Biomedical subjects

M Kita

Publications and source records attributed to M Kita.

At least 73 records · Page 4Linked to original sources

PubMed1999

Relation between clinical presentation, Helicobacter pylori density, interleukin 1beta and 8 production, and cagA status.

BACKGROUND: It is not known whether cagA+ Helicobacter pylori in duodenal ulcer (DU) have enhanced virulence compared with non-DU cagA+ H pylori. AIMS: To investigate the relation between presentation, H pylori density, interleukin 1beta (IL-1beta) and IL-8 production, and cagA status. METHODS: Fifty DU and 50 gastritis patients with cagA+ H pylori and 11 with cagA- infections were studied. Bacterial density and cytokine production were assessed using the same biopsies. Cytokine production was also measured from supernatants of medium following coculture of H pylori with MKN-45 cells. RESULTS: There was no relation between H pylori density and cagA status. There was a dose dependent relation between mucosal cytokine levels and density of cagA+ H pylori. H pylori density increased to a threshold, followed by a rapid increase in cytokines and then a plateau. IL-1beta and IL-8 levels in the antrum were greater in DU than in gastritis; in the corpus the cytokine level/H pylori differed irrespective of similar H pylori densities. However, cytokine production was similar in vitro, independent of presentation or biopsy site, suggesting that host factors are critical determinants of the inflammatory response. Mucosal IL-8 and IL-1beta levels were low with cagA- and cagA+, cagE- H pylori infections. CONCLUSIONS: The increase in antral IL-1beta and IL-8 production and inflammation in DU is related to increased numbers of bacteria and not to an increase in cytokine production per cagA+ isolate. There was no evidence of enhanced virulence of H pylori from DU compared with cagA+ non-DU H pylori.

Adult↗

PubMed1999

Regulation and transfer of a murine model of thyrotropin receptor antibody mediated Graves' disease.

In order to replicate a recently described murine model of Graves' disease, we immunized AKR/N (H-2k) mice i.p., every 2 weeks, with either a clone of fibroblasts expressing both the human TSH receptor (hTSHR) and murine major histocompatibility complex (MHC) class II molecules or with fibroblasts expressing the MHC class II molecules alone. Mice were bled, and their thyroid hormone levels measured, at 6, 12, and up to 18 weeks after the first immunization. Between 11-12 weeks after immunization, a significant number of mice began to die spontaneously and were found to have developed large goiters. Thirty to 40% of mice immunized with hTSHR transfected fibroblasts showed markedly increased serum T3 and T4 hormone levels by 12 weeks compared with controls, with the highest thyroid hormone levels being T3: 420 ng/dl (normal < 70) and T4: 16.5 microg/dl (normal < 5). The murine serum demonstrated the presence of antibodies to the TSHR, as evidenced by inhibition of labeled TSH binding to the hTSHR, and these sera had in vitro thyroid stimulating activity. Many of the hyperthyroid mouse exhibited weight loss and hyperactivity and, on examination, their thyroids had the histological features of thyroid hyperactivity including thyroid enlargement, thyroid cell hypertrophy, and colloid droplet formation--all consistent with Graves' disease. In contrast, a small number of mice (< 5%) developed hypothyroidism with low serum T4 levels and markedly increased TSH concentrations and evidence of thyroid hypoplasia. Both hyperthyroidism and hypothyroidism were successfully transferred to naive mice using ip cells of immunized mice. Surprisingly, hypothyroidism occurred in many recipient mice even after transfer from hyperthyroid donors. These results confirmed that immunization with naturally expressed hTSHR in mammalian cells was able to induce functional TSHR autoantibodies that either stimulated or blocked the mouse thyroid gland and induced hyperthyroidism or thyroid failure. Furthermore, both blocking and stimulating antibodies coexisted in the same mice as evidenced so clearly by the transfer of hypothyroidism from hyperthyroid mice. The addition of a Th2 adjuvant (pertussis toxin) caused approximately 50% of the animals to become hyperthyroid beginning early at 9 weeks, whereas a Th1 adjuvant (CFA) delayed the disease onset such that only 10% were hyperthyroid by 12 weeks. As with human autoimmune thyroid disease, the T cell control of this murine model may be critical and requires more extensive investigation.

