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Biomedical subjects

K Sudo

Publications and source records attributed to K Sudo.

At least 145 records · Page 8Linked to original sources
PubMed1994

Usefulness of dialysate fibrin degradation products and lactic dehydrogenase isoenzyme patterns in assessing the clinical course of peritonitis.

OBJECTIVE: To establish the usefulness of fibrin degradation products (FDP) and lactic dehydrogenase isoenzyme patterns (LDH isoenzyme) in assessing the clinical course of peritonitis. DESIGN: A retrospective study of patients with peritonitis who were divided into three groups according to their clinical course. SETTING: Single dialysis unit of a general hospital. INTERVENTIONS: Patients were treated by intraperitoneal and oral antibiotics. PATIENTS: Twenty-six patients with 34 episodes of peritonitis were studied. Group 1 consisted of 21 patients with 26 recoveries from peritonitis; Group 2 consisted of 5 patients with 5 relapsing episodes of peritonitis, and Group 3 consisted of 3 patients with 3 persistent episodes of peritonitis. MAIN OUTCOME MEASURES: Concentrations of WBCs, FDP, LDH isoenzyme and microbiological culture of the dialysate were determined. RESULTS: In most of Group 1, WBCs, FDP, and LDH isoenzyme returned to normal within 2 weeks. In 4 patients of Group 1, who had complications (diverticulitis, cholecystitis, cystitis, and tunnel infection), WBCs, FDP, and LDH isoenzyme returned to normal gradually within 3 weeks. In Group 2, WBCs returned to normal, but FDP remained relatively high and LDH isoenzyme did not normalize. In Group 3, WBCs, FDP and LDH isoenzyme did not normalize. CONCLUSIONS: Failure of normalization of FDP and LDH isoenzyme suggests an incomplete recovery from peritonitis. FDP and LDH isoenzyme are useful in assessing the course of peritonitis.

Biomarkers↗
PubMed1994

Premature termination mutations in two patients with deficiency of lactate dehydrogenase H(B) subunit.

Two patients with low lactate dehydrogenase (LD) activity were discovered during healthcare examinations and were found to be homozygous for LD-H (heart) subunit deficiency by electrophoretic isoenzyme analysis of serum and erythrocyte hemolysate. The molecular nature of the genetic mutations was characterized by amplification by the polymerase chain reaction and DNA sequencing. In one case, a single-base substitution (T-->G transversion) at codon 147 of the LD-H(B) gene resulted in a nonsense mutation; in the other case, a deletion of 2 base pairs had occurred at codon 139, resulting in a frameshift translation and premature termination.

Adult↗
PubMed1994

[A case of IgA nephropathy with numerous interstitial foam cells--analysis of infiltrating mononuclear leucocytes in renal tissue].

A 27-year-old female was admitted to our hospital in order to examine proteinuria and microscopic hematuria. Light microscopic findings of her kidney showed proliferation of mesangial cells and numerous interstitial foam cells. Immunofluorescent and electron microscopic findings revealed IgA nephropathy. Immunoperoxidase studies using monoclonal antibodies disclosed that interstitial foam cells were positive for antibodies of the monocyte/macrophage lineage and also expressed adhesion molecules (CD11a, b, c, LFA-1) and MHC-class II antigens. Hereditary nephritis as Alport syndrome was negated by her familial history and electron microscopic study. We considered that it was a rare and interesting case with numerous interstitial foam cells, because the patient did not have hyperlipidemia as in nephrotic syndrome.

Adult↗
PubMed1993

Angiogenesis inhibitor TNP-470 (AGM-1470) potently inhibits the tumor growth of hormone-independent human breast and prostate carcinoma cell lines.

The angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470) showed antitumor activity in three human cancer xenograft systems. TNP-470 potently inhibited the tumor growth of hormone-independent prostate cancer PC-3 cells and breast cancer MDA-MB-231 cells dose dependently at weekly s.c. doses of 50-200 mg/kg with maximum inhibition of 96 and 88% (tumor growth, 4 and 12% of that in the respective control). In experiments of combination therapy with chemotherapeutic agents, the combination of TNP-470 (100 mg/kg) and cisplatin (5 mg/kg) showed an additive antitumor effect (from treated versus control, 38 and 22% to 5%) against PC-3 carcinoma. 5-Fluorouracil and Adriamycin alone did not significantly inhibit MDA-MB-231 tumor growth (treated versus control, 131 and 64%, respectively). TNP-470 also inhibited tumor growth of WiDr colon cancer; although the inhibition was less marked (treated versus control, 39%) than that observed with the hormone-independent cancers used in this study. In an in vitro study, all the cell lines tested were considerably insensitive to TNP-470 in monolayer cultures (50% inhibitory concentration, approximately 5 micrograms/ml), whereas TNP-470 inhibited the anchorage-independent growth of PC-3 and MDA-MB-231 cells (50% inhibitory concentration, 0.05 and 470 ng/ml, respectively). The inhibitory activity of TNP-470 against anchorage-independent growth correlated well with the in vivo antitumor activity among the cell lines tested. Thus, this inhibitory action may partly contribute to the potent antitumor activity of the angiogenesis inhibitor TNP-470, at least in the case of PC-3 and MDA-MB-231. These results suggest that hormone-independent prostate and breast cancers may be appropriate target diseases for TNP-470 clinical trials.

Animals↗
PubMed1993

Inhibition of tumor growth and metastasis of rodent tumors by the angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470; AGM-1470).

The effect of the potent angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), a semisynthetic analogue of fumagillin, on tumor growth and metastasis was studied using rodent tumors. Injection of TNP-470 s.c. inhibited tumor growth in a dose-dependent manner, and the tumor sizes of B16BL6 melanoma, M5076 reticulum cell sarcoma, Lewis lung carcinoma, and Walker 256 carcinoma were maximally reduced to 16, 10, 17, and 4% of that in the respective control. The activity of TNP-470 upon i.v. injection was slightly weaker than that following s.c. injection. This tendency was observed for all the tumors tested. Injection i.v. (infusion) of TNP-470 increased the life span of Walker 256 carcinoma-bearing rats by 183% over the control, while bolus i.v. injection increased the life span by only 47%. TNP-470 reduced the number of pulmonary metastatic foci of i.v. inoculated B16BL6 melanoma in a dose-dependent manner, and the number of metastatic foci was reduced to 10% of that in the control by treatment with TNP-470 at 60 mg/kg, 3 times/week. The mean survival time of B16BL6 tumor-bearing mice treated with TNP-470 using this regimen was extended by 56% over that of control mice. TNP-470 at 10 mg/kg every day also reduced the number of metastatic foci of M5076 sarcoma in the liver after resection of the tumor from the primary site. Adriamycin at the same dose only slightly reduced the number of metastatic foci, even though TNP-470 and Adriamycin showed roughly equal inhibitory activity against M5076 sarcoma growth. TNP-470 extended the mean survival time of M5076 tumor-bearing mice by more than 100% over that of control mice at 30 mg/kg every 3 days, while Adriamycin extended mean survival times by maximally 20% at 10 mg/kg. These results show that the angiogenesis inhibitor TNP-470 has strong inhibitory activities against in vivo growth and metastasis of a wide variety of tumors.

Animals↗
PubMed1993

Fifty sequenced-tagged sites on human chromosome 11.

Fifty novel sequenced-tagged sites (STSs) were identified from cosmid clones mapped to human chromosome 11. DNA sequences were determined for one or both cloning ends of 69 cosmid markers that had each been localized to 1 of 24 subchromosomal regions by means of hybridization to somatic cell hybrid panels. Proper primer sequences and appropriate conditions for a polymerase chain reaction (PCR) were determined for each marker. Twenty-one of the cosmids were not suitable for generating STSs, mainly because both of their ends contained repetitive elements such as Alu and L1 sequences; however, some were inappropriate because the sizes of their PCR products from human DNA, used as template, were same as those from yeast DNA. Finally, 50 STSs were established from 48 clones: 20 were derived from markers localized on the short arm and 30 from the long arm. These STSs can serve as new reagents for investigating human DNA in somatic cell hybrids and for isolating yeast artificial chromosomes to anchor large DNA contigs and fine-scale physical maps of chromosome 11.

