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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 415 records · Page 23Linked to original sources

Conditions for balance between lower normal pressure control and hypotony in mitomycin trabeculectomy.

BACKGROUND: Striving for low to ultra-low postoperative intraocular pressure (IOP) through filtering surgery usually increases the incidence of prolonged hypotony. Early postoperative prognostic indicators for IOP control to lower normal level and prolonged hypotony in trabeculectomy with mitomycin C were examined to determine conditions required to obtain an optimum balance between them. METHODS: Records of initial trabeculectomy with mitomycin C (0.4 mg/ml, 3 min) in 59 consecutively operated Japanese patients with primary open-angle glaucoma who had used multiple medications before operation were retrospectively analyzed. IOP control to lower normal level was defined as having failed if IOP could not be maintained below 15 mm Hg without medication. Prolonged hypotony was defined as postoperative IOP below 5 mm Hg for more than 2 months, excluding the first month. The Cox proportional hazards model was applied to identify early postoperative factors contributing to the two surgical outcomes. RESULTS: Among the factors studied, only the mean IOP on postoperative days 9-14 was significantly correlated with the surgical outcome. A receiver operating characteristic plot suggested that mean IOP of 8 mm Hg in this period would give an optimum balance between the two. CONCLUSION: IOP of 8 mm Hg 9-14 days after surgery may be advisable in patients with preoperative multiple medications in whom IOP control to lower normal level is attempted with mitomycin C trabeculectomy. Knowledge of this may be helpful in deciding when laser lysis of sutures is indicated.

Female↗

Extracellular matrix of opacified anterior capsule after endocapsular cataract surgery.

BACKGROUND: We determined the types and distribution of glycosaminoglycans (GAGs) and collagens, in anterior capsular opacification after endocapsular phacoemulsification and aspiration (ECPEA) and intraocular lens implantation. METHODS: Opacified anterior capsules were removed from human eyes after ECPEA. Immunohistochemical staining was performed to determine GAGs with monoclonal antibodies to chondroitin, chondroitin-4-sulfate (C4S), chondroitin-6-sulfate (C6S), dermatan sulfate (DS), and keratan sulfate (KS); collagens with monoclonal antibodies to types I, II, and III collagens; and cellular characteristics with monoclonal antibodies to vimentin, desmin, alpha-smooth muscle actin, and cytokeratin. Decorin mRNA and type I collagen mRNA were detected by in situ hybridization. RESULTS: In the capsules, the C6S, DS, KS, and types I and III collagens were similar to the chemical components found at the adhesion site of the anterior and posterior capsules after extracapsular cataract extraction, and cellular components contained vimentin, desmin, alpha-smooth muscle actin, cytokeratin, decorin mRNA, and type I collagen mRNA. CONCLUSIONS: The GAGs and collagens in opacified anterior capsule after ECPEA were similar to those found during wound healing, although KS is present in normal anterior segment tissue during development and only in the cornea postnatally. These chemical components may be produced by myofibroblast-like cells presumably transformed from lens epithelial cells.

Aged↗

Nonsense mutation in exon 4 of human complement C9 gene is the major cause of Japanese complement C9 deficiency.

Deficiency of the ninth component of human complement (C9) is the most common complement deficiency in Japan but is rare in other countries. We studied the molecular basis of C9 deficiency in four Japanese C9-deficient patients who had suffered from meningococcal meningitis. Direct sequencing of amplified C9 cDNA and DNA revealed a nonsense substitution (CGA-->TGA) at codon 95 in exon 4 in the four C9-deficient individuals. An allele-specific polymerase chain reaction system designed to detect exclusively only one of the normal and mutant alleles indicated that all the four patients were homozygous for the mutation in exon 4 and that the parents of patient 2 were heterozygous. The common mutation at codon 95 in exon 4 might be responsible for most Japanese C9 deficiency.

Adolescent↗

Genomic structure of the human glucose 6-phosphate translocase gene and novel mutations in the gene of a Japanese patient with glycogen storage disease type Ib.

