Hepatitis C virus infection in kidney transplantation and a pilot study of the effects of interferon-alpha therapy.
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Hepatitis C↗
Biomedical subjects
Y Ichikawa
Publications and source records attributed to Y Ichikawa.
Positive effects of kidney transplantation on bone mass.
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Adult↗
Detection of regional lymph node metastases in colon cancer by using RT-PCR for matrix metalloproteinase 7, matrilysin.
Lymph node metastasis is the most important prognostic factor in colon cancer. However, more accurate screening for metastasis than that afforded by conventional pathology remains elusive. We have employed a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for a matrix metalloproteinase (MMP), 'matrilysin', because this gene is epithelial-specific and consistently expressed in colorectal cancer cells. The sensitivity of this assay was examined with the matrilysin-producing rectal cancer cell line 'CaR-1'. Matrilysin mRNA was detected in this system when more than 10(4) matrilysin-positive cells existed in a lymph node of ordinary size. Fourteen of 15 (93%) primary colon cancers and none of the surrounding normal tissues expressed matrilysin. All 10 histologically-positive lymph nodes were positive for matrilysin, while of 60 histologically-negative lymph nodes, eight were positive for matrilysin. When the additional sequential sectioning and histological re-examination was performed on five of these eight 'matrilysin-positive, but histologically-negative' lymph nodes, micrometastases were detected in three. Only one of the lymph nodes that were histologically-positive, but negative by matrilysin assay was from a patient with colon cancer in which matrilysin was not detected. In conclusion, RT-PCR assay for matrilysin is a sensitive method for detecting occult metastases in patients with colon cancer, and may complement histologic examination.
Adult↗
Steroidogenic acute regulatory protein (StAR) transcripts constitutively expressed in the adult rat central nervous system: colocalization of StAR, cytochrome P-450SCC (CYP XIA1), and 3beta-hydroxysteroid dehydrogenase in the rat brain.
Steroidogenic acute regulatory protein (StAR) is a 30-kDa protein involved in the transport of cholesterol to the inner mitochondrial membrane and thus plays a key role in steroid biosynthesis. To clarify the implications of this protein in neurosteroid biosynthesis, we examined the possible expression of a StAR transcript in the adult rat CNS and detected it. cDNA cloning and sequencing analysis revealed that two forms of StAR mRNAs are expressed in the brain in the same manner as in the adrenal gland, indicating that they are fully functional and not minor gene transcripts. An RNase protection assay quantitatively revealed that the amount of the rat StAR transcript in brain was two to three orders of magnitude lower than that in the adrenal gland. An in situ hybridization study, involving antisense riboprobes, revealed that StAR transcripts were abundant in the cerebral cortex, hippocampus, dentate gyrus, olfactory bulb, cerebellar granular layer, and Purkinje cells. Furthermore, other steroidogenic enzymes, side-chain cleavage cytochrome P-450SCC (CYP XIA1) and 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase (EC 1.1.1.145), were found to be coexpressed in the hippocampus, dentate gyrus, cerebellar granular layer, and Purkinje cells. These findings strongly indicate that neurosteroids are synthesized in a region-specific manner in the brain.
3-Hydroxysteroid Dehydrogenases↗
Succinylated collagen crosslinked by thermal treatment for coating vascular prostheses.
