Biomedical subjects

M Yano

Publications and source records attributed to M Yano.

At least 163 records · Page 9Linked to original sources

PubMed2000

Potentialities and problems of a novel bilateral ventricular assist system without thoracotomy.

Mechanical cardiac assistance can be critical in saving the lives of patients with acute cardiac failure. However, currently used methods of ventricular assistance require advanced technical knowledge and equipment, and only small numbers of patients can be provided with them. Our aim was to develop new cannulas to construct a less invasive biventricular assist system that would permit easy application without thoracotomy. We prepared 2 centrifugal pumps and 4 uniquely shaped cannulas and conducted experiments to investigate the potential and problems of the system. In the first experiment, the system was attached to 6 dogs with ventricular fibrillation to confirm whether our system could maintain cardiac output. In the second experiment, the system was installed for 3 days in 3 goats, and changes in aminotransferases, BUN, creatinine, and plasma free hemoglobin levels were examined. In Experiment 1, it was demonstrated that the system was able to maintain circulation in dogs. In Experiment 2, although the flow rate of the pumps was maintained over 3 days, increased hemolysis and deteriorating renal function were observed. Although these problems need to be solved, the system was still helpful in the management of acute biventricular failure for short periods and may be clinically useful in the near future.

Acute Disease↗

PubMed2000

Increased insulin sensitivity and decreased insulin secretion in offspring of insulin-sensitive type 2 diabetic patients.

To investigate the early defects of glucose metabolism in insulin-sensitive type 2 diabetes, we performed oral and frequently sampled intravenous glucose tolerance tests (OGTT and FSIGT) with minimal model analysis in 15 offspring of Japanese type 2 diabetics with normal insulin sensitivity (insulin resistance index of homeostasis model assessment [HOMA-R] < 2.0) and in 20 healthy control subjects without a family history of type 2 diabetes. The frequency of impaired glucose tolerance (IGT) was 40% (6 of 15) in the offspring and 0% (0 of 20) in the controls. Fasting plasma glucose (4.8 +/- 0.1 v4.6 +/- 0.1 mmol/L, P = .18) and immunoreactive insulin ([IRI] 29.9 +/- 2.5 v 28.3 +/- 2.5 pmol/L, P = .64) were comparable between the offspring and the controls. The rate of glucose disappearance (KG) was significantly lower in the offspring versus the control group (2.00 +/- 0.22 v 2.60 +/- 0.17 min(-1), P= .03). The insulin sensitivity index (Si) was significantly greater in the offspring versus the controls (2.68 +/- 0.41 v 1.71 +/- 0.17 x 10(-4) min(-1) x pmol/L , P = .02). First-phase insulin secretion (FPI) to intravenous glucose was significantly lower in the offspring versus the control group (886 +/- 110 v 2,296 +/- 267 min x pmol/L, P< .01). Glucose effectiveness (SG) was comparable between the offspring and control groups. The disposition index (Si x FPI) was significantly lower in the offspring versus the controls (2,106 +/- 256 v 3,652 +/- 490 x 10(-4), P = .02). When the offspring were subdivided into 2 groups by glucose tolerance status, both normal glucose tolerance (NGT) offspring and IGT offspring showed a significant decrease in FPI and increase in Si. Thus, although the offspring of insulin-sensitive type 2 diabetics had increased insulin sensitivity, the impairment in insulin secretion was more dominant. Our results suggest that the early metabolic abnormality in insulin-sensitive type 2 diabetes is an insulin secretory dysfunction despite increased insulin sensitivity.

Adult↗

PubMed2000

Long-term effects of bisoprolol compared with imidapril on left ventricular remodeling after reperfusion in acute myocardial infarction: an angiographic study in patients with maintained vessel patency.

