Search PubMed⌕ Search

Biomedical subjects

T Nagashima

Publications and source records attributed to T Nagashima.

At least 19 recordsLinked to original sources
PubMed1992

Insulin stimulates novel protein kinase C in rat adipocytes.

Insulin is known to rapidly stimulate and/or translocate Ca2+/phospholipid-dependent protein kinase (conventional PKC; cPKC) in rat adipocytes. Presently we examined whether insulin also stimulates/translocates Ca(2+)-independent, phospholipid-dependent protein kinase (novel PKC; nPKC). Total Mono Q column-elutable nPKC (like cPKC) activities were decreased in cytosolic and increased in membrane fractions with insulin treatment. Immunoblot study of novel PKC epsilon also showed insulin-induced translocation of immunoreactive PKC from cytosol to membrane, similar to the translocation of cPKC, PKC beta. These results suggest that nPKC has an important role in insulin-induced signal transduction.

Adipose Tissue↗
PubMed1992

Peptide synthesis by proteases in organic solvents: medium effect on substrate specificity.

The substrate specificities of alpha-chymotrypsin and subtilisins for peptide synthesis in hydrophilic organic solvents were investigated. Chymotrypsin exhibited high specificity to aromatic amino acids as acyl donors, while subtilisin Carlsberg and subtilisin BPN' were specific to aromatic and neutral aliphatic amino acids, in accordance with the S1 specificities of the enzymes for peptide hydrolysis in aqueous solutions. On the contrary, chymotrypsin exhibited higher specificities to hydrophilic amino acid amides as acyl acceptors (nucleophiles) for peptide synthesis with N-acetyl-L-tyrosine ethyl ester, in contrast to the S1' specificity for peptide hydrolysis and peptide synthesis in aqueous solutions. Furthermore, nucleophile specificity changed with the change in water-organic solvent composition; the increase in water content led to increase in relative reactivity of leucinamide to that of alaninamide. It was also found that protection of the carboxyl group of alanine by amidation is much preferable to protection by esterification in terms of reactivity as nucleophiles.

Chymotrypsin↗
PubMed1992

Properties of rhythmically active reticular neurons around the trigeminal motor nucleus during fictive mastication in the rat.

Response properties of the neurons in the reticular formation around the trigeminal motor nucleus (MoV) were examined during cortically-induced fictive mastication (CIFM) in anesthetized and immobilized rats. Forty-three neurons were rhythmically active (RA neurons) during CIFM, most of which were located in the supratrigeminal nucleus and the reticular formation medial to the oral spinal trigeminal nucleus. The firing frequency of 36 of the RA neurons was modulated in the same rhythm as that of masseteric or digastric nerve activities during CIFM. We divided these neurons into four groups according to the phase of activation: sixteen neurons fired mainly in the phase of masseteric activity (type 1), 11 fired in the transition phase from masseteric activity to digastric activity (type 2), 5 fired in the phase of digastric activity (type 3) and 4 fired in the transition phase from digastric activity to masseteric activity (type 4). Thirty-nine (91%) of the 43 RA neurons responded to at least one of the tested peripheral stimuli. The responses were mostly excitatory but inhibitory responses were sometimes obtained, especially for types-1 and 2 neurons. RA neurons in the reticular formation medial to the oral spinal trigeminal nucleus responded to stimulation of inferior alveolar nerve at a shorter latency than RA neurons in the supratrigeminal nucleus. Fifteen (48%) of 31 RA neurons responded to triple-pulse stimulation of the contralateral cortex. In contrast, only 5(26%) of the 19 RA neurons responded to the ipsilateral cortical stimulation. Stimulation of the ipsilateral MoV was performed on 24 RA neurons, of which 9 responded antidromically (A-RA neurons) at latencies of 0.4-1.4 ms. Eight (89%) of the 9 A-RA neurons received peripheral inputs. The spike triggered averaging method was applied to 4 of the 9 A-RA neurons, ad in all cases short latency field potentials were recorded in the MoV. We conclude that trigeminal premotor neurons receive convergence from central and peripheral inputs. This integration can adjust the appropriate level of motoneuronal excitability during mastication.

