Biomedical subjects

K Higuchi

Publications and source records attributed to K Higuchi.

At least 163 records · Page 9Linked to original sources

PubMed1998

A novel isolate of Bacillus thuringiensis serovar leesis that specifically exhibits larvicidal activity against the moth-fly, Telmatoscopus albipunctatus.

A soil isolate designated 88-KO-14-45, belonging to Bacillus thuringiensis serovar leesis (H33), exhibited larvicidal activity against the moth-fly, Telmatoscopus albipunctatus (Diptera: Psychodidae), but not for larvae of the culicine and aedine mosquitoes and Lepidoptera. Purified parasporal inclusions had an LC50 value of 5.78 micrograms/ml for the larval moth-fly, but gave no mortality against larvae of Culex pipiens molestus (Diptera: Culicidae) at protein concentrations up to 10 mg/ml. Electron microscopic observations revealed that the parasporal inclusions are homogeneous round-shaped bodies enclosed with thick, electron dense envelopes. Haemolytic activity against sheep erythrocytes was not detected in the solubilized inclusions. SDS-PAGE showed that the inclusions are composed of 72, 68, 56 and 30 kDa proteins. Immunologically, these proteins were unrelated to the inclusion proteins of B. thuringiensis serovar israelensis, while a 70 kDa protein of the strain 73-E-10-2 (B. thuringiensis serovar darmstadiensis) was seroactive to antibodies against proteins of 88-KO-14-45.

Animals↗

PubMed1998

A novel class of mosquitocidal delta-endotoxin, Cry19B, encoded by a Bacillus thuringiensis serovar higo gene.

Partially digested HincII fragments of DNA from a mosquitocidal strain of Bacillus thuringiensis serovar higo were cloned into pBluescript II SK(+) and propagated in Escherichia coli. Recombinant cells were screened immunologically for the production of parasporal inclusion antigens. One E. coli clone harboring a recombinant plasmid exhibited larvicidal activity to Culex pipiens molestus, but not to Anopheles stephensi. Hybridization experiments revealed that the gene of the toxin protein is located on a 110 kb plasmid of B. thuringiensis serovar higo. Sequence analysis detected an open reading frame of 2046 nucleotides encoding a polypeptide of 682 amino acid residues with a predicted molecular weight of 78,467. The gene encoded five block regions commonly conserved in the insecticidal protein genes of B. thuringiensis. Amino acid sequence of the 78 kDa protein shared 49% identity and 56% similarity with that of the Cry19A protein from B. thuringiensis serovar jegathesan. A new class of delta-endotoxin protein, designated Cry19B, was established on the basis of this protein.

Amino Acid Sequence↗

PubMed1998

Characterization of mosquito larvicidal parasporal inclusions of a Bacillus thuringiensis serovar higo strain.

The parasporal inclusion proteins of the type strain of Bacillus thuringiensis serovar higo (H44), that have moderate mosquitocidal activity, were characterized. The purified parasporal inclusions, spherical in shape, were examined for activity against the two mosquito species, Culex pipiens molestus and Anopheles stephensi and the moth-fly, Telmatoscopus albipunctatus. The LC50 values of the inclusion for the two mosquitoes were 3.41 and 0.15 microgram.ml-1, respectively. No mortality was shown for T. albipunctatus larvae by the inclusions at concentrations up to 1 mg ml-1. Solubilized parasporal inclusions exhibited no haemolytic activity against sheep erythrocytes. Parasporal inclusions consisted of eight proteins with molecular masses of 98, 91, 71, 63, 59, 50, 44 and 27 kDa. Of these, the 50 and 44 kDa proteins were the major components. Analysis with immunoblotting revealed that, among several inclusion proteins of B. thuringiensis serovar israelensis, only two proteins of 130 kDa and 110 kDa reacted weakly with antibodies against higo proteins. N-terminal amino acid sequences of the 98, 91, and 71 kDa proteins showed 85-100% identity to those of the two established Cry protein classes, Cry4A and Cry10A.

