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Biomedical subjects

T Kodama

Publications and source records attributed to T Kodama.

At least 415 records · Page 23Linked to original sources

Cytotoxicity and suppression of immunoglobulin production against human Namalwa cells caused by oxidized cholesterol.

The effects of oxidized cholesterols on proliferation and IgM production of human lymphoblastoid Namalwa cells were examined. An oxidized cholesterol mixture, in contrast to cholesterol, was a potent cytotoxin to Namalwa cells. Among oxidized cholesterols examined, 25-hydroxycholesterol was the most cytotoxic. However, no oxidized cholesterol examined suppressed IgM production, although cholestanetriol and 7-ketocholesterol did suppress it. Thus, oxidized cholesterols are cytotoxic to lymphocytes, while the influence on the immunoglobulin production may be marginal.

Burkitt Lymphoma↗

Purification and characterization of ferredoxin from Hydrogenobacter thermophilus strain TK-6.

Ferredoxin was purified from cells of Hydrogenobacter thermophilus strain TK-6. Purification was performed aerobically by the addition of octyl-beta-glucoside to the buffers. The purified ferredoxin had a molecular mass of 13,000 and contained a [4F3-4S] cluster. The protein had a long stretch at the N-terminal region; however, the sequence was not similar to the sequences of ferredoxins with a long stretch from Archaebacteria.

Amino Acid Sequence↗

Clinicopathological analysis and therapy in hepatitis C virus-associated nephropathy.

We analyzed the clinicopathological features and therapy in 19 patients with kidney disease accompanied by hepatitis C viral infection, including 12 patients with mesangial proliferative glomerulonephritis (including eight with IgA nephropathy), six with membranoproliferative glomerulonephritis (MPGN), and one with membranous nephropathy. Persistent hematuria and/ or proteinuria (10 patients) was the most common finding, followed by nephrotic syndrome (8 patients). Cryoglobulinemia was detected in six of 19 patients examined (four of six patients with MPGN). Analysis of hepatitis C virus (HCV)-RNA genotype in 13 patients revealed that nine of them had type II genotype. All four patients with MPGN, who had serum positive for HCV-RNA, had type II genotype. Five patients were treated with interferon-alpha (IFN-alpha) without a demonstrable effect on renal impairment, whereas five of 11 patients treated with steroids showed improvement of the renal impairment. During the course of steroid therapy, the serum titer of HCV-RNA decreased in 5 of 7 patients. These observations suggest that HCV infection may be associated with several forms of glomerulonephritis. Type II HCV-RNA may have a strong association with MPGN in Japan. Steroid therapy is not contraindicated in patients with HCV-associated nephropathy if they are resistant to IFN-alpha treatment.

Adolescent↗

(+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502) as a novel substrate for cytochrome P450 2A6 in human liver microsomes.

(+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) was oxidized by human liver microsomes to produce the S-oxide as a sole metabolite. Indirect evidence suggested that the S-oxidation was catalyzed by cytochrome P450 (CYP). Eadie-Hofstee plots showed biphasic pattern, suggesting that at least two enzymes were involved in the S-oxidation in human liver microsomes. Kinetic parameters of the S-oxidase with high-affinity showed Km and Vmax values of 20.9 +/- 4.4 microM and 0.111 +/- 0.051 nmol/min/mg microsomal protein, respectively. The S-oxidase activity was inhibited by coumarin and anti-CYP2A antibody. Among the contents of forms of CYP 20 samples of human liver microsomes, the content of CYP2A6 correlated with S-oxidase activity measured with 50 microM SM-12502 (r = .808, P < .0005). A close correlation (r = .908, P < .0001) was observed between activities of SM-12502 S-oxidase and coumarin 7-hydroxylase. Microsomes from genetically engineered human B-lymphoblastoid cells expressing CYP2A6 metabolized SM-12502 to the S-oxide efficiently. The results indicate that CYP2A6 isozyme is a major form of CYP responsible for the S-oxidation of SM-12502 in human liver microsomes. Thus, SM-12502 will be a useful tool in further research to analyze a human genetic polymorphism of CYP2A6.

Animals↗

Increased serum concentrations of pro-gastrin-releasing peptide in patients with renal dysfunction.

