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Biomedical subjects

T Yasuda

Publications and source records attributed to T Yasuda.

At least 451 records · Page 25Linked to original sources

Enhanced attachment and elastase-releasing capacity of neutrophils after surgery.

Perioperative changes in neutrophil attachment level and neutrophil elastase-releasing capacity were examined in patients who underwent surgery for either esophageal or gastric cancer. The neutrophil attachment level was significantly increased in both groups to approximately three times that of the preoperative value. The elastase-releasing capacity of nonstimulated neutrophils was not significantly changed, but it was significantly increased in neutrophils stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). Moreover, both neutrophil attachment and elastase-releasing capacity of FMLP-stimulated neutrophils were more enhanced in patients with postoperative complications than in patients without complications. Peak levels of serum interleukin 6, serum alpha 1 proteinase inhibitor, and plasma neutrophil elastase were also significantly higher in patients with postoperative complications than in patients without. These results suggest that during the postoperative period, neutrophils may be primed and activated in response to inflammatory mediators such as cytokines, and that such an alteration of neutrophil functions may reflect the extent of inflammation and may, at times, be implicated in postoperative complications.

Aged↗

Detection of deoxyribonucleases I and II (DNases I and II) activities in reproductive organs of male rabbits.

Deoxyribonucleases (DNases) I and II activities in 13 different organs and body fluids from healthy male rabbits were measured using the single radial enzyme diffusion method. We now show that testis, epididymis, ampulla, seminal vesicle, vesicular gland, prostate, and semen have both of the DNases I and II activities, whereas spermatozoa do not. DNase I activities were highest in epididymis and seminal vesicle, whereas DNase II activities were highest in epididymis and prostate among the reproductive organs. The presence of these two enzyme activities outside the digestive system suggests that they have another biological function in addition to their digestive roles.

Animals↗

Familial amyloidotic polyneuropathy with late-onset and well-preserved autonomic function: a Japanese kindred with novel mutant transthyretin (Ala97 to Gly).

We report the characteristics of one patient and two asymptomatic carriers from a Japanese family with familial amyloidotic polyneuropathy (FAP). The clinical features were somatic sensory and motor neuropathy with well-preserved autonomic function and late onset with slow insidious progression. These symptoms and signs are different from those of type 1 FAP. There were massive amyloid deposits with transthyretin (TTR) in the myocardium and the sural nerve. DNA sequencing of the TTR gene and amino acid sequence analysis of serum TTR revealed a new mutation in which Gly97 was substituted for Ala. We suggest that patients with somatic sensory and motor neuropathy of unknown origin without apparent autonomic dysfunction should be further studied for TTR mutation.

Age of Onset↗

Aberrant androgen action and increased size of tandem CAG repeat in androgen receptor gene in X-linked recessive bulbospinal neuronopathy.

Plasma levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after 3 or 6 days of administration of the synthetic androgenic hormone fluoxymesterone (10 mg/day) were measured in 26 patients with X-linked recessive bulbospinal neuronopathy (X-BSNP) and 22 age-matched male controls. The testosterone, LH and FSH levels in the controls were markedly suppressed after administration, but in the patients with X-BSNP, they were suppressed significantly less. The level of suppression varied considerably with the patients, and those of plasma testosterone and FSH were significantly correlated with the number of CAG repeats in the androgen receptor gene. These findings suggest that the androgen action was aberrantly transduced in the target organs in the patients with X-BSNP and which is related to the elongated CAG repeat in the androgen receptor gene.

Adult↗

A radiological analysis of heart sympathetic functions with meta-[123I]iodobenzylguanidine in neurological patients with autonomic failure.

