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Biomedical subjects

A Fukuda

Publications and source records attributed to A Fukuda.

At least 109 records · Page 6Linked to original sources
PubMed1996

3-Nitropropionic acid produces striatum selective lesions accompanied by iNOS expression.

Systemically administered 3-nitropropionic acid (3-NPA) that inhibits the mitochondrial oxidative phosphorylation induces selective lesions in the striatum. To investigate the nature of these selective lesions, we administered 3-NPA (20 mg/kg, s.c. daily for 2 or 3 days) to Wistar rats and investigated the behavioral disturbance, striatal lesions and their variations after modulating the activity of nitric oxide synthase (NOS). On the second or third day of 3-NPA administration, half the animals manifested behavioral disturbances (paddling, rolling, tremor, abnormal gait, and recumbence). A strong extravasation of immunoglobulin G (IgG) and a decrease in immunoreaction for glial fibrillary acidic protein (GFAP) were detected, and iNOS-like (iNOS-L) immunoreactive small cells appeared in the lateral and central striatum especially around the vessels. A week later, lesions lacking GFAP-immunoreaction were detected in the striatum in survived animals. Pretreatment with N-nitro-L-arginine methyl ester (L-NAME) along with each injection of 3-NPA did not improve the behavioral disturbances nor the survival rate, but attenuated the extravasation of IgG and iNOS-L immunoreaction. Pretreatment with aminoguanidine or FK506 improved the behavioral symptoms and survival rate. Extravasation of IgG and expression of iNOS-L immunoreactivity were attenuated, and the striatal lesion was reduced. Data indicate the involvement of NO in the high vulnerability of the striatum, and that iNOS, one of inflammatory markers, is induced following exposure to 3-NPA.

Animals↗
PubMed1996

Second primary neoplasms in thyroid cancer patients.

To determine risk patterns for second primary neoplasms after the occurrence of thyroid cancer, we conducted a retrospective cohort study of 3321 thyroid cancer patients who were operated and histologically confirmed at the Noguchi Thyroid Clinic and Hospital Foundation between 1946 and 1985. They were followed from the date of operation through the end of 1990 with an observation period from 45 to 5 years. The average observation period of the patients was 13.4 years and the follow-up rate reached 98%. The standardized mortality ratio (SMR) was computed to assess possible risk increase by cancer site. In this computation, the time period less than 5 years after operation was omitted to reduce the influence of deaths related to the original thyroid cancer. A total of 103 deaths from malignant neoplasms other than thyroid cancer were observed during this time period (SMR = 1.6, 95% confidence interval [CI] = 1.3-2.0). Analyses of site-specific cancer mortality revealed significantly elevated risks for the central nervous system (SMR = 16.1, CI = 5.2-37.6) and respiratory organs (SMR = 2.6, CI = 1.5-4.1). Based on a review of available medical records with histological findings, we concluded that the risk increases for these sites were most likely to be attributable to second primary neoplasms. Whether or not the patients had received radiotherapy was not significantly associated with elevated risk. Further investigations are needed to clarify the risk factors responsible for the above findings.

Adolescent↗
PubMed1996

Quantification of leucocyte elastase and cathepsin G in plasma by a simple method: effect of elastase in plasma levels of D-dimer and thrombomodulin.

The purpose of this study was to determine levels of leucocyte elastase and cathepsin G in the plasma of patients in various pathological states, in which plasma increases or decreases in coagulation and fibrinolytic factors were seen. Simple methods were developed to measure the leucocyte proteinases and the results were correlated with conventional assays of coagulation and fibrinolytic factors. The total number of patients and total number of plasma samples examined were 340 and 1292, respectively. No correlation was observed between the plasma levels of elastase and cathepsin G, and plasminogen, fibrinogen and leucocyte counts. There was a weak overall correlation, however, between the leucocyte proteinases and each of the four parameters: D-dimer, thrombomodulin, antithrombin III and platelet count. There was a strong correlation between leucocyte proteinases and D-dimer and thrombomodulin in those patients with plasminogen levels within the normal range. Increased D-dimer levels, as well as plasmin, may suggest that elevated leucocyte proteinases contribute to elevated fibrinolytic mechanisms in these instances.

