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Biomedical subjects

N Murakami

Publications and source records attributed to N Murakami.

At least 361 records · Page 20Linked to original sources

Roles of interleukin-1 alpha and -1 beta in endotoxin-induced suppression of plasma gonadotropin levels in rats.

Using specific antagonists to rat interleukin (IL)-1 alpha and IL-1 beta, the roles of these IL-1s in endotoxin-induced suppression of plasma gonadotropin levels in freely-moving rats were studied. In orchiectomized rats, recombinant rat IL-1 alpha and IL-1 beta administered into the lateral ventricles almost equipotently suppressed plasma LH levels. Twenty five micrograms of bacterial endotoxin or lipopolysaccharide (LPS) administered similarly showed a comparable effect as that of 1 microgram IL-1 alpha or IL-1 beta, and completely lowered plasma LH levels by 60 min after the injection. To examine the roles of endogenous IL-1 alpha and IL-1 beta, anti-rat IL-1 alpha antiserum (anti-IL-1 alpha) and a recombinant human IL-1 receptor antagonist (IL-1ra) were used as specific blockers for IL-1 alpha and IL-1 beta, respectively. Anti-IL-1 alpha (10 microliters) or IL-1ra (10 micrograms) administered intracerebroventricularly (icv) with 25 micrograms LPS, significantly attenuated the LPS-induced effect on plasma LH levels during the first 60 min after LPS infusion, but not during the second 60 min. LPS at a dose of 5 micrograms induced smaller but still significant changes in plasma LH levels compared with 25 micrograms LPS or 1 microgram IL-1 beta. IL-1ra (10 micrograms) completely blocked LH suppression induced by 1 microgram IL-1 beta, but did not completely reverse the changes of LH induced by 5 micrograms LPS. IL-1ra injected iv also significantly attenuated the early suppressive effect of iv administered LPS, but not its late effect on plasma LH levels. However, iv administered IL-1ra had no influence on the effects of icv administered LPS. These data indicate that at least a part of plasma LH suppression caused by icv administered LPS is mediated via IL-1 alpha and IL-1 beta synthesized within the brain, while factor(s) other than IL-1 also participate in the LPS-induced change, particularly during the later period. A similar mechanism may also work peripherally in the case of iv administered LPS-induced plasma LH suppression.

Animals↗

Studies on the chemical modification of monensin. IV. Synthesis, sodium ion permeability, and biological activity of 7-O-acyl- and 7-O-alkylmonensins.

7-O-Acyl-(4a-e) and 7-O-alkylmonensins (5a-d) were prepared from monensin (1). Their lipophilicity, sodium ion permeability in human erythrocytes, antibacterial activity and effect on rat tail artery were examined. There was a correlation between lipophilicity and sodium ion permeability as well as between lipophilicity and antibacterial activity. We also found that the compound having larger sodium ion permeability, showed stronger contraction of rat tail artery. 7-O-Benzylmonensin (5c) exhibited higher lipophilicity and larger sodium ion permeability than monensin (1) among the tested monensin derivatives. In addition, antibacterial activity and contractile effect on rat tail artery of 5c were comparable to those of 1.

Animals↗

Thunberginols A, B, and F, new antiallergic and antimicrobial principles from hydrangeae dulcis folium.

Six new antiallergic and antimicrobial principles, thunberginols A, B, C, D, E, and F, were isolated from Hydrangeae Dulcis Folium, the fermented and dried leaves of Hydrangea macrophylla SERINGE var. thunbergii MAKINO. The chemical structures of thunberginols A, B, and F have been determined on the basis of chemical and physiocochemical evidence. Thunberginols A, B, and F showed more potent antiallergic activity than phyllodulcin, hydrangenol, and AA-861 in the in vitro test using the Schults-Dale reaction in sensitized guinea pig bronchial muscle. Thunberginols A, B, and F also exhibited antimicrobial activity against oral bacteria.

Animals↗

Studies on cardiac ingredients of plants. IX. Chemical transformation of proscillaridin by utilizing its 1,4-cycloadducts as key compounds and biological activities of their derivatives.

Three aromatic compounds (2-4) possessing a carbomethoxyl group or a dimethoxyphthaloyl group, prepared by the Diels-Alder reaction of the cardiac glycoside, proscillaridin (1), with dimethyl acetylenedicarboxylate and methyl propiolate, were transformed into alcohols, carboxylic acids and amides. The biological activities of the resulting derivatives were evaluated by the use of Na+, K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) from dog kidney and isolated guinea-pig papillary muscle. Although the biological activities of the resulting derivatives were less potent than that of 1, a para-substituted benzylalcohol (5), methylbenzamides (9a and 10a), and ethylbenzamides (9b and 10b) inhibited the activity of Na+,K(+)-ATPase almost as potently as naturally occurring cardiac glycosides such as digoxin and digitoxin.

