Biomedical subjects

T Itoh

Publications and source records attributed to T Itoh.

At least 307 records · Page 17Linked to original sources

PubMed1999

Keratinocytes from patients with lupus erythematosus show enhanced cytotoxicity to ultraviolet radiation and to antibody-mediated cytotoxicity.

Keratinocyte cytotoxicity is an important component of the immunopathology of photosensitive lupus erythematosus, and antibody-dependent cell-mediated cytotoxicity (ADCC) has been shown to be an important mechanism by which autoantibodies, especially those specific for SS-A/Ro, can induce keratinocyte damage in models of photosensitive lupus. We provide further evidence that keratinocytes from patients with photosensitive lupus show significantly greater ultraviolet radiation (UVR)-induced cytotoxicity, and that ADCC of these targets is especially enhanced by autologous patient's serum or by anti-SS-A/Ro+ sera. Keratinocytes from normal uninvolved skin of 29 patients with cutaneous lupus erythematosus (LE) were grown in cell culture and tested as targets in cytotoxicity experiments in vitro. Cultured keratinocytes from patients with systemic lupus erythematosus (SLE) and subacute cutaneous lupus erythematosus (SCLE) showed significantly greater cytotoxicity following UVR treatment than did keratinocytes from normal adult controls or from neonatal foreskins (P < 0.01). The same cultures also showed greater UVR-induced binding of IgG from fractionated anti-SS-A/Ro+ preparations. ADCC experiments were also performed using keratinocytes cultured from patients with SLE, SCLE, discoid lupus erythematosus (DLE), and normal controls. When keratinocytes were incubated in autologous serum plus a standard mononuclear cell effector population, the percentage of ADCC observed was significantly greater in cultures containing keratinocytes and sera from the SLE and SCLE patients (P < 0.001). When cultured keratinocytes were added to different IgG antibody probes, plus standard mononuclear effector populations, greater ADCC was seen using the anti-SS-A/Ro probe and keratinocytes from patients with SLE or SCLE. With normal human neonatal keratinocyte targets, the anti-SS-A/Ro probe induced greater ADCC than that seen with anti-ssDNA or normal human serum. We have shown that keratinocytes from patients with some forms of lupus erythematosus (SLE and SCLE) show greater cytotoxicity in vitro when irradiated with UVR, and greater susceptibility to ADCC whether the antibody source is their own serum or an anti-SS-A/Ro probe.

Adult↗

PubMed1999

Growth of moulds inoculated into commercial mineral water.

The growth of mould spores of Penicillium sp. and Cladosporium sp. inoculated in a commercial mineral water product was studied. The strains had been isolated as fungal foreign bodies in commercial mineral waters. In product A, which was not originally sterilized and was contaminated with psychrophilic bacteria, the inoculated mould spores of the strains did not grow; no increases in viable colony counts or beta-glucans concentration in the samples were observed during storage. In a sterilized product A, inoculated spores of the strains grew into visible foreign bodies. The viable colony counts and the beta-glucans concentration in the samples increased during storage. These results showed that in a sterilized mineral water product, mould spores could grow into visible foreign bodies.

Cladosporium↗

PubMed1999

Treatment of obstructive sleep apnea syndrome with a Kampo-formula, San'o-shashin-to: a case report.

The following describes a 76-year-old male with obstructive sleep apnea syndrome successfully treated with a Kampo-formula, San'o-shashin-to (Formula medicamentorum tres ad dispellendi cordis). Polysomnography, performed before and after administration of San'o-shashin-to, revealed that the apnea index decreased from 11.1 events/hour to 4.1 events/hour, and that the apnea plus hypopnea index decreased from 18.4 events/hour to 10.7 events/hour. The patient was normo-weight (body mass index: 20.4 kg/m2), and events of sleep apnea and hypopnea were mostly noted during a non-rapid eye movement sleep. It is possible that San'o-shashin-to has some alleviating effects on the upper airway resistance during sleep.

