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Biomedical subjects

M Fujimoto

Publications and source records attributed to M Fujimoto.

At least 109 records · Page 6Linked to original sources
PubMed2000

Plasma endotoxin and serum cytokine levels in patients with alcoholic hepatitis: relation to severity of liver disturbance.

BACKGROUND: Endotoxin plays an important role in the initiation and aggravation of alcoholic liver disease. In this study, we evaluated plasma endotoxin levels and serum concentrations of cytokines and lipopolysaccharide binding protein (LBP) during the acute and recovery phase of patients with alcoholic hepatitis; we also explored the prognostic factors associated with a fatal outcome. METHODS: Fourteen patients, consisting of eight patients with alcoholic hepatitis (AH), five cirrhotics with superimposed AH (LC+AH), and one patient with severe alcoholic hepatitis (SAH), were studied. Among these, two with LC+AH died of hepatic failure. RESULTS: Plasma endotoxin levels in the acute phase were higher in patients with AH (184.4 +/- 159.4 pg/ml) and LC+AH (206.9 +/- 174.9 pg/ml) than in healthy subjects (10.4 +/- 5.5 pg/ml, p < 0.001). In particular, in one patient with SAH and one of two nonsurvivors, plasma endotoxin levels were markedly high relative to the other cases. In most survivors, plasma endotoxin levels decreased in the recovery phase, whereas they further increased at the terminal stage in one of two nonsurvivors. Serum interleukin (IL)-6 and IL-8 levels in the acute phase were significantly higher in patients with AH and LC+AH as compared with healthy subjects. These levels were especially high in nonsurvivors and in one patient with SAH. IL-10 increased in two nonsurvivors, one patient with SAH, and one with LC+AH. In the recovery phase, these cytokine levels in survivors tended to decrease, but in nonsurvivors, IL-6 remained high, and IL-8 and IL-10 further increased. Tumor necrosis factor-alpha levels were below the detection limit throughout the course in all patients. Serum lipopolysaccharide binding protein (LBP) generally was elevated in the acute phase and decreased in the recovery phase in all survivors, but in one of the nonsurvivors, LBP was elevated markedly at the terminal stage. In the acute phase, plasma endotoxin levels were correlated positively with white blood cell counts, neutrophil counts, and serum IL-8. IL-8 was correlated positively with neutrophil counts and negatively with serum cholinesterase, hepaplastin test, and serum albumin levels. IL-6 was correlated positively with white blood cell and neutrophil counts, C-reactive protein, and serum total bilirubin and negatively with hepaplastin test and serum total protein levels. Serum LBP was correlated positively with white blood cell and neutrophil counts. CONCLUSIONS: Endotoxemia and related elevation of IL-8 may play an important role in the activation and migration of neutrophils in patients with alcoholic hepatitis. Marked elevation of inflammatory cytokines, IL-6 and IL-8, are related to severity and poor prognosis of alcoholic hepatitis. Serum LBP may serve as an index of inflammatory reaction in alcoholics.

Acute-Phase Proteins↗
PubMed2000

Adult T-cell leukemia successfully treated with allogeneic bone marrow transplantation.

Adult T-cell leukemia (ATL) is associated with human T-cell leukemia virus type 1 (HTLV-1) and is known to be a refractory disease of highly poor prognosis. We describe a case of ATL treated with allogeneic bone marrow transplantation (allo-BMT). The allo-BMT successfully induced complete remission in the patient. Currently, at 24 months post BMT, there has been no evidence of minimal residual disease (MRD) detected by polymerase chain reaction (PCR) assay for the T-cell receptor gamma chain gene. By contrast, PCR analysis demonstrated the reappearance of the cells harboring the integrations of the HTLV-1 proviral DNA 9 months after the BMT. These findings may imply a reversion to the carrier state rather than the recurrence of the leukemia from the MRD. The clinical consequence of our case illustrates that allo-BMT is an effective therapy, at least for achieving longer disease-free survival in ATL.

