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Biomedical subjects

K Oka

Publications and source records attributed to K Oka.

At least 343 records · Page 19Linked to original sources

Adenocarcinoma of the cervix treated with radiation alone: prognostic significance of S-100 protein and vimentin immunostaining.

Fifty-nine patients with adenocarcinoma of the cervix were treated with radiation alone (eight stage I, 15 stage II, 25 stage III, and 11 stage IV patients). The disease-free 5-year survival rates for each stage were 63, 58, 30, and 9%, respectively. The incidence of vimentin-positive cancer cells in 20 women with adenosquamous carcinoma was significantly higher than that in 34 with endocervical adenocarcinoma (25 versus 6%; P less than .05). The outcome of stage III patients with S-100 protein-positive dendritic cells (Langerhans cells) or without vimentin-positive cancer cells was significantly better than that of women negative for S-100 protein or positive for vimentin (P less than .025 and P less than .05, respectively). These findings indicate that, along with clinical stage, Langerhans cell infiltration and the vimentin negativity of cancer cells are favorable prognostic factors in stage III adenocarcinoma of the cervix treated with radiation alone.

Adenocarcinoma↗

Promotion of lymphocyte blastogenesis by hemodialysate of chronic renal failure.

Effects of hemodialysate of patients with chronic renal failure (CRF) on blastogenesis of human peripheral blood lymphocytes in the presence of concanavalin A or phytohemagglutinin was investigated. Hemodialysates from 11 CRF patients significantly promoted lymphocyte blastogenesis when compared with control dialysis fluids (p less than 0.01). The strongest activity (39% promotion of the lymphocyte blastogenesis) was observed with a hemodialysate obtained at 0.5 h after beginning dialysis. The activity decreased thereafter. On the contrary, the blastogenesis-promoting activity in plasma decreased significantly after hemodialysis (p less than 0.01, n = 11). To further confirm the presence of low-molecular-weight factor(s) in CRF, ultrafiltration of plasma obtained from CRF and healthy subjects was conducted using a membrane filter with a molecular cutoff of 3,000 D. The filtrate of CRF plasma significantly promoted lymphocyte blastogenesis when compared to that of healthy subjects (p less than 0.01). Heat treatment (100 degrees C, 40 min) did not abolish the activity of the hemodialysate. None of the drugs taken by the patients nor creatinine accumulated in CRF promoted the lymphocyte blastogenesis. Chromatographic analysis of a hemodialysate demonstrated several peaks which were absent in the control dialysis fluid. These results showed the presence of a novel lymphocyte-stimulating factor(s) in CRF, which is heat stable and has a low molecular weight (less than 3,000 D).

Allopurinol↗

[Asymptomatic multilocular cystic renal cell carcinoma].

From January 1982 to December 1989, we experienced seven multilocular cystic renal cell carcinomas (MLCRCCs) in 36 asymptomatic renal cancers incidentally diagnosed, and none in 23 symptomatic renal cancers (p less than 0.05). No multiocular cystic nephromas (MLCNs) appeared in either group. Though MLCRCCs have been considered to be, in general, extremely rare, they do occur in asymptomatic renal cancers. A multiloculated renal mass with thick septum discovered in an adult by ultrasonography or CT scan should be suspected as being a MLCRCC rather than a MLCN.

Adult↗

Malignant histiocytosis. A report of three cases.

Three cases of malignant histiocytosis were immunohistochemically studied. The cases included the following three patients: a 38-year-old man, a 44-year-old man, and a girl aged 5 years 9 months. All three patients died within 3 months of hospitalization. They had a high fever (temperature over 38.5 degrees C), lymph node swelling, hepatosplenomegaly, and pancytopenia. Blastoid and hemophagocytic cells proliferated in the bone marrow and lymph nodes, especially in the sinuses of the latter. We diagnosed malignant histiocytosis in the three cases based on clinical features, extremely poor prognoses, and the morphologic features and growth pattern of blastoid and hemophagocytic cells. Blastoid and hemophagocytic cells expressed phenotype Mac-387+/KP1+/lysozyme+/polyclonal CD3+. The Mac-387 and KP1 antigens and lysozyme are markers for monocytes/macrophages, and polyclonal CD3 is a marker for T lymphocytes. Therefore, we suggest that a certain number of cases of malignant histiocytosis have a biphenotypic nature, namely, the T cell and macrophage, although many cases of malignant histiocytosis have been reported as expressing only T-lymphocyte antigens.

