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Biomedical subjects

H Nagao

Publications and source records attributed to H Nagao.

At least 37 records · Page 2Linked to original sources
PubMed1995

Remarkable activity enhancement of thermolysin mutants.

Most attempts to modify the properties of enzymes by amino acid substitution around the active sites have resulted in suppression of the biological activity, suggesting that the structure of natural enzymes should be almost optimized evolutionally to show the highest activity. In contrast, we found an interesting site of a well-known metalloendopeptidase, thermolysin (EC.3.4.24.4), where almost all the amino acid replacement causes a remarkable increase in the hydrolytic activity. Negative correlation between the activity and the thermal stability was observed. The flexibility around the substrate binding site is suggested to be a key to the correlation. Nature may have selected the amino acid at this site, which suppresses the flexibility of the molecule, to get the highest thermal stability at the expense of the activity.

Enzyme Activation↗
PubMed1995

Effects of adenylyl cyclase-linked neuropeptides on the expression of ciliary neurotrophic factor-mRNA in cultured astrocytes.

Ciliary neurotrophic factor (CNTF) is a molecule which has profound effects on various neural cell types. In the central nervous system, expression of CNTF-mRNA is highly concentrated in olfactory bulb. In the present study, we examined the regulatory mechanism of CNTF-mRNA expression in cultured astrocytes from newborn rat brain. Cultured astrocytes from new born rat brain expressed CNTF-mRNA at levels comparable to the level in olfactory bulb in vivo. Treatment of the astrocytes with forskolin, an activator of adenylyl cyclase, led to a decrease of CNTF-mRNA level. The effect of forskolin was mimicked by cAMP-linked agonists, such as VIP, PACAP, isoproterenol and dopamine. Cycloheximide, an inhibitor of protein synthesis, did not abolish the forskolin-induced decrease of CNTF-mRNA. Measurement of the half-life of CNTF-mRNA in the presence of actinomycin D, an inhibitor of transcription, indicated that the degradation of CNTF-mRNA is not destabilized by the forskolin-treatment. These data taken together suggest that the cAMP-induced suppression of CNTF-mRNA is mainly caused by the inhibition of CNTF gene transcription.

Adenylyl Cyclases↗
PubMed1995

The pathogenic role of the NMDA receptor in hyperthermia-induced seizures in developing rats.

Hyperthermia-induced seizures (HS) in rats have been used as a model of febrile seizures. Activation of the N-methyl-D-aspartate (NMDA) receptor by increased extracellular glutamate (Glu) in the cortex during hyperthermia may be involved in the induction of HS and HS kindling. To confirm this hypothesis, the effects of a potent blocker of the NMDA receptor, MK-801, on the threshold and pattern of HS were evaluated. The threshold temperatures for rats given 0.1 (low dose) and 0.5 (high dose) mg/kg MK-801 (i.p.) for the first time were 41.6 degrees C (39.7-42) (median, range) and 42.0 (41.2-42.0), respectively, which were significantly higher than the 40.5 (39.4-41.2) for rats without MK-801 administration (P < 0.01). The recurrent occurrence of HS suppressed the increase in the threshold temperature with age, and changed the seizure from partial to generalized seizures (HS kindling), whereas these effects of recurrent HS on the threshold and pattern of HS were inhibited by the high dose (0.5 mg/kg) of MK-801. MK-801 blocks HS and HS kindling. The activation of the NMDA receptor during hyperthermia plays an important role in the induction of HS and HS kindling.

Age Factors↗
PubMed1995

Estimating bone change in patients with severe disability.

To evaluate bone change in severely disabled patients, bone density was assessed on X-ray pictures by the microdensitometry (MD) method, and urinary hydroxyproline (U-HYP), urinary glycosaminoglycans (U-GAG) serum calcium (S-Ca) and serum alkaline phosphatase (S-AP) were assessed in 43 patients (mean age 16 years) at the National Sanatrium Ehime Hospital. On division of the severity of bone change into grades 0 to 3 using the MD method. U-HYP was found to be significantly higher in grades 2 and 3 than in controls. Tendencies were similar for U-GAG and S-AP. U-HYP in immobile patients was significantly higher than in mobile patients. Immobilisation was one of the most important contributors to the development of bone change and results obtained using the MD method, U-HYP and U-GAG were valuable-indices of the bone change in severely disabled patients.

Alkaline Phosphatase↗
PubMed1995

Molecular analysis of Japanese isolates of Verticillium dahliae and V. albo-atrum.

