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Biomedical subjects

T Inui

Publications and source records attributed to T Inui.

At least 109 records · Page 6Linked to original sources

Vasopressor activities of N-terminal fragments of adrenomedullin in anesthetized rat.

Adrenomedullin (AM) is a vasorelaxant peptide that was recently isolated from human pheochromocytoma. In contrast to human (h) AM, which has vasodepressor activity, a synthetic N-terminal fragment of hAM, hAM-(1-25)-NH2 showed vasopressor activity in the anesthetized rat. The N-terminal peptides hAM-1-31)-NH2, hAM-(1-25)-OH, hAM-(1-21)-NH2, acetyl-hAM-(16-21)-NH2, and acetyl-hAM-(16-36)-OH all showed vasopressor activities. The potency of hAM-(1-21)-NH2, acetyl-hAM-(16-21)-NH2 was greater than that of hAM-(1-25)-NH2. Pretreatment with phenoxybenzamine, guanethidine, or reserpine attenuated vasopressor activities of these peptides. These data suggested that vasopressor activity of N-terminal fragment of hAM is due to a stimulation of endogenous catecholamine release.

Adrenal Gland Neoplasms↗

Cerebral revascularization using omentum and serratus anterior muscle free flap transfer for adult moyamoya disease: case report.

BACKGROUND: Use of the omentum in the treatment of moyamoya disease is now widely accepted, and, especially in patients with ischemic symptoms of anterior or posterior cerebral artery distribution, omental transplantation or other indirect revascularizations are indicated. CASE REPORT: A 39-year-old man, who developed left homonymous hemianopia, was discovered to have occlusion of the distal portion of bilateral internal carotid arteries. We performed indirect revascularization with an omental flap on the left cerebral hemisphere and a serratus anterior muscle flap on the right cerebral hemisphere. RESULTS: Subsequent clinical course was uneventful. Cerebral blood flow study and angiography revealed good collateral circulation in both the omentum and muscle flap. The collateral circulation was more developed than that arising from the omental transfer on the contralateral side at the same postoperative period. CONCLUSIONS: This type of encephalomyosynangiosis (EMS)-EMS with free muscle flap-is as effective as that with the omental flap in adult moyamoya disease. Especially in a patient who is in need of vascular reconstruction of an extensive ischemic area, serratus anterior muscle flap transfer is one of the alternative methods.

Adult↗

Internal representation of two-dimensional shape.

The psychological space of shapes has been studied in many experiments. However, how shapes are represented in the brain has not been a major issue in psychological literature. Here, the characteristics of internal representation and how it was formed have been considered and an attempt has been made to explain the results of experiments in a unified manner. First, the data of similarity of alphabetic characters and random-dot patterns were reexamined. Multivariate analysis suggested that those patterns were represented by the combination of global features. Second, three-layer neural networks were trained to perform categorization or identity transformation of the same sets of patterns as used in psychological experiments, and activation patterns of the hidden units were analyzed. When the network learned categorization of the patterns, its internal representation was not similar to the representation suggested by psychological experiments. But a network which learned identity transformation of the patterns could acquire such an internal representation. The transformation performed by this kind of network is similar to principal-component analysis in that it projects the input image onto a lower-dimensional space. From these results it is proposed that two-dimensional shapes are represented in human brain by a process like principal-component analysis. This idea is compatible with the findings in neurophysiological studies about higher visual areas.

Animals↗

Precise determination of TSH receptor antibody activity in serum containing bovine TSH (bTSH) binding antibody by absorption using denatured bTSH or sheep FSH.

