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T Akatsu

Publications and source records attributed to T Akatsu.

At least 37 records · Page 2Linked to original sources
PubMed1997

Regulation by calcitonin and glucocorticoids of calcitonin receptor gene expression in mouse osteoclasts.

We previously studied regulation of the calcitonin (CT) receptor (CTR) by glucocorticoid (GC) and CT in cultures of mature mouse osteoclast-like cells (OCLs). The present studies were designed to examine the interaction of CT and GC in regulation of the CTR in osteoclasts and the molecular mechanisms involved. Treatment of OCLs with 10(-7) M dexamethasone (Dex) increased the CTR number in a time-dependent manner, whereas treatment with 10(-9) M salmon CT (sCT) reduced CTR number; neither treatment changed receptor affinity. Dex pretreatment somewhat antagonized the CT-induced reduction in [125I]sCT specific binding. Dex increased, and sCT pretreatment decreased, the sCT-responsive adenylate cyclase activity in parallel with the change in receptor binding. Dex treatment resulted in an increase in CTR messenger RNA (mRNA) levels, as assessed by reverse transcription-PCR, indicating that the increased CTR number was mediated by de novo CTR synthesis. This effect was specific to GCs and was not reproduced by mineralocorticoids or sex steroids. Treatment with sCT resulted in a rapid and profound reduction in CTR mRNA expression, and this reductions was somewhat delayed by Dex pretreatment. OCLs were treated with 5,6-dichloro-1 beta-D-ribofuranosyl benzimidazole to enable estimation of the mRNA decay rates in the absence of ongoing transcription. The stability of CTR mRNA was similar to the control value in Dex-treated OCLs, suggesting that the effect of Dex may be due to changes in transcriptional activity. Interestingly, transcriptional inhibition by 5,6-dichloro-1 beta-D-ribofuranosyl benzimidazole abolished the ability of CT to reduce CTR mRNA levels, suggesting that CT may act by increasing the rate of CTR mRNA decay, and that this effect requires ongoing transcription. The 3'-untranslated region of the mouse CTR mRNA contains four copies of the AUUUA motif, as well as other A/U-rich sequences, which have been shown to determine the stability of other mRNA transcripts. The stability results were consistent with the results of the nuclear transcript run-on assay, which indicated that treatment with Dex enhanced the rate of transcription, whereas CT had no effect. These results show that GC and CT influence CTR expression by distinct mechanisms and provide the basis for identification of the cellular factors involved.

Animals↗
PubMed1997

Lack of association between the Trp64 Arg mutation in the beta 3-adrenergic receptor gene and obesity in Japanese men: a longitudinal analysis.

The beta 3-adrenergic receptor (beta 3AR) is implicated in the regulation of thermogenesis and lipolysis, and it is suggested that the Trp64 Arg mutation in this receptor may contribute to the development of obesity. To examine whether the Trp64 Arg mutation had any effect on body weight during adult life, the beta 3AR genotype was determined in 186 unselected Japanese men, most of whom had records of body weight measured yearly from 25-53 yr of age. Of them, 26 subjects were diagnosed as having noninsulin-dependent diabetes mellitus (NIDDM) and 41 as having impaired glucose tolerance. There were 6 subjects (3%) with homozygous mutation, 67 (36%) with heterozygous mutation, and 113 (61%) with normal allele. Among the 3 genotypes, there were no significant differences in body mass index (BMI) at any age between 25-53 yr and the prevalence of NIDDM at the age of 53 yr. When longitudinal changes in body weight were compared between subjects with and without mutation, the former were less prone to gain weight than the latter. The frequency of the mutant allele was 1) not different among obese (BMI, > 26.4), intermediate (BMI, 22-26.4), and nonobese (BMI, < 22.0) subjects (0.21, 0.22, and 0.26, respectively; P = 0.77); 2) lower in subjects with NIDDM than in those without it, but the difference was insignificant (0.12 vs. 0.23; P = 0.07); and 3) similar between 186 unselected men and another group of 100 patients with NIDDM that were randomly selected for comparison (0.21 vs. 0.23). These results suggest that the beta 3AR is not a major contributing factor to obesity or NIDDM in Japanese men.

Adult↗
PubMed1997

[PTH infusion test].

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Diagnosis, Differential↗
PubMed1997

Orthotopic liver transplantation for adult-onset type II citrullinaemia.

