Biomedical subjects

K Higuchi

Publications and source records attributed to K Higuchi.

At least 253 records · Page 14Linked to original sources

PubMed1995

Establishment and characterization of a new human lung poorly differentiated adenocarcinoma cell line, GLL-1, producing carcinoembryonic antigen (CEA) and CA19-9.

A new human lung poorly differentiated adenocarcinoma cell line producing carcinoembryonic antigen (CEA) and CA19-9, designated GLL-1, was established from a serial xenograft established in our laboratory. In this paper, we investigated the characteristics of GLL-1 cells. The cell line grew in a monolayer and had a polygonal epithelioid appearance in phase-contrast microscopy. The doubling time of GLL-1 cells during exponential growth was approximately 28 h in RPMI-1640 with 10% fetal calf serum. Positive reactions for CEA and for CA19-9 were seen within the cytoplasm of GLL-1 cells by immunohistochemical staining. In log phase, the fractions for G0/G1, S and G2/M were 76.2%, 20.0% and 3.8%, respectively. Chromosome analysis revealed that GLL-1 cells contained the modal number of 72 chromosomes (range 66-97). GLL-1 cells exhibited numerous numerical and structural abnormalities. The Do value for radiation sensitivity, calculated by taking the reciprocals of the slope of the radiation dose response curve, was 109 cGy. The extrapolation number (n) for the radiation response curve was 1.57. Tumor take was observed in nude mice inoculated subcutaneously in the back with 2 x 10(6) GLL-1 cells. The histopathological features of the tumor induced by inoculation of GLL-1 cells were also the same as the original lung cancer.

Adenocarcinoma↗

PubMed1995

Effects of lansoprazole on ethanol-induced injury and PG synthetic activity in rat gastric mucosa.

Lansoprazole, a proton pump inhibitor, has been reported to inhibit ethanol-induced injury in rats. However, the mechanism of the protective effect is not known. This study was carried out to investigate the role of prostaglandin (PG) in the protective effect of lansoprazole. Male Wistar rats were given either 30 mg/kg of lansoprazole or vehicle alone intragastrically 30 min before administration of ethanol. They were killed to measure the gross mucosal lesions in the stomach as the ulcer index. In another experiment, 5 mg/kg of indomethacin was injected 30 min before administration of lansoprazole. The effects of 16,16-dimethyl PGE2 (dmPGE2) on ethanol-induced injury over time were compared with lansoprazole. PGE2 synthesis in gastric mucosa after administration of lansoprazole was measured by radioimmunoassay. Lansoprazole reduced gastric mucosal injury by lansoprazole. DmPGE2 significantly reduced gastric mucosal injury from 5 min after exposure to ethanol. Lansoprazole did not affect PGE2 synthesis in the gastric mucosa. These results suggest that PG may not be involved in the protective effect of lansoprazole.

16,16-Dimethylprostaglandin E2↗

PubMed1995

Bacillus thuringiensis serovar higo (flagellar serotype 44), a new serogroup with a larvicidal activity preferential for the anopheline mosquito.

Eight strains of Bacillus thuringiensis, isolated in Japan, formed spherical parasporal inclusions and exhibited low to moderate larvicidal activities for two mosquito species, Anopheles stephensi and Culex pipiens molestus, but not for another dipteran, Telmatoscopus albipunctatus, or two lepidopterans, Bombyx mori and Hyphantria cunea. The anopheline toxicity (LC50 = 6.3 micrograms ml-1) was > 10 times greater than the activity on the Culex mosquito. These strains were assigned to a previously undescribed flagellar (H) antigenic group. On the basis of the representative strain, 92-KU-137-4, a serogroup with H antigen 44, Bacillus thuringiensis serovar higo was established as new.

Animals↗

PubMed1995

Prediction of prognosis of primary biliary cirrhosis in Japan.

The clinical profile of primary biliary cirrhosis in Japan was clarified on the basis of data on 1066 patients attending 212 hospitals and institutions in this country. Six hundred and twelve patients (57.4%) were asymptomatic. The majority of the patients were middle-aged women. Pruritus was the most frequent initial symptom of symptomatic primary biliary cirrhosis. Antimitochondrial antibodies were positive in 877 patients (82.5%). Sjögren's syndrome was the most common associated autoimmune disease. Liver biopsy was performed in 753 patients at the time of diagnosis, and histological staging by Scheuer's classification indicated that 307 (43.7%) patients were in stage I and 222 (31.6%) were in stage II. The most frequent causes of death were hepatic failure and/or gastrointestinal bleeding, which affected 166 (78.3%) of the 212 patients who died. Statistical analysis using Cox's regression method revealed that the patient's age and the serum bilirubin, albumin, and total cholesterol concentrations were significant predictors of the prognosis. A prognostic index was also calculated that could be used to predict the duration of survival for patients with primary biliary cirrhosis.