Amino Acid Sequence↗

PubMed1998

Larvicidal toxicity of Japanese Bacillus thuringiensis against the mosquito Anopheles stephensi.

Japanese isolates of Bacillus thuringiensis were screened for larvicidal activity against the mosquito Anopheles stephensi, the urban malaria vector of the Indian subcontinent. Among more than 30 strains identified, larvicidal activity causing > 80% mortality in 72 h was demonstrated for 41/1449 (2.8%) isolates. The majority of strains and isolates (97.2%) exhibited little or no larvicidal activity. Anopheles-active strains belonged to more than 12 H serotypes, especially H3ade (serovar fukuokaensis) and H44 (serovar higo). SDS-PAGE profiles of inclusion proteins showed 4 distinct types among 6 active strains examined. The most active Japanese isolates were H20 strain 89-T-34-14 (LC50 4.4 micrograms/ml) and H44 serovar higo strain 74-E-45-24 (LC50 7.6 micrograms/ml), respectively, 13-fold and 23-fold less active than the international standard H14 serovar israelensis (LC50 0.33 microgram/ml).

Animals↗

PubMed1998

Accelerated aging of dermal fibroblast-like cells from the senescence-accelerated mouse (SAM): acceleration of changes in DNA ploidy associated with in vitro cellular aging.

Accelerated changes in the DNA ploidy associated with in vitro aging were examined in fibroblast-like cells isolated from the dorsal dermis of newborn SAMP11 (accelerated senescence-prone, short-lived) mice, and were compared to changes observed in cell lines from SAMR1 (accelerated senescence-resistant, long-lived) mice. Flow cytometric analysis of the DNA content in confluent cells and chromosome analysis in mitoses revealed that the diploid cells were being replaced with tetraploid cells until a growth crisis; thereafter, hypotetraploid cells became predominant, accompanied by immortalization. The number of mitoses decreased as the crisis ensued, then increased. Although these changes were observed in the cell lines from both strains of mice, the changes occurred more rapidly and at earlier population doublings in the cell lines from the SAMP11 mice. These results suggest that the cell lines from SAMP11 mice might have higher susceptibility to factors that cause polyploidization, including oxidative stress.

Aging↗

PubMed1998

Prostaglandins in the stomach: an update.

Prostaglandins (PGs) are responsible for regulation of various physiologic activities in many tissues and organs, including the stomach. Recent studies have shown new crucial roles of PGs in the stomach. Activation of inflammatory cytokines and neutrophils may cause acute gastric mucosal lesions and recurrence of ulcers, which are induced by noxious stimuli such as nonsteroidal antiinflammatory drugs (NSAIDs), stress and Helicobacter pylori (H. pylori). These phenomena are PG-dependent because exogenous PGs reverse them. PG deficiency and H. pylori may worsen the quality of ulcer healing in terms of inflammatory responses, which are related to future ulcer recurrence. Neutrophils, monocytes/macrophages, and adhesion molecules are involved in the mechanism of recurrence caused by inflammatory cytokines. PGs accelerate ulcer healing, possibly via angiogenesis, epithelial cell proliferation, production of growth factors such as hepatocyte growth factor and transforming growth factor beta, reconstruction of extracellular matrices, and suppression of inflammatory cell infiltration, in addition to gastroprotective mechanisms. The PG synthase cyclooxygenase (COX) has two forms, COX-1 and COX-2. COX-2, but not COX-1, contributes to ulcer healing. Moreover, recent studies suggest the involvement of COX-2 in development of gastric and colon carcinoma. This may be linked to the chemopreventive effect of NSAIDs.

Humans↗

PubMed1998

A morphological and morphometrical study of the retina in aging SAM mice.