Glycogen storage disease (GSD) type Ib is an autosomal recessive disorder caused by a deficiency in microsomal glucose 6-phosphate (G6P) translocase. A gene mutated in GSD type Ib patients has recently been isolated. We have determined the entire sequence of the human G6P translocase gene by PCR-directed sequencing. The gene spans approximately 5 kb of genomic DNA and contains eight exons. Analysis of DNA from a Japanese patient with GSD type Ib revealed new compound heterozygous mutations; a T to C transition at cDNA position 521 resulting in W118R, and an A to C transversion at the -2 splicing acceptor site of intron 1. Reverse transcription (RT)-PCR from leukocyte RNA of the patient revealed the abnormally spliced transcript. These results further support the suggestion that the gene is causative for GSD Ib and should be useful in the molecular diagnosis of such patients.

Antiporters↗

Efficacy and safety of fluorescein angiography with orally administered sodium fluorescein.

PURPOSE: To report the efficacy and safety of fluorescein angiography after oral administration of fluorescein solution in a large number of patients during a period of 8 years. METHODS: A total of 1,787 patients (2,625 eyes) underwent fluorescein angiography after oral administration of sodium fluorescein at Hara Eye Hospital, Utsunomiya, Japan, between January 1989 and March 1997. The ingestible solution was 10 ml of 10% sodium fluorescein, the same material generally used for injection in conventional fluorescein angiography. Retinal photography began 15 minutes after ingestion and continued for 1 hour. The camera and the photography and film processing techniques were the same as those used for conventional fluorescein angiography using injected sodium fluorescein. RESULTS: In 2,554 (97.3%) of 2,625 eyes, photographs adequate for clinical use were obtained. In 1,787 patients, no anaphylactic or other severe adverse effects were observed, and only 31 patients (1.7%) experienced minimal itching, discomfort, or nausea after oral sodium fluorescein intake. For conditions such as central serous chorioretinopathy, retinal vein occlusion, diabetic retinopathy, and cystoid macular edema, sufficient information for clinical use was obtained. CONCLUSIONS: Fluorescein angiography using orally administered sodium fluorescein is generally effective and safe in standard clinical practice.

Administration, Oral↗

Mass screening for neuroblastoma at 6 months of age: difficult to justify.

BACKGROUND/PURPOSE: A statistical analysis of the mass screening for neuroblastoma in Japan based on a population study rarely has been reported. This study aims to evaluate retrospectively the effectiveness of mass screening at 6 months of age using the available population data. METHODS: The data on the neuroblastoma cases registered by the Committee for Pediatric Solid Malignant Tumors in the Kyushu area were analyzed based on both screened and unscreened populations in the Kyushu area. RESULTS: From 1988 to 1992, the cumulative incidence of neuroblastoma in children less than 5 years of age was 82 in 484,599 for screened children, and 11 in 92,966 for unscreened children, respectively. Fourteen of the 82 screened patients had negative findings at 6 months of age (MS-negative cases). No significant difference was observed in the cumulative mortality rates from neuroblastoma in children younger than 5 years of age between the screened children and the unscreened children. Six of seven patients who died among the screened children were MS-negative cases with stage III or IV disease. In addition, no significant difference was found in the cumulative mortality rates from the neuroblastoma cases in patients less than 5 years of age between the children screened from 1988 to 1992 (7 of 484,599) and all children from 1980 to 1984 (14 of 668,084). CONCLUSIONS: These findings suggests that the majority of the patients detected by mass screening had a favorable prognosis, and, mass screening in Japan for children less than 6 months of age was not observed to reduce the incidence and mortality from neuroblastoma. Therefore, mass screening at 6 months of age was not found to improve substantially the prognosis of patients with unfavorable neuroblastoma identified over 1 year of age, which is the primary purpose of such mass screening for neuroblastoma.

Evaluation Studies as Topic↗

The actions of a novel lipoprotein lipase activator, NO-1886, in hypertriglyceridemic fructose-fed rats.

