Biomedical subjects

K Aoki

Publications and source records attributed to K Aoki.

At least 217 records · Page 12Linked to original sources

PubMed1999

Acute follicular conjunctivitis caused by adenovirus type 34.

PURPOSE: Adenovirus type 34 belongs to adenovirus subgenus B. The prototype virus of adenovirus 34 was isolated from a renal transplant recipient. However, no case of acute conjunctivitis caused by adenovirus 34 has been reported. Recently, we encountered two cases of acute follicular conjunctivitis in which adenovirus 34 was isolated. METHODS: The clinical isolates were identified by the standard neutralization test. The sequences of seven hypervariable regions in the hexon protein of these cases were compared with those of several prototype strains of adenovirus subgenus B. RESULTS: The cases were middle-aged, 34 and 41 years old, and male, and they exhibited moderate conjunctivitis with upper respiratory tract symptoms. Isolates from cell culture were identified as adenovirus 34 by NT. The mean homology rate (percentage of total number of coincident amino acids in the total length of amino acids in seven hypervariable regions) between clinical isolates and the adenovirus 34 prototype was 96.5%; in contrast, those between clinical isolates and the prototypes of adenovirus 11, adenovirus 14, and adenovirus 35 were 55.6%, 66.7%, and 57.9%, respectively. The results of conventional serotyping by neutralization test were confirmed by these values. CONCLUSIONS: These results indicate that adenovirus 34 may induce acute conjunctivitis in immunocompetent subjects and that special attention should be paid to adenovirus 34 as a causative agent for adenoviral conjunctivitis.

Acute Disease↗

PubMed1999

Risk modification in lung cancer by a dietary intake of preserved foods and soyfoods: findings from a case-control study in Okinawa, Japan.

To disclose the association of dietary intake of preserved foods and soyfoods with lung cancer risk, we analyzed the data from a case-control study conducted in Okinawa, Japan, from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched population controls, provided the following major findings. (1) The more the miso soup intake, the higher the risk (test for trend: P = 0.001 for males; P = 0.043 for females). (2) Frequent intake of pickles (excluding salted fish) tended to be linked with an elevated risk in males. The adjusted odds ratio (OR) for once or twice per week or more, relative to less than once a month was 1.88 (95% confidence interval (CI): 1.26-2.81). (3) Frequent intake of soybeans was associated with a decreased risk in men (OR: 0.63, 95% CI: 0.40-0.98 for once or twice per week or more, relative to less than once a month). (4) Daily consumers of tofu were at a decreased risk, particularly for squamous cell carcinoma; the OR (95% CI) being 0.55 (0.34-0.89) in males and 0.14 (0.02-0.89) in females. These findings suggested deleterious effects of preserved foods and protective ones of soyfoods rich in isoflavones.

Adenocarcinoma↗

PubMed1999

Role of polysialic acid on outgrowth of rat olfactory receptor neurons.

Towards elucidating the role of polysialic acid (PSA) in developing olfactory neuron of the rat, we injected neuraminidase (endo-N) into the olfactory nerve pathway under whole embryo culture, then employed immunohistochemistry to (i) detect expression of highly sialylated neural cell adhesion molecules (NCAM-H) and (ii) identify olfactory neurons via anti-microtubule-associated protein 1B (MAP1B) antibody. Olfactory axonal outgrowth from basal lamina occurred at the 31-somite stage and reached the olfactory bulb primordium at the 42-somite stage, being coincident with the timing and expression of NCAM-H immunoreactivity. Enzymatic removal of PSA by endo-N remarkably affected developmental processes of axonal outgrowth, extension, and pathfinding, i.e. individual axons appeared to have become stuck in the mesenchyme. Results indicate that PSA is critically involved with anti-adhesion cues associated with individual axonal growth during olfactory system development.

Animals↗

PubMed1999

The tyrosine phosphatase SHP-1 is a negative regulator of osteoclastogenesis and osteoclast resorbing activity: increased resorption and osteopenia in me(v)/me(v) mutant mice.