A previous report demonstrated that sera with bovine TSH (bTSH) binding antibody showed abnormally negative TSH receptor antibody (TRAb) activity in the standard TRAb assay method. The corrected TRAb activity calculated by the determination of the nonspecific binding of the labeled bTSH for each test serum [NSB(T)] resulted in positive TRAb activity. However, the precise calculation was difficult because NSB(T) level was significantly higher than the nonspecific binding in normal pool serum [NSB(N)] level. In the present experiment the determination of the TRAb activity was performed after absorption of bTSH binding antibodies by the heat-denatured bTSH to obtain more precise TRAb activity. In addition, absorption by sheep FSH (sFSH) was performed because almost all bTSH binding antibodies showed specific binding to the alpha-subunit of mammalian pituitary glycoprotein hormones in our previous study. Three days absorption of test serum using 1 mU of the heat-denatured bTSH (100 degrees C for 1 h) or 5 mU of sFSH was chosen as optimal because NSB(T) decreased remarkably to NSB(N) levels. The corrected TRAb determined after these absorptions decreased significantly compared to the corrected TRAb activity without the absorption. When the complete absorption of bTSH binding antibody was performed by the decrease of the NSB(T) level to the NSB(N) level, the TRAb activity determined by these two different absorptions was almost similar (difference was less than 10%). However, it was difficult to obtain the precise TRAb activity in the cases with extremely high bTSH binding antibody, because the NSB(T) level was higher than the NSB(N) level by the incomplete absorption of bTSH binding antibody.

Absorption↗

Changes in taste perception following mental or physical stress.

Taste perception depends not only on the chemical and physical properties of tastants, but may also depend on the physiological and psychological conditions of those who do the tasting. In this study, the effects of mood state on taste sensitivity was evaluated in humans who were exposed to conditions of mental or physical fatigue and tension. Taste responses to quinine sulfate (bitter), citric acid (sour) and sucrose (sweet) were tested. The intensity of the taste sensations were recorded by a computerized time-intensity (Tl) on-line system. Subjects performed mental tasks by personal computer or physical tasks by ergometer for 10-40 min. Before and after these sessions, the duration of the after-taste and the intensity of the sensation of taste were recorded by the Tl system, and in addition, psychological mood states were evaluated with POMS (Profile of Mood State). Tl evaluation showed that after the mental tasks, the perceived duration of bitter, sour and sweet taste sensations was shortened relative to the control. Total amount of bitterness, sourness and sweetness was also significantly reduced. Furthermore, the maximum intensity of bitterness was significantly reduced. There were no significant differences in bitterness and sweetness sensations following physical tasks. However, relative to before the physical task, the duration of the after-taste of sourness was significantly shortened by the physical task. After the physical task, the buffering capacity of saliva was significantly increased. Thus mental and physical tasks alter taste perception in different ways; the mechanisms underlying these changes remain to be determined.

Adult↗

Enzyme-linked immunoassay for midkine, and its application to evaluation of midkine levels in developing mouse brain and sera from patients with hepatocellular carcinomas.

Midkine (MK) is a growth factor that promotes neurite outgrowth and survival of neurons, and enhances the plasminogen activator in endothelial cells. A highly sensitive enzyme-linked immunoassay for MK was developed, involving affinity-purified anti-MK antibodies, their biotinylated form, and avidin-beta-galactosidase. The amount of bound avidin-beta-galactosidase was determined using a fluorogenic substrate, 4-methylumbelliferyl-beta-D-galactoside. This method allowed the detection of human and mouse MK in the range of 50 pg-10 ng. Pleiotrophin, which is related to MK in its amino acid sequence, did not show any cross reactivity. Employing this method, the MK levels in the developing mouse brain were determined. The MK level was 2 micrograms/g of wet tissue on the 12th day of gestation, and then steadily decreased during embryogenesis and postnatal development to 30 ng/g two months after birth. The assay method can also be applied to serum samples. Although the MK levels in the sera of normal human subjects were low or undetectable, 0.6-8 ng/ml of MK was detected in samples in the majority of cases of hepatocellular carcinomas.

Animals↗

Eosinophilic granuloma associated with intratumoral hemorrhage--case report.

A 2-year-old boy presented with a rapidly growing soft scalp mass in the left parietal region. Surgical exploration and histological examination demonstrated an eosinophilic granuloma associated with intratumoral hemorrhage. Eosinophilic granuloma should also be considered when a scalp mass lesion exhibits rapid growth.