Aged↗

PubMed1999

Caspase-3 expression by cerebellar granule neurons is regulated by calcium and cyclic AMP.

Caspase-3 enzyme activity is induced, and cell death follows, when cerebellar granule neurons (CGNs) from 8-day-old rats are transferred from an extracellular concentration of 25 mM K+ (25 mM [K+]e) to 5 mM [K+]e. Death of these neurons is diminished by an inhibitor of caspase-3 but not by an inhibitor of caspase-1. Actinomycin D and cycloheximide inhibit induction of caspase-3 and prevent death. Experiments in which CGN intracellular Ca2+ concentration ([Ca2+]i) was manipulated by either changing [K+]e or adding a voltage-gated Ca2+ channel antagonist or a Ca2+ ionophore to the medium showed that caspase-3 mRNA rises 2.5-fold when [Ca2+]i is diminished from 300 to 150 nM, with a corresponding rise in peak caspase enzyme activity. Whereas the caspase-3 mRNA level does not rise further with a still greater diminution in [Ca2+]i, peak caspase enzyme activity continues to increase, reaching sevenfold induction when [Ca2+]i is reduced to 55 nM. In CGNs in which [Ca2+]i is set at 55 nM by incubation in 5 mM [K+]e, treatment with forskolin or dibutyryl 3',5'-cyclic adenosine-5'-monophosphate delays caspase-3 induction and diminishes death but does not alter [Ca2+]i. We conclude that, in immature CGNs, both caspase-3 transcription and the subsequent processing of caspase-3 are induced by a fall in [Ca2+]i. Elevating cyclic AMP content delays caspase-3 induction by a mechanism that does not require an increase in [Ca2+]i.

Amino Acid Chloromethyl Ketones↗

PubMed1999

A newly identified patient with clinical xeroderma pigmentosum phenotype has a non-sense mutation in the DDB2 gene and incomplete repair in (6-4) photoproducts.

We report here a patient (Ops1) with clinical photosensitivity, including pigmented or depigmented macules and patches, and multiple skin neoplasias (malignant melanomas, basal cell carcinomas, and squamous cell carcinomas in situ) in sun-exposed areas. These clinical features are reminiscent of xeroderma pigmentosum. As cells from Ops1 showed normal levels in DNA repair synthesis in vivo (unscheduled DNA synthesis and recovery of RNA synthesis after ultraviolet irradiation), we performed a postreplication repair assay and recovery of replicative DNA synthesis after ultraviolet irradiation to investigate if Ops1 cells belonged to a xeroderma pigmentosum variant pattern. Ops1 cells were normal, but there was an incomplete pattern repair in (6-4) photoproducts in contrast to a normal pattern repair in cis-syn cyclobutane pyrimidine dimers by repair kinetics using the enzyme-linked immunosorbent assay. Moreover, Ops1 cells were defective in a damage-specific DNA binding protein and carried a non-sense mutation in the DDB2 gene. These results suggest that (i) the DDB2 gene is somewhat related to skin carcinogenesis, photoaging skin, and the removal of (6-4) photoproducts; (ii) although it is believed that cyclobutane pyrimidine dimers are the principal mutagenic lesion and (6-4) photoproducts are less likely to contribute to ultraviolet-induced mutations in mammals, Ops1 is one of the ultraviolet-induced mutagenic models induced by (6-4) photoproducts.

Caffeine↗

PubMed1999

Evaluation of apoptotic cells induced by ultraviolet light B radiation in epidermal sheets stained by the TUNEL technique.