Adult↗

[A case of tranilast-induced cystitis with transient ECG changes].

A case of tranilast (Rizaben)-induced cystitis accompanied with possibly hypereosinophilic heart syndrome was described. A 75-year-old male, who had been taking tranilast for allergic dermatitis for two months, was admitted for severe bladder stimulating symptoms which was unresponsive to antibiotic therapies. Clinical examination revealed tenderness of the prostate, aseptic pyuria, eosinophilia, liver dysfunction and electrocardiographic disorders including atrial fibrillation, T-wave inversions and lowered ST segment without any cardiac symptoms. Cystitis symptoms, pyuria, eosinophilia and liver dysfunction improved within several days after discontinuance of tranilast, and ST-T changes on ECG gradually normalized within a few months. Tranilast-induced cystitis has been demonstrated as a type of eosinophilic cystitis. Since pathologic findings of eosinophilic cystitis and hypereosinophilic heart syndrome are markedly similar and all symptoms and signs disappeared after deprivation of tranilast, it appears likely that eosinophilic inflammation was induced to the heart, liver, bladder and prostate of the current patient by tranilast.

Aged↗

[Prophylaxis of thrombosis in a pregnant woman with congenital antithrombin III deficiency: changes in hemostatic molecular markers before the onset of thrombosis].

A pregnant woman with congenital antithrombin III (AT III) deficiency was given AT III concentrate and warfarin at the first and after 36th week of gestation periods and at the other gestation period, respectively. The patient developed thrombosis in the left leg, but fibrinopeptide A (FPA) and thrombin-AT III complex (TAT) had already shown high values one week before, suggesting the possibility of their being forecast markers of thrombosis. The administration of AT III concentrate caused an improvement in thrombosis. Therefore, in case of high FPA and TAT values as determined one or two times a week, the administration of AT III concentrate was thought necessary. In case of warfarin, however, non-administration during the 6th-9th weeks of gestation for the purpose of avoiding teratogenicity and frequent blood coagulation tests taking heed of overdosage for the purpose of avoiding fetal central nervous system abnormalities were suggested necessary. Delivery was uneventful, both mother and child being doing very well; umbilical blood AT III activity was 18%. It is generally difficult for us to form the diagnosis as AT III deficiency only from AT III activity at neonatal stage, but in the present study, we analyzed the restriction fragment length polymorphism of the AT III gene using umbilical blood, and succeeded in diagnosing the neonatal child as AT III deficiency.

Adult↗

Expression of human milk fat globule-1 in carcinomas of the uterine cervix treated with radiation therapy alone.

Expression of human milk fat globule-1 (HMFG-1) and HMFG-2 in cancer cells was studied in 269 patients with stage III and IV uterine cervical carcinomas that were treated with radiation therapy alone. They consisted of 233 patients with squamous cell carcinomas and 36 with adenocarcinomas. Of 233 patients with squamous cell carcinomas, 33 were negative for HMFG-1, and the other 200 were positive for HMFG-1. The 5-year survival rate was 36.4% (12/33) in HMFG-1-negative cases and 52.0% (104/200) in HMFG-1-positive ones. Patients who were negative for HMFG-1 showed a somewhat poorer prognosis than those who were positive for HMFG-1. The local control rates of HMFG-1-negative and -positive patients with squamous cell carcinomas were 58.6% (17/29) and 75.3% (125/166), respectively. Patients who were negative for HMFG-1 tended to show a lower local control rate than those who were positive for HMFG-1. In the uterine cervix, about one third of cells, only in the basal layer of stratified squamous epithelium, were positive for HMFG-1. These findings suggest that expression of HMFG-1 in cancer cells may mean the radiosensitivity.