Cardiac scintigraphy with meta-[123I]iodobenzylguanidine (MIBG) is used to assess cardiac sympathetic function. We performed [123I]MIBG scintigraphy in 7 patients with neurological diseases presenting orthostatic hypotension and other autonomic failures (AF), 22 neurological patients without AF, and 9 healthy subjects. Thallium scintigraphy and echocardiography were also performed in all subjects. In this series, patients with any evidence of cardiac dysfunction were excluded. No [123I]MIBG accumulation was observed in all patients with AF, and cardiac defects were noted in 7 patients (5 with Parkinson's disease [PD], 2 with spinocerebellar degenerations [SCD]), and in some patients without AF. In contrast, the distribution of [123I]MIBG was normal in all the healthy subjects. No decrease in [123I]MIBG accumulation was resulted from drug therapy (droxidopa, amezinium and thyrotropin-releasing hormone). In conclusion, reduced accumulation on [123I]MIBG scintigraphy may be due to myocardial beta-adrenoceptor dysfunction or reduced central sympathetic activity of the heart, or both.

3-Iodobenzylguanidine↗

Immunohistochemical demonstration of ganglioside GD3 in the central nervous system.

Immunohistochemical staining for GD3 in adult rat brain was carried out using mouse IgM anti-GD3 monoclonal antibody (DSG-1). Neuronal cells in the cerebral cortex, striatum, hippocampus and various nuclei of the thalamus were immunoreactive. In the cerebellum, Purkinje cells, granule cells and also basket cells were immunoreactive. However, astrocytes and oligodendrocytes in the cerebrum and cerebellum were not immunoreactive. The GD3 immunoreactivity was located in the cytoplasm. These findings are of considerable interest, being the first reported demonstration of GD3 in the adult rat brain. The implications and possible significance of the presence of GD3 are discussed.

Animals↗

Expression of the pancreatic secretory trypsin inhibitor gene in the liver infected with hepatitis B virus.

Pancreatic secretory trypsin inhibitor, an acute phase reactant protein, is expressed in the liver in response to inflammatory cytokines, especially in hepatocellular carcinoma. Northern blots of 25 dissected liver tissues from non-hepatitis, chronic hepatitis and cirrhosis patients revealed that 10 (40%) expressed pancreatic secretory trypsin inhibitor. The expression seemed to be closely associated with hepatitis B viral infection, since among the 11 hepatitis B virus-infected samples, nine (81%) were pancreatic secretory trypsin inhibitor-positive. In contrast, this augmented expression was absent in non-infected livers (0/5; 0%), and rare in those infected with hepatitis C virus (1/9; 11%). There was no significant correlation between the pancreatic secretory trypsin inhibitor expression in the liver and the serum level of glutamic pyruvic transaminase, the hepaplastin test, the 15-min retention rate of indocyanine green, or the histological findings of the liver tissues such as lymphocyte infiltration and pseudolobular formation. Furthermore, we identified an almost three-fold increase in the transactivation of pancreatic secretory trypsin inhibitor gene expression in HepG2 cells after transient transfection with HBV-DNA or the X gene in an expression vector. These results suggest that the induction of pancreatic secretory trypsin inhibitor gene expression in livers with chronic hepatitis and cirrhosis is directly affected by hepatitis B virus.

Adult↗

Sclerodermatous renal crisis in a patient with mixed connective tissue disease.

We report a patient with mixed connective tissue disease who developed accelerated hypertension, acute renal insufficiency, and microangiopathic hemolytic anemia. A renal biopsy specimen showed marked vascular changes in small arteries consisting of laminated endothelial cell proliferation and luminal thrombosis, which were similar to those of scleroderma renal crisis. This patient was successfully treated with an angiotensin-converting enzyme inhibitor as well as analogues of prostaglandin E1 and prostaglandin I2. In patients with mixed connective tissue disease, a fatal complication like scleroderma renal crisis should be considered when the blood pressure rapidly increases. The combined administration of angiotensin-converting enzyme inhibitors and analogues of prostaglandin E1 and prostaglandin I2 may be an effective treatment for this complication.

Acute Kidney Injury↗

Mechanism of optical isomerization of (S)-N-[1-(2-fluorophenyl)-3,4,6,7- tetrahydro-4-oxopyrrolo[3,2,1-jk] [1,4]-benzodiazepine-3-yl]-1H- indole-2-carboxamide (FK480) in soft capsules containing polyethylene glycol 400 and glycerol.