Animals↗

PubMed1999

[Use of personal computers by diplomats of anesthesiology in Japan].

Use of personal computers by diplomats of the Japanese Board of Anesthesiology working in Japanese university hospitals was investigated. Unsigned questionnaires were returned from 232 diplomats of 18 anesthesia departments. The age of responders ranged from twenties to sixties. Personal computer systems are used by 223 diplomats (96.1%), while nine (3.9%) do not use them. The computer systems used are: Apple Macintosh 77%, IBM compatible PC 21% and UNIX 2%. Although 197 diplomats have e-mail addresses, only 162 of them actually send and receive e-mails. Diplomats in fifties use e-mail most actively and those in sixties come second.

Adult↗

PubMed1999

[Effectiveness of 3 ways method in intra-arterial infusion chemotherapy for advanced or recurrent cervical cancer with or without radiotherapy].

We analyzed 58 cases of advanced or recurrent cervical cancer treated with intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. Two separate IAIC regimens were administered since 1985: group I consisted of 5-FU + MMC +/- ADR (30 patients) and group II consisted of CDDP + MMC +/- 5-FU (28 patients). The tip of a catheter was placed in the bifurcation of the abdominal aorta (1 way method: 45 patients regimen II: 15) between 1977-1984. We have used selective catheterization (2 ways method: 9) since 1995 in order to get good drug distribution. However we experienced grade 4 toxic effect of cutaneous and pain with this method, so we have used a 3 ways method (4 patients) since 1998. The two-year survival rete was 60% with the 1 way method, and 67% with the 2 ways method and regimen II. Severe adverse effects (grade 3 + 4) were found in 53, 56, 0%, respectively, by each of the three methods (1, 2, 3 ways) hematologically, 13, 22, 0% in gastrointestinally, 0, 44, 0% in cutaneously and 0, 56, 0% in pain or neurotoxicity. These data suggest that IAIC by the 3 ways method is a useful treatment for advanced or recurrent cervical cancer. However, one should check the blood flow distribution periodically, and control concentration of drugs.

Adult↗

PubMed1999

[Three-phase gadolinium infusion in moving-table three-dimensional MR angiography].

Moving-table three-dimensional (3D) MR angiography provides images of long segments of arteries. However, deep veins are sometimes superimposed on the arteries below the knee, and peripheral arteries sometimes fail to be visualized. We have developed an imaging method with three-phase gadolinium infusion according to the mean blood flow velocity of the leg. Nineteen patients with various blood flow velocities were studied. Eighteen of the patients had no venous superimposition. All 19 patients showed good configuration of peripheral arteries with 16-18 ml of gadolinium. This method is useful for better visualization of peripheral arteries without venous superimposition.

Adult↗

PubMed1998

Characterization of a cDNA homologous to carotenoid-associated protein in citrus fruits.

A cDNA (CitPAP) homologous to a gene encoding for Cucumis sativus carotenoid-associated protein (CHRC) has been isolated from satsuma mandarin (Citrus unshiu Marc.). Unlike ChrC whose expression was limited only in mature fruits (containing chromoplasts), CitPAP transcripts were detected in all the tissues examined including fruits, flowers and leaves. In this respect, CitPAP was rather close to a gene encoding for pepper plastid-lipid-associated protein (PAP), which exhibits ubiquitous expression in bell pepper organs containing chloroplasts or chromoplasts. CitPAP, however, differed from PAP in the magnitude and pattern of RNA accumulation. These results might indicate a novel function of CitPAP.

Amino Acid Sequence↗

PubMed1998

Characterization of gene repertoires at mature stage of citrus fruits through random sequencing and analysis of redundant metallothionein-like genes expressed during fruit development.