Base Sequence↗
PubMed1993

Analysis of a genetic mutation in an electrophoretic variant of the human lactate dehydrogenase-B(H) subunit.

An electrophoretic variant of the lactate dehydrogenase (LDH)-B(H) subunit was discovered in a patient with diabetes mellitus. His LDH activity in serum was slightly lower than normal and the LDH isozyme pattern showed an abnormal migration indicating an LDH-B subunit variant of the fast type. The LDH containing the variant subunit revealed a decreased heat stability. DNA analysis of the variant allele detected a base substitution, an A to G transition, at codon 6 (AAA-->GAA). The mutation resulted in the replacement of a lysine by a glutamic acid (K6E). The change may cause the heat instability and affect the net charge of the variant subunit, resulting in an electrophoretic LDH-B subunit variant of the fast type.

Aged↗
PubMed1993

Detection and characterization of new genetic mutations in individuals heterozygous for lactate dehydrogenase-B(H) deficiency using DNA conformation polymorphism analysis and silver staining.

Human lactate dehydrogenase (LDH)--B(H) mutant genes were analyzed by polymerase chain reaction (PCR) and DNA conformation polymorphism. We used polyacrylamide gradient gel and silver staining procedures for DCP analysis, and observed abnormal migration patterns in individuals heterozygous for the LDH-B deficiency. Subsequent sequence determination of the mutant alleles consistently resulted in detection of three single base substitutions (transversions), viz., a C to A at residue "35" (GCG, Ala-->GAG, Glu), a T to G at residue "172" (TTT, Phe-->GTT, Val), and an A to T at residue "176" (ATG, Met-->TTG, Leu). Furthermore, mismatched PCR or amplification refractory mutation system was developed for the rapid screening and confirmation of these mutations. These amino acid replacements may cause conformational changes in neighboring residues; this probably affects the active site arrangement and results in the loss of enzyme activity.

Amino Acid Sequence↗
PubMed1993

Establishment of a human small cell lung carcinoma cell line carrying amplification of c-myc gene and chromosomal translocation of t(3p;6p) and t(12q;17p).

A transplantable tumor and an in vitro culture cell line (GK-T3) were established from metastatic liver tissue of human small cell lung carcinoma (SCLC). Southern blot analysis revealed about 30-fold amplification of c-myc gene in the tumor cells in liver, xenografts, and in vitro cell line. The degree of c-myc amplification was essentially conserved through serial passages in nude mice and cultivation in vitro. The level of c-myc mRNA was significantly increased in these cells. Cytogenetically, numerical and complex structural abnormalities were observed in GK-T3 cells, including t(3p;6p), t(12q;17p), two homogeneously staining regions (hsrs) and several double minutes (dmins). These results suggest that activation of c-myc gene and alteration of gene(s) around these chromosomal breakpoints may play a role in tumorigenesis of GK-T3 SCLC.

Aged↗
PubMed1993

Hot water epilepsy with pineal cyst and cavum septi pellucidi.

A case of reflex epilepsy accompanied by pineal cyst and cavum septi pellucidi induced by hot water bathing is presented. The patient is a 25-year-old male who has had six episodes of convulsions during the last three years. The seizures were diagnosed as a complex partial epilepsy followed by generalized tonic seizures. We have succeeded in recording his electroencephalogram (EEG) during convulsions. Moreover, a magnetic resonance imaging (MRI) study revealed a pineal cyst and cavum septi pellucidi. This is quite a rare form of adult hot water epilepsy accompanied by intracranial malformations.

Adult↗
PubMed1993

Membranous nephropathy associated with nodular sclerosing Hodgkin's disease.

A 61-year-old man developed steroid-resistant nephrotic syndrome in which renal biopsy showed membranous nephropathy. Six months after the initial presentation, nodular sclerosing Hodgkin's disease was diagnosed. Cyclophosphamide, vincristine, prednisolone and procariazine chemotherapy was administered, after which proteinuria gradually decreased resulting in complete remission in the course of 7 months. A second renal biopsy, which was undertaken 4 months after complete remission, revealed significant histological improvement with disappearance of immune deposit.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Pharmacokinetics of nefiracetam and three metabolites in humans and stereoselective hydroxylation of its pyrrolidine ring.