FK480 is a new synthetic non-peptide antagonist of cholecystokinin (CCK)-A receptors. The dosage form of FK480 is a soft capsule containing a solution of FK480 in a mixture of polyethylene glycol 400 (PEG 400) and glycerol to improve its bioavailability. Studies on the stability of this FK480 dosage form revealed that the main degradation occurred by optical isomerization at the asymmetric C-3 position of the pyrrolobenzodiazepine ring. The degradation reaction was accelerated by formic acid formed in a mixture of PEG 400 and glycerol. Addition of amino acids to the capsule solution retarded the isomerization by reacting with formic acid. Therefore, formic acid appears to accelerate optical isomerization of FK480.

Benzodiazepinones↗

Establishment of monoclonal antibodies specific for ganglioside GM1: detection of ganglioside GM1 in small cell lung carcinoma cell lines and tissues.

Three kinds of anti-GM1 monoclonal antibodies, AGM-1, -2, and -3, of the IgM class were produced by the immunization of BALB/c mice with ganglioside GM1 inserted into liposomes with Salmonella minnesota R595 lipopolysaccharides and fusion of the spleen cells with a mouse myeloma cell line. The specificities of the monoclonal antibodies obtained were elucidated through complement-dependent liposome immune lysis assay and enzyme immunostaining on thin-layer chromatograms. All of the monoclonal antibodies reacted only with ganglioside GM1, and structurally related glycosphingolipids, such as fucosyl-GM1, asialo-GM1, GM2, and GD1b, and the other gangliosides (GM3 and GD1a) tested showed no reactivity to the 3 monoclonal antibodies. These findings suggest that the monoclonal antibodies obtained may be specific for ganglioside GM1. These anti-GM1 monoclonal antibodies were used to define the expression of ganglioside GM1 on small cell lung carcinoma (SCLC) cell lines and tissues. In flow cytometric analysis and immunostaining studies, we observed that ganglioside GM1 was highly expressed on the SCLC cell lines. Results obtained with flow cytometry and immunohistochemistry agreed well with the immunochemical determination of ganglioside GM1 in lipid extracts of cell lines. Furthermore, expression of ganglioside GM1 in tumor tissues from patients with SCLC was ascertained by the immunohistochemical examination of acetone-fixed paraffin-embedded tissue sections. Ganglioside GM1 was detected in 5 of 19 SCLC tissues. These results suggest that ganglioside GM1 is expressed in SCLC cells.

Animals↗

Improvement of therapeutic effect by using Fab' fragment in the treatment of carcinoembryonic antigen-positive human solid tumors with adriamycin-entrapped immunoliposomes.

To improve the therapeutic efficiency adriamycin entrapped in antibody-conjugated liposomes, Fab' fragment was used instead of the whole antibody molecule. The murine monoclonal antibody, 21B2, against human carcinoembryonic antigen (CEA) was digested with pepsin, and the thiol residue of intra-heavy chain produced by reduction of F(ab')2 with dithiothreitol was conjugated to liposomes containing adriamycin. The tissue distribution of adriamycin delivered with these liposomes was studied in BALB/c nu/nu female mice bearing CEA-positive human gastric cancer strain MKN-45. An increase in delivery of adriamycin to the tumor was observed in the mice given liposomes with Fab' fragment as compared to those given liposomes with whole antibody. However, the preferential distribution of adriamycin in liposomes to the reticuloendothelial cells remained the same regardless of the use of Fab' fragment. For investigation of in vivo therapeutic effect, three i.v. injections of free adriamycin or adriamycin in liposomes equivalent to 5 mg/kg were given, and adriamycin in Fab' fragment-conjugated liposomes was found most effective in the inhibition of tumor growth. This was confirmed in terms of actual tumor weights excised and CEA concentration in the blood, as well as by pathological observations. The advantages of using Fab' fragment instead of whole antibody are discussed.

Animals↗

Suppression of sex steroids by a gonadotrophin-releasing hormone agonist increases serum growth hormone-binding protein activity in girls with central idiopathic precocious puberty.

