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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

At least 505 records · Page 28Linked to original sources

Interactions between novel tumor necrosis factor-alpha mutants and receptors on tumor and normal cells.

We prepared several TNF mutants by protein engineering techniques and compared their biological properties with those of the wild-type TNF. The mutant that lacked 7 N-terminal amino acids had higher cytotoxicity and higher binding activity to receptors on tumor cells. In contrast, the mutagenesis of Arg32 or Ala84, in combination with the deletion of 7 N-terminal amino acids, eliminated the cytotoxicity and the receptor binding. These mutants also lacked acute lethal toxicity in normal mice. Therefore, we concluded that the N-terminus, Arg32 and Ala84 of TNF might be concerned with binding to the TNF receptor. It was also suggested that the receptor molecules on tumor cells bound to the same or neighboring sites on TNF molecules as normal cell receptors.

Animals↗

Sjögren's syndrome and pregnancy.

We analyzed 117 histories of pregnancy obtained from 40 female patients with Sjögren's syndrome (SS) including 13 patients with primary SS and 27 patients with secondary SS. The frequency of spontaneous abortions did not differ in the 40 patients and those with primary SS compared with 129 healthy women. However, both spontaneous abortions and premature deliveries were significantly more frequent in the SS patients with systemic lupus erythematosus (SLE). Anti-SS-A and anti-SS-B antibodies were not associated with the outcomes of pregnancy although spontaneous abortions were more frequent in secondary SS patients with false positive serological tests for syphilis, anti-erythrocyte antibodies, thrombocytopenia or prolonged activated partial thromboplastin time. Neither congenital anomalies nor connective tissue disease was found in the 77 neonates of the patients. We concluded that SS does not influence the outcome of pregnancy except in patients with SLE or those with serological and hematological abnormalities related to lupus anticoagulants or antiphospholipid antibodies.

Abortion, Spontaneous↗

The effect of lipo-prostaglandin E1 on the production of interleukin 1 and platelet-activating factor by hepatic sinusoidal endothelial cells in mice.

We first studied the production of interleukin 1 (IL1) and platelet-activating factor (PAF) by mouse hepatic sinusoidal endothelial cells and then the effect of Lipo-prostaglandin E1 (Lipo-PGE1) on IL1 and PAF production by these cells. The incubation of mouse hepatic sinusoidal endothelial cells with lipopolysaccharide (LPS) or calcium-ionophore (CaI) A23187 resulted in a concentration-dependent production of IL1 and PAF. However, Lipo-PGE1 dose-dependently decreased the LPS- or CaI A23187-induced production of IL1 and PAF. These results suggested that Lipo-PGE1 acts on hepatic sinusoidal endothelial cells to decrease the production of IL1 and PAF, thereby ameliorating inflammatory reactions in the liver.

Alprostadil↗

Effect of sho-saiko-to (TJ-9, Japanese herbal medicine) on estradiol receptors in the cytosol of hepatic sinusoidal endothelial cells.

We first confirmed the presence of estradiol receptors in the cytosol of rat hepatic sinusoidal endothelial cells and then studied the effects of Sho-saiko-to (TJ-9) on the level of these cytosol estradiol receptors. As a result, we found that estradiol receptors are present in the cytosol of hepatic sinusoidal endothelial cells from rats. Moreover, when these cells were incubated with TJ-9, the level of cytosol estradiol receptors increased. These results suggested that TJ-9 acts on hepatic sinusoidal endothelial cells to increase the level of estradiol receptors, thereby affecting the immune reactions in the liver.

Animals↗

"Yellow nail syndrome" and rheumatoid arthritis.

A nail dystrophy characterized by the slow growth of nails and their yellowish discoloration, the so-called yellow nail syndrome (YNS), has been associated with various conditions including rheumatoid arthritis (RA). We reviewed the histories of RA patients reported in the literature and our own cases. Most of the RA patients with YNS had been treated with the anti-rheumatic agents D-penicillamine and bucillamine. In non-treated patients, spontaneous YNS was very rare. However, pulmonary diseases, edema and other systemic complications were frequently observed in both drug-induced and spontaneous YNS associated with RA. Although the nail changes and systemic complications are probably due to different causes in drug-induced YNS, a careful search for systemic complications are necessary in patients who develop nail changes. The exact mechanism of nail growth retardation is not understood in patients with YNS, including those with drug-induced YNS. The nail changes in the latter were not associated with deficiencies of inorganic elements in either nails or sera.