BACKGROUND: Gastrin-releasing peptide has a prominent role as a tumour marker in the diagnosis of small-cell lung carcinoma. This study was designed to assess the validity of a newly developed enzyme-linked immunosorbent assay (ELISA) for pro-gastrin-releasing peptide in patients with renal and systemic diseases. METHODS: Pro-gastrin-releasing peptide concentrations in sera from normal subjects and patients with small-cell lung carcinoma, diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, chronic glomerulonephritis, or undialysed or dialysed chronic renal failure were measured with the TND-4 Kit, a newly developed ELISA for pro-gastrin-releasing peptide. RESULTS: All of the patients with normal renal function, whether they had diabetes mellitus (n=16), rheumatoid arthritis (n=10), systemic lupus erythematosus (n=12) or chronic glomerulonephritis (n=14), had serum pro-gastrin-releasing peptide concentrations less than 46 ng/l, the upper limit in normal subjects. In contrast, 14 or 16 patients (88%) with small-cell lung carcinoma, who had normal renal function, and 25 of 26 (96%) patients with chronic renal failure on haemodialysis had serum pro-gastrin-releasing peptide concentrations greater than 46 ng/l. The highest serum pro-gastrin-releasing peptide levels in patients with chronic renal failure, before and after initiating haemodialysis were 183 and 290 ng/l respectively. Ten of 16 (63%) small-cell lung carcinoma patients had serum pro-gastrin-releasing peptide concentrations greater than 290 ng/l, the highest level in haemodialysed patients. Serum pro-gastrin-releasing peptide concentrations were also elevated in patients with chronic glomerulonephritis or diabetes mellitus when their serum creatinine concentrations were greater than 120 micromol/l. And, there was a significant correlation, y=23.5+0.15x(n=22, r=0.82, P<0.001),between serum pro-gastrin-releasing peptide (y, in ng/l) and serum creatine (x in micromol/l) concentrations in those patients with renal dysfunction. The correlation between serum pro-gastrin-releasing peptide and serum urea nitrogen concentrations was likewise significant. CONCLUSIONS: The evaluation of patients as to their renal functional state may be mandatory when serum pro-gastrin-releasing peptide levels are to be applied as one of the diagnostic tools for small-cell lung carcinoma or as a marker monitoring their clinical course.

Adult↗

[A case with superficial siderosis of the central nervous system accompanied by sensory high tone hearing loss and recurrent headache and vomiting].

A 13-year-old boy with superficial siderosis of the central nervous system was reported. There were many members, including the proband, with sensory high tone hearing loss in his maternal family, but they did not have other neurological symptoms. Paroxysmal and pulsatile severe headache, and vomiting without aura appeared recurrently at the age of 8. His consciousness was alert and no other abnormal sign or symptom was seen during the attacks. The electroencephalogram and cranial computed tomogram revealed no abnormality. The T2 weighted magnetic resonance image of the cranium showed a superficial low intensity zone on the cerebellar vermis, frontal and parietal lobes of the cerebrum, and cervical and upper portion of the thoracic spinal cord at the age of 12, when he had severe headache and vomiting. Cerebrospinal fluid showed xanthochromia with mild elevation of the protein level during an attack, and a light bloody appearance during the asymptomatic state. The diagnosis of superficial siderosis of the central nervous system was made by these findings of magnetic resonance image and cerebrospinal fluid. The bleeding sources to the subarachnoid space could not be detected by cerebral angiography.

Adolescent↗

Bcl-2 protein expression in lung cancer and close correlation with neuroendocrine differentiation.

For determination of the cellular distribution of bcl-2 expression in lung cancer and clarification of its correlation with cell neuroendocrine differentiation, Bcl-2 immunostaining was carried out on a large series of formalin-fixed, paraffin-embedded lung cancer samples, and four general neuroendocrine marker and seven peptide hormone stainings were carried out on all Bcl-2-positive squamous cell carcinomas and adenocarcinomas of the lung as well as on 8 pulmonary neuroendocrine carcinomas histologically diagnosed. In addition, 3 small cell lung cancer cell lines were studied by Western blotting. Neuroendocrine differentiation in Bcl-2-negative squamous cell carcinomas and adenocarcinomas was examined with chromogranin A and alpha-subunit of Go protein stainings. Bcl-2 protein was detected in 104/111 small cell carcinomas, 8/8 neuroendocrine carcinomas, 0/6 typical (well differentiated) carcinoids, 23/64 squamous cell carcinomas, 4/65 adenocarcinomas, and all 3 small cell lung cancer cell lines. All 8 neuroendocrine carcinomas, 11 of the Bcl-2-positive squamous cell carcinomas, and all 4 Bcl-2 positive adenocarcinomas expressed multiple neuroendocrine markers. The distributions of Bcl-2 and neuroendocrine marker immunoreactivity closely paralleled each other on consecutive sections. In squamous cell carcinomas, Bcl-2-positive cells could be roughly subdivided into those with neuroendocrine differentiation features, usually demonstrating intense Bcl-2 staining, with basaloid tumor cells usually expressing weak to moderate Bcl-2 staining. The present study clearly shows Bcl-2 protein expression to be remarkably differentially regulated according to histological types of lung cancers and to appear to quite likely be closely associated with neuroendocrine differentiation of tumor cells, indicating that bcl-2 is importantly involved in cell development and differentiation, in addition to protecting cells from apoptosis. Bcl-2 might be usable as a neuroendocrine marker in lung cancers and possibly also in neural-crest-derived tumors.