Cerebral Hemorrhage↗

[Optimum dose study of cefozopran in the pediatric field].

Cefozopran (SCE-2787, CZOP) was administered to patients with pediatric infections three to four times daily by intravenous injection or 30-minute intravenous drip infusion, and investigations were made in individual cases, on relationships among doses, pharmacokinetics, effects on pathogenic bacteria and MIC against them, and clinical effects. The following results on optimal doses of CZOP were obtained. 1. Clinical cases in which CZOP was administered at a dose of 10 mg (potency)/kg The subjects were 7 patients including 4 patients with pneumonia. Severities of the diseases were severe in one of the patients with pneumonia, and moderate in the other patients. The MIC against pathogenic bacteria (4 strains) isolated from these cases ranged from 0.2 to 1.56 micrograms/ml. The serum concentrations were in a range between 1.4 and 7.6 micrograms/ml at 4 hours after administration. In some cases, the serum concentrations were lower than the MICs, though slightly. In the clinical evaluation, CZOP was excellent in 3 cases, good in 2 cases and fair in 1 case. The evaluation was impossible in 1 case. The efficacy rate was 83.3% (5/6). In bacteriological evaluation, 3 out of the 4 strains disappeared. Adverse reactions and abnormal laboratory test values were not observed. 2. Cases in which CZOP was administered at a dose of 20 mg (potency)/kg The subjects were 5 patients including 2 with pneumonia, and severities were severe in one of the patients with pneumonia, and moderate in the other patients. The MICs against the pathogenic bacteria (3 strains) isolated from these cases ranged from 0.1 to 1.56 micrograms/ml. While, serum concentrations at 4 hours after administration were in a range between 3.0 and 7.7 micrograms/ml sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 1 case and good in four cases, with an efficacy rate of 100% (5/5). In the bacteriological evaluation, all the 3 strains disappeared. No adverse reactions were observed, but an abnormal laboratory test value showing eosinophilia was noted in one case. 3. Cases in which CZOP was administered at a dose of 40 mg (potency)/kg The subjects were 5 patients including 3 with pneumonia. The severity was moderate in 2 of the pneumonia patients, and severe in the other three cases. The MICs against the pathogenic bacteria (4 strains) isolated from these cases were in a range between 0.1 and 0.78 micrograms/ml. The serum concentrations at 4 hours after administration ranged from 6.5 to 21.9 micrograms/ml, sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 4 cases and good in 1 case, with an efficacy rate of 100% (5/5). The efficacy rate in the bacteriological evaluation was also 100%. As adverse reaction, red urine was observed in one case. Eosinophlia was noted in one case in the laboratory tests. When CZOP was administered to patients with pediatric infections at a dose of 10 mg (potency)/kg, the clinical effect of the drug was insufficient in a case in which serum concentration of CZOP at 4 hours after administration was lower than the MICs against the pathogenic bacteria. When CZOP was administered at a dose of 20 mg (potency)/kg, sufficient concentrations were obtained, and the drug efficacies were found to be excellent or good in all cases. Therefore, the effective dose normally used is considered to be 20 mg (potency)/kg. When CZOP was administered at a dose of 40 mg (potency)/kg, the drug was found to be excellent or good in all of the cases although the severities were high in more than half of the cases tested. In addition, the rate of excellent efficacies was 80% (4/5). Furthermore, no severe adverse reactions were observed. It was, therefore, confirmed that CZOP should be administered at a dose of 40 mg (potency)/kg in severe or intractable cases.

Bacterial Infections↗

Midkine is a heat and acid stable polypeptide capable of enhancing plasminogen activator activity and neurite outgrowth extension.

