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Biomedical subjects

K Koyama

Publications and source records attributed to K Koyama.

At least 163 records · Page 9Linked to original sources
PubMed1998

Relatively high F-18 fluorodeoxyglucose uptake in paranasal sinus aspergillosis: a PET study.

We report a case of maxillary sinus (MS) aspergillosis studied by positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) and by 67Ga-citrate (Ga) single photon emission computed tomography (SPECT). The FDG uptake existed in the lesion and along the inflammatory edematous mucous membrane of the MS. Ga uptake occurred not only in the lesion and in the mucous membrane but also in the MS. Relative quantification, the standardized uptake value (SUV) of the lesion showed relatively high FDG uptake (3.7). But in other reports, many malignant head and neck tumors had a SUV below 3.7. It was thought to be difficult to differentiate between aspergillosis and malignant head and neck tumors by FDG-PET.

Aged↗
PubMed1998

Molecular analysis of the androgen receptor gene in 4 patients with complete androgen insensitivity.

Androgen insensitivity syndromes are due to defects in the androgen receptor gene. In this study, we analyzed the androgen receptor gene in four cases with complete androgen insensitivity syndrome. In patient 1, one substitutional mutation [arginine (codon CGC) to cysteine (codon TGC) at position 774] of exon F was identified. This position was located in the hormone binding domain and appeared to be one hot spot of mutations because the mutations at the same position in several unrelated cases were reported before. In patient 2, one substitutional mutation [tyrosine (codon TAT) to cysteine (codon TGT) at position 571] of exon B was identified. This position was located in the DNA binding domain. In patients 3 and 4 (siblings), one substitutional mutation [arginine (codon CGA) to glutamine (codon CAA) at position 752] of exon E was identified. Taken together, these abnormalities might be related to the pathogenesis of complete androgen insensitivity.

Adolescent↗
PubMed1998

Effects of decreased plasma glutamine concentrations on peripheral lymphocyte proliferation in rats.

The relationship between exercise-induced lowering of plasma glutamine concentrations and proliferation of peripheral lymphocytes was investigated in male Wistar rats. The T-lymphocyte proliferative responses to the mitogen, concanavalin A, were determined by incorporation of radiolabelled thymidine into the DNA in vitro. The rats ran 2 h x day(-1), 6 days x week(-1) for 4 weeks. Analysis immediately after the final period of exercise showed T-lymphocyte proliferation to be significantly depressed, together with a marked decrease in plasma glutamine concentrations. There were also significant increases in serum corticosterone concentrations immediately after exercise. However, following 24-h recovery, this exercise-induced immunosuppression was not statistically significant when compared with the age-matched control group. In the second experiment, in order to clarify the importance of glutamine for immunological function in vivo, methionine sulfoximine, an effective inhibitor of glutamine synthetase was injected intraperitoneally (12.5 mg x kg body mass[-1]). Plasma glutamine concentrations were decreased 4 h after the injection, compared with the placebo control group, and this resulted in a significant decrease in the rate of T-lymphocyte proliferation. This treatment had no effects on serum corticosterone concentrations. These results would suggest that the chronic exercise-induced reduction in proliferation of peripheral T-lymphocytes is a transient reversible phenomenon, which returns to normal levels within 24 h of the final training period. It is also conceivable that this exercise-induced immunosuppression is associated with a decrease in circulating glutamine concentrations.

Amino Acids↗
PubMed1998

Localization of the gene responsible for Peutz-Jeghers syndrome within a 6-cM region of chromosome 19p13.3.

Patients with Peutz-Jeghers syndrome (PJS), an autosomal dominant disease characterized by hamartomatous polyposis of the gastrointestinal tract, are thought to be predisposed to malignancies of the digestive tract, genital tract, and other organs. Using microsatellite markers on chromosome 19p, we have closely defined the region containing the gene responsible for this disorder through linkage analysis in seven affected families. The lack of obligate recombinants at two of these loci, D19S883 and D19S878, with maximum LOD scores of 2.88 and 3.75, confirmed the localization of the PJS locus to chromosome 19. Furthermore, haplotype analysis placed the PJS locus within a 6-cM telomeric region of chromosome 19p, between D19S886 and D19S565.

