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Biomedical subjects

M Sano

Publications and source records attributed to M Sano.

At least 433 records · Page 24Linked to original sources

Changes in levels of microtubule-associated proteins in relation to the outgrowth of neurites from PC12D cells, a forskolin- and nerve growth factor-responsive subline of PC12 pheochromocytoma cells.

Immunoblotting analysis and immunofluorescence studies of proteins that react with MAP1- and MAP2-specific antibodies in PC12 rat pheochromocytoma cells were carried out. When cells of the PC12D subline of PC12 cells, which rapidly extend neurites in response to NGF or drugs that elevate intracellular levels of cyclic AMP, were examined, they were found to contain a relatively higher level of MAP1 or of a MAP1-like protein than conventional PC12 cells. Immunoblotting study showed that levels of MAP1 and MAP2 or of MAP1 or MAP2-like proteins increased in PC12D cells, but not in conventional PC12 cells, in response to forskolin. Immunofluorescence studies also revealed increases in levels of MAP1 and MAP2 or of MAP1 or MAP2-like proteins in conjunction with the outgrowth of neurites from the cells. These results support the hypothesis that the induction of MAPs may be one of the first steps required for outgrowth of neurites from PC12 cells. Furthermore, PC12D cells may contain a sufficiently high level of MAP1 or MAP1-like protein to permit the extension of neurites in the absence of the lag period normally required by PC12 cells. The MAP1 or a MAP1-like protein was localized in the cell soma and neurites. An increase of MAP2-specific immunoreactivity in perikarya was observed in the differentiated cells. After immunostaining with a monoclonal antibody that reacted with phosphorylated MAP1, intense fluorescence was seen in the growth cones of neurites. This observation supports the hypothesis that the phosphorylation of MAP1 or of a MAP1-like protein may play a regulatory role in the formation of neurites in growth cones.

Adrenal Gland Neoplasms↗

Morphine-induced metabolic changes in human brain. Studies with positron emission tomography and [fluorine 18]fluorodeoxyglucose.

Morphine sulfate effects (30 mg, intramuscularly) on cerebral glucose utilization and subjective self-reports were examined in 12 polydrug abusers by positron emission tomography and [fluorine 18]fluorodeoxyglucose in a double-blind placebo-controlled crossover study. During testing, subjects sat with eyes covered, listening to white noise and "beep" prompts. Morphine significantly reduced glucose utilization by 10% in whole brain and by about 5% to 15% in telencephalic areas and the cerebellar cortex, assuming no contribution of hypercapnia. When the contribution of PaCO2 (45 minutes after morphine was administered) was partialled out, significant morphine-induced reductions persisted in whole brain and six cortical areas. Irrespective of morphine, left-greater-than-right asymmetry occurred in the temporal cortex, and an interaction between hemisphere and drug was noted in the postcentral gyrus. In most cases, effects on glucose utilization were not significantly related to measures of euphoria.

Blood Pressure↗

Buerger's colour.

Cyanosis of the hands and feet in Buerger's disease is known as 'Buerger's colour'. This characteristic skin colour is produced by the subpapillary venous plexus. The reactions of the subpapillary venous plexus in patients with Buerger's disease were observed by analysing the fractional blood volume of tissue using a visible light reflective spectrophotometer. Capillary morphology was investigated using an intravital video-microscopic system. Twenty-seven subjects, comprising 13 normals and 14 patients with Buerger's disease, were studied. In the nailbeds of patients with Buerger's disease, an increase in the number of loops, cyanotic colour change and dilatation were observed. In this condition there was incompetence of venular tonus and regurgitation at venular valves. Buerger's colour is probably due to excessive congestion of venous blood in the subpapillary venous plexus which is produced by these mechanisms.

Adult↗

A controlled trial of piracetam in intellectually impaired patients with Parkinson's disease.

Twenty patients with Parkinson's disease and marked intellectual impairment or dementia participated in a double-blind placebo controlled trial of the nootropic, piracetam. A standardized neurological examination, a neuropsychological test battery, and a functional scale, The Sickness Impact Profile, were completed for all patients. They were then assigned by blind randomization to drug or placebo conditions receiving 3.2 g of piracetam or an identical amount of placebo for 12 weeks. The dose was increased to 4.8 g for an additional 12 weeks. Neurological, psychological, and functional measures were rated as improved, unchanged, or worsened in comparison to baseline performance. Twenty-five percent of the patients did not complete the trial for reasons unrelated to the medication. Although there was a significant improvement on one subtest of the functional scale, no significant effects were demonstrated in cognitive or neurological measures.

