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Biomedical subjects

M Koike

Publications and source records attributed to M Koike.

At least 199 records · Page 11Linked to original sources

A case of silent 21-hydroxylase deficiency with persistent adrenal insufficiency after removal of an adrenal incidentaloma.

A case of an adrenal incidentaloma in a 57-year-old man with silent 21-hydroxylase deficiency is reported. Abdominal computed tomography revealed a right adrenal tumour of 6cm in diameter. There was no evidence of adrenal hormone excess. However, after surgical removal of the adrenal tumour, the patient developed acute adrenal insufficiency. Adrenocortical function has remained low ever since surgery. Pathological examination of the tumour revealed a cortical adenoma. On the basis of increased plasma renin activity and serum 17 alpha-hydroxyprogesterone concentration and decreased 21-hydroxylase activity of the adenoma tissue, the patient was diagnosed as having systemic 21-hydroxylase deficiency. There are two possible mechanisms for the persistent adrenal insufficiency; first the residual left adrenal gland may have been originally hypo-functioning for some reason and, second, the left gland may have lost the ability to regenerate following prolonged suppression by the adenoma. In cases of adrenal incidentalomas with 21-hydroxylase deficiency, the indications for surgical removal should be carefully considered.

Adenoma↗

Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer.

BACKGROUND & AIMS: Microsatellite instability (replication error [RER]) is a characteristic of tumors in hereditary nonpolyposis colon cancer (HNPCC), but the mechanism of HNPCC carcinogenesis is not yet understood. To clarify the nature of HNPCC tumors, RER and genetic changes were compared between HNPCC and non-HNPCC tumors. METHODS: RER and genetic changes were analyzed in 21 HNPCC, 389 familial adenomatous polyposis, and 206 sporadic tumors using polymerase chain reaction, single-strand conformation polymorphism, sequencing, and Southern hybridization. RESULTS. in HNPCC, 95% tumors at all stages showed RER positivity (altered loci, 4.3 of 5). In familial adenomatous polyposis and sporadic tumors, RER positivity (1.7 of 5) was 3% in adenoma and intramucosal carcinoma, 13%-24% in invasive carcinoma, and 35% in carcinoma metastasized to liver. Fifty percent of RER-positive HNPCC tumors had both germline and somatic mutations of hMSH2 or hMLH1 gene, whereas 6% of RER-positive non-HNPCC had somatic mutation. APC, p53, and K-ras-2 mutations and loss of heterozygosity of tumor-suppressor genes were significantly less frequent (P = 0.03 to 0.0006) but transforming growth factor beta type II receptor mutation was significantly more frequent (P = 0.000001) in HNPCC than in non-HNPCC. CONCLUSIONS: RER positivity occurs from an early stage of carcinogenesis in HNPCC but in later stages in non-HNPCC. Most HNPCC tumors may develop through different genetic changes from those in the adenoma-carcinoma sequence, although a certain percentage develops through APC mutation.

Adaptor Proteins, Signal Transducing↗

Study of the changes of serum hyaluronic acid during porcine liver transplantation: influence of warm ischemia.

Twelve porcine liver transplantations were performed to investigate whether serum hyaluronic acid (HA) serves as a marker of warm ischemic injury. Group 1 was a control without warm ischemia (n = 7), and pigs in Group 2 were sacrificed by intracardiac KCl injection 60 min before harvesting (n = 5). All pigs survived more than 4 days in Group 1. In Group 2, all died within 2 days due to graft failure. Arterial and hepatic venous glutamic-oxaloacetic transaminase (GOT) in Group 2 were higher after revascularization. However, there were no differences between the 2 groups in arterial and hepatic venous HA levels. HA clearance by the graft also showed no differences between the groups. Although GOT reflected the degree of warm ischemia, HA and its hepatic clearance were not influenced by warm ischemic damage. In conclusion, HA was not thought to serve as a marker of liver injury when the graft suffered from warm ischemia.

Animals↗

Optimal oxygen tension conditions for functioning cultured hepatocytes in vitro.

