Is cyclosporine-associated glomerulopathy a new glomerular lesion in renal allografts using CyA?
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Adult↗
Biomedical subjects
A Takeda
Publications and source records attributed to A Takeda.
[Long-term retrospective study of patients with connective tissue diseases accompanied by pulmonary hypertension].
To determine clinical and serological features that are related with the prognosis of connective tissue diseases with pulmonary hypertension (PH), we studied a long-term prognosis of 14 patients (4 SLE, 1 PSS, 3 MCTD, 2 primary Sjögren's syndrome, and 5 OL) accompanied by PH. The patients were divided into three groups; group A (4 cases) that is alive for 5-12 years until present, group B (6 cases) in which PH was the main cause of death, and group C (4 cases) was dead of pulmonary fibrosis and pericardial tamponade. No significant difference was observed in background connective tissue diseases among the three groups. However, the mean ages at the onset of PH was obviously younger in group B (25.7 yrs.) than both in group A (38.3 yrs.) and in group C (42.0 yrs.) (group A vs group B, p < 0.02, and group B vs group C, p < 0.05). Sudden death occurred in 5 of the 6 in group B, whereas it was not observed either in group A or in group C. Also, the interval between onset of PH and death was shorter in group B (1.3 yrs.) than in group C (3.5 yrs.). The incidence of digital necrosis and pericardial effusion was higher in group B (83% and 83%, respectively) than both in group A (0% and 25%, respectively) and in group C (25% and 40%, respectively). A large amount of pericardial effusion was detected in 4 of 5 cases in group B. The incidence of digital necrosis between group A and group B was significantly different (p < 0.05, Fisher's test).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[A case report--pulmonary cryptococcosis associated with systemic lupus erythematosus and review of 44 cases in Japan].
A case of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) associated with pulmonary cryptococcosis which was successfully treated with fluconazole (FCZ) and flucytosine (5-FC) is described. A 63-year-old woman who had been treated with steroid for SLE and low dose methotrexate (MTX) for RA was admitted to Jichi Medical School Hospital because of abnormal shadow in the chest X-ray film. Physical examination revealed no abnormality. A chest CT film showed multiple nodular shadows localized in the right lower lobe. An ultrasonically guided trans-cutaneous lung biopsy performed on 10th hospital day established a diagnosis of pulmonary cryptococcosis. Following the treatment with FCZ and 5-FC for a month, her abnormal lung shadows improved and serum cryptococcal antigen level was decreased. A survey of the literature from 1955 to 1990 revealed 44 cases of SLE associated with cryptococcosis in Japan, in addition to our case, most of whom were on corticosteroid therapy. The majority of patients were young women, representing the usual population of patients with SLE. 34 of these patients had cryptococcal meningitis; 22, pulmonary cryptococcosis; 6, sepsis; 6 cutaneous cryptococcosis. Twenty patients died. Deep fungal infections should be considered whenever patients with SLE have fever of unknown origin, diffuse pulmonary infiltrates, or unexplained CNS symptoms.
Arthritis, Rheumatoid↗
Elevation of hepatic levels of metallothionein and zinc in mice bearing experimental tumors.
A tumor growth-dependent elevation in the hepatic levels of Zn and metallothionein (MT), without a change in the level of Cu, was found in mice and rats bearing solid tumors in the inguinal region. The levels of Zn and MT thus elevated gave a significant correlation (r = 0.95) between them. Nevertheless, when tumor-bearing mice and rats were fed a Zn-deficient diet, the hepatic levels of Zn and MT did not increase. In mice in which inflammation was induced at the same region, on the other hand, hepatic levels of Zn and MT increased transiently after the injection of turpentine or carrageenan even when they were fed the Zn-deficient diet. These results suggest that the elevation of MT and Zn levels can be a helpful marker for detecting malignancy.
Animals↗
Demonstration of cathepsins B, H and L in xenografts of normal and Duchenne-muscular-dystrophy muscles transplanted into nude mice.