Vascular prostheses coated with collagen carefully prepared to avoid contamination were tested to see if it could induce endothelial cell lining throughout the graft surface in a natural way. The collagen fibers were succinylated. Hydrogel produced with the succinylated collagen was used for the sealant to reduce the amount of solid substance. To avoid contamination and the side effects of chemical reagents, the collagen thermally crosslinked under sterile conditions. A suspension of the collagen fibers was enmeshed in the interstices of Dacron fibers of fabric prostheses, which were then thermally crosslinked at 130 degrees C for 20 h. The prostheses were porous when the collagen fiber network was dry. Under wet conditions, however, the water permeability of the grafts was reduced to 0.1 ml/min from the 1,250 ml/min of the original prostheses. Three weeks after implantation in the abdominal aortas of dogs, 81.2 +/- 11% of the luminal surface was macroscopically thrombus free, and 56 +/- 14% was endothelialized. More than 95% of the coated collagen had been absorbed. Numerous fibroblasts had migrated into the graft walls, and capillary blood vessels had infiltrated the inside of the graft walls without foreign body reaction. In the controls, thrombus free areas averaged 9.0 +/- 5%, and endothelialized areas averaged 5.2 +/- 4%. Many giant cells, plasma cells, and lymphocytes had migrated into the graft walls, but no fibroblasts. These results suggest that rapid endothelialization is possible when clean collagen is used.
Animals↗
The origin and differentiation of the heteromorphic sex chromosomes Z, W, X, and Y in the frog Rana rugosa, inferred from the sequences of a sex-linked gene, ADP/ATP translocase.
Sex chromosomes of the Japanese frog Rana rugosa are heteromorphic in the male (XX/XY) or in the female (ZZ/ZW) in two geographic forms, whereas they are still homomorphic in both sexes in two other forms (Hiroshima and Isehara types). To make clear the origin and differentiation mechanisms of the heteromorphic sex chromosomes, we isolated a sex-linked gene, ADP/ATP translocase, and constructed a phylogenetic tree of the genes derived from the sex chromosomes. The tree shows that the Hiroshima gene diverges first, and the rest form two clusters: one includes the Y and Z genes and the other includes the X, W, and Isehara genes. The Hiroshima gene shares more sequence similarity with the Y and Z genes than with the X, W, and Isehara genes. This suggests that the Y and Z sex chromosomes originate from the Hiroshima type, whereas the X and W chromosomes originate from the Isehara-type sex chromosome. Thus, we infer that hybridization between two ancestral forms, with the Hiroshima-type sex chromosome in one and the Isehara-type sex chromosome in the other, was the primary event causing differentiation of the heteromorphic sex chromosomes.
Animals↗
Malignant neoplasm in kidney transplantation.
BACKGROUND: The kidney recipient is at a higher risk for cancer than is the general population, although the incidence of neoplasms in general is considered lower in Japan than in Western countries. The cause of this increased risk associated with either transplantation or geography has not yet been established. METHOD: The incidences and sites of malignant neoplasms were analyzed in 285 kidney recipients, who had been followed up for 3007 patient-years. The relationship between immunosuppressive states, the numbers of CD4-positive T lymphocytes, and the presence of malignant neoplasms was studied retrospectively. RESULTS: Eighteen malignant neoplasms were found in 17 of the 285 patients (6%). The malignancies developed in these patients an average of++ 1 26.5 months after transplantation. The incidence was only 3.9% at 10 years, increasing to 13.9% at 20 years. No difference in the time-course incidence was found between azathioprine-based and cyclosporin-based immunosuppressive regimens. The malignancies developed in the digestive organs in more than half of the patients, and were mainly in the liver, colon and rectum, and stomach, with a relatively low incidence of skin cancer and lymphoma. There was only one case of Epstein-Barr virus genome found in 5 specimens that were tested. Concerning the immunosuppressive state, CD4-positive T lymphocyte counts were not related directly with malignancies in our series. CONCLUSION: The cumulative incidence of malignancy increased markedly in the second posttransplant decade. The site of cancers in kidney recipients mirrors that of general Japanese malignancies. Our results revealed neither the cause nor predictor for malignancies in kidney transplant patients.
Adolescent↗
Anisakidosis: a cause of intestinal obstruction from eating sushi.
We report a case of strangulating small bowel obstruction in a 60-yr-old Japanese woman caused by anisakidosis (previously known as anisakiasis). With the increasing popularity of Japanese cuisine such as sushi in the United States, the incidence of anisakidosis is expected to increase. Intestinal anisakidosis can now be treated temporarily, but this condition may cause a serious obstruction afterwards, as evidenced by this particular case. Over 13,500 cases were reviewed in both the Japanese and English literature, and we discuss the prevention of anisakidosis without negatively altering the taste of the raw fish.