Two major components of epidermal cells, keratinocytes and Langerhans cells, are injured by ultraviolet light B radiation, resulting in sunburn cell (apoptotic cell) formation, impaired function, and a reduced number of Langerhans cells. Quantitative analysis of Langerhans cell damage is usually performed using epidermal sheets, whereas that of keratinocytes has been performed by counting the number of sunburn cells in vertical tissue sections. In this study we assessed the influences of ultraviolet light B radiation on epidermal cells by apoptotic cell formation, using murine epidermal sheets stained by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique. Ten to 75 mJ per cm2 of ultraviolet light B radiation induced apoptotic cells in abdominal skin of C3H mice. The cells were induced in 6 h after 50 mJ per cm2 of ultraviolet light B irradiation with the peak in number in 24 h, 18.8 +/- 5.0 per mm2 and 97.7 +/- 7.4 per mm2, respectively. One week later, the apoptotic cells were not visualized. As C3H/He, BALB/C, and C57BL/6 mice showed almost the same frequency of apoptosis in epidermal sheets from 50 mJ per cm2 ultraviolet light B-irradiated skin, the induction of the cells by ultraviolet light B radiation did not depend on the genetic trait of the mouse. Xeroderma pigmentosum type A gene-deficient mice, however, showed a greater induction of apoptotic cells (216.9 +/- 25.2 per mm2) by ultraviolet light B radiation than xeroderma pigmentosum type A wild-type mice (89.5 +/- 13.6 per mm2) and conventional mice. Pretreatment with a SPF 60 sunscreen agent was quite effective in reducing the induction of apoptotic cells. Using confocal laser scanning microscopy and double staining, 1.5 +/- 2.7% of apoptotic cells were Ia-positive cells in 24 h after 50 mJ per cm2 of ultraviolet light B radiation. Apoptotic Ia-positive cells were not observed 48 h after the radiation. On the other hand, no apoptotic dendritic epidermal T cells were observed in up to 75 mJ per cm2 of ultraviolet light B radiated skin. Thus, nearly all apoptotic cells were keratinocytes, and Langerhans cells and dendritic epidermal T cells appeared resistant to ultraviolet light B-induced apoptosis. Compared with the assessment in vertical tissue sections, the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique with epidermal sheets appeared to be a more physiologically relevant method for quantitative evaluation of apoptotic epidermal cells induced by ultraviolet light B radiation.

Animals↗

PubMed1999

The putative mechanism of thrombosis in antiphospholipid syndrome: impairment of the protein C and the fibrinolytic systems by monoclonal anticardiolipin antibodies.

The mechanism of thrombosis in patients with antiphospholipid syndrome is not clear. To investigate it, we examined the effect of monoclonal anticardiolipin (aCL) antibodies and beta2-glycoprotein I (beta2-GPI), which is required for formation of the aCL epitopes, on activated protein C (APC) and on fibrinolytic activity. First, APC activities were measured in the presence and absence of beta2-GPI or gamma M immunoglobulin (IgM) monoclonal aCLs (EY1C8 and EY2C9), or both, established from peripheral blood lymphocytes obtained from a patient with aCL. beta2-GPI exhibited a procoagulant activity by inhibiting APC activity as well as an anticoagulant activity by inhibiting thrombin generation. Any further inhibition of APC activity was caused by monoclonal aCL, and then only in the presence of beta2-GPI. The remaining tissue plasminogen activator (t-PA) of the sample consisting of beta2-GPI, two-chain recombinant t-PA, and plasminogen activator inhibitor (PAI)-1 was measured by a chromogenic assay using the synthetic substrate S-2251, Glu-plasminogen, and soluble fibrin monomer. beta2-GPI protected t-PA activity from inhibition by PAI-1. However, monoclonal aCLs (EY1C8 and EY2C9) inhibited the effect of beta2-GPI on fibrinolytic activity; that is, monoclonal aCLs inhibited fibrinolytic activity by elevating PAI-1 activity. Thrombosis in patients with aCL can be explained in part by both the inhibition of APC anticoagulant activity and the impairment of fibrinolytic activity by aCL.

Antibodies, Anticardiolipin↗

PubMed1999

Analysis of phospholipase C gene in patients with subarachnoid hemorrhage due to ruptured intracranial saccular aneurysm.