With a view toward furthering the development of artificial liver systems, we have been culturing hepatocytes in vitro. The object of this research was to investigate the ideal conditions of oxygen tension for the efficient functioning of hepatocytes. Viable hepatocytes isolated from rat livers were cultured under five different oxygen tensions: 5, 10, 20, 50 and 90% O2. DNA contents, gluconeogenesis, urea synthesis, adenosine triphosphate (ATP) levels, and lipid peroxidation of hepatocytes were evaluated. Under the 5% oxygen conditions, the function of hepatocytes was very inferior and was accompanied by a low ATP level. However, hepatocytes cultured under 90% oxygen tension functioned less effectively than the control (20% O2) with elevated lipid peroxidation. The data in this study suggest that the optimum oxygen condition for cultured hepatocytes is 10 approximately 50%, and that especially under conditions of 20% oxygen tension, i.e., that of the ordinary atmosphere, hepatocytes can function most effectively.

Adenosine Triphosphate↗

Function of culturing monolayer hepatocytes by collagen gel coating and coculture with nonparenchymal cells.

Since 1987, we have been developing a bioartificial liver (BAL) using multiplated cultured hepatocyte monolayers. With the goal of promoting hepatic functions of cultured hepatocyte monolayers, we combined the use of a collagen gel layer over the monolayers of hepatocytes and/or cocultured hepatocytes with nonparenchymal cells (NPCs). The study was divided into four groups according to culture configurations: Group 1: hepatocyte monolayer culture (control); Group 2; coculture of hepatocytes and NPCs; Group 3: hepatocyte monolayer with a overlaid collagen gel layer; and Group 4: coculture with a overlaid collagen gel layer. The culture continued for 14 days. Morphological changes and hepatic functions were evaluated by urea and albumin syntheses. The morphological status of the hepatocytes remained for 2 weeks in Groups 3 and 4. Deterioration and detachment of hepatocytes and/or NPCs started in Group 1 and 2 on the third day in culture. Significantly high urea synthesis was noted in Group 4 (p < 0.001 compared with Group 1 and 2: p = 0.0014 compared with Group 3). Although there was no significant difference in albumin synthesis among the four groups, those hepatocytes covered by the collagen gel (Groups 3 and 4) tended to secrete albumin throughout the observation period. These results indicted that the environment, although artificial (but close to the in vivo state), supplied with collagen gel and the coculture, enhanced the activities of the cultured hepatocyte monolayers. We suggest that use of cocultured hepatocytes under a collagen gel is a promising candidate for a bioreactor of multiplated BAL.

Albumins↗

Biotin deficiency in an infant fed with amino acid formula and hypoallergenic rice.

An amino acid formula produced in Japan is not supplemented with biotin since biotin is not permitted as a food additive. Biotin deficiency developed in an 11-month-old Japanese infant who had been diagnosed as a neonate with cow milk and soy bean allergy and fed with an amino acid formula and hypoallergenic rice processed by protease. Serum levels of zinc, essential fatty acids and biotinidase were within the normal range while that of biotin was below the normal range. Urinary 3-hydroxy-isovalerate and slightly elevated levels of plasma branched-chain amino acids disappeared 1 week after oral supplementation with 1 mg day-1 of biotin as did the symptoms of orificial skin lesions, lethargy, hypotonia and alopecia later. In summary, to prevent biotin deficiency, biotin should be added to the Japanese amino acid formula.

Biotin↗

[Nasopharyngeal natural killer cell lymphoma with pericardial infiltration].

A 77 year-old woman was admitted to the hospital because of nasal obstraction on March 1994. Tumorectomy of the nasopharyngeal tumor disclosed non-Hodgkin's lymphoma (LSG : diffuse, medium sized). The patient was treated with local radiotherapy to nasopharyngeal region and combined chemotherapy (2 courses of CHOP) to reduce residual tumor. On July, the pericardial effusion appeared and the large granular lymphocyte (LGL) like lymphoma cells were observed in the effusion. Flow cytometic analysis of these cells showed that they expressed CD 2, CD 7, CD 56 and HLA-DR, but did not express CD 3. T-cell receptor gene (TCR beta) rearrangement was not observed and natural killer activity was detected in these lymphoma cells. The patient was treated with ProMACE and the pericardial infusion of methotrexate, carboplatin and prednisolone, but the patient died of heart failure. Monoclonarity of lymphoma cells in the pericardial effusion was determined by southernblot analysis, using the terminal repeat of Epstein-Barr virus (EBV) for probe. It was suggested that EBV participated in tumorgenesis in this case.

Aged↗

[Chemotherapy for two patients with non-Hodgkin's lymphoma in hemodialysis].