The activities and contents of the lysosomal cysteine proteinases cathepsins B, H and L were examined in xenografts of biopsied muscles transplanted from age-matched normal subjects and Duchenne-muscular-dystrophy (DMD) patients into nude mice. The activity of cathepsin B increased 9-fold and that of B-plus-L increased 24-fold in the first week after transplantation in normal muscle xenografts. By the third week, the activity of cathepsin B increased a total of 20-fold and B-plus-L increased to 36-fold the original level. The activity levels of cathepsin B, B-plus-L, H and D, and acid phosphatase in normal and DMD xenografts were not significantly different when compared 2 weeks after transplantation. However, the protein content of cathepsin B in DMD muscle xenografts was more than 3-fold that of normal xenografts at 2 weeks. The profile of cathepsin H activity in normal muscle xenografts was different than those of cathepsins B and B-plus-L. In the first week, the cathepsin H diminished sharply to about one-third of the biopsied muscle level and then, by 3 weeks after transplantation, it had increased slightly to about half the original level. The amount of endogenous cysteine-proteinase inhibitor changed in parallel with the activity of cathepsins B and B-plus-L. Cathepsins B and H, but not cathepsin L, were found immunohistochemically in regenerating muscle fibres of normal and DMD xenografts 2 weeks after transplantation. Staining of cathepsin B in DMD xenografts was slightly stronger than that in normal subjects. There was no immunostaining in degenerating or necrotic muscle fibres 2 weeks after transplantation. Western-blot analysis revealed that the cathepsin B band at 29 kDa was increased in normal xenografts 2 and 3 weeks after transplantation. Also, 2 weeks after transplantation the staining intensity of this band was slightly stronger in DMD xenografts than in normal xenografts. These results suggest that cathepsin B participates in the regeneration of transplanted muscle, both normal and DMD, and in the DMD muscle fibre-wasting processes, during regeneration.
Acid Phosphatase↗
Evidence for monomeric and dimeric forms of CD45 associated with a 30-kDa phosphorylated protein.
Glycoprotein CD45, a transmembrane protein tyrosine phosphatase of leukocytes, is topographically similar to the epidermal growth factor receptor, a transmembrane tyrosine kinase. Since the latter is thought to be allosterically regulated through conversion between monomeric and dimeric forms, we sought to determine whether CD45 undergoes similar oligomerization. Our analysis, employing a thiol-cleavable and homobifunctional chemical cross-linker, dithiobis succinimidyl propionate, revealed that CD45 indeed formed homodimers. In addition, a protein of molecular mass 30,000 daltons (30 kDa) was found to be associated with both the CD45 monomer and dimer. The 30-kDa protein was phosphorylated and was not labeled by cell surface radioiodination. Distinct differences in protein tyrosine phosphatase activity were detected among the various populations of CD45 separated by sucrose gradient ultracentrifugation. However, the differences observed could not be explained simply by dimerization and instead suggest the presence of other factor(s) involved in the regulation of CD45 enzyme activity.
Animals↗
Enzyme-linked immunosorbent assay for the detection of cathepsin-kininogen complexes in human plasma.
A simple and sensitive enzyme-linked immunosorbent assay (ELISA) for the determination of cathepsins B-, H- and L-kininogen (B-KG, H-KG, and L-KG) complexes was constructed using a microtiter plate based sandwich technique. The assay range was 7.5-480 ng/ml with three cross-linked cathepsin-kinin-free low molecular weight KG (LMWKGf) complexes. The average within-run coefficients of variation (CV) using three concentrations were 7.5, 7.2 and 9.9% for B-LMWKGf, H-LMWKGf, and L-LMWKGf complexes, respectively. The between-run CV values indicated satisfactory reproducibility for the method. Recoveries of cross-linked B-LMWKGf, H-LMWKGf, and L-LMWKGf complexes from negative control plasma were 127 +/- 7.1, 112 +/- 5.8 and 102 +/- 8.8% (n = 10, mean +/- SD), respectively, whereas the average recovery from phosphate buffer (pH 7.2) containing 0.15 M NaCl, 0.05% Tween-20 and 0.1% bovine serum albumin was 93.1 +/- 8.2% (n = 10, mean +/- SD). It was possible to detect B-KG and H-KG complexes in the plasma of 5/280 and 14/280 patients manifesting acute phase responses. Levels in plasma from healthy individuals were negligible. This ELISA should permit the study of cathepsin metabolism in acute phase disorders.