We investigated whether neuronal cell loss occurred as a part of normal aging of the retina in the Senescence-Accelerated Mouse, strains SAMP1 and SAMR1, and in the BALB/c mouse. All three strains showed age-related atrophy of the retina after histologically normal development. Morphometrical study revealed the following facts. The rate of loss of photoreceptor cells in the peripheral retina was greater than in the central retina in all three strains. In the central retina, the rate of loss of photoreceptor cells was greater in the SAMP1 and SAMR1 mice than in the BALB/c mice. In the peripheral retinal, the SAMR1 and SAMP1 strains had fewer cells than the BALB/c strain at all ages, but the rate of loss of these cells did not differ among the three strains. The rate of loss of ganglion cells did not differ between the peripheral and central retinas in the three strains. The SAMR1 and SAMP1 strains had fewer ganglion cells in the peripheral retina than the BALB/c strain at all ages. Because the rate of age-related loss of these cells in SAMP1 mice was not accelerated, and they were short-lived, SAMP1 mice did not show marked age-related loss. On the contrary, the SAMR1 mice showed a marked loss of photoreceptor cells and ganglion cells late in life because of their longer life span, and we propose that this strain is a suitable animal model for the study of mechanisms of age-related loss of neuronal cells in the retina.

Aging↗

PubMed1998

Calcium ion as a second messenger for o-nitrophenylsulfenyl-adrenocorticotropin (NPS-ACTH) and ACTH in bovine adrenal steroidogenesis.

o-Nitrophenyl sulfenyl-modified ACTH (NPS-ACTH) stimulated steroidogenesis acutely in bovine fasciculata-reticularis cells without increase in cellular cAMP synthesis. Application of NPS-ACTH to the cultured cells induced Ca2+ signals in individual cells as detected by video-enhanced microscopic fluorescence measurements. The percentage of Ca2+ signaling cells corresponded well with the increase of steroidogenesis induced by NPS-ACTH below 1 nM. Treatment of the cells with nicardipine, a Ca2+ channel blocker, suppressed the Ca2+ signals except for the transient increase just after the addition of NPS-ACTH and also blocked completely the stimulative effect on the steroidogenesis of NPS-ACTH below 1 nM. At a dosage of NPS-ACTH higher than 10 nM, the stimulative effect of steroidogenesis was partly suppressed by nicardipine and also by AA-861, a lipoxygenase inhibitor. The action of NPS-ACTH might be mediated by both Ca2+ and lipoxygenase metabolite(s) of arachidonic acid as dual second messengers. The effect of ACTH in pM range on the steroidogenesis was suppressed completely by the treatment with nicardipine and AA-861 at the same time, indicating that the action was mediated by both Ca2+ and the lipoxygenase metabolite(s) but not by cAMP. cAMP plays a significant role as a second messenger for ACTH action only at ACTH concentrations greater than 10 pM.

Adrenal Glands↗

PubMed1998

Retroperitoneal Castleman's disease of the hyaline vascular type presenting arborizing calcification.

Castleman's disease (CD) usually manifests as a solitary mediastinal tumor and only rarely as an isolated retroperitoneal mass. In the latter instances it is difficult to distinguish radiographically from other retroperitoneal masses. We report a 22-year-old female patient with retroperitoneal CD of the hyaline vascular type presenting with arborizing calcification. This characteristic calcification pattern is considered unique to CD, and is useful in diagnosis when present.

Adult↗

PubMed1998

Age-related changes in blood pressure in the senescence-accelerated mouse (SAM): aged SAMP1 mice manifest hypertensive vascular disease.

Age-related changes in systolic blood pressure were assessed, using the senescence-accelerated mouse (SAM) model for aging research with strains SAMR1, SAMP1, and SAMP8. Each of the strains manifested a characteristic change in blood pressure with age. The SAMR1 strain, with normal aging, did not have chronologic changes from 2 to 27 months of age. The SAMP1 strain, with accelerated senescence, had a significant increase in blood pressure with age, and some (8 of 39) mice manifested hypertensive vascular disease characterized by high blood pressure, cardiac hypertrophy, and arteriolar fibrinoid necrosis at 11 to 14 months of age. The gradual increase in blood pressure after 8 to 10 months was considered to be preceded by progressive renal changes, from glomerulonephritis to contraction of the kidney, suggesting that the high blood pressure in the SAMP1 strain was of renal origin. Blood pressure in the SAMP8 strain, with age-related deficits in learning and memory, gradually decreased after 5 to 7 months of age, and was suggested to be due to the astrogliotic changes in response to spongiform degeneration in the medulla oblongata at 11 to 14 and 15 to 18 months of age.

