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Biomedical subjects

Y Ichikawa

Publications and source records attributed to Y Ichikawa.

At least 307 records · Page 17Linked to original sources
PubMed1995

[Isotypes and subtypes of anti-SS-A and/or SS-B antibodies in different subgroups of Sjögren's syndrome].

Profiles of anti-SS-A/SS-B antibodies, including their isotypes and subtypes, in patients with primary Sjögren's syndrome (SS) were similar to those in SS patients with systemic lupus erythematosus (SLE), except for anti-SS-A52-Kd/60-Kd antibody profiles. The incidence and titers of these antibodies in SS patients with rheumatoid arthritis, however, were lower than those in primary SS or SS patients with SLE. It is suggested that IgA anti-SS-A/SS-B antibodies are produced in the salivary gland. In addition, IgG1 anti-SS-A antibodies were dominant in all groups of SS patients examined. The results indicate a preferential activation of Th2 helper T cells in SS.

Antibodies, Antinuclear↗
PubMed1995

[Clinical and pathological features of Sjögren's syndrome associated with autoimmune thyroid diseases].

Sjögren's syndrome (SS) is a chronic inflammatory disease of the exocrine glands accompanied by mononuclear cell infiltration. The histopathological features of the salivary and lacrimal glands of SS resemble those of the thyroid glands of autoimmune thyroiditis (chronic thyroiditis; CT). In addition, both SS and CT frequently recognized in the patients with other organ-specific or systemic autoimmune diseases (collagen-vascular diseases; CVD). We analyzed the incidences of CT among patients with SS or CVD, and compared clinical, immunological and endocrinological profiles between the SS patients with and those without CT. CT was the most frequent organ-specific auto-immune disease recognized in both primary and secondary SS patients. The thyroid disease similarly associated with CVD patients, regardless of the presence of SS. Several studies have also suggested that subclinical diseases are frequent in both CT and SS patients. The clinical and immunohematological features were almost identical between SS patients with and those without CT. Furthermore, the clinical, serological and endocrinological profiles of thyroid disease were very similar between SS patients with CT and CT patients without SS. These results indicate that CT and SS are independent autoimmune diseases, and the thyroid involvement observed in patients with primary or secondary SS is not an extraglandular manifestation of SS.

Chronic Disease↗
PubMed1995

[Microorganisms cultured from sputum and blood in association with episodes of fever during anti-cancer therapy in patients with lung cancer].

We examined the clinical features and significance of pathogenic microbes isolated from sputum and blood of patients with lung cancer during anti-cancer therapy. Pathogenic bacteria were more likely to be isolated from patients with episodes of fever than from afebrile patients. The major species of bacteria isolated from sputum were Staphylococcus aureus, including methicillin-resistant strains, and Gram-negative bacilli, which are known to be frequently involved in hospital-acquired infections. The presence of an indwelling central venous catheter for intravenous hyperalimentation was an important risk factor for the development of a febrile episode, which indicates that bacteremia was a major cause of fever. In one quarter of the blood cultures from the patients with persistent fever, various species of pathogenic microbes were recovered, one-third of which were fungi. Bacteriological examinations done before and after the introduction of granulocyte-colony stimulating factor (G-CSF) revealed that strains of Klebsiella spp. decreased and those of methicillin-resistant S. aureus increased. There was no firm evidence that G-CSF decreased the incidence of episodes of fever. However, remains G-CSF may a allow the dose intensity of anti-cancer agents to be increased, which would lead to severe leukocytopenia. However, more detailed investigation is needed to clarify the role of G-CSF against bacterial infection during anti-cancer therapy.

Aged↗
PubMed1995

[A case of systemic lupus erythematosus with various central and peripheral neurological disorders presenting with motor paralytic bladder as a major manifestation].

Myelopathy is a rare central nervous system manifestation in systemic lupus erythematosus (SLE). We present a case of SLE, who developed motor paralytic bladder and various other neurological abnormalities. A 29-year-old female with SLE was admitted to our hospital because of complete dysuria without any troubles on defecation. Accelerated hypertension had been noticed 2 weeks before the admission. Physical examinations revealed that she had muscle weakness in right brachial biceps, bilateral carpal extensor and flexor, and flexor muscles of bilateral lower extremities. Slight sensory disturbance was present on her soles. Bilateral Chaddok and Babinski's signs were positive. Electromyographic studies including nerve conduction velocities of her limbs were normal, however, neurogenic discharges were observed in anal sphincter muscles. Cystometry demonstrated atonic bladder, but any pathological findings such as lupus cystitis and interstitial cystitis were not observed in the biopsied specimens from her bladder. Antibodies to single-stranded DNA, U1 RNP, Sm and SS-A/Ro were positive in her serum, and lupus anticoagulant and anticardiolipin antibodies (IgG) were also detected. In her cerebral spinal fluid (CSF), elevated protein level and albuminocytologic dissociation were recognized, while glucose level was low. Magnetic resonance imaging (MRI) study detected high signal intensities in the inner part of medulla oblongata and in the spinal cord at second lumbar spine level. After two courses of methyl-prednisolone pulse therapy, the patient's neurological symptoms including dysuria had completely recovered and abnormal findings previously observed on MRI had also disappeared. After 7 months of the episode, she became normotensive. The proteins and glucose levels in her CSF had gradually returned to normal. Among patients with SLE, correlations of antiphospholipid antibodies with myelitis/myelopathy or accelerated hypertension have been reported. Therefore, possible roles of antiphospholipid antibodies were considered in the pathogenesis of neurologic abnormalities observed in our patient. In addition, low glucose level in CSF might be a good indicator for the diagnosis of lupus-associated myelopathy.

