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Biomedical subjects

K Higuchi

Publications and source records attributed to K Higuchi.

At least 235 records · Page 13Linked to original sources
PubMed1996

A radioresistant variant cell line, NMT-1R, isolated from a radiosensitive rat yolk sac tumour cell line, NMT-1: differences of early radiation-induced morphological changes, especially apoptosis.

A radioresistant variant cell line, NMT-1R, was isolated by repeated radiation exposure of a radiosensitive rat yolk sac tumour cell line, NMT-1, producing alpha-fetoprotein, with the potential for lymphatic metastasis in the inbred Wistar rat. Cultured NMT-1R cells showed more cobblestone-like appearances, although the morphological features were almost the same as radiosensitive NMT-1 cells reported previously. The doubling time of NMT-1R cells was 13.6 h, being shorter than that of NMT-1 cells (16.0 h). For NMT-1R cells, D0 for radiation sensitivity was 165 +/- 3 cGy, 1.7 times as large as for NMT-1 cells. The extrapolation number, n, was 1.48 +/- 0.17 for NMT-1R cells although that for NMT-1 cells was 1.08 +/- 0.15. The surviving fractions at 2 Gy (SF2) were 0.42 for NMT-1R cells and 0.28 for NMT-1 cells. The population of G2-M phase for NMT-1R cells was larger than for NMT-1 cells (32.5 versus 26.8%) in exponentially growing cells. Although a clear G2 delay was observed after irradiation with a dose of 182 cGy for both cell lines, NMT-1R cells had a shorter recovery time from G2 block than NMT-1 cells, G1 arrest was observed in NMT-1 cells. NMT-1 cells showed much higher incidence of early morphological changes, especially apoptosis, after irradiation with a dose > 500 cGy compared with NMT-1R cells.

Animals↗
PubMed1996

Clinical significance of measurements of antithyroid antibodies in the diagnosis of Hashimoto's thyroiditis: comparison with histological findings.

Measurements of antithyroglobulin and antimicrosomal (antiperoxidase) antibodies have been performed widely for the clinical diagnosis of autoimmune thyroid diseases. The present study was designed to compare these antibody titers with histological findings of the thyroid in patients with diffuse goiter who were suspected of having Hashimoto's thyroiditis. One hundred and ten euthyroid or hypothyroid patients (10 males and 100 females; age 48 +/- 15 (SD) years old) with diffuse goiter were studied for the measurement of antithyroglobulin and antimicrosomal or antiperoxidase antibodies by a hemagglutination technique (TGHA and MCHA, respectively) and by a newly developed radioassay (TgAb and TPOAb, respectively). The antibody titers were compared with the histological findings obtained by needle biopsy. TgAb, TPOAb, TGHA, and MCHA were detected in 80 (96.4%), 61 (73.5%), 37 (44.6%), and 54 (65.1%) of 83 patients with histologically proven Hashimoto's thyroiditis, respectively, but in only one (3.7%) of 27 patients without any inflammatory changes in the biopsy specimen. In 55 patients with negative TGHA and MCHA, the TgAb positivity was more closely associated with the histological diagnosis of Hashimoto's thyroiditis than the TPOAb positivity was, the incidence of each antibody in Hashimoto's thyroiditis being 89.7% (26/29) and 27.6% (8/29), respectively. In conclusion, the histological diagnosis of Hashimoto's thyroiditis can most precisely be predicted by the newly developed radioassay for TgAb.

Adolescent↗
PubMed1996

Accelerated senile amyloidosis induced by amyloidogenic Apoa-II gene shortens the life span of mice but does not accelerate the rate of senescence.

The SAMP1 strain is a mouse model for accelerated senescence and severe senile amyloidosis. We studied the effects of the amyloidogenic apolipoprotein A-II gene (Apoa2c) on senile amyloidosis and the life span and progress of senescence of congenic mice (R1.P1-Apoa2c) which have Apoa2c of the SAMPI strain on the genome of the normally aging SAMR1 strain. Age-associated and severe amyloid deposits were detected in R1.P1-Apoa2c, as well as a 20% shorter life span than that of SAMR1. The scores of senescence increased more rapidly with age in R1.P1-Apoa2c than that of SAMR1, and the Gompertz function showed a bigger Y intercept but the same slope of regression line. These results suggest that severe senile amyloidosis induced by the Apoa2c gene shortens the life span of mice but does not accelerate the rate of senescence.