Aged↗

Studies on new, centrally active and reversible acetylcholinesterase inhibitors.

We have synthesized the tertiary amines of pyridostigmine and neostigmine, 3-pyridinol dimethylcarbamate (norpyridostigmine) and 3-dimethylaminophenol dimethylcarbamate (norneostigmine) respectively, and we have tested their abilities to cross the blood-brain barrier and inhibit mouse brain AChE activity. The in vivo inhibition of AChE activity by norpyridostigmine reaches 72% at 10 minutes which is comparable to that seen with physostigmine (73% at 10 minutes). Inhibition by norneostigmine is less effective (50% at 10 minutes) and approaches that obtained with tetrahydroaminoacridine (57% at 10 minutes). These data show that both norpyridostigmine and norneostigmine cross the blood-brain barrier and that they are effective inhibitors of mouse brain AChE activity. These drugs could be useful in the treatment of memory impairment associated with Alzheimer's disease, and other memory disorders.

Acetylcholinesterase↗

Giant chest wall tumor resulting from tissue reaction to foreign bodies.

Three patients are reported in whom chest wall tumors developed 19 to 28 years after thoracoplasty and increased in size with time. The tumors could be removed operatively with good results. All tumors were composed of hematoma and necrotic material, and in all cases they revealed foreign bodies microscopically. Diagnosis and possible etiological factors are discussed.

Female↗

A developmental change in the content of parvalbumin in normal and dystrophic mouse (mdx) muscle.

A highly sensitive enzyme immunoassay for mouse parvalbumin was developed in this study. The amount of parvalbumin was determined by a sandwich enzyme immunoassay method using anti-parvalbumin IgG-coated polystyrene balls and an anti-parvalbumin Fab'-horseradish peroxidase conjugate. Parvalbumin could not be detected in normal and dystrophic skeletal muscles of newborn mice. In normal mice, it appeared in the first postnatal week and increased linearly thereafter until the 12th week in fast twitch muscle. Rapid increase in parvalbumin was seen during 3rd and 8th week. On the other hand, parvalbumin detected in the first postnatal week increased gradually, but did not yet reach the adult level at the 16th postnatal week in slow twitch muscle. In mdx mice, fast twitch muscles such as the gastrocnemius and tibialis anterior were found to contain significantly decreased amounts of parvalbumin, compared with those in control mice. In fast twitch muscle parvalbumin in mdx mice could not be detected in the newborn, increased until 4th week and thereafter did not increase as that in normal mice. In slow twitch muscle the postnatal increase in parvalbumin content was not different from that in control mice. These results suggest that the decrease in the content of parvalbumin in dystrophic muscle may contribute to the elevation of the level of sarcoplasmic free Ca2+ and the activated Ca2(+)-dependent proteolysis.

Aging↗

Antitumor activities of IKP-104, a 4(1H)-pyrizinone derivative, on cultured and implanted tumors.

Antitumor activities of IKP-104, a 4(1H)-pyrizinone derivative, were investigated with cultured tumor cell lines and implanted tumors in mice. IKP-104 inhibited the growth of cultured murine tumor cell lines (L1210 leukemia, Lewis lung carcinoma and B16 melanoma) and human tumor cell lines (K562 leukemia and HeLa cervical carcinoma). It also had antitumor effects on implanted murine ascitic tumors (L1210 leukemia and sarcoma 180) and a murine solid tumor (Lewis lung carcinoma). IKP-104 could be classified as a phase-dependent cytostatic drug based on the mode of growth inhibition of cultured B16 melanoma cells compared with those of several other antitumor agents. The effect of IKP-104 on the cell cycle traverse of cultured B16 melanoma cells was estimated by morphological and flow cytometric analyses. Cells accumulated in the mitotic phase, and abortive mitosis or polyploidy or multinucleation was induced from 6 h after exposure to IKP-104. Based on these results, IKP-104 is expected to be useful for the treatment of tumors, and its mode of action seemed to be similar to that of metaphase arrestants such as colchicine or vinca alkaloids.