There are few reports on chemotherapy of non-Hodgkin's lymphoma (NHL) in patients with chronic renal failure. Two long-term hemodialysis patients were treated for NHL with modified CHOP therapy. The plasma pharmacokinetics of adriamycin (ADR) and etoposide (VP-16) were investigated in these patients. In the first case, NHL was diagnosed in a 37-year-old male (diffuse pleomorphic, T cell type, stage I E). After 4 courses of chemotherapy, he achieved complete remission. The second case, was a 56-year-old male who was admitted to our hospital with melena and abdominal pain. A diagnosis of NHL (diffuse mixed, B cell type, stage III E) was made. Complete remission was achieved with 2 courses of chemotherapy. Levels of hematological and neurological toxicity were moderately severe but tolerable. Pharmacokinetics of ADR and VP-16 in these patients were similar to those in patients with normal renal function. These results suggested that ADR and VP-16 were effective drugs for hemodialysis patients with NHL.

Adult↗

[Rearrangements of immunoglobulin heavy chain gene in Waldenstr"om's macroglobulinemia].

We investigated rearrangements of immunoglobulin heavy chain (Ig(H)) gene of the bone marrow mononuclear cells by Southern hybridization in 7 patients with Waldenström's macroglobulinemia. Three of 7 cases showed the rearrangement of Ig (H) gene. The cases with Ig (H) gene rearrangements showed high rates of CD19 and CD20 positive cells compared to the cases with no rearrangements. Two out of 3 cases included less than 3 g/dl IgM. On the other hand, 4 cases without rearrangements had lower percentage of B cells in the bone marrow and higher serum IgM (4/4; more than 3g/dl) than the cases with the rearrangements. Thus, the rearrangements of Ig (H) chain gene did not correlate with serum IgM level and related to the quantity of B cells in the bone marrow in WM.

Aged↗

Helicobacter pylori infection in childhood: H. pylori isolation rate in gastric juice in relation to positive serum antibody rates.

We investigated the prevalence of Helicobacter pylori infection by isolation of H. pylori and by antibody detection in the serum of Japanese children. The children were distributed into four groups by age: group I, under 1 year; group II, 1-5 years; group III, 6-11 years; and group IV, 12-15 years. For the isolation of H. pylori, gastric juice was obtained from 115 children from middle class families. In the 103 samples obtained from asymptomatic children, H. pylori was not isolated in any from group I. The isolation rate in groups II, III, and IV was 3% (1/32), 20% (5/25), and 75% (3/4), respectively. In symptomatic children, H. pylori was isolated only in group IV (66.7%). The antibody positive rate in group I, II, III, and IV was 13% (6/47), 10% (11/112), 18% (16/89), and 26% (11/43), respectively, in asymptomatic children. In group I, however, 4 of 25 samples (18%) were obtained from babies under 3 months of age; this result was regarded as reflecting maternal antibodies. Nineteen samples were obtained from children with hepatitis A who lived in Nanki hospital for handicapped children, where hygiere was poor. The antibody positive rate in this population was 60% (3/5) in group III and 90% (9/10) in group IV. These results suggest that H. pylori infection in Japanese children is related to age and hygiene conditions. The antibody positive rate was similar to that reported in other countries.

Adolescent↗

Nourishment of hepatocellular carcinoma cells through the portal blood flow with and without transcatheter arterial embolization.

BACKGROUND: Although transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) is very effective, local recurrence is not so rare. The reason is thought to be related to portal blood flow. The changes in the nourishing vessels in HCC after TAE were examined from the viewpoint of cell kinetics with direct reference to intracellular transportation of biochemical substrates, namely 5 bromo-2'-deoxyuridine (BrdU), an analogue of thymidine. METHODS: To examine the cell kinetics of carcinoma cells, BrdU was infused intraoperatively in 23 patients with HCC (12 without TAE and 11 post-TAE patients) directly into the portal branch feeding the region to be resected. Specimens were prepared for immunohistochemical staining using BrdU monoclonal antibodies and analyzed using the labeling index (LI). The distribution of the labeled S-phase cell was also examined. RESULTS: The LI in post-TAE patients was about six times higher than patients without TAE, with a significant difference at P < 0.001. Labeled cells were distributed not only peripherally but in the central part of the tumor, although the number was extremely small. CONCLUSIONS: Some HCC cells, although small in number, are nourished by the portal blood flow directly throughout the viable tumor mass, which may act as the main blood supplier during the period after TAE. For greater local control of HCC, complete resection of HCC and/or the use of chemotherapy via not only the hepatic artery but also the portal blood flow are beneficial.