Adult↗

PubMed1995

Suppression of natural killer cell activity by monocytes following immunotherapy for recurrent spontaneous aborters.

PROBLEM: Natural killer (NK) cell activity has previously been shown to decrease in normal pregnancy as compared with the nonpregnancy state. The purpose of this study was to determine NK cell activity in recurrent aborters and to investigate the kinetics of NK cell activity following immunotherapy. METHODS: Recurrent aborters (N = 17) were immunized with husbands' mononuclear cells (1 x 10(8)) twice during the early stage of current pregnancy. NK cell activity of recurrent aborters as well as that of normal pregnant (N = 12) and nonpregnant (N = 6) women (controls) was determined by 51Cr release assay. Monocytes were depleted from the mononuclear cell fraction and its effect on the NK cell activity was determined as well. RESULTS: At around 5 wk of gestation, NK cell activity in recurrent aborters before treatment was significantly higher (28.0 +/- 5.1%) than that in normal pregnancy (18.9 +/- 4.3%) (P < 0.01). Following immunotherapy, NK cell activity of recurrent aborters (N = 13) who maintained their pregnancy decreased significantly (21.7 +/- 8.9%) (P < 0.05). In contrast, NK cell activity of recurrent aborters (N = 4) who aborted their current pregnancy did not decrease. Depletion of monocytes resulted in a significant increase in NK cell activity (P < 0.05). CONCLUSIONS: This study suggests that the immunotherapy induces suppression of NK cell activity which may contribute for the maintenance of pregnancy. Moreover, monocytes may be involved in this suppression.

Abortion, Habitual↗

PubMed1995

Calcitonin reduced corticosterone-induced muscle proteolysis.

Two-experiments were conducted to clarify the effect of calcitonin (CT) on growth, muscle protein breakdown, plasma corticosterone (CTC) concentration and urinary calcium excretion in young growing rats treated with CTC. Rats received hormonal treatments for 6 days (Experiment 1) or 24 h (Experiment 2). Dose levels of CTC were 10 mg and 5 mg/100 g body weight/day in experiment 1 and 2, respectively, and that of CT was 100 m unit/100 g body weight/day in both experiments. Muscle protein degradation was evaluated by urinary N tau-methylhistidine excretion. CT increased 24-h urinary calcium excretion but not 6-day calcium excretion. CTC markedly inhibited growth, accelerated muscle protein degradation and increased calcium excretion in both experiments. However, very interestingly, CT minimized CTC-induced muscle proteolysis, and normalized the CTC-induced decrease in urinary calcium excretion. Furthermore, CT decreased the CTC-induced increase in the plasma CTC concentration. The present observations indicate that CT reduces CTC-induced muscle protein breakdown by reducing the plasma CTC concentration and that increased urinary calcium excretion due to CT treatment may also play a role in reducing CTC-induced muscle protein breakdown.

Animals↗

PubMed1995

Serum concentration of intercellular adhesion molecule-1 in patients with hepatocellular carcinoma is a marker of the disease progression and prognosis.

Serum levels of soluble forms of intracellular adhesion molecule-1 (sICAM-1) and lymphocyte function-associated antigen-3 (sLFA-3) in 122 patients with chronic liver disease including hepatocellular carcinoma (HCC) were measured by enzyme-linked immunosorbent assays. Serum levels of sICAM-1 in patients with HCC were significantly higher than those of chronic hepatitis (CH) and cirrhosis. On the other hand, serum levels of sLFA-3 in patients with HCC were almost the same as those of cirrhosis. Western blot analyses showed that molecular sizes of sICAM-1 and sLFA-3 detected in the sera were 90 kd and 50 kd, respectively, indicating that both molecules include whole extracellular domains. In patients with HCC, circulating sICAM-1 levels were significantly (P < .001) correlated with tumor volume (r = .50), total bilirubin (r = .38), serum aspartate aminotransferase levels (r = .51), and gamma-globulin (r = .63). Furthermore, serum sICAM-1 levels were significantly elevated in patients with multiple HCC (tumor number > 3) or HCC with tumor embolus in the first branch or trunk of portal vein. Survival periods were analyzed in relation to serum sICAM-1 levels in patients with HCC who had been treated by transcatheter arterial chemoembolization. The HCC patients with < 1,000 ng/mL of serum ICAM-1 showed significantly (P = .0005) longer survival than those with higher levels of the molecule. The same results were obtained when only patients with moderately differentiated HCC were analyzed (P = .02). Analyses by Cox's proportional hazard model showed that sICAM-1 is a significant (P = .032) prognostic factor for patients with HCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Ulcerogenicity and effect on inhibition of prostaglandin generation of indometacin farnesil, a prodrug of indomethacin, in rat gastric mucosa: comparison with indomethacin or loxoprofen.