Naturally occuring inactivating mutations of the Src homology 2 (SH2) domain-containing tyrosine phosphatase 1 (SHP-1) in mice give rise to the motheaten (me) phenotype. me/me mice have multiple hematopoietic abnormalities, suggesting that this phosphatase plays an important role in hematopoiesis. SHP-1 binds to and is activated by several hematopoietic surface receptors, including the colony-stimulating factor type 1 receptor. We have examined the role of SHP-1 in osteoclastogenesis and osteoclast function using mice with the viable motheaten (me(v)/me(v)) mutation, which has markedly decreased SHP-1 activity. Histomorphometric analysis of 6-week-old me(v)/me(v) mice and control littermates showed a marked osteopenia with an increase in bone resorption indices. The number of formed osteoclast-like cells (OCLs) in cocultures of me(v)/me(v) hematopoietic cells with normal osteoblasts was significantly increased. In contrast, the number of OCLs formed in the coculture of normal bone marrow cells with the me(v)/me(v) osteoblasts was not significantly different from controls. The bone-resorbing activity of me(v)me(v) OCLs and authentic osteoclasts was also found to be increased. Finally, Western blotting of proteins from me(v)/me(v) and control OCLs revealed an overall increase in tyrosine phosphorylation in the me(v)/me(v) lysates. These in vivo and in vitro results suggest that SHP-1 is a negative regulator of bone resorption, affecting both the formation and the function of osteoclasts.

Animals↗

PubMed1999

Trabecular bone turnover, bone marrow cell development, and gene expression of bone matrix proteins after low calcium feeding in rats.

Low-calcium-fed animals have been accepted as one of the experimental models showing a reduction in bone mass. However, the effects of short-term low-calcium feeding on bone turnover, the development of osteoprogenitor cells, and gene expression of bone matrix proteins have not been reported. In this study, we examined the effect of a low-calcium diet on rat tibia and analyzed the changes in the bone by histomorphometry, bone marrow cell culture, and in situ and Northern hybridization of the bone matrix proteins. Rats were fed either a low-calcium diet (0.05% Ca) or a normal calcium diet (0.5% Ca) using the pair feeding technique. They were killed at day 0, 12 h, and days 1, 2, and 3. In the low-calcium group, the serum parathyroid hormone (PTH) level was temporarily increased in 12 h after feeding the low-calcium diet. Bone mineral density in the trabecular bone was significantly decreased from 1 day after the low-calcium feeding, but cortical bone did not show any changes during the experimental period. The bone volume per tissue volume in the proximal tibia also decreased from day 1 in the low-calcium group. The number of osteoclasts and osteoblasts on the trabecular bone surface was increased in the low-calcium group compared with the normal-calcium group. An ex vivo study showed that the number of progenitors of osteoclasts and osteoblasts in bone marrow was also increased in the low-calcium group of rats. The localization of type I collagen mRNA was observed in osteoblasts in the low-calcium group. The Northern hybridization study showed that the gene expression of type I collagen, osteopontin, and osteocalcin was increased at day 3 in the low-calcium group. These results indicated that the trabecular bone surface quickly responded to the low-calcium feeding and that bone remodeling activity was activated probably by PTH. The changes in bone marrow cell populations and the gene expression of bone matrix proteins are closely associated with increased bone turnover induced by the low-calcium diet, resulting in rapid bone loss of the trabecular bone.

Animals↗

PubMed1999

Relationship between blood pressure and heart-rate variability during graded head-up tilt.