Acute-Phase Reaction↗
Decreased expression of neurotrophin-3 mRNA in the rat hippocampus following transient forebrain ischemia.
The expression profile of neurotrophin-3 (NT-3) mRNA in the rat hippocampus after forebrain ischemia was investigated by Northern blot and S1 nuclease protection analyses. The NT-3 transcripts in the hippocampus immediately decreased after ischemic insult, became undetectable within 3 h and remained at undetectable levels for at least 7 days. In contrast, the expression of c-fos and c-jun mRNA transiently increased both in the cerebral cortex and in the hippocampus. These results suggest that brain ischemia triggers dynamic changes in gene expression including a neurotrophic factor, which may cause functional and/or morphological changes of the neuronal network.
Animals↗
A silver-sulfadiazine-impregnated synthetic wound dressing composed of poly-L-leucine spongy matrix: an evaluation of clinical cases.
The management of severe burns requires the suppression of bacterial growth, particularly when eschar and damaged tissue are present. For such cases, silver sulfadiazine (AgSD) cream has been traditionally applied. This antibacterial cream, however, cannot be used in conjunction with a temporary wound dressing that is needed to promote healing. The authors developed a synthetic wound dressing with drug delivery capability for clinical use by impregnating a poly-L-leucine spongy matrix with AgSD, which is released in a controlled, sustained fashion. In general, the dressing adhered firmly to the wound in the case of superficial second-degree burns, and during the healing process it separated spontaneously from the re-epithelialized surface. In the management of deep second-degree burns where eschar and damaged tissue were present, the dressing had to be changed at intervals of 3 to 5 days until it adhered firmly to the wound. Once the dressing had firmly attached to the wound, it was left in place until it separated spontaneously from the re-epithelialized surface. Dressing changes were fewer than with other treatments and the pain was effectively reduced. Cleansed wounds were effectively protected from bacterial contamination. Of 52 cases treated with this wound dressing, 93% (14/15) of superficial second-degree burns, 75% (3/4) of deep second-degree burns, 85% (6/7) of superficial and deep second-degree burns, and 75% (12/16) of split-thickness skin donor sites were evaluated as achieving good or excellent results.
Adult↗
Conformation of concanavalin A and its fragments in aqueous solution and organic solvent-water mixtures.
The conformations of concanavalin A (con A), an all-beta protein, and its three CNBr-cleaved fragments were studied by CD. Con A in buffer showed a 197 nm maximum and a 223 nm minimum, which were red-shifted by 6-7 nm from those of regular all-beta proteins and beta-sheet of (Lys)n. Fragment 1 (residue 1-42) resembled an unordered form with a CD maximum at 200 nm, but fragments 2 (residues 43-129) and 3 (residues 130-237) showed a regular CD spectrum with two extrema at 192-193 nm (+) and 214-216 nm (-). Equimolar mixture of the three fragments showed some degree of interaction, but did not reconstitute the conformation of native con A, probably because of the loss of bound Ca2+ and Mn2+ ions in the fragments. In ethanol-, methanol-, and dioxane-water mixed solvents, con A and its fragments remained as beta-sheet. In contrast, addition of trifluoroethanol and sodium dodecyl sulfate induced alpha-helix at the expense of beta-sheet for con A and its fragments in aqueous solution. In 80% trifluoroethanol, the induced helicities exceeded their sequence-predicted helix-potentials, but in 10 mM sodium dodecyl sulfate the helicities agreed well with corresponding predictions.