Sixteen isolates of different pathogenicity groups of the plant pathogen Verticillium dahliae and four isolates of V. albo-atrum from Japan were analysed by means of an RAPD (random amplified polymorphic DNA) method using a PCR (polymerase chain reaction). Verticillium dahliae and V. albo-atrum could be distinguished by RAPD analysis. Four pathogenicity groups of V. dahliae could also be classified to a certain extent by this method. Similarities and differences in banding patterns obtained by RAPD may be a useful molecular tool in phylogenetic studies of the pathogenicity groups.

Base Sequence↗
PubMed1995

[A case of acute idiopathic pandysautonomia with SIADH].

We reported a 6-year-old girl with acute idiopathic pandysautonomia (AIPD) associated with syndrome of inappropriate secretion of anti-diuretic hormone (SIADH). She showed various symptoms indicating the impairment of widespread sympathetic and parasympathetic nervous functions and SIADH, which followed common cold. Sural nerve biopsy showed severe reduction of both myelinated and unmyelinated fibers. The main site of the lesion of AIPD has been assumed to be the peripheral autonomic nervous system. However, there are a few reports indicating the involvement of the central nervous system in AIPD. The present case also indicates the involvement of hypothalamus in addition to the peripheral autonomic nervous system.

Acute Disease↗
PubMed1993

Electrical impedance in the lower limbs of patients with Duchenne muscular dystrophy: a preliminary study.

Electrical impedances were measured, at a range of frequencies from 2 to 200 kHz, in the lower limbs of nine patients with Duchenne muscular dystrophy and 12 normal subjects. The specific admittance was calculated from the impedance, based on the assumption that the shape of the part of the limb measured is a truncated cone. Curve-fitting to the admittance locus on the complex plane gave the intracellular and extracellular resistances and the membrane capacitance. The intracellular resistance was higher and the membrane capacitance was lower in the patients than in the normal subjects. The membrane capacitance in the normal subjects increased with age. In the patients, the membrane capacitance decreased, and the intracellular resistance increased with the stage of disability, which was assessed by a physician. These experimental results agree well with the theoretical explanation, which uses simplified spherical models to represent living tissue.

Adolescent↗
PubMed1993

Lymphatic transport of eicosapentaenoic and docosahexaenoic acids as triglyceride, ethyl ester and free acid, and their effect on cholesterol transport in rats.

Lymphatic transport of docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids given in the forms of triglyceride, ethyl ester of free acid and their effect on cholesterol transport was compared in lymph-cannulated rats. Lymphatic recovery of DHA and EPA given by stomach tube in the form of triglyceride in which they were mainly located at the 2-position was significantly higher than that of the ethyl ester or free acid during the first 6 hr after the administration and the tendency continued until 9 hr. In contrast, the 9 to 24 hr recovery of DHA and EPA in the forms of ethyl ester and free acid was considerably higher than that of triglyceride. Consequently, cumulative 24 hr recovery of EPA was comparable among the three forms. However, the 24 hr recovery of DHA was highest in free acid, lowest in ethyl ester and intermediate in triglyceride. Recovery of the free acid between 9 and 24 hr after administration was significantly higher than that given in the forms of triglyceride or ethyl ester. Cholesterol recovery in lymph of rats given with ethyl ester or free acid was lower than that given with triglyceride at an early stage after the administration in both EPA and DHA. Cumulative 24 hr recovery of cholesterol in rats given these fatty acids as ethyl ester was significantly lower than in those given as the other two forms.

Animals↗
PubMed1993

[Effects of intravenous infusion of isosorbide dinitrate on hemodynamics during anesthesia and surgery].

Ninety nine patients with ischemic changes of the heart on preoperative and intraoperative ECG tracings were studied to evaluate effects of intravenous infusion of isosorbide dinitrate on hemodynamics during anesthesia and surgery. These patients ranging in ages from 24 to 80 years were administered intravenous isosorbide dinitrate at a rate of either 0.5 or 1 microgram.kg-1 x min-1 during anesthesia and surgery. Arterial blood pressure was not influenced with intravenous isosorbide dinitrate at the speed of 0.5 microgram.kg-1 x min-1 during anesthesia and surgery. The arterial pressure of the patients decreased slightly but significantly 30 min after the start of 1 microgram.kg-1 x min-1 of isosorbide dinitrate infusion, but it recovered to the control level at the end of administration of isosorbide dinitrate. Heart rate was unchanged with intravenous isosorbide dinitrate during anesthesia and surgery in both groups, except a mild increase at the end of isosorbide dinitrate infusion of 1 microgram.kg-1 x min-1. Arterial blood oxygen tension showed no decrease during the administration of isosorbide dinitrate and no adverse reactions associated with administration of the drug was detected in this study. Significant improvement of ischemic changes on ECG tracings were observed in about 25% of the patients who received 1 micrograms.kg-1 x min-1 of intravenous isosorbide dinitrate.

