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Biomedical subjects

H Inagaki

Publications and source records attributed to H Inagaki.

At least 127 records · Page 7Linked to original sources

[A case of advanced gastric cancer treated effectively with neo-adjuvant chemotherapy using l-leucovorin and 5-FU].

A 59-year old man was diagnosed as having advanced gastric cancer, liver metastasis and lymph node metastases after a closed medical examination. Because Schnitzler metastasis was also suspected, chemotherapy was started pre-operatively. The schedule of administration was as follows. One course was l-LV 250 mg/m2 and 5-FU 600 mg/m2 injected intravenously every week and continued for 6 weeks. The UGI examination showed partial response in stomach cancer, and liver metastasis disappeared on CT-scan after 2 courses. We performed total gastrectomy, lymphadenectomy, splenectomy and partial resection of liver. Histological effects showed Grade 1a on main tumor, Grade 2 on liver metastasis, and No. 3 lymphnode metastasis. The survival time was 476 days.

Adenocarcinoma↗

Expression of the tyrosinase-encoding gene in a colorless melanophore mutant of the medaka fish, Oryzias latipes.

In the medaka fish Oryzias latipes many mutants for body colors have been isolated. Among them, a colorless melanophore mutant b, carrying b alleles homozygously, has pigmented black eyes but orange-colored skin with amelanotic melanophores, suggesting the presence of a tissue-specific mechanism of melanin formation. To cast light on the molecular basis of the mechanism, we have cloned cDNAs for tyrosinase (Tyr), a key enzyme in melanin biosynthesis, from the wild-type (wt) fish. DNA sequence analysis revealed that all clones encode a protein of 540 amino acids, having five potential glycosylation sites and two copper-binding sites that are characteristic features of Tyr. Genomic DNA blot analysis disclosed that the Tyr gene is present as a single copy in the fish genome. Using a cDNA clone as a probe, RNA blot analysis was carried out. In the wt, the 2.2-kb Tyr mRNA was expressed in eyes and skin but not in liver, corresponding to tissue-specific melanin formation. In the b mutant, contrary to expectation, the mRNA was detected not only in eyes but also in amelanotic skin. Therefore, pigmentation of the skin controlled by b is not directly related to expression of the Tyr gene.

Alleles↗

Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients.

Interleukin (IL)-1 beta, IL-6, epidermal growth factor (EGF), and transforming growth factor-alpha (TGF-alpha) were measured for the first time in the brain (caudate nucleus, putamen and cerebral cortex) from control and parkinsonian patients by highly sensitive sandwich enzyme immunoassays. The concentrations of IL-1 beta, IL-6, EGF, and TGF-alpha in the dopaminergic, striatal regions were significantly higher in parkinsonian patients than those in controls, whereas those in the cerebral cortex did not show significant differences between parkinsonian and control subjects. Since these cytokines and growth factors may play important roles as neurotrophic factors in the brain, the present results suggest that they may be produced as compensatory responses in the nigrostriatal dopaminergic regions in Parkinson's disease, and may be related, at least in part, to the process of neurodegeneration in Parkinson's disease.

Aged↗

Identification and cloning of an mRNA coding for a germ cell-specific A-type lamin in mice.

The nuclear lamins are karyoskeletal proteins which have important functions, such as maintaining nuclear envelope integrity and organizing high order nuclear structure during mitosis in higher eukaryotes. In somatic mammalian cells, the A-type and B-type lamins, composed of lamins A and C and lamins B1 and B2, are major components of the nuclear lamina. However, A-type lamins have as yet not been identified in germ cells and undifferentiated embryonic cells. Here we report the cloning of a new 52-kDa A-type lamin from mouse pachytene spermatocytes, termed lamin C2 because of its similarities with lamin C. It has a sequence identical to that of lamin C except that the N-terminal segment, containing the head and the alpha-helical coil 1A domains, is replaced with a short non-alpha-helical stretch of amino acids. In mice, lamin C2 was found to be specifically expressed in germ cells. This specific expression and unique structure suggests a role for lamin C2 in determining the organization of nuclear and chromosomal structures during spermatogenesis.