To investigate the relationship between change in blood pressure and autonomic nerve activity, two types of head-up tilt experiments were performed. One was a 30 degrees, 45 degrees, 60 degrees, and 90 degrees graded tilt-up, in which tilt angles were changed at 6-min intervals and 5 min were spent at each angle. The other was a 10-min lasting head-up tilt at 60 degrees. Electrocardiogram (ECG) and blood pressure (Finapres) of 18 healthy non-smoking subjects (9 men, 9 women) were recorded during the experiments. Heart-rate variability was examined by general spectral analysis (GSA). The high-frequency/total-area ratio (HF/TO) showed a decrease as the tilt angle increased. Compared with the values at the 0 degrees position, these changes were statistically significant (P < 0.05). The low-frequency/HF ratio (LF/HF) showed a significant (P < 0.05) difference between 0 degrees and 90 degrees, and between 30 degrees and 90 degrees. Some of the subjects could not maintain their blood pressure during either of the head-up tilt experiments, and they showed only a slight change in HF/TO and LF/HF. This result confirmed that immediate responses to head-up tilt reflect autonomic nerve activity. Hence, changes in the frequency components were found to be an index of autonomic nerve activity, and they explained the individual differences observed in the ability to control blood pressure during a transition to upright posture.

Adolescent↗

PubMed1999

Relationship between skin blood flow and sweating rate in prepubertal boys and young men.

We sought the mechanisms in the maturation-related change of skin blood flow to heat stress. Eight prepubertal boys (7-11 years) and 11 young men (21-25 years) were exposed to a mild passive heating [by placing the lower legs and feet in a 42 degrees C water bath for 60 min while sitting in a neutral air condition (25 degrees C, 45% relative humidity)]. No age-related differences were observed for the increase in rectal temperature [0.61 +/- 0.05 (SEM) vs. 0.62 +/- 0.09 degrees C in the boys and men at the end of the passive heating, respectively], mean skin temperature (34.51 +/- 0.28 vs. 34.81 +/- 0.27 degrees C) or metabolic heat production (68 +/- 4 vs. 60 +/- 3 W m-2) during the passive heating. During the heating age-related differences in skin blood flow by laser Doppler flowmetry (LDF) and local sweating rate (m(sw)) varied by site; the boys had greater LDF on the chest and back, similar LDF on the forearm and thigh, lower m(sw) on the chest and thigh, similar (m)sw on the back, and greater m(sw) on the forearm, compared with the men. The relationship between LDF and m(sw) during the heat exposure was divided into three temporal phases: (a) an increase of LDF without an increase in m(sw), (b) an increase of m(sw)without the secondary increase of LDF, (c) a proportional increase of LDF and m(sw) increase of LDF in phase (a) and the slopes of the regression lines between the LDF and m(sw) in phase (c) were significantly greater on the chest and back for the boys (P < 0.05), compared with the men, but not on the forearm and thigh. These results suggest that the greater LDF observed on the trunk in the boys may be owing to a greater withdrawal of vasoconstrictor tone and a greater active vasodilation. Regional differences may exist in the maturation-related alterations in vasoconstriction and vasodilation.

Adult↗

PubMed1999

Functional interleukin-5 activity in peripheral blood mononuclear cells from adolescents with mite antigen asthma in remission.

BACKGROUND: Asthma improves in most children during adolescence such that a small minority of patients exhibit clinically significant symptoms by the age of 20 years. OBJECTIVE AND METHODS: To investigate late allergic reactions, including eosinophil inflammation, associated with outgrowing mite antigen-induced bronchial asthma during adolescence, the relationship between clinical status and functional activity of interleukin (IL)-5 produced by Dermatophagoides farinae (Df)-stimulated peripheral mononuclear cells (PBMCs) in culture was assessed in mouse IL-3-dependent cells transfected with the human IL-5 receptor gene. RESULTS: Activity of IL-5 spontaneously produced by PBMCs from either patients with mite-sensitive bronchial asthma or nonatopic control subjects was low. The activity of IL-5 produced by PBMCs stimulated with concanavalin A was significantly higher. Upon challenge with specific allergens, such as Df antigen, but not with irrelevant antigens, including ovalbumin, the in vitro activity was increased in patients with active disease and decreased in patients in remission. CONCLUSION: Results suggest that the antigen-specific up-regulation of functional IL-5 activity in late allergic reactions is reduced in patients in remission and likely to result in an improvement in clinical status. The Df antigen may suppress Df-induced responses in patients with asthma in remission.

Adolescent↗

PubMed1999

Management of acute metabolic decompensation in maple syrup urine disease: a multi-center study.

