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Biomedical subjects

H Imai

Publications and source records attributed to H Imai.

At least 289 records · Page 16Linked to original sources
PubMed1995

Autoantibody to DNA topoisomerase II in primary liver cancer

A patient with chronic hepatitis associated with hepatitis C virus infection was observed to convert from antinuclear antibody-negative to antinuclear antibody-positive status at the time when liver cancer was detected. The newly recognized antibodies reacted with a nuclear protein doublet of 170 and 180 kDa in immunoblotting, and in fluorescence-activated flow cytometry the antigens were shown to vary in expression level in a cell cycle-related manner: minimum in G1, increasing in S, and maximum in G2 and M. In synchronized HeLa and HEp-2 cells, immunofluorescence microscopy showed uniformly distributed staining of the nucleoplasm in S-phase, with increased intensity of nucleoplasmic staining in G2, at which time nucleolar staining was also present. In M, condensed chromosomes were uniformly stained. Using previously characterized polyclonal antibodies to DNA topoisomerase II (topo II) as reference markers, the antigens recognized by the patient's serum were shown in Western blotting to have the same mobilities as DNA topo IIalpha (170 kDa) and beta (180 kDa) isoforms. The patient's serum was also highly efficient in inhibiting DNA topo II in an in vitro functional assay. Antibody to DNA topo II appeared de novo in close association with transformation to cancer, and since dysregulation of DNA topo II is considered to be involved in some forms of tumorigenesis, the observed antibody response in this patient could conceivably be an immune reaction to the abnormally regulated protein.

Journal Article↗
PubMed1994

Direct observation of the thermal equilibria among lumirhodopsin, metarhodopsin I, and metarhodopsin II in chicken rhodopsin.

Using low-temperature time-resolved spectroscopy, we have directly observed thermal back reaction of metarhodopsin I (meta I) to lumirhodopsin (lumi) and that of metarhodopsin II (meta II) to meta I in chicken rhodopsin to demonstrate the presence of thermal equilibria among lumi, meta I, and meta II. The back reaction from meta I to lumi was observed when the rhodopsin sample irradiated at -35 degrees C was warmed to -20 degrees C, while that from meta II to meta I was observed when the sample irradiated at -10 degrees C was cooled to -20 degrees C. Thermodynamic parameters of lumi, meta I, and meta II were calculated from the equilibrium constants estimated by analyzing the spectra of the equilibrium states at temperatures ranging from -30 to -10 degrees C. The results showed that meta I has an enthalpy and an entropy considerably smaller than those of lumi and meta II, while the difference in thermodynamic parameters between lumi and meta II is not so large. These results suggest that meta I is a crucial stage of conversion of the light energy captured by the chromophore into restricted conformations of the chromophore and/or protein, from which a large conformational change of the protein starts to form meta II.

Animals↗
PubMed1994

Thermal recovery of iodopsin from its meta I-intermediate.

The thermal reaction of meta I-intermediate of iodopsin (metaiodopsin I), a chicken red-sensitive cone pigment, was studied by low-temperature spectrophotometry at -20 degrees C. Irradiation of iodopsin at -20 degrees C produced metaiodopsin I, whose absorption maximum was at about 470 nm. An incubation of metaiodopsin I at -20 degrees C resulted in a conversion to metaiodopsin II having absorption maximum at about 380 nm, as well as a concurrent formation of a red-shifted product stable at room temperature. Since the absorption spectrum and photo-reactivity of the red-shifted product were identical with those of iodopsin, the red-shifted product should be iodopsin. Thus a part of metaiodopsin I can revert to iodopsin by the thermal reaction unlike metarhodopsin I.

Animals↗
PubMed1994

Natural autoantibody against apolipoprotein A-I. Detection and characterization of the monoclonal antibody established from normal unimmunized BALB/c mice.