Amino Acid Sequence↗

Proliferative cell nuclear antigen expression in follicular tumours of the thyroid with special reference to oxyphilic cell lesions.

The expression of proliferative cell nuclear antigen (PCNA) in follicular tumours of the thyroid was examined by immunohistochemistry. Both usual nonoxyphilic cell follicular tumours (non-OCT) and oxyphilic cell tumours (OCT) were subdivided into benign, indeterminate, encapsulated carcinoma, and widely invasive carcinoma types. Among non-OCT the percentages of PCNA-positive cells in benign tumours, encapsulated carcinomas, and widely invasive carcinomas was 2.5%-8.6%, 11.8%-39.1%, and 18.6%-20.0%, respectively. There was a statistically significant difference between benign tumours and encapsulated or widely invasive carcinomas, as in previous studies. A value of 10% was appropriate to distinguish benign from malignant lesions. PCNA-positive cells in indeterminate-type non-OCT were not significantly different from those in benign tumours, ranging from 4.3%-19.6%, and occurring at more than 10% in three of six tumours. Among OCT the positivity was less than 10% in benign tumours (4.5%-7.8%) and more than 10% in malignant tumours (14.1%-35.9%) and all the eight indeterminate tumours (12.5%-27.3%), with a statistically significant differences between the benign tumour and each of the latter types. These results indicate that the examination of PCNA is valuable in diagnosis of thyroid follicular tumours and that the use of similar diagnostic criteria may be warranted in both non-OCT and OCT.

Adenocarcinoma, Follicular↗

An enzyme-linked immunosorbent assay for hippuric acid: its potential application for biological monitoring of toluene exposure.

An enzyme-linked immunosorbent assay (ELISA) for hippuric acid (HA) was developed using polyclonal anti-HA antibodies. Anti-HA antibodies were obtained by immunizing rabbits with N-benzoyl-cysteine (B-Cys) or N-alpha-benzoyl-lysine (B-Lys). An antibody with highest reactivity to HA was obtained from anti-B-Lys antiserum by affinity chromatography with B-Cys-Sepharose. The ELISA system was composed of solid-phase B-Cys, anti-HA antibody, and horseradish peroxidase-conjugated anti-rabbit immunoglobulin antibody. The detection limit of the ELISA for HA was around 1 microgram/ml. The urinary HA concentration determined by the ELISA system correlated well with that obtained by high-performance liquid chromatography (HPLC). The ELISA system was considered to be useful in the biological monitoring of toluene exposure, and to be more advantageous than time-consuming HPLC, especially when measuring a large number of samples.

Adult↗

cDNA cloning and functional characterization of a meiosis-specific protein (MNS1) with apparent nuclear association.

It is well known that cytoskeleton and karyoskeleton proteins are associated with changes in cell shape and with the rearrangement of the dynamic structures involved in cell division and motility. In higher vertebrates, there are three major skeletal protein groups: microfilaments, microtubules and intermediate filaments, each representing a multigene family. Some of these skeletal proteins are expressed in a temporally- and spatially-specific fashion, and they establish cell-specific cytoplasmic and nucleoplasmic organization during development. Here we report the cDNA cloning of a novel 60 kDa skeletal protein from mouse spermatocytes, termed MNS 1 (meiosis-specific nuclear structural protein), whose computer-predicted protein configuration indicates long alpha-helical coiled-coil domains flanked by non-helical terminal domains. Functional characterization of MNS1 by ectopic expression in culture cells indicated that it is a detergent- and high salt-resistant skeletal protein which is involved in organization of the nuclear or perinuclear architecture. The MNS1 protein is specifically expressed at the pachytene stage during spermatogenesis, so that its function may involve the determination and maintenance of the appropriate nuclear morphology during meiotic prophase.