Centromere↗
PubMed1998

Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome.

Peutz-Jeghers Syndrome (PJS) is an autosomal dominant hereditary disease characterized by hamartomatous polyposis involving the entire bowel. Recently STK11, a gene bearing a mutation responsible for PJS, was isolated. We investigated the entire coding region of STK11 in 15 unrelated PJS families by the PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) method and PCR-direct sequence analysis, and found nine different, novel mutations among ten of those families. One nonsense mutation and five different frameshift mutations (two families carried the same mutation), all of which would cause truncation of the gene product, were found in seven families; mutations found in five families were clustered within exon 6. Among these five mutations, three occurred at the mononucleotide-repeat region (CCCCCC) of codons 279-281, suggesting that this region is likely to be a mutational hotspot of this gene. One of the remaining three families carried a 3-bp in-frame deletion that would eliminate an asparagine residue within a kinase domain of the product; the other two carried intronic mutations at or adjacent to the consensus dinucleotide sequences of splice-acceptor or -donor sites, which were likely to lead to aberrant splicing.

AMP-Activated Protein Kinase Kinases↗
PubMed1998

Pancytopenia associated with 5-aminosalicylic acid use in a patient with Crohn's disease.

We report a case of pancytopenia in a 23-year-old man with Crohn's disease who was treated with 5-aminosalicylic acid (Pentasa; Nisshin, Tokyo, Japan) 3.0 g/day. He developed fever, nausea, diarrhea, and malaise and stopped taking on the third day after commencing Pentasa. Ten days after withdrawal of Pentasa, he was admitted to hospital because of worsening symptoms. Hematologic evaluation disclosed pancytopenia: red blood cells 283 x 10(4)/mm3; white blood cells 700/mm3; and platelets 8000/mm3. Other pertinent laboratory data, including liver and renal function tests results, serology for virus infection, and serum levels of vitamin B12 and folic acids, were normal. Bone marrow examination showed a generalized hypocellular picture, suggestive of drug-induced bone marrow suppression. He received blood transfusion and recombinant human granulocyte colong-stimulating factor (filgrastim). The leucopenia and thrombocytopenia resolved on the 7th and 13th days of hospitalization, respectively. The anemia continued because of bloody stool caused by Crohn's disease. However, reticulocytes were markedly increased in number on the 13th day of hospitalization. He is well at 9 months follow-up. Excluding other causes, Pentasa-associated pancytopenia was considered. The increasing use of this agent is expected, because of the increasing number of patients with inflammatory bowel disease. Careful clinical and hematological monitoring should be performed, especially for the first 3 months, in patients beginning treatment with Pentasa. The drug should be withdrawn immediately if there is a suspicion of blood disorders.

Adult↗
PubMed1998

Characteristics of two cancer cell lines derived from metastatic foci in liver and peritoneum of a patient with colon cancer.

Two cancer cell lines were established in vitro from a single patient with colon cancer; AKT-CC-K-LM cells from liver metastatic nodules and AKT-CC-K-PC cells from peritoneal dissemination nodules. The two cell lines were similar in doubling time, number of chromosomes, and chromosomal abnormalities. However, they differed in morphology in vitro, in the expression level of cell surface adhesion molecules (carcinoembryonic antigen; CEA, E-cadherin, sialyl Le(a), sialyl Le(x), and CD44v6), and in their metastatic properties. AKT-CC-K-LM cells grew in vitro as adherent clusters and AKT-CC-K-PC cells as adherent single cells. The expression levels of CEA, E-cadherin, sialyl Le(a), and sialyl Le(x) was significantly higher in AKT-CC-K-LM cells. The expression of CD44v6 was significantly higher in AKT-CC-K-PC cells. After the injection of AKT-CC-K-LM cells to the spleen or peritoneal cavity of severe combined immune deficiency mice, metastatic nodules were observed only in the liver. In contrast, the injection of AKT-CC-K-PC cells to the spleen or peritoneal cavity yielded metastatic nodules only in the peritoneal cavity. These cell lines may contribute to elucidating the relationship between cell surface adhesion molecules and the metastatic properties of cancer cells.