Aging↗

PubMed1998

Progression to moderate or severe mitral regurgitation after percutaneous transvenous mitral commissurotomy using stepwise inflation technique.

Progression to moderate or severe mitral regurgitation (MR) was studied after Inoue balloon percutaneous transvenous mitral commissurotomy (PTMC) using the stepwise inflation technique, performed at increments of 1 mm of balloon diameter, in 49 consecutive patients with rheumatic mitral stenosis (aged from 32-73 years; 8 males, 41 females). The patients were classified on the basis of the degree of MR after PTMC, compared with that before PTMC, into either Group A, development of moderate or more severe (> or = grade 2) MR (n = 8) or Group B, no increase in MR or development of mild (grade 1) MR (n = 41). Progression to moderate or severe MR was significantly associated only with advanced age (60 +/- 8 vs 52 +/- 10 years, p < 0.05) and narrower mitral valve area (0.87 +/- 0.35 vs 1.11 +/- 0.29 cm2, p < 0.05), but other characteristics before PTMC were similar in both groups. There was no difference between the two groups in the total number and degree of balloon inflation. Immediately before the final inflation, the left atrial mean pressure and v wave pressure were decreased in smaller degrees in Group A compared with Group B (-2 +/- 2 vs -5 +/- 4 mmHg, p < 0.05; -2 +/- 2 vs -6 +/- 6 mmHg, p < 0.05, respectively). Thus, the stepwise inflations require careful monitoring of changes in the left atrial pressure and waveform to recognize the aggravation of MR, especially in older patients with severe stenosis. Patients who do not have a significant drop in left atrial mean pressure and v wave pressure during stepwise inflations of the balloon might be at risk of development of moderate or severe MR after further dilations.

Adult↗

PubMed1998

Nine patients with hepatocellular carcinoma surviving for more than six years after treatment, including two patients who have survived without recurrence after hepatic lobectomy.

Of patients treated for hepatocellular carcinoma (HCC) accompanied by liver cirrhosis at our University Hospital between 1985 and 1990, clinical background factors in nine patients (7.0% of all patients) who survived for more than six years were examined to clarify the conditions that facilitate long-term survival. In particular, we describe two cases among these patients who have survived without the recurrence of a liver tumor for more than six years after hepatic lobectomy. In eight of nine patients, surgery was performed as the initial treatment. In seven patients, HCC was solitary and there was no portal invasion. Six patients were evaluated as Stage I according to clinical staging. Furthermore, the two patients without recurrence after treatment have been taking immunostimulators since their initial treatment until the present. The above observations suggest that surgical treatment should be considered in patients in whom hepatic reserve capacity is well maintained despite a tumor size greater than 2 cm. Subsequent recurrence should be detected earlier, and percutaneous ethanol injection therapy (PEIT) with a focus on maintaining liver function should be repeated. In addition, multi-disciplinary treatment including medication with immunostimulators is beneficial.

Aged↗

PubMed1998

Ulcer recurrence: cytokines and inflammatory response-dependent process.

H. pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are important factors in the recurrence of peptic ulcer diseases. However, H. pylori-negative recurring ulcers can also be found in nonusers of NSAIDs. The aim of this paper is to review recent data pertaining to mechanisms of ulcer recurrence. Prostaglandin E2 generation is impaired in the tissues of the ulcer scar site and prostaglandin depletion induced by administration of indomethacin during the healing of experimental gastric ulcer predisposes to future ulcer recurrence. Therefore, the prostaglandin deficiency may impair the quality of ulcer healing and thus increase the likelihood of future ulcer recurrence. Persistent infiltration of polymorphonuclear cells is the most prominent finding in the gastric ulcer scar in rats treated with indomethacin. Concomitant administration of prostaglandin E1-analog with indomethacin attenuates inflammatory infiltration and reduces future ulcer recurrence. Therefore, the inflammatory responses at the ulcer scar site may be a key to the quality of ulcer healing. Recent clinical findings suggest a close relationship between the quality of ulcer healing, infiltration of neutrophils and mononuclear cells, and future ulcer recurrence. Gastroprotective drugs such as prostaglandin analogs and prostaglandin inducers improve the quality of ulcer healing and reduce future recurrence. Production of inflammatory cytokines is stimulated by ulcerogenic factors such as NSAIDs, stress, and H. pylori infection. Inflammatory cytokines such as interleukin-1beta and tumor necrosis factor-alpha cause recurrence of healed ulcer. Synthetic prostaglandin E2 inhibits recurrence as well as the production of the cytokines.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Protective effect of rebamipide against ammonia-induced gastric mucosal lesions.

We investigated the protective effect of rebamipide against ammonia-induced gastric mucosal lesions. Participation of prostaglandin E2 and nitric oxide in the action of rebamipide was also examined. Rebamipide was administered intraperitoneally (10-100 mg/kg) to male Wistar/ST rats (150-325 g) fasted for 24 hr. Thirty minutes later, 1% NH4OH (1 ml) solution was given intragastrically. One hour later, the length of the mucosal lesions was measured (lesion index), and prostaglandin E2 (PGE2) was determined by radioimmunoassay. A 1% NH4OH solution caused gastric mucosal lesions with hemorrhagic necrosis and submucosal edema. PGE2 synthesis was not affected by NH4OH but was significantly increased by rebamipide. Rebamipide decreased the severity of NH4OH-induced gastric mucosal lesions in a dose-dependent manner. Pretreatment with indomethacin (5 mg/kg, subcutaneously) did not affect the protective effect of rebamipide; however, pretreatment with N(omega)-nitro-L-arginine (L-NNA, 1-10 mg/kg, intravenously), an inhibitor of nitric oxide synthase, attenuated the protective effect of rebamipide in a dose-dependent manner. Simultaneous administration of L-arginine (100 mg/kg) and L-NNA completely restored the protective effect of rebamipide, whereas D-arginine was inactive. These results suggest that nitric oxide contributes significantly to the protective effect of rebamipide against ammonia-induced gastric mucosal lesions.

Alanine↗

PubMed1998

Rebamipide prevents recurrence of gastric ulcers without affecting Helicobacter pylori status.

Rebamipide, a gastroprotective drug developed in Japan, accelerates ulcer healing and reduces recurrence of experimental gastric ulcers. We examined the effects of rebamipide, given during healing of human gastric ulcers infected with Helicobacter pylori, on the quality of ulcer healing and ulcer recurrence. Sixty H. pylori-positive patients with gastric ulcers were randomly allocated to three treatment groups: group O (N = 20) received 20 mg of omeprazole every day for eight weeks, group OR (N = 20) received the same dose of omeprazole and 300 mg of rebamipide three times a day for eight weeks, and group OA (N = 20) received the same dose of omeprazole for eight weeks and 1500 mg of amoxicillin three times a day for the first two weeks. After this treatment was completed no other medication was given. Endoscopic examinations were performed at the end of therapy (for healing rate), one month later (for rate of H. pylori eradication) and every three months for follow-up (for ulcer recurrence rate). At the end of therapy, biopsy specimens were taken from the gastric ulcer scar and examined under the microscope for neutrophil and mononuclear cell infiltration. The ulcer healing rate of the three groups was almost the same; H. pylori in group OA was 65% and that of the other two groups was 0%. The number of patients with a flat ulcer scar pattern (good quality of ulcer healing) was increased and the neutrophil infiltration was significantly improved in groups OR and OA compared to group O. The ulcer recurrence rate was significantly lower in group OA and group OR than in group O. In conclusion, rebamipide is almost equipotent to amoxicillin plus omeprazole for the reduction of ulcer recurrence. The decreased recurrence rate by rebamipide may be due to improvement of the quality of ulcer healing, reflected as in the suppression of inflammatory cell infiltration in the scar, which results from either cure of H. pylori infection and/or treatment with a gastroprotective drug such as rebamipide.