Adult↗
PubMed1992

Tea catechins decrease micellar solubility and intestinal absorption of cholesterol in rats.

A(-)-epicatechin (EC) and (-)-epigallocatechin (EGC) mixture and a mixture of their gallates (ECG and EGCG, respectively) markedly lowered lymphatic cholesterol absorption in rats with a cannulated thoracic duct. A mixture of ECG and EGCG was more effective in reducing cholesterol absorption than the EC and EGC mixture. These catechins also tended to decrease lymphatic absorption of triacylglycerols, although not so pronounced as in cholesterol absorption. An in vitro study on micellar solubility of cholesterol showed that these catechin mixtures precipitated cholesterol solubilized in mixed bile salt micelles in a dose-dependent manner. A mixture of ECG and EGCG more effectively precipitated micellar cholesterol than a mixture of EC and EGC. When purified EC, EGC, ECG and EGCG were used, EGCG was more effective in precipitating micellar cholesterol than ECG. The effect of EC and EGC was comparable and weaker than their gallate esters. The bile acid concentration in the micelles was not affected by these catechins. A positive correlation was observed between the amount of coprecipitated EGCG and cholesterol. These results clearly show that tea catechins, in particular their gallate esters, effectively reduce cholesterol absorption from the intestine by reducing solubility of cholesterol in mixed micelles. The observation accounts for the hypocholesterolemic effect of tea catechins.

Animals↗
PubMed1992

MRI in poliomyelitis-like syndrome.

We report the MRI findings in a patient with poliomyelitis-like syndrome. MRI demonstrated a lesion extending from the dorsal region of the pons to the upper level of the thoracic spinal cord. The spinal cord was particularly affected in a region involving the bilateral anterior horns. Although its pathology is unknown, the lesion of the spinal cord seemingly reflects the pathological features of this disease.

Humans↗
PubMed1992

Three types of hyperthermic seizures in rats.

Three types of rat hyperthermic seizures were observed. The first comprised generalized clonic convulsions preceded by intermittent myoclonus. Ictal EEG showed diffuse intermittent spikes and sequential rapid spike-wave bursts (type 1 seizures). In the other types of seizures, the paroxysmal discharges originated in the occipital region without (type 2a seizures) or with (type 2b seizures) secondary generalization. Type 2a seizures involved no convulsive movement whereas type 2b seizures involved clonic convulsions. The threshold temperatures for type 1, 2a and 2b seizures were 44.1 +/- 0.60, 40.9 +/- 1.47 and 42.1 +/- 0.75 degrees C, respectively. Of these seizures, the type 2 seizures (2a and 2b) did not severely affect the general condition of rats and thus may be an appropriate model for the investigation of febrile seizures.

Animals↗
PubMed1992

A female patient with Lesch-Nyhan syndrome.

The authors report the second case of a female with typical Lesch-Nyhan syndrome. She exhibited athetoid movement, self-multilation, mental retardation and spasticity. Laboratory investigations revealed hyperuricaemia, hyperuricosuria and decreased erythrocyte hypoxanthine guanine phosphoribosyl transferase activity. She has normal female external genitalia and karyotype. Her parents are non-consanguineous and there is no family member with gout, nephropathy or any psychoneurological disorder. To prevent self-stimulation, it was necessary to fix the patient's upper extremities to the backrest of her wheelchair. The authors also describe an apparatus that limits elbow flexion.

Child↗
PubMed1992

[Neurophysiologic and histopathologic studies in a case of congenital sensory neuropathy with anhidrosis].

