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Biomedical subjects

M Kogure

Publications and source records attributed to M Kogure.

At least 19 recordsLinked to original sources

Gene expression profiles in human gastric cancer: expression of maspin correlates with lymph node metastasis.

To seek for a candidate gene that would regulate tumour progression and metastasis in gastric cancer, we investigated gene expression profiles by using DNA microarray. Tumour tissue and adjacent normal tissue were obtained from 21 patients with gastric cancer and then examined for their gene expression profiles by the Gene Chip Human U95Av2 array, which includes 12 000 human genes and EST sequences. A total of 25 genes were upregulated and two genes were downregulated by at least four-fold in the tumour tissue. In a further analysis according to lymph node metastasis, the expressed levels of maspin, as well as carcinoembryonic antigen and nonspecific crossreacting antigen were significantly higher in tumours with lymph node metastasis than in those without it. Maspin expression in 85 gastric cancer patients was further investigated by using immunohistochemistry. Maspin expression was not observed in normal gastric epithelia without intestinal metaplasia. In contrast, maspin was expressed in 74 of 85 tumour tissues. There was a significant correlation between the incidence of maspin-positive tumour staining and lymph node metastasis. These results suggest that maspin has a potential role for tumour metastasis in gastric cancer.

Adult↗

Ulcerative duodenitis accompanying ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon of unknown etiology. There are varied manifestations in the natural course of UC. However, duodenum is not generally considered a target organ of UC. Here, we report two patients with steroid-responsive ulcerative duodenitis with colitis that was consistent with UC, but not with Crohn's disease. We also reviewed six cases of ulcerative duodenitis with UC. Duodenal lesion with UC may be a more common phenomenon, although infrequently clinically manifested under steroid therapy. Upper gastrointestinal tract inflammation in UC warrants further studies to ascertain whether the duodenum is a target organ in UC, especially in steroid-free conditions.

Adult↗

Overexpression of fatty acid synthase in oesophageal squamous cell dysplasia and carcinoma.

OBJECTIVE: The expression of fatty acid synthase (FAS), an enzyme necessary for de novo fatty acid synthesis, has been examined in several types of tumours so far, but not in oesophageal cancer and dysplasia. METHODS: We examined the immunohistochemical reactivity of FAS in 4 normal adult oesophagi, 14 dysplastic oesophageal lesions, and 80 squamous cell carcinomas and 6 cases with 4 special types of malignancies of the oesophagus. We also analysed the correlation between FAS expression and various clinicopathological features and long-term survival in patients with oesophageal cancer. RESULTS: In the normal oesophagus, only faint cytoplasmic FAS expression was observed in cells of the basal layer. In contrast, FAS-positive cells were found in 92.9% of cases of dysplasia and 96.5% of cases of carcinoma including 6 cases with a specific histological subtype. However, high expression of FAS did not correlate with either clinicopathological features or prognosis of patients with oesophageal cancer. CONCLUSION: Our results demonstrate that FAS is expressed in almost all oesophageal carcinomas of both usual and special types and dysplastic lesions, suggesting that FAS may be upregulated continuously from the early stage of oesophageal squamous cell carcinogenesis to established carcinoma.

Adult↗

A case of pedunculated tubulovillous adenoma of the duodenum.

Tubulovillous adenoma of the duodenum is a rare tumor. Almost all of the lesions have been reported endoscopically and are recognized as small, sessile, polypoid lesions. This article discusses an unusual case of pedunculated tubulovillous adenoma of the duodenum in a 48-yr-old woman. The lesion was discovered on the upper part of the descending duodenum during a gastric mass survey. The polyp was removed using an electrocautery snare and was histologically diagnosed as tubulovillous adenoma.

Adenoma, Villous↗

Identification of Bombyx mori midgut receptor for Bacillus thuringiensis insecticidal CryIA(a) toxin.