Aging↗
PubMed1996

Abnormal expression of sphingomyelin acylase in atopic dermatitis: an etiologic factor for ceramide deficiency?

Previously, we demonstrated that there is a marked reduction in the amount of ceramide in the stratum corneum of both lesional and nonlesional forearms in atopic dermatitis (AD), suggesting that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry and barrier-disrupted skin. In this study, we investigated, as a possible mechanism involved in the ceramide deficiency, whether sphingomyelin (SM) metabolism is altered in AD as compared to normal controls. In stripped stratum corneum and biopsied whole epidermis of patients with AD, SM hydrolysis as measured at pH 4.7 using [choline-methyl-14C]sphingomyelin as a substrate were markedly increased by 27- and 7-fold, respectively. Radio-thin-layer chromatography of the reaction products revealed that, whereas the SM hydrolysis in age-matched normal controls were associated with sphingomyelinase (SMase) that degrades SM to yield ceramides and phosphorylcholine (PC), most of the SM hydrolysis detected in AD were attributable not to the SMase but to a hitherto undiscovered epidermal enzyme, SM acylase, which releases free fatty acid and sphingosyl-PC (Sph-PC) instead of ceramides. The potential of this acylase-like enzyme to generate Sph-PC through SM hydrolysis was corroborated by thin-layer chromatographic analysis of the reaction products obtained using porcine kidney acylase, followed by high-performance liquid chromatography-mass spectrometry. Furthermore, Sph-PC was also detected by high-performance liquid chromatography-mass spectrometry after incubation of SM with atopic stratum corneum samples. On the other hand, the stratum corneum of patients with contact dermatitis or chronic eczema exhibited neither increased SM hydrolysis nor the generation of Sph-PC upon radio-thin-layer chromatographic analysis. These findings suggest that SM metabolism is altered in AD, resulting in a decrease in levels of ceramides, which could be an etiologic factor in the continuous generation of atopic dry and barrier disrupted skin observed in AD.

Amidohydrolases↗
PubMed1996

Immunohistochemical study with anti-advanced glycation end-products antibody in murine amyloidosis.

Advanced glycation end-products (AGE) are formed in the late phase of the non-enzymatic glycosylation reaction in conditions such as diabetes mellitus and aging. In amyloidosis, AGE have been found in the A beta 2M amyloid associated with long-term hemodialysis and in the beta-protein in Alzheimer's disease. Murine AApoAII and AA amyloidosis were examined immunohistochemically using anti-AGE monoclonal antibody, 6D12. AApoAII amyloid deposits studied in one senescence-accelerated mouse P1 (SAMP1), congenic mice that have the amyloidogenic apolipoprotein A-II of SAMP1 mice, and AKR mice all reacted with biotinylated 6D12 by formic acid pretreatment, whereas AA amyloid deposits did not react with the antibody. The immunoreaction with anti-apolipoprotein A-II for amyloid deposits in senile mice was approximately homogeneous in intensity; on the other hand the reaction with biotinylated 6D12 was irregular in distribution and intensity over the amyloid deposits. These findings suggest that amyloid precursor proteins are not associated uniformly with AGE modification before deposition as amyloid; it is more likely that the AGE modification progresses gradually and unevenly after amyloid deposition. Murine amyloidosis may be a useful model to elucidate the role of AGE in amyloidosis.

Amyloidosis↗
PubMed1996

Salivary duct carcinoma: a clinicopathologic study of three cases with a review of the literature.