BACKGROUND: Therapeutic modalities in acute metabolic decompensation in maple syrup urine disease (MSUD) are variable, and outcomes of each therapeutic measure have been known only individually. Factors that affect neurological outcome are not clear. METHODS: A questionnaire was sent throughout Japan to each pediatrician treating any of the 42 MSUD patients. RESULTS: Necessary information was available for 13 patients through the questionnaire, and through a publication for one patient. In nine of the 14 patients episodes of metabolic decompensation developed in the neonatal period. In the other five, the onset of disease was delayed until infancy or later. In the nine patients with neonatal onset, a pretreatment level of plasma leucine greater than 40 mg/100 mL or a duration of altered level of alertness longer than 10 days was associated with a poor neurological outcome. The therapeutic measures employed included intravenous infusion of glucose and electrolyte solution or hypertonic glucose and electrolyte solution, exchange transfusion, peritoneal dialysis, a large dose of thiamine and intravenous hyperalimentation. All patients had survived the episodes and were alive at the time of the survey. Five of the nine patients with neonatal onset have developed neurological sequelae to varying degrees. Episodes of metabolic decompensation in infancy or thereafter did not affect, or only minimally affected, the neurological outcome. CONCLUSION: Therapeutic goals to improve neurological outcome are to shorten the duration of the altered level of consciousness, and to minimize the peak plasma leucine level as much as possible.

Acute Disease↗

PubMed1999

Increased glomerular cytosolic phospholipase A2 activity of OLETF rats with early diabetes.

In view of the potential role of prostaglandins (PGs) in development of glomerular hyperfiltration leading to diabetic nephropathy, we studied the temporal relationship of the activity of cytosolic phospholipase A2 (cPLA2), a rate-limiting enzyme for eicosanoid biosynthesis, with hyperfiltration and the histological changes in glomeruli using OLETF rats, a model for non-insulin-dependent diabetes mellitus (NIDDM). Diabetes mellitus and associated histopathological changes, which developed spontaneously by 30-46 weeks after birth of OLETF rats, were accompanied by approximately 65% increase in glomerular cPLA2 activity that showed significant correlations with elevated plasma glucose levels and creatinine clearance. Moreover, mesangial cells cultured for 5 days with high glucose exhibited approximately 2-fold higher cPLA2 activity than those cultured with physiologic level of glucose. These data suggest that increased glomerular cPLA2 activity leads to production of PGs, which may promote the progression of early diabetic glomerular hyperfiltration and subsequent diabetic nephropathy.

Aging↗

PubMed1999

Relationship between severity of middle ear mucosal lesion and middle ear pneumatic space volume in patients with otitis media with effusion.

If we assume that the state of suppression of pneumatic cells is the result of suppression of pneumatic cell growth by inflammatory stimulation in the middle ear pneumatic space, it is possible to improve the state of suppression by performing sufficient treatment during the growth period of the pneumatic cells. We indwelt a tympanic membrane ventilation tube (hereinafter referred to as tube) for treatment of otitis media with effusion (OME) in child patients aged 3-13 years and investigated the following points: i) relationship between the severity of inflammation of the lamina propria of middle ear mucosal specimens (hereinafter referred to as lamina propria) collected at the time of tube indwelling and the degree of growth of the pneumatic space; and ii) changes in the pneumatic space associated with treatment by tube indwelling, which was studied by comparing the above-described mucosal severity with the pneumatic space area of 2 years after tube indwelling, and with increase in the pneumatic space volume measured periodically after tube indwelling. The results indicated that mastoid cell growth suppression is higher in patients with a higher degree of inflammatory changes in the lamina propria. In association with treatment by tube indwelling, effusion accumulated in the pneumatic space and mucosal swelling disappeared early after the treatment, or 2 months of tube indwelling. After that, in patients with severe mucosal lesion, a long time, 1.5-2 years, was found to be required for repneumatization accompanying regrowth of the temporal bone. We confirmed that the severity of inflammation of the lamina propria is deeply involved in the growth and repneumatization of the pneumatic cells.