Adenocarcinoma↗

Tubulointerstitial nephritis with renal tubular acidosis and asymptomatic primary biliary cirrhosis accompanied by antibody to a 52-kDa mitochondrial protein alone.

We report a patient presenting with a mixed type of renal tubular acidosis, who demonstrated anti-mitochondrial antibodies on immunofluorescent study. However, study of anti-M2 antibody (enzyme immunoassay) was negative. Renal biopsy revealed lymphocyte infiltration in the interstitium compatible with chronic tubulointerstitial nephritis. Liver biopsy demonstrated a mild degree of primary biliary cirrhosis (PBC) but biochemical liver function tests were normal, resulting in a diagnosis of asymptomatic PBC. Using affinity chromatography conjugated with the patient's IgG, we purified a 52-kDa protein from a porcine renal mitochondrial fraction. This protein was identified as a component of a mitochondrial multienzyme complex such as dihydrolipoamide acyltransferase of the branched-chain alpha-keto acid dehydrogenase complex (BCKD), based on the molecular mass analysis and partial amino acid sequence of the purified protein. This is the first report of the detection of antibody to 52-kDa mitochondrial protein alone in a patient who showed predominantly tubulointerstitial damage in the kidney rather than liver damage.

Acidosis, Renal Tubular↗

[Reye syndrome evaluated by 99mTc-ECD SPECT: a case report].

We report a three-year-old boy with Reye syndrome evaluated by 99mTc-ECD SPECT. On acute stage, 99mTc-ECD brain SPECT disclosed diffuse high uptake in the cerebral cortex in spite of normal findings on brain X-ray CT. These lesions changed to general low uptake on the chronic state and multiple high intensity areas were shown on T2 weighted MRI image. Such a change of cerebral tracer uptake was considered to reflect the neuropathological change of Reye syndrome. 99mTc-ECD SPECT was a useful modality to diagnose Reye syndrome complementary.

Brain↗

[Normal distribution of CBF with advancing age measured by HMPAO SPECT].

SPECT with Tc-99m HMPAO was used to determine global and regional cerebral blood flow (CBF) in 52 healthy subjects ranging from 2 to 85 years old. These subjects were divided into six groups according to age. SPECT images were obtained using a three-headed gamma camera system equipped with low-energy ultra-high-resolution fan beam collimators (LEUHR-FAN). Absolute CBF values were estimated in 21 of 52 subjects using a Patlak plot technique. The SPECT images were obtained 5-10 minutes after the injection of 740MBq of Tc-99m HMPAO. A supercomputer system was used to reconstruct transverse section images at levels of 8, 32, 44 and 67 mm above the orbitomeatal line (2.7 mm thickness), and oblique transverse section images parallel to the temporal lobe (1.56 mm thickness). Lassen's linearization correction was applied. The average counts of four or five ROIs in eight regions were calculated. The cerebral to cerebellar activity ratio (C/C ratio) was estimated by dividing counts in the cerebral regions by those in the cerebellum. The interhemispheric differences in C/C ratios in the eight regions of all the groups were not significant. In elderly subjects there was a tendency for C/C ratios to decrease except in the thalamus and basal ganglia. Mean global CBF in 21 of 52 subjects was 49.3 +/- 10 ml/100g/min. A significant negative correlation was found between global CBF and advancing age (p < 0.05), particularly in males (p < 0.01).

Adolescent↗

[A case of ectopic amylase-producing lung cancer].

A case of amylase-producing lung cancer is reported. A 58-year-old man was admitted to our hospital because of abnormal shadow on chest X-rays. Transbronchial lung biopsy showed adenocarcinoma at the right upper lobe. Amylase levels were elevated to 915 IU/l in the serum and 960 IU/l in urine. Amylase isozyme pattern identified "salivary-type" amylase. Right upper lobectomy was performed. Both serum and urine, amylase levels were decreased within normal limits after operation. Enzyme labeled immunoperoxidase method on this specimen proved that tumor cells were producing amylase ectopically.

Adenocarcinoma↗

[Surgical treatment of aortic stenosis with polycythemia vera: a case report].