Biological Assay↗
PubMed1996

Rheumatoid factor in the serum of hepatitis C virus-infected patients: an increase in the titre during cold storage.

Storage of serum at 4 degrees C elevated the titre of rheumatoid factor (RF) as measured by nephelometry with IgG-coated latex in 12 of 38 specimens positive for hepatitis C virus. Increased RF following cold storage was not detected in HCV-negative sera. Most of the sera showing the cold-dependent elevation of RF had decreased complement hemolytic activity (CH50) after the cold storage. The RF titre elevated by cold storage decreased to the level of fresh serum by the addition of guinea pig serum as a complement supplement in a dose-dependent fashion. Thus, in the serum of some HCV-infected patients, the affinity of RF appears to be weak, and the binding between the RF and IgG coated on latex may be inhibited by the complement components of fresh serum.

Cold Temperature↗
PubMed1996

[Surgical treatment of aorto-iliac occlusive disease].

Recently, various endovascular techniques were applied to the short segmental stenosis of aorto-iliac artery. However, bypass operation is the most reliable treatment for multiple stenotic or occlusive lesion. Preoperative systemic evaluation is important for the adequate selection of the patients and the operations. Dipyridamole-thallium scintigraphy is more useful than exercise stress testing to assess cardiac risks of patients with peripheral arterial diseases. Anatomical bypass is the standard operation resulting in favorable patency. Despite of relatively inferior long term patency, extra-anatomical bypass operations are useful alternatives for the patients having high systemic risks or severe sclerosis of aorto-iliac arteries. The improved medical care of the elderly patients with severe systemic diseases results in the increase of extra-anatomical bypass and extended operation combined with infrainguinal revascularization.

Aorta↗
PubMed1995

A renal carcinogen ferric nitrilotriacetate mediates a temporary accumulation of aldehyde-modified proteins within cytosolic compartment of rat kidney.

Iron overload with ferric nitrilotriacetate (Fe-NTA) induces acute renal proximal tubular necrosis, a consequence of oxidative tissue damage, that eventually leads to a high incidence of renal adenocarcinoma in rodents. A recent immunohistochemical study has revealed that the materials immunoreactive to the antibody against the aldehyde (4-hydroxy-2-nonenal)-modified proteins are generated in the renal proximal tubules of rats treated with Fe-NTA (S. Toyokuni et al. (1994) Proc. Natl. Acad. Sci. USA 91, 2616-2620). Here we present further evidences that cytosolic proteins modified with lipid peroxidation-derived aldehydes (4-hydroxy-2-nonenal and malondialdehyde) are indeed accumulated in the kidney of rats treated with Fe-NTA. A single intraperitoneal Fe-NTA treatment (15 or 30 mg Fe/kg body wt) induced a rapid accumulation of thiobarbituric acid-reactive substances, a direct consequence of membrane lipid peroxidation, mostly within the cytosolic compartment of rat kidney. The accumulation of lipid peroxidation-derived aldehydes was associated with an apparent accumulation (from 67.9 nmol in untreated controls to 83.3 nmol/mg protein in Fe-NTA-treated rats at 3 h after treatment) and subsequent elimination of aberrant proteins as assessed by a 2,4-dinitrophenylhydrazine postlabeling assay. Immunoblot analysis with two different polyclonal antibodies against 4-hydroxy-2-nonenal-modified and malondialdehyde-modified proteins detected a temporary accumulation of aldehyde-modified proteins in the cytosol. An immunohistochemical technique with serial sectioning revealed that immunoreactivities of these antibodies were observed in the identical portion of the renal proximal tubules. The implications of these data in relation to the nephrotoxicity of Fe-NTA are discussed.

Adenocarcinoma↗
PubMed1995

Appearance of deteriorated neurons on regionally different time tables in rat brain thin slices maintained in physiological condition.

Brain slices are widely used for electrophysiological experiments. However, the time table of the chronological cell deterioration and its regional difference in slices are unknown. The argyrophil III staining method can demonstrate deteriorated ('collapsed') neurons specifically. Therefore we studied the appearance of the 'collapsed' neurons with time in coronal brain 'thin' slices maintained in vitro to evaluate possible regional differences in vulnerability. In the hippocampus, CA1 pyramidal, dentate gyrus granule, and non-pyramidal cells in any subfield became argyrophilic most easily, as did layer V-VI pyramidal neurons in the neocortex. These results suggest that some subclasses of neurons in brain slices degrade earlier than others even when maintained in physiological condition.