Animals↗
The erythrophore in the larval and adult dorsal skin of the brown frog, Rana ornativentris: its differentiation, migration, and pigmentary organelle formation.
To determine whether or not the erythrophore originates from xanthophores in the dorsal skin of the brown frog, Rana ornativentris, we morphologically examined the differentiation and migration of the two chromatophore types and their pigmentary organelle formation. At an early tadpole stage, three kinds of chromatophores, xanthophores, iridophores, and melanophores, appeared in the subdermis, whereas the erythrophore did so just before the foreleg protrusion stage. By the middle of metamorphosis, most chromatophores other than erythrophores had migrated to the subepidermal space. Erythrophores, which appeared late in the subdermis, proliferated actively there during metamorphosis and finished moving into the subepidermal space by the completion of metamorphosis. Carotenoid vesicles and pterinosomes within the erythrophores and xanthophores showed several significant differences in structure. In xanthophores, carotenoid vesicles were abundant throughout life, whereas those in erythrophores decreased in number with the growth of the frogs. The fibrous materials contained in the pterinosomes were initially scattered but soon formed a concentric lamellar structure. In erythrophores, the lamellar structure began to form at the periphery of the organelles but at the center in xanthophores. In addition, the pterinosomes of erythrophores were uniform in size throughout development, while those of xanthophores showed a tendency to become smaller after metamorphosis. The pterinosomes of xanthophores were significantly larger than those of erythrophores. These findings suggest that an erythrophore is not a transformed xanthophore, although they resemble each other closely in many respects.
Animals↗
Indomethacin interferes with EGF-induced activation of ornithine decarboxylase in gastric cancer cells.
BACKGROUND/AIMS: Epidermal growth factor (EGF) has a wide variety of biological activities in the protection of gastric mucosa against acute injury and the healing of gastric ulcer. However, the molecular basis of the EGF action remains unknown. EGF-induced activation of ornithine decarboxylase (ODC) was examined, because ODC is a key enzyme for the cell proliferation. METHODS: The effects of epidermal growth factor (EGF) and indomethacin on ornithine decarboxylase (ODC) mRNA and enzyme activity were examined in gastric cancer derived KATO-III cells. RESULTS: EGF induced both ODC mRNA expression and enzyme activation in a biphasic manner with the peaks at 0.5 and 3 h for mRNA and at 5 and 9 h for enzyme activity, respectively. Indomethacin pretreatment significantly reduced EGF-induced ODC activation and was completely abolished for the first 5 h. CONCLUSION: Since it has been reported that both EGF and ODC are involved in cell migration and proliferation, two actions of EGF for gastric mucosal healing may be through, at least in part, this biphasic activation of ODC. Indomethacin suppresses and changes the response of ODC induced by EGF.
Adenocarcinoma↗
A novel variant of B-lymphoid leukemia expressing kappa/lambda light chains.
We studied a patient with an indolent leukemia which behaved similarly to chronic lymphocytic leukemia (CLL). Leukemic cells, however, showed larger cell diameters and lower nuclear/cytoplasmic ratios than typical CLL cells, and contained numerous cytoplasmic vacuoles. The cells also demonstrated some morphologic characteristics of hairy cell leukemia. Furthermore, flow-cytometric analysis demonstrated a distinct population of kappa/lambda double-positive tumor cells, as well as kappa single and lambda single populations. Southern blot analysis confirmed rearranged bands for both light chains with a monoclonal heavy chain rearrangement. Despite a decision not to treat this asymptomatic patient, disease progression was not observed. This case may represent a unique variant of B lymphoid leukemia. Possible mechanisms of abnormal light chain expression are discussed.
