Novel usage of alendronate to prevent profound hypocalcemia immediately after parathyroidectomy in patients with severe secondary hyperparathyroidism.
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Alendronate↗
Biomedical subjects
T Hosoya
Publications and source records attributed to T Hosoya.
Clinical and neuroradiological features of intracranial vertebrobasilar artery dissection.
BACKGROUND AND PURPOSE: We sought to determine the clinical and neuroradiological features of intracranial vertebrobasilar artery dissection. METHODS: The clinical features and MR findings of 31 patients (20 men and 11 women) with intracranial vertebrobasilar artery dissections confirmed by vertebral angiography were analyzed retrospectively. The vertebral angiography revealed the double lumen sign in 11 patients (13 arteries) and the pearl and string sign in 20 patients (28 arteries). RESULTS: The patients ranged in age from 25 to 82 years (mean, 54.8 years). Clinical symptoms due to ischemic cerebellar and/or brain stem lesions were common, but in 3 cases the dissections were discovered incidentally while an unrelated disorder was investigated. Headache, which has been emphasized as the only specific clinical sign of vertebrobasilar artery dissection, was found in 55% of the patients. Intramural hematoma on T1-weighted images has been emphasized as a specific MR finding. The positive rate of intramural hematoma was 32%. Double lumen on 3-dimensional (3-D) spoiled gradient-recalled acquisition (SPGR) images after the injection of contrast medium was identified in 87% of the patients. The 3-D SPGR imaging method is considered useful for the screening of vertebrobasilar artery dissection. CONCLUSIONS: Intracranial vertebrobasilar artery dissection is probably much more frequent than previously considered. Such patients may present no or only minor symptoms. Neuroradiological screening for posterior circulation requires MR examinations, including contrast-enhanced 3-D SPGR. Angiography may be necessary for the definite diagnosis of intracranial vertebrobasilar artery dissection because the sensitivity of the finding of intramural hematoma is not satisfactory.
Adult↗
Positive and negative regulations of the renal 25-hydroxyvitamin D3 1alpha-hydroxylase gene by parathyroid hormone, calcitonin, and 1alpha,25(OH)2D3 in intact animals.
Reflecting the prime role of 1alpha,25(OH)2D3 in calcium homeostasis, the activity of 25-hydroxyvitamin D3 1alpha-hydroxylase, a key enzyme for 1alpha,25(OH)2D3 biosynthesis, is tightly regulated by 1alpha,25(OH)2D3, PTH and calcitonin. Its significant activity is found in kidney, though the enzymatic activity is also reported in extra-renal tissues. In the present study, we found that the 1alpha-hydroxylase gene abundantly expresses in kidney, and at low levels in other tissues and in some cell lines. Positive and negative regulations of 1alpha-hydroxylase gene by PTH, calcitonin, or 1alpha,25(OH)2D3 were observed at transcriptional levels in kidneys of animals and in a mouse proximal tubule cell line. Moreover, the protein kinase A inhibitor abrogated the PTH-mediated positive regulation. In mice lacking the vitamin D receptor, the 1alpha-hydroxylase gene expression was overinduced, and the inducible effect of either PTH or calcitonin, but not the repression by 1alpha,25(OH)2D3, was evident. Thus, vitamin D receptor is essential for the negative regulation by 1alpha,25(OH)2D3. Moreover, we demonstrate that renal 1alpha-hydroxylase gene expression in chronic renal failure model rats was decreased and the positive effect by PTH and calcitonin was diminished. The present study demonstrates that PTH and calcitonin positively regulate renal 1alpha-hydroxylase gene expression via PKA-dependent and independent pathway, respectively, and that 1alpha,25(OH)2D3 negatively regulates it mediated by vitamin D receptor. Furthermore, in a moderate state of chronic renal failure, renal cells expressing the 1alpha-hydroxylase gene appear to have diminished potential in response to PTH and calcitonin.
25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
p120 acts as a specific coactivator for 9-cis-retinoic acid receptor (RXR) on peroxisome proliferator-activated receptor-gamma/RXR heterodimers.
p120 was originally isolated as a novel nuclear co-activator for thyroid hormone receptor. In this study, we characterized its interaction and transactivation of peroxisome proliferator-activated receptor-gamma (PPARgamma) and 9-cis-retinoic acid receptor (RXR) heterodimers. Transient transfection study revealed that p120 enhanced the transcriptional activation of PPARgamma/RXR induced by PPARgamma- or RXR-specific ligands. In the glutathione-S-transferase pull-down assay, while steroid receptor coactivator-1 showed apparent interactions with both RXR and PPARgamma, p120 bound only to RXR in a 9-cis-retinoic acid (RA)-dependent manner and also did not bind to PPARgamma even in the presence of thiazolidinediones. The yeast two-hybrid analysis showed no interaction of p120 with PPARgamma under any conditions, and electophoretic mobility shift assay showed apparent DNA-PPARgamma/RXR/p120 complex formation only in the presence of 9-cis-RA. Furthermore, the yeast three-hybrid assay clearly revealed a significant interaction between p120 and PPARgamma via RXR of PPARgamma/RXR heterodimer only in the presence of 9-cis-RA. These findings indicate that p120 acts as a specific co-activator for the RXR of PPARgamma/RXR heterodimer in a 9-cis-RA-dependent manner.
