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S Sugai

Publications and source records attributed to S Sugai.

At least 55 records · Page 3Linked to original sources
PubMed1998

The region of alpha-lactalbumin recognized by GroEL.

The binding constants between disulfide-intact or various disulfide-reduced bovine alpha-lactalbumins and an Escherichia coli chaperonin, GroEL, were determined by using the equilibrium dialysis method. The disulfide-intact and one-disulfide (Cys6-Cys120)-reduced alpha-lactalbumins were shown not to bind with GroEL both in the presence and absence of Ca2+. The two-disulfide (Cys6-Cys120 and Cys28-Cys111)-reduced alpha-lactalbumin, which has the native-like tertiary structure in its beta-domain region and an unfolded alpha-domain in the presence of Ca2+, showed considerable binding with GroEL. The binding free energy of the two-disulfide-reduced alpha-lactalbumin in the presence of Ca2+ is close to that of the molten globule state of disulfide-intact alpha-lactalbumin. This result suggests that GroEL binds to the unfolded alpha-domain of alpha-lactalbumin regardless of the conformation of the beta-domain. The fully disulfide-reduced and two-disulfide-reduced alpha-lactalbumins were found to bind more strongly with GroEL in the absence of Ca2+ than the two-disulfide-reduced alpha-lactalbumin in the presence of Ca2+, thus indicating that the unfolding of the beta-domain of alpha-lactalbumin leads to stronger interaction with GroEL.

Binding, Competitive↗
PubMed1998

Remarkable destabilization of recombinant alpha-lactalbumin by an extraneous N-terminal methionyl residue.

A recombinant bovine alpha-lactalbumin, possessing an additional N-terminal methionyl residue, was expressed in Escherichia coli. In order to address the effects of the N-terminal methionyl residue on conformational stability, the thermal stability of the recombinant alpha-lactalbumin was investigated by measuring temperature-dependence of circular dichroism spectra, and it was compared with that of authentic alpha-lactalbumin from bovine milk. The thermal stability of the recombinant alpha-lactalbumin was significantly lower than that of authentic alpha-lactalbumin. The enthalpy change of unfolding of the recombinant protein was found to be the same as that of the authentic one when compared at the same temperature. Therefore, the N-terminal methionyl residue seems to destabilize the conformation of recombinant alpha-lactalbumin through some entropic effects.

Animals↗
PubMed1998

[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na (1). Fertility study in rats].

Fertility study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in Sprague-Dawley (SD) rats. ONO-5046.Na was administered intravenously at doses of 18.75, 37.5 and 75 mg/kg/day to male rats from 64 prior to mating, through the mating period and until necropsy, and to female rats from 15 days prior to mating until Day 7 of gestation, in order to examine its effects on fertility and reproductive performance of males and females and the development of their fetuses. There were no changes attributable to ONO-5046.Na in general signs, body weight, food consumption or autopsy findings in males and females. No drug-related changes were observed in estrous cycles, copulation and fertility indices in males and females. Pituitary weight of dams was decreased in each of the ONO-5046.Na treated groups, but no histopathological changes were observed in the pituitary. In the cesarean section findings in dams, ONO-5046.Na had no effects on the number of corpola lutea, the number of live fetuses, the implantation ratio, the resorbed and dead fetus ratio, fetal or placental weight, or the incidences of external, skeletal or visceral anomalies of the fetuses. From these results, it is considered that the NOAEL of ONO-5046.Na is 75 mg/kg/day for general and reproductive toxicity in males and females and for developmental toxicity in their fetuses.

Animals↗
PubMed1998

[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (2). Study for effects on pre- and postnatal development in rats, including maternal function].