Bone Marrow Transplantation↗
PubMed2000

[Adenomatoid tumor of the tunica albuginea: a case report].

A case of male adenomatoid tumor of tunica albuginea of the testis is reported. A 45-year-old man referred to our hospital because of intrascrotal mass on the right side. The mass increased in size for eight months. Then we excised the tumor, and spared the right testis. The tumor was arising from the tunica albuginea of the testis with a pedicle. The histological diagnosis was adenomatoid tumor. Adenomatoid tumor is a rare benign tumor. A total of 97 cases of adenomatoid tumor of epididymis have been reported in males, but only 23 cases of adenomatoid tumor of the testis have been reported in Japan. Herein, 24 cases of adenomatoid tumor of testis including our case are discussed and reviewed.

Adenomatoid Tumor↗
PubMed2000

[Antithymocyte globulin treatment in 11 patients with aplastic anemia].

We report the response to, and toxicity of antithymocyte globulin (ATG) treatment in 11 consecutive patients (7 men and 4 women; median age 46 years) with aplastic anemia (AA). Six of the patients had severe disease and 5 had moderate disease; all were treated within one year from diagnosis. The ATG regimen was the initial treatment for 6 patients, but a sequential treatment for the other 5. Cyclosporin A was administered orally 1-3 weeks after the ATG treatment. All patients were assessed for over 6 months (median, 20.4 months); 8 showed a good response, 1 a minimal response, and 2 no response. Disease severity had no influence on the response. In 1 patient, ATG treatment had to be discontinued because of hepatic toxicity. However, adverse reactions were not severe in the other 10 patients. These findings suggest that ATG treatment is a safe and effective therapy for AA.

Adult↗
PubMed2000

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between April 1997 and March 1998].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in 19 facilities in Japan since July 1982. This paper describes the results obtained during the period from April 1997 to March 1998. The number of cases investigated as objectives was 215 for one year. A total of 420 strains (170 strains from primary infections and 250 strains from postoperative infections) were isolated from 174 cases (80.9% of total cases). In primary infections, the isolation rate of anaerobic bacteria was higher than in postoperative infections, while in postoperative infections, those of aerobic Gram-positive bacteria and Pseudomonas aeruginosa were higher than in primary infections. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was the highest, followed by Staphylococcus aureus, which was frequently isolated from postoperative infections. Among anaerobic Gram-positive bacteria, Peptostreptococcus spp. and Streptococcus spp. were commonly isolated from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was most predominantly isolated from primary infections, followed by P. aeruginosa, Klebsiella pneumoniae in this order, and from postoperative infections, P. aeruginosa was most predominantly isolated, followed by E. coli and K. pneumoniae. Among anaerobic Gram-negative bacteria, Bacteroides fragilis group was the majority of isolates from both types of infections. We found neither vancomycin nor arbekacin resistant strains of S. aureus, and found no vancomycin resistant strains of Enterococcus spp. The susceptibility of P. aeruginosa against carbapenems did not decline in the year 1997, while resistance of B. fragilis group against cephems advanced increasingly.

Anti-Bacterial Agents↗
PubMed2000

[Rapid development of multiple meniscal signs complicating invasive pulmonary aspergillosis in a patient receiving chemotherapy for acute leukemia].

This report describes the rapid development of multiple meniscal signs complicating invasive pulmonary aspergillosis in a 53-year-old man receiving chemotherapy for acute leukemia. While undergoing first induction therapy for AML, he developed chest pain, and multiple bilateral infiltrations were seen in chest roentgenograms. Administration of antibiotics, antifungal agents, steroid pulse therapy and G-CSF was begun. Pulmonary cavities with meniscal signs developed. The next day, pneumothorax and hemothorax were noted. Although drainage and mechanical ventilation were performed, the patient died after massive hemoptysis. Invasive pulmonary aspergillosis was diagnosed at autopsy.

Aspergillosis↗
PubMed2000

[A case of mortor neuron syndrome with onset 9 months after electrical injury].