Adipose Tissue↗
Asymmetric cell division of thoracic neuroblast 6-4 to bifurcate glial and neuronal lineage in Drosophila.
In the development of the Drosophila central nervous system, some of the neuroblasts designated as neuroglioblasts generate both glia and neurons. Little is known about how neuroglioblasts produce these different cell types. NB6-4 in the thoracic segment (NB6-4T) is a neuroglioblast, although the corresponding cell in the abdominal segment (NB6-4A) produces only glia. Here, we describe the cell divisions in the NB6-4T lineage, following changes in cell number and cell arrangement. We also examined successive changes in the expression of glial cells missing (gcm) mRNA and protein, activity of which is known to direct glial fate from the neuronal default state. The first cell division of NB6-4T occurred in the medial-lateral orientation, and was found to bifurcate the glial and neuronal lineage. After division, the medial daughter cell expressed GCM protein to produce three glial cells, while the lateral daughter cell with no GCM expression produced ganglion mother cells, secondary precursors of neurons. Although gcm mRNA was present evenly in the cytoplasm of NB6-4T before the first cell division, it became detected asymmetrically in the cell during mitosis and eventually only in the medial daughter cell. In contrast, NB6-4A showed a symmetrical distribution of gcm mRNA and GCM protein through division. Our observations suggest that mechanisms regulating gcm mRNA expression and its translation play an important role in glial and neuronal lineage bifurcation that results from asymmetric cell division.
Animals↗
Antiplatelet therapy decreases the incidence of erythropoietin-induced hypertension in predialysis patients.
The observation that antiplatelet therapy may decrease the incidence of Epo-induced hypertension in dialysis patients remains a subject of particular interest. The aim of the present study was to test this hypothesis in patients at the predialysis stage. Predialysis patients with renal anemia were treated with EPO (6000 IU/week) for 6-12 months. Patients were divided into two groups, one of which received antiplatelet therapy and the other did not, and a comparison was made between them with respect to the incidence of EPO-induced hypertension. Logistic regression analysis was used to determine the risk factors for developing hypertension during the EPO therapy. Such predictors included age, gender, antecedent of hypertension, antiplatelet drugs and diabetes mellitus. Overall, 66 patients were enrolled in the study and 18 developed hypertension (27%). Out of the 35 patients not receiving antiplatelet therapy, 15 developed hypertension (43%). In contrast, out of the 31 patients receiving antiplatelet therapy, only 3 (10%) developed hypertension (p=0.003 by Chi square test). Multiple regression analysis showed that the best predictive variables for the development of hypertension were antecedent of hypertension (odds ratio: 0.064, p=0.0118), and use of antiplatelet drugs (odds ratio: 5.081, p=0.0295). The present data provide evidence that antiplatelet therapy may prevent EPO-induced hypertension in predialysis patients. However, the mechanism to explain such an effect still remains to be elucidated.
Adult↗
Scyphostatin, a neutral sphingomyelinase inhibitor from a discomycete, Trichopeziza mollissima: taxonomy of the producing organism, fermentation, isolation, and physico-chemical properties.
We performed experiments to screen for neutral sphingomyelinase inhibitors using rat brain microsomes as an enzyme source. Among more than 10,000 microbial extracts tested, a mycelial extract of Trichopeziza mollissima SANK 13892 exhibited potent inhibitory activity. The active compound, scyphostatin, was purified by a series of chromatographies. Scyphostatin inhibited the enzyme with an IC50 value of 1.0 microM.
Amides↗
[A study of association between lean body mass and serum insulin-like growth factor-1 in continuous ambulatory peritoneal dialysis patients].