Three cases of salivary duct carcinoma are presented. They occurred in a 60 year old man, a 66 year old man and a 57 year old woman. All of the lesions were located in the parotid gland. The tumor size ranged from 3 to 5 cm across the largest diameter. Facial paralysis was observed in two cases. Histologically, intraductal and invasive adenocarcinoma showing papillary, cribriform, and solid patterns with comedolike necrosis was observed. Immunohistochemically, the tumor cells were positive for keratin and epithelial membrane antigen. No myoepithelial cells were demonstrated within the tumor by staining for S-100 protein, alpha-smooth muscle actin or muscle specific actin. Ultrastructurally, intracytoplasmic lumina with microvilli, a moderate number of mitochrondria, lysosomes, and tight junctions were found. Regional lymph node metastasis was observed in one case, and distant metastasis developed in two cases. All of the patients were treated with adjuvant postoperative irradiation. One patient died of disease at 11 months after the initial diagnosis, another was alive with disease at 8 months, and the third patient was alive without disease at 2 years and 3 months. Salivary duct carcinoma should be differentiated from low-grade salivary gland carcinomas using morphologic and clinical criteria because of its poor prognosis even with aggressive therapy.

Adenocarcinoma↗
PubMed1996

15-lipoxygenase metabolite(s) of arachidonic acid mediates adrenocorticotropin action in bovine adrenal steroidogenesis.

The acute activation of adrenal glucocorticoid synthesis by ACTH has long been believed to be mediated by cAMP as the major second messenger, although increases in cellular cAMP concentration have not been observed at low concentrations of ACTH. We found that steroidogenesis in bovine adrenal fasciculata-reticularis cells was activated by the addition of arachidonic acid or its 15-lipoxygenase metabolite, 15-hydroperoxyeicosatetraenoic acid. The cellular 15-lipoxygenase pathway was significantly activated by 1 pM ACTH, at which concentration no increase in cellular cAMP synthesis was observed. The 1 pM ACTH-induced stimulation of steroidogenesis was completely suppressed by a lipoxygenase inhibitor, AA-861. The stimulation was independent of the increase in cellular cAMP. These results show that the action of 1 pM ACTH on steroidogenesis may be mediated by the 15-lipoxygenase metabolite(s) as a solo second messenger. The addition of ACTH at concentrations higher than 10 pM increased both the 15-lipoxygenase activity and cellular cAMP synthesis. Under these conditions, the 15-lipoxygenase metabolite(s) and cAMP were shown to mediate the activation of steroidogenesis synergistically. The presence of a dual second messenger system could explain the stimulation of steroidogenesis by ACTH at physiological concentrations.

Animals↗
PubMed1996

Calcitonin decreases corticosterone-induced skeletal muscle calpain activity.

The effects of calcitonin (CT) administration on calcium (Ca) concentrations in plasma and skeletal muscle as well as the calpain activity of skeletal muscle were examined in young growing male rats treated with corticosterone (CTC). The rats received subcutaneous injections of CTC (5 mg/100 g body weight/day), or both CTC and CT (100 m unit/100 g body weight/day) for four days. Control rats received placebos. The rats were sacrificed 24 h after the final injections, and blood was taken followed by dissections to remove gastrocnemius and extensor digitorum longus muscles. Plasma Ca concentration was increased and muscle Ca concentration and its calpain activity tended to be increased by CTC. The CTC-induced increases in muscle Ca concentration and its calpain activity were significantly minimized by the simultaneous injection of CT. However, CTC-induced hypercalcemia was not minimized by CT. The present observations indicate that CT decreases Ca concentration in skeletal muscle cell and its calpain activity, followed by a suppression of muscle proteolysis in rats treated with CTC.

Animals↗
PubMed1996

Basic performance of a miniature intraventricular axial pump.

A miniature intraventricular axial pump for left ventricular (LV) support is under development. This pump was designed for placement in the LV cavity by insertion through the LV apex with the outlet located at the ascending aorta via the aortic valve. The basic hydrodynamic characteristics represented as a relationship between pump head (H) and flow (Q) showed a negative linear relationship under a constant head. This characteristic was generally the same as that obtained by other axial rotation pumps. However, the actual H-Q relationship was represented as anticlockwise "loops" caused by the contraction of the natural LV. The comparative in vitro data on these H-Q loops showed that the shape of the loops was changed drastically by the connecting condition between the pump and natural cardiovascular system.