Adolescent↗

PubMed1999

Expression and activity of chimeric molecules between human UDP-galactose transporter and CMP-sialic acid transporter.

Human UDP-galactose transporter (hUGT1) and CMP-sialic acid transporter (hCST) are related Golgi proteins with eight putative transmembrane helices predicted by computer analysis. We constructed chimeric molecules in which segments of various lengths from the C- or N-terminus of hUGT1 were replaced by corresponding portions of hCST. The chimeras were transiently expressed in UGT-deficient mutant Lec8 cells, and their UGT activity was assessed by the binding of GS-II lectin to the transfected cells. The replacement of either the N- or C-terminal cytoplasmic segment by that of hCST did not affect the expression or activity of hUGT1. A chimera in which the eighth helix and the C-terminal tail were replaced also retained the UGT activity, indicating that this helix is not involved in the determination of substrate specificity. In contrast, three types of chimeras, in which the first helix, the first and the second helices, and a segment from the seventh helix to the C-terminus were replaced, respectively, were expressed very infrequently in the transfected cells, and had no UGT activity. They are likely folded incorrectly and degraded by a quality-control system, since the amounts of their mRNAs were normal and the proteins were mainly localized in the ER. The first and the seventh helices are important for the stability of the transporter protein.

Animals↗

PubMed1999

Indispensability of transmembrane domains of Golgi UDP-galactose transporter as revealed by analysis of genetic defects in UDP-galactose transporter-deficient murine had-1 mutant cell lines and construction of deletion mutants.

UDP-galactose transporter is a membrane protein localized in the Golgi apparatus. It translocates UDP-galactose from the cytosol into the Golgi lumen, thus providing galactosyltransferases with their substrate. We characterized murine UDP-galactose transporter through molecular cloning for the following purposes: (i) to elucidate the molecular bases underlying the genetic defects of murine Had-1 mutants, which are deficient in UDP-galactose transporting activity, and (ii) to obtain information that would help us in planning rational approaches to identify functionally essential regions, based on comparison of primary structures between human and murine UDP-galactose transporters. We identified five nonsense mutations, one missense Gly178Asp mutation, and two aberrant splicing mutations. Although glycine178 is highly conserved among nucleotide-sugar transporters, a Gly178Ala variant was functional. The species-differences between human and murine UDP-galactose transporters were largely confined to the N- and C-terminal regions of the transporters. Substantial deletions in the N- and C-terminal regions did not lead to loss of UDP-galactose transporting activity, indicating that these cytosolic regions are dispensable for the transporting activity. The transporter was fused with green-fluorescent protein at the C-terminal cytosolic tail without impairing the functions of either protein. Our results demonstrate the importance of the transmembrane core region of the UDP-galactose transporter protein.

Amino Acid Sequence↗

PubMed1999

Prevalence of autoantibodies in patients with recurrent miscarriages.

PROBLEM: It is well known that the prevalence of several autoantibodies is higher in patients with recurrent miscarriages than in normal women. However, links between individual autoantibodies are unclear. The present study focuses on the possible association between beta 2-glycoprotein I (beta 2-GPI)-dependent anticardiolipin antibody (aCL), lupus anticoagulant (LA), and antinuclear antibody (ANA) in patients with recurrent miscarriages. METHOD OF STUDY: Three hundred and one patients, with a history of two or more unexplained miscarriages, were studied. The titers of beta 2-GPI-dependent aCL and LA were then compared between single-antibody-positive and three-antibody-positive groups. RESULTS: The prevalences of beta 2-GPI-dependent aCL, LA, and ANA were 3.3, 10.0, and 25.2%, respectively. Four of the 301 patients had all three antibodies. The LA titers in patients with positive values for three antibodies was significantly higher than in cases with only LA. CONCLUSION: beta 2-GPI-dependent aCL, LA, and ANA define three distinct, but partly related populations in patients with recurrent miscarriage. We should test at least two kinds of autoantibodies in recurrent aborters, because it has been found that, e.g., beta 2-GPI-dependent aCL and LA are predictors for miscarriages.