A three year-old boy with congenital sensory neuropathy with anhidrosis (CSNA) was described. Sural nerve biopsy specimens revealed an almost complete absence of unmyelinated fibers and a marked decrease of the density of small myelinated fibers with preservation of the density of large myelinated fibers. No evidence of active degeneration of unmyelinated or myelinated fibers was found. Skin biopsy specimens revealed the absence of nerve terminals and fibers innervating sweat glands, although sweat glands seemed to be apparently normal in their morphological findings. Therefore, it was concluded that the absence of pain and temperature sensations with preservation of touch sensation in our patient was compatible with the morphometric findings of nerve fibers of the sural nerve described. Similarly anhidrosis was concluded to be well explained by the absence of the innervation of sweat glands and the vessels around them. On the other hand, electrophysiologic studies, such as motor and sensory nerve conduction, short latency somatosensory evoked potential and auditory brainstem response, in which the function of the large myelinated fibers is presumably tested, were all normal. Therefore, the structure and function of such large myelinated fibers were spared in this case. From clinical viewpoints, electrophysiologic studies described above are useful to differentiate CSNA from other types of congenital sensory neuropathies, in which large myelinated fibers are affected.

Electrophysiology↗
PubMed1992

[The first case of infantile type neuronal ceroid-lipofuscinosis in Japan].

We reported the first case of typical infantile-type neuronal ceroid-lipofuscinosis (INCL) in Japan. The patient was a 1-year-old girl presenting with rapidly progressive psychomotor deterioration and blindness. Muscular hypotonia, microcephaly and myoclonic jerks became marked with the progression of her disease. Diminution in amplitude of EEG, VEP and ERG was prominent in the initial stage, but ABR was normal. MRI showed progressive brain atrophy. Electron microscopic examination of the biopsied skin revealed granular matrix, the specific inclusion bodies, in the epithelial cell of sweet glands. Many sea-blue histiocytes were demonstrated in her bone marrow samples. INCL is a common progressive encephalopathy in the Scandinavian countries, but a typical case had not yet been fully reported in Japan. This prompted us to report our case. Future reports are need for the study of INCL in Japan.

Biopsy↗
PubMed1992

[Clinical evaluation of prostaglandin E1 during anesthesia in non-elderly and elderly patients].

The effects of prostaglandin E1 (PGE1) on blood pressure during anesthesia and the postoperative changes in organ functions were examined and compared in 358 cases. Two hundred and eighty patients were under 64 years of age and 128 patients were over 65 years. It was possible to control blood pressure satisfactorily with PGE1 in both non-elderly and elderly groups. However in the elderly group, it was more difficult to control blood pressure with PGE1 under NLA as compared with enflurane anesthesia. In both groups, urinary flow increased during and after the administration of PGE1, and the livers and kidneys showed neither dysfunction nor deterioration after operation. We had very few incidences of side effects with this drug. PGE1 is also considered safe and useful for elderly people during and after surgery.

Adolescent↗
PubMed1991

Structure/activity relationship of eel calcitonin. A study using a newly devised method for designing analogs.

A series of analogs of eel calcitonin (eCT) was synthesized according to a newly devised scheme, 'the insertion-inactivation method', to clarify the structure/activity relationship of a given peptide. This method consists of two steps: the deletion of a residue of the peptide is first chosen and then a series of analogs with the residue reinserted into serial positions is synthesized and biological activities are assessed in each step. An analog lacking Lys18 (dK), selected as a deleted analog for the first step, showed marked loss of activities determined by inhibition of 125I-eCT binding, growth inhibition, and cAMP production in a porcine kidney cell line LLC-PK1. Activities of a set of 20 analogs with the reinserted lysine residue at serial positions from 12 to 32 (K12-K32) were then evaluated. The results showed the following three patterns of the expression of activities according to the position of the reinsertion: (a) analogs K12-K16 (positions 12-16) and K25 (position 25) showed lower activities than eCT in all assays; (b) K17-K24 (positions 17-24) showed slightly lower activities than eCT in the receptor binding and the growth inhibition and similar level in cAMP production; (c) K26-K32 (positions 26-32) showed considerably lower activities in the former two assays and slightly lower activity in cAMP production. Further, analogs considerably less active than eCT showed unchanged alpha-helix contents and destroyed amphiphilicity by the insertion of a lysine residue, indicating that amphiphilicity is one of important factors for expressing the activity. The results obtained here lead to a conclusion on the significance of each region of eCT molecule as follows: (a) the presence of Lys18 is necessary for the complete expression of biological activity; (b) the length of amphiphilic alpha-helix to be required for the activity is at most 10 residues ranging from position 8 to position 17; (c) the receptor binding region is located within 9 residues ranging from position 24 to position 32.

Amino Acid Sequence↗