Animals↗
PubMed1996

[Neoadjuvant intra-arterial infusion chemotherapy in over stage III and inflammatory carcinoma of the breast].

From 1991 to 1996, 11 eligible patients (median age 50.4 years, range 33-71 years) with over Stage III and inflammatory breast carcinoma have been treated with neoadjuvant intra-arterial infusion chemotherapy. There were three Stage III a, one III b, three IV and four inflammatory carcinoma. Patients were treated with Epirubicin (10) and Doxorubicin (1), with a total amount of 120-190 mg. Three cases were combined with endocrine therapy (MPA 1,200 mg). In terms of morphological efficacy, 10 of 11 achieved PR, and three of those with endocrine therapy had over Grade 2 in histological efficacy. Carcinoma cells were especially deceased in one inflammatory carcinoma with MPA. Three of 11 died of liver metastasis, the others are still alive (median 24.5 months, range 7-51 months). Combined endocrine therapy should be considered applicable for the treatment strategy of the breast carcinoma.

Adult↗
PubMed1995

Purification and biochemical characterization of membrane-bound epidermal ceramidases from guinea pig skin.

Ceramidase (CDase) catalyzes the hydrolysis of ceramides to yield sphingosine and fatty acid. In this paper, two forms of membrane-bound alkaline ceramidase, have been, for the first time, purified from guinea pig epidermis by chromatography on DEAE-cellulose, phenyl-Superose, HCA-hyroxyapatite, isoelectric focusing, Mono Q, and TSK-3000SW column. One species (CDase-I) migrated upon SDS-polyacrylamide gel electrophoresis as a single band with an apparent molecular mass of 60 kDa; the other (CDase-II) was only partially purified with apparent M(r) of about 148,000 estimated by gel filtration. The specific activities of the two species increased by 1.130- (for CDase-I) and 400-fold (for CDase-II) over the original tissue extract. The activity of both enzymes for ceramide species decreased in the order of linoleoyl > oleoyl > palmitoylsphingosine. The optimal pH for enzyme activity was approximately 7.0-9.0 for CDase-I and 7.5-8.5 for CDase-II. Interestingly, both enzymes were inhibited by the reaction product sphingosine with a concentration for half-maximal inhibition (ID50) of 100-130 microM, compared to the apparent kinetic parameters with CDase-I (Km = 90 microM, Vmax = 0.62 unit) and CDase-II (Km = 140 microM, Vmax = 0.50 units). Some lipids, such as phosphatidylcholine and sphingomyelin, are also inhibitory with IC50 values of 50-250 microM, suggesting well controlled CDase activity by sphingolipid metabolites. These studies begin to elucidate a regulatory mechanism for the balance of the ratio of ceramide/sphingosine which can serve as an intracellular effector molecule in epidermis.

Amidohydrolases↗
PubMed1995

Minimal deviation adenocarcinoma of endometrioid type may arise in the isthmus: clinicopathological and immunohistochemical study of two cases.

Clinicopathological and immunohistochemical features of minimal deviation adenocarcinoma (MDA) of endometrioid type which may have arisen in the isthmus are presented. Hysterectomy specimens from two women, one 39 years of age and the other 64 years of age, showed the presence of endometrioid-type adenocarcinoma with minimal atypia and without back-to-back arrangement of the glands, which was consistent with a histological diagnosis of endometrioid MDA. However, the tumorous glands were most abundant in the isthmus, and extensively infiltrated into the cervical stroma, vagina, parametrium, and corpus in one case, and the tumor was confined to the isthmus in the other. Immunohistochemically, the tumorous glands were CEA-positive and vimentin-negative in both cases. p53 protein expression was found in one case. Histogenetic origin of MDA of endometrioid type is discussed.

Adult↗
PubMed1995

Short-latency trigemino-cervical reflexes in man.