During the course of studying the immunogenicity of soybean lipids, we observed frequent production of the mAbs that bind to apolipoprotein A-I (apoA-I) when spleen cells from unimmunized normal BALB/c mice were employed for fusion. Of the 986 colonies from six fusions, 38 (3.9% of the total) were directed against apoA-I and 13 mAbs (IgM) were established for further analysis. The following lines of evidence indicate that this family of mAb may form a novel family of natural autoantibodies against apoA-I: 1) The mAbs were shown to bind effectively to high density lipoprotein from various species, including BALB/c mouse, and immunoblotting analyses revealed that the mAbs bound specifically to the 28-kDa protein of high density lipoprotein. 2) The 28-kDa protein was purified to homogeneity and identified as apoA-I by amino acid sequence analyses and by its cross-reactivity with a xenogenic anti-apoA-I mAb (clone A/11). 3) Differing from the xenogenic anti-apoA-I mAb, the present mAb did not bind to native apoA-I, whereas an effective binding was observed only when the apoA-I had formed a complex with neutral lipids containing polyunsaturated fatty acids such as trilinoleoylglycerol and 5-cholesten-3 beta-ol 3-linoleate. 4) Sera from unimmunized BALB/c mice had readily detectable Abs against apoA-I and the majority of the serum autoantibodies were of the IgA and IgM isotype. 5) The anti-apoA-I mAbs displayed a functional heterogeneity in their reactivity with polyanionic substances and some of the mAbs established showed an extensive cross-reaction with polyanionic substances such as ssDNA and cardiolipin.

Animals↗
PubMed1994

Is chicken green-sensitive cone visual pigment a rhodopsin-like pigment? A comparative study of the molecular properties between chicken green and rhodopsin.

Chicken green is a visual pigment present in chicken green-sensitive cones and has an amino acid sequence more similar than any other cone visual pigments to the rod visual pigments, rhodopsins. Here we have investigated the molecular properties of chicken green and compared them with those of rhodopsin to elucidate whether or not chicken green is a rhodopsin-like pigment. While chicken green has a molecular extinction coefficient and a photosensitivity very similar to those of rhodopsin, it displays faster regeneration from 11-cis-retinal and opsin and faster formation and decay of the physiologically active meta II intermediate than rhodopsin. These differences correlate with the physiological difference between cones and rods. Thus in spite of the similarity in amino acid sequence, chicken green displays molecular properties required for a cone visual pigment that are clearly different from those of rhodopsin.

Animals↗
PubMed1994

Geographical variation in urinary mercury concentrations among populations living in highland and lowland Bolivia.

Mercury (Hg) concentrations were determined in spot urine samples of populations living in the highland and lowland areas of Bolivia. The mean levels of the Hg (U-Hg) were 0.43 and 0.34 micrograms Hg/g creatinine in lowlanders and in highlanders, respectively, which did not suggest existence of high-level exposure to Hg in these populations. In both highlanders and lowlanders, there was a marked difference in levels of U-Hg among different populations. Several lines of evidence suggested that local dietary patterns resulted in the observed difference in U-Hg among different populations. Several lines of evidence suggested that local dietary patterns resulted in the observed difference in U-Hg levels, although the responsible food items could not be specified. In most of the populations examined, females showed higher U-Hg levels than males. Other factors possibly related to the observed geographical differences are discussed.

Altitude↗
PubMed1994

Iron accumulation in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian monkeys.

The mechanism of abnormal iron accumulation in the substantia nigra (SN) pars compacta of patients with Parkinson's disease (PD) is unknown. To explore this question, we made a hemiparkinsonism model in monkeys by injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the caudate or putamen on one side, and compared iron content in the SN and other basal ganglia structures by histochemistry. The injected side, especially the SN pars compacta, showed a marked increase in iron staining. Our study indicates that an injury to the nigrostriatal system by MPTP injection can induce iron accumulation in the SN.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Effects of tumour necrosis factor alpha and interleukin 1 beta on the proliferation of cultured glomerular epithelial cells.

Rat glomerular epithelial cells were cultured with human monocyte supernatant or with recombinant cytokines. A primary glomerular culture and a glomerular epithelial cell culture were made; supernatant from monocyte cultures derived from healthy humans, and recombinant tumour necrosis factor alpha (TNF alpha) or recombinant interleukin 1 beta (IL-1 beta) were added. Cell proliferation rates were assayed by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. In serum-free media, consistent proliferation of glomerular epithelial cells (GEC) was observed throughout the 3 week culture period. Significant growth-stimulatory effects were induced by lipopolysaccharide-treated monocyte conditioned medium and by 1-50 ng/ml of TNF alpha, growth being up to 400% more than in the control culture. The effect of TNF alpha depended mainly on its interaction with epidermal growth factor (EGF). In contrast to TNF alpha, IL-1 beta inhibited GEC proliferation; this was due to the early appearance and proliferation of mesangial cells, despite the culture being serum-free. This study showed that activated monocytes secrete growth factors for GEC in vitro, and that interaction between both TNF alpha and IL-1 beta and between TNF alpha and EGF can modulate GEC proliferation. These findings suggest that, under pathological conditions, monocytes or macrophages affect GEC proliferation, probably being involved in crescent formation.