Indometacin farnesil was compared with indomethacin and loxoprofen in rats to ascertain whether it caused less gastric mucosal damage than the two older drugs. Damage was evaluated in terms of the size of ulcers that formed after oral administration and the changes in concentrations of prostaglandins E2 and I2 in the mucosa. Indometacin farnesil caused less damage than indomethacin and tended to cause less damage than loxoprofen. Indometacin farnesil was less potent than indomethacin in inhibiting prostaglandin generation by gastric mucosa. This property of indometacin farnesil may contribute to the low ulcerogenicity of this compound.

Animals↗

PubMed1995

Liver penetration and gastrobronchial fistula: unusual complication of a peptic ulcer.

The authors present the first case report on a patient with liver penetration and a gastrobronchial fistula from a gastric ulcer. Liver penetration was diagnosed by endoscopy, and the gastrobronchial fistula was noted on a computed tomography scan. An emergent total gastrectomy was performed because of uncontrolled massive gastric bleeding not responsive to conventional treatment. The initial treatment of choice for these patients should be conservative because both complications could potentially have been controlled by H2 blockers and percutaneous drainage of the abscess.

Bronchial Fistula↗

PubMed1995

Apolipoprotein A-II gene and development of amyloidosis and senescence in a congenic strain of mice carrying amyloidogenic ApoA-II.

BACKGROUND: Apolipoprotein A-II (ApoA-II), a major apoprotein of serum high density lipoprotein (HDL) deposits as an amyloid fibril (AApoAII) in murine senile amyloidosis. Type C ApoA-II gene (Apoa2c) in the SAMP1 strain of mice, a murine model of severe senile amyloidosis and accelerated senescence was transferred on the genetic background of the SAMR1 strain, in which senile amyloidosis is rare and has a normal aging process, and a congenic strain of mouse (R1.P1-Apoa2c) was developed (Higuchi K, Kitado H, Kitagawa K, Kogishi K, Naiki H, Takeda T. FEBS Lett 1993;317:207-10). EXPERIMENTAL DESIGN: We identified AApoAII amyloid deposits in the 14-month-old congenic R1.P1-Apoa2c strain and compared these findings with the deposits in the progenitor SAMP1 and SAMR1 strains. The progression of senescence was estimated using a grading system and the age-associated changes in the metabolism of ApoA-II and HDL were investigated in the three strains of mice. RESULTS: At 14 months of age, severe amyloid deposition as compared with the donor SAMP1 strain was present in the congenic R1.P1-Apoa2c strain, but AApoAII was not evident in the progenitor SAMR1 strain which has type B ApoA-II. No obvious differences in the progression of senescence were observed between the R1.P1-Apoa2c and SAMR1 strains. In the R1.P1-Apoa2c strain, the serum HDL-cholesterol concentrations decreased in parallel with ApoA-II levels with advancing age and the decrease was much accelerated compared with the decrease seen in SAMR1 mice. CONCLUSIONS: Based on these results, we propose that the genetic type of ApoA-II plays an important role in the development of senile amyloidosis and age-associated changes in HDL metabolism. However, it has a minor role in the accelerated senescence in the mouse strains we used.

Aging↗

PubMed1995

[Evaluation of gastric adaptive relaxation in isolated stomach from the guinea-pig].

To evaluate the mechanism of gastric adaptive relaxation (GAR), we designed and established the experimental system for the measurement of GAR in isolated stomach from the guinea-pig by modifying the method of Desai. We also investigated the roles of non-adrenergic, non-cholinergic (NANC) nerves and endogenous nitric oxide (NO) in GAR by using this system. The rapid increase in the capacity of isolated stomach was observed over a certain pressure as GAR. GAR was abolished by tetrodotoxin (10(-6) M) in the presence of atropine (3 x 10(-6) M) and guanethidine (5 x 10(-6) M). NG-nitro L-arginine (LNNA) (10(-4) M), a NO synthesis inhibitor, also abolished GAR. L-arginine (10(-3) M), a precursor for NO synthesis, reversed LNNA-induced impairment of GAR. Sodium nitroprusside (10(-6)-10(-4) M), a NO-donor, induced the gastric relaxation. These results suggest that GAR is mediated by NANC nerves, possibly via endogenous NO.