A 72-year-old man noticed progressive weakness of both upper limbs, more severe on the left side, 9 months after an electric shock of a 20,000 V alternating current. He had diffuse scars of superficial burns with skin graft in four limbs, more on the right side. A neurological examination revealed diffuse muscle atrophy, weakness and fasciculation in both upper limbs, predominantly on the left side, hyper-reflexia in four limbs with mildly exaggerated jaw jerk, left Babinski sign, and mild decrease of touch and pain sensation in the right C6 and C7 segments. Painful dysesthesia was present in the left hand and right lower limb. The search for serum antibodies against GM1, GM2, GM3, GD1a, Gd1b, GQ1b, GA1, and GT1b was negative. No abnormality except mild cervical spondylotic changes was evident in the magnetic resonance imaging of the brain and spinal cord. The upper limb motor evoked potentials (MEPs) were not elicited by the left cortical stimulation and the central motor conduction time by the right cortical stimulation was remarkably prolonged in the upper limb MEPs. Nerve conduction study showed a delay of motor conduction velocity and distal latency in the right median and bilateral ulnar nerves with low amplitude and delayed velocity of sensory nerves of those nerves. Needle EMG revealed diffuse ongoing denervation potentials in bilateral upper limbs and giant motor unit potentials in the right triceps and first dorsal interossei muscles. These findings indicate that the delayed motor neuron syndrome induced by electrical shock is characteristic for having demyelination as well as axonal changes in both central and peripheral nervous systems.

Aged↗
PubMed1999

Isolation and characterization of Cox17p from porcine heart by determining its survival-promoting activity in NIH3T3 cells.

We have found that the gel filtration fraction of porcine heart extract clearly promoted the survival of NIH3T3 fibroblast cells in the serum-free medium condition. A structural analysis showed that the active fraction contained a novel peptide, porcine Cox17p (p-Cox17p), which was recently reported by Chen et al. as dopuin (Z. W. Chen et al., Eur. J. Biochem. 249 (1997) 518-522). Porcine Cox17p/dopuin possesses high sequence homology to the product of human COX17 gene (h-Cox17p). Although Cox17p has been implied to be involved in copper recruitment to mitochondria and in the functional assembly of cytochrome oxidase in yeast, its role in mammalian cells is unknown. In this study, we chemically synthesized p-Cox17p to investigate its biological effects. Refolding experiments of synthesized linear p-Cox17p revealed the existence of mostly one pattern of three intrachain disulfide bridges similar to that of native p-Cox17p, because the main oxidized p-Cox17p was completely co-eluted with the natural product. The addition of heavy metal ions such as copper, zinc and cadmium significantly inhibited the formation of the oxidized form, suggesting that reduced p-Cox17p may interact directly with these metal ions. The reduced and oxidized forms of p-Cox17p were also confirmed to promote the survival of NIH3T3 cells in serum-free medium as observed with the natural product, indicating that Cox17p may be a bioactive peptide.

3T3 Cells↗
PubMed1999

Different roles of two types of endothelin receptors in partial ablation-induced chronic renal failure in rats.