As part of a study of the mechanism by which Bacillus thuringiensis insecticidal crystal protein acts, a Bombyx mori receptor to the CryIA(a) toxin specific for lepidopterans was examined. Histological examination showed that the toxin acted on the brush-border membrane of the midgut columnar cells and broke its infolding structure, causing cell lysis. The membrane vesicles were purified, and a 175-kDa protein binding the toxin was found that accounted for some 0.015% of membrane proteins. The protein, designated BtR175, was a glycoprotein that reacted with concanavalin A. Anti-BtR antibodies inhibited the binding of toxin to membrane vesicles in vitro and decreased the effect of the toxin to silkworms in vivo. BtR175, although found in the gut, was not found in fat bodies, integument, or silk glands. These results indicated that BtR175 was the receptor protein for the insecticidal toxin. Proteins (137 and 107 kDa) binding the CryIA(a) toxin also were found in the gut membranes of Tenebrio moritor larvae, a coleopteran not sensitive to the toxin. The specificity of the toxin could not be explained only in term of the existence of its binding protein.

Animals↗

Cloning, sequencing, and expression of the Bombyx mori receptor for Bacillus thuringiensis insecticidal CryIA(a) toxin.

Bacillus thuringiensis strains produce insect-specific Bt toxins. Bt CryIA(a) toxin binds to a 175-kDa glycoprotein (BtR175) on the microvillus membranes of columnar cells in the Bombyx mori midgut and causes lysis of the cells. BtR175 was purified, and its cDNA was cloned. The cDNA encodes a newly identified 193.3-kDa preproprotein form of BtR175 that includes nine extracellular cadherin repeats, a 23.5-kDa membrane-proximal domain, a membrane-spanning region, and a 13.6-kDa cytoplasmic domain. Spodoptera frugiperda cells transfected with a recombinant baculovirus DNA carrying the cDNA produced a 175-kDa protein that reacted with anti-BtR antibodies and the Bt CryIA(a) toxin.

Amino Acid Sequence↗

Role of gammadelta T lymphocytes in the development of Behçet's disease.

Phenotypic and functional properties of gammadelta T cells, which play an important role in mucocutaneous immunity, were examined to elucidate whether immunological abnormality in Behcet's disease may be related to a specific T cell population. We found that CD45RA+ Vgamma9+ Vdelta2+ gammadelta T cells, which constitute a minor population of gammadelta T cells in healthy individuals, were increased in number in Behçet's disease irrespective of disease activity. This CD45RA+ subset of gammadelta T cells in the active, but not inactive, phase of this disease expressed IL-2Rbeta and HLA-DR, suggesting that they are activated in vivo in active Behçet's disease. In addition, the CD45RA+ gammadelta T cells produced extreme amounts of tumour necrosis factor and contained perforin granules. These data indicate that a phenotypically distinct subset of gammadelta T cells, CD45RA+ CD45RO- Vgamma9+ Vdelta2+, may contribute to immunological abnormalities which may lead to complexity of pathophysiology in Behçet's disease.

Adult↗

[Complement regulatory proteins CR 1, MCP, DAF, and MACIF levels in patients with Behçet's disease].

We previously reported that serum complements in patients with Behçet's disease were extremely low just before the ocular attack. On the other hand, C3a and C5a levels, which have anaphylactic activity and chemotactic activity for polymorphonuclear leucocytes, were higher just before the ocular attack than at the time of the ocular attack, and there was negative correlation between C3a/C5a and CH50. In this report, we evaluated complement regulatory proteins. The results of low levels of C3b/C4b receptor (CR1) and membrane cofactor protein (MCP), and low tendency of decay accelerating factor (DAF) and membrane attack complex inhibition factor (MACIF) suggested that the function of complement regulatory proteins in patients with Behçet's disease decreases as a whole. But mean levels of both CH50 and ACH50 were significantly higher than in the controls. Although it is unclear which is the cause and which is the result, we suppose the function of complement production works excessively and these phenomena are caused by making up for the lack of complement regulatory proteins.

Adult↗

Effects of several 5-HT1A agonists on hippocampal rhythmical slow activity in unanesthetized rats.

We examined the effect of 5-hydroxytryptamine (5-HT)1A agonists on walking related, atropine-resistant, rhythmical slow activity (wr-RSA) of the hippocampus in rats. Selective 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), flesinoxan, buspirone and ipsapirone significantly decreased the power value of 7-9 Hz band activity and the median frequency of wr-RSA. The order of potency was 8-OH-DPAT > flesinoxan = buspirone in power reduction. The 5-HT1A antagonists, (-)pindolol, (-)propranolol and spiperone, inhibited the effect of 8-OH-DPAT on wr-RSA. Pretreatment with parachlorophenylalanine did not abolish the effect of 8-OH-DPAT. These results indicate that 5-HT1A agonists reduce both power and median frequency values of wr-RSA through activation of post-synaptic 5-HT1A receptors in the forebrain in unanesthetized rats, in vivo.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

[Treatment of ocular manifestation of sarcoidosis].