Adenocarcinoma↗

A missense mutation (Trp86----Arg) in exon 3 of the lipoprotein lipase gene: a cause of familial chylomicronemia.

We have investigated a patient of English ancestry with familial chylomicronemia caused by lipoprotein lipase (LPL) deficiency. DNA sequence analysis of all exons and intron-exon boundaries of the LPL gene identified two single-base mutations, a T----C transition for codon 86 (TGG) at nucleotide 511, resulting in a Trp86----Arg substitution, and a C----T transition at nucleotide 571, involving the codon CAG encoding Gln106 and producing Gln106----Stop, a mutation described by Emi et al. The functional significance of the two mutations was confirmed by in vitro expression and enzyme activity assays of the mutant LPL. Linkage analysis established that the patient is a compound heterozygote for the two mutations. The Trp86----Arg mutation in exon 3 is the first natural mutation identified outside exons 4-6, which encompass the catalytic triad residues.

Amino Acid Sequence↗

A missense (Asp250----Asn) mutation in the lipoprotein lipase gene in two unrelated families with familial lipoprotein lipase deficiency.

We have identified the molecular basis for familial lipoprotein lipase (LPL) deficiency in two unrelated families with the syndrome of familial hyperchylomicronemia. All 10 exons of the LPL gene were amplified from the two probands' genomic DNA by polymerase chain reaction. In family 1 of French descent, direct sequencing of the amplification products revealed that the patient was heterozygous for two missense mutations, Gly188----Glu (in exon 5) and Asp250----Asn (in exon 6). In family 2 of Italian descent, sequencing of multiple amplification products cloned in plasmids indicated that the patient was a compound heterozygote harboring two mutations, Arg243----His and Asp250----Asn, both in exon 6. Studies using polymerase chain reaction, restriction enzyme digestion (the Gly188----Glu mutation disrupts an Ava II site, the Arg243----His mutation, a Hha I site, and the Asp250----Asn mutation, a Taq I site), and allele-specific oligonucleotide hybridization confirmed that the patients were indeed compound heterozygous for the respective mutations. LPL constructs carrying the three mutations were expressed individually in Cos cells. All three mutant LPLs were synthesized and secreted efficiently; one (Asp250----Asn) had minimal (approximately 5%) catalytic activity and the other two were totally inactive. The three mutations occurred in highly conserved regions of the LPL gene. The fact that the newly identified Asp250----Asn mutation produced an almost totally inactive LPL and the location of this residue with respect to the three-dimensional structure of the highly homologous human pancreatic lipase suggest that Asp250 may be involved in a charge interaction with an alpha-helix in the amino terminal region of LPL. The occurrence of this mutation in two unrelated families of different ancestries (French and Italian) indicates either two independent mutational events affecting unrelated individuals or a common shared ancestral allele. Screening for the Asp250----Asn mutation should be included in future genetic epidemiology studies on LPL deficiency and familial combined hyperlipidemia.

Amino Acid Sequence↗

Predominant expression of lambda light chain in adult cases with non-T-cell acute lymphocytic and chronic myelogenous leukemia in lymphoid blast crisis.

The authors investigated cytoplasmic immunoglobulins of the leukemic cells from 20 adult cases with non-T-cell acute lymphocytic leukemia (ALL) and from three cases with chronic myelogenous leukemia in lymphoid blast crisis using immunoelectron microscopy. They also studied these cases using various monoclonal antibodies. Of the 23 examined cases, nine were negative for both heavy and light chains of immunoglobulins; the authors defined these as common ALL. Two cases were positive for the mu chain but were negative for light chains; the authors defined these as pre-B-cell ALL. The remaining 12 cases were positive for either kappa or lambda light chains; these were defined as B-cell ALL. Of the 12 cases positive for light chains, 11 were positive for the lambda chain. Seven cases of the 11 positive cases for the lambda chain were negative for heavy chains. Eleven cases were positive either for both My4 and My9 or for one of the two antibodies. From these results, the authors conclude the following: (1) the ratio of pre-B-cell ALL among non-T-cell ALL cases (two of 23 cases) was lower in adults than in children; (2) of the light chain-positive cases, the lambda light chain-positive cases predominated (11 of 12 cases); (3) heavy chain-negative, lambda chain-positive cases (seven cases) were observed; and (4) one half of the leukemia cases showed dual phenotypes of B-cell and myeloid cell lineages.