We carried out a random sequencing of cDNA library derived from mature citrus fruit (Citrus unshiu Marc.) for identifying the gene repertoires expressed at the mature stage. Among 297 clones analyzed, 195 cDNA clones (65.7%) were putatively identified to previously characterized genes with optimized (OPT) scores of >/=200 through a homology search to DNA database, whereas 102 clones (34.3%) resulted in low OPT scores (<200) and did not show any significant sequence identity with previously published genes. Among them, clones homologous to metallothionein (MT)-like genes appeared 62 times, being mostly redundant, and accounting for about 20.9% of the total 297 clones. To gain a better understanding of the MT-like genes, two types of cDNA clones were isolated. One clone (CitMT36) resembled the type 2 MT gene containing Cys-X-Cys motifs in both N- and C-terminal, but the consensus sequence in the N-terminal domain, Cys-Cys and Cys-X-X-Cys was modified in CitMT36 to X-Cys and Cys-X-X-X, respectively. We suggest that these form a 'novel type 2' group of MT-like clones. The other clone (CitMT45) showed homology to type 3 MT-like genes, which have been found in mostly fruit tissues so far. By Southern blot analysis, both clones showed one or two bands, suggesting that both CitMT36 and CitMT45 are present in single or a few copies in the citrus genome. Transcripts of CitMT36 were evenly detected in all tissues examined, whereas those of CitMT45 were detected primarily in fruit during the developmental phase. Neither of the MT-like genes was induced in leaves by Zn and Cu. Collectively, MT-like genes from citrus would be regulated differentially depending on the fruit developmental stage and organs, indicating a change in their expression under the different physiological and molecular environment of fruit cells.

Amino Acid Sequence↗

PubMed1998

Function of aberrant EGFR in malignant gliomas.

The most common alteration of the epidermal growth factor receptor (EGFR) gene in human malignant gliomas is an in-frame deletion of exon 2-7 from the extra-cellular domain. To study the relationship between the expression of this aberrant EGFR and cell proliferation, as well as apoptosis in malignant gliomas, we have developed U-87MG cell transfectants that express the aberrant (mutant-type) or normal (wild-type) EGFR. We analyzed cell number, tumor volume, and MIB-1 positive rate as proliferation markers, and found that in tissue culture, tumors derived from U-87 MG cells (mutant-type) have the same proliferative activity as those derived from U-87 MG cells (wild-type). However, when cells expressing mutant EGFR were implanted into nude mice subcutaneously, the tumorigenic capacity was much enhanced. We also found that the apototic index of tumors derived from U-87 MG cells (mutant-type) was less than 0.1%, whereas that of wild-type tumor was 1%. These results suggest that aberrant EGFR affects the malignancy of glioma by stimulating proliferation and inhibiting apoptosis.

Animals↗

PubMed1998

Quantitative assessment of macular edema with retinal vein occlusion.

PURPOSE: To evaluate the retinal thickness analyzer, a new image analyzer involving laser-slit biomicroscopy, for quantitative assessment of retinal thickness in patients with macular edema secondary to retinal vein occlusion. METHODS: Fifty-eight patients (central retinal vein occlusion, 22 eyes; branch retinal vein occlusion, 36 eyes) with a clinical diagnosis of macular edema associated with retinal vein occlusion were evaluated. Retinal thickness analysis was performed with the retinal thickness analyzer. A green helium-neon laser slit directed into the eye was scanned to generate optical cross-sections of the retina. Images were analyzed by an automated software algorithm, and a detailed map of the retinal thickness was obtained. RESULTS: Laser-slit images obtained with the retinal thickness analyzer in patients with macular edema associated with retinal vein occlusion disclosed intraretinal changes such as retinal edema, cystoid spaces, and hemorrhages. Linear regression analysis showed a significant relationship between the macular thickness in the central fovea and corrected visual acuity reported on a logMAR scale (P = .002, adjusted R2 = 0.40 in central retinal vein occlusion; P = .002, adjusted R2 = 0.34 in branch retinal vein occlusion). CONCLUSION: We confirmed the capability of the retinal thickness analyzer to provide rapid and precise evaluation of macular thickening in patients with retinal vein occlusion.