We studied about the physicochemical stability of a novel heparin-binding growth/differentiation factor, midkine (MK). It was found that synthetic human MK was heat and acid stable. Neither incubation at 80 degrees C for 90 sec nor treatment at low pH affected the elution profile of MK molecule on the high performance liquid chromatography. This physicochemical stability was maintained in the biological activities of MK to enhance plasminogen activator (PA) activity in bovine endothelial cells as well as to promote neurite outgrowth of rat brain cells. A similar stability was observed both with recombinant murine MK and with its homologous protein, recombinant human pleiotrophin. Comparison of physicochemical stability with other several growth factors suggested that MK/pleiotrophin was a unique family of heat and acid stable polypeptides capable of enhancing PA activity and neurite outgrowth.

Animals↗

Synthetic peptides derived from midkine enhance plasminogen activator activity in bovine aortic endothelial cells.

Chemically synthesized human midkine enhanced plasminogen activator activity and decreased its inhibitor levels in bovine aortric endothelial cells. These activities were preserved in the C-terminal half, but not in the N-terminal half of the midkine molecule. Furthermore, a synthetic peptide of 43 amino acids designated as "C-domain", which formed the compact structure held by two disulfide bonds in the C-terminal half, mimicked intact midkine. Chemically synthesized C-domain of pleiotrophin (43 amino acids), which was 53% identical to midkine C-domain in amino acid sequence, expressed the similar activities. These 43 amino acid peptides are, so far, the shortest peptide able to enhance the fibrinolytic activities of the endothelial cells.

Amino Acid Sequence↗

Vascularized omental graft to brain surface in ischemic cerebrovascular disease.

The application of vascularized omental graft for the treatment of four patients with ischemic cerebrovascular disease is presented. The superficial temporal artery and vein were used as recipient vessels, and vascular anastomosis was applied in an end-to-end fashion. The distal parts of the omentum were exteriorized as monitoring segments for about 1 week. Angiography and cerebral blood flow (CBF) studies were performed in all patients postoperatively. There were no major complications, and all patients showed increases of CBF and apparent clinical improvement. It is suggested that this method is effective in selected patients with ischemic cerebrovascular disease.

Brain↗

Demonstration of thyroactive smaller components released from TSAb-IgG by protease digestion.

Thyroid stimulating (TS) activity (cAMP production in thyroid cells) and TSH binding inhibition (TBI) activity (determined by TSH receptor assay) in fragments released from TSAb-IgG by protease digestion were examined. The unbound fraction (UF) and the bound fraction (BF) were separated using a protein A-Sepharose column after papain hydrolysis (more hydrolysis at pH 5.0 than pH 7.5) of TSAb-IgG. When both fractions were gel filtrated on a Sephadex G-100 column, the TS and TBI activity were found in both Fab fraction (Mr 50 kDa) and the retarded fraction (between Mr 50 and 20 kDa) in the UF, and also in the first fraction (undigested IgG, Mr 160 kDa), the second fraction (Fc with tracer amounts of Fab, Mr 50 kDa), and the retarded fraction (between Mr 50 and 20 kDa) of the BF. The biological activity in the second fraction was suggested as being derived from Fab, because the activity bound to the anti-F(ab')2 column but did not bind to the anti-Fc column. Anti-Tg and anti-TPO activities were found in Fab, but were not found in the retarded fraction that consisted of Mr 20-30 kDa. In pepsin hydrolysis the UF from the protein A column consisted of both F(ab')2 (Mr 100 kDa) and pF'c (CH3) (Mr 25 kDa), and the BF consisted of only the undigested IgG. The biological activities were found in both the F(ab')2 fraction and the retarded fraction (between Mr 100 and 25 kDa). Anti-Tg and anti-TPO activities were found in F(ab')2, but no activity was observed in the Mr 25-kDa fraction. The present study showed that the biological activity of TSAb is distributed in not only the Fab or F(ab')2 fragment, but also in thyroactive smaller components (TSC) (Mr 20-30 kDa) without antigen-binding activity such as anti-Tg and anti-TPO. We suggest that TSC may be released from the Fab fragment region of TSAb-IgG by protease hydrolysis.

Animals↗

Adhalin gene mutations in patients with autosomal recessive childhood onset muscular dystrophy with adhalin deficiency.