Aged↗
Higher sensitivity in induction of apoptosis in fibroblast cell lines derived from LEC strain rats to UV-irradiation.
The proportion of S-phase cells in a WKAH rat cell population decreased and that of G1-phase cells increased at 8 and 18 hr post-incubation following UV-irradiation, although no significant change was observed in the ratio of the proportion of S-phase to G1-phase cells in a LEC rat cell population. Thus, UV-radiation-induced delay in the progression from the G1 to S phase was observed in WKAH rat cells but was not apparent in LEC rat cells. The fraction of LEC rat cells containing a sub-G0 DNA content increased with post-incubation time after UV-irradiation, but not that of WKAH rat cells. The proportion of the sub-G0 fraction in LEC rat cells increased with increasing doses of UV-rays. Low molecular weight DNAs extracted from UV-irradiated LEC rat cells exhibited an intense DNA ladder pattern at 18 and 24 hr post-irradiation by electrophoretic analysis, but not those from UV-irradiated WKAH rat cells. These results showed a higher sensitivity of LEC rat cells in induction of apoptosis than that of WKAH rat cells to UV-irradiation, although there was no difference in the survival curves among the cell lines from LEC and WKAH rats after UV-irradiation.
Animals↗
Higher sensitivity in LEC rat cells to a topoisomerase II inhibitor, ellipticine.
A concentration of ellipticine, an inhibitor of topoisomerase II, required to reduce cell survival to 37% (D37) is used as an index to compare the cellular sensitivity. D37 values of LEC and WKAH rat cells were 1.2 and 2.2 microM, respectively. Thus, LEC rat cells were approximately 1.8-fold more sensitive than WKAH rat cells to ellipticine. There was no significant difference between the topoisomerase II activities in nuclear extracts of LEC and WKAH rat cells. These results suggested that the high sensitivity of LEC rat cells to ellipticine is not associated with the level of topoisomerase II activity.
Animals↗
Fatal alveolar hemorrhage in a patient with mixed connective tissue disease presenting polymyositis features.
A 22-year-old female with Raynaud's phenomenon, swollen hands and a high titer of anti-RNP antibodies developed fever and myositis. Prednisolone (40 mg/day) was considered effective for myositis since circulating myogenic enzymes rapidly decreased. However, she suddenly developed respiratory distress with bilateral pulmonary infiltrates and bloody sputum. Under the diagnosis of alveolar hemorrhage (AH), intravenous methylprednisolone pulse therapy was given, but she died of respiratory failure. Autopsy findings demonstrated massive AH with hematoma formation, and myositis in the iliopsoas muscle. Depositions of immune complex and vasculitic lesions were not recognized in her lungs.
Adult↗
[Clinical relapse of rheumatoid arthritis (escape phenomenon) during low-dose methotrexate therapy].
OBJECTIVE: To clarify the incidence and background of clinical relapse (escape phenomenon) during low-dose methotrexate therapy for rheumatoid arthritis. METHODS: Seventy one patients with rheumatoid arthritis (RA) were analyzed. They were started on therapy with methotrexate (MTX) between April 1, 1991 and May 30, 1995. Among them, 60 patients showed clinical improvement within 6 months after the start of the therapy and were subjected to the analysis for clinical relapse (escape phenomenon). RESULTS: Twelve patients showed an initial improvement followed by a relapse with increased serum CRP and number of painful joints despite the MTX therapy was continued. Two types of the relapses were seen; (1) early, escape (relapse after an initial brief improvement) in 7 patients, and (2) late escape (relapse after a long-term improvement with MTX therapy) in 5 patients. The early escape was seen at 9.0 +/- 0.7 months after the start of therapy while the late escape was seen at 23.3 +/- 4.8 months. Patients with both types of escape phenomenon had the longer duration of the disease and more advanced stage. There was no relationship between clinical relapse and age, baseline RA activity, MTX dose, or concurrent use of corticosteroids and other disease modifying anti-rheumatic drugs. The efficacy of MTX for RA was restored by increasing dose of MTX in 11 patients. CONCLUSION: These results suggest that clinical relapse is not rare in RA patients during low-dose methotrexate therapy, but could be improved by increasing dose.