Adolescent↗

Transition of Ki-67 index of uterine cervical tumors during radiation therapy. Immunohistochemical study.

Histopathologic and Ki-67-staining features of cancer cells were investigated in biopsy specimens before and during radiation therapy in 29 patients with cervical squamous cell carcinoma. No morphologic changes were observed up to doses of 540 cGy. A few intact cancer cells remained up to doses of 2700 cGy. Moderate changes in the cancer cells were noticed in patients who received 900 cGy or more, i.e., multinuclei, swollen nuclei and cytoplasms, and prominent large nucleoli. At doses of 1800 cGy or greater, many cancer nests had severely damaged cancer cells with features such as cytolysis, karyolysis, karyorrhexis, pyknosis, and bizarre giant cells. There was no mitosis in the cells of patients who received doses greater than 1800 cGy. The Ki-67-positive cancer cells showed diffuse nuclear-stainings and dot-stainings before radiation therapy. Radiation doses more than 900 cGy changed the staining pattern of the Ki-67 antibody; large irregular spot-stainings and ring-stainings were observed predominantly. The Ki-67 index initially increased with the radiation dose; the mean Ki-67 indices before radiation therapy and at radiation doses of 180 cGy, 540 cGy, and 900 cGy were 41%, 50%, 63%, and 68%, respectively. The indices decreased when the dose was increased further, and they were 39% and 20% at doses of 1800 cGy and 2700 cGy, respectively. Possible explanations, including recruitment of quiescent cells, for the change in Ki-67 staining are discussed.

Adult↗

Simple and accurate determination of methylpyrazines in biofluids using high-performance liquid chromatography.

The determination of six methylpyrazines was performed using high-performance liquid chromatography (HPLC). Methylpyrazines were simultaneously extracted and injected onto a silica gel column with a syringe-type minicolumn packed with diatomaceous earth granules. The extraction-injection solvent used was dichloromethane and the mobile phase solvent for HPLC was dichloromethane containing 0.08% of 1.65 M ammonia solution and 0.5% of methanol. Methylpyrazines were detected using an ultraviolet detector set at 275 nm. Linear relationships between the amount of sample and peak height were confirmed from 50 ng/ml to 10 micrograms/ml of the biofluids. When an aliquot of 10 microliters of biofluid was introduced to the minicolumn, the detection limit of methylpyrazines was as low as 30 ng/ml with each pyrazine derivative. The method is simple and accurate and is thus applicable to pharmacokinetic studies which are performed on animals. The results showed that the possible pharmacological effects of methylpyrazines might be evaluated pharmacokinetically using this newly developed technique.

Animals↗

Molecular cloning of mouse hepatic triacylglycerol lipase: gene expression in combined lipase-deficient (cld/cld) mice.

cDNA clones coding for mouse hepatic triacylglycerol lipase (HL) were isolated from a mouse liver cDNA library with a human HL cDNA as a probe. The cloned HL cDNA of 1652 nucleotides predicts a mature protein of 488 amino acids preceded by a signal peptide of 22 amino acids. Two potential sites for N-glycosylation are identified, which are both conserved in rat and human HL. Combined lipase deficiency (cld) is a recessive mutation in mice, which causes the functional deficiency of HL and lipoprotein lipase, the isolated cDNA was used to study the expression of HL gene in cld/cld mice. Northern blot analysis of total cellular RNA from livers of cld/cld and normal mice showed that there are two mRNA species for HL with the sizes of 1.8 and 1.9 kilobases in both groups. However, the mRNA for HL was more abundant in cld/cld than in normal mice. RNase A protection assay of HL mRNA suggested that the multiple mRNA species for HL in cld/cld and normal mice are generated by differential utilization of polyadenylation signals and that there is no mutation in the structural gene for HL in cld/cld mice. The present study supports our hypothesis that the defect of HL activity in cld/cld mice is caused by abnormal post translational modification or processing of the lipase.