Buffers↗
Protein binding of four antiepileptic drugs in maternal and umbilical cord serum.
The total and protein free levels of 4 antiepileptic drugs (AEDs) in serum from 35 maternity patients who had been treated with AED monotherapy throughout pregnancy were studied. Results were compared with those in the umbilical cord serum at the time of delivery, and the placental transfer of AEDs was evaluated from the viewpoint of the protein binding capacity of the drug. The materials consisted of 35 samples of maternal and umbilical cord serum in total and included 13 patients on phenobarbital (PB), 7 on phenytoin (PHT), 7 on carbamazepine (CBZ) and 8 on valproic acid (VPA). The mean fetal/maternal total concentration ratios were 0.86, 0.91, 0.73 and 1.59 for PB, PHT, CBZ and VPA, respectively, only the VPA ratio being above 1. On the other hand, the mean fetal/maternal free fraction ratios were 1.13, 1.10, 1.42 and 0.50 for PB, PHT, CBZ and VPA, respectively, only the VPA ratio being less than 1. Correlation of the 2 ratios showed a reciprocal proportion with a correlation coefficient of -0.90 (P < 0.005). It was considered that the fetal/maternal total concentration ratio of 4 AEDs was regulated by the fetal/maternal free fraction ratio of the corresponding AEDs and that the difference in fetal/maternal free fraction ratio depended on the type of drug being administered.
Anticonvulsants↗
Cloning and sequence analysis of the tyrosinase gene from a patient with tyrosinase-positive oculocutaneous albinism.
Tyrosinase is synthesized on membrane-bound ribosomes and transported into melanosomes through smooth endoplasmic reticulum and Golgi apparatus. Melanin polymers are produced only in melanosomes but never in smooth endoplasmic reticulum or Golgi apparatus, indicating that posttranslational modifications of tyrosinase are completed with melanosomes where tyrosinase becomes an active form. Based on a working hypothesis that tyrosinase-positive oculocutaneous albinism is a consequence of the structurally altered tyrosinase due to a point mutation in the gene of its gene coding for a glycosylation site or a membrane-binding site, which leads to the impairment in the posttranslational modification of tyrosinase and its catalytic activity, we have cloned the tyrosinase gene of one patient affected with tyrosinase-positive oculocutaneous albinism and determined its nucleotide sequence. Thus demonstrated all exons' nucleotide sequence of the patient's tyrosinase gene was found to be identical to that of the wild-type gene. The results indicate that the patient's tyrosinase itself is not altered. We therefore propose that the molecular basis for the development of tyrosinase-positive oculocutaneous albinism exists as a defect in other proteins required for the activation of tyrosinase or in other regions of the tyrosinase gene.
Adult↗
A case of rapidly progressive glomerulonephritis associated with bucillamine-treated rheumatoid arthritis.
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Anti-Inflammatory Agents, Non-Steroidal↗
Strong immunoreactivity of cathepsin L at the site of rimmed vacuoles in diseased muscles.
Skeletal muscle samples from four patients with myopathies showing autophagic vacuole formation were examined by immunohistochemical, biochemical and immunoblot analyses. Immunochemical studies demonstrated strongly positive reactions of cathepsins B and L in and around the rimmed vacuoles and weak reactions in intramyofibral portions of degenerating muscle fibres. Faint staining of cathepsin H was also seen at the sites of rimmed vacuoles. Biochemical analyses showed increased activity of cathepsin B and L in muscle specimens from the patients with rimmed vacuole formation. However, there was no remarkable cathepsin H activity in the muscle specimens from these patients. Cathepsin L immunoblot analysis of muscle extracts showed three bands with molecular masses of 30 kDa, 36 kDa and 39 kDa. The immunostaining of cathepsin L from patients with rimmed vacuole formation was stronger than that of normal controls. Cathepsin B immunoblot analysis showed only faint bands in samples from patients with rimmed vacuole formation and normal controls. This study demonstrated, for the first time, strong immunoreactivity of cathepsin L at the sites of rimmed vacuoles. Possible mechanisms of rimmed vacuole formation are discussed.