OBJECTIVE: The high-affinity growth hormone (GH)-binding protein corresponds to the extracellular domain of GH receptor. The direct role of sex steroids in pubertal bone growth may be an increased GH receptor-coupled GH action. We examine the GH-binding protein (GHBP) activity before and after the suppression of female sex steroids and the relation of GHBP to pubertal growth. PATIENTS: We studied six girls with central idiopathic sexual precocity without any prior gonadal suppression therapy. DESIGN: We measured GHBP activity before and 12, 24 and 48 weeks after the treatment with s.c. injection of a GnRH agonist (leuprolide acetate) every 4 weeks. MEASUREMENT: GHBP activity was measured by immunoprecipitation using anti-GH receptor monoclonal antibody. RESULTS: The treatment caused a decrease in the LH and FSH responses to GnRH test and plasma oestradiol, which resulted in decreased urinary GH excretion, plasma IGF-I levels, height velocity and bone age maturation. GHBP activity before the start of the treatment was normal (75 +/- 27% relative to adult pooled serum, mean +/- SD), and it was increased above adult level (122 +/- 29% at 48 weeks, P < 0.01) by the suppression of the pituitary-gonadal axis. There were significant negative correlations between GHBP and oestradiol (r = 0.452, n = 24, P < 0.05) and between GHBP and urine GH excretion (r = -0.462, n = 24, P < 0.05). CONCLUSIONS: The high-affinity GHBP is increased by the withdrawal of female sex steroid. The clinical significance of this finding may be interference with the binding of GH to its receptor resulting in a reduced IGF-I level and decreased height velocity. The mechanism warrants further study.

Body Height↗

Anti-obesity and anti-diabetic effects of carteolol in non-insulin-dependent diabetic mice.

1. When carteolol, a beta-adrenergic blocker, was administered to KK-Ay/Ta Jc1 mice that are obese and develop spontaneously non-insulin dependent diabetes, their increase in bodyweight was arrested from the age of 16 weeks. Since their intake of food and water was not influenced by carteolol treatment, compared with the control KK-Ay/Ta Jc1 mice, abolition of the weight gain might be attributed to increased energy metabolism. 2. Non-fasting serum glucose levels in carteolol-treated mice at the age of 17 weeks were within normal range (118 +/- 4 vs 186 +/- 12 mg/dL). An intraperitoneal glucose-tolerance test revealed that the carteolol treatment markedly restored glucose metabolism; fasting plasma glucose (88 +/- 6 mg/dL) was within normal range, and immunoreactive insulin (IRI; 5.8 +/- 0.8 vs 33.3 +/- 10.5 ng/mL) and plasma glucose levels at 60 min post glucose (361 +/- 44 vs 541 +/- 32 mg/dL) were significantly lower in carteolol-treated mice than those in the control group at the age of 20 weeks. 3. From these findings, carteolol is considered to have little effect on the growth of mice but to correct the obesity that develops after age 16 weeks, when their growth terminates. In addition, the normalization of blood glucose and marked decrease in IRI levels suggests that carteolol improves glucose tolerance by increasing the insulin sensitivity. 4. Since brown adipose tissue (BAT) is closely associated with thermogenesis and energy consumption, we tested whether carteolol may affect BAT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗

Two cases of insulin-dependent diabetes mellitus under insulin treatment with slow height velocity: relationship of growth hormone-binding protein, metabolic control and growth.

Inadequate blood sugar control in children with insulin-dependent diabetes mellitus (IDDM) sometimes results in low insulin-like growth factor-I (IGF-I) and sluggish height growth. High affinity growth hormone-binding protein (GHBP), which is identical to the extracellular domain of growth hormone (GH) receptor, is present in the human sera. We have determined GHBP activity in two cases of poorly controlled IDDM with low height velocity in relation to metabolic control in order to determine the mechanism of resistance to GH in this condition, as indicated by low levels of GH-dependent growth factor IGF-I in the face of high serum GH levels. GHBP activity was within the normal range in two cases of IDDM with slow height velocity, low IGF-I and high hemoglobin-A1. In both cases, improved blood sugar control normalized IGF-I to result in accelerated height velocity without a major change in GHBP levels. These results may indicate either normal peripheral GH receptor or normal free portion of serum GH, and may suggest that the major defect in slow growth in poorly controlled diabetes is due to the post GH receptor.