Adult↗
PubMed1995

[Systemic sclerosis with various gastrointestinal problems including pneumoperitoneum, pneumatosis cystoides intestinalis and malabsorption syndrome].

We describe here an experience of successful treatment of systemic sclerosis (SSc) complicated with various gastrointestinal (GI) problems including pneumoperitoneum, pneumatosis cystoides intestinalis and malabsorption syndrome. A 35-year-old female had developed selerodactyly since February, 1990. She had been treated under the diagnosis of SSc at other hospital. She had required several hospitalizations because of nausea, vomitting and abdominal distension, but her GI symptoms had gradually deteriorated. In April 1993, she was referred to our hospital and admitted for the treatment of her GI problems. On admission, she had systemic cutaneous sclerosis and marked abdominal distension without peritoneal signs was recognized. Chest and abdominal roentgenograms demonstrated massive free air under the diaphragm, marked dilation of small and large bowels, and multiple intestinal cysts (pneumatosis cystoides intestinalis ; PCI). We treated her GI problems with various modalities combined with medications, oxygen breathing, intravenous hyperalimentation and hyperbaric oxygen therapy. Pneumoperitoneum and PCI had disappeared after 8 courses of hyperbaric oxygen therapy and her GI symptoms had been well controled by intravenous hyper alimentation. Thereafter, she has been on intermittent parenteral nutrition through subcutaneous port inplantation. During the courses of this treatment, she developed an episode of Wernicke-Kolsakoff (W-K) syndrome which was considered to associate with malabsorption syndrome. The W-K syndrome had recovered by intravenous administration of vitamin B1.

Adult↗
PubMed1994

Two different enzymes are primarily responsible for retinoic acid synthesis in rabbit liver cytosol.

Retinoic acid biosynthesis in rabbit liver was catalyzed by cytosolic NAD(+)-dependent dehydrogenase and oxygen-dependent oxidase, with an activity ratio of 59% and 41% in the presence of 2 mM dithiothreitol under aerobic conditions. The two enzymes could be well separated by fractionation involving ammonium sulfate precipitation. Purification of the enzymes indicated that the oxygen-dependent enzyme was a flavoenzyme, retinal oxidase (EC 1.2.3.11), composed of two 135 kDa subunits; and the NAD(+)-dependent enzyme was a basic pI retinal dehydrogenase composed of four 55-kDa subunits. A high concentration (1-2 mM) of DTT was required to stabilize the activity of retinal dehydrogenase during the purification procedures and storage, but inhibited the activity of retinal oxidase by 13-38%. The physiological roles of the two retinoic acid synthases in liver cytosol were discussed.

Aerobiosis↗
PubMed1994

Purification and comparative characterization of cytochrome P-450scc (CYP XIA1) from sheep adrenocortical mitochondria.

Cytochrome P-450scc (CYP XI A1) was purified from sheep adrenocortical mitochondria. The purified cytochrome was found to be homogeneous on SDS-polyacrylamide gel electrophoresis and to have a heme content of 20.8 nmol/mg of protein. Its amino acid composition and NH2-terminal amino acid sequence were determined, and compared with those of other known mammalian and fish cytochromes P-450scc. EPR spectra of the cytochrome P-450scc were measured for oxidized and NO-reduced forms in the presence or absence of cholesterol and/or adreno-ferredoxin. Spectral properties of these various forms were very similar to those of the bovine enzyme. Circular dichroism spectra of the purified sheep cytochrome P-450scc in the oxidized and dithionite-reduced forms, and of their complexed forms with cholesterol or adreno-ferredoxin were analyzed in the region from 200 to 700 nm. The difference CD spectrum of the oxidized cytochrome P-450scc complexed with adreno-ferredoxin minus the oxidized form suggests an increase in the high-spin form upon the addition of adreno-ferredoxin. This may suggest a direct influence of the adreno-ferredoxin binding to the heme moiety of the oxidized cytochrome P-450scc.