Amino Acid Sequence↗

pH-dependent column fractionation for characterization of endogenous digoxin-like immunoreactive factors in pregnant urine.

Samples of pregnant urine were treated with three diatomaceous earth columns to fractionate organic solvent-soluble components. The first column was pre-injected with the urine sample. The second and the third columns were pre-injected with sodium bicarbonate and sodium hydroxide solutions, respectively; these played an important role in capturing acidic components in the urine extract from the first column. Neutral components could be eluted out from the columns with the organic solvent, while the basic components were retained in the first column. Once strongly and weakly acidic components were captured on the alkaline columns, they were separately treated with an acidic mobile phase and recovered. The digoxin-like activities of each fraction were examined for cross-reactivity to antidigoxin antibody and inhibitory effects on dog kidney Na+, K(+)-ATPase. Both types of reactivity were found in all three fractions and decreased in the following order: strongly acidic, neutral and weakly acidic. The neutral fraction of pregnant urine showed significantly greater cross-reactivity than that of the non-pregnant urine. Following hydrolysis of the pregnant urine with beta-D-glucuronidase, the cross-reactivity of the neutral fraction increased significantly. High performance liquid chromatographic analysis showed that several components in the neutral fraction had apparently increased after the hydrolysis, showing the possible presence of unknown digoxin-like components in the pregnant urine.

Antibodies↗

Detection of loss of heterozygosity in the p53 gene in renal cell carcinoma and bladder cancer using the polymerase chain reaction.

The human p53 gene, a putative tumor suppressor gene, has a polymorphism in amino acid residue 72. We recently developed a method of detecting codon 72 polymorphism in this gene by digestion of polymerase chain reaction-amplified DNA using an allele-specific restriction endonuclease. This polymorphism allows the identification of loss of heterozygosity for the coding region of the p53 gene in limited tissue samples in a short time without using radioactive materials. We examined 33 patients with renal cell carcinoma and 29 with bladder cancer; heterozygosity in the p53 gene was lost in 60% (6 of 10 cases) and 73% (8 of 11 cases) of the renal and bladder tumors, respectively. Additionally, the assay's sensitivity could be improved by using DNA extracted from frozen sections of the tumors. Because the proportions of tumor cells and nontumor cells could be assessed by microscopic evaluation of the frozen sections, we were able to minimize contamination from nontumor cells, which occasionally causes false readings of retained heterozygosity. This simple and sensitive method for detecting loss of heterozygosity in the p53 gene makes it possible to rapidly screen a large number of tissue samples and has the potential to be a useful diagnostic tool for a wide variety of human neoplasms.

Carcinoma, Renal Cell↗

Morphometric analysis of the glomerular capillary area--a comparison of minimal change nephrotic syndrome, focal glomerular sclerosis, and pre-eclampsia.

A morphometric analysis was performed to compare the capillary area in non-sclerotic glomeruli in focal glomerular sclerosis (FGS), pre-eclampsia with focal sclerotic change of the glomeruli, and minimal change nephrotic syndrome (MCNS). The mean and standard deviation of the capillary area was greater in FGS than in pre-eclampsia and MCNS. Tubulo-interstitial lesions, such as tubular atrophy, interstitial fibrosis, and lymphocytic infiltration, were more severe in FGS than in pre-eclampsia. The presence of tubulo-interstitial changes including tubular atrophy and interstitial fibrosis with lymphocytic infiltration is thought to be an important prognostic factor in pre-eclampsia as well as in FGS. Unequal dilatation of the glomerular capillaries in non-sclerotic glomeruli may be harmful to the glomeruli and may lead to the development of glomerular sclerosis.

Adolescent↗