Amino Acid Sequence↗

Duration and extent of antianginal effects of a sustained-release formulation of nifedipine in angina.

Twenty-four patients with chronic stable exertional angina pectoris were randomized in a double-blind, placebo-controlled, crossover trial to assess the efficacy and durability of a newly developed, sustained-release formulation of nifedipine (nifedipine CC) in a single 40-mg oral dose. Symptom-limited graded treadmill exercise tests were performed just before, and at 4, 7, and 24 h after a single administration of the drug or the placebo was given. Exercise tolerance at 4, 7, and 24 h after the drug were compared with the corresponding placebo values. Data could be analysed for 19 patients. Maximal exercise time, time to the onset of angina, and time to 1 mm ST segment placebo. The average maximal exercise time was significantly increased by 72, 76, and 37 s at 4, 7, and 24 h. Rate-pressure product at rest and at peak exercise showed significant changes only at 24 h compared with placebo (both P < 0.05). The maximal increase in exercise tolerance was most marked at 7 h nifedipine CC, at which time plasma drug concentration was 99.4 +/- 14.0 ng.ml-1. Thus, in patients with chronic stable exertional angina pectoris, nifedipine CC showed a prolonged improvement in exercise tolerance up to 24 h after a single oral administration.

Angina Pectoris↗

[Relationships between serum lipid peroxide level (serum TBA level) and smoking, alcohol drinking, food frequency, serum vitamin C and E in subjects with multiphasic screening].

Relationships between serum thiobarbituric acid (TBA) level and smoking, alcohol drinking, differences in food intake with alcohol drinking, serum vitamin C (VC) and E (VE) were studied in 283 non-treated men (aged 20-69 years) who visited a human dock conducted in an urban area of Hyogo prefecture in 1989-1991 (annually May-July). The results were as follows: 1. An effect of smoking on serum TBA level was not observed. 2. The subjects were divided into three groups according to weekly sake intake levels, i.e., non-drinkers including ex-drinkers (ND), mild drinkers (MD, weekly sake intake: < or = 1260 ml), and heavy drinkers (HD, > 1260 ml). The serum TBA level of HD, but not of MD, was significantly higher than that of ND. 3. Serum TBA level had significant positive correlations with age, GPT, gamma-GTP, TC (total cholesterol), TG (triglycerides), PL (phospholipids), total serum lipids (TLP, i.e., TC+TG+PL), VE, eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6), but had no significant correlations with VC and VE/TLP. 4. The subjects (N+M) D, which included ND and MD, and those of HD were divided respectively into three groups according to weekly food intake levels, i.e., non-intake group (NF), low frequent intake group (LF, 1-3 days/week), and high frequent intake group (HF, > or = 4 days/week). The fish intake level of HD was significantly higher than that of (N+M) D, while the intake levels of vegetables, fruits and soft drinks of HD were significantly lower than those of (N+M) D. 5. Serum TBA level, GOT, GPT, gamma-GTP, TG, PL, TLP, VE, EPA and DHA of HD were significantly higher than those of (N+M) D. On the other hand, VC of HD was significantly lower than that of (N+M) D. 6. When the subjects of (N+M) D were divided into three groups according to weekly fish intake levels as mentioned above, serum TBA level, EPA and DHA of HF in (N+M) D were significantly higher than those of NF in (N+M) D. 7. Serum TBA level of HD in non-fish intake group was significantly higher than that of (N+M) D in the same group. These results suggest that increased serum TBA level in HD is closely related to the increased intake frequency of fish in addition to the effect of alcohol drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Inhibitory action of chloramine on formate-metabolizing system. Studies suggested by an unusual case record.