This study is designed to determine whether patients with aneurysmal subarachnoid hemorrhage have mutations in the phospholipase C-delta 1 (PLC-delta 1) gene, which was identified as a gene responsible for hypertension in spontaneously hypertensive rats. Seventy-two cases (31 male and 41 female) with intracranial saccular aneurysms were analyzed. The mean age was 60.1 +/- 11.5 years (mean +/- SD) (range 24-85 years). There were 35 patients (48.6%) with hypertension, 5 (6.9%) with diabetes mellitus, 12 (16.7%) with hyperlipidemia, 8 (11.1%) with ischemic heart disease, and 25 (34.7%) who were active smokers. The location of aneurysm was distributed as follows: 33 (33%) were at anterior cerebral artery, 23 (23%) were at middle cerebral artery, 28 (28%) were at internal carotid artery, and 16 (16%) were at vertebro-basilar artery. Six patients (8.3%) had a family history of intracranial aneurysms. There were 20 patients (27.8%) with multiple aneurysms, and 8 patients (11.1%) with a large or giant aneurysm. The four regions of PLC-delta 1 gene (bases 1099-1271, 1254-1401, 1343-1481, and 1882-2023) where genetic mutations were found in spontaneously hypertensive rats, were screened by PCR-SSCP analysis and their nucleotide sequences of all patients were determined. However, no mutations were detected in all patients. These results suggest that mutations of PLC-delta 1 gene previously implicated in hypertensive factor in rats may not be the case with human patients and therefore may be poorly related with aneurysmal subarachnoid hemorrhage.

Adult↗

PubMed1999

Non-Hodgkin's lymphoma followed by plasmacytoma, both arising in A thyroid gland with Hashimoto's disease.

We describe here a rare case of malignant lymphoma followed by plasmacytoma in Hashimoto's thyroiditis. The patient developed malignant lymphoma (small, non-cleaved cell, and non Burkitt's type by Working Formulation classification), and remained in remission for 2 years after receiving combination chemotherapy, and then developed plasmacytoma in the same lesion. Rearrangement bands for IgH from both specimens showed different bands, indicating that both were of monoclonal type but of a different clonal origin. Considering the clinical course in this case, thyroidectomy may be indicated for lymphoproliferative diseases in Hashimoto's thyroiditis treated with chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Two distinct signaling pathways downstream of Janus kinase 2 play redundant roles for antiapoptotic activity of granulocyte-macrophage colony-stimulating factor.

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) induces proliferation and sustains the viability of the mouse interleukin-3-dependent cell line BA/F3 expressing the hGM-CSF receptor. Analysis of the antiapoptosis activity of GM-CSF receptor betac mutants showed that box1 but not the C-terminal region containing tyrosine residues is essential for GM-CSF-dependent antiapoptotic activity. Because betac mutants, which activate Janus kinase 2 but neither signal transducer and activator of transcription 5 nor the MAPK cascade sustain antiapoptosis activity, involvement of Janus kinase 2, excluding the above molecules, in antiapoptosis activity seems likely. GM-CSF activates phosphoinositide-3-OH kinase as well as Akt, and activation of both was suppressed by addition of wortmannin. Interestingly, wortmannin did not affect GM-CSF-dependent antiapoptosis, thus indicating that the phosphoinositide-3-OH kinase pathway is not essential for cell surivival. Analysis using the tyrosine kinase inhibitor genistein and a MAPK/extracellular signal-regulated kinase (ERK) kinase 1 inhibitor, PD98059, indicates that activation of either the genistein-sensitive signaling pathway or the PD98059-sensitive signaling pathway from betac may be sufficient to suppress apoptosis. Wild-type and a betac mutant lacking tyrosine residues can induce expression of c-myc and bcl-x(L) genes; however, drug sensitivities for activation of these genes differ from those for antiapoptosis activity of GM-CSF, which means that these gene products may be involved yet are inadequate to promote cell survival.