Adult↗

Relapsing oral and colonic ulcers with monoclonal T-cell infiltration. A low grade mucosal T-lymphoproliferative disease of the digestive tract.

BACKGROUND: Some cutaneous T-cell lymphoproliferative diseases (LPD), such as lymphomatoid papulosis and pityriasis lichenoides et varioliformis acuta, are characterized by an indolent or waning and waxing clinical course. However, such T-cell LPD are rarely documented in other organs. METHODS: A patient with T-cell LPD of the digestive tract characterized by repetitive episodes of self-healing ulcers in the oral and intestinal mucosa over the course of 17 years is reported. Biopsy specimens from oral and intestinal mucosa were studied by conventional pathology, immunocytochemistry, and Southern blot analysis of T-cell receptor (TCR)-beta and -gamma gene rearrangement. RESULTS: Immunocytochemically, the infiltrating lymphocytes were lamina propria T cells with a dominant phenotype CD3+, CD4+/-, CD8-, and HML-1-. DNA study revealed the same rearranged configuration of TCR-beta and -gamma genes in specimens from both oral and colonic lesions. CONCLUSIONS: The present case may represent a novel T-cell lymphoproliferative disease (i.e., a digestive-tract mucosal counterpart of cutaneous dysplastic LPD).

Colonic Diseases↗

Growth enhancement of normal human keratinocytes by the antisense oligonucleotide of retinoblastoma susceptibility gene.

We have found that the growth of normal human keratinocytes, grown in serum-free medium, was significantly stimulated by the antisense oligonucleotide of retinoblastoma susceptibility gene (Rb). Normal human keratinocytes were exposed to phosphorothionate oligonucleotides which were complementary to translation initiation codon of Rb gene. The growth of keratinocytes was enhanced by the antisense, but not the sense, oligonucleotide of Rb gene in a dose-dependent manner from 1 to 10 microM. The Rb antisense oligonucleotide, however, did not result in any appreciable change in transcription of the gene when examined by reverse-transcription polymerase chain reaction (RT-PCR) analysis or in the protein expression and the phosphorylation pattern when examined by immunoprecipitation and Western blotting.

Base Sequence↗

Germ line mutations of hMSH2 and hMLH1 genes in Japanese families with hereditary nonpolyposis colorectal cancer (HNPCC): usefulness of DNA analysis for screening and diagnosis of HNPCC patients.

Mutations in hMSH2 and hMLH1 genes were analyzed in patients from 11 Japanese families that had been diagnosed as carrying hereditary nonpolyposis colorectal cancer (HNPCC) by clinical examination. Germ line mutations of hMSH2 gene were identified in 5 independent families in which colorectal (87% of patients), endometrial (30%), ovarian (17%), gastric (14%), and other cancers existed. Five mutations detected between codons 136 and 811 included single-base substitutions (C-->T and T-->G), a T deletion, and an A insertion, all of which produced stop codons resulting in truncated proteins, and an A-->T substitution at splice donor site of exon 5 which resulted in deletion of this exon. Moreover, one HNPCC family was presumed to have germ line mutation of hMSH2 gene because a somatic mutation of hMSH2 gene was detected in a cancer from a patient in this family. In addition to these 11 families already diagnosed with HNPCC, 3 new families with germ line mutations of hMSH2 gene and hMLH1 gene were found through analysis of DNA from patients who had multiple cancers with alteration in microsatellite DNA. These mutations included an AG deletion at codons 877-878 of hMSH2 gene, an AAG deletion at codons 616-618 of hMLH1 gene, and a C-->T single-base substitution at codon 217 of hMLH1 gene. Seven of eight germ line mutations found in this study are new mutations that have not been reported previously. In families in which germ line mutations were identified presymptomatic examination was then carried out using polymerase chain reaction single-strand conformation polymorphism analysis of DNA from peripheral blood, and the result was the detection of family members predisposed to HNPCC who did not yet show signs of cancer. These results indicate the value of DNA analysis in the screening and diagnosis of HNPCC patients and families.

Adult↗