Adaptation, Physiological↗

PubMed1995

Effects of endothelin on serum gastrin level and acid secretion in rats.

Endothelin (ET) is a potent ulcerogen in gastric mucosa. Disordered microcirculation due to vasoconstriction may cause gastric mucosal injury. In a previous study we found ET in gastric mucosal cells, especially chief cells and endocrine cells, and in vascular endothelial cells. Most endocrine cells staining for ET-1 are G cells. This study was done to find whether ET affects G-cell function, particularly gastrin release and acid secretion. ET-1 or ET-3 (5 nmol/kg) was injected i.v. into male Wistar rats. Blood samples were collected just before and 15, 30, or 60 min after injection and serum gastrin levels were assayed by RIA. The effects of BQ123-Na (Banyu), an ET receptor antagonist, pirenzepin, or an intragastric pH of 2 on changes in the gastrin levels brought about by ET-1 were examined. The gastric contents of rats with the pylorus ligated were collected for 1 h and then for the next 4 h after the ET-1 injection, and the acid output was calculated. After ET-1 administration, the gastric mucosa of the pyloric gland area was immunostained with antigastrin. The serum gastrin levels at 15, 30, and 60 min after ET-1 injection (220 +/- 94, 204 +/- 77, and 366 +/- 191 pg/ml, respectively) were significantly higher than those before the injection (75 +/- 18 pg/ml). ET-1 decreased the number of cells stained for gastrin. ET-3 had no effect on gastrin levels. BQ123-Na inhibited the increase in gastrin caused by ET-1, but pirenzepin had no effect. At pH 2, ET-1 had no effect on gastrin. ET-1 decreased acid output (2.6 +/- 2.3 microEq/h and 239 +/- 80 microEq/4 h, respectively) vs. controls (63 +/- 55 microEq/h and 346 +/- 81 microEq/4 h). Therefore, ET-1 increases rat serum gastrin levels, an effect that may be related to its reduction of acidity.

Animals↗

PubMed1995

Role of extracellular matrix in attachment, migration, and repair of wounded rabbit cultured gastric cells.

The aim of this study was to determine whether extracellular matrix components affect attachment, proliferation, migration, and repair of wounded rabbit gastric cells in primary culture. Gastric cells were inoculated on culture plates coated without or with collagen type I, type IV, laminin, or fibronectin. The number of attached cells was counted at 3, 5, 24, 48, and 72 h after inoculation. Cell proliferation was assessed with [3H]thymidine incorporation. To assess cell migration and repair after wounding, a confluent monolayer was cut in a standardized manner and the size of the wound area was measured with a computerized analysis system. The number of attached cells increased significantly in plates coated with the extracellular matrix components within 3 h after inoculation. Collagen type I was the most potent stimulator of attachment. Extracellular matrix components did not affect thymidine incorporation. Wound healing was significantly accelerated in the plates coated with collagen type I, type IV, and laminin (70.2 +/- 1.0%, 68.0 +/- 1.0%, and 69.2 +/- 0.9% of initial wound area, respectively, vs. 74.0 +/- 0.6% of initial wound area in controls). Extracellular matrix components play an important role in attachment, migration, and repair of wounded cultured gastric epithelial cells.

Animals↗

PubMed1994

Molecular genetic characterization of the senescence-accelerated mouse (SAM) strains.

Senescence-Accelerated Mouse (SAM) is a murine model of accelerated senescence, which consists of the senescence-prone P series and the senescence-resistant R series of strains. In order to characterize these SAM strains molecular genetically, we have performed a series of Southern hybridization experiments using oligonucleotide probes designed to recognize the endogenous mouse retrovirus sequences. The repertoires of endogenous retroviruses in different SAM strains indicated that each SAM strain is distinct. Comparisons of the SAM strains with the parental AKR/J strain revealed significant differences between them, suggesting the involvement of other strains in the course of the development of SAM. While some of the endogenous retroviruses were found in all of the SAM strains, others were found to be distributed uniquely, indicating their potential usefulness as genetic markers in the analysis of strain-specific phenotypes, and possibly of the phenomenon of accelerated senescence itself.

Aging↗

PubMed1994

Effects of body weight on responses of serum prolactin to metoclopramide and thyrotrophin-releasing hormone in secondary amenorrhoeic women.