Animals↗

PubMed1999

A simple method for estimating the intensity of purifying selection in protein-coding genes.

We propose a method by which the intensity of purifying selection on a functional protein-coding gene is estimated by using three aligned homologous sequences: a processed pseudogene (psi), a functional paralog from the same species (g), and a functional ortholog from a different species (o). For each such trio, we calculate the numbers of nucleotide substitutions along the branches leading to psi and g, i.e., K psi and K(g). If we assume that the mutation rates are the same in the genes and the pseudogenes and that mutations occurring in a pseudogene do not affect the fitness of the organism, we can show that the fraction of mutations that are selectively neutral, fg, is equal to the ratio K(g)/K psi. Since advantageous mutations occur only very rarely, such that they do not contribute significantly to the rate of molecular evolution, the fraction of deleterious mutations that are subject to purifying selection is 1-fg. Therefore, the K(g)/K psi ratio can be used directly to estimate the intensity of purifying selection, thereby isolating its effects on the rate of evolution from those of mutation. We compared the selection intensities of 12 orthologous protein-coding pairs from humans and murids. As expected, the fraction of mutations that are subject to purifying selection is strongest in the second codon position and weakest in the third. Interestingly, the mean fractions of effectively neutral mutations in the third codon position were only 41% and 42% for murids and humans, respectively, indicating that many synonymous mutations are subject to selective constraint. In several orthologous genes, we found that the intensity of purifying selection is very different between murid and human orthologous genes. There was no statistically significant difference in overall intensity of purifying selection between humans and murids. Thus, purifying selection does not seem to be an important factor contributing to the observed differences in the rates of evolution between these two taxa.

Animals↗

PubMed1999

Evolutionary instability of operon structures disclosed by sequence comparisons of complete microbial genomes.

Gene orders have been shown to be generally unstable by comprehensive analyses in several complete genomes. In this study, we examined instability of genome structures within operons, where functionally related genes are clustered. We compared gene orders of known operons obtained from Escherichia coli and Bacillus subtilis with corresponding those of operons in 11 complete genome sequences. We found that in many cases, gene orders within operons could be shuffled frequently during evolution, although several operon structures, such as ribosomal protein operons, were well conserved. This suggests that shuffling of a genome structure is virtually neutral in long-term evolution. Moreover, degrees of instability of the operon structures depended on the genomes examined. Variation in degrees of instability of the genome structures was likely to be related to differences in amounts of insertion sequences. Effects on transcription regulation are also discussed in association with operon destruction.

Bacillus subtilis↗

PubMed1999

Inhibitory effects of propofol on acetylcholine-induced, endothelium-dependent relaxation and prostacyclin synthesis in rabbit mesenteric resistance arteries.

BACKGROUND: Propofol (2,6-diisopropylphenol) modulates endothelium-dependent relaxation in some arterial preparations. The effect of propofol on endothelium-dependent, prostacyclin-mediated responses in mesenteric resistance arteries has not yet been clarified. METHODS: The effect of propofol was examined on acetylcholine-induced membrane potential changes in the presence of N(G)-nitro-L-arginine (L-NOARG) in endothelium-intact rabbit mesenteric resistance arteries in vitro. The effects of propofol were also examined on the endothelium-dependent relaxation and prostacyclin synthesis that was induced by acetylcholine in the presence of L-NOARG and nicardipine. The effect of propofol on the relaxation induced by a prostacyclin analogue was examined in strips treated with L-NOARG and diclofenac. RESULTS: Acetylcholine produced an initial and a slow membrane hyperpolarization. Propofol, 10 microM, and diclofenac each inhibited the acetylcholine-induced slow hyperpolarization, but not the initial hyperpolarization. Acetylcholine produced an endothelium-dependent relaxation that was significantly inhibited by propofol, 10 microM, and diclofenac. Propofol, 10 microM, greatly inhibited the acetylcholine-induced synthesis of prostacyclin, as did diclofenac. Propofol, 10 microM, had no effect on the relaxation induced by a prostacyclin analog. CONCLUSIONS: In rabbit mesenteric resistance arteries, propofol inhibits the synthesis of prostacyclin and thus attenuates acetylcholine-induced, endothelium-dependent responses. Our results may help to explain why some actions seen with propofol in some preparations (e.g., vasoconstriction) are not seen after the endothelium is removed.