Animals↗

A nerve growth factor-dependent protein kinase that phosphorylates microtubule-associated proteins in vitro: possible involvement of its activity in the outgrowth of neurites from PC12 cells.

We have established a subline of PC12 cells (PC12D) that extend neurites very quickly in response not only to nerve growth factor (NGF) but also to cyclic AMP (cAMP) in the same way as primed PC12 cells (NGF-pretreated cells). When phosphorylation of brain microtubule proteins by extracts of these cells was monitored, two distinct kinase activities were found to be increased [from three-to eightfold in terms of phosphorylation of microtubule-associated protein (MAP) 2] by a brief exposure of cells to NGF or to dibutyryl cAMP (dbcAMP). The effect of the combined stimulation with both NGF and dbcAMP was additive in terms of the phosphorylation of MAP2. The apparent molecular mass of the kinase activated by dbcAMP was 40 kDa, and this kinase appears to be cAMP-dependent protein kinase. The molecular mass of the kinase activated by NGF was 50 kDa. The latter was activated to a measurable extent after 5 min of exposure of cells to NGF: it required Mg2+ for activity but not Mn2+ or Ca2+. This kinase appears to be distinct from previously reported kinases in PC12 cells, and it has been designated as NGF-dependent MAP kinase, although its physiological substrates are not known at present. An inhibitor of protein kinases, K-252a, selectively inhibited the outgrowth of neurites from PC12D cells in response to NGF but not to dbcAMP. When this inhibitor was added to the incubation medium of cells exposed simultaneously to NGF or dbcAMP, the increase in activity of the NGF-dependent MAP kinase was selectively abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗

Measurement and prediction of functional capacity in Alzheimer's disease.

Functional loss in Alzheimer's disease is difficult to measure or predict. The Blessed Dementia Rating Scale (Part 1) correlates well with postmortem changes but is not an effective antemortem index of functional change since disparate behavioral domains are assessed. We performed a factor analysis of the Blessed items in 187 patients with clinically diagnosed Alzheimer's disease and identified 4 independent factors: (I) cognitive, (II) personality, (III) apathy, and (IV) basic self-care. An endpoint, consisting of a score indicative of moderate disability, was determined for each factor. We then used life table analyses to compare the probability of reaching these endpoints over time in longitudinally followed patients. Patients with extrapyramidal signs at their initial visit reached the factor IV endpoint sooner, and those with psychosis or no family history of dementia also reached the factor I endpoint faster. These data illustrate the utility of a multifactorial approach to the assessment of functional capacity in Alzheimer's disease, and also indicate that extrapyramidal symptoms and psychosis are powerful predictors of the rate of decline in basic self-care activities and cognition.

Aged↗

Studies on the formation of aliphatic aldehydes in the plasma and liver of vitamin E-deficient rats.

The effects of vitamin E (E) deficiency on the formation of aliphatic aldehydes in rat plasma and liver were studied. Three-week-old Wistar male rats were fed either an E supplemented diet (2-ambo-alpha-tocopheryl acetate 20 mg/kg diet, designated as E supplemented diet group) or an E deficient diet (E deficient diet group). After 8 weeks, n-hexanal and (E)-4-hydroxy-2-nonenal (4-HN) in the plasma of the E deficient diet group were found to be 2.0 and 2.5-fold greater than those of the E supplemented diet group, respectively. The contents of aldehydes such as n-pentanal, n-hexanal, 4-HN in the liver were also significantly higher in the E deficient diet group than in the E supplemented diet group. These results indicate that some aldehydes, arising possibly from lipid peroxides, are produced and detected in the plasma and liver of rats under the condition like E deficiency. In this study we further found that the activity of the liver aldehyde dehydrogenase (ALDH, EC 1.2.1.3) was significantly changed; 5 and 8 weeks after the start it was lower in the E deficient diet group when compared to that in the E supplemented diet group. The decrease of enzyme activity was related to the increase of aldehydes such as n-hexanal in the liver. the aldehyde increase in the plasma of the E deficient diet group was thought to raise the injury of cells, namely, a strong hemolysis on erythrocytes prepared from the blood of rats fed the E deficient diet.

Aldehyde Dehydrogenase↗

Protein breakdown in submandibular glands rendered hypertrophic by amputation of lower incisor teeth in rats.