Recent work has drawn attention to endothelin as a likely contributor to renal pathogenesis. To elucidate the mechanism of progressive renal disease, we investigated the mRNA expression of endothelin and endothelin receptors, and the effect of endothelin ET(A), and/or ET(B) receptor antagonists on disease progression in the remnant kidney model. Proteinuria progressively increased in rats subjected to 5/6 nephrectomy (Nx) after 8 weeks (from 25+/-3 to 221+/-28 microg min(-1) kg(-1)). Creatinine clearance (Ccr) after renal ablation gradually decreased by 8 weeks (from 5.04+/-0.42 to 2. 68+/-0.26 ml min(-1) kg(-1)). Together with maximal proteinuria and decreased renal function, there was an increase in cortical mRNA expression of prepro endothelin-1 and endothelin ET(A) receptor expression, but a decrease in endothelin ET(B) receptor expression and in urinary excretion of endothelin-1. Administration (1-3 mg/day) of S-0139, (+)-disodium 27-[(E)-3-[2-[(E)-3-carboxylatoacryloylamino]-5-hydroxyphenyl]a crylay loxy]-3-oxoolean-12-en-28-oate, an endothelin ET(A) receptor-specific antagonist, had a beneficial effect on the evolution of the disease, preventing the appearance of intense proteinuria (113+/-11) and decreased Ccr (3.97+/-0.33). High blood pressure was observed in rats with 5/6 Nx and was decreased by S-0139 administration. To examine whether treatment modalities that decrease endothelin ET(B) receptor signaling have a deleterious effect on the kidney remnant, the effect of 97-618, an endothelin ET(B) receptor-specific antagonist, 4-tert-butyl-N-[5-(2-methoxyphenoxy)-6-(4-oxobutoxy)pyromidine+ ++-4-yl]b enzenesulfonamide, was also examined on the action of S-0139. Concomitant administration of S-0139 and 97-618 reversed the beneficial effect of S-0139 alone in the remnant kidney on proteinuria and renal functional impairment. These findings indicate that endothelin participates in the pathogenesis of proteinuria and glomerular injury and that an endothelin ET(A) receptor-specific antagonist could be useful in the treatment of some forms of human nephritis. The loss of endothelin ET(B) receptor seems to be important in the progression of renal disease.

Animals↗
PubMed1999

1,3-Disubstituted benzazepines as novel, potent, selective neuropeptide Y Y1 receptor antagonists.

A novel series of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Chemical modification of the R(1) and R(3) substituents in structure 1 (Chart 1) yields several compounds that show high affinity for the Y1 receptor (K(i) values of less than 10 nM). SAR studies revealed that introduction of an isopropylurea group at R(1) and a 3-(benzo-condensed-urea) group, 3-(fluorophenylurea) group, or a 3-(N-(4-hydroxyphenyl)guanidine) group at R(3) in structure 1 afforded potent and subtype-selective NPY Y1 receptor antagonists. 3-(3-(Benzothiazol-6-yl)ureido)-1-N-(3-(N'-(3-isopropylureido++ +))benzyl )-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (21), which was one of the most potent derivatives, competitively inhibited specific [(125)I]peptide YY (PYY) binding to Y1 receptors in human neuroblastoma SK-N-MC cells (K(i) = 5.1 nM). 21 not only inhibited the Y1 receptor-mediated increase in cytosolic free Ca(2+) concentration in SK-N-MC cells but also antagonized the Y1 receptor-mediated inhibitory effect of peptide YY on gastrin-induced histamine release in rat enterochromaffin-like cells. 21 showed no significant affinity in 17 receptor binding assays including Y2, Y4, and Y5 receptors.

Animals↗
PubMed1999

Nucleic acid duplex stability: influence of base composition on cation effects.

The effects of counter ion on a nucleic acid duplex stability were investigated. Since a linear free energy relationship for the thermostability of oligonucleotide duplexes between those in 1 M and in 100 mM NaCl-phosphate buffer were observed regardless of whether they are DNA-DNA, RNA-RNA or RNA-DNA duplexes, simple prediction systems for [Delta] G degrees 37as well as T mvalues in 100 mM NaCl-phosphate buffer were established. These predictions were successful with an average error of only 2.4 degrees C for T mand 5. 7% for G degrees 37values. The number of Na+newly bound to a duplex when the duplex forms (-[Delta] n) was significantly influenced by the base composition, and -[Delta] n for d(GCCAGTTAA)/d(TTAACTGGC) was different for MgCl2, CaCl2, BaCl2and MnCl2(from 0.70 to 0.76 with the same order of the duplex stability). Almost no additive effects on the duplex stability was observed for NaCl and MgCl2, suggesting a competitive binding for these cations. The sequence-dependent manner of [Delta] n suggests the presence of preferential base pairs or nearest-neighbor base pairs for the cation binding, which would affect nearest-neighbor parameters.