Anti-Inflammatory Agents, Non-Steroidal↗

Genetic factors and metastatic potential of prostatic cancer.

When a non-metastatic subline from the Dunning rat prostatic cancer was transfected with the v-Ha-ras oncogene, some transfectants acquired metastatic potential. Molecular analysis demonstrated that there was no simple dose-response relationship between v-Ha-ras expression and metastatic potential in this prostatic cancer system. Cytogenetic analysis on the same system demonstrated increased genetic instability following v-Ha-ras transfection. Progression of prostatic cancer from no metastatic to high metastatic potential may involve the loss of a metastasis suppressor gene. To test this possibility, non-metastatic and highly metastatic Dunning rat prostatic cancer cells were fused. Hybrid clones were isolated that conserved the chromosomes from their parental cells. When these hybrids were injected into animals, none developed distant metastases. When the non-metastatic primary tumours were passaged in vivo, distant metastases developed in occasional animals. Cytogenetic analysis of eight of these metastatic revertants demonstrated a consistent loss of normal chromosome 2. These studies show that metastasis is associated with the loss of a specific chromosome. These studies also suggest that a metastasis suppressor gene for rat prostatic cancer is located on chromosome 2. A more direct approach to identify a chromosome(s) carrying metastasis suppressor gene(s) by using microcell mediated chromosome transfer is currently progressing.

Adenocarcinoma↗

Glucocorticoid receptors in normal leukocytes: effects of age, gender, season, and plasma cortisol concentrations.

We measured glucocorticoid receptors (GR) in mononuclear leukocytes (MNL) isolated from peripheral blood of 145 apparently healthy volunteers (86 men and 59 women). An age-related decrease in the number of GR was suggested between subjects younger than 20 years and elderly subjects; there was no apparent seasonal variation in GR. Gender difference in the number of GR was not significant, although women showed slightly fewer GR. Eight patients with dermatomyositis/polymyositis were examined to determine whether the number of GR in MNL could be down-regulated by their cognate ligands. The number of GR in MNL from these patients was significantly decreased one month after the initiation of prednisolone therapy. However, in normal subjects, the GR in MNL did not demonstrate circadian variation, in contrast to concentrations of plasma cortisol.

Adult↗

[Active bronchial tuberculosis--a clinical study on 36 cases].

A total of 36 patients (16 male and 20 female) with tracheobronchial tuberculosis were admitted during the last nine years and were evaluated for their clinical features. The chief complaint in three quarters of the patients was intractable cough, in particular, in those with tracheal tuberculosis. One of three patients who suffered from wheezing was prescribed steroid, being diagnosed as having bronchial asthma instead of tuberculosis. Plain chest X-rays of two patients revealed no abnormality. Pleural effusion was observed in three patients, and miliary tuberculosis in two patients. Bronchial biopsy was carried out in 23 patients, however, in only 11 patients a histopathological diagnosis of tracheobronchial tuberculosis could be made. In contrast, in all 36 patients smear and/or culture for tubercle bacilli were positive. Therefore, bronchial biopsy was considered not to be essential in making a definite diagnosis of bronchial tuberculosis, although it did not exacerbate the lesion to lead to endobronchial stenosis. Only seven out of 36 patients were in the habit of smoking but three of the four had already broken the habit at least one year before being diagnosed as having the disease. The remaining four patients were still smoking but less than 10 cigarettes a day, with one exceptional patient who was smoking 30 cigarettes on average a day. It has been well known that there is a sexual difference in the incidence of bronchial tuberculosis, namely among females with relatively low population of smokers, the incidence is high. Another probable reason for the higher female incidence is assumed to be due to the structural susceptibility of the bronchus with smaller diameter lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Three cases of localized pleural tuberculosis which looked exacerbated during antituberculous chemotherapy].

We reported three cases whose pleural tumorous shadows enlarged during the intensive chemotherapy for tuberculosis. The patients were 39 year-old female, 63 year-old female, and 22 year-old male. Their chest X-ray films on admission showed pleural effusion or infiltration, but no tumorous shadows. Eight to 16 weeks after starting the antituberculous therapy with INH, RFP and SM, new tumorous shadows appeared in the right chest wall (case 1, 3) or the left chest wall (case 2). The mass extracted from case 1 contained granuloma with caseous necrosis. The tumorous shadows on chest X-ray films in case 2 and 3 disappeared by continuous antituberculous therapy. We can not definitely conclude that the disease of these 3 cases were same diseases to be called either percostal tuberculosis, peripleural abscess or peripleuritis tuberculosa as observed in case 1. The phenomenon observed in case 2 and 3 is suspected to be caused by some allergic mechanism eg. Jarisch-Herxheimer reaction which is observed during the therapy for syphilis.