We previously reported on a patient exposed simultaneously to methyl chloride and chloramine gas who developed metabolic acidosis and permanent blindness [M. Minami et al., Hum Exp Toxicol 11: 27-34, 1992]. The case report suggested the possibility of potentiation of methyl chloride toxicity by chloramine. The potentiating mechanism was investigated by exposing mice to methyl chloride followed by ammonia chloramine, and then the level of formate in urine samples was measured with an enzyme coupling method to detect disturbance of formate metabolism. Mice dosed with 0.05 mL 1.0 mM chloramine after methyl chloride exposure excreted a significantly larger amount of urinary formate than mice treated with only methyl chloride. There was no difference in urinary formate levels between mice treated with only 0.05 mL 1.0 mM chloramine and those given only the vehicle (0.1 M phosphate buffer pH 6.0) for chloramine. The underlying biochemical mechanism of deterioration of formate metabolism was found to be the inhibition of the enzyme, N10-formyl tetrahydrofolate (N10-f-THF) dehydrogenase by 0.56-3.35 microM chloramine in the in vitro experiment using the purified enzyme. Positive control mice, given orally 0.1 mL 10% methanol in 0.1 M phosphate buffer (pH 6.0) excreted the same amount of urinary formate as those receiving 0.05 mL 1.0 mM chloramine after methanol administration. This was ascribed to the inhibitory effect of chloramine on formaldehyde dehydrogenase and depletion of substrate for further metabolism. The inhibition of the enzyme by chloramine (2.7-100.8 microM) was confirmed by in vitro experiments, using the purified enzyme, formaldehyde dehydrogenase.

Aldehyde Oxidoreductases↗

Aldolase C in neuroendocrine tumors: an immunohistochemical study.

The expression of cerebral type aldolase C was investigated immunohistochemically in six varieties of neuroendocrine (n = 57) and six types of non-endocrine tumor (n = 76) using the avidin-biotin complex method. Aldolase C expression in the neuroendocrine tumors was also compared with those of chromogranin and gamma enolase. Aldolase C was detected in all the islet cell (7/7) and carcinoid tumors (10/10), thyroid medullary carcinomas (7/7), and pheochromocytomas (10/10), as well as in the majority of neuronal tumors (8/10) and bronchial small cell carcinomas (10/13). Chromogranin immunoreactivity was restricted to the tumors with abundant neuroendocrine granules. Gamma enolase positivity was generally similar to that of aldolase C, but there were some differences. Amongst the bronchial small cell carcinomas, three tumors negative for gamma enolase were positive for aldolase C, while another three tumors were positive for gamma enolase only. However all the small cell carcinomas were positive for at least one of these two enzymes. Aldolase C was detected in 28 (37%) of the 76 non-endocrine tumors and tended to be expressed preferentially in the differentiated portions of these tumors. Although aldolase C was expressed in many bronchial squamous cell carcinomas, the immunoreactivity was localized mainly in keratinizing foci and the less differentiated parts of these tumors expressed the enzyme only occasionally. Thus aldolase C, in conjunction with other neuroendocrine-associated markers, may be of value in identifying tumors of neuroendocrine type.

Adenoma, Islet Cell↗

Age-related changes in left and right ventricular filling velocity profiles and their relationship in normal subjects.

To confirm age-related changes in left and right ventricular filling velocity profiles and to compare left and right ventricular filling parameters in normal subjects, we performed pulsed Doppler echocardiographic studies in 108 normal subjects (72 men and 36 women) aged 15 to 78 years. An age-related decrease in peak early velocity (E velocity), an increase in peak atrial velocity (A velocity), and augmented ratio of A velocity to E velocity (A/E) were observed in left ventricle (r = -0.71, 0.63, and 0.83, respectively). Similar age-related changes were found in right ventricle (r = -0.71, 0.54, and 0.78). Aging had a greater effect on the filling of the left ventricle than the right one (i.e., a steeper slope). The difference between left and right ventricular filling increased with advancing age. Left ventricular filling indexes exceeded those of the right ventricle. Significant correlations were observed between the right and left ventricular filling parameters (r = 0.58 to 0.90). A strong relation was noted in A/E (r = 0.90). There was no significant relation between age and left ventricular mass. The left ventricular mass appeared to have little effect on left and right ventricular filling in normal individuals. Thus in clinical studies the age-related decrease in early diastolic filling and the increased atrial filling in both left and right ventricles should be considered. The atrial contribution to ventricular filling may be more pronounced in the left ventricle than the right ventricle in older subjects.