Abortion, Habitual↗

PubMed1999

Adenovirus strains of subgenus D associated with nosocomial infection as new etiological agents of epidemic keratoconjunctivitis in Japan.

Adenovirus strains of a new type were isolated from patients with epidemic keratoconjunctivitis. They were not completely neutralized by any antiserum against adenovirus prototypes. PCR followed by restriction endonuclease analysis demonstrated that they were type 8. PCR followed by sequencing revealed a high homology rate between them and type 9.

Adenoviridae↗

PubMed1999

Serotyping of adenoviruses on conjunctival scrapings by PCR and sequence analysis.

To detect and identify adenovirus (Ad), we investigated hypervariable regions (HVRs) of Ad by using a combination of PCR and direct sequencing (PCR-sequence) method. Primers for nested PCR to amplify the conserved region in the hexon protein containing HVRs were designed based on hexon gene sequences derived from GenBank. These two primer sets amplified a DNA fragment of 7 HVRs from 16 prototypes of Ad, which were divided into five subgenera, including seven serotypes that are the predominant causative agents of acute conjunctivitis in Japan, and from 31 recent conjunctival scraping specimens from patients with adenoviral conjunctivitis. HVR DNA sequences were determined by means of universal sequence primers. Analysis of the predicted amino acid homology of HVRs among Ad prototypes suggested three regions, HVR4, -5, and -7, to be candidates for the neutralization epitopes. The clinical serotype of specimens was determined by the PCR-sequence method with reference to these three HVRs. The serotype determined according to this method was identical to that obtained by culture isolation and the neutralization test (NT) in all scraping samples, whereas the results of this method did not match PCR and restriction fragment length polymorphism (PCR-RFLP) analysis in five samples. It took only three days to detect Ad and to identify the serotype, in contrast to culture isolation-NT, which took at least 2 weeks. These findings indicate that our newly developed PCR-sequence method is applicable for the detection and serotyping of human Ads.

Adenovirus Infections, Human↗

PubMed1999

Simulation model of an eyeball based on finite element analysis on a supercomputer.

BACKGROUND/AIMS: A simulation model of the human eye was developed. It was applied to the determination of the physical and mechanical conditions of impacting foreign bodies causing intraocular foreign body (IOFB) injuries. METHODS: Modules of the Hypermesh (Altair Engineering, Tokyo, Japan) were used for solid modelling, geometric construction, and finite element mesh creation based on information obtained from cadaver eyes. The simulations were solved by a supercomputer using the finite element analysis (FEA) program PAM-CRASH (Nihon ESI, Tokyo, Japan). It was assumed that rupture occurs at a strain of 18.0% in the cornea and 6.8% in the sclera and at a stress of 9.4 MPa for both cornea and sclera. Blunt-shaped missiles were shot and set to impact on the surface of the cornea or sclera at velocities of 30 and 60 m/s, respectively. RESULTS: According to the simulation, the sizes of missile above which corneal rupture occurred at velocities of 30 and 60 m/s were 1.95 and 0.82 mm. The missile sizes causing scleral rupture were 0.95 and 0.75 mm at velocities of 30 and 60 m/s. CONCLUSIONS: These results suggest that this FEA model has potential usefulness as a simulation tool for ocular injury and it may provide useful information for developing protective measures against industrial and traffic ocular injuries.

Aged↗

PubMed1999

Mast cell chymase in pulmonary hypertension.

Mast cells are known to be involved in various types of tissue remodelling but their role in pulmonary hypertension is still poorly understood. Two subtypes of mast cells have recently been identified by demonstrating one protease, chymase. This enzyme might be implicated in vascular remodelling. The changes in mast cells in lung tissue from three patients with primary or secondary pulmonary hypertension were therefore investigated. Compared with tissue from four control subjects the number of mast cells in the three patients was markedly increased, which suggests that chymase containing mast cells are involved in tissue remodelling accompanied by fibrotic changes in primary and secondary pulmonary hypertension.

Adult↗