Adenocarcinoma↗
PubMed1998

Preparation of a conjugate of mitomycin C and anti-neural cell adhesion molecule monoclonal antibody for specific chemotherapy against biliary tract carcinoma.

To develop a specific chemotherapy modality for the perineural invasion of neural cell adhesion molecule (NCAM) positive biliary tract cancer, an anticancer drug, mitomycin C (MMC), was covalently bound to anti-NCAM monoclonal antibody (anti-NCAM MoAb) to form a conjugate using the cyanogen bromide method. The substitution ratio of the conjugate determined spectrophotometrically was 3.5 (MMC mol/immunoglobulin G mol). The cytotoxic activity of the conjugate, which was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test in the growth inhibition of the neuroblastoma cell line with NCAM expression, was maintained at 65.8% to 94.5% compared with the same concentration of MMC solution. The binding activity of the conjugate to the NCAM-positive bile duct cancer was examined by immunohistochemical staining and proved to be the same level as that of free anti-NCAM MoAb. The conjugate prepared in this study therefore appeared to be a potentially useful tool for immunotargeting specific chemotherapy against biliary tract cancer with NCAM expression.

Antibiotics, Antineoplastic↗
PubMed1998

Novel germline mutations of hMSH2 in a patient with hereditary nonpolyposis colorectal cancer (HNPCC) and in a patient with six primary cancers.

We screened for germline mutations of mismatch repair genes, hMLH1 and hMSH2, in five Japanese families carrying hereditary nonpolyposis colorectal cancer (HNPCC) and in a patient with multiple primary cancers. Screening the entire coding regions of both genes using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we found two novel germline mutations in hMSH2. One was a 1-bp insertion in exon 12, detected in a patient who had undergone surgery six times for independent tumors (four primary colorectal carcinomas, a small intestinal carcinoma, and an endometrial cancer). The other, in a second patient, was a missense mutation from CTT to TTT at codon 390 in exon 7 that resulted in substitution of phenylalanine for leucine. This conservative alteration was not found in any of 50 normal controls, but we cannot exclude the possibility that it may represent a rare polymorphism rather than a factor in the disease.

Adult↗
PubMed1998

VNTR (variable number of tandem repeat) sequences as transcriptional, translational, or functional regulators.

VNTR (variable number of tandem repeat) markers, also called single-copy minisatellites, were originally isolated from human DNA as highly informative restriction fragment length polymorphisms for mapping purposes. Evidence has lately emerged that some VNTR sequences play significant roles in the regulation of transcription, and that some may also influence the translational efficiency or stability of mRNA, or modify the activity of proteins by altering their structure. Some apparent associations of VNTR sequences with personality traits or with susceptibility to diseases have strengthened the likelihood that these tandemly-repeated genomic elements are of physiological and biological importance. In this review, we summarize recent progress in efforts to clarify mechanisms involving VNTR sequences.

Gene Expression Regulation↗
PubMed1998

Novel missense mutation resulting in the substitution of tyrosine by cysteine at codon 597 of the type X collagen gene associated with Schmid metaphyseal chondrodysplasia.

Schmid metaphyseal chondrodysplasia (SMCD) is one of the most common forms of the osteochondrodysplasias. Mutations or deletions in the COL10A1 gene that encodes type X collagen have been shown to cause this disorder. Most of the gene mutations and deletions are located in the non-collagenous carboxy (C)-terminal (NC1) domain. We describe a novel missense mutation in a patient with SMCD that leads to the substitution of Tyr at codon 597 by Cys in the NC1 domain. Sequence analysis indicated that the proband was heterozygous for the mutation. Her parents were homozygous for the normal sequence, indicating the de-novo occurrence of this mutation.

Adult↗
PubMed1998

Quantitative analysis of anti-emetic principle in the tubers of Pinellia ternata by enzyme immunoassay.

