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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 217 records · Page 12Linked to original sources

[Anti-thyroglobulin antibodies].

Measurement of anti-thyroglobulin antibody(TgAb) is used for diagnosis of autoimmune thyroid disease(AITD). Approximately 82-100% of patients with Hashimoto's thyroiditis and 60-70% of patients with Graves' disease are TgAb positive using high sensitive radioimmunoassay. In patients with subacute thyroiditis(SAT), TgAb is usually negative. Therefore, measurement of TgAb is useful to diagnose painless thyroiditis or acute worsening of Hashimoto's thyroiditis from SAT. To predict the post-partum thyroid dysfunction and thyroid dysfunction after interferon treatment, TgAb measurement is important, since patients with positive TgAb are apt to progress thyroid dysfunction.

Autoantibodies↗

[Typical thymic carcinoid tumor with multiple metastases diagnosed by pleural effusion cytology].

A 57-year-old man was referred and admitted to our hospital because of anterior mediastinal tumors and pericardial effusion. Although his condition had been diagnosed as thymic cancer by another hospital, a cytologic examination of pleural effusion specimens obtained a positive stain for chromogranin A, and yielded a diagnosis of thymic carcinoid tumor with multiple metastases. Despite irradiation and relief therapy, the patient died 8 months later. A histopathologic examination of the thymic tumor at autopsy revealed typical carcinoid patterns. The cytologic examination proved capable of accurately diagnosing the carcinoid tumor. Although such tumors are usually considered to have a good prognosis, unfavorable outcomes are also a possibility, as was demonstrated in this case.

Carcinoid Tumor↗

[Spinal lipoma in children: analysis of magnetic resonance image for upward displacement of medullary-conus on 44 consecutive surgical cases].

Medullary conus-untethering operation was conducted on 52 infants with spinal lipoma. Magnetic resonance (MR) image was used in order to evaluate the untethering results in 44 out of these 52 patients who could be followed-up after Osaka Medical Center & Research Institute for Maternal & Child Health was opened. Talking into account the changes in vertebral body during the growth period of infants, the authors studied the upward displacement of the conus-lipoma interface by four fractional MR sagittal image, using the vertebral body-intervertebral disc space as the baseline. Upward displacement was confirmed in 27 of 44 (61.4%). The mean, median and trimmed mean of upward displacement were 1.78 +/- 0.80, 2.0, 1.70 fractions, respectively. Sixteen (59.3%) were caudal type, 10 (37.0%) were transitional type and 1 (3.7%) was dorsal type. By type of spinal lipoma, upward displacement was observed in 16 of 23 caudal type patients (69.6%), 10 of 16 transitional type patients (62.5%) and 1 of 5 dorsal type patients (20%). While the rate of upward displacement was almost equal between the caudal and transitional type, that of dorsal type was lower. However, statistical analysis for the difference in population percentage of the three groups showed that significant difference existed only in the caudal type group.

Female↗

A new system to detect native microaggregates of platelets in vivo, with a novel platelet aggregometer employing laser light scattering.

Circulating platelets are susceptible to various stimuli in vessels, and a certain portion of platelets may thereby form native microaggregates (NMAs), which can be visualized by a bother scanning electron microscopy (SEM). We developed an easy method to evaluate the existence and extent of NMAs and the subsequent spontaneous platelet aggregation (SPA) induced by not any agonist but stirring force with a novel platelet aggregometer (PA-200; Kowa, Tsukuba, Japan) employing a particle-counting method based on laser light scattering. In this system, platelet-rich plasma obtained by a delicate centrifugation was infused in a cuvette to replace the content and to avoid stirring shear. An insertion attachment was designed in a coaxial shape to maintain a constant sample volume. Our data indicated that NMAs, tentatively defined as a "small" division by their light scattering (25-400 of the intensity threshold), could be detected by not only a complicated SEM but also by our simple system with the PA-200 in a few minutes. No correlation was found in the comparison of the existence of NMAs and the SPA generation, in aliquot platelets, respectively. These results suggested that NMAs and SPA might be mutually different cluster and have meanings as representations of platelet status.

Blood Platelets↗

Transforming growth factor-beta1 increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells.