Aged↗

PubMed1998

Increased mRNA levels of transforming growth factor-beta1 and monocyte chemoattractant protein-1 in ulcer relapse caused by interleukin-1beta in rats.

This study investigated the mRNA expression of transforming growth factor-beta1 (TGF-beta1) and monocyte chemoattractant protein-1 (MCP-1) in rat gastric tissues in which ulcers had relapsed due to interleukin-1beta (IL-1beta) administration. Rats with healed ulcers were administered IL-1beta (1 microg/kg) and killed after 0, 12, 24, or 48 hr. Both TGF-beta1 and MCP-1 mRNA levels were increased in the scarred gastric tissues at 24 hr (fourfold), when ulcers had not relapsed. Furthermore, the expression of these genes also increased in the ulcerated gastric tissues at 48 hr (fivefold), when 90% of healed ulcers had relapsed. On the other hand, the number of macrophages that had infiltrated the scarred gastric tissues at 24 hr was two times higher than that at 0 hr. At 48 hr, the number of macrophages that had infiltrated gastric tissues in which ulcers had relapsed was similar to that at 24 hr. Thus, TGF-beta1 and MCP-1 may be implicated in the macrophage infiltration, thereby leading to ulcer relapse due to IL-1beta.

Animals↗

PubMed1998

Effect of rebamipide on Helicobacter pylori infection in patients with peptic ulcer.

This study was designed to assess whether the gastroprotective drug, rebamipide, aids in eradication of H. pylori. One hundred twenty patients, endoscopically diagnosed with gastric or duodenal ulcers and H. pylori infection, were randomly allocated to two treatment groups. Sixty patients received 40 mg of omeprazole twice a day, 1500 mg of amoxicillin three times a day, and 300 mg of rebamipide three times a day (group OAR); the other 60 patients received the same dosage of omeprazole and amoxicillin but no rebamipide for two weeks (group OA). All patients subsequently received an H2-receptor antagonist for six weeks. At the end of the treatment, endoscopy was performed to assess the status of the ulcers as well as the extent of H. pylori infection. In the intent-to-treat (73.3 vs 51.7%, P = 0.014) and per-protocol analyses (75.9 vs 55.3%, P = 0.021) the cure rates for H. pylori infection in group OAR were found to be significantly higher than those in group OA. Our findings suggest that rebamipide aids in curing H. pylori infection. This drug does not induce formation of resistant colonies and has few side effects.

Adult↗

PubMed1998

[The mechanisms of gastrointestinal mucosal injury and repair].

Peptic ulcer disease are usually accompanied by diffuse inflammation over the gastroduodenal mucosa in addition to severe local inflammation at the site of ulceration. It is well known that inflammatory cytokine are the main mediators of inflammation. Cytokines may also play a part in acute gastroduodenal mucosal lesions (AGML) caused by NSAID, H. pylori, and stress. Among cytokines most involved in AGML, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL) 1, IL-6, and IL-8 modulate chemotaxis, chemokinetics, and aggregation and release of lysosomal enzymes from neutrophils. Ulcer healing requires interaction of various cellular and connective tissue components. The stimulus for increased cell proliferation is most likely initiated by EGF and/or TGF-alpha which are mitogenic peptides for gastric epithelial cell at the initial stage in ulcer healing after ulcer induction. Transforming growth factor-beta (TGF-beta) also potentially involved in the ulcer healing process. During the chronic stage of ulceration, the growth of granulation tissue and generation of new microvessels by angiogenesis is stimulated by the fibroblast growth factors, platelet derived growth factor, TGF-beta, prostaglandins and/or IL-1 and TNF-alpha. The quality of mucosal restoration may be the most important factor in determining whether ulcers will recur. The proper restoration of the mucosal architecture requires balanced stimulation and interaction of both epithelial and connective tissue components, as well as, activation of growth factors which controls these components.

Animals↗