BACKGROUND: Although angiotensin-converting enzyme inhibitor attenuates ventricular enlargement, whether beta-blocker therapy induces regression of left ventricular remodeling is not known. The purpose of this study was to compare the effects of bisoprolol therapy with those of imidapril therapy on left ventricular remodeling after acute myocardial infarction (AMI). METHODS: Sixty patients with AMI who underwent reperfusion therapy were randomly assigned to an imidapril group (20 patients), a bisoprolol group (20 patients), or a control group (20 patients). Administration was started within 24 hours. Left ventricular function on admission and 3 months and 1 year after AMI was investigated. RESULTS: Baseline characteristics on admission were similar in the 3 groups except for sex distribution. Mean pulmonary capillary wedge pressure and left ventricular end-diastolic pressure in the bisoprolol group were higher than those in the imidapril group 1 year after admission (pulmonary capillary wedge pressure: 12 +/- 7 vs 8 +/- 2 mm Hg, left ventricular end-diastolic pressure: 17 +/- 8 vs 11 +/- 4 mm Hg, P <. 01). Left ventricular end-diastolic volume index (EDVI) increased in the bisoprolol group throughout the 1-year period (P <.01), whereas EDVI in the imidapril group decreased (P <.01). The increases in EDVI during 1 year in the bisoprolol group were greater than those of the other 2 groups (bisoprolol: 12 +/- 10, imidapril: -9 +/- 7, control: 4 +/- 11 mL/m2, P <.01). CONCLUSIONS: Early treatment with bisoprolol in AMI cannot prevent left ventricular remodeling, whereas imidapril attenuates left ventricular dilation by decreasing preload.

Adrenergic beta-Antagonists↗

PubMed2000

Clinical application of malignancy potential grading as a prognostic factor of human esophageal cancers.

BACKGROUND: Various biologic markers have been reported to be prognostic factors in human esophageal cancers. In the current study, we established a new tumor-grading system representing the malignancy potential of cancer cells and compared it with the clinical-stage system. METHODS: Tumor samples from 77 patients with squamous cell carcinoma of the esophagus were immunohistochemically evaluated for the expression of 10 molecules: the cell cycle-related molecules of cyclin D1, Rb, p16INK4, p27KIP1, and PCNA; the cell-cell adhesion molecules of E-cadherin, alpha-catenin, and beta-catenin; and the heat shock proteins of HSP27 and HSP70. RESULTS: P27KIP1, beta-catenin, and HSP70 were selected for their high hazard ratio in multivariate analysis, and the number of their disordered molecules was used to define the malignancy grade (MG). Five-year survival rates were 83%, 54%, 17%, and 0% for MG1, MG2, MG3, and MG4. The gradation of survival curves was better for MGs than for clinical stages. MGs and clinical stages showed significant correlation; however, 55% of those in higher clinical stages (stage 3 or 4) had lower MG (MG1 or 2) and showed better prognosis than others in their group (stage 3 or 4 and MG3 or 4). The proportions of shorter survival span to cancer death patients (less than 1 year) were 0%, 33%, 75%, and 100% in MG1, 2, 3, and 4, but the clinical stage was not associated with the survival span. CONCLUSIONS: The grading of malignancy potential is clinically useful, especially for selecting patients who may show good prognosis in the advanced clinical stage and for predicting short survival span. These predictions are not possible with the clinical-stage system, which is based on the anatomic spread of cancer cells.

Cell Cycle Proteins↗

PubMed2000

Identification of heading date quantitative trait locus Hd6 and characterization of its epistatic interactions with Hd2 in rice using advanced backcross progeny.

A backcrossed population (BC(4)F(2)) derived from a cross between a japonica rice variety, Nipponbare, as the recurrent parent and an indica rice variety, Kasalath, as the donor parent showed a long-range variation in days to heading. Quantitative trait loci (QTL) analysis revealed that two QTL, one on chromosome 3, designated Hd6, and another on chromosome 2, designated Hd7, were involved in this variation; and Hd6 was precisely mapped as a single Mendelian factor by using progeny testing (BC(4)F(3)). The nearly isogenic line with QTL (QTL-NIL) that carries the chromosomal segment from Kasalath for the Hd6 region in Nipponbare's genetic background was developed by marker-assisted selection. In a day-length treatment test, the QTL-NIL for Hd6 prominently increased days to heading under a 13.5-hr day length compared with the recurrent parent, Nipponbare, suggesting that Hd6 controls photoperiod sensitivity. QTL analysis of the F(2) population derived from a cross between the QTL-NILs revealed existence of an epistatic interaction between Hd2, which is one of the photoperiod sensitivity genes detected in a previous analysis, and Hd6. The day-length treatment tests of these QTL-NILs, including the line introgressing both Hd2 and Hd6, also indicated an epistatic interaction for photoperiod sensitivity between them.

Chromosome Mapping↗

PubMed2000

Docosahexaenoic acid and vitamin E can reduce human monocytic U937 cell apoptosis induced by tumor necrosis factor.