High circulating fasting and prandial triglyceride levels are associated with both insulin resistance and the development of cardiovascular disease. The aim of this investigation was to study the effects of NO-1886, a novel lipoprotein lipase (LPL) activator, on triglyceride levels, fat oxidation, and glucose tolerance in fructose-fed rats, a hypertriglyceridemic model of insulin resistance. Adult male Wistar rats were fed for 4 weeks with a high-starch diet or a high-fructose diet without and with NO-1886 (50 mg x kg[-1] x d[-1] orally). Fructose feeding increased plasma triglyceride levels, an effect that was ameliorated by NO-1886 treatment (week 1/week 4: starch-fed, 2.4 +/- 0.1/2.8 +/- 0.2 mmol/L; fructose-fed, 3.6 +/- 0.5/5.5 +/- 0.5; fructose + NO-1886, 2.7 +/- 0.2/3.6 +/- 0.3). The mean 24-hour respiratory quotient (RQ) was significantly lower in the fructose + NO-1886 group compared with fructose-fed rats, indicating increased oxidation of fat. Fructose feeding elevated liver triglyceride levels by 74% (P < .01), an effect not altered by NO-1886. Red and white quadriceps hindlimb muscle triglyceride levels were not different between groups. Glucose tolerance (intravenous test in long-term cannulated rats) was mildly deteriorated and fasting insulin and glucose levels were elevated in fructose-fed rats, effects which were ameliorated by NO-1886. In conclusion, in the fructose-fed rat model of hypertriglyceridemia and insulin resistance, addition of a LPL activator reduced circulating triglyceride levels without causing increased muscle triglyceride accumulation or deterioration in glucose tolerance. LPL activators may prove to be a fruitful avenue to explore in the search for new therapeutic agents in the treatment of dyslipidemias and insulin resistance.

Animals↗

Effect of controlled hypotension combined with hemodilution on gastric intramural pH.

STUDY OBJECTIVE: To evaluate the effect of controlled hypotension combined with hemodilution on gastric intramural pH in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Nagasaki Rosai Hospital. PATIENTS: 30 ASA physical status I and II patients scheduled for total hip arthroplasty. INTERVENTIONS: Patients were randomly divided into two groups. Group A (n = 15) received controlled hypotension with mild hemodilution. Group B (n = 15) received controlled hypotension with moderate hemodilution. Hemodilution was carried out after induction of anesthesia. Drawn blood was replaced with 6% hydroxyethyl starch solution. Final hematocrit values were 32 +/- 2% (mean +/- SD) in Group A and 23 +/- 2% in Group B. Controlled hypotension was induced with prostaglandin E1 (PGE1) to maintain mean arterial blood pressure at 55 mmHg for 80 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements included gastric intramural pH (pHi), arterial blood pH (pHa), and plasma lactate. These indices were measured before hemodilution, after hemodilution, 80 minutes after starting hypotension, 60 minutes after recovery from hypotension, and on the first postoperative day. The value of pHi was measured by tonometry. The pHa and lactate values showed no change in either Group A or Group B throughout the time course. Gastric pHi values showed no change in Group A throughout the time course. The pHi value in Group B showed a significant decrease from 7.420 +/- 0.028 to 7.339 +/- 0.034 (p < 0.05) after hemodilution, while it showed no further decrease at 80 minutes after starting hypotension (7.331 +/- 0.039) and 60 minutes after recovery from hypotension (7.330 +/- 0.048). CONCLUSION: The results suggest that moderate hemodilution, such as 23% of hematocrit value, might impair oxygenation in gastrointestinal mucosa, whereas controlled hypotension induced by PGE1 combined with the hemodilution would not increase this impairment.

Aged↗

Renal function in patients during and after hypotensive anesthesia with sevoflurane.