Base Composition↗
PubMed1999

CD19 amplifies B lymphocyte signal transduction by regulating Src-family protein tyrosine kinase activation.

Ligation of the B cell Ag receptor (BCR) induces cellular activation by stimulating Src-family protein tyrosine kinases (PTKs) to phosphorylate members of the BCR complex. Subsequently, Src-family PTKs, particularly Lyn, are proposed to phosphorylate and bind CD19, a cell-surface costimulatory molecule that regulates mature B cell activation. Herein, we show that B cells from CD19-deficient mice have diminished Lyn kinase activity and BCR phosphorylation following BCR ligation. Tyrosine phosphorylation of other Src-family PTKs was also decreased in CD19-deficient B cells. In wild-type B cells, CD19 was constitutively complexed with Vav, Lyn, and other Src-family PTKs, with CD19 phosphorylation and its associations with Lyn and Vav increased after BCR ligation. Constitutive CD19/Lyn/Vav complex signaling may therefore be responsible for the establishment of baseline signaling thresholds in B cells before Ag receptor ligation, in addition to accelerating signaling following BCR engagement or other transmembrane signals. In vitro kinase assays using purified CD19 and purified Lyn revealed that the kinase activity of Lyn was significantly increased when coincubated with CD19. Thus, constitutive and induced CD19/Lyn complexes are likely to regulate basal signaling thresholds and BCR signaling by amplifying the kinase activity of Lyn and other Src-family PTKs. These in vivo and in vitro findings demonstrate a novel mechanism by which CD19 regulates signal transduction in B lymphocytes. The absence of this CD19/Src-family kinase amplification loop may account for the hyporesponsive phenotype of CD19-deficient B cells.

Animals↗
PubMed1999

Characterization of a cDNA encoding a precursor of Carassius RFamide, structurally related to a mammalian prolactin-releasing peptide.

We have characterized the cDNA encoding Carassius RFamide (C-RFa), which is structurally related to mammalian prolactin-releasing peptides (PrRPs), from the brain of the crucian carp. The deduced C-RFa precursor has been shown to comprise 117 amino acids, encoding a single C-RFa sequence. A comparative study of amino acid sequences has revealed that several sequences conserved in preproPrRPs are also found in the C-RFa precursor. Furthermore, the abundant presence of the C-RFa mRNA in the telencephalon, optic tectum, medulla oblongata, and proximal half eye ball was demonstrated by Southern blot analysis of RT-PCR products.

Amino Acid Sequence↗
PubMed1999

Molecular characterization of the hnRNP A2/B1 proteins: tissue-specific expression and novel isoforms.

hnRNP A2/B1 proteins are among the most abundant pre-mRNA-binding proteins of vertebrates and structurally similar to hnRNP A1. We have produced two specific monoclonal antibodies against A2 and B1 and studied their molecular characteristics and in vivo expression in rat tissues. Immunoprecipitation demonstrated that the hnRNP A2/B1 complexes contain many snRNP (small nuclear ribonucleoprotein) proteins, consistent with their role in pre-mRNA splicing. RNA polymerase II inhibition causes nucleocytoplasmic shuttling of A2 and B1. In most tissues, they are localized in the nucleus; however, in the squamous epithelium of the skin and esophagus A2 is also distributed in the cytoplasm. The relative amounts of A2 and B1 are not constant among different tissues. In the adrenal, only A2 is extremely abundant in the medulla but not in the cortex. In the testis the expression of A2 and B1 are observed through spermatogenesis, and different from A1 which is stringently repressed in spermatocytes. We also found and cloned a novel testis-specific isoform of A2/B1, namely hnRNP B0. The difference of expression of A2, B1, and A1 provides new information on their in vivo roles. The diversity of A/B group hnRNP proteins may have important effects on the posttranscriptional regulation of cell-specific gene expression.

Amino Acid Sequence↗
PubMed1999

Lack of class II transactivator causes severe deficiency of HLA-DR expression in small cell lung cancer.