Homozygous adhalin gene mutations were found in three patients from two consanguineous families with autosomal recessive childhood onset muscular dystrophy. Muscle biopsies from patients in each family showed complete absence of adhalin. Sequencing of adhalin cDNA prepared from skeletal muscle by reverse transcription PCR demonstrated a cytosine to thymidine substitution at nt 229 in the patient in family 1 and an adenine to guanine substitution at nt 410 and a 15-base insertion between nt 408 and 409 in the two patients in family 2. Sequencing of genomic DNA prepared from peripheral blood leukocytes by PCR confirmed these mutations. The parents in each family were found to be heterozygous for the respective mutations. These adhalin gene mutations are presumed to be responsible for the absence of adhalin in the skeletal muscle. Adhalin deficiency likely causes disruption of the muscle cell membrane, resulting in dystrophic changes in the skeletal muscle similar to dystrophin deficiency in Duchenne muscular dystrophy.

Adult↗

[Complete deficiency of adhalin (50 kDa DAG) in skeletal muscle of malignant limb-girdle muscular dystrophy].

Malignant limb-girdle muscular dystrophy was first described by Miyoshi and co-workers in 1966, and has clinical features similar to Duchenne muscular dystrophy but is inherited through an autosomal recessive trait. This paper describes a patient with malignant limb-girdle muscular dystrophy with complete deficiency of adhalin (50 kDa dystrophin-associated glycoprotein (DAG)) in skeletal muscle. The patient was an 11-year-old Japanese girl whose parents were cousin. She learned to walk at one year and 3 months of age. Her gait became unsteady at 3 years of age, and motor dysfunction in the lower extremities progressed thereafter. At 8 years of age, she had difficulty in standing up from a sitting position, but could walk without assistance. At 11 years, she could walk with support, but could not stand up without assistance. Her intelligence was normal. Muscle atrophy was not apparent due to obesity, but her calves appeared hypertrophic. She had generalized muscle weakness, predominantly in the pelvic girdle muscle. Muscle tone was slightly hypotonic, and deep tendon reflexes of the legs were absent or hypoactive. Her sensory system appeared normal. Serum creatine kinase level was elevated to 30 times above the upper limit of the normal range in the patient and normal in her parents. EMG showed a mild myopathic pattern. CT scan of muscle revealed marked low density in the upper legs and mild in the lower legs. Muscle histology showed muscle fiber necrosis with a small number of regenerating fibers. Opaque fibers were occasionally observed, but not as many as in Duchenne type. Fiber splitting was seen frequently.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Localization of heparin-binding, neurite outgrowth and antigenic regions in midkine molecule.

Midkine is a 13kDa heparin-binding polypeptide rich in basic amino acids and cysteine and has neurite outgrowth, neuronal cell survival and other activities. We used chemically synthesized MK half molecules as well as recombinant MK deficient in N-terminal and C-terminal sequences to localize its active regions. The principal and conformation-dependent heparin-binding site was found in the C-terminal half. On the other hand, 13 amino acid residues in the C-terminal end were responsible for the MK antigenicity. The C-terminal half, but not the N-terminal half, had potent neurite outgrowth activity. However, in contrast to the whole molecule, the C-terminal half could not support the survival of embryonic brain neurons.

Amino Acid Sequence↗

Risk factors for repeatedly reactive HIV-1 EIA and indeterminate western blots. A population-based case-control study.