Body Height↗

Attainment of normal height in severe juvenile hypothyroidism.

Prolonged juvenile hypothyroidism results in a permanent loss in height that is related to the duration of thyroxine deficiency before adequate thyroxine replacement treatment. A 13 year old girl with severe juvenile hypothyroidism was studied prospectively. She had an undetectable serum thyroxine concentration, a height SD score of -6.6 SD, and a bone age of 5.8 years. The enlarged pituitary gland involuted with thyroxine treatment to produce an empty sella. In addition to thyroxine the girl was treated with a gonadotrophin releasing hormone agonist to avoid the progression of puberty for 18 months and with growth hormone to achieve normal adult height.

Adolescent↗

Mechanical stretch/relaxation of cultured rat mesangial cells induces protooncogenes and cyclooxygenase.

In cultured rat glomerular mesangial cells, continuous cycles of stretching and relaxation (stretch/relaxation) stimulate cell proliferation, protein synthesis, and prostaglandin production. We examined regulation of gene expression that may underlie these alterations in cell functions. Stretch/relaxation caused time-dependent induction of the immediate early genes, c-fos and zif 268/egr-1, with maximal increases occurring between 15 and 30 min. The mitogen-inducible prostaglandin G2/H2 synthase (PGH2S-2) gene was also induced within 30 min of stretch/relaxation, with concomitant increases in the immunoreactive PGH2S-2 protein. These gene inductions were preceded by transient translocation of protein kinase C activity from cytosol to membrane as well as by increases in 45Ca2+ uptake and total cellular calcium content. The stretch/relaxation-induced expression was suppressed by protein kinase C inhibition, whereas less profound inhibition was observed with inhibition of calcium influx in low (100 nM) calcium buffer. These findings indicate that in mesangial cells mechanical stress induces expression of the protooncogenes and the mitogen-inducible cyclooxygenase primarily through protein kinase C-dependent mechanisms.

Animals↗

Decrease in ventricular stroke volume at apnea termination is independent of oxygen desaturation.

Patients with obstructive sleep apnea experience nocturnal hemodynamic oscillations in association with repetitive respiratory events. Apnea termination (recovery) is accompanied by the nadir of arterial O2 saturation (SaO2), changes in intrathoracic pressure, and arousal from sleep. To investigate separately the contributions of hypoxemia and of arousal from sleep to changes in cardiac function, we continuously measured left ventricular stroke volume (LVSV) and mean arterial pressure (MAP) in eight subjects with severe obstructive sleep apnea (apnea-hypopnea index > 30 events/h associated with SaO2 < or = 82%) during two experimental conditions: 1) subjects slept without intervention for 1-2 h and then supplemental O2 was administered to maintain SaO2 > or = 90% (mean SaO2 nadir 92.7%) throughout the apnea-recovery cycle and 2) upper airway obstructions were abolished using nasal continuous positive airway pressure and subjects were aroused from sleep by an auditory signal. Recovery was associated with an increase in MAP and a decrease in LVSV both with and without supplemental O2. Arousal from sleep on nasal continuous positive airway pressure reproduced the postapneic elevation of MAP but not a decrease in cardiac function of the magnitude that occurred at apnea termination. We conclude that elevation of blood pressure and reduction of LVSV that occurred at apnea termination may be due to different physiological mechanisms.

Adult↗

Gm haplotypes in chronic inflammatory demyelinating polyradiculoneuropathy in Japanese patients.

We studied the serum Gm allotype of 58 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and 236 nonrelated normal controls in Japan. The incidences of the Gm phenotype and haplotype in the patients were not significantly different from those in the normal controls. When CIDP was classified into two subgroups in terms of clinical course, the chronic relapsing (CR) and chronic nonrelapsing type (CNR), the distribution of all Gm haplotypes was significantly different between CR and CNR (total chi 2 = 8.319; corrected p < 0.05). Our findings suggest that the clinical course of CIDP may be associated with the Gm haplotype.

Chronic Disease↗