Adult↗

[Clinical evaluation of sultamicillin in lower respiratory tract infections].

Clinical efficacy and safety of sultamicillin (SBTPC) in patients with lower respiratory tract infections, mainly pneumonia and bronchitis, have been evaluated in a multicenter trial by 19 institutions in the Kyushu area during a period of 12 months from December 1988 to November 1989. 1. Clinical evaluation was made in 132 patients and efficacy rates of SBTPC were 80.0% (28/35) for pneumonia, 78.5% (73/93) for bronchitis and 100% for the remaining 1 patient with other respiratory tract infections. The overall efficacy rate was 79.1% (102/129). 2. Clinical efficacy rate of SBTPC for respiratory tract infections in patients with underlying diseases such as chronic bronchitis, old pulmonary tuberculosis etc., was 75.0% (60/80) which was not significantly different from the efficacy rate of 85.7% (42/49) in patients without underlying diseases. 3. Of 13 patients who failed to respond to previous antibiotic treatments, 8 (61.5%) were effectively treated with SBTPC. 4. Clinical efficacy rates against infections caused by single species of organisms were 90.9% (10/11) for Haemophilus influenzae, 100% (8/8) for Streptococcus viridans and 100% (3/3) for Staphylococcus aureus. The overall clinical efficacy rate in all cases of monomicrobial infections was 88.6% (31/35), in polymicrobial infection 45.5% (5/11) and the overall efficacy rate in cases in which causative bacteria were identified was 78.3% (35/46). 5. Adverse reactions occurred in 6.8% (9/132) of the patients. The symptoms included allergic reaction in 1 patient, gastrointestinal system disorders in 7 patients and general fatigability in 1 patient. As abnormalities in laboratory test values, elevations of A1-P, GOT, and GPT were observed in 3 patients during the study, but returned to normal after discontinuation of SBTPC administration. 6. SBTPC is a useful antibiotic in the treatment of lower respiratory tract infections under the current medical environment where resistant organisms which produce beta-lactamases have been increasing.

Adolescent↗

[Blood coagulation and fibrinolysis in patients with Behçet's disease].

In patients with Behçet's disease, venous thrombosis has often been described as a complication. The pathogenesis of this complication, however, has not been fully understood. In this work, various parameters of blood coagulation and fibrinolysis were studied in 20 patients with Behçet's disease and 13 sex-matched healthy volunteers. Patients were classified into three subgroups according to the number of clinical signs involved; group I (no sign): 4 patients; group II (one or two signs): 11 patients; group III (more than three signs): 5 patients. Patients with Behçet's disease, showed an activation of blood coagulation, such as the shortening of prothrombin time (p less than 0.001), decreases in concentrations and activities of plasma antithrombin III (AT-III) (p less than 0.01) and elevated levels of plasma thrombin-antithrombin-III complex (TAT) (p less than 0.01), compared to the control group. Plasma levels (p less than 0.01) and activities (p less than 0.01) of protein C (PC) and total protein S (PS) levels (p less than 0.05) were increased in the patients. Decreased levels of alpha 2-plasmin inhibitor (p less than 0.001) also indicated an activation of fibrinolysis in the patients. When analyzed among the subgroups, patients belong to group II and III showed higher levels of plasma FDP D-dimer (p less than 0.05) and lower levels of plasminogen (p less than 0.05), as compared with patients in group I or control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism.

A cDNA clone encoding human aldosterone synthase cytochrome P-450 (P-450aldo) has been isolated from a cDNA library derived from human adrenal tumor of a patient suffering from primary aldosteronism. The insert of the clone contains an open reading frame encoding a protein of 503 amino acid residues together with a 3 bp 5'-untranslated region and a 1424 bp 3'-untranslated region to which a poly(A) tract is attached. The nucleotide sequence of P-450aldo cDNA is 93% identical to that of P-450(11) beta cDNA. Catalytic functions of these two P-450s expressed in COS-7 cells are very similar in that both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate. However, they are distinctly different from each other in that P-450aldo preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone while P-450(11)beta substantially fails to catalyze the reaction to form aldosterone. These results suggest that P-450aldo is a variant of P-450(11)beta, but this enzyme is a different gene product possibly playing a major role in the synthesis of aldosterone at least in a patient suffering from primary aldosteronism.