Animals↗
PubMed1992

Site-directed mutagenesis of catalytic active-site residues of Taka-amylase A.

The cDNA encoding Taka-amylase A (EC.3.2.1.1, TAA) was isolated to identify functional amino acid residues of TAA by protein engineering. The putative catalytic active-site residues and the substrate binding residue of TAA were altered by site-directed mutagenesis: aspartic acid-206, glutamic acid-230, aspartic acid-297, and lysine-209 were replaced with asparagine or glutamic acid, glutamine or aspartic acid, asparagine or glutamic acid, and phenylalanine or arginine, respectively. Saccharomyces cerevisiae strain YPH 250 was transformed with the expression plasmids containing the altered cDNA of the TAA gene. All the transformants with an expression vector containing the altered cDNA produced mutant TAAs that cross-reacted with the TAA antibody. The mutant TAA with alteration of Asp206, Glu230, or Asp297 in the putative catalytic site had no alpha-amylase activity, while that with alteration of Lys209 in the putative binding site to Arg or Phe had reduced activity.

Amylases↗
PubMed1992

[HTLV-I associated myelopathy with bilateral abductor vocal cord paralysis--case report].

We have reported a 50-year-old woman with HTLV-I associated myelopathy (HAM) who had bilateral abductor vocal cord paralysis. The symptoms and signs were slowly progressive spastic paraplegia, dysuria, inspiratory stridor, and snoring during sleep. She had no hoarseness. Titers of anti-HTLV-I antibody were elevated in both the serum and cerebrospinal fluid. FEV1.0% on the spirogram was reduced to 66%. The fiberscopic examination demonstrated the abductor limitation of the vocal cords during the inspiratory phase. During induced sleep after the intravenous administration of thiopental sodium, this abductor paralysis was worsened, producing a high pitched inspiratory stridor. The adduction was not disturbed at all. Needle electromyogram of the posterior crico-arytenoid muscle which is a sole abductor muscle revealed the high amplitude up to approximately 1.0 mV (normal less than 0.8 mV) with poor interference pattern, indicating neurogenic changes. After 2 months course of prednisolone (60 mg/alternative day), FEV1.0% was recovered to be 92% with the improvement of the gait disturbance, which suggests the abductor vocal cord paralysis is related to HAM. The abductor vocal cord paralysis in HAM would require a careful follow-up observation to protect the respiratory failure in the advanced stage.

Electromyography↗
PubMed1991

Pseudopseudohypoparathyroidism with recurrent polyneuropathy: an autopsy report with special reference to the peripheral nervous system.

The clinical and pathological findings of a 21-year-old girl suffering from pseudopseudohypoparathyroidism (PPHP) with relapsing neuropathy are described. Episodic exacerbations were accompanied by intracranial hypertension and were relieved by the administration of corticosteroids. At autopsy, pathologic changes were almost restricted to the peripheral axons and showed distal dominant depletion of myelinated fibers without any active myelin breakdown or inflammatory changes. The neuropathy is thought to be similar to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); however, the relationship, if any, between PPHP and CIDP is unknown.

Adult↗
PubMed1991

[Can fluorodeoxyglucose-positron emission tomography evaluate the functional differentiation of hepatocellular carcinoma].