Animals↗
PubMed1995

Acute nephrotoxicity of a carcinogenic iron chelate. Selective inhibition of a proteolytic conversion of alpha 2U-globulin to the kidney fatty acid-binding protein.

The mechanism of acute nephrotoxicity of an iron chelate in vivo has been investigated. Administration of a renal carcinogen ferric nitrilotriacetate (Fe-NTA) (15 mg Fe/kg body weight, intraperitoneally) led to selective loss of a renal protein with an apparent molecular mass of 17 kDa. Analysis of the 17 kDa protein by NH2-terminal sequence demonstrated its identity over 16 NH2-terminal residues as a kidney fatty acid-binding protein (k-FABP) that is a proteolytically modified form of alpha 2U-globulin, a major urinary protein of adult male rats. An immunochemical study using anti-alpha 2U-globulin polyclonal antibodies confirmed that a single injection of Fe-NTA led to a decrease in k-FABP levels. However, a 19-kDa protein identical to the alpha 2U-globulin progressively appeared in the kidney, suggesting that the proteolytic processing of alpha 2U-globulin in the renal proximal tubules was suppressed by the treatment with Fe-NTA. By monitoring k-FABP and its precursor alpha 2U-globulin, it was determined that repeated exposure to Fe-NTA caused suppression of both proteolytic and endocytotic activity of the kidney. The implications of these data in relation to the nephrotoxicity of Fe-NTA are discussed.

Alpha-Globulins↗
PubMed1995

Chronically administered 3-nitropropionic acid produces selective lesions in the striatum and reduces muscle tonus.

Systemically administered 3-nitropropionic acid (3- NPA), irreversible inhibitor of succinate dehydrogenase, produced characteristic bilateral lesions in the striatum (STR) in the rat. Inside the lesion, neutrophils invaded and strong immunoreaction for IgG as well as complement factor C3b/C4b receptor (C3b/C4br) were observed. The core of the lesion lost the immunoreaction for glial fibrillary acidic protein (GFAP) while the marginal area had abundant GFAP-labeled astrocytes around the vessels. Intoxicated rats often became somnolent and were awkward in cooperative movement on a pole climbing test, but they had a quite good memory retention in a passive avoidance learning. Muscle tonus in some of the intoxicated rats became hypotonic with low voltage electromyogram (EMG) activity, especially in lower limbs. In summary, 3-NPA intoxicated rats had selective bilateral lesions in the STR and exhibited disturbances in a cooperative movement owing to the impairment in muscle tonus, thus it would be a useful animal model to deduce the central pathogenesis of Huntington's disease.

Animals↗
PubMed1995

Alcohol inhibits epidermal growth factor-stimulated progesterone secretion from human granulosa cells.

In this study, luteinized human granulosa cells (GC) obtained during in vitro fertilization procedures were used as a model system to evaluate the effects of ethanol (EtOH), a well-known reproductive toxin, on epidermal growth factor (EGF) and gonadotropin-stimulated steroidogenesis. Our results demonstrate that the basal progesterone (P4) and estradiol (E2) secretion by human GC in vitro was dependent on the ovarian stimulation protocol. EGF significantly enhanced P4, but not E2, secretion in human GC from clomiphene citrate (CC), human menopausal gonadotropin (hMG), and hMG/gonadotropin-releasing hormone agonist (GnRH-a)-treated patients. The effects of EGF plus luteinizing hormone (LH) were additive in cells from the CC group, but less than additive in hMG and hMG/GnRH-a groups. EtOH at 20 mM or more inhibited EGF stimulated P4 secretion in human GC from all three patient groups. EtOH inhibited P4 secretion stimulated by EGF and LH cotreatment in the CC and hMG/GnRH-a groups, but not in human GC from the hMG-treated patients. These results suggest that basal and EGF or LH-stimulated P4 secretion by human GC, as well as the effects of EtOH, are profoundly influenced by the follicle's hormonal milieu.

Cells, Cultured↗