STUDY OBJECTIVES: To evaluate renal function during and after hypotensive anesthesia with sevoflurane compared with isoflurane in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Rosai Hospital. PATIENTS: 26 ASA physical status I and II patients scheduled for orthopedic surgery. INTERVENTIONS: Patients received isoflurane, nitrous oxide (N2O), and fentanyl (Group I = isoflurane group; n = 13) or sevoflurane, N2O, and fentanyl (Group S = sevoflurane group; n = 13). Controlled hypotension was induced with either isoflurane or sevoflurane to maintain mean arterial pressure at 60 mmHg for 120 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements included serum inorganic fluoride (previously speculated to influence renal function), creatinine clearance (CCr; to assess renal glomerular function), urinary N-acetyl-beta-D-glucosaminidase (NAG; to assess renal tubular function), blood urea nitrogen (BUN), and serum creatinine (as clinical renal function indices). Serum fluoride, CCr, and NAG were measured before hypotension, 60 minutes, and 120 minutes after the start of hypotension, 30 minutes after recovery of normotension, and on the first postoperative day. BUN and serum creatinine were measured preoperatively and on the third and seventh postoperative days. Minimum alveolar concentration times hour was 3.6 +/- 1.8 in Group I and 4.0 +/- 0.7 in Group S. In both groups, BUN and serum creatinine did not change, and CCr significantly decreased after the start of hypotension. In Group I, serum fluoride and NAG did not change. In Group S, serum fluoride significantly increased after the start of hypotension compared with prehypotension values and compared with Group I values. In addition, NAG significantly increased at 120 minutes after the start of hypotension and at 30 minutes after recovery of normotension, but returned to prehypotension values on the first postoperative day. CONCLUSIONS: Two hours of hypotensive anesthesia with sevoflurane under 5 L/min total gas flow in patients having no preoperative renal dysfunction transiently increased NAG, which is consistent with a temporary, reversible disturbance of renal tubular function.

Adult↗

In vitro expansion of murine multipotential hematopoietic progenitors from the embryonic aorta-gonad-mesonephros region.

The origin of hematopoietic stem cells (HSCs) and their growth factor requirement are poorly understood. Here we describe a new in vitro culture system of the aorta-gonad-mesonephros (AGM) region, where long-term repopulating HSCs first arise. We demonstrate that oncostatin M (OSM) is expressed in the AGM and is absolutely required for the expansion of multipotential hematopoietic progenitors in vitro. In addition, OSM enhances the formation of endothelial cell clusters. Thus, OSM appears to be a key cytokine for the development of multipotential hematopoietic progenitors in the AGM, possibly acting on common precursor cells between HSCs and endothelial cells. By using the AGM culture derived from macrophage colony-stimulating factor (M-CSF)-deficient op/op mutant embryos, we also show a pivotal role for M-CSF in fetal myelopoiesis.

Animals↗

A novel second isoenzyme of the human UDP-N-acetylglucosamine:alpha1,3-D-mannoside beta1,4-N-acetylglucosaminyltransferase family: cDNA cloning, expression, and chromosomal assignment.

We isolated a novel cDNA encoding a second isoenzyme of UDP-N-acetylglucosamine:alpha1,3-D-mannoside beta1,4-N-acetylglucosaminyltransferase (GnT-IV; EC 2.4.1.145). The nucleotide and deduced amino acid sequences of the cDNA were homologous to those of the previously cloned human GnT-IV cDNA (63% and 62% identity, respectively). The new cDNA is also confirmed to express GnT-IV activity, suggesting that two isoenzymes of human GnT-IV exist. Although genomic Southern analysis suggested that both genes exist in many mammalian species and the chicken, northern analysis revealed that both genes are expressed in different ways in human tissues. This is the first report concerning the gene family of an N-acetylglucosaminyltransferase in mammals.

Amino Acid Sequence↗

High frequency of fusion transcripts of exon 11 and exon 4/5 in AF-4 gene is observed in cord blood, as well as leukemic cells from infant leukemia patients with t(4;11)(q21;q23).