Amino Acid Sequence↗

Active site of bovine adrenocortical cytochrome P-450(11) beta studied by resonance Raman and electron paramagnetic resonance spectroscopies: distinction from cytochrome P-450scc.

Cytochrome P-45011 beta was purified as the 11-deoxycorticosterone-bound form from bovine adrenocortical mitochondria and its active site was investigated by resonance Raman and EPR spectroscopies. Resonance Raman spectra of the purified sample revealed that the heme iron adopts the pure pentacoordinated ferric high-spin state on the basis of the nu 10 (1629cm-1) and nu 3 (1490 cm-1) mode frequencies, which are higher than those of the hexacoordinated ferric high-spin cytochrome P-450scc-substrate complexes. In the ferrous-CO state, a Fe2(+)-CO stretching mode was identified at 481.5 cm-1 on the basis of an isotopic substitution technique; this frequency is very close to that of cytochrome P-450scc in the cholesterol-complexed state (483 cm-1). The EPR spectra of the purified sample at 4.2 K showed ferric high-spin signals (at g = 7.98, 3.65, and 1.71) that were clearly distinct from the cytochrome P-450scc ferric high-spin signals (g = 8.06, 3.55, and 1.68) and confirmed previous assignments of ferric high-spin signals in adrenocortical mitochondria. The EPR spectra of the nitric oxide (NO) complex of ferrous cytochrome P-45011 beta showed EPR signals with rhombic symmetry (gx = 2.068, gz = 2.001, and gy = 1.961) very similar to those of the ferrous cytochrome P-450scc-NO complex in the presence of 22(S)-hydroxycholesterol and 20(R),22-(R)-dihydroxycholesterol at 77 K.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

Studies of the immunohistochemical and biochemical localization of the cytochrome P-450scc-linked monooxygenase system in the adult rat brain.

Immunohistochemical and biochemical studies were performed on the brains of adult female and male rats using a specific antibody against bovine adrenocortical cytochrome P-450scc. The results showed that in both male and female rats, the myelinated regions of the white matter are selectively immunostained throughout the brain and that even in rats pretreated with colchicine, there is never positive staining of neuronal cell bodies and their dendrites in any brain region. Western immunoblotting with the P-450scc antibody and enzymatic assays revealed that P-450scc and cholesterol side-chain cleavage activity were present in a homogenate derived from the cortical white matter, but not detectable in that from the cerebral cortex. Furthermore, quantitation of the P-450scc protein in the immunoblots indicated that the concentration of P-450scc in the cortical white matter of both female and male rat brains is approx. 3-4 pmol per mg tissue protein. Thus it could be concluded that in the adult rat brain, P-450scc and cholesterol side-chain cleavage activity are selectively localized only in the myelinated region of the white matter.

Adrenal Cortex↗

Binding characteristics of galactoside-binding lectin (galaptin) from human spleen.

Binding characteristics of human spleen soluble galactoside-binding protein (galaptin) were studied using simple galactosides, galactose-terminated disaccharides, cluster glycosides containing up to 6 terminal lactosyl residues, bovine serum albumin derivatives containing 7 to 40 lactosyl residues, desialylated serum glycoproteins, and glycopeptides derived thereof as inhibitors in a newly developed binding assay. In this assay, aminohexyl lactoside was attached to divinyl sulfone-activated Sepharose, which was then used to bind 125I-galaptin. Similarly derivatized Sepharose containing mannoside served as a control. The assay is sensitive, maintains linearity in the concentration range of 125I-galaptin tested, and has very low nonspecific binding. The following new findings were made. 1) All the alpha-D-galactopyranosides with non-sugar aglycon were better inhibitors than the corresponding beta-D-galactopyranoside. 2) The S-galactosides were better inhibitors than the corresponding O-galactosides, regardless of the anomeric configuration. 3) Many Gal beta 1-4- and Gal beta 1-3-linked disaccharides were tested. Although the galaptin did not appear to recognize N-acetylglucosamine as a monosaccharide, the presence of this sugar penultimate to galactose increased the binding affinity by as much as 500-fold, as was the case for N-acetyllactosamine. Of a particular importance is the presence of an equatorial 3-OH group on this sugar. We synthesized the 3-deoxy derivative of N-acetyllactosamine and found that it had 50-fold lower binding affinity compared to N-acetyllactosamine. 4) The binding sites of this lectin do not seem to be operating in a cooperative fashion, since synthetic lactose-containing divalent ligands with various inter-galactose distances did not increase the binding affinity significantly.

Binding Sites↗