Acetylcholine↗

PubMed1999

Caldivirga maquilingensis gen. nov., sp. nov., a new genus of rod-shaped crenarchaeote isolated from a hot spring in the Philippines.

Two novel hyperthermophilic, rod-shaped crenarchaeotes were isolated from an acidic hot spring in the Philippines. Cells were mostly straight or slightly curved rods 0.4-0.7 micron in width. Bent cells, branched cells, and cells bearing globular bodies were commonly observed. The isolates were heterotrophs and grew anaerobically and microaerobically. The addition of archaeal cell extract or a vitamin mixture to the medium significantly stimulated growth. The isolates grew over a temperature range of 60-92 degrees C, and optimally around 85 degrees C and grew over a pH range of 2.3-6.4, and optimally at pH 3.7-4.2. The isolates utilized glycogen, gelatin, beef extract, peptone, tryptone and yeast extract as carbon sources. They required sulfur, thiosulfate or sulfate as electron acceptors. The lipids mainly consisted of various cyclized glycerol-bisdiphytanyl-glycerol tetraethers. The G+C content of the genomic DNAs was 43 mol%. The 16S rDNA contained two small introns. The comparison of the 16S rDNA exon sequences revealed that they represented an independent lineage in the family Thermoproteaceae. The two strains were included in a single species because of high levels of DNA-DNA relatedness. From these results, Caldivirga maquilingensis gen. nov., sp. nov. is proposed in the family Thermoproteaceae to accommodate these isolates. The type strain of C. maquilingensis is strain IC-167T (= JCM 10307T = MCC-UPLB 1200T = ANMR 0178T).

DNA, Archaeal↗

PubMed1999

Immunogold labeling of rosette terminal cellulose-synthesizing complexes in the vascular plant vigna angularis

The catalytic subunit of cellulose synthase is shown to be associated with the putative cellulose-synthesizing complex (rosette terminal complex [TC]) in vascular plants. The catalytic subunit domain of cotton cellulose synthase was cloned using a primer based on a rice expressed sequence tag (D41261) from which a specific primer was constructed to run a polymerase chain reaction that used a cDNA library from 24 days postanthesis cotton fibers as a template. The catalytic region of cotton cellulose synthase was expressed in Escherichia coli, and polyclonal antisera were produced. Colloidal gold coupled to goat anti-rabbit secondary antibodies provided a tag for visualization of the catalytic region of cellulose synthase during transmission electron microscopy. With a freeze-fracture replica labeling technique, the antibodies specifically localized to rosette TCs in the plasma membrane on the P-fracture face. Antibodies did not specifically label any structures on the E-fracture face. Significantly, a greater number of immune probes labeled the rosette TCs (i.e., gold particles were 20 nm or closer to the edge of the rosette TC) than did preimmune probes. These experiments confirm the long-held hypothesis that cellulose synthase is a component of the rosette TC in vascular plants, proving that the enzyme complex resides within the structure first described by freeze fracture in 1980. In addition, this study provides independent proof that the CelA gene is in fact one of the genes for cellulose synthase in vascular plants.

Journal Article↗

PubMed1999

Inhibitory role of plasminogen activator inhibitor-1 in invasion and proliferation of HLE hepatocellular carcinoma cells.