Antirheumatic Agents↗
[The efficacy of combination therapy with prednisolone (PSL) and methotrexate (MTX) on radiographic progression in patients with rheumatoid arthritis (RA)].
A case-controlled study was performed, based on early active RA patients treated with MTX; Prednisolone (PSL) was also given in sixteen patients (PSL + MTX group) and each of them was matched for age and sex with a control who have never received PSL (MTX group). No significant differences in radiographic progression were found between the 2 groups. Analysis of radiographic parameters showed that CRP, erythrocyte sedimentation rate, and titers of serum rheumatoid factors after 6 months treatment and their integral amounts during cource were significantly high in the patients with marked radiographic progression. There was no relationship between radiographic progression and treatment with PSL. These results suggested that the indication of PSL therapy for RA is limited for patients with the poor decrease in the level of CRP, erythrocyte sedimentation rate, and rheumatoid factor by MTX treatment.
Anti-Inflammatory Agents↗
Inhibitory effect of matrilysin antisense oligonucleotides on human colon cancer cell invasion in vitro.
In colorectal cancer, matrilysin (matrix metalloproteinase-7) is mainly produced by the tumor cells themselves and is thought to play an important role in tumor invasion and metastasis. In the study reported here, we examined the effects of matrilysin antisense phosphorothioate oligonucleotides on both the expression of matrilysin and the invasive potential of the human colon cancer cell line CaR-1 in vitro. To select the most specific and potent oligonucleotide sequence, we performed extensive analyses of the binding specificities of all antisense candidates in the GenBank database by using a computer program we developed. As a result, a 15-mer matrilysin-specific antisense oligonucleotide that hybridizes to the coding region of matrilysin mRNA (AS-1) and a random control oligonucleotide (CL-1) were designed. Reverse transcription-polymerase chain reaction and western blot analysis demonstrated that 10 microM AS-1 suppressed matrilysin expression at both the mRNA level (92%) and protein level (64%). In vitro invasion assays demonstrated that this same concentration of AS-1 inhibited the ability of cells to invade a reconstituted basement membrane by 50% as compared with the ability of untreated cells to do so. On the other hand, CL-1, which had the same length and GC content as AS-1, did not show any inhibitory effect. These results demonstrate that the antisense oligonucleotide AS-1 inhibits matrilysin activities in a sequence-specific manner and suggest that AS-1 has the potential to be used as an anti-metastatic agent in an in vivo experimental model of colon cancer.
Antineoplastic Agents↗
[Osteoporosis in rheumatoid arthritis].
Patients with rheumatoid arthritis (RA) develop both periarticular and generalized osteoporosis. Periarticular osteopenia in appendicular bones occurs early in the course of RA and is one of the earliest radiological signs of RA. An uncoupled state in bone resorption-formation linkage, contributes to the development of periarticular osteopenia and it might be mediated through an increased productions of cytokines and prostaglandins by synovium and bone marrow. Accordingly, early suppression of rheumatoid synovitis is necessary for the prevention of periarticular osteopenia. Generalized osteoporosis is also common in RA and leads to increased risk of fractures. Generalized osteoporosis considered to be multifactorial and factors contributing to lumbar osteoporosis might be different from those to loss of appendicular bones, such as femur and radius. Corticosteroids and menopausal state are important risk factors for lumbar osteoporosis. Rheumatoid activity and reduced physical activity are also important determinants. According to the previous studies, however, the influence of functional impairment is more prominent in the femoral BMD compared to spinal BMD. In addition to control of RA and maintenance of physical activity, hormone replacement therapy (HRT) and bisphosphonate are possible agents for the treatment of osteoporosis in RA patients, especially postmenopausal women.
Arthritis, Rheumatoid↗