Adult↗

PubMed1998

Traumatic cataract with a ruptured posterior capsule from a nonpenetrating ocular injury.

An 11-year-old boy had posterior lens capsule rupture resulting from a nonpenetrating (blunt trauma) injury to the eye. A rapidly developing cataract required pars plana lensectomy. This report suggests that posterior capsule rupture may occur secondary to blunt trauma and progressive cataract formation after posterior capsule rupture may require surgery soon after the injury.

Cataract↗

PubMed1998

Inhibition of leukotriene synthesis by terfenadine in vitro.

To determine the inhibitory mechanisms of terfenadine on the synthesis of leukotriene C4 (LTC4), an important mediator in allergic diseases, we evaluated the action of terfenadine on the IgE-dependent production of LTC4 in rat basophilic leukaemia 2H3 cells. Rat IgE-loaded cells were stimulated with anti-IgE in the presence or absence of various concentrations of terfenadine and the level of LTC4 released into the medium was measured by performing a specific radio immunoassay. Terfenadine inhibited the synthesis of LTC4 to 67.2% at a concentration of 5 microg/ml. LT synthesis was directly suppressed by inhibition of 5-lipoxygenase (5-LO) through calcium ion-independent mechanisms, and was also possibly suppressed by inhibition of cytosolic phospholipase A2 and 5-LO by blocking the influx of intracellular calcium ion that was initiated by IgE-related stimulation.

Animals↗

PubMed1998

Effect of dexamethasone on leukotriene synthesis in DMSO-stimulated HL-60 cells.

Human leukemia (HL) 60 cells were differentiated by dimethylsulfoxide (DMSO) treatment to granulocyte-like cells, leukotriene (LT) synthesizing activity of which was increased in response to the differentiation of the cells. Four synthesizing enzymes, cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LO), LTA4 hydrolase and LTC4 synthase, and an enzyme associated protein, 5-lipoxygenase activating protein (FLAP) are involved in the generation of LTC4 and LTB4. We examined the expression of messenger RNA (mRNA) for these LT synthesizing enzymes and an associated protein in DMSO differentiated HL-60 cells by reverse transcriptase polymerase chain reaction (RT-PCR). The production of LTC4 and LTB4, measured by radioimmunoassay (RIA), was increased after the incubation with DMSO for more than 3 days. Messenger RNA abundance for 5-LO, LTC4 synthase and LTA4 hydrolase was increased, that for FLAP was stable, but that for cPLA2 was decreased. These results indicate that DMSO induced increase of LT synthesis is associated with the increase of mRNA expression of 5-LO, LTC4 synthase and LTA4 hydrolase, although the precise regulatory mechanisms of the increased mRNA expression are not determined. We also investigated an action of dexamethasone (DEX) on DMSO-induced enhancement of LT synthesis. DEX suppressed DMSO induced increase of LTC4 synthesis, but rather enhanced DMSO induced LTB4 production. The DEX attenuated the DMSO-induced increase of mRNA expression for LTC4 synthase, but showed no effect on that for LTA4 hydrolase. The inhibition of LTC4 synthesis is associated with the suppression of mRNA expression for LTC4 synthase. However, increased LTB4 synthesis by DEX is regulated by the mechanisms which are independent from mRNA level of LTA4 hydrolase.

5-Lipoxygenase-Activating Proteins↗

PubMed1998

The full expression of the ity phenotype in ityr mice requires C3 activation by Salmonella lipopolysaccharide.