Plasminogen activator inhibitor (PAI)-1, a serine protease inhibitor, inactivates urokinase-type plasminogen activator (uPA) and regulates degradation of the extracellular matrix; whether it functions for or against tumor progression, however, has been the subject of controversy. To assess the role of PAI-1 in invasion and proliferation of hepatocellular carcinoma (HCC) cells, HLE cells were transfected with a vector capable of expressing an antisense PAI-1 transcript. Analysis of seven stably transfected clones (PAI-1-) showed reductions of 81% in PAI-1 mRNA by northern blot analysis and 63% in the cellular PAI-1 antigen level by enzyme-linked immunosorbent assay (ELISA). There was no change in the levels of secreted PAI-1 or PAI-2. The activity of cellular uPA increased by 54%, without change in the protein level or the secreted uPA activity evaluated by ELISA. Morphologically, PAI-1 antisense induced a spindle shape with narrower cytoplasmic processes in HLE cells. The forced inhibition of PAI-1 increased the invasion and the growth of PAI-1- cells by 75% and 82%, respectively. These results suggest that PAI-1 plays a role in inhibiting invasion and proliferation, and the balance between uPA and PAI-1 expression is important to assess the invasiveness of HCC cells.

Carcinoma, Hepatocellular↗

PubMed1999

Wakame seaweed suppresses the proliferation of 7,12-dimethylbenz(a)-anthracene-induced mammary tumors in rats.

We examined the anti-tumor proliferation effects of wakame seaweed on 7,12-dimethylbenz(a)-anthracene (DMBA)-induced rat mammary tumor. DMBA was administered to 8-week-old female Sprague-Dawley rats, and rats which developed mammary tumors were assigned randomly to three groups. Commercial rat feed was used in a control group (group I-A), and two feed mixtures were prepared, which contained commercial rat feed blended with wakame at 1.0% (group I-B) and 5.0% (group I-C) by weight. The respective feeds were given to each group for 8 weeks, and changes in mammary tumor size were compared. At the end of the experiment, mammary tumors and thyroid glands were resected to compare their weights. Serum total iodine and thyroxin (T4) levels were measured. Immunohistochemical studies for bromodeoxyuridine (BrdU) labeling, transforming growth factor (TGF)-beta, and apoptosis were carried out in the resected tumor. Significant suppression of tumor growth was observed in groups I-B and I-C compared with I-A. In groups I-B and I-C, the weights of resected mammary tumors were significantly lower and serum total iodine concentration was significantly higher than in I-A. BrdU indices were significantly lower in groups I-B and I-C, compared with I-A. TGF-beta and apoptotic index were inversely related to BrdU. These results suggest that iodine is transported from the serum into mammary tissues and induces apoptosis through the expression of TGF-beta. In conclusion, wakame suppressed the proliferation of DMBA-induced mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

Histochemical study of hyaluronate in alcoholic liver disease.

Recently, it has been reported that serum hyaluronate (hyaluronic acid; HA) concentrations increase in various liver diseases, especially in alcoholic liver disease (ALD), and serum HA concentration has been used as a marker for hepatic fibrosis. However, it is unknown whether hepatic HA contents in ALD increase by alcohol or not. In this study, we histochemically stained HA in liver biopsy specimens obtained from ALD patients while actively drinking and after abstinence to clarify the effects of alcohol on hepatic HA contents. Liver biopsy specimens were obtained from 13 patients with ALD and 10 patients with non-ALD. In ALD patients, liver biopsy was performed twice within 3 days, and 4 to 8 weeks after abstinence when serum levels of AST and ALT normalized. HA in biopsy specimens was stained histochemically with biotinylated HA binding protein. Staining intensity of HA in liver tissue was also determined by computer-assisted imaging analyzer. HA staining was clearly observed in sinusoidal wall and fibrous regions around the portal tract and central vein in liver diseases. HA staining intensities in patients actively drinking with ALD increased markedly, compared with those in patients with non-ALD, and these intensities decreased with abstinence. These results clearly suggest that hepatic HA contents in ALD may be increased by alcohol in addition to hepatic fibrosis, and, therefore, increased HA deposition in the liver may be reversible by abstinence of alcohol.

Biopsy↗