Citrullinaemia is a rare autosomal recessive disorder due to a deficiency of argininosuccinate synthetase (ASS). While the clinical course of the adult onset form (Type II) is unpredictable, many patients undergo sudden deterioration with progressive cerebral oedema. Two patients with Type II citrullinaemia were referred for liver transplantation. One patient was successfully transplanted, and his plasma citrulline level decreased from 300 to 69 mumol/l (normal range 20-60 mumol/l); Fisher's ratio increased to a normal range within 24 h of transplantation. The other patient died from cerebral oedema, despite Optimal pharmacological measures, while awaiting a suitable donor organ. Dietary and pharmacological treatment is vital before liver transplantation. The level of serum arginine requires regulation, as it can rise secondary to citrullinaemia in Type II disease. An immunocytochemical study of the liver in both patients showed a clustered distribution of ASS which is associated with a dismal prognosis compared with patients who have a homogenous distribution. Distribution of ASS was normal in the transplanted liver. Liver transplantation is effective therapy for adult-onset Type II citrullinaemia. A clustered pattern of ASS distribution in a liver biopsy is a significant feature to activate early referral for liver transplantation.

Adult↗
PubMed1996

Role of nonenzymatic glycosylation of type I collagen in diabetic osteopenia.

Formation of advanced glycation end products (AGEs) in extracellular matrix (ECM) is implicated in the development of chronic diabetic complications. However, the involvement of AGEs in diabetic bone disease has not been well established. We have examined whether AGEs are increased in the bone collagen of streptozotocin-induced diabetic rats in vivo and whether glycation of type I collagen affects the functions of osteoblastic cells in vitro. During 12 weeks of observation, AGEs in collagen extracted from the tibiae of diabetic rats increased in a time-dependent manner and were significantly higher than controls at every time point. In vitro, the incubation of collagen with glucose-6-phosphate resulted in a time-dependent increase of AGEs. When osteoblastic cells isolated from fetal rat calvaria were cultured on AGE-modified type I collagen, it dose-dependently inhibited phenotypic expressions of osteoblasts. Among osteoblastic parameters, nodule formation was the most sensitive, being inhibited by approximately 70% by the glycation of collagen for only 1 week. Alkaline phosphatase activity and osteocalcin secretion were inhibited by 20-30% and 15-70%, respectively, by the glycation of collagen for 1-5 weeks. These results indicate that AGE-modified collagen affects osteoblastic cell differentiation and function in vitro and suggest that similar changes occurring in vivo may contribute to diabetic osteopenia.

Animals↗
PubMed1996

Parathyroid hormone regulates osteoblast differentiation positively or negatively depending on the differentiation stages.

The effects of parathyroid hormone (1-34) (PTH (1-34) on osteoblast differentiation were investigated using primary osteoblast-like cells isolated from newborn mouse calvaria. The osteoblast-like cells cultured at low cell densities, in which the cells remained in a subconfluent state at the end of culture, were exposed for 7 days to PTH. This stimulated alkaline phosphatase (ALP) activity in a dose-dependent manner. In contrast, PTH dose-dependently inhibited both ALP activity and osteocalcin production in cells inoculated at high cell densities, in which they had reached a confluent state before the end of culture. The changes of ALP activity by PTH were accompanied with the expression of ALP messenger RNA. PTH induced no changes of the hydroxyproline content in the cell layer when the cells were exposed to the hormone at a subconfluent state, but reduced the content at a postconfluent state. The stimulation of ALP activity by PTH at a preconfluent state was retained even after the removal of PTH from the culture media. The opposite effect of PTH, observed between the preconfluent and the postconfluent state, was reproduced by adding dibutyryl cyclic adenosine monophosphate (cAMP) or forskolin, but not by adding phorbol myristate acetate. In a colony-forming unit fibroblastic (CFU-F) assay, using bone marrow cells isolated from tibiae of 10-week-old mice, PTH induced no changes in the total number of CFU-Fs, but increased the proportion of ALP-positive colonies. These results indicate that PTH exerts opposite effects on the phenotypic expression of osteoblasts, depending on their differentiation stages of osteoblasts. PTH may preferentially stimulate osteoblast differentiation in immature osteoblasts but inhibit it in more mature cells.

Alkaline Phosphatase↗
PubMed1996

Assessment of the antiexudative and antiproliferative activities of non-steroidal anti-inflammatory drugs in inflammatory models developed in rats by subcutaneous implantation of bacterial cell walls from the dental plaque.