Osteoclastogenesis inhibitory factor (OCIF), also termed osteoprotegerin (OPG), is a secreted member of the tumor necrosis factor (TNF) receptor family. It inhibits bone resorption in vivo and osteoclast-like cell (OCL) formation in vitro. To better understand the biological role of OCIF, we first examined the effects of various osteotropic agents on OCIF mRNA levels in mouse calvarial osteoblasts. Northern blot analysis showed that stimulators of OCL formation such as 1,25-(OH)2D3, prostaglandin E2 (PGE2), parathyroid hormone (PTH), and interleukin 1 (IL-1) decreased OCIF mRNA levels. In contrast, transforming growth factor (TGF)-beta1 increased OCIF mRNA levels in primary osteoblasts as well as in osteoblastic/stromal cell lines. Since it was reported that both TGF-beta1 and OCIF not only inhibited OCL formation but also impaired the survival of OCL by inducing apoptosis in vitro, we next examined the possible involvement of OCIF in TGF-beta1-induced impairment of OCL survival. In a mouse bone marrow culture, we confirmed that addition of OCIF or TGF-beta1 decreased the number of surviving OCL. Anti-OCIF IgG, which completely neutralized the effect of OCIF, partially prevented the TGF-beta1-induced decrease in the number of OCL. Our results suggest that (i) downregulation of OCIF expression is one of the mechanisms for the stimulatory effects of 1,25(OH)2D3, PGE2, PTH, and IL-1 on osteoclastogenesis; and (ii) the TGF-beta1-induced apoptosis of OCL is mediated, at least in part, by upregulation of OCIF expression.

Animals↗

Asialoglycoprotein receptor-mediated gene transfer using novel galactosylated cationic liposomes.

We synthesized three novel galactosylated cholesterol derivatives, cholesten-5-yloxy-N-(4-((1-imino-c-beta-D-thiogalactosyl+ ++-ethyl)amino) butyl)formamide (Gal-C4-Chol) and its ethyl formamide and hexyl formamide analogues (Gal-C2-Chol, Gal-C6-Chol), to prepare liposomal gene carriers possessing the cationic charge necessary for plasmid DNA binding and galactose residues as a targetable ligand for liver parenchymal cells. Liposome/DNA complexes prepared with these lipids showed low cytotoxicity in human hepatoma HepG2 cells. Gal-C4-Chol/DC-Chol/DOPE(3:3:4) liposomes, consisting of 3:3:4 mixtures of Gal-C4-Chol, 3beta[N',N', N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol), and dioleoylphosphatidylethanolamine (DOPE), showed higher transfection activity and [32P]DNA uptake than DC-Chol/DOPE(6:4) liposomes. The presence of 20 mM galactose significantly inhibited both transfection efficiency and uptake of DNA of Gal-C4-Chol/DC-Chol/DOPE(3:3:4) and Gal-C4-Chol/DOPE(6:4) liposomes, but not those of DC-Chol/DOPE(6:4) liposomes. These results indicate that the liposome/DNA complexes prepared using novel galactosylated cholesterol derivatives are efficiently recognized by asialoglycoprotein receptors and internalized and lead to gene expression. In addition, we found that the galactosylated cholesterol derivative with a longer spacer showed higher transfection activity.

3T3 Cells↗

Quantitative measurements for type 1 deiodinase messenger ribonucleic acid in human peripheral blood mononuclear cells: mechanism of the preferential increase of T3 in hyperthyroid Graves' disease.

To evaluate the regulatory mechanism of human Type 1 iodothyronine deiodinase (D1) gene expression, we measured the D1 mRNA levels in peripheral blood mononuclear cells (PBMC) in normal control subjects and in patients with Graves' disease. We used competitive reverse transcriptase-polymerase chain reaction with the deleted complimentary RNA of D1 as the standard for quantification. The D1 mRNA levels in PBMC were increased significantly in patients with Graves' disease compared with that in normal controls. There was a significant (p < 0.01) positive correlation (r=0.698) between D1 mRNA level and serum T3 concentration. When PBMC from the normal volunteers were cultured with various doses of T3, the quantity of D1 mRNA increased significantly in a dose-dependent manner. These findings indicate that PBMC D1 mRNA is actually up-regulated by T3 in vivo, and we postulate that a vicious spiral of increasing T3 and D1 is responsible for the exacerbation of thyrotoxicosis in hyperthyroid Graves' disease.

Gene Expression Regulation↗

Topography of modular subunits in the mushroom bodies of the cockroach.