Prenatal and postnatal toxicity of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel inhibitor of human neutrophil elastase, was studied in Sprague-Dawley (SD) rats. ONO-5046.Na was injected intravenously at doses of 0, 18.75, 37.5 and 75 mg/kg/day to pregnant rats from day 7 of pregnancy to day 20 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. No adverse effects on dams were observed in clinical signs, body weight change, food consumption, pregnant, delivery or lactating performances. ONO-5046.Na did not affect the postnatal development of offspring, including birth index, survival index, physical and functional development, motor activity, emotionality, learning ability and reproductive performance. From these results, it is considered that the NOAEL of ONO-5046.Na is 75 mg/kg/day for dams and their offspring.

Animals↗
PubMed1998

[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (3). Teratogenicity study in rabbits].

Teratogenicity of sodium N[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel inhibitor of human neutrophil elastase, was studied. ONO-5046.Na was injected intravenously at doses of 0, 7.5, 15 and 30 mg/kg/day to pregnant Kbl: NZW rabbits from day 6 to day 18 of pregnancy. All female rabbits were sacrificed on day 29 of pregnancy and their fetuses were examined. There were no clinical signs or death attributable to ONO-5046.Na. One dam in the control group and 3 dams in the 30 mg/kg/day group aborted. Body weight gain in the 15 and 20 mg/kg/day groups and food intake in the 30 mg/kg/day group were decreased during the administration period. These changes had recovered by the end of the study. Kidney weight was increased in the 30 mg/kg/day group. There were no effects of ONO-5046.Na in necropsy findings at cesarean section in dams at any dose levels. Developmental toxicity of ONO-5046.Na was not found at any dose levels. From these results, it is considered that the NOAEL of ONO-5046.Na is 7.5 mg/kg/day for pregnant animals and 30 mg/kg/day for fetuses.

Animals↗
PubMed1998

MR sialography in patients with Sjögren syndrome.

PURPOSE: The purpose of this study was to evaluate the effectiveness of MR sialography of the parotid gland ducts in the diagnosis and staging of Sjögren syndrome. METHODS: MR imaging was performed on a 1.5-T unit with a neck phased-array coil. MR sialographic source images were obtained using a heavily T2-weighted fast spin-echo sequence with spectral fat suppression. All images were analyzed on the basis of maximum intensity projection reconstruction. Five healthy control subjects and 51 patients with definite Sjögren syndrome (43 with primary disease and eight with secondary disease) were examined with MR sialography. A labial gland biopsy was performed in all patients and histopathologic grading was done by means of focal scores. The findings of MR sialography were compared with the results of labial gland biopsy to determine the effectiveness of the technique in the diagnosis and staging of Sjögren syndrome. RESULTS: In all five control subjects, the main duct and the primary branching ducts of the parotid glands were clearly visible on MR sialographic images. In patients with Sjögren syndrome, a punctate, globular, cavitary, or destructive appearance was well seen within the parotid glands. Findings obtained at MR sialography correlated well with the results of labial gland biopsy. CONCLUSION: MR sialography has the potential to produce diagnostic findings in the parotid gland ducts of patients with Sjögren syndrome. Our results suggest that this method will augment and possibly replace X-ray sialography.

Adolescent↗
PubMed1997

Molten globule state of equine beta-lactoglobulin.

The acid-unfolded state of equine beta-lactoglobulin was characterized by means of circular dichroism, nuclear magnetic resonance, analytical gel-filtration chromatography, and analytical centrifugation. The acid-unfolded state of equine beta-lactoglobulin has a substantial secondary structure as shown by the far-ultraviolet circular dichroism spectrum but lacks persistent tertiary packing of the side chains as indicated by the near-ultraviolet circular dichroism and nuclear magnetic resonance spectra. It is nearly as compact as the native conformation as shown by the gel filtration and sedimentation experiments, and it has the exposed hydrophobic surface as indicated by its tendency to aggregate. All of these characteristics indicate that the acid-unfolded state of equine beta-lactoglobulin is a molten globule state. The alpha helix content in the acid-unfolded state, which has been estimated from the circular dichroism spectrum, is larger than that in the native state, suggesting the presence of nonnative alpha helices in the molten globule state. This result suggests the generality of the intermediate with nonnative alpha helices during the folding of proteins having the beta-clam fold.