Malnutrition is one of the major issues associated with high mortality and morbidity in chronic dialysis patients. Several methods to evaluate the nutritional status of these patients have been attempted for example anthropometric measurement and biochemical parameters. Recently, it was reported that insulin-like growth factor-1 (IGF-1) has been valuable for estimating nutritional status. In this study, we measured lean body mass (LBM) by dual energy X-ray absorptiometry (DXA), IGF-1 and other biochemical parameters in 35 patients on CAPD. Two years later, the second measurement of LBM was performed, and we assessed the percent changes of LBM and biochemical parameters. There was negative correlation between the percent changes of LBM and the duration of CAPD. In patients treated with CAPD for less than 36 months (group I) LBM increased, however, it decreased significantly in those treated for more than 36 months (group II). On the other hand, in group I there was a positive correlation between the percent changes of LBM and IGF-1. In group II there was no correlation between the percent changes of LBM and any other biochemical parameters. It could be concluded that IGF-1 is one of the predisposing factors for improving LBM of patients on CAPD for a limited duration.
Absorptiometry, Photon↗
[Diffusion images on brain MRI in Creutzfeldt-Jakob disease].
We report a 72-year-old man with Creutzfeldt-Jakob disease. He showed a progressive dementia, myoclonus, and other neurological symptoms. DNA analysis showed a normal variation of prion gene (codon 129, Met/Met: codon 219, Glu/Glu). He had periodic synchronous discharge on electroencephalogram and brain atrophy on CT scan and MRI. Diffusion images on his brain MRI revealed a marked increase in signal intensity in the caudate nuclei, putamen, and cerebral cortices. These changes may represent spongy changes of the brain and seem to be a feature of brain MRI in Creutzfeldt-Jakob disease.
Aged↗
[Clinical characteristics of renal damage in patients with accidental hypothermia].
We have investigated the clinical characteristics of renal damage and associated complications of 79 patients with accidental hypothermia whom we encountered over the last 5 years. All patients were male, with an average age of 58.9 +/- 9.2 years. Most of these patients were homeless. Body temperature on admission was 29.3 +/- 3.0 degrees C. The most common clinical manifestations on admission were consciousness disturbance and severe hypotension. Complications, including increase in serum transaminase, alcoholism, pneumonia, liver cirrhosis, sepsis, diabetes mellitus, hypoglycemia, acidosis, and an increased level of serum CPK and amylase were found frequently on admission. Death within 48 hours after admission occurred in 23 cases (the death rate; 23/79 = 29%). Renal damage was found in 36 cases (36/79 = 46%), consisting of acute renal failure (ARF) in 27, and acute on chronic in 6. Urinary diagnostic indices suggested that the etiological factor for ARF was pre-renal, which responded well to passive rewarming and an appropriate fluid replacement therapy, resulting in full recovery in most of the cases (the recovery rate; 25/27 = 93%). Among patients with renal damage, there were no cases requiring dialysis. The present data suggest that accidental hypothermia is a fatal condition with an extremely high death rate. It also is associated with multiple complications including ARF. The main cause for ARF is pre-renal, possibly caused by cold diuresis or dehydration superimposed on the underlying diseases such as alcoholism, diabetes mellitus, liver cirrhosis. Such complications, independent of renal damage, determine the patient's prognosis.
Acute Kidney Injury↗
Evaluation of the substantia nigra in patients with Parkinsonian syndrome accomplished using multishot diffusion-weighted MR imaging.
BACKGROUND AND PURPOSE: Although it is important to evaluate the substantia nigra in patients with parkinsonian syndrome, it is difficult to depict its anatomy, even by MR imaging. Using anatomic studies of the direction of nerve fibers around the substantia nigra, we attempted to depict this entity with multishot diffusion-weighted MR imaging to evaluate its topographic changes in patients with Parkinson's disease and secondary parkinsonism. METHODS: We measured the substantia nigra on 72 diffusion-weighted axial MR images obtained in 36 healthy control subjects, on 47 images obtained in 25 patients with Parkinson's disease, and on 10 images obtained in five patients with secondary parkinsonism. We considered the width of the minor axis of the substantia nigra as its "thickness," which appeared as a crescent-shaped region in the midbrain. RESULTS: Diffusion-weighted imaging portrayed the substantia nigra distinctly better than did T2-weighted imaging, because the surrounding white matter appeared as an area of high signal intensity. The mean (+/- SD) thickness values of the substantia nigra were 5.1+/-0.89 mm in control subjects, 4.8+/-0.75 mm in patients with Parkinson's disease, and 3.4+/-0.53 mm in patients with secondary parkinsonism. CONCLUSION: Multishot diffusion-weighted imaging is a better imaging technique than T2-weighted imaging for demonstrating a change in size of the substantia nigra in vivo. The substantia nigra is not reduced in size in patients with Parkinson's disease, but it is reduced in patients with secondary parkinsonism.
Adult↗
[Analysis of risk factor for patients and renal survival in anti-myeloperoxidase antibody (MPO-ANCA) associated glomerulonephritis].