The MLL gene located on chromosome 11q23 and its translocation to the AF-4 gene located on chromosome 4q21 play a pivotal role in leukemogenesis in infancy. Studies of identical leukemic twins have provided evidence of the MLL rearrangement as a fetal event during pregnancy. We analyzed the presence and frequency of the MLL/AF-4 rearrangement in normal cord blood. Although no chimeric mRNA of MLL or AF-4 was detected in 65 cord blood samples, in-frame fusion transcripts of exon 11 and exon 4 or 5 of the AF-4 gene were detected in three of the samples by a nested polymerase chain reaction. When primers of exon 11 and exon 5 of the AF-4 gene were used, two forms of fusion transcripts (AF-4 exon 11/4 or exon 11/5) were detected in 20 of the 65 cord blood samples (31%) and also four of six leukemic cell samples with t(4;11) (67%), whereas such transcripts were not observed in any of 21 peripheral blood samples nor in fetal fibroblasts. These findings suggest that the in-frame fusion of exon 11 and exon 4 or 5 of the AF-4 gene frequently occurs in hematopoietic cells during the intrauterine period, even in a healthy fetus. Although it is unknown whether the proteins of the AF-4 fusion transcripts have some functions, the instability of the AF-4 gene may be associated with the leukemogenesis of infant leukemia.

Chromosomes, Human, Pair 11↗

Post-translational modification and intracellular localization of a splice product of CD46 cloned from human testis: role of the intracellular domains in O-glycosylation.

We obtained a unique CD46 cDNA, STc/CY4, from the human testis, the predicted amino acid sequence of which suggested the presence of a novel isoform of CD46. This message was present predominantly in the testis, and the predicted isoform possessed a short (11 amino acids) transmembrane section (TM) and an unidentified cytoplasmic tail (CY). When expressed in Chinese hamster ovary (CHO) cells, this CD46 isoform underwent no O-glycosylation and was mostly retained in the endoplasmic reticulum. This unusual behaviour of the new isoform was due in part to the short TM and the unusual sequences of the CY. The molecular mass of this isoform was 42,000, approximately 20,000 smaller than conventional CD46. These properties of the STc/CY4 isoform were similar to those of sperm CD46. The only difference between sperm CD46 and the STc/CY4 isoform expressed on CHO cells was that only the latter possessed N-linked sugars of high mannose types. Since the STc/CY4 isoform may behave like sperm CD46 in cellular localization and post-translational modification, studies of sperm-egg interassociation were performed using hamster eggs and CHO cell clones expressing various isoforms including the STc/CY4. Rosette formation was seen most effectively between hamster eggs and STc/CY4-expressing CHO cells. These results infer that O-glycosylation perturbs CD46-mediated sperm-binding to eggs and thus sperm CD46 lacking O-linked sugars can serve as an adhesion molecule. The possible role of CD46 in fertilization and the structural differences between sperm and conventional CD46 are discussed.

Alternative Splicing↗

The effect of diabetes mellitus on histopathological changes in the tissues under denture base and without mechanical pressure.

Histopathological changes in the tissues under a denture base were studied with respect to the difference between diabetic and normal rats. Diabetes mellitus was induced in Wistar rats by streptozotocin. The experimental denture base was designed to make contact with the palatal mucosa without any continuous nor masticatory pressure. Histopathological observation periods were 1, 2, 4, 8, 12 and 20 weeks after the insertion of the denture base. Histopathological examination revealed that only the transient slight proliferative reaction observed in mucosal epithelium under a denture base in normal non-diabetic rats, was lessened by induced diabetes mellitus. Moreover, covering the palatal mucosa with a denture base without any continuous nor masticatory pressure and with the maintenance of mucosal cleanliness under it and of the denture itself, did not cause any inflammatory change or bone resorption in the tissues under the base.

Acrylic Resins↗

Intestinal mast cell response and mucosal defence against Strongyloides venezuelensis in interleukin-3-hyporesponsive mice.