OBJECTIVE: Causes of indeterminate results of Western blot testing (IWB) for human immunodeficiency virus (HIV) type 1 include seroconversion, HIV-2 cross-reactivity, and autoimmune disease, but most IWB results remain unexplained. This case-control study assessed risk factors for IWB results, including early HIV infection, other retroviral infection, autoantibodies, and other medical conditions. DESIGN: Prospective study to determine HIV seroconversion rate, with a case-control design to assess other risk factors for IWB. Cases (persons with one or more repeatedly reactive HIV-1 enzyme immunoassay with IWB), their current sexual partners, and controls (persons with negative enzyme immunoassay and Western blot results) were recruited from blood banks, health department and prenatal clinics, and private providers in Washington and Oregon. RESULTS: Of 244 cases enrolled, 206 were followed up for 6 months or longer, and six (3.0%; 95% confidence interval [CI], 0.7% to 5.3%) with recent HIV risk behaviors seroconverted. The Western blot banding patterns differed among groups; cases usually had p17 or p24 bands, while controls and cases' sexual partners usually had polymerase bands. Conditional logistic regression indicated that independent risk factors for IWB among male cases and controls were a tetanus booster in the past 2 years (odds ratio, 3.2; 95% CI, 1.2 to 8.6) and sexual contact with a prostitute (odds ratio, 3.0; 95% CI, 1.0 to 9.5). Independent risk factors for women were parity (odds ratio, 1.2; 95% CI, 1.02 to 1.4) and autoantibodies, either rheumatoid factor or antinuclear antibodies (odds ratio, 2.3; 95% CI, 1.03 to 5.6). No cross-reactivity was detected with HIV-2, human T-lymphotrophic virus type 1, feline immunodeficiency or feline leukemia, or bovine immunodeficiency viruses. CONCLUSIONS: Evaluation of persons with reactive HIV-1 enzyme immunoassays and IWB should include an assessment of HIV risk and other possible risk factors, such as alloimmunization (ie, parity or recent immunization) or autoantibodies (ie, antinuclear antibodies and rheumatoid factor). The relationship of IWB among men who reported sex with prostitutes is intriguing and warrants further study.

Adolescent↗

Characteristics of dynamic mutation in Japanese myotonic dystrophy.

To study the characteristics, if any, of unstable CTG repeat sequence in Japanese myotonic dystrophy (DM), we analyzed DNA from 351 at risk individuals (including affected and non-affected carriers and their descendants) from 105 families in Japan. A total of 93 DM families (196 affected and 116 unaffected individuals), including 84 DM parent-child pairs (44 father-child and 40 mother-child pairs), were examined, many of which had been previously tested by linkage analysis. We detected unstable CTG repeat mutations between 0.15 kb and 8.7 kb in size. The size of the mutation correlated with the age of onset of symptoms. There was a significant difference in DM allele size among the four groups (congenital, juvenile onset, classical, and minimal). Congenital DM had on average the largest repeat sizes. Comparison of parent-child pairs showed that most offspring had a larger repeat size than their parents, with only 2 of 84 showing a definite decrease in repeat size. The correlation coefficients for maternal and paternal transmission were 0.41 and 0.15, respectively. The parental age (maternal and paternal) did not correlate with intergenerational change of repeat. These observations are similar to those reported in Caucasians.

Adolescent↗

Production of thyroid stimulation blocking antibody without TSH receptor binding activity in rabbits with experimental autoimmune thyroiditis.

When rabbits were immunized with porcine thyroid plasma membrane, some cases of produced antibodies showed the blocking activity for TSH stimulated cAMP production in cultured porcine thyroid cells in spite of negative TSH binding inhibitory immunoglobulin (TBII) activity. The inhibitory effect of these thyroid stimulation blocking antibodies (TSBAbs) on cAMP increase by forskolin and GTP gamma S in porcine thyroid cells was observed in 1 and 3 rabbits, respectively. When the blocking activity of these antibodies for stimulated cAMP production by forskolin, GTP gamma S and NaF was examined in the isolated porcine thyroid membrane, no blocking activity for these 3 stimulators except in 1 case was found. The blocking activity of these antibodies could be absorbed significantly by incubation with porcine thyroid plasma membrane as antigen. The blocking activity was not observed in rabbits immunized with porcine thyroglobulin. The present experiment demonstrated that the produced antibody in rabbits against porcine thyroid membrane had the blocking activity for TSH stimulation to thyroid cells without affecting TSH binding to its receptor. These facts suggest that this type of blocking antibody may be produced against any antigen of thyroid membrane origin except the TSH receptor.

Adenylyl Cyclases↗