Acids↗
PubMed1997

Association of a new allele of the TAP2 gene, TAP2*Bky2 (Val577), with susceptibility to Sjögren's syndrome.

OBJECTIVE: To investigate the polymorphisms of TAP (transporters associated with antigen processing) genes among patients with primary Sjögren's syndrome (SS) in order to clarify the potential association of the polymorphisms with disease susceptibility. METHODS: Polymorphisms of the TAP1 and TAP2 genes in 108 Japanese SS patients were determined by analyzing TAP genes using the polymerase chain reaction-single-stranded conformation polymorphism technique. RESULTS: The allelic frequency of the TAP1 gene was not significantly different between SS patients and normal subjects. In addition to all known TAP2 alleles, a new allele (Bky2), which had a unique substitution at codon 577 (ATG-->GTG: Met-->Val), was identified in both groups. The allelic frequency of Bky2 was significantly higher in SS patients (12.0%) than in normal subjects (5.1%) (P < 0.05). Moreover, a significantly greater frequency of SS-A antibody was found among SS patients with Bky2 (18 of 23; 78%) than among those without Bky2 (33 of 85; 39%) (P = 0.001). CONCLUSION: The mutation in TAP2 (Val577) may be involved in SS-A autoantibody production and could be a genetic factor that determines susceptibility to SS.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Genetic detection of colorectal cancer cells in circulation and lymph nodes.

PURPOSE: This study was undertaken to investigate the clinical implications of detection of genetic alterations in blood and lymph nodes in colorectal cancer patients. METHODS: The reverse transcriptase polymerase chain reaction product of the cytokeratin gene in blood was examined as a cancer cell-specific expression in 35 colorectal cancer patients. The K-ras or p53 gene mutations in the lymph nodes histopathologically negative for metastasis were studied by the mutant-allele-specific amplification method in 26 colorectal cancer patients. RESULTS: The reverse transcriptase polymerase chain reaction assay was able to detect a cytokeratin reverse transcriptase polymerase chain reaction product at a concentration from a single to ten colon cancer cells per 10(6) normal peripheral blood mononuclear cells. Cytokeratin reverse transcriptase polymerase chain reaction products were detected in nine patients' blood samples, although none of the samples were cytologically detectable. The blood's cytokeratin positivity correlated with the invasive mode of the tumor (P < 0.05) and the presence of distant metastasis (P < 0.01). Two (50 percent) of four patients whose blood was positive for cytokeratin had recurrences. Of 17 patients with the K-ras or p53 gene mutation in primary tumors, 9 (53 percent) had the corresponding mutations in lymph nodes. Mutation positivity in lymph nodes correlated with the presence of lymphatic invasion of the primary tumor (P < 0.05). All patients with mutation-negative lymph nodes remained disease-free for more than two years after surgery. CONCLUSION: Detection of cytokeratin reverse transcriptase polymerase chain reaction products in the blood and K-ras or p53 gene mutations in the lymph nodes histologically negative for metastasis may be applicable for clinical use, despite some limitations, and may serve as a useful clinical factor for stratifying patients who are at high or low risk for recurrence after surgery.

Biomarkers, Tumor↗
PubMed1997

Increased number of IgE positive Langerhans cells in the conjunctiva of patients with atopic dermatitis.