Recently several inbred strains of mice were found to be hyporesponsive to Interleukin (IL)-3 because of a 5-bp deletion in the intron 7 of the gene that encodes IL-3 receptor alpha subunit (IL-3R alpha). Due to this mutation, mast cells were not generated in vitro from bone marrow cells of these mice under the presence of IL-3. Intestinal mucosal mast cells, of which growth/differentiation is dependent on IL-3, are important effector cells in immune-mediated expulsion of intestinal nematodes, Stronglyoides spp. In the present study, therefore, we examined intestinal mast cell response and mucosal defence against Strongyloides venezuelensis in IL-3-hyporesponsive C58/J and A/J mice. After subcutaneous inoculation with 10,000 infective larvae, C58/J and IL-3-responsive C57BL/6 mice showed identical kinetic patterns of daily faecal egg output and intestinal mast cell response. When these mice were infected with 3000 L3 and, five weeks later, they were challenged by intraduodenal implantation of 800 S. venezuelensis adult worms, the timing of logarithmic decline of faecal egg count as well as intestinal mastocytosis was delayed for two days in C58/J mice. Kinetics of intestinal mastocytosis and faecal egg excretion after a primary and challenge infection in A/J mice, another IL-3-hyporesponsive strain, were identical with those seen in C58/J mice. These results suggest that intestinal mast cell response and mucosal defence against S. venezuelensis of the mutant mice were almost completely compensated in vivo. Possible mechanisms of induction of intestinal mast cell response in IL-3R alpha-defective mice are discussed.

Animals↗

Prevention of hypoglycaemia in a patient with type Ib glycogen storage disease by an amylase (alpha-glucosidase) inhibitor.

Patients with type Ib glycogen storage disease (GSD Ib) are susceptible to hypoglycaemic episodes. To determine whether an amylase (alpha-glucosidase) inhibitor, voglibose, can be useful in the control of hypoglycaemia, we tried it in a 14-y-old male with GSD Ib. Oral administration of voglibose prolonged the duration of normoglycaemia and reduced the incidence of hypoglycaemia attacks. These findings indicate that voglibose may be useful for preventing hypoglycaemia in GSD Ib patients.

Adolescent↗

Characteristic changes of large granular lymphocytes that strongly express CD56 in endometrium during the menstrual cycle and early pregnancy.

Large granular lymphocytes that strongly express CD56 (CD56++ LGL) constitute a major population of leukocytes in the secretory endometrium and pregnancy decidua and are considered to be involved in reproductive immunity and in maintaining the pregnancy. The present study aimed to reveal the relationship between the characteristic changes of CD56++ LGL and altered hormonal environment and/or trophoblast invasion in the endometrium. Cell surface markers of CD56++ LGL obtained from the endometrium during the menstrual cycle and early pregnancy were analysed using flow cytometry. The percentages of both CD56++ LGL that express activation antigens (CD69, HLA-DR) and those that express lymphocyte function associated antigen-1 (LFA-1) (CD11a/CD18) were highest in the proliferative phase and decreased gradually throughout the menstrual cycle. Expression of these antigens was further suppressed in the late secretory phase, as well as in the early stage of pregnancy. However, the percentage of CD56++ LGL that express these antigens was significantly higher in spontaneous abortions than in normal pregnancies. On the other hand, the percentage of CD56++ LGL that express CD45RA was lower during normal pregnancy than during the menstrual cycle. The present results suggest that characteristics alterations of CD56++ LGL are regulated by altered hormonal environment and by trophoblast invasion.

Abortion, Spontaneous↗

Integrin-associated protein (IAP, also termed CD47) is involved in stroma-supported erythropoiesis.

Erythropoiesis is regulated by the hematopoietic microenvironment of the spleen, fetal liver, and bone marrow in mice. We previously showed that established stromal cells from these organs selectively support erythropoiesis in vitro. To identify the cell surface molecule(s) on the stromal cells involved in erythropoiesis, we raised monoclonal antibodies (MAbs) to MSS62 stromal cells derived from newborn spleen and obtained MAb100.1, which partially inhibited the stroma-supported erythropoiesis in vitro. Using an expression cDNA library of MSS62 cells, we cloned a gene encoding the protein recognized by MAb100.1 and identified it as integrin-associated protein (IAP, also termed CD47), which may play a general role in integrin-mediated signal transduction. IAP/CD47 is expressed in the stromal cells of spleen, fetal liver, and bone marrow, and in a variety of hematopoietic cells including erythroblasts. Thus, IAP may be partly involved in the erythropoietic supporting ability of the stromal cells.

Amino Acid Sequence↗