We describe a reflex evoked in neck muscles by stimulation of afferent fibres in the trigeminal nerve. The clearest responses were seen in averaged, unrectified, monopolar surface electromyographic (EMG) recordings from active sternocleidomastoid muscles after stimulation of the infraorbital nerve. They consisted of a bilateral positive/negative (p19, n31) wave with a mean onset latency of 12.9 ms which corresponded to a period of inhibition in the underlying motor unit activity. Responses also could be seen in splenius and trapezius, but not in arm muscles. Stimuli to other branches of the trigeminal nerve (supraorbital or mental) did not produce such clear effects. The threshold for the reflex was relatively low (2-4 times perceptual threshold) and its size scaled with the level of background EMG in an approximately linear fashion. Responses to infraorbital stimulation did not interact with other short-latency inhibitory responses in the sternocleidomastoid muscle evoked by loud acoustic clicks or stimulation of the median nerve at the wrist. We suggest that the infraorbital response is part of a head withdrawal reflex involving an oligosynaptic trigemino-cervical system similar to that described in the cat.

Acoustic Stimulation↗
PubMed1995

Age-related decrease of nerve growth factor-like immunoreactivity in the basal forebrain of senescence-accelerated mice.

The senescence-accelerated mouse P10 (SAMP10) is a murine model of accelerated senescence characterized by the deterioration of learning and memory with advancing age. In the present study, we examined the distribution of nerve growth factor (NGF) immunohistochemically in SAMP10 mice and its control strain, SAMR1. In both strains, NGF-like immunoreactivity (NGF-IR) was observed in neurons throughout the entire forebrain and in glial cells in a particular location. In aged SAMP10 mice, each layer of the cerebral cortex retained its NGF-IR, although the thickness of the cortical mantle was markedly decreased in comparison with younger animals. There was an age-related decline in NGF-IR in the substantia innominata of SAMP10 mice at the age of 10 months, when compared to 2-month-old SAMP10. These results indicate age-related decrease of NGF in the basal forebrain in SAMP10 mice.

Age Factors↗
PubMed1995

Zinc deficiency delays gastric ulcer healing in rats.

Zinc is an important element in wound healing. Zinc compounds hasten the healing of gastric ulcers, by an unknown mechanism(s). We studied the effect of the induction of zinc deficiency on gastric ulcer healing. Rats were given a control or zinc-deficient diet for six weeks and then subjected to the induction of acetic acid-induced chronic gastric ulcers. Four days later, zinc-deficient rats were divided into two groups. In the first group, the zinc-deficient diet was continued. In the second group, the diet was changed to the control diet. Zinc-deficient rats had a mean serum zinc concentration approximately 70% of that in controls. Zinc deficiency did not affect the formation of gastric ulcers; however, it reduced cell proliferation by day 4 and delayed ulcer healing. Zinc supplementation brought zinc to control levels within a week, but failed to reverse the delay in ulcer healing. We conclude that zinc is crucial for healing of gastric ulcers, especially at the early stage.

Acetates↗
PubMed1995

Age-related changes in the static and dynamic mechanical properties of mouse lungs.

To investigate the effects of aging on pulmonary mechanical properties in mice, we devised a new experimental apparatus to measure the respiratory impedance of excised lungs in mice and examined age-related changes in both static and dynamic properties. In an accelerated senescence-resistant strain of mice, SAMR1 (Takeda, T., Y. Fukuchi, Y. Uejima, K. Teramoto, T. Oka and H. Orino, J. Am. Geriatr. Soc. 39: 911-919, 1991), ranging from 3 to 24 months of age, static compliance (Cst) as well as total lung capacity increased significantly with age, whereas specific compliance and the K value, as determined by exponential analysis, showed no significant change. In the dynamic study, dynamic compliance (Cdyn) increased significantly with age, whereas the frequency dependence of Cdyn (Cdyn/Cst) did not vary with age. From these results we concluded that lung elasticity, normalized to lung volume, remained constant with age and that the effects of aging on pulmonary mechanics might be solely derived from increases in lung volume in the SAMR1 strain of mice.

Age Factors↗