Corticosteroid are the main treatment in both systemic and ocular sarcoidosis. Most cases of ocular sarcoidosis, such as iridocyclitis, retinal periphlebitis, optic disc inflammation, vitritis and snowballs can be managed with topical or subconjunctival injections of corticosteroids. However, only rarely cases are systemic steroids indicated. High doses of systemic steroids are effective in unusual manifestations of retinal vein occlusions, retinal and optic disc neovascularization and vitreous hemorrhage. Systemic corticosteroids starting with moderately high doses (40-60 mg/day) with slow tapering according to the clinical response is necessary. Photocoagulation has not been widely used in the treatment of neovascularization, secondary to sarcoidosis.

Adrenal Cortex Hormones↗

A clinical trial of FK506 in refractory uveitis.

We performed a clinical open trial to evaluate the efficacy and the adverse side effects of a single therapy with FK506 in refractory uveitis as a multicenter study in Japan. Fifty-three patients (41 patients with Bechçet's disease, five with Vogt-Koyanagi-Harada disease, four with idiopathic retinal vasculitis, and three with other forms of uveitis) were enrolled in the study. FK506 was given orally for 12 weeks. Treatment with FK506 exhibited therapeutic effects in a dosage-dependent manner: the effectiveness was 38% in patients treated with an initial dosage of 0.05 mg/kg of body weight per day, 60% with 0.10 mg/kg of body weight per day, 83% with 0.15 mg/kg of body weight per day, and 79% with 0.20 mg/kg of body weight per day. Overall efficacy with dosage adjustment when needed was 76.5% at the conclusion of the study at the end of the 12th week. The FK506 therapy induced a variety of adverse side effects, the incidence of which depended on the dosage. The major side effects were renal impairment (28.3%, 15 of 53 patients), neurologic symptoms (20.8%, 11 of 53 patients), gastrointestinal symptoms (18.9%, ten of 53 patients), and hyperglycemia (13.2%, seven of 53 patients). The trough level of FK506 in the whole blood correlated with both the efficacy of the therapy and with the incidence of adverse effects. It is recommended to maintain the trough level between 15 and 25 ng/ml. On the basis of these results, a daily dosage of 0.10 to 0.15 mg/kg of body weight per day was suggested as an appropriate therapeutic dosage for refractory uveitis.

Administration, Oral↗

Effect of systemic administration of N-methyl-D-aspartic acid on extracellular taurine level measured by microdialysis in the hippocampal CA1 field and striatum of rats.

The extracellular concentrations of amino acids in the hippocampal CA1 field and striatum of conscious freely moving rats were monitored simultaneously by in vivo brain microdialysis using HPLC with electrochemical detection. Under basal conditions, aspartate, glutamate, glutamine, glycine, taurine, and alanine were detected, but gamma-aminobutyric acid was undetectable in both regions. Intraperitoneal injection of N-methyl-D-aspartic acid (NMDA; 10 mg/kg) caused a significant increase (three- to fivefold) in the taurine concentration in the dialysate obtained from both the hippocampal CA1 and striatum, whereas other amino acids (aspartate, glutamate, and alanine) did not show significant changes. Local application of NMDA (300 microM) to both regions via the dialysis probes also caused a similar increase (three- to fivefold) in both regions. Under infusion of hypertonic Ringer's solution containing 150 mM sucrose, the effect of NMDA on the level of taurine in both the regional dialysates was not affected. The effect of NMDA was totally reduced by intraperitoneal administration of MK-801 (0.3-1.0 mg/kg), a noncompetitive antagonist of NMDA receptors. Continuous infusion of DL-2-amino-5-phosphonovaleric acid (1.0 mM), a competitive antagonist of NMDA receptors, via the dialysis probes completely inhibited the effect of NMDA. These findings suggest that systemic administration of NMDA is effective as well as local administration into the brain and that NMDA receptors might be involved in the regulation of the extracellular taurine level in the brain without dependence on cell swelling.