Adrenal Cortex↗
PubMed1994

Characteristic properties and kinetic analysis with neurotoxins of porcine FAD-containing monooxygenase.

An FAD-containing monooxygenase (EC 1.14.13.8) was purified from porcine liver microsomes by a new purification procedure and confirmed to give an electrophoretically single protein band. The optical and CD spectra, fluorescence and molar extinction coefficients of the FMO were investigated. The activity of the FMO was examined kinetically with neurotoxins, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1,2,3,4-tetrahydroisoquinoline (TIQ), and 1-methyl-6,7-dihydroxytetrahydroisoquinoline (MDTIQ), as substrates. The kinetic parameters of the FMO for the neurotoxins, molecular oxygen and electron donors were determined, in comparison with those of dimethylaniline. The CD spectrum of the FMO was measured in the absence and presence of NADP+, dimethylaniline or both. The results showed that the FMO metabolized the neurotoxins, and that NADH was a weak electron donor for it. The CD spectrum of the FMO in the oxidized form, which acts as an oxidase and oxygenase, unlike that of D-amino-acid oxidase, showed negative ellipticity, the secondary structure of the FMO changed, and the alpha-helix structure of the monooxygenase was affected by the formation of a complex of the FMO with NADP+, DMA or both.

Amino Acids↗
PubMed1994

Kinetics, stoichiometry, and identification of the reactive thiolate in the inactivation of UDP-GlcNAc enolpyruvoyl transferase by the antibiotic fosfomycin.

Fosfomycin [(1R,2S)-1,2-epoxypropylphosphonic acid] has been shown to exert its antibiotic effect through the inhibition of UDP-GlcNAc enolpyruvoyl transferase [Kahan, F. M., et al. (1974) Ann. N.Y. Acad. Sci. 235, 364], the enzyme responsible for catalyzing the first committed step in bacterial cell wall biosynthesis. Time-dependent inactivation of MurZ by fosfomycin was found to be greatly accelerated by the presence of cosubstrate UDP-GlcNAc but could also be speeded appreciably by the unreactive substrate analog 3-deoxy-UDP-GlcNAc. These results argue against a reaction-based participation of the cosubstrate and suggest that UDP-GlcNAc has a role in influencing active site conformation critical to the inactivation event. A study of the influence of UDP-GlcNAc and fosfomycin on the kinetics of inactivation allowed the determination of dissociation constants for fosfomycin (KF = 8.6 microM) and UDP-GlcNAc (KS = 14 microM), in addition to a limiting inactivation rate constant (k(inact) = 7.4 min-1) at saturating UDP-GlcNAc and fosfomycin concentrations. Mass spectrometry of inactivated MurZ demonstrated an increase in molecular weight of 138, consistent with the covalent addition of a molar equivalent of fosfomycin (136 kDa). Titration of MurZ with fosfomycin revealed a stoichiometry of 1 molecule of inhibitor per active site when assessed using either enzyme activity or mass spectrometry as an index of modification. Peptide mapping of tryptic digests of fosfomycin-inactivated MurZ revealed modification of a unique 41-mer, the sequence of which revealed that Cys115 was the site of attachment of fosfomycin.

Alkyl and Aryl Transferases↗
PubMed1994

Interaction of NADPH-adrenoferredoxin reductase with NADP+ and adrenoferredoxin. Equilibrium and dynamic properties investigated by proton nuclear magnetic resonance.

NADPH-adrenoferredoxin reductase, a flavoprotein from bovine adrenocortical mitochondria, has been investigated to elucidate the equilibrium and dynamic properties of the interaction with NADP+ and adrenoferredoxin (adrenodoxin) using proton NMR spectroscopy. The line width of the signals from NADP+ depends on the presence of the reductase. The off rate constant of NADP+ from the reductase is estimated to be about 15-20 s-1 on the basis of line width measurements. No appreciable difference in off rate is detected between adenine and nicotinamide moieties of NADP+. Transferred nuclear Overhauser effect experiments for NADP+ indicate the time-dependent magnetization transfer profiles with a long lag phase. The proton NMR spectra during the titration of the reductase with adrenodoxin reveal that the reductase possesses distinct binding sites for both NADP+ and adrenodoxin. The sharp resonances in the aromatic region due to His-10 and His-62 of adrenodoxin were utilized as a probe to explore the interaction with the reductase. IN the mixture of adrenodoxin and the reductase at the mol ratio of 6:1, T1 values of the histidine residue in adrenodoxin were measured by the inversion recovery method. At low ionic strength, T1 values of the resonances are not affected in the presence or absence of the reductase. In the presence of the reductase, T1 values of resonances resulting from the histidine residues become shorter as the concentration of KCl increases because of rapid exchange between bound and free states. At low ionic strength (10 mM phosphate buffer), the off rate from the reductase is estimated to be less than about 4 s-1. The off rate of adrenodoxin from the reductase could be the rate-limiting step in cytochrome c reductase activity at low ionic strength.