We investigated the clinical and histological features and the outcome of 15 patients with antimyeloperoxidase antibody(MPO-ANCA) associated glomerulonephritis. The patients were divided into two groups on the basis of renal functional outcome: Group 1 consisted of 7 patients where an initial deterioration in renal function was improved at the final observation. Group 2 included 8 patients who had a progressive deterioration in renal function leading to end stage renal disease or chronic dialysis, or who died. We compared the clinical and histological features at renal biopsy and the outcome following steroid therapy between the two groups. Group 1 patients had significantly lower levels of serum creatinine and UN, and higher values for creatinine clearance (Ccr) than Group 2 patients(1.9 +/- 0.6 vs. 6.7 +/- 4.7 mg/dl, 29 +/- 7 vs. 73 +/- 39 mg/dl, 30 +/- 9 vs. 10 +/- 5 ml/min, p < 0.05, respectively). Histologically, Group 1 patients had a significantly lower percentage of crescent formation than Group 2 patients(41 +/- 6 vs. 74 +/- 4%, p < 0.05), whereas there was no significant difference in tubulo interstitial damage between the 2 groups. Moreover, in 4 patients of Group 1 where a second renal biopsy was performed two months after steroid therapy, marked attenuation in acute tubulo-interstitial changes was observed in association with a rapid improvement of renal function. These results suggest that diffuse tubulo-interstitial inflammatory changes despite a relatively low frequency of cellular crescent formation may be a prognostically important histological feature showing a good response to steroid therapy.
Adolescent↗
[Factors influencing residual renal function of CAPD patients].
It is generally accepted that residual renal function has significant meaning in dialysis adequacy of CAPD patients. However, the factors influencing the residual renal function have not been investigated yet. We evaluated the consequences of following factors on residual urine volume in 50 CAPD patients: deterioration rate of renal function (slope of I/serum creatinine) before dialysis, renal creatinine clearance at the initial point of dialysis and the episodes of rapid reduction of residual urine volume. There was no correlation between the deterioration rate of renal function before dialysis and the residual urine volume. On the contrary, there was significant correlation between renal creatinine clearance at the initial point of dialysis and the residual urine volume in the first 4 years on CAPD. We recognized 67 episodes of rapid reduction of residual urine volume after initiation of CAPD. Inappropriate management or complications attributed to the rapid urine volume reduction in 50 episodes. The residual urine volume did not recover to the previous level in 40 episodes. We concluded that early initiation of CAPD and evasion of decreasing residual urine volume caused by inappropriate management or complications have important meaning and will preserve residual renal function of CAPD patients.
Adult↗
Molecular identification of the antigens recognized by monoclonal antibody JT95 specific for thyroid carcinomas.
JT95 is a monoclonal antibody (MAb) raised against the membrane fraction of differentiated thyroid carcinoma. JT95 specifically reacts to differentiated thyroid carcinoma, but not to benign thyroid tumor, normal tissue or other cancers. In this study, we purified the antigen by affinity-chromatography using MAb JT95 from spent culture medium of cell line SW1736, which was derived from a human thyroid carcinoma. The antigen was a glycoprotein having a molecular weight of 250,000 and its partial sequences obtained by peptide sequencing coincided with fibronectin. However, MAb JT95 reacted to the fibronectin purified from SW1736 but not to normal fibronectin, indicating modification of fibronectin was responsible for its antigenicity. Furthermore, immunochemical analysis of glycolipids extracted from SW1736 cells demonstrated that a second antigen was displayed on ganglioside. These results show that MAb JT95 recognized a novel antigenic epitope on a glycochain carried by both fibronectin and by a ganglioside produced by thyroid carcinoma cells.
Antibodies, Monoclonal↗
Urocortin, a newly identified corticotropin-releasing factor-related mammalian peptide, stimulates atrial natriuretic peptide and brain natriuretic peptide secretions from neonatal rat cardiomyocytes.
The effect of urocortin (UCN), a recently characterized mammalian member of corticotropin-releasing factor (CRF)-related peptide and a putative endogenous ligand for CRF type 2 beta receptor in the regulation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) release, was investigated using cultured neonatal rat cardiomyocytes. Treatment with UCN (10(-10)-10(-6)M) resulted in significant increase in ANP and BNP secretions, and the effect of UCN on ANP and BNP secretions was more potent than that of CRF on an equimolar basis. The effect of UCN (10(-7)M) was completely blocked by alpha-helical CRF (9-41), a specific CRF type 2 receptor antagonist. The effect of UCN (10(-7)M) was not only blunted by cAMP-dependent protein kinase A (PKA) inhibitor, H-89 (10(-5)M), but also diltiazem (10(-7)M), a voltage-dependent Ca2+ channel blocker. Further, UCN stimulated cAMP production in cardiomyocytes. Also, UCN (10(-7)M) itself stimulated [3H]leucine uptake into neonatal rat cardiomyocytes and potentiated endothelin-1-induced increase of [3H]leucine uptake. These results suggest that activation of CRF type 2 receptor, especially type 2 beta receptor, with UCN induces ANP and BNP secretions, at least in part, via PKA pathway during cardiac hypertrophy.