2-Amino-5-phosphonovalerate↗

[Postoperative arrhythmia after operation of esophageal cancer].

The postoperative arrhythmias (exclusive of sinus tachycardia) was reviewed in 77 patients (male: 69, female: 8, mean age: 63.9 years) who underwent esophagectomy for esophageal carcinoma. The results were as follows: 1. The incidence of postoperative arrhythmias in all patients but seven who had preoperative chronic atrial fibrillation (af) or pacemaker rhythm was 47.1%, and af was observed most frequently (45.5%). Postoperative arrhythmias occurred in patients with abnormal preoperative electrocardiographic findings more often than in those with normal preoperative electrocardiographic findings (53% vs 41%). The incidence of postoperative arrhythmias in aged patients (> or = 66 years old) was significantly higher than that in younger patients (< or = 65 years old) (64% vs 35%, p < 0.05). Other risk factors for postoperative arrhythmias were sex and history of hypertension. 2. Postoperative arrhythmias occurred more often in patients who underwent blunt dissection of the thoracic esophagus and reconstruction using the whole stomach via the posterior mediastinal route than in those who underwent esophagectomy with right thoracotomy and reconstruction using the gastric tube via the poststernal route (60.0% vs 45.0%). 3. Most supraventricular premature contractions and ventricular premature contractions occurred immediately after surgery or on the first postoperative day, and af often occurred during the first postoperative night or the second postoperative day. 4. For treatment, various antiarrhythmic agents were administered according to the patient's condition. Glucose-insulin-kalium therapy was especially effective (63%). None of the arrhythmias was fatal.

Aged↗

Naloxone affects both pharmacokinetics and pharmacodynamics of morphine. Application of direct correlation analysis.

Direct correlation analyses between the distribution of morphine (pharmacokinetics) and the biochemical effects of the drug on monoamine metabolism (pharmacodynamics) are reported for dissected regions of the brain. Determinations of morphine and monoamine-related substances were carried out in the same sample by high performance liquid chromatography with electrochemical detection. Naloxone, an antagonist of morphine, significantly shortened the biological half lives of morphine in both the blood and brain tissue. Such pharmacokinetic behavior appeared to be related to the contractive effect of morphine on the bile duct, and naloxone facilitated the excretion of morphine via this route. In the striatum, significant correlations were observed between the concentrations of the metabolites of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and morphine with a shift to the right in the concentration-response curve on naloxone treatment indicating competitive antagonism. While significant correlations were also observed in this brain region for the metabolites of noradrenaline, 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), and 5-hydroxytryptamine, 5-hydroxyindoleacetic acid (5-HIAA), a shift to the right did not occur. Significant correlations and shifts were noted for DOPAC, HVA and MOPEG in the hypothalamus. However, no correlation was found between the concentrations of 5-HIAA and morphine in this region. In other regions such as the hippocampus and medulla oblongata, similar correlations and shifts were not observed for MOPEG and 5-HIAA or for DOPAC and HVA.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Effect of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta-(b)-quinoline monohydrate hydrochloride (NIK-247) on cholinergic enzyme activity in rats.

An in vitro comparison demonstrated that the concentration of NIK-247 that inhibited cholinesterase (ChE) activities to half the normal level (ID50) was 1.3 x 10(-6) M. This value was higher than those for both physostigmine (PHY; 1.2 x 10(-7) M) and tetrahydroaminoacridine (THA; 3.6 x 10(-7) M), which are used as cholinesterase inhibitors in the treatment of cholinergic deficits. Neither NIK-247 nor THA affected the activity of choline acetyltransferase (ChAT). These inhibitions of ChE by NIK-247 and PHY lasted for 2 h, while that by THA lasted for over 4 h. In the effects of NIK-247 and PHY, the concentrations of intrastriatal acetylcholine (ACh) were changed in relation to the inhibition of the ChE activity. However, THA caused a transient increase in the ACh level lasting for only 2 h instead of inhibiting the enzyme activity for over 4 h. These findings suggest that NIK-247 is a drug with a similar profile in its effect on cholinergic neurons to PHY, the prototype drug among ChE inhibitors. The data indicate that NIK-247 may be useful as a drug for the treatment of central as well as peripheral deficits of the cholinergic mechanism.

Acetylcholine↗