A purified bacterial cell walls suspension from human dental plaque were biochemically prepared to serve as flogogenous agent in producing experimental inflammatory models in rats. In the vascular permeability inhibition assay (edemogenic test), the subcutaneous implantation of the flogogenous agent elicited an acute inflammatory reaction highly susceptible to the effects of the non-steroidal anti-inflammatory drugs (NSAIDs). The intradermal injection of the flogogenous agent in the dorsum of rats developed experimental granulomas also susceptible to the anti-inflammatory effects of the NSAIDs. Otherwise, the antimitotic effect of drugs was carried out in the model of cellular proliferation of duodenal mucosa of rats by incorporation of tritiated thymidine (3H TdR) in the DNA. These models of acute and chronic inflammation, and the antimitotic model permitted us to evaluate the anti-inflammatory and antimitotic effects of sulindac, ibuprofen, naproxen and glucametacin. In the antiexudative activity, evaluated by the edemogenic test, naproxen was the more effective drug followed by sulindac, ibuprofen and glucametacin (in a decreasing order of potency) to inhibit the exudative response induced by the bacterial cell walls suspension, in all experimental periods. In the chronic anti-inflammatory activity, evaluated by the granuloma inhibition assay, all drugs were capable to demonstrate effectiveness against the development of the experimental granulomas induced by an intradermal injection of the flogogenous agent. In the model of cellular proliferation, all tested drugs demonstrated antimitotic activity in all experimental periods (4, 6 and 8 days), also. Sulindac induced the higher antimitotic effect, in all experimental periods, followed by ibuprofen, naproxen and glucametacin in a decreasing order of efficacy. There was a positive correlation between the antiexudative, anti-proliferative, and antimitotic effects.

Animals↗
PubMed1996

Bisphosphonates act on osteoblastic cells and inhibit osteoclast formation in mouse marrow cultures.

We examined the mode of action of bisphosphonates on osteoclastic cell recruitment using mouse marrow cultures with or without osteoblastic cells. Tartrate-resistant acid phosphatase-positive multinucleated cells [TRAP(+)MNC] formed in cultures were determined to be osteoclastic cells. In marrow cultures, TRAP(+) MNC formation in the presence of 10(-8) mol/L 1,25(OH)2D3 was not affected by the addition of 10(-6) mol/L dihydrogen (cycloheptylamino)-methylenebisphosphonate monohydrate (YM175). However, it was inhibited in cocultures of marrow cells with osteoblastic cells. The inhibitory effect was evident throughout the entire culture period. YM175 dose dependently inhibited TRAP(+) MNC formation, and other bisphosphonates--pamidronate and alendronate--also inhibited TRAP(+) MNC formation in the coculture. Similar observations were also made in the coculture of spleen cells with osteoblastic cells. The conditioned media of osteoblastic cells treated with 10(-6) mol/L YM175 inhibited TRAP(+) MNC formation in marrow cultures. The presence of YM175 in methylcellulose cultures affected neither the colony formation of monocyte-macrophage lineage, nor TRAP(+) MNC formation in the succeeding cocultures of recovered cells with osteoblastic cells. These results indicate that YM175 and probably other bisphosphonates as well preferentially inhibit the later stage of osteoclastogenesis through its action on osteoblastic cells. Our findings suggest that part of the inhibitory action by osteoblastic cells in the presence of bisphosphonates is mediated through soluble factor(s).

Acid Phosphatase↗
PubMed1995

A nationwide epidemiological survey of spinal cord injuries in Japan from January 1990 to December 1992.

This survey of traumatic spinal cord injuries in Japan from January 1990 to December 1992 was carried out by a statistical method of the nationwide epidemiological study. The number of the registered patients during these 3 years was 9752 and the mean response rate of every of the 47 prefectures was 51.4%. The registered patients with neurological deficits (Frankel A-D) were 7471 and the annual spinal cord injury incidence was 40.2 per million. The ratio of cervical cord injuries to more caudal SCI was 3:1. The age distribution and the causes of spinal cord injuries are presented in detail. From the results of this study, the prevention campaign should be focused mainly on the following topics: sports and motorcycle accidents involving young people; traffic accidents involving adults; falling accidents involving aged people.

Accidents, Occupational↗
PubMed1995

[Pseudohypoparathyroidism].

Pseudohypoparathyroidism (PsH) is a disease (or syndrome) characterized by biochemical abnormalities of hypoparathyroidism, increased serum PTH levels and the resistance to exogenous PTH. Since the first description of this disease by Albright et al, there has been substantial progress in understanding the pathogenesis of PTH resistance and the genetic basis for this disease. The differential diagnosis includes other forms of hypoparathyroidism, especially idiopathic hypoparathyroidism. Normocalcemic PsH, a rare and atypical subtype, has to be differentiated from pseudo-PsH (Albright's hereditary osteodystrophy without hypoparathyroidism). This review discusses current concepts and classification of PsH (types I a, I b, I c and II) and the recent demonstration of genetic defects in patients with type I a or I b of PsH. The pathophysiology and treatment of PsH will also be discussed.