The mushroom body (MB), a conspicuous neuropil structure in the insect brain, is implicated in associative memory and in some aspects of motor control. Intrinsic neurons of the MB (Kenyon cells) extend dendrites into the calyx, and their axons run through the pedunculus and then bifurcate to form the alpha and the beta lobes. At the pedunculus and the lobes, Kenyon cells make synaptic connections with dendrites of extrinsic (output) neurons. Previously, we reported that the alpha lobe of the cockroach MB consists of repetitive modular subunits (Mizunami et al. [1997] Neurosci. Lett. 229:153-156). Each subunit is composed of a dark layer and a light layer, and the layers are refereed to as slabs. Each slab is composed of axons of a specific subset of Kenyon cells. In the present study, we examined serial sections of reduced silver preparations and found that each dark and light slab continues throughout the length of the pedunculus and the alpha and beta lobes. We also found that Golgi-impregnated Kenyon cells often exhibit a characteristic grouping, forming a thin sheet interlaced by dozens or hundreds of axons. The sheet is much thinner than the slab, and each sheet remains within a particular slab throughout the length of the pedunculus and the lobes. Thus, the sheet is a component forming the slab. In the pedunculus and the beta lobe, a class of Golgi-impregnated extrinsic neurons exhibit segmented dendritelike arbors that interact with every other slab, i.e., either with only dark or light slabs. Because each neuron of this class interacts with each particular set of dark or light slabs, we conclude that the slabs are units for transmitting output signals from the MB.

Animal Structures↗

Topography of four classes of Kenyon cells in the mushroom bodies of the cockroach.

Mushroom bodies (MBs), which are higher centers in the insect brain, are implicated in associative memory and in the control of some behaviors. Intrinsic neurons of the MB, called Kenyon cells, receive synaptic inputs from axon terminals of input neurons in the calyx. Axons of Kenyon cells project into the pedunculus and to the alpha and beta lobes, where they make synaptic connections with dendrites of extrinsic (output) neurons. In this study, we examined the morphology of Kenyon cells in the cockroach by using Golgi stains and found that they can be classified into four classes (K1, K2, K3, and K4), according to the diameter, location, and morphology of the cell bodies, dendrites, and axons. The somata of Kenyon cells of different classes occupy different concentric zones; K1 cells occupy the most central zone, and K4 cells occupy the most peripheral zone. The main processes of Kenyon cells of different classes also occupy different concentric zones in the calyx. Dendrites of K2 and K3 cells are distributed throughout the calycal neuropil, whereas those of K1 and K4 cells cover the outer and inner halves of the depth of the neuropil, respectively. In the pedunculus and the alpha and beta lobes, axons of Kenyon cells of different classes occupy different zones, although the separation is not complete. A class of extrinsic neurons in the a lobe has dendrite-like arbors that cover the zones where either K1, K2, or K3 are located. These neurons probably transmit signals of each class of Kenyon cells. We conclude that, in the cockroach, four classes of Kenyon cells subdivide the cell body region, pedunculus, and lobes of the MBs, whereas subdivision is less prominent in the calycal neuropil.

Animal Structures↗

Osteoclastogenesis inhibitory factor suppresses osteoclast survival by interfering in the interaction of stromal cells with osteoclast.

Osteoclastogenesis inhibitory factor (OCIF) was originally identified as a factor inhibiting osteoclast (OC) formation. The number of OC in rats treated with OCIF decreased, suggesting that OCIF inhibits OC formation in vivo; however, it is also possible that OCIF affects the number of OC by promoting apoptosis of OC. To address this issue, the effects of OCIF on the survival of OC were examined using well established mouse culture systems. OCIF dose-dependently inhibited OC formation in mouse marrow cultures. Addition of OCIF during day 0-3 did not alter the peak levels of OC formation on day 7 and 8. However, the addition of OCIF during day 5 and thereafter resulted in the rapid decrease of the number of OC. OCIF inhibited the survival of OC formed in mouse marrow cultures in dose- and time-dependent manners. The involvement of stromal cells in OC survival was examined using crude and stromal cell-depleted OC populations. OCIF dramatically inhibited the survival of crude OC populations rich with stromal cells. However, in stromal cell-depleted OC populations, OC spontaneously decreased in the absence of OCIF and OCIF did not enhance the decrease further at least up to 48 h. Apoptotic OC were detected in detached cell populations treated with OCIF in mouse marrow cultures and a specific inhibitor for caspase-3 rescued the death of OC. OCIF mutant lacking the death domain homologous regions inhibited OC survival, though the potency was much less than native OCIF. Taken together, OCIF inhibited not only OC recruitment but also OC survival. OCIF inhibited OC survival by interfering the interaction of stromal cells with OC.

