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K Tashima

Publications and source records attributed to K Tashima.

At least 55 records · Page 3Linked to original sources
PubMed1996

Overexpression of Ca2+/calmodulin-dependent protein kinase II inhibits neurite outgrowth of PC12 cells.

To investigate the physiological role of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in neuronal differentiation, we transfected the cDNA of the alpha subunit of mouse CaM kinase II (CaM kinase II alpha) into PC12 cells and established clonal cell lines that constitutively express the transfected CaM kinase II alpha gene. The expression of CaM kinase II alpha was confirmed by northern blot and immunoblot analyses. Northern blot analysis showed that the gamma and delta subunits of CaM kinase II are mainly expressed in PC12 cells. Treatment of the cells with ionomycin activated CaM kinase II alpha through autophosphorylation and generation of the Ca2+/calmodulin-dependent form. It is interesting that the neurite outgrowth induced by dibutyryl cyclic AMP was inhibited in these cell lines in accordance with the activities of overexpressed CaM kinase II alpha. The activity of cyclic AMP-dependent protein kinase showed similar levels among these cell lines. These results suggest that CaM kinase II is involved in the modulation of the neurite outgrowth induced by activation of the cyclic AMP system.

Animals↗
PubMed1996

Update of HIV and AIDS in North America.

The second wave of the HIV epidemic, which increasingly affects injection drug users, women, and minorities, necessitates the development of primary care HIV services so that these individuals may benefit from new therapies. The ability to dramatically decrease vertical transmission of HIV from mother to child with antiretroviral therapy is encouraging. Better understanding of HIV pathogenesis, disease progression, antiviral therapy, and opportunistic infection prophylaxis are leading to more effective therapy and prevention. Clinical trials are ongoing to assess the efficacy of protease inhibitors in combination with nucleoside analog antiretroviral therapy to provide long term viral suppression and alter the natural history of HIV. Prophylaxis of pneumocystis, toxoplasma, MAC, TB, and invasive fungal infections is cost effective and leads to improved quality of life.

AIDS-Related Opportunistic Infections↗
PubMed1995

Change in variant transthyretin levels in patients with familial amyloidotic polyneuropathy type I following liver transplantation.

Three patients with familial amyloidotic polyneuropathy (FAP) type I underwent liver transplantation from heart-beating cadaveric donors. Since 2 patients underwent blood transfusion during the operation, variant transthyretin (TTR) levels in the plasma did not decrease time dependently. However, in 1 patient without blood transfusion variant TTR levels decreased in a time dependent manner and plasma half life of variant TTR was calculated to be 2.1 days. Total protein, normal, and variant TTR levels in cerebrospinal fluid (CSF) remained unchanged after liver transplantation.

Adult↗
PubMed1995

Dephosphorylation of abnormal sites of tau factor by protein phosphatases and its implication for Alzheimer's disease.

The abnormally phosphorylated forms of tau factor are major constituents of neurofibrillary tangles in Alzheimer's disease brain. In order to investigate protein phosphatases which are related to dephosphorylation of abnormal phosphorylation sites, we examined the dephosphorylation of tau factor phosphorylated by three proline-directed type protein kinases. Tau factor phosphorylated by cdc2 kinase and tau protein kinase II was dephosphorylated by the holoenzyme of protein phosphatase 2A and calcineurin, while either the catalytic subunit of protein phosphatase 2A or protein phosphatase 2C could not catalyze the dephosphorylation. From the kinetic analysis, we concluded that tau factors phosphorylated by the protein kinases serve as good substrates for protein phosphatase 2A and calcineurin. On the other hand, tau factor phosphorylated by glycogen synthase kinase 3 alpha was dephosphorylated by the catalytic subunit of protein phosphatases 2A as well as the holoenzyme of protein phosphatase 2A and calcineurin. It has been reported that serines 199, 202 and 396 according to the numbering of the longest human tau isoform are among the major abnormal phosphorylation sites of tau factor. We synthesized two phosphopeptides which contained phosphoserines 199 and 202 or phosphoserine 396 and prepared the polyclonal antibodies specific for the phosphopeptides. Using these antibodies, we confirmed that the holoenzyme of protein phosphatase 2A and calcineurin could dephosphorylate phosphoserines 199, 202 and 396 in tau factor. The catalytic subunit of protein phosphatase 2A could dephosphorylate phosphoserine 396 but not phosphoserines 199 and 202. Neurofibrillary tangles in Alzheimer's disease brain were immunostained with both antibodies but the normal neurons in the normal aged brains were not. The results suggest that protein phosphatase 2A and calcineurin can be involved in the dephosphorylation of abnormal phosphorylation sites in tau factor and that the dephosphorylation of phosphoserine 396 is differently regulated from phosphoserines 199 and 202.

Aged↗
PubMed1995

Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) by proline-directed protein kinases and its dephosphorylation.

We identified two major substrates for the proline-directed protein kinases--cdc2 kinase and tau protein kinase II (TPKII)--in the cytosol fraction from rat brains. The molecular masses of the proteins were 80 and 46 kDa. Because the 80-kDa protein was phosphorylated by protein kinase C and was heat stable, we examined the possibility that the protein might be myristoylated alanine-rich C kinase substrate (MARCKS). On the basis of a comparison between the properties of the 80-kDa protein and purified MARCKS, we concluded that the 80-kDa protein is indeed MARCKS. The amounts of phosphate incorporated into MARCKS by protein kinase C, cdc2 kinase, and TPKII were 1.7, 1.4, and 0.6 mol/mol of the protein, respectively. Two-dimensional tryptic peptide mapping indicated that phosphorylation sites by protein kinase C and proline-directed protein kinases completely differed. Only the seryl residue was phosphorylated by protein kinase C, whereas both seryl and threonyl residues were phosphorylated by cdc2 kinase and TPKII. Phosphorylation of MARCKS by protein kinase C inhibited the binding to calmodulin, whereas phosphorylation by cdc2 kinase and TPKII significantly increased the binding to calmodulin. The holoenzyme of protein phosphatase 2A dephosphorylated MARCKS that had been phosphorylated by protein kinase C, cdc2 kinase, or TPKII, whereas calcineurin was unable to dephosphorylate it. These results suggest that cdc2 kinase and TPKII regulate the functions of MARCKS in different ways from protein kinase C.

Animals↗
PubMed1995

Dephosphorylation of fetal-tau and paired helical filaments-tau by protein phosphatases 1 and 2A and calcineurin.

We have reported that many sites of tau in fetal brain (fetal-tau) as well as in paired helical filaments (PHF-tau) are phosphorylated. In the present study, we used site-specific antibodies and peptide mapping to examine protein phosphatases involved in dephosphorylation of fetal-tau and PHF-tau. Immunoblot analysis and electrophoretic mobility showed that protein phosphatases 1 and 2A and calcineurin could dephosphorylate fetal-tau and PHF-tau. Phosphoserines 199, 202, 396, and 413 and phosphothreonine 231, numbered according to the longest human tau isoform, were dephosphorylated, as shown by the immunoblot analysis. Phosphoserine 422 was dephosphorylated by protein phosphatase 2A and calcineurin, but not by protein phosphatase 1. Peptide mapping with Achromobacter lyticus protease 1 showed that phosphoserines 199, 202, 235, and 396 and phosphothreonine 231 were dephosphorylated by protein phosphatases. Fetal-tau was more rapidly dephosphorylated by protein phosphatase 2A and calcineurin than PHF-tau. Interestingly, PHF-tau which had not been solubilized with guanidine HCl was little dephosphorylated by protein phosphatases. Thus, PHF-tau in neurofibrillary tangles of Alzheimer's disease brain is likely to be resistant to dephosphorylation by protein phosphatases.

Amino Acid Sequence↗
PubMed1995

Change in the age of onset in patients with familial amyloidotic polyneuropathy type I.

To investigate the influence of environmental factor(s) on the pathogenesis of familial amyloidotic polyneuropathy (FAP) type I, the age of onset in 33 FAP patients in the Arao district of Kumamoto Prefecture in Japan and in 20 of their ancestors to the 3rd prior generation was carefully examined. The age of onset in FAP patients progressively became younger. This tendency was more apparent in female FAP patients than in male patients. Since the pathogenesis of amyloid formation in FAP as well as other amyloidosis diseases is not still elucidated, this phenomenon may be of interest.

Adolescent↗
PubMed1995

[Familial amyloidotic polyneuropathy (FAP) type I and the therapies].

Since autonomic dysfunction in familial amyloidotic polyneuropathy (FAP) Type I is recognized in the early stage of FAP patients and restricts their daily life, we developed various therapies for various autonomic manifestations: Loading glucose was often effective for faintness caused by hypoglycemia and erythropoietin was also good therapy for orthostatic hypotension as well as anemia found in the end stage of FAP patients. Stoma and nasal drop of L-threo-DOPS were useful to control diarrhea and orthostatic hypotension. Duplex ultrasonography of the 4 vessels revealed that reverse flow was always recognized in FAP patients with faintness, which was effectively treated by the administration of L-threo-DOPS. Orthotopic liver transplantation revealed effective therapy for autonomic dysfunction in FAP patients. Precise analysis of protein metabolism in FAP patients revealed that among apolipoproteins, only apolipoprotein AII decreased as the progression of the disease and high density lipoprotein gained the negative charge by agarose electrophoresis study. Concerning low density lipoprotein (LDL) study, only variant transthyretin in the circulation associated with LDL in FAP patients, suggesting that LDL may play an important role in the amyloid formation of FAP.

Amyloid Neuropathies↗
PubMed1994

Role of nitric oxide in the peripheral vessels of patients with familial amyloidotic polyneuropathy (FAP) type I.

In order to establish the generation of endothelial derived relaxating factor (EDRF) in patients with familial amyloidotic polyneuropathy (FAP) type I, the muscle temperature of the lower limb was measured with a deep portion thermometer. The temperature of the gastrocunemius muscle in FAP patients was significantly decreased compared with control subjects. In order to investigate the generation of EDRF in FAP patients, we administered NG-monomethyl-L-arginine (L-NMMA), specific inhibitor of nitric oxide, from the brachial artery and measured the changes in blood flow. Although 61.7 +/- 18.2% of the blood flow was transiently decreased after administration of L-NMMA in control subjects, FAP patients showed poor responses. In contrast, in the same way as in control subjects, significant vasodilatation was seen in FAP patients after administration of L-arginine. The urinary secreted NO2-/NO3- levels per day, which reflect the synthesis of nitric oxide in the systemic circulation, was a great deal lower in FAP patients than in control subjects. These results suggest that, although peripheral vessels can be dilated when a large amount of the substrate for NO synthase, L-arginine, is supplied, production of nitric oxide may be suppressed, and, as the result of this phenomenon, blood flow is decreased in the peripheral tissues of FAP patients in a static state.

Adult↗
PubMed1994

Magnetic resonance imaging of heterotaxia in infants.

OBJECTIVES: This study assessed the usefulness and safety of magnetic resonance imaging (MRI) for systematically diagnosing heterotaxia in infants. BACKGROUND: Although it is important to diagnose and treat infants with heterotaxia, which is associated with viscerobronchial cardiovascular anomalies, systematic diagnosis of these anomalies by a single imaging technique is difficult. METHODS: Twenty patients with heterotaxia were evaluated. The infants ranged in age from 21 days to 12 months (average 5.2 months, average body weight 4.3 kg). Electrocardiographically gated MRI was performed by spin echo imaging techniques operating at 0.5 tesla. RESULTS: In all 20 patients, MRI results were sufficient to evaluate these anomalies without serious complications. In 17 patients, neither a spleen nor splenules were detected, but in 3 patients, a polymorphous spleen was visualized. In all 20 patients, bronchial anatomies were clearly visualized (bilateral eparterial bronchi in 14 patients, bilateral hyparterial bronchi in 2 and normal bronchial patterns in 4). Additionally, in a comparison of 149 observations of cardiovascular anatomy by MRI with those by angiography, discrepancies were found in only 10 observations (6.7%). CONCLUSIONS: Magnetic resonance imaging was found to be safe and very useful for the systematic diagnosis of heterotaxia in infants.

Abnormalities, Multiple↗
PubMed1994

Treatment of a Japanese patient with familial amyloidotic polyneuropathy with orthotopic liver transplantation.

A 28-year-old male patient with familial amyloidotic polyneuropathy (FAP) underwent a liver transplantation from a heart-beating cadaveric donor in Sweden. He had suffered from the disease for 2.5 years. It took 5.5 hours to carry out the operation without blood transfusion. After the liver transplantation, serum amyloidgenic variant transthyretin (TTR) levels became extremely low and diarrhea stopped after the 7th day. On day 13, the patient was discharged from the hospital and one month after the transplantation, his general condition remained quite good. This is the first case of a Japanese patient with congenital metabolic disorders as well as FAP to receive a liver transplantation from a heart-beating cadaveric donor.

Adult↗
PubMed1990

Antidromically evoked facial nerve responses in guinea pigs: a basis for clinical applications in patients with facial palsy.

We investigated the differences in wave form in antidromically evoked facial nerve responses in guinea pigs with and without facial nerve dysfunction. The antidromic facial nerve responses were evoked with alternative stimulation of positive and negative square-wave pulses of 0.1 ms duration and recorded at the bony fallopian canal near the geniculate ganglion. One hundred responses were summed by a signal processor. The application of alternative stimulations made it possible to eliminate stimulus artifacts and to analyze precisely the waves with latencies shorter than 0.5 ms in the test animals. Normal antidromic facial nerve responses showed a triphasic wave form with two positive and one negative peaks. A blockade of the nerve between the recording and stimulating sites resulted in transformation of the wave into a monophasic one. A proximal blockade to the recording site changed the wave form to a biphasic shape. These findings suggest that the site of an intratemporal facial nerve lesion can be predicted from the wave forms evoked by antidromic facial nerve responses.

Animals↗
PubMed1990

Magnetic resonance imaging of myocardial infarction in Kawasaki disease.

We performed magnetic resonance imaging in patients with Kawasaki disease following myocardial infarction to assess the usefulness of the technique in detecting myocardial infarction and coronary artery lesions. In six patients (group A), the interval after myocardial infarction was from 7 days to 7 months, and in five patients (group B), it was from 1 to 4 years. Imaging was performed with a superconducting magnet operating at 0.5 T with spin-echo sequence and ECG-gated multiple slices of 5 mm thickness. Myocardial signals were increased in group A, and the region of high signal intensity corresponded to the site of myocardial infarction. The signal intensity within the myocardium was homogeneous in five patients in group B. Coronary arteries were visualized in 20 of 22 instances. Signals within the coronary artery were observed in all 14 instances with poor contrast runoff from the coronary aneurysm, and 11 of these vessels showed high signal intensity. In all six instances in which large aneurysms with severe stenosis were present, signals in the coronary artery were increased. In contrast, high signal intensity in the coronary artery was not observed in five of six instances with good contrast runoff. Signals in the coronary arterial cavity and high signal intensity in the coronary artery persisted in five of six instances with turbulent coronary flow. The findings of increased coronary arterial signals suggested stagnant blood flow in the coronary aneurysm. In conclusion, magnetic resonance imaging was a useful modality for assessment of myocardial infarction and coronary artery lesions in Kawasaki disease.

Adolescent↗