AIM: To determine the role of Langerhans cells (LCs) found to bear IgE in patients with atopic dermatitis (AD) by evaluating the surface distribution of these cells in the conjunctival epithelium and epidermis of skin lesions in patients with AD. METHODS: The double labelling method was used to evaluate IgE positive cells that were positive for anti-CD1a or anti-CD23 antibody in an epithelial sheet of the conjunctival limbus. Specimens of conjunctiva were obtained from 12 men, six of whom had AD and ocular complications. Five patients without atopic disease served as controls, plus one additional patient with asthma but no AD. A similar study was conducted using epidermal sheets obtained from two patients with AD and from one without AD. RESULTS: The number of CD1a+ cells present in the conjunctival epithelium of the patients with AD significantly exceeded that of the patients without AD. Most CD1a+ cells in the conjunctival epithelium and epidermis from the patients with AD bore IgE on their surfaces. Few such cells from patients without AD bore IgE. No CD23+ cells were found in the patients with or without AD. CONCLUSIONS: The presence of an increased number of LCs bearing IgE on their surfaces in the conjunctival epithelium of patients with AD suggests that these cells may be involved in eliciting the hypersensitivity reaction and participate in ocular inflammation.

Adolescent↗
PubMed1997

[Reproductive and developmental toxicity studies of landiolol hydrochloride (ONO-1101) (2). Teratogenicity study in rats].

A teratogenicity study of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously at a dose level of 0 (control), 25, 50 or 100 mg/kg/day to pregnant rats from day 7 to 17 of gestation, and effects of ONO-1101 on dams, fetuses and their offspring, were examined. In the 100 mg/kg/day group, hypoactivity, bradypnea, reddish lacrimation, clonic convulsion and loss of righting reflex were observed and 2 animals died. Food consumption in the 100 mg/kg/day group decreased during the treatment period. No drug-related changes were observed in dams for their body weights, necropsy findings or organ weights. Decrease in placental weight was seen in the 100 mg/kg/day group, but no effect was found in fetal weight. ONO-1101 had no effects on delivery and lactation. On day 4 after birth, viability of offspring were decrease in the 50 or 100 mg/kg/day group, and body weight of males were decreased in the 100 mg/kg/day group, but no change caused by the treatment was observed in growth of offspring thereafter. On skeletal examination in offsprings culled on day 4 after birth, increase in the incidence of unossificated talus were seen in the 50 or 100 mg/kg/day group. But no drug-related anomalies were observed in external, skeletal or visceral findings in fetuses. It was not also found any influence of ONO-1101 on external differentiations, functional, behavioral or learning abilities or reproductive performance in offspring. From the above results, it is estimated that the no-toxic dose level of ONO-1101 under these experimental conditions is 50 mg/kg/day for dams, and 25 mg/kg/day for their offspring.

Adrenergic beta-Antagonists↗
PubMed1997

[Reproductive and developmental toxicity studies of landiolol hydrochloride (ONO-1101) (4). Perinatal and postnatal study in rats].

A perinatal and postnatal study of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley(SD) rats. ONO-1101 was administered intravenously at a dose level of 0 (control), 25, 50 or 100 mg/kg/day from day 17 of gestation to day 20 after parturition to examine the effects on pregnancy, delivery, lactation and the effects on postnatal growth and development of offspring. In the 100 mg/kg/day group, hypoactivity, reddish lacrimation, clonic convulsion and bradypnea/apnea were observed after administration and 5 animals died in the treatment period, and body weight on day 21 and food consumption on day 14-21 of dam at weaning were lower than control group. In the 50 mg/kg/day group, reddish lacrimation was occasionally seen in some animals. ONO-1101 had no effects on pregnancy, delivery, lactation and necropsy findings or organ weights of dams. In the 100 mg/kg/day group, viability of offspring on day 4 after birth decreased and body weight gain of the suckling suppressed, but those changes recovered after weaning. On the skeletal examination of offspring culled on day 4 after birth, decrease in the mean number of osiffied phalanges of hindpaw and increase in the incidence of unossified talus bone were seen in the 100 mg/kg/day group, however, no delay of ossification was found form the weanling. There were no influence of ONO-1101 on external differentiation, functional, behavioral or learning abilities or reproductive performance in offspring. From the above results, it is estimated that the no-toxic dose level of ONO-1101 under these experimental conditions is 50 mg/kg/day for dam and offspring.

Adrenergic beta-Antagonists↗