Adult↗
Studies of antibody-dependent enhancement of human immunodeficiency virus (HIV) type 1 infection mediated by Fc receptors using sera from recipients of a recombinant gp160 experimental HIV-1 vaccine.
Subneutralizing concentrations of sera from human immunodeficiency virus (HIV)-1-infected patients augment HIV infection mediated by Fc receptor uptake by human monocytes and the monocytic cell line U937. Antibody-dependent enhancement (ADE) and neutralization activity were studied in the sera of HIV-1 antibody-negative volunteers who had been immunized with three 40-micrograms doses of a recombinant gp160 (rgp160) candidate HIV vaccine. Volunteers were vaccinated with rgp160 or a hepatitis B vaccine as a control on days 0, 30, and 180. Sera were obtained before and after three doses of vaccine and were tested for ADE and neutralization activity. Serum samples collected before vaccination showed neither neutralization nor ADE activity. Thirteen sera from volunteers who received gp160 and four from placebo recipients failed to show ADE. Three sera showed low levels of neutralization of strain IIIB of HIV. Vaccination with this dose of rgp160 produced neutralizing antibodies in some subjects but did not induce detectable enhancing antibodies.
AIDS Vaccines↗
Diurnal rhythm in body temperature in different phases of the menstrual cycle.
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Adult↗
Long-term effectiveness of antiepileptic drug treatment and seizure recurrence in patients with epilepsy.
We studied the rate of seizure recurrence in 334 patients with epilepsy who had received antiepileptic drug (AED) therapy for at least eight years. During the three-year "observation period" (April 1985-March 1988), 163 or 48.8% of the 334 patients were considered to be seizure-free. Seizures were absent in 53 or 81.5% of 65 patients with idiopathic generalized epilepsy, 48 or 40% of 120 with temporal lobe epilepsy, 39 or 39.4% of 99 with partial epilepsy other than those involving the temporal lobe, 2 or 8.3% of 24 with symptomatic generalized epilepsy and 21 or 80.8% of 26 with other epilepsies. Of the 163 patients, 15 or 9.2% suffered seizure(s) during the three-year "follow-up period" (April 1988-March 1991). There was no difference among the different types of epilepsy with respect to seizure recurrence rates. Compared with the 15 patients whose seizures recurred, more of the 148 patients with nonrecurring seizures received AED monotherapy (p < 0.05). However, no significant differences were seen between the two groups for other background factors.
Adult↗
Molecular bases of tyrosinase-negative oculocutaneous albinism: a single base insertion or a missense point mutation in the tyrosinase gene.
We have identified two different mutations in the tyrosinase genes of Japanese patients with tyrosinase-negative oculocutaneous albinism (OCA). One is a single base insertion in the exon 2 of the tyrosinase gene that shifts the reading frame and introduces a premature termination codon (TGA) after the amino acid residue 298 (codon 316). The other is a G to A transition at residue 312, leading to a single amino acid substitution, arginine at position 59 (codon 77) to glutamine. The promoter activity of the patients' tyrosinase genes was evaluated in the cell-free transcription system prepared from pigmented melanoma cells, indicating that the patients' genes were accurately transcribed in vitro. It is therefore conceivable that the tyrosinase gene is expressed in their melanocytes. Furthermore, transient expression of the mutated genes indicates that the truncated tyrosinase or the tyrosinase containing glutamine 59 is unable to form melanin in melanocytes. We therefore propose that these mutations in the tyrosinase genes lead to a phenotype of tyrosinase-negative OCA.
Albinism, Oculocutaneous↗