Tumor uptake of 18F-fluorodeoxyglucose (FDG) was studied by dynamic positron emission tomography (PET) in 23 cases of hepatocellular carcinoma. The metabolic rate constants, K1 to K4, were generated by non-linear least square fitting method. We confirmed that K3 from the PET study significantly correlated with directly measured hexokinase activity of the cancer tissue. The region of HCC always had higher K3 values, which represents the hexokinase activity compared with the non-cancerous region. By FDG images, however, in 50% of cases the cancer region could not be clearly defined from the surrounding noncancerous hepatic tissue. These HCC cases without accumulation of FDG had a high ratio of K4/K3 (K4 represents glucose-6-phosphatase activity), which correlated well with the inverse ratio of FDG accumulating images on PET. According to the PET images which is represented by K4/K3 and the hexokinase activity which is represented by K3, we divided these 23 cases into three groups and retrospectively compared their survival rates. The groups with high K4/K3 (greater than or equal to 0.40) had longer survival than other groups. From the view point of glucose metabolism, the value of K4/K3 calculated from dynamic studies of FDG-PET may represent the functional differentiation of HCC.

Carcinoma, Hepatocellular↗
PubMed1991

[Post-poliomyelitis late progressive muscular atrophy (PPMA)--clinical analyses of Japanese cases].

Clinical and epidemiologic analyses of PPMA in Japan based on the nation-wide case survey were reported, and differences between PPMA and ALS were discussed. The present survey covering the years from 1984 through 1991 cited 42 PPMA cases (30 male:12 female). The absolute incidence of PPMA is estimated 0.12/10(5) of the Japanese population (about 150 cases in total), which indicates 0.5% of the polio survivors. In Japan an actual increase of patients is noticed in these 10 years, which reflects the big epidemic of polio around 1950-60. The antecedent poliomyelitis occurred at the mean age of 2.6, mostly between 1940 and 1960. Residual paralysis was generally absent or only minimal. Late muscular atrophy and weakness were noticed at age from 16 to 63 y (mean:41.5), with the mean latency of 40.1 years after polio. Both polio-affected and unaffected site of the limb were equally involved by PPMA, but the left leg tends to be predominantly involved. Neurological symptoms were summarized as an asymmetrical proximal muscular atrophy and flaccid motor paresis in one or two limbs with decreased tendon reflexes. Fasciculation in 45.2%, myalgia in 28.6%, and hypesthesia in 28.5% were noticed. Electromyography and muscle CT scan showed marked selective neurogenic changes. In most cases symptoms are stable or slowly progressive, with some recovery by rest or rehabilitation and deterioration by over work and/or trauma. On regarding these clinical features, PPMA is essentially different from classical ALS. Long-term hyperfunction of survived neurons with potential fragility by polio infection is suspected to mediate PPMA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

[Congenital facioscapulohumeral muscular dystrophy associated with tongue atrophy and sensorineural hearing disturbance].

An 18-year-old high-school boy presented facial muscle weakness since birth, and then developed wasting around the neck, shoulder girdle, upper arms, and thighs. He was born to un-consanguineous parents. His father had suffered from similar but milder muscle atrophy with predominance on the right side of the face and shoulder girdle since adolescence. His mother and his only sibling were clinically unaffected. Hearing disturbance was detected at the age of 6, and he also noted atrophy of the tongue and the bilateral thighs at the age of 10. The symptom progressed gradually. Neurological examination on admission revealed a well-developed boy (166 cm/60 kg) with a prominent facial diplegia with distinct proximal muscular atrophy of the extremities. Muscles of the tongue, neck, upper arms, shoulder and pelvic girdles, and hamstrings were markedly involved. The anterior tibial muscles were also affected, while the calf muscles were hypertrophic. High arched palate, X legs, mild lordoscoliosis were also noted. Serum CK was slightly increased (424 IU/l), and needle EMG in the extremities including the tongue revealed myopathic changes. Muscle CT demonstrated marked atrophy of the proximal muscles in the lower limbs and hypertrophy of the calf muscles. Audiogram showed bilateral sensorineural hearing disturbance. Muscle biopsy of the gastrocnemius showed myogenic as well as neurogenic changes consisting of atrophic and hypertrophic fibers with interstitial cellular infiltration, and type I fiber predominance. With these family history as well as clinical and laboratory examinations, this case could be diagnosed as "congenital facioscapulohumeral muscular dystrophy".(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Mechanisms of 2'-deoxyguanosine toxicity in mouse T-lymphoma cells with purine nucleoside phosphorylase deficiency and resistance to inhibition of ribonucleotide reductase by dGTP.