Calcitriol↗
PubMed1995

[Pseudoidiopathic hypoparathyroidism].

Pseudoidiopathic hypoparathyroidism (PIHP) is a disease entity proposed by Nusynowitz et al. in 1973. The authors reported a patient with hypoparathyroidism who had normal to high levels of immunoreactive parathyroid hormone (PTH). Since the patient responded normally to exogenous PTH, they concluded that the most likely explanation for the pathogenesis was the production of PTH that was biologically inactive. PIHP is a very rare disorder and a limited number of patients have been reported, up to the present. Although some mutation of PTH gene is thought to be a possible cause of PIHP, no previous studies have detected genetic abnormalities. After briefly reviewing the original case of PIHP and other relevant case reports, this review discusses the diagnostic criteria for PIHP and a few problems in the differential diagnosis.

Diagnosis, Differential↗
PubMed1995

[Calcium].

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Calcium↗
PubMed1994

Glucocorticoid regulation of calcitonin receptor in mouse osteoclast-like multinucleated cells.

Abundant multinucleated cells (MNCs) are formed in cocultures of mouse osteoblastic cells and marrow cells in the presence of 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3], and these cells have the properties of osteoclasts (OCs). In this study using the mammalian OCs, we tried to clarify the role of glucocorticoids (GCs) in calcitonin receptors (CTR) and CT-responsive cAMP production in OCs. Dexamethasone (DEX) dose and time dependently enhanced the specific binding of [125I]salmon calcitonin (sCT). When the MNCs were preincubated with DEX for 24 h, the effect was evident at 10(-9) M and the maximum effect was obtained at 10(-7) M. The effect developed over 12-48 h at doses of 10(-9) and 10(-6) M DEX. The numbers of CTR-positive mononuclear cells and MNCs were not altered by the DEX treatment. Prednisolone and triamcinolone reproduced the DEX effect, but 17 beta-estradiol, progesterone, testosterone, aldosterone, and 1 alpha, 25(OH)2D3 did not. RU486, a GC receptor antagonist, attenuated the effect of DEX to enhance the specific binding of [125I]sCT. From a Scatchard plot analysis, DEX enhanced CTR number (212 +/- 64%) with a minimal change in the affinity to sCT. Autoradiographic studies using [125I]sCT showed that DEX enhanced the density of the grains on the tartrate-resistant acid phosphatase (TRAP)-positive MNCs and mononuclear cells, but not on other types of cells. DEX preincubation also enhanced sCT-stimulated but not prostaglandin E2- or forskolin-stimulated cAMP production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Spinal cord injuries in Japan: a nationwide epidemiological survey in 1990.

To survey the situation of traumatic spinal cord injuries (SCI) in Japan, the SCI Prevention Committee of the Japanese Medical Society of Paraplegia sent out by mail study charts in the form of questionnaires to institutions nationwide. Using the statistical method of the nationwide epidemiological survey described by Hashimoto et al,1 the annual estimated incidence was obtained from the number of patients registered, and from the questionnaire reply rate at each prefecture. The number of registered patients in 1990 was 3465 and the mean reply rate was 56.6%. There were 2665 registered patients with a neurological deficit (Frankel A-D) and the annual SCI incidence was 39.4 per million. The male:female ratio was 4.3:1 and the ratio of cervical cord injures to those caudal to the cervical cord was 2.9:1. The mean age at the time of injury was 48.5 years. The cause most frequently seen was traffic accidents, the second most frequent being falls from a height. Besides those two, sports injuries and falls on level ground were the third most frequent causes of SCI in the young generation and in elderly people respectively.

Accidental Falls↗
PubMed1994

Selective intrathecal phenol block to improve activities of daily living in patients with spastic quadriplegia. A preliminary report.

To eliminate severe leg spasms of 15 quadriplegics, 0.3 ml 10% phenol-glycerin was injected into the subarachnoid space at the T12/L1 interspace. The effectiveness for leg spasm was evaluated by the Penn spasticity and Ashworth rigidity scales. Three patients remained completely flaccid; however three had slight, six had moderate and three had complete recurrence of spasms in a follow up period of observation for 1 to 22 (average 13) months. The result of selective intrathecal phenol block was significantly valuable, improving the activities of daily living (ADL) of quadriplegic patients. There were no systemic side effects nor disturbance of bladder, bowel or sexual functions.

Activities of Daily Living↗