The effects of polyunsaturated fatty acids and vitamin E on tumor necrosis factor (TNF)-induced apoptosis of human monocytic U937 cells was explored to assess to what extent these nutrients could attenuate apoptosis. Preincubation of U937 cells with arachidonic acid for 24 h did not affect TNF-induced apoptosis. Eicosapentaenoic acid slightly but significantly reduced the proportion of apoptotic cells only when apoptosis was induced by TNF without cycloheximide (CHI). In contrast, preincubation with docosahexaenoic acid (DHA) greatly (40 approximately 70%) attenuated apoptosis induced by stimulation with either TNF or TNF + CHI for 3 h. The inhibition of apoptosis was accompanied by enrichment of DHA in membrane phospholipids, indicating that DHA probably exerted its inhibitory activity after being incorporated into the phospholipids. Vitamin E also played a role as a partial inhibitor of apoptosis 3 h after TNF addition. This vitamin could further reduce the apoptosis of DHA-treated cells, and such an additive effect was obvious when apoptosis was induced at a low frequency. Longer-range stimulation of U937 cells with TNF showed that inhibition of apoptosis by preincubating cells with either DHA or vitamin E was not significant 9 h after TNF addition, but that preincubation with both DHA and vitamin E could reduce the proportion of apoptotic cells even at this time point. Our findings suggested that ingestion of nutrients such as DHA and vitamin E might exert beneficial effects on organ dysfunction associated with various TNF-related diseases.

Apoptosis↗

PubMed2000

Rice NPH1 homologues, OsNPH1a and OsNPH1b, are differently photoregulated.

The members of nonphototropic hypocotyl 1 (NPH1) family of genes in plants are considered to be the blue-light photoreceptors for phototropism. We isolated and characterized two NPH1 homologues from rice named as OsNPH1a and OsNPH1b. The predicted proteins of both OsNPH1 genes include LOV (LOV1 and LOV2) and protein kinase domains which are typically conserved regions in all the members of NPH1 family. Comparison of OsNPH1 apoproteins with those from other plant species revealed a close homology of OsNPHla with Arabidopsis, maize and oat NPH1, while the OsNPH1b appeared to be more closer to the recently found Arabidopsis NPL1. These structural homologies indicate that NPH1 homologues can be grouped into two classes namely "NPH1 type" and "NPL1 type". Northern blot analysis showed that OsNPH1a was strongly expressed in coleoptiles, whereas OsNPH1b was highly expressed in leaves of dark-grown rice seedlings. When the dark-grown seedlings were transferred to the continuous white light, the abundance of the OsNPH1a transcript in coleoptiles rapidly declined to the minimum levels, whereas the OsNPH1b transcript level in leaves gradually increased. These results lead us to conclude that expression of OsNPH1a and OsNPH1b is differently photoregulated in different tissues of rice seedlings.

Amino Acid Sequence↗

PubMed2000

Wound-induced ethylene synthesis and expression and formation of 1-aminocyclopropane-1-carboxylate (ACC) synthase, ACC oxidase, phenylalanine ammonia-lyase, and peroxidase in wounded mesocarp tissue of Cucurbita maxima.

1-Aminocyclopropane-1-carboxylate (ACC) synthase was rapidly induced in mesocarp tissue of Cucurbita maxima after wounding in the cut surface layer in 1 mm thickness (ca. 9 cells) (first layer) in both the enzyme activity and the levels of transcript. This led to a rapid accumulation of ACC and hence ethylene production. In the inside tissue (1-2 mm) (second layer), no significant induction of ACC synthase was observed, which resulted in a low level of ACC, although ethylene was evolved at a much lower rate than the first one. In contrast to ACC synthase, ACC oxidase was induced markedly in both the first and second layers and the development of its activity and the levels of mRNA remained high until later stages. It was considered that wound ethylene was closely associated with the development of ACC oxidase, since 2,5-norbornadiene (NBD), an inhibitor of ethylene action, substantially suppressed it. Phenylalanine ammonia-lyase (PAL) greatly increased in activity after wounding similarly to that of ACC synthase, in which increase in PAL activity occurred predominantly in the first layer. Induction of peroxidase activity after wounding had a close correlation in profile with that of ACC oxidase in that marked increases in the activity were observed in both the first and second layers and were strongly suppressed by NBD application. Four peroxidase isozymes were found by PAGE, among which a fraction was newly detected after wounding.