Animals↗

Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. Osaka Hepatocellular Carcinoma Prevention Study Group.

BACKGROUND: The effect of interferon therapy on the incidence of hepatocellular carcinoma in chronic hepatitis C is poorly defined. OBJECTIVE: To compare the incidence of hepatocellular carcinoma in interferon-treated patients with chronic hepatitis C to that of historical controls and to examine whether response to therapy is related to incidence of hepatocellular carcinoma in patients with chronic hepatitis C. DESIGN: Retrospective cohort study. SETTING: One university hospital and seven university-affiliated hospitals. PATIENTS: 419 consecutive patients with chronic hepatitis C who started interferon therapy between January 1992 and December 1993 (interferon group) and 144 patients with chronic hepatitis C who had liver biopsy between January 1986 and December 1989 and did not receive interferon (controls). INTERVENTION: Patients in the interferon group received human lymphoblastoid interferon, recombinant interferon-alpha2a, or recombinant interferon-alpha2b for 6 months. MEASUREMENTS: The end point was development of hepatocellular carcinoma on abdominal ultrasonography or computed tomography. Sustained response was defined as persistent normalization of alanine aminotransferase (ALT) levels during interferon therapy and follow-up. Relapse was defined as a normal serum ALT level at the end of treatment with an increase to an abnormal level after cessation of treatment. Nonresponse included all other ALT patterns. RESULTS: Median follow-up in the interferon and control groups was 47.6 and 46.8 months, respectively. During follow-up, hepatocellular carcinoma was found in 28 interferon-treated patients and 19 controls. Cox proportional hazards regression analysis that included all patients revealed that interferon therapy (P=0.041), older age (P=0.003), greater histologic activity (P=0.029), and higher histologic stage (P=0.049) were independent factors associated with the development of hepatocellular carcinoma. The risk ratios for development of hepatocellular carcinoma in patients with sustained response, relapse, and nonresponse were 0.06 (95% CI, 0.01 to 0.46), 0.51 (CI, 0.20 to 1.27), and 0.95 (CI, 0.48 to 1.84), respectively, compared with controls. CONCLUSIONS: The incidence of hepatocellular carcinoma was lower in patients with sustained response to interferon therapy than historical controls and nonresponders. Interferon therapy may decrease the risk for hepatocellular carcinoma in patients with chronic hepatitis C.

Alanine Transaminase↗

Helicobacter pylori generates superoxide radicals and modulates nitric oxide metabolism.

During studies of the bactericidal action of nitric oxide (NO), we found that it reversibly inhibited the respiration of Escherichia coli and irreversibly inhibited the respiration of Helicobacter pylori. Peroxynitrite, a reaction product of NO and superoxide, irreversibly inhibited the respiration of both H. pylori and E. coli. H. pylori, but not E. coli, generated substantial amounts of superoxide radicals. These results suggest that NO directly inhibits the respiration of E. coli whereas it rapidly reacts with endogenously generated superoxide radicals in H. pylori. The resulting peroxynitrite inactivates the respiration of H. pylori.

Escherichia coli↗

Targeted delivery of plasmid DNA complexed with galactosylated poly(L-lysine).

Galactose was introduced to poly(L-lysine) (PLL) with an average molecular weight of 13,000 to develop a hepatocyte-specific carrier for gene drugs. The pharmacokinetic characteristics of a model plasmid, pCAT (plasmid DNA encoding chloramphenicol acetyltransferase reporter gene), complexed with galactosylated PLL (Gal-PLL) was studied in mice in relation to its physicochemical properties. pCAT/Gal-PLL complex at a ratio of 1:0.6 (w/w) has a zeta potential of -20 mV and a mean particle size of about 180 nm. After intravenous injection, [32P]pCAT/Gal-PLL was rapidly eliminated from the circulation and preferentially taken up by the liver's parenchymal cells. The hepatic uptake of [32P]pCAT/Gal-PLL was significantly inhibited by prior administration of Gal-bovine serum albumin, suggesting that the uptake was mediated by the asialoglycoprotein receptors on hepatocytes. In vitro transfection experiments using a hepatoma cell line expressing the asialoglycoprotein receptor revealed that pCAT/Gal-PLL gave a high CAT gene expression whereas pCAT complexed with unmodified PLL failed to transfect the cells.

Animals↗