Animals↗

Thunberginols C, D, and E, new antiallergic and antimicrobial dihydroisocoumarins, and thunberginol G 3'-O-glucoside and (-)-hydrangenol 4'-O-glucoside, new dihydroisocoumarin glycosides, from Hydrangeae Dulcis Folium.

New antiallergic and antimicrobial dihydroisocoumarins, thunberginols C, D, and E, were isolated from Hydrangeae Dulcis Folium, the fermented and dried leaves of Hydrangea macrophylla SERINGE var. thunbergii MAKINO, together with new dihydroisocoumarin glycosides, thunberginol G 3'-O-glucoside and (-)-hydrangenol 4'-O-glucoside. Their chemical structures have been determined on the basis of chemical and physicochemical evidence. Thunberginols C, D, E, G, and (-)-hydrangenol 4'-O-glucoside showed antiallergic activity in the in vitro bioassay using the Schults-Dale reaction in sensitized guinea pig bronchial muscle, and they also exhibited antimicrobial activity against oral bacteria.

Animals↗

[Studies on cardiac ingredients of plants. X. Preparation of nitrates of tetrahydroproscillaridin and their pharmacological activities].

To reduce the vascular contracting effect of the hydrogenated cardiac glycosides, 20-(R)- and 20-(S)-tetrahydroproscillaridins (THPs, 1a, 1b), and to extend the concentration-dependent range, mono- and dinitrates of THPs were prepared. The pharmacological activities of the nitrates of THP were evaluated by use of isolated guinea-pig papillary muscle preparations and Na+,K(+)-adenosine triphosphatase preparations from dog kidney. Furthermore, the effect for smooth muscle was examined using the helical strips isolated from 13-week-old spontaneously hypertensive rat. The positive inotropic effects of mononitrates (11a, 11b, 2a, 2b, 8a, and 8b) were more potent than those of THPs. Nitration of the sugar moiety in THPs resulted in a vascular relaxing effect unobserved in the case of THPs.

Animals↗

[Effects of sodium hyaluronate on the nociceptive response of rats with experimentally induced arthritis].

Antinociceptive effects of sodium hyaluronate (Na-HA) were studied on the basis of improvement in the graded abnormal gait elicited by arthritis induced by intra-articular administration of monosodium urate crystal (MSU) to rats. One hour before MSU injection, intra-articular administration of a 1.0% solution of Na-HA with different molecular weights, ranging from 4.70 x 10(5) to 2.02 x 10(6) (HA-200), improved the score of abnormal gait in a molecular weight-dependent manner in the experimental arthritis model. Similarly, administrations of HA-200 at concentrations ranging from 0.1 to 1.0% prior to MSU treatment resulted in improvement of the score in abnormal gait in a dose-dependent manner. To elucidate the antinociceptive mechanisms of Na-HA, effects of pretreatment with Na-HA (1.0%) of different molecular weights on prostaglandin E2 (PGE2) and bradykinin (BK) releases in synovial fluid 3 hr after MSU injection were studied. Increases in PGE2 and BK concentration in the synovial fluid were depressed in a molecular weight-dependent manner by Na-HA (1.0%) pretreatment. These results indicate that Na-HA attenuates the nociceptive responses inflicted by the MSU-induced arthritis. Such an antinociceptive effect may be due to the inhibition of PGE2 and BK synthesis in the synovial joint of rats.

Analgesics↗

Prediction of the outcome of postoperative hypocalcemia in Graves' disease.

Symptomatic hypocalcemia sometimes follows subtotal thyroidectomy for Graves' disease. Irreversible damage to the parathyroids contributes to permanent hypocalcemia and the mechanism for a transient hypocalcemia is thought to be different from that of a permanent one. However, sensitive assays for parathyroid hormones (PTH), which had recently become available, revealed that levels of PTH decrease in patients with transient hypocalcemia. In order to differentiate a prolonged hypocalcemia from a transient one, calcium and inorganic phosphate concentrations in serum as well as in urine, and whole molecule-PTH levels were determined in 18 Graves' disease patients with postoperative hypocalcemia just after the initial symptoms for hypocalcemia appeared. In 13 patients, medication was withdrawn within one month since serum calcium levels had returned to normal (transient hypocalcemia). In five other patients, medication was required for six months or more to maintain normocalcemia (prolonged hypocalcemia). The same parameters were determined after surgery in eight Graves' disease patients without hypocalcemia. Urinary inorganic phosphate concentrations in patients with prolonged hypocalcemia (0.02 +/- 0.01 mmol/mmol Cr) were