The present study was designed to investigate the influence of body weight on the prolactin responsiveness to metoclopramide and thyrotrophin-releasing hormone (TRH) in secondary amenorrhoeic women. The responses of serum prolactin to metoclopramide and TRH were assessed in relation to body mass index (BMI). Doses of 10 mg of metoclopramide hydrochloride and 500 micrograms of TRH were administered i.v. to 42 secondary amenorrhoeic women and six women with primary ovarian failure. The increment of serum prolactin at 30 min after the administration of metoclopramide was significantly lower (P < 0.01, respectively) in amenorrhoeic women with a BMI of > or = 30 or < 19 than in amenorrhoeic women with a BMI of 19-24. A significant correlation ration (eta = 0.63; P < 0.01) was found between the BMI and the increment of serum prolactin at 30 min after metoclopramide administration in amenorrhoeic women. The increment of serum prolactin at 15 min after TRH administration was slightly lower in amenorrhoeic women with a BMI of > or = 30 or < 19 than in amenorrhoeic women with a BMI of 19-24, but these differences were not statistically significant. These results indicate that the body weight influences the responsiveness of serum prolactin to metoclopramide in secondary amenorrhoeic women.

Adult↗

PubMed1994

Pseudo-acylceramide with linoleic acid produces selective recovery of diminished cutaneous barrier function in essential fatty acid-deficient rats and has an inhibitory effect on epidermal hyperplasia.

Pseudo-acylceramides with different acyl properties were investigated for their capacity to restore diminished barrier function in essential fatty acid-deficient rats. Daily topical applications of synthetic pseudo-acylceramides containing ester-linked linoleic acid caused a dose-dependent, significant reduction of transepidermal water loss (TEWL). Both other pseudo-acylceramides with ester-linked oleic acid or saturated alkyl chains and ordinary ceramides exhibited a poor effect on recovery of TEWL. Furthermore, pseudoceramide containing ether-linked linoleic acid, which is biologically inactive in terms of degradation by hydrolytic enzymes, also induced a significant and similar increase in the barrier function. This restoration of barrier function by pseudo-acylceramides with linoleic acid was accompanied by suppressed DNA synthesis in the EFAD rat epidermis. In UVB-irradiated guinea pig skin, topical applications of the pseudo-acylceramides with linoleic acid immediately after the exposure significantly reduced epidermal hyperplasia, secondary to markedly diminished barrier disruption, whereas linoleic acid itself did not. A comparison of both the anti-hyperplasia and the barrier recovery effects in the series of pseudo-ceramide derivatives examined revealed that the suppressive effect on the induced epidermal hyperplasia was paralleled by the recovery of the barrier defect in EFAD rats. These findings directly suggest that acylceramide with an ester-linked linoleic acid has an essential role in the epidermal permeability barrier.

Animals↗

PubMed1994

Intracoronary acetylcholine-induced prolongation of the QT interval and Torsade des Pointes in long QT interval syndrome.

A 75-year-old female had syncopal episodes from Torsade des Pointes (TdP). Her electrocardiogram showed a prolonged QT interval which was not associated with electrolyte imbalances or drug therapy. Similar electrocardiographic abnormalities were found in three family members. Electrophysiologic study showed a mildly prolonged effective refractory period of 260-290 msec, but no tachyarrhythmia was induced. Coronary arteriography was normal but intracoronary acetylcholine unexpectedly induced a prolongation of the QT interval and TdP. Direct action of acetylcholine on the ventricular muscle was suggested.

Acetylcholine↗

PubMed1994

Analysis of beta-glucocerebrosidase and ceramidase activities in atopic and aged dry skin.

To elucidate the mechanisms that are involved in the decrease of ceramide levels in atopic dry skin and in aged skin, we examined both the activities of beta-glucocerebrosidase, which is a major enzyme in ceramide production, and of ceramidase, which is an essential enzyme in ceramide degradation, in the stratum corneum of atopic dry skin and aged skin. The specimens of the stratum corneum of forearm skin were obtained by tape-stripping from 61 healthy volunteers and 23 patients with atopic uninvolved skin. The beta-glucocerebrosidase activity in the stratum corneum extracts was estimated using fluorescent 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate. Ceramidase activity was determined using 14C-palmitoylsphingosine as the substrate. Among the atopic skin samples, neither beta-glucocerebrosidase nor ceramidase activities were different from those of age-matched healthy controls. Nor was the beta-glucocerebrosidase activity deficient in the aged skin samples as compared to that seen in samples from the young, healthy group. In contrast, there was an age-related upregulation in ceramidase activity. The results indicate that the decrease of ceramides in atopic dry skin may not be accompanied by reduced synthesis or by enhanced degradation, each of which is primarily attributable to the above two enzymes, respectively. The pathogenesis of aged dry skin can be explained, at least partially, in terms of elevated ceramidase activity, which results in a disturbance of the lamellar structure of the stratum corneum lipids.

Adolescent↗