Protein breakdown in submandibular glands rendered hypertrophic by amputation of the lower incisor teeth in rats was investigated. Reduced protein breakdown was observed in the hypertrophic gland tissues, and was found to be inhibited by 20 mM epsilon-amino-n-caproic acid, an inhibitor of serine protease, and 50 microM leupeptin, an inhibitor of trypsin, plasmin, papain and cathepsin B, but not by 2 mM PMSF (phenylmethylsulfonyl fluoride), an inhibitor of serine protease, 10 microM pepstatin, an inhibitor of cathepsin D and 20 microM antipain, an inhibitor of cathepsin A and B. These results suggest that some serine proteases and leupeptin-sensitive proteases (presumably cathepsin B) participate in protein breakdown in hypertrophic gland tissues, and that hypertrophy of the submandibular glands is closely related to the reduced protein breakdown in these tissues.

Aminocaproic Acid↗

[Factors of gastric lesions following after transcatheter arterial embolization for primary hepatoma].

To clarify the influence of Transcatheter Arterial Embolization (TAE) on the stomach, endoscopic examination was carried out before and after TAE. Forty-six TAE were performed in 27 patients with primary hepatoma. New gastric lesions, erosions and ulcers, were developed in 25 of 46 TAE. There was no significant relationship between the incidence of the lesions in the cases with esophageal varices (15/24) and the cases without (10/22) and there was no significant relationship between the incidence of the lesions after the first TAE (12/22) and after the second TAE (5/14). Period between the first and the second TAE had no statistical influence on the lesions after the second TAE. Hepatic functions (Child's classification; Rmax, K, R15 of ICG; serum total protein; serum albumin; total bilirubin; prothrombin time; hepaplastin test) before TAE were not statistically related to the appearance of the gastric lesions following TAE (Table 1). On the other hand, the cases which showed apparent effects of TAE including 0.2 time decrease of AFP had the more gastric lesions (P less than 0.05) (Table 2). The cases with upper abdominal pain after TAE had more gastric lesions (24/38) than the cases without (2/8) (P less than 0.05). But the cases undergone TAE with high possibility of the influx of gelatin sponge pieces, lipiodol or anticancer agents into the supplying vessels for the stomach did not exhibit significant incidence of the lesions (Table 3). Thus, when TAE is followed by a 0.2 time decrease in AFP, it is necessary to pay more attention to the gastric lesions. The prophylactic administration of H2 antagonist before or just after TAE did not seem useful to prevent the gastric lesions. These findings suggest that the influx of gelatin sponge pieces, lipiodol or anticancer agents to the stomach does not always cause gastric ulcer or erosion.

Aged↗

Scanning electron microscopic observations of first- and third-stage larvae and adults of Angiostrongylus costaricensis.

The surfaces of larval and adult Angiostrongylus costaricensis, causative agent of human abdominal granuloma, were studied by the use of scanning electron microscopy. Cuticular annulations were clearly demonstrated on the surface of larvae and adults. Differences in the appearance of alae in larval stages and in the shape of the tail at different stages of development are described and illustrated. Several aspects of morphology previously unreported for this parasite are also described.

Angiostrongylus↗

[Clinical, cytogenetic and immunological studies of 2 cases with B-cell acute lymphocytic leukemia. Comparison between B-ALL and Burkitt's lymphoma reported in Japan].

Two patients with acute lymphocytic leukemia of B-cell phenotype (B-ALL) are described. They were 77-year-old female and 34-year-old male. One patient presented with marked splenomegaly, and the other with rupture of spleen on admission. Leukemic morphology revealed a typical L3 profile by FAB classification system in both cases. Immunologic analysis showed the presence of surface immunoglobulins in both cases, and one phenotype was IgM kappa, whereas the other was IgG kappa. Cytogenetic study revealed the typical translocations (8; 14) in both cases. Following chemotherapy, complete remission was achieved in one case, but the other died 36 days after admission. Including our two cases, we studied 12 cases of B-ALL and 77 cases of Burkitt's lymphoma reported in Japan, investigating the clinical prognosis as well as the biological features. We concluded that there are no significant difference of survival between B-ALL and Burkitt's lymphoma. We estimated it is due to oncogenesis from the same original cell in despite of the difference in main tumor site between two diseases.

Adult↗