Amino Acid Oxidoreductases↗

PubMed2000

Evaluation of filtration leucocytapheresis for use in the treatment of patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the efficacy of filtration leucocytapheresis (LCP) for rheumatoid arthritis (RA). METHODS: LCP was carried out three times, with 1 week separating each session, in 25 drug-resistant RA patients. RESULTS: During each session, 96, 98, 61, 84 and 8% of the granulocytes, monocytes, lymphocytes, platelets and erythrocytes, respectively, that entered the LCP filter were removed. The number of granulocytes, monocytes and lymphocytes in the peripheral blood significantly decreased during each session of LCP. However, there was no significant decrease in the number of circulating blood cells during the study period. On average, 110 x 10(8) granulocytes, 5.23 x 10(8) monocytes, and 20.5 x 10(8) lymphocytes were removed during LCP therapy. Assessment of RA before and after LCP showed a substantial and rapid improvement in the tender joints counts, swollen joint counts, and patient's and physician's assessments. No adverse reactions or complications were noted. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels decreased following LCP, although the change in the latter parameter was statistically insignificant. The concentrations of serum albumin, gamma-globulin, IgG, IgM, CH50 and rheumatoid factor titres did not change during or after LCP. Careful analysis indicated that 16 of 25 patients with RA showed > or =20% improvement following LCP therapy. CONCLUSIONS: Our results suggest that filtration LCP to remove leucocytes from the peripheral blood exerts an immunomodulatory effect in patients with RA.

Arthritis, Rheumatoid↗

PubMed2000

Vasodilator responses of coronary conduit and resistance arteries to continuous nitroglycerin infusion in humans: a Doppler guide wire study.

To examine the responses of coronary conduit and resistance arteries to the continuous i.v. administration of nitroglycerin in 15 patients with atypical chest pain, we measured coronary blood flow velocity in the left anterior descending coronary artery using a Doppler guide wire and the lumen diameter and cross-sectional area by quantitative coronary angiography. Systolic flow, diastolic flow, total coronary flow, and coronary vascular resistance were calculated. Stepwise increases in dose of nitroglycerin resulted in significant dose-dependent decrease in mean aortic pressure (p < 0.01) and increase in lumen diameter (p < 0.05). After nitroglycerin administration of 0.5 microg/kg/min, systolic flow decreased significantly by 89.9+/-15.7% (p < 0.01), and diastolic flow increased significantly by 74.2+/-37.1% (p < 0.05). Total coronary flow did not change significantly with the various doses of nitroglycerin. However, coronary vascular resistance decreased significantly at concentrations greater than 0.5 microg/kg/min nitroglycerin. Continuous nitroglycerin infusion did not reduce either diastolic or total coronary blood flow despite a significant reduction in coronary perfusion pressure. These results indicate that subendocardial blood flow might be maintained during continuous i.v. infusion of nitroglycerin within the clinical dose range.

Angiography↗

PubMed2000

Hd1, a major photoperiod sensitivity quantitative trait locus in rice, is closely related to the Arabidopsis flowering time gene CONSTANS.

A major quantitative trait locus (QTL) controlling response to photoperiod, Hd1, was identified by means of a map-based cloning strategy. High-resolution mapping using 1505 segregants enabled us to define a genomic region of approximately 12 kb as a candidate for Hd1. Further analysis revealed that the Hd1 QTL corresponds to a gene that is a homolog of CONSTANS in Arabidopsis. Sequencing analysis revealed a 43-bp deletion in the first exon of the photoperiod sensitivity 1 (se1) mutant HS66 and a 433-bp insertion in the intron in mutant HS110. Se1 is allelic to the Hd1 QTL, as determined by analysis of two se1 mutants, HS66 and HS110. Genetic complementation analysis proved the function of the candidate gene. The amount of Hd1 mRNA was not greatly affected by a change in length of the photoperiod. We suggest that Hd1 functions in the promotion of heading under short-day conditions and in inhibition under long-day conditions.

Amino Acid Sequence↗

PubMed2000

Mutations in interferon sensitivity-determining region of hepatitis C virus: its relation to change in viral load.