Small cell lung cancer (SCLC) is characteristically not associated with tumour-infiltrating lymphocytes. Since SCLC has been reported to show marked reduction of class I HLA, the reduced expression has been considered a means of escaping anti-cancer immunity. However, HLA-DR expressed in cancer cells is now known to contribute to anti-cancer immunity. To clarify the difference in HLA-DR expression between SCLC and non-small cell lung cancer (NSCLC), and the mechanism, the expression and the cis- and trans-acting factors involved were investigated. HLA-DR was not immunohistochemically detected in any SCLC and could not be induced by interferon gamma (IFN-gamma) in any SCLC cell line, whereas HLA-DR was expressed to varying degrees and was easily induced in NSCLC. SCLC cell lines lacked class II transactivator (CIITA) even after IFN-gamma induction, whereas NSCLC cell lines expressed CIITA. The other class II HLA-specific transcription factors were expressed and genomic DNA of HLA-DR, including the promoter, was conserved well both in SCLC and in NSCLC cell lines. CIITA transfection improved the expression of HLA-DR in SCLC. In conclusion, the lack of CIITA results in severe deficiency of HLA-DR expression in SCLC. Since CIITA has also been reported to induce class I HLA, CIITA transfection might make it possible to establish effective anti-cancer immunotherapy against SCLC through the up-regulation of class I and class II HLA.

Blotting, Northern↗
PubMed1999

Effects of "body compression" on parameters related to ascites formation: therapeutic trial in cirrhotic patients.

Decreased effective circulating blood volume is an important factor in ascites formation in liver cirrhosis. We designed a "body compression" apparatus as a means to restore effective blood volume and investigated its effectiveness in reducing ascites formation in cirrhotics in terms of its effect on parameters of ascites formation noted below. The subjects, eight cirrhotics with ascites and eight cirrhotics without ascites were given spironolactone (50-75 mg/day) and furosemide (40-80 mg/day) while they received a diet containing 85 mEq of sodium per day. All four limbs and the lower abdomen were compressed with constant pressure [height (cm) divided by 13.6 mmHg] once, for 3h, using stroke rehabilitation splints, while patients lay supine. In cirrhotics both with and without ascites, urine volume, urinary sodium excretion, and creatinine clearance during the body compression were greater than values during control (non-compression) periods (urine volume, means 285 vs 169 ml/3h; P < 0.001, urinary sodium excretion 15.8 vs 9.5 mEq/3h; p < 0.001, creatinine clearance 74 vs 59 ml/min, P < 0.001, respectively). The increased basal plasma renin activity, angiotensin II, aldosterone, and norepinephrine levels in all cirrhotics were significantly decreased by the body compression. In another group of six cirrhotics who received no diuretics or albumin, repeat body compression alleviated ascites in three with well preserved renal function, but was ineffective in three with markedly impaired renal function. These results suggest that the improvement in renal function brought about by the body compression is attributable to an increase in effective circulating blood volume. This maneuver may be a useful complementary therapy in patients with cirrhotic ascites with well preserved renal function.

Adult↗
PubMed1999

A clinico-pathological study of cervical myelopathy in rheumatoid arthritis: post-mortem analysis of two cases.

Two patients who developed cervical myelopathy secondary to rheumatoid arthritis were analyzed post mortem. One patient had anterior atlanto-axial subluxation (AAS) combined with subaxial subluxation (SS), and the other had vertical subluxation (VS) combined with SS. In the patient with AAS, the posterior aspect of the spinal cord demonstrated severe constriction at the C2 segment, which arose from dynamic osseous compression by the C1 posterior arch. A histological cross-section of the spinal cord at the segment was characterized by distinct necrosis in the posterior white columns and the gray matter. In the patient with VS, the upper cervical cord and medulla oblongata showed angulation over the invaginated odontoid process, whereas no significant pathological changes were observed. At the level of SS, the spinal cord was pinched and compressed between the upper corner of the vertebral body and the lower edge of the lamina. Histologically, demyelination and gliosis were observed in the posterior and lateral white columns.

Arthritis, Rheumatoid↗