Adult↗

Rises in urinary bicarbonate contents and pH of adult Tokyo citizens.

Urinary bicarbonate has been considered to be negligible, and the pH of urine to be low (around pH 5.5) for these fifty years. It was, however, found that the contents of bicarbonate and pH of the urine of adult Tokyo citizens (435 adults including 148 males and 287 females) substantially increased. The findings may be correlated with increased inhaled amounts of carbon dioxide which finally causes the increase of urinary excretion of bicarbonate, though evidence that the gas accumulates in the atmosphere of Tokyo due to air pollution has not been directly demonstrated.

Adult↗

Immunohistochemical studies on choroidal epithelial cyst and neuroepithelial cyst: in comparison with normal choroid plexus and ependyma.

Immunohistochemical evaluations with antibodies against S-100 protein, glial fibrillary acidic protein, cytokeratin and prealbumin were applied to 2 intracranial cysts of choroidal epithelial and neuroepithelial origin, and to the normal choroid plexus and ependyma. All specimens showed various immunoreactivities with the 4 antigens: especially, prealbumin-positive cells were detected in normal choroid plexus, part of normal ependyma, and part of choroidal epithelial cyst. The epithelium of neuroepithelial cysts presumably has multipotentials in cellular differentiation.

Brain Diseases↗

Mesenteric venous thrombosis in familial free protein S deficiency.

Protein S deficiency reportedly is associated with a high risk for thromboembolism, but mesenteric venous thrombosis is a rare manifestation of this hereditary disorder. We describe an additional case of mesenteric venous thrombosis in a 25-yr-old man with type I protein S deficiency. Total protein S level remained just below the normal range, but free protein S level was less than 10% of normal. Family study revealed that his father had had the same type of disorder. We have reviewed six well-documented cases of mesenteric venous thrombosis with protein S deficiency. It is particularly interesting that those with type I deficiency have had no previous thrombotic episodes (p < 0.05). Our patient was successfully treated with extended bowel resection, but unusual perioperative management was required. Because of extremely edematous mesentery and small bowel, we had to treat him with the abdomen wide open for 2 days between the primary and second laparotomies.

Adult↗

Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency.

Pit-1 is a pituitary-specific transcription factor that binds to and transactivates promoters of growth hormone and prolactin genes. In three unrelated Japanese children with combined pituitary hormone deficiency, we identified three point mutations in the Pit-1 gene, Pro24Leu, Arg143Gln, and Arg271Trp, located on the major transactivation region, POU-specific domain, and POU-homeodomain, respectively.

Amino Acid Sequence↗

Identification of immuno-reactive lipocortin 1-like molecules in serum and plasma by an enzyme immunoassay for lipocortin 1.

A two-site enzyme immunoassay for lipocortin 1 (LC1) has been developed. The detection limit of LC1 was 0.2 ng/tube and the optimal assay range was 1 to 100 ng/tube. The assay system enabled us to identify immunoreactive lipocortin 1-like molecules (IR-LC1) in human serum and plasma. Normal human serum and plasma IR-LC1 concentrations were 44.6 ng/ml for males and 43.1 ng/ml for females with no significant difference between both sexes. The age-related analysis among nine age groups from newborn to 69 years old revealed that the serum or plasma level was high in infants (77.5 ng/ml for newborn and 75.6 ng/ml for 1 month-1 year group), and the 40-year-old (52.2 ng/ml) and 50-year-old (51.3 ng/ml) groups. The major population of plasma IR-LC1 was of 70 kDa in size corresponding to that of the LC1 homodimer. The present enzyme immunoassay system is sufficiently sensitive for the clinical study of LC1 in human body fluids, tissues and organs.

Adolescent↗