OBJECTIVE: Interferon sensitivity-determining region (ISDR) in nonstructural region 5A of hepatitis C virus (HCV) genotype-1b has been reported to be associated with viral load. Viral load is usually small in the patients with mutant type (four or more amino acid substitutions, compared with HCV-J) and large in those with wild (identical to HCV-J) or intermediate type (from one to three amino acid substitutions). A possible correlation was investigated between mutations in ISDR and alterations of viral load during the course of disease. METHODS: The sequences of ISDR were determined in eight patients with significant changes of viral load and in 11 patients without changes. RESULTS: In two of the eight patients with significant alterations of viral load, ISDR sequences changed significantly. In one patient whose viral load increased after a course of interferon therapy, the number of substitutions, compared with HCV-J, decreased from five to zero or one; the type of ISDR converted from mutant type to wild or intermediate type. In one patient whose viral load decreased significantly after two courses of interferon therapy, the number of substitutions increased from one to six; ISDR changed from intermediate type to mutant type. In the remaining six patients with changes of viral load and in the other 11 patients without changes, the sequences of ISDR did not change significantly. CONCLUSIONS: The mutations in ISDR are one of the viral factors involved in the changes in viral load during the course of disease, although the majority of other factors involved are still unknown.

Adult↗

PubMed2000

Identification and functional analysis of human Tom22 for protein import into mitochondria.

Mitochondria have a receptor complex in the outer membrane which recognizes and translocates mitochondrial proteins synthesized in the cytosol. We report here the identification and functional analysis of human Tom22 (hTom22). hTom22 has an N-terminal negatively charged region exposed to the cytosol, a putative transmembrane region, and a C-terminal intermembrane space region with little negative charge. Tom22 forms a complex with Tom20, and its cytosolic domain functions as an import receptor as in fungi. An import inhibition assay, using pre-ornithine transcarbamylase (pOTC) derivatives and a series of hTom22 deletion mutants, showed that the C-terminal segment of the cytosolic domain is important for presequence binding, whereas the N-terminal domain is important for binding to the mature portion of pOTC. No evidence for pOTC interaction with the Tom22 intermembrane space domain was obtained. Binding studies revealed that the presequence is critical for pOTC binding to Tom20, whereas both the presequence and mature portion are important for binding to Tom22. A cell-free immunoprecipitation assay indicated that an internal segment of the Tom22 cytosolic domain is important for interaction with Tom20.

Amino Acid Sequence↗

PubMed2000

Tom20-mediated mitochondrial protein import in muscle cells during differentiation.

Mitochondrial biogenesis is accompanied by an increased expression of components of the protein import machinery, as well as increased import of proteins destined for the matrix. We evaluated the role of the outer membrane receptor Tom20 by varying its expression and measuring changes in the import of malate dehydrogenase (MDH) in differentiating C2C12 muscle cells. Cells transfected with Tom20 had levels that were twofold higher than in control cells. Labeling of cells followed by immunoprecipitation of MDH revealed equivalent increases in MDH import. This parallelism between import rate and Tom20 levels was also evident as a result of thyroid hormone treatment. Using antisense oligodeoxynucleotides, we inhibited Tom20 expression by 40%, resulting in 40-60% reductions in MDH import. In vitro assays also revealed that import into the matrix was more sensitive to Tom20 inhibition than import into the outer membrane. These data indicate a close relationship between induced changes in Tom20 and the import of a matrix protein, suggesting that Tom20 is involved in determining the kinetics of import. However, this relationship was dissociated during normal differentiation, since the expression of Tom20 remained relatively constant, whereas imported MDH increased 12-fold. Thus Tom20 is important in determining import during organelle biogenesis, but other mechanisms (e.g., intramitochondrial protein degradation or nuclear transcription) likely also play a role in establishing the final mitochondrial phenotype during normal muscle differentiation.

Cell Differentiation↗

PubMed2000

Mechanism of preserved positive lusitropy by cAMP-dependent drugs in heart failure.

In tachycardia-induced heart failure (HF), positive lusitropic effects of milrinone or dobutamine were assessed by evaluating the time constant of left ventricular (LV) pressure decay (tau) and Ca(2+)-ATPase activity of the sarcoplasmic reticulum (SR). The peak value of the positive first derivative of LV pressure (+dP/dt) was less increased, either by dobutamine (2-10 microg x kg(-1) x min(-1)) or by milrinone (4-20 microg/kg), in HF than in control (P < 0.05), whereas tau was shortened to an extent similar to that in control with dobutamine [P = not significant (NS)] and to an even greater extent with milrinone (P < 0.05). Ca(2+)-ATPase activity increased similarly in HF and control with dobutamine (1 microM; +11% in HF vs. +12% in control, P = NS), whereas it increased more with milrinone (1 microM; +19% in HF vs. +11% in control, P < 0.05). Ca(2+)-ATPase activity-cAMP relationships were shifted to the left by milrinone or dobutamine in HF compared with control. Thus, in HF, the sensitivity of Ca(2+)-ATPase activity to cAMP was increased on addition of cAMP-dependent inotropic agents, contributing to the preservation of positive lusitropy.