Our previous study has shown that the rapid and sufficient activation of complement by Salmonella lipopolysaccharide occurs in genetically resistant (Ityr) A/J mice. To assess whether the level of complement activation by a virulent strain of Salmonella typhimurium regulates the level of murine natural resistance, we compared levels of serum complement activation by S. typhimurium and kinetics of serum-opsonized S. typhimurium grown in macrophages using several strains of resistant (Ityr) and susceptible (Itys) mice. Itys macrophages killed intracellular S. typhimurium to the same extent as did Ityr macrophages when the pathogen was opsonized with Ityr serum. Opsonization of S. typhimurium with Itys serum reduced intracellular killing activity in Ityr macrophages to the same level as seen with Itys macrophages. Incubation of S. typhimurium with 25% Mg2+ EGTA (5 mm MgCl2-3 mm ethylene glycol-bis (beta-aminotheyl either)-N,N,N',N'-tetraacetic acid)-chelated Ityr serum resulted in higher levels of C3 deposition onto the surface of this bacteria, C3b generation and also C3 consumption, compared with that with Mg2+ EGTA-chelated Itys serum. Opsonization of S. typhimurium with A/J serum prior to infection increased early resistance in Itys mice. Infection with a virulent strain of S. typhimurium induced the expression of interleukin-10 (IL-10) mRNA at higher levels in C57BL/6 mice than in A/J mice. However, opsonization of S. typhimurium with A/J serum decreased bacterial growth in the spleen of C57BL/6 mice to the same level as observed for A/J mice in association with decreased expression levels of IL-10 mRNA. Moreover, administration of anti-C3 antibodies reduced the resistance of A/J mice in association with a decrease in serum levels of C3. These results indicate that the high level of complement activation via the alternative pathway in Ityr serum by a virulent strain of S. typhimurium reduces the virulence of this pathogen, which may contribute to the full expression of Ity phenotype in Ityr mice.

Animals↗

PubMed1998

Relationship of vacA genotypes of Helicobacter pylori to cagA status, cytotoxin production, and clinical outcome.

BACKGROUND: Mosaicism in vacA alleles with three distinct families of vacA signal sequences (s1a, s1b and s2) and two distinct families of middle region alleles (m1 and m2) has been reported. It was suggested that the vacA s1a genotype was closely associated with duodenal ulcer disease and with high cytotoxin production. The aim of this study was to evaluate the role of vacA genotyping with respect to gastric inflammation and injury, cytotoxin activity, and clinical presentation. METHODS: H. pylori from patients with gastritis, peptic ulcer disease, or gastric cancer were characterized by vacA typing by polymerase chain reaction (PCR) and DNA sequencing. In vitro cytotoxin activity was assessed by vacuolation assay using Vero cells as well as with Hela cells. RESULTS: Four hundred ninety-one strains were tested. vacA genotype s1a/m1 was present in more than 95% of strains independent of presentation with gastritis, peptic ulcer, or gastric cancer. No vacA genotype was associated with high average cytotoxin activity. The s2/m2 isolates had low or absent cytotoxin activity. All cagA negative strains (n = 18) were s1a strains and both s2/m2 strains were cagA positive. One strain that was a recombinant of m1 and m2 strains was identified and had low cytotoxin activity. The nucleotide and amino acid sequences between original m1 strains and Japanese m1 strains (new m1 strains) were about 85% and 81%, respectively. Strains with the new m1 genotype had nucleotide and amino acid sequences similarity of more than 96%. There was no difference in cytotoxin activity between strains with the Western type m1 and the new type m1 genotype. CONCLUSION: In this as in other reported studies ( approximately 1500 patients overall) vacA genotype was strongly but not exclusively associated with the presence of cagA. Overall, the studies did not support a role for vacA genotyping in relation to cytotoxin activity, virulence, histologic finding, or risk of a particular H. pylori disease. vacA genotype s1 is likely to be a surrogate marker for the presence of the cag pathogenicity island.

Adult↗

PubMed1998

Chemokines in the gastric mucosa in Helicobacter pylori infection.