Animals↗
The promoter of the human 25-hydroxyvitamin D3 1 alpha-hydroxylase gene confers positive and negative responsiveness to PTH, calcitonin, and 1 alpha,25(OH)2D3.
25-Hydroxyvitamin D3 1 alpha-hydroxylase (1 alpha-hydroxylase) catalyzes hydroxylation, mainly in the kidney, of 25-hydroxyvitamin D3 [25(OH)D3] into 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], a hormonal form of vitamin D, acting as a key enzyme of vitamin D biosynthesis. Reflecting its biological significance, this enzymatic activity is differentially regulated by several factors involving calcium homeostasis, though the molecular mechanism is poorly understood. In our recent study (K. Takeyama, et al., 1997), we cloned the cDNA of mouse 1 alpha-hydroxylase, and this led us to investigate the regulation of gene expression and the function of the promoter of this gene. Here we report the isolation of the 5' flanking region of the human 1 alpha-hydroxylase gene and the identification of the human 1 alpha-hydroxylase promoter by a primer extension assay. We found that in the identified promoter, a positively regulatory region to parathyroid hormone (PTH) and calcitonin and a negatively regulatory region to 1 alpha,25(OH)2D3 are located around -4 and -0.5 kb, respectively. Thus, we provide direct evidence that the positive and negative regulation of 1 alpha-hydroxylase gene expression by hormones takes place at transcriptional levels through two distinct promoter regions.
Animals↗
Inflamed site-specific gene delivery using bone marrow-derived CD11b+CD18+ vehicle cells in mice.
We report a novel technique that may allow site-specific gene delivery into inflamed tissues. Bone marrow cells from DBA/2 mice were incubated for 7 days in L-929 cell-conditioned medium containing elements that favor the development of mononuclear cells, such as colony-stimulating factors. Flow cytometric analysis revealed that 99.1 +/- 0.9% of the subcloned cells were positive for CD11b and CD18, both of which are ligands of the intercellular adhesion molecule 1 (ICAM-1). These vehicle cells were labeled with a fluorescent lipophilic probe and returned intravenously to the DBA/2 mice. The mice then received, for 1 week, intraperitoneal injections of either lipopolysaccharide (LPS) to enhance ICAM-1 expression in the glomerulus, or saline as a control. In the LPS-treated mice, labeled vehicle cells were detected within the glomerulus cross-section (gcs) 24 hr after the first injection (0.73 +/- 0.10/gcs). The number of labeled vehicle cells within the glomerulus gradually increased for 1 week (1.47 +/- 0.19/gcs) and decreased after discontinuation of the LPS injections. However, in the saline-treated control group, only a negligible number of vehicle cells could be detected in the glomerulus (0.05 +/- 0.03/gcs). A second administration of LPS 4 weeks after injection of the vehicle cells was also able to promote accumulation in the glomerulus. Furthermore, immunohistochemical analysis revealed that the kinetics of the vehicle cell recruitment into the glomerulus corresponded to the level of ICAM-1 expression. On the assumption that the LPS-induced ICAM-1 expression may regulate the site and timing of the delivery of vehicle cells into the glomerulus, vehicle cells were transduced with human glucocerebrosidase (GC) gene, using an adenovirus vector, and reintroduced into the mice. The basal expression of GC gene in the isolated glomeruli of vehicle cell-treated mice rose by 1.7-fold compared with endogenous activity, whereas the GC activity was enhanced 3.2-fold by LPS treatment. Polymerase chain reaction designed to detect human GC-specific sequence revealed that isolated glomeruli of vehicle cell-treated mice contained exclusively the vehicle cell-oriented GC. This indicates that vehicle cells can be used to carry a certain gene to a specific inflamed site. Injection of vehicle cells, with or without LPS, had small effect on urinary protein excretion or serum creatinine levels. These findings suggest that our novel method allows site-specific gene delivery into inflamed glomeruli through interaction of adhesion molecules.
Animals↗
[IgD-type multiple myeloma with confirmation of improvement in renal pathology achieved by chemotherapy].
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Adult↗