Animals↗
PubMed1994

Treatment of choice for unresectable small liver cancer: percutaneous ethanol injection therapy or transarterial chemoembolization therapy.

Early detection of hepatocellular carcinoma (HCC) has become easier with recent advances in imaging diagnosis, but the tumor is frequently unresectable due to underlying advanced liver cirrhosis. In this study, we evaluated the therapeutic effect of percutaneous ethanol injection therapy (PEIT) and transarterial chemoembolization therapy (TACE) for small liver cancers measuring 3 cm or less in diameter and discussed the treatment of choice for unresectable cases. The tumors were divided into two groups on the basis of size: 1.5 cm or less (group A) and 1.6-3 cm in diameter (group B). In group A, the estimated 1- and 3-year survival rates were both 82% for a total of 19 cases. The survival value determined for 10 patients treated with PEIT was slightly higher than that found for 9 patients treated with TACE. In group B, the overall 1-, 2-, and 3-year survival values for a total of 56 patients were estimated at 83%, 60%, and 35%, respectively. The survival rates for 41 patients treated with TACE were 82%, 53%, and 28% at 1, 2, and 3 years, respectively. PEIT was performed on only 6 patients, whose survival rate was equivalent to that of a surgical resection group. The 1-, 2-, and 3-year survival rates for 9 patients who underwent surgical resection were estimated to be 100%, 85%, and 68%, respectively. Based on these results, PEIT seems to be the treatment of first choice for patients with small liver cancers measuring less than 1.5 cm in diameter if the tumor is thought to be unresectable because of associated severe liver cirrhosis. On the other hand, tumors measuring 1.6-3 cm in diameter must first be treated with TACE using a long-acting Lipiodol-carcinostatic suspension, even if resectable. In addition to the tumor size, dynamic CT is also useful for prospective decision of the therapeutic strategy. If the mass is demonstrated to be a hypervascular lesion by dynamic CT, TACE must be selected as the treatment of first choice, even for small lesions measuring 1.5 cm or less in diameter.

Aged↗
PubMed1994

Immunocytochemical characterization of human NOR-90 (upstream binding factor) and associated antigens reactive with autoimmune sera. Two MR forms of NOR-90/hUBF autoantigens.

The 90-kDa nucleolus organizer region autoantigen (NOR-90) was previously shown to be identical to the human upstream binding factor (hUBF) and composed of two Mr forms. In this study, thirteen human anti-NOR-90/hUBF autoimmune sera were used to further characterize NOR-90/hUBF and its associated autoantigens. Nucleolar and nucleoplasmic staining of interphase cells and NOR staining in mitosis were observed with all sera by immunofluorescence. All sera showed equal reactivity with both high and low Mr forms in Western blotting and immunoprecipitation, suggesting that the cellular content and distribution for both Mr forms were approximately equal. Using extracts of [35S]methionine- and [32P]orthophosphate-labeled cells, phosphorylated and nonphosphorylated NOR-90/hUBF were identified for both Mr forms and these two populations were recognized by human autoantibodies. In immunoprecipitation analyses, the nonphosphorylated population was readily extracted while the phosphorylated population was tightly bound. Clinical data were available for 8 patients in whom anti-NOR-90/hUBF autoantibodies were present. They had diverse diagnoses including SLE, rheumatoid arthritis and malignancies. Although only one patient was diagnosed as scleroderma, Raynaud's phenomenon was observed in 4 of the 8 patients. Interestingly, one NOR-90/hUBF serum was shown to contain additional antibodies to RNA polymerases I and II.

Adult↗
PubMed1994

Detection of anti-double and anti-single stranded DNA antibodies in chronic liver disease: significance of anti-double stranded DNA antibody in autoimmune hepatitis.