BACKGROUND: Although chemokines have been suggested to play an important role in Helicobacter pylori associated gastritis, few studies have investigated the role of chemokines other than interleukin 8 (IL-8) in gastric mucosa. AIMS: To investigate the expression and production patterns of various chemokines using gastric biopsy specimens. METHODS: In 192 patients, expression patterns of C-X-C chemokines (IL-8 and growth regulated alpha (GRO alpha)) and C-C chemokines (regulated on activation, normal T cell expressed and presumably secreted (RANTES), monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta) were examined using reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). cagA gene was identified using PCR. RESULTS: H pylori infection was associated with increased rates of expression of mRNA for IL-8, GRO alpha, RANTES, and MIP-1 alpha and with increased levels of mucosal IL-8 and GRO alpha. IL-8 and GRO alpha levels correlated with the density of H pylori in both the antrum and corpus. The levels of these chemokines correlated with cellular infiltration in the antrum but not the corpus. cagA gene positive H pylori infection was associated with increased rates of expression of mRNA for IL-8 and GRO alpha and with increased levels of these chemokines. CONCLUSION: H pylori infection is associated with increased expression rates and production of C-X-C chemokines (IL-8 and GRO alpha), but not with increased production of C-C chemokines. Although H pylori infection is associated with increased C-X-C chemokines in the antrum and corpus, there is a difference in the inflammatory response between these two areas of the stomach.

Adult↗

PubMed1998

Paradoxical response to valproic acid in a patient with a hypothalamic hamartoma.

OBJECTIVE: To report a patient who developed the paradoxical effect of increasing electrical seizure activity and confusion with initiation of valproic acid therapy. CASE SUMMARY: A 25-year-old African-American woman with a hypothalamic hamartoma had an electroencephalogram (EEG) that demonstrated frequent bursts of generalized spike and wave activity. The prevalence of spike and wave activity increased dramatically and the patient became increasingly somnolent as valproic acid was added to carbamazepine and phenobarbital therapy. Her EEG and mental status changes resolved when the valproic acid was discontinued. There was a strong positive correlation between the prevalence of spike and wave activity and the valproic acid concentration, but not between spike and wave activity and the concentrations of carbamazepine or phenobarbital. DISCUSSION: Although this is a complex case, it is clear that the addition of valproic acid produced an increase in spike and wave activity. Possible mechanisms and pathophysiologic significance of this paradoxical effect are discussed in light of the differences between this epileptic syndrome and the primary generalized epilepsies.

Adult↗

PubMed1998

Direct evidence that LTC4 and LTB4 but not TXA2 are involved in asthma attacks in children.

There are substantial numbers of reports showing that leukotrienes (LTs) play important roles in adult asthma. No definite evidence has been demonstrated that LTs are involved in asthma attacks in children, although it is highly expected. In this report, we demonstrated that the levels of LTB4 and LTC4 but not thromboxane B2 (TXB2), a stable metabolite of TXA2, were significantly elevated in the bronchoalveolar lavage fluid, which was obtained from intubated and mechanically ventilated children with severe asthma attacks. This is direct evidence that LTB4 and LTC4 predominantly participate in asthma attacks in pediatric patients.

Adolescent↗

PubMed1998

[Role of cytokines in the pathogenesis of gastrointestinal diseases associated with Helicobacter pylori infection].

It is well known that Helicobacter pylori can cause gastritis, gastroduodenal ulcers and malignant diseases. The infiltration of polymorphonuclear leukocytes is recognized in the lesions of these diseases, and the infiltration disappears by antibiotic therapy. However, it is not yet clarified how Helicobacter pylori induces the formation of lesions including leukocyte infiltration. Recently, we have confirmed that several kinds of cytokines are expressed in the gastric biopsy specimens of gastroduodenal diseases. Especially, it is conjectured that chemokines such as interleukin-8 (IL-8) which are expressed in the specimens, induce leukocyte infiltration, gastric mucosal inflammation and gastroduodenal ulcers. It is possible that Helicobacter pylori CagA gene is closely related with IL-8 expression because this cytokine is more strongly expressed in the specimens from the patients infected with CagA-positive Helicobacter than those with CagA-negative one.

Anti-Bacterial Agents↗