Adrenal Cortex↗
PubMed1994

Characteristic properties of retinal oxidase (retinoic acid synthase) from rabbit hepatocytes.

Retinal oxidase (retinoic acid synthase) (EC 1.2.3.11) was purified electrophoretically, as a single protein band, from rabbit liver cytosol. The characteristic properties, enzymatic reaction mechanism, substrate specificity and kinetic parameters for retinals and molecular oxygen of the retinal oxidase were investigated. The Km values for all-trans-retinal of the retinal oxidase was the lowest than those for the other retinal derivatives. The retinal oxidase is a metalloflavoenzyme containing 2 FADs as the coenzyme, and 8 irons, 2 molybdenums, 2 disulfide bonds and 8 inorganic sulfurs. Its relative molecular mass was determined to be 270 kDa by gel filtration HPLC on a TSKgel G3000swXL column. Its minimum molecular mass was estimated to be 135 kDa by SDS-PAGE. The optical spectrum of the retinal oxidase showed absorption peaks at 275, 340 and 450 nm, and shoulders at 420 and 473 nm, in the oxidized form. The molecular extinction coefficients of the oxidase at selected wavelengths were determined. Circular dichroism spectra of the retinal oxidase were measured in the ultraviolet and visible regions. These spectra showed positive absorption in the visible region. The amino-acid composition was determined. The activity of the oxidase was not affected by any cofactors, such as NADP+, NAD+, NADPH and NADH, and it did not occur under anaerobic conditions. The oxidase was not inhibited by BOF-4272, a potent inhibitor of xanthine dehydrogenase, or rat anti-xanthine dehydrogenase IgG. Experiments on retinoic acid formation under 18O2 or H2(18)O demonstrated that the oxygen of water was incorporated into retinoic acid by the retinal oxidase, but not molecular oxygen.

Aldehyde Oxidoreductases↗
PubMed1994

Mutation of K-ras protooncogene is associated with histological subtypes in human mucinous ovarian tumors.

A series of 57 mucinous and 47 serous ovarian tumors (adenomas, tumors of borderline malignancy, and carcinomas) were examined by polymerase chain reaction-single strand conformation polymorphism analysis and direct sequencing for mutations in codons 12, 13, and 61 of K-ras gene. Higher incidence of K-ras mutations was observed in mucinous tumors compared to serous ones. Mutations were detected in 4 of 30 mucinous adenomas (13%), in 4 of 12 mucinous tumors of borderline malignancy (33%), and in 7 of 15 mucinous carcinomas (46%). Only 1 of 17 serous carcinomas (6%) had a mutation of K-ras in serous ovarian tumors. All mutations identified were in codon 12. Detailed analysis revealed that more K-ras mutations in mucinous adenomas were observed in intestinal type (identified in 4 of 13) than in endocervical type (identified in 0 of 17). Thus, K-ras gene codon 12 mutations in mucinous ovarian adenomas appear to be associated with the occurrence of intestinal type adenomas.

Adenocarcinoma, Mucinous↗
PubMed1994

Distorted microangioarchitecture and impaired angiogenesis in gastric mucosa of portal hypertensive rats.

BACKGROUND/AIMS: Portal hypertensive (PHT) gastropathy is now recognized as a distinct entity, but the size of microvessels has been a subject of controversy. Angiogenesis in PHT gastric mucosa has not been explored. The aim of this study was to examine the angioarchitecture of PHT and non-PHT gastric mucosae before and after ethanol-induced injury utilizing microvascular cast techniques. METHODS: Portal hypertension was produced by staged portal vein occlusion. Fourteen days later, gastric vascular casts were made in both PHT and control (sham-operated) rats by Mercox resin infusion. After tissue dissolution, casts were examined under a scanning electron microscope. To examine angiogenesis in injured gastric mucosa, the above study was repeated in PHT and control rats 18 hours after intragastric administration of 100% ethanol. RESULTS: The capillary casts in PHT gastric mucosa (mean diameter, 6.3 +/- 0.03 microns) were significantly narrower than those of controls (mean diameter, 8.6 +/- 0.02 microns; P < 0.01). After ethanol injury, 5.5% +/- 0.3% of microvessels in gastric mucosa of sham-operated rats contained buds, showing angiogenesis. In contrast, PHT gastric mucosa had a paucity of capillary angiogenesis (buds in only 0.4% +/- 0.2% of microvessels; P < 0.01 vs. control). CONCLUSIONS: This study shows prominent persistent abnormalities in the microangioarchitecture of PHT gastric mucosa. Moreover, PHT gastric mucosal microvessels have a marked impairment of angiogenic response to ethanol injury.

Animals↗