Anti-DNA antibodies were determined by an enzyme-linked immunosorbent assay in 116 patients with chronic liver disease consisting of 21 cases of autoimmune hepatitis (AIH), 17 of primary biliary cirrhosis (PBC), and 78 of non-autoimmune-type of chronic liver disease. The assay was also performed on 83 patients with collagen disease, as a control group. Anti-double stranded DNA antibody (anti-dsDNA) was detected in 10/21 (48%) of the AIH patients and in 3/17 (17%) of the PBC patients, but not in those with other liver diseases. In contrast, anti-single stranded DNA antibody (anti-ssDNA) was positive not only in AIH and PBC, but also in those with non-autoimmune-types of chronic liver disease. Follow-up liver histology disclosed that the 2 patients with AIH who were positive for anti-dsDNA developed liver cirrhosis, whereas the 4 patients who were negative for anti-dsDNA, and those who showed a disappearance of anti-dsDNA following corticosteroid therapy, improved from chronic active to chronic persistent hepatitis.

Adult↗
PubMed1994

Transmission of hepatitis C in an isolated area in Japan: community-acquired infection. The South Kiso Hepatitis Study Group.

BACKGROUND/AIMS: The spread of hepatitis C virus (HCV) infection not due to drug needle sharing or transfusion is largely unknown in communities. A search for risk factors for HCV infection in an endemic area might elucidate inapparent modes of transmission. METHODS: We conducted screening for hepatitis virus markers and parenteral exposures to blood among 435 inhabitants in an isolated area known for its endemicity for non-A, non-B hepatitis and in a nonendemic area with 1542 inhabitants. RESULTS: The prevalence of hepatitis B surface antigen was the same in both areas. The prevalence of antibody to HCV verified by the recombinant immunoblot assay was 32.4% in the highly endemic area and 2.3% in the nonendemic area (P < 0.001). Risk factors for HCV infection in the highly endemic area were complex but included folk remedies such as acupuncture and "vacuuming" for congested blood in muscle by the use of a warm glass bottle. CONCLUSIONS: Folk remedies such as acupuncture and cutting of the skin using nonsterilized knives should be considered as possible routes of HCV transmission not associated with blood transfusion or sharing of drug paraphernalia.

Adolescent↗
PubMed1994

Sclerodermatous renal crisis in a patient with mixed connective tissue disease.

We report a patient with mixed connective tissue disease who developed accelerated hypertension, acute renal insufficiency, and microangiopathic hemolytic anemia. A renal biopsy specimen showed marked vascular changes in small arteries consisting of laminated endothelial cell proliferation and luminal thrombosis, which were similar to those of scleroderma renal crisis. This patient was successfully treated with an angiotensin-converting enzyme inhibitor as well as analogues of prostaglandin E1 and prostaglandin I2. In patients with mixed connective tissue disease, a fatal complication like scleroderma renal crisis should be considered when the blood pressure rapidly increases. The combined administration of angiotensin-converting enzyme inhibitors and analogues of prostaglandin E1 and prostaglandin I2 may be an effective treatment for this complication.

Acute Kidney Injury↗
PubMed1994

Comparative study of CA242 and CA19-9 for the diagnosis of pancreatic cancer.

A comparative study of a new tumour marker, CA242, and CA19-9 was conducted with special reference to their diagnostic usefulness in pancreatic cancer. CA242 showed sensitivity similar to that of CA19-9 for overall cases and early cases (stage I tumour) of pancreatic cancer. For other malignancies, the positive rates of CA242 were lower than those of CA19-9 except for colorectal cancer. An important characteristics of CA242 was that it was only slightly and infrequently elevated in the sera of patients with benign diseases such as chronic pancreatitis, chronic hepatitis and liver cirrhosis. This characteristic was more apparent in the patients with benign obstructive jaundice, indicating that the serum level of this marker was scarcely affected by cholestasis. Using cut-off levels corresponding to a 90% specificity, the clinical results obtained with CA242 in the diagnosis of pancreatic cancer were similar to those obtained with CA19-9, except that CA19-9 was falsely negative in some patients with early-stage pancreatic cancer. These findings suggest the usefulness of this marker for screening pancreatic cancer in patients on their first hospital visit. However, CA242 was found to be influenced by the Lewis blood group system. This unfavourable result is attributed to the C241 catcher antibody of this assay system, which has almost the same epitope specificity as the C50 and the NS19-9 monoclonal antibodies. In conclusion, CA242 is superior to CA19-9 in diagnosing pancreatic cancer by virtue of its higher specificity.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

Rate of thrombus accumulation on intravenacaval IVOX devices explanted from human clinical trial patients with acute respiratory failure.