A crude globulin fraction was isolated from the tubers of Pinellia ternata (Thunb.) Breit. Tubers of P. ternata are one of the well known Chinese traditional medicines. It is used on account of its anti-emetic effect. 6KDP was separated by means of gel filtration and chromatography on CM-Toyopearl 650 M from the crude globulin fraction. 6KDP is a glycoprotein of M.W. 6 kDa. 6KDP has an anti-emetic activity and hemagglutination activity. Both activities dropped during heat treatment. For the purpose to evaluate the quality of the powdered tubers of P. ternata, the quantitative analysis by means of EIA was established. The contents of 6KDP varied from 5.75 to 8.30%. The assay demonstrated a low cross-reaction with the crude globulin fraction of Colocasia antiquorum, a member of the same family as P. ternata. 6KDP is one of major proteins in the tubers of P. ternata. Thus 6KDP is a marker for quantitative analysis of the tubers of P. ternata.

Antiemetics↗
PubMed1998

Fluorine-18 fluorodeoxyglucose positron emission tomography imaging of parotid mass lesions.

Using X-ray CT or magnetic resonance imaging (MRI), fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) studies were performed in 28 patients with parotid lesions. All lesions except two showed higher accumulation of FDG than normal parotid gland. High accumulation was found in all of 5 carcinomas, all of 6 Warthin's tumors, and 8 of 12 pleomorphic adenomas, with standardized uptake values (SUVs) over 3.0. The mean SUVs of carcinomas, Warthin's tumors, and pleomorphic adenomas were 5.92 +/- 2.05, 7.03 +/- 2.49, and 4.07 +/- 1.55, respectively. On the other hand, all 5 inflammatory lesions demonstrated low accumulation, with mean SUVs of 1.66 +/- 0.89. It is thus difficult to differentiate malignant from benign parotid lesions by SUV on FDG-PET.

Adult↗
PubMed1998

Relationship between human in-vitro fertilization and intracytoplasmic sperm injection and the zona-free hamster egg penetration test.

The zona-free hamster egg penetration test (HEPT) is widely used for evaluating the fertilizing ability of human spermatozoa. However, the relationship between the HEPT and microassisted fertilization has yet to be determined. To evaluate the efficiency of HEPT in selecting the most appropriate method of in-vitro fertilization (IVF), including intracytoplasmic sperm injection (ICSI) in couples with male factor infertility, clinical laboratory data was analysed retrospectively. The patients were divided into groups according to the sperm penetration index as determined by the HEPT: group A (sperm penetration index = 0), group B (sperm penetration index < 15) and group C (sperm penetration index > or = 15). A total of 405 oocytes were collected and inseminated by conventional methods in 69 couples with male factor infertility. In all, 31 out of 148 (20.9%) oocytes fertilized in group A; 35 out of 117 (29.9%) in group B; and 73 of 140 (52.1%) in group C. The clinical pregnancy rates per transfer in groups A, B and C were 0% (0/13), 0% (0/14) and 25.9% (7/27) respectively. Both the fertilization rate and pregnancy rate in group C was significantly higher than in groups A and B. ICSI was carried out in a total of 57 couples and 334 oocytes in metaphase II stage were manipulated. The normal fertilization (2 pronuclear) rate per oocyte was 65.6 +/- 26.0% (mean +/- SD). Out of 127 oocytes, 76 (59.8%) fertilized in group A, 57 out of 87 oocytes (65.5%) in group B and 86 out of 120 oocytes (71.7%) in group C. Of the 56 transfers, 17 clinical pregnancies were obtained, giving an average pregnancy rate of 30.4% per transfer. The clinical pregnancy rates per transfer in groups A, B and C were 17.4% (4/23), 40.0% (4/10) and 39.1% (9/23) respectively. No significant differences were observed in the fertilization rates or in the pregnancy rates between the three groups. In addition, there were no differences in the fertilization and pregnancy rates between the ICSI and IVF patients in group C. These findings suggest that the results of the HEPT are well correlated with the fertilizing ability of human spermatozoa in the patients treated by conventional IVF. Couples suffering from male factor infertility with a sperm penetration index of < 15 (as determined by HEPT) should consider treatment with ICSI, while those with a sperm penetration index of > or = 15 should attempt conventional IVF.

Animals↗