1. The kinetics of nefiracetam (I) and three metabolites (II-IV) were investigated in healthy volunteers. Compounds I-IV in serum and urine were measured by h.p.l.c. 2. After a single 200 mg dose of nefiracetam the drug was absorbed rapidly and showed peak serum levels of 16.3 +/- 0.9 nmol/ml. Cmax values of the three metabolites were comparatively low (0.96-4.89 nmol/ml), and tmax and t1/2 values of the metabolites (4.1-9.6 h and 7.8-21.9 h, respectively) were longer than those of I (1.6 h and 3.9 h respectively). Urinary excretion of I in 24 h was about 5% of the dose. The major urinary metabolite, a pyrrolidine ring scission product (IV), had a mean total excretion of 17.8% dose. The total of all four compounds in urine amounted to 43.4% dose. 3. In a multiple-dose study (daily 3 x 200 mg doses of nefiracetam for 7 days), the serum concentration profile of each compound indicated that the steady state was reached in 7 days. 4. Metabolite II existed as a racemate and III mainly as the (-)-enantiomer in human urine.

Adult↗
PubMed1993

TAN-1120, a new anthracycline with potent angiostatic activity.

A potent angiogenesis-inhibitory compound TAN-1120 was found to be produced by a Streptomyces species isolated from a soil sample. The producing organism was characterized as a new subspecies of S. triangulatus and named S. triangulatus subsp. angiostaticus subsp. nov. due to its specific ability to produce the compound. This substance was isolated as a red powder by a combination of organic solvent extraction, silica gel column chromatography and preparative HPLC using an ODS column. Its structure was elucidated by chemical reactions and spectral analyses to be a new baumycin-group anthracycline. Reduction of TAN-1120 gave two compounds, a deoxy derivative and baumycin A1. TAN-1120 showed remarkably potent angiostatic activity in two conventional angiogenesis assay systems in vivo, while doxorubicin and daunomycin had far weaker activity. It strongly inhibited proliferation of vascular endothelial cells did not prevent capillary cord formation in vitro by the endothelial cells on extracellular matrix-coated plates. TAN-1120 is one of the most potent angiostatic agents reported.

3T3 Cells↗
PubMed1993

Early intensive therapy for clinical remission of active IgA nephropathy: a three-year follow-up study.

To achieve clinical remission, intensive therapy in active IgA nephropathy was conducted on a trial basis. Forty-five patients with active IgAN in which cellular crescents were present were divided into two groups. The patients in one group (Group A, N = 19) were treated with a combined regimen of steroid pulse, cyclophosphamide (4 months), dipyridamole (36 months) and warfarin. The patients in the other group (Group B, N = 26) were treated with tonsillectomy in addition to the same regimen as Group A. Three years after the initiation of treatment, proteinuria and hematuria had significantly decreased in both groups, and the renal function in Group B was significantly improved. Remission of proteinuria and hematuria was achieved in five patients (26.3%) and eight patients (42.1%), respectively, in Group A, and 14 patients (53.8%) and 20 patients (76.9%), respectively, in Group B. These results indicate that early intensive therapy combined with tonsillectomy in active IgAN is potentially of great benefit from both the medical and socioeconomic points of view.

Adolescent↗
PubMed1993

Predictive value of small crescents in IgA nephropathy: analysis of four patients showing a deteriorated renal function during a long follow-up period.

Four patients with IgA nephropathy developed a chronic renal failure during a long follow-up period ranging from three to 8.5 years (mean 6.4 years). All patients showed a normal renal function, normal blood pressure and mild proteinuria at the time of the first renal biopsy. The first biopsies showed focal mesangial proliferation with small cellular crescents in a small percentage of the observed glomeruli. No case showed sclerotic changes in the interstitium and vessels. In contrast, at the second biopsies, all of them exhibited a deteriorated renal function, hypertension and massive proteinuria. The second biopsies revealed marked sclerotic changes in the glomeruli, interstitium, and vessels with significant focal segmental glomerular sclerosis and adhesions. Since no established factors predisposing the patients to chronic renal insufficiency had been observed at the time of the first biopsy, it was suggested that small crescents, even if focal, should be regarded as indicating an unfavorable prognosis.

Adolescent↗