The weight gain of IVOX devices removed from the first 49 human clinical trials patients after from 1 to 29 days of implantation into the venae caval blood stream has been assessed. Each patient had received sufficient systemic heparin to maintain activated clotting times between 150 and 200 s while the IVOX device was indwelling. The nature of the material accumulating on the IVOX device was documented histologically as being thrombus in various stages of development. The weight gain findings indicate that an average of 2.0 g of thrombus accumulates per 24 h on IVOX devices indwelling in the venous blood stream of moderately anticoagulated human acute respiratory failure patients. The rate of weight gain per 24 h of the IVOX device was more rapid during the first 96 h after its implantation than during its second, third, or fourth week of implantation. The accumulated thrombus on the IVOX hollow fibers was associated with a small but measurable decrease (approximately 1%/day) in gas transfer efficiency of the implanted device. The data support the conclusion that IVOX can function effectively and safely without major thrombus formation for up to 29 days in moderately anticoagulated human acute respiratory failure patients.

Acute Disease↗
PubMed1994

Late pathophysiologic sequelae after utilization of an intravenacaval oxygenator in experimental animals.

The intravenacaval hollow fiber oxygenator (IVOX) has been shown to be remarkably free from acute adverse effects on the venae cavae, right heart, and lungs when indwelling experimentally in sheep and in human clinical trial patients. However, all pathophysiologic assessments reported to date have been carried out during or immediately after IVOX utilization. It is recognized that IVOX indwelling in the venae cavae for up to 3 weeks could produce minor or unrecognized acute injury that could become more evident or more harmful after several weeks had elapsed following removal of the device. Therefore, this current study was designed and carried out to assess any pathophysiologic sequelae that could be recognized on follow-up examination 4 months after removal of an IVOX device that had been indwelling in the venae cavae for from 7 to 13 days. Extensive clinical and physiologic assessments of the blood, hemodynamics, and pulmonary functional status of 8 sheep were carried out 4 months after removal of IVOX devices that had been indwelling for 7 to 13 days. Each animal was then euthanized and complete necropsy examination was conducted looking especially for gross or histologic lesions in the venae cavae, access veins, right heart, and lungs. Findings indicated that all animals were normal, without clinically or pathologically significant pathophysiologic abnormalities or adverse effects from the IVOX utilization. Detailed hematologic, hemodynamic, blood chemistry, pulmonary function, and gross and histopathologic findings, presented in graphic, tabular, and photographic form, document the conclusion that utilization of an IVOX device in normal sheep for from 7 to 13 days produces no significant adverse late pathophysiologic sequelae.

Animals↗
PubMed1994

Two-dimensional left ventricular deformation during systole using magnetic resonance imaging with spatial modulation of magnetization.

BACKGROUND: Myocardial tissue tagging with the use of magnetic resonance imaging allows noninvasive regional analysis of heart wall motion and deformation. However, any evaluation of the effect of disease or treatment requires a baseline reference of normal values and variation. We studied the two-dimensional motion of material points imaged within the left ventricular wall using spatial modulation of magnetization (SPAMM) in 12 normal human volunteers. METHODS AND RESULTS: Five parallel short-axis and five parallel long-axis slices were acquired at five times during systole. SPAMM tags were generated at end diastole using a 7-mm grid. Intersection point data were analyzed for displacement, rotation, and torsion, and triangles of points were analyzed for local rotation and principal strains. Short-axis displacement was the least in the septum for all longitudinal levels (P < .001). Torsion about the long axis was uniform circumferentially because of the motion of the centroids used to reference the rotation. In the long-axis images, the base displaced longitudinally toward the apex, with the posterior wall moving farther than the anterior wall (13.4 +/- 2.2 versus 9.7 +/- 1.8 mm, P < .001) in this direction. The largest principal strain (maximum lengthening) was approximately radially oriented in both views. In the short-axis images, the minimum principal strain (maximum shortening) increased in magnitude toward the apex (P < .001) with little circumferential variation, except at midventricle, where the anterior wall showed greater contraction than the posterior wall (-0.21 +/- 0.03 versus -0.19 +/- 0.02, P < .02). CONCLUSIONS: Consistent regional variations in deformation are seen in the normal human heart. Displacement and maximum shortening strains are well characterized with two-dimensional magnetic resonance tagging; however, higher-resolution images will be required to study transmural variations.

Adult↗