Animals↗

PubMed2000

Effect of milrinone on left ventricular relaxation and Ca(2+) uptake function of cardiac sarcoplasmic reticulum.

Milrinone, a phosphodiesterase 3 (PDE3) inhibitor, is known to enhance left ventricular (LV) contractility by an inhibition of the breakdown of cAMP through the mechanism inhibiting PDE3. However, it is unclear whether milrinone also exerts positive lusitropy, like dobutamine. Here, we assessed the effects of milrinone on in vivo LV relaxation, as well as the Ca(2+)-ATPase activity and the Ca(2+) uptake function of the cardiac sarcoplasmic reticulum (SR), compared with the effect of dobutamine on those functions. After dobutamine (3 microg x kg(-1) x min(-1)) was administered, the peak value of the first derivative of LV pressure (+dP/dt) increased by 46%, whereas the time constant (tau) of LV pressure decay decreased by 6.9%, respectively. After milrinone (10 microg/kg) was administered, the peak +dP/dt increased to a similar extent as dobutamine (46%), whereas tau decreased much more than dobutamine (19.9%; P < 0.05). In LV crude homogenate, the thapsigargin-sensitive, Ca(2+)-ATPase activity-cAMP relationships was significantly less increased by milrinone compared with dobutamine (P < 0.05), indicating the higher sensitivity of the SR Ca(2+)-ATPase activity on cAMP by milrinone than by dobutamine. In the SR vesicles purified from LV muscles, the addition of cAMP increased the SR Ca(2+) uptake in a dose-dependent fashion, and the PDE3 inhibitors (milrinone and cGMP) significantly augmented this response (P < 0.05). Hence, milrinone substantially improved LV relaxation in association with an acceleration of the SR Ca(2+)-ATPase activity and the SR Ca(2+) uptake. This acceleration might be due to an inhibition of the membrane-bound PDE3 in the SR, leading to a local elevation of cAMP.

Adrenergic beta-Agonists↗

PubMed2000

Loss of p27(KIP1) expression predicts poor prognosis in patients with esophageal squamous cell carcinoma.

Immunohistochemical studies of cell cycle-regulating proteins were conducted on tissue samples from 106 patients with esophageal squamous cell carcinoma. Reduction of p27(KIP1) was observed in 41 (39%) cases and was significantly associated with a poor prognosis by univariate and multivariate analyses (p = 0.015). In contrast, p16(INK4) expression was reduced in 55 (52%) of the cases and was not correlated with prognosis. p27(KIP1) was not correlated with the PCNA index, while p16(INK4) expression was inversely correlated with the PCNA index (p = 0.01). The expression of these two proteins was not correlated with the clinicopathological parameters of the patients. Nodal status was shown by univariate analysis (p = 0.01) to be a prognostic factor, and poorly differentiated tumors were significantly associated with a poor prognosis by multivariate analysis (p = 0.027). Thus, reduction of p27(KIP1) plays an important role in the progression of esophageal squamous cell carcinomas and is considered to be an independent prognostic indicator of this disease.

Adult↗

PubMed2000

Existence of TT virus DNA in extracellular body fluids from normal healthy Japanese subjects.

Although recent studies indicate a high prevalence (12-92%) of TT virus (TTV) DNA in sera of healthy Japanese individuals, there is a paucity of information regarding the route of transmission of this virus. Analyzing the nucleotide sequences of the existing polymerase chain reaction (PCR) primers of TTV DNA, we developed a set of noble primers (HM-1) and looked for the prevalence of TTV DNA in sera from 39 normal healthy Japanese individuals using PCR. The existence of TTV DNA was also checked in saliva, urine, sweat, stool, and tears from 11 and in semen from 10 serum TTV-positive normal subjects. TTV DNA was detected in sera from 23 of 39 (59.0%) normal subjects. TTV DNA was also detected in saliva, stool, semen and tears from all cases with TTV-DNA-positive serum, but not in body fluids from subjects with TTV-DNA-negative serum. TTV DNA remained undetected in urine and sweat from all cases. Data from these experiments showing the existence of TTV DNA in different body fluids suggest that the high rates of prevalence of TTV among normal healthy subjects might be due to a possible fecal-oral, droplet, or sexual route of transmission of TTV.

Adult↗