We report a case of 67-year-old woman with severe aortic stenosis complicated by polycythemia vera (PV). She has been treated for PV with busulfan over the past three years. On admission, she had increase in white blood cell, red blood cell and platelet count. The pressure gradient between left ventricle and aorta was 170 mmHg. Aortic valve was bicuspid and replaced with a 21 mm Carpentier-Edwards pericardial xenoprosthesis. Ascending aorta with a diameter 6.0 cm was replaced simultaneously with a 30 mm Dacron graft (Hemashield). Post-CPB course was uneventful except for a tendency to the prolongation of activated clotting time. She was discharged from the hospital in good condition.

Aged↗

Differentiation of atypical adenomatous hyperplasia and adenocarcinoma of the lung by use of DNA ploidy and morphometric analysis.

Atypical adenomatous hyperplasia (AAH) of the lung has been regarded as a precancerous lesion of lung adenocarcinoma, but the biologic significance of this lesion is still not well understood. In this study, DNA histogram patterns and nuclear size were examined, using an image cytometer. We studied 14 cases of Type II pneumocyte hyperplasia (HP), 7 cases of adenomatous hyperplasia with slight or no nuclear atypia (AH), 21 cases of AAH, and 26 cases of adenocarcinoma. The difference in mean nuclear sizes between the HP (32.08 microns2) and the AH (32.86 microns2) was not significant but between the AH, the AAH (38.52 microns2), and the well-differentiated adenocarcinomas with mild nuclear atypia (51.12 microns2), statistically significant differences were observed (P < 0.05). Seven (33%) of the 21 cases of AAH and 22 (85%) of the 26 cases of adenocarcinoma showed aneuploid histogram patterns. The difference in the incidence of aneuploid pattern between AAH and adenocarcinomas was statistically significant (P < 0.01). All of the cases of HP and AH were diploid. Two of the seven aneuploid cases of AAH showed hyperdiploid DNA histogram patterns, and the remaining five showed polyploid histogram patterns with diploid and hyperdiploid stemlines. In these five cases, the small-sized nuclei showed a diploid stemline and the large-sized nuclei showed a hyperdiploid stemline. Our data indicated that AAH can be distinguished from HP, AH, or adenocarcinoma by morphometric analysis and that some cases of AAH that display aneuploid histogram patterns are precancerous lesions that may lead to adenocarcinoma.

Adenocarcinoma↗

L-arginine prevents heart transplant arteriosclerosis by modulating the vascular cell proliferative response to insulin-like growth factor-I and interleukin-6.

BACKGROUND: L-arginine, a nitric oxide precursor, inhibits myointimal hyperplasia induced by balloon injury in native vessels. No studies are published on L-arginine effects on transplant arteriosclerosis. Insulin-like growth factor-I and interleukin-6 are mitogenic for smooth muscle cells and are involved in the cell-mediated and humoral immune response. METHODS: New Zealand White rabbits received cardiac allografts from Dutch Belted rabbits. All animals were fed a 0.5% cholesterol diet and received drinking water with (eight pairs) or without (eight pairs) L-arginine (2.5%) from day 7 to until they were killed at day 42. The recipients received cyclosporine A 10 mg/kg/day from transplantation until the time they were killed. RESULTS: Dietary L-arginine reduces myointimal hyperplasia in allograft coronary arteries from 44% +/- 4% in the non-L-arginine group to 16% +/- 2% (p < 0.002). The L-arginine significantly inhibits graft vascular cell proliferation induced by (1) insulin-like growth factor-I, from 328% +/- 66% to 154% +/- 28% (p < 0.05), (2) interleukin-6, from 376% +/- 97% to 138% +/- 30% (p < 0.05) and (3) the combination of insulin-like growth factor-I and interleukin-6 from 710% +/- 201% to 226% +/- 72% (p < 0.05). In recipient native aorta explants L-arginine also abolishes vascular cell proliferation stimulated by insulin-like growth factor-I and interleukin-6. The rejection grading is similar in the L-arginine (2.9 +/- 0.1) and control groups (2.7 +/- 0.1). Class II major histocompatibility antigen expression, T-lymphocyte, and macrophage infiltration in the cardiac allograft are unaffected by L-arginine. However, the diet significantly increased plasma nitric oxide from 15.4 +/- 2.3 to 45.1 +/- 11 mumol (p < 0.05). CONCLUSIONS: Dietary L-arginine attenuates transplant arteriosclerosis in vivo without affecting rejection. The protective effect seen in these experiments may relate to the generation of sufficient nitric oxide to prevent smooth muscle cell response to mitogens like insulin-like growth factor-I and interleukin-6.

Animals↗