insulin level of female VMH-lesioned GK rats was unchanged from that of female sham-operated GK rats. The insulin content was significantly greater in the VMH-lesioned Wistar group than in the sham-operated Wistar group, regardless of sex.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Ribbon enchephalo-duro-arterio-myo-synangiosis for moyamoya disease.
In patients with advanced moyamoya disease, reconstructive surgery alone may not prevent the deterioration of blood flow in the territory of the anterior cerebral artery. These types of surgery include superficial temporal artery-to-middle cerebral artery anastomosis and encephalo-duro-arterio-myo-synangiosis (EDAMS). Bilateral encephalo-duro-arterio-synangiosis (EDAS) gradually reduced the transient ischemic attacks in one of our patients who experienced motor weakness in the left extremities. After surgery, however, persistent bilateral attacks still occurred in the patient's legs. In a subsequent maneuver, we inserted the pedicle of the galea on both sides into the interhemispheric fissure, which induced marked vascularization in the territory of the anterior cerebral artery, and the attacks disappeared. Since then, we have combined this "ribbon" technique with EDAMS to treat eight patients with moyamoya disease. Postoperative angiograms showed widespread collateral circulation on the ischemic brain surface in six patients undergoing ribbon EDAS or EDAMS. Postoperative measurements of cerebral blood flow revealed improved circulation in the frontal region in four patients. The clinical results were excellent in six patients, and good in one, and we lost follow-up in one. The ribbon EDAMS procedure is effective on moyamoya disease with symptomatic cerebral ischemia of the anterior circulation.
Adolescent↗
Polymorphisms of transporter associated with antigen processing genes in atopic dermatitis.
We investigated polymorphisms of transporter associated with antigen process (TAP) genes in atopic dermatitis. We developed a polymerase chain reaction-restriction fragment length polymorphism method for discriminating TAP alleles. Genomic DNA was obtained from 29 Japanese patients with atopic dermatitis and 35 control subjects. Dimorphic regions of TAP1 and TAP2 genes were amplified by polymerase chain reaction. Amplified products were digested with restriction endonucleases to determine TAP alleles: Sau3A1 for TAP1 codon 333 (Ile-Val), AccI for TAP1 codon 637 (Asp-Gly), and EcoRII for TAP2 codon 687 (Gln-Stop). We observed four alleles for TAP1 and dimorphism for TAP2 codon 687. Six of 35 controls had the TAP1 D allele, which has been reported to be a rare allele in Caucasian populations. Gene frequency of TAP1 637Asp exhibited a tendency to increase in the patients with atopic dermatitis. TAP1 637Asp and TAP1 A alleles were estimated to constitute a haplotype with DRB1* 1302-DQB1*0604 and DRB1*0803-DQB1*0601 in the Japanese population. Because TAP1 and TAP2 genes are located between HLA-DQB1 and -DPB1 loci, analysis of TAP gene polymorphisms will be useful for a better understanding of susceptibility loci in HLA class II-associated disease.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
HLA and atopic dermatitis with high serum IgE levels.
Patients with atopic dermatitis usually exhibit allergen-specific IgE antibodies against several environmental antigens. HLA restriction is presumed to be involved in the recognition of such antigens, but several previous reports have so far failed to find a significant association between atopic dermatitis and HLA antigens. In this study we examined 38 unrelated Japanese patients with severe atopic dermatitis and high serum IgE levels (greater than 800 U/ml). We investigated the serological HLA types and HLA class II alleles in this group of patients with atopic dermatitis. Frequencies of HLA-A24, A33, Cwblank, B44, DR13 and HLA-DRB1*1302, DQB1*0604, DPB1*0301 alleles were increased in the patients. In contrast, frequencies of HLA-Cw1, Bw6, DR4, DR53, and HLA-DQB1*0302 allele were decreased. However, none of these remained significant after p values were corrected. Further study on HLA association with atopic dermatitis through characterization of specific antigens or antigen epitopes is needed.
Adolescent↗
Pathophysiology and pathogenesis of visceral fat obesity.
Based on the analysis of fat distribution by CT scanning, we have proposed a classification of obesity: visceral fat obesity, in which fat accumulation is predominant in the intra-abdominal cavity. This type of obesity is more frequently accompanied by disorders of glucose and lipid metabolism, and also with hypertension, than subcutaneous fat obesity. We also showed that almost 90% of obese patients with ischemic heart disease have visceral fat accumulation. From clinical and basic experiments, aging, imbalance of sex hormone, overintake of sucrose and lack of physical exercise have been suggested to be major factors for visceral fat accumulation. Since intra-abdominal fat (mesenteric and omentum fat) have been show to have high activities of both lipogenesis and lipolysis, its accumulation induces a high content of free fatty acids, a product of lipolysis, in portal circulation which goes into the liver directly. Excess free fatty acid may cause the enhancement of lipid synthesis and gluconeogenesis as well as insulin resistance, resulting in hyperlipidemia, glucose intolerance and hypertension and finally atherosclerosis.
Adipose Tissue↗
A simple method of HLA-DRB typing using enzymatically amplified DNA and immobilized probes on microtiter plate.
We have developed a simple and economical method for HLA-DNA typing, called microtiter plate hybridization (PCR-MPH), which could replace standard PCR-SSO. This method is similar to that of an ELISA. Briefly, the PCR products labeled at the 5' termini with biotin were hybridized with probes immobilized on a microtiter well, and the bound PCR products were detected by streptavidin-conjugated enzymes followed by color development. A system for HLA-DRB1 "generic" typing (e.g., DR1, DR2), using microtiter wells coated with 12 different SSOs has been established. The HLA-DRB types classified using this method agreed well with those obtained by conventional serologic typing. The advantages of this microtiter plate-hybridization method for routine HLA-DNA typing are a short assay time, easy processing of large numbers of samples, and the potential for automation.
Base Sequence↗
Identification of the gene encoding a novel HLA-B39 subtype. Two amino acid substitutions on the beta-sheet out of the peptide-binding floor form a novel serological epitope.
Serological analysis suggests the existence of a novel HLA-B39 subtype (HLA-B39N) in the Japanese population. To identify this novel allele, a gene encoding HLA-B39N was cloned and the exons were sequenced. A gene encoding HLA-B39N (B*3904) and B*39011 differs by two nucleotide substitutions at codons 11 and 12 whereas B*3904 and B*39013 differ by three nucleotide substitutions at codons 11, 12, and 312. One nucleotide difference at codon 11 produces a change from serine in B*3901 to alanine in B*3904 whereas another difference at codon 12 changes valine in B*3901 to methionine in B*3904. The residues 11 and 12 are located on the beta-sheet out of the peptide-binding floor and are completely buried in the molecule. These results suggest that the substitutions at these residues alter the conformation of other residues forming epitopes of alloantibodies. Analysis of HLA-B*3901 genes in the Japanese population showed that both B*39011 and B*39013 were observed in the Japanese population. The present study suggests that B*3904 may have evolved from B*39011 rather than B*39013.
Amino Acid Sequence↗
Sequences of four splits of HLA-A10 group. Implications for serologic cross-reactivities and their evolution.
Nucleotide sequences of alleles encoding four serologically defined splits of the HLA-A10 group, A26.1, A26.3, A26.4, and A10SA, were determined. It was confirmed that the alleles coding for A26.1 and A26.3 are identical with A*2602 and A*2601, respectively. On the other hand, alleles for A26.4 and A10SA are thus far undescribed. A26.4 (A*2603) was different from the other A26 splits at three positions: 74 histidine, 76 valine, and 77 aspartate. A10SA (A*2604) was different from A26.3 (A*2601) by a single substitution of arginine by leucine at position 163. A comparison of amino acid sequences of HLA-A10 cross-reacting antigens revealed that all of the A10 group antigens share specific amino acids: 142 isoleucine, 144 glutamine, 145 arginine, 149 threonine, and 152 glutamate. Moreover, A26.1, A26.3, A10SA, and A43 share 76 alanine and 77 asparagine, which is consistent with the reported serologic cross-reactivity. The close relationship between the alleles for the A10 cross-reacting group was supported by a phylogenetic tree analysis for the HLA-A alleles.
Alleles↗