Purine nucleoside phosphorylase (PNP; EC 2.4.2.1) deficiency is thought to cause T-lymphocyte depletion by accumulation of dG and dGTP, resulting in feedback inhibition of ribonucleotide reductase (RR; EC 1.17.4.1) and hence DNA synthesis. To test for additional toxic mechanisms of dG, we selected a double mutant of the mouse T-lymphoma S-49 cell line, dGuo-L, which is deficient in PNP and partially resistant to dGTP feedback inhibition of RR. The effects of dG on dGuo-L cells (concn. causing 50% inhibition, IC50 = 150 microM) were compared with those on the wild-type cells (IC50 = 30 microM) and the NSU-1 mutant with PNP deficiency only (IC50 = 15 microM). Fluorescence flow cytometry showed that equitoxic dG concentrations arrested wild-type and NSU-1 cells at the G1-S interface while allowing continued DNA synthesis in the S-phase, whereas the double mutant dGuo-L cells progressed through the cell cycle normally. dGuo-L cells accumulated high levels of dGTP in G1-phase, but not in S-phase cells, because of the utilization of dGTP for DNA synthesis and limited capacity to synthesize dGTP from dG. These results support the hypothesis that dG/dGTP toxicity occurs in the G1-phase or at the G1-S interface. Failure of dG to arrest the double mutant dGuo-L cells at the G1-S interface allows these cells to escape into S-phase, with an accompanying drop in dGTP levels. Thus the partial resistance of dGuo-L cells to dG toxicity may result from their shorter residence time in G1, allowing them to sustain higher dGTP levels. Hence RR inhibition by dGuo may not be the primary toxic mechanism in S-49 cells; rather, it may serve as an accessory event in dG toxicity by keeping the cells in the sensitive phase of the cell cycle. Among the possible targets of dG toxicity is RNA synthesis, which was inhibited at an early stage in dGuo-L cells.

Animals↗
PubMed1990

Hydrocephalic oedema in normal-pressure hydrocephalus.

The hydrocephalic oedema in normal-pressure hydrocephalus (NPH) was evaluated by measurement of the relaxation time of protons of the water molecules of brain tissue. Patients with NPH were divided into two groups: shunt responders and shunt non-responders. In the group of shunt responders both T1 and T2 of periventricular white matter were significantly prolonged compared to those of controls, and shortened after shunting. Both T1 and T2 of white matter were significantly longer than of gray matter, while a reversed relationship was seen in normal controls. However, in the group of shunt non-responders, T1 of white matter was significantly prolonged, while T2 of the same area not. There was no change in either T1 or T2 of this region after shunting. Both T1 and T2 were almost the same in white and gray matter in shunt non-responders. It is suggested that periventricular abnormalities seen in various diseases may be distinguished on the basis of the relaxation behavior of protons of tissue water.

Body Water↗
PubMed1990

Changes in free water content and energy metabolism of the brain in experimental hydrocephalus.

In acute and subacute hydrocephalus periventricular oedema is most prominent. At these stages of hydrocephalus, the free water content is increased and the bound water content, to the contrary, significantly decreased in the periventricular white matter. The bioenergetic state is also altered. In the chronic stage the ratio of free-to-bound water content returns to a level near the control value, leading to a decrease of periventricular oedema by formation of alternative pathways of CSF absorption. The bioenergetic state was slightly altered at this stage.

Acute Disease↗
PubMed1990

The finite element analysis of brain oedema associated with intracranial meningiomas.

The mathematical model of vasogenic brain oedema, which was presented at the previous meeting in 1987, was applied to the analysis of peritumoural brain oedema associated with meningiomas. Magnetic resonance images of 90 patients with intracranial meningiomas were reviewed to analyze the spatial extension of peritumoural brain oedema. It is assumed that the heterogeneous pattern of distribution of peritumoural oedema reflects the variability of the compact density of the fibers in the white matter. A two dimensional finite element model was constructed with 786 triangular elements from a horizontal section of the human brain. The development of oedema, the change of interstitial pressure, the deformation of the brain and the absorption of oedema fluid could be simulated by the finite element method. The result of computer simulation represented interactive behaviour of the brain tissue, extracellular fluid, and cerebrospinal fluid in the clinical situation. The finite element method (FEM) may provide a new experimental tool to analyze the pathophysiology of vasogenic brain oedema.

Brain↗
PubMed1990

A two-dimensional, finite element analysis of vasogenic brain edema.

The authors constructed a two-dimensional model of vasogenic brain edema, using the finite element method (FEM). The model incorporates the following physical parameters: cerebrovascular hydraulic conductivity, metabolic water production, tissue hydraulic conductivity and compliance, tissue and plasma osmotic and hydrostatic pressures, cerebrospinal fluid hydrostatic pressure and absorption, intracerebral stress, and shift of brain tissue. These parameters, related by partial differential equations, were approximated numerically in time and space by the FEM. The results of computer simulation of brain edema by the FEM were compared with experimental data obtained in a feline cold injury brain edema model. Computer simulation predicted the changes observed in interstitial pressure, extent of edema, intracerebral stress distribution, and shift of brain tissue. The results indicate that the FEM, applied to a model of vasogenic brain edema, can be used to predict the time course and regional distribution of fluid accumulation and the accompanying regional stress and deformation of brain tissue.

Animals↗
PubMed1990

Changes in the components and content of biological water in the brain of experimental hydrocephalic rabbits.

Changes in biological water components and their respective content in the cortical gray matter and periventricular white matter were studied in rabbits rendered hydrocephalic by intracisternal kaolin injection. There was no change in either total water content or free or bound water content in the cortical gray matter at the various stages of hydrocephalus development. While there was no significant change in total water content in the periventricular white matter at any stage of hydrocephalus, free water content was significantly elevated and bound water content was decreased at the acute and subacute stages, with a return to relatively normal levels at the chronic stage. It is concluded that in the periventricular white matter, free water enters the brain across the ependymal lining during the acute and subacute stages of experimental hydrocephalus with a simultaneous reduction in the bound water and that there is some recovery at the chronic stage. It is suggested that alternative drainage pathways may develop in chronic hydrocephalus allowing drainage of free water in the periventricular white matter, which in turn permits bound water to return to relatively normal levels.

Animals↗
PubMed1990

[Establishment and characterization of human cholaginocarcinoma, MEC, producing carbohydrate antigen 19-9].

A new tumor cell line MEC was established from pleural effusion of a patient of cholaginocarcinoma. In tissue culture, the cell line grew in the sheet of variant cells and showed the epithelial-like pattern. Histologically, the cell line almost showed the same pattern as those in bile and preural effusion from the patient. Electron microscopic observation of this cell line showed the irregular microvilli on the surface of the cell and the desmosome between cells. The doubling time of the cell line was 40.8 hours. Chromosome counts ranged from 61 to 86. The cell line had 9 marker chromosomes and some variant chromosomes. The cell line was transplanted into the subcutaneous of nude mice and formed the tumor. It showed the moderately differentiated tubular adenocarcinoma the same pattern as the primary tumor. We have recognized the producing and releasing of CA19-9 in the serum from the tumor bearing nude mouse and supernate of the medium as the serum from the patient. The presentation of CA19-9 in the cytosol of the cell line and the tumor cells of nude mouse was recognized in Avidin-Biotin-Peroxidase Complex in immunoloperoxidase techniques. The cell line can grow in serum-free medium. On September, 1990, the cell line has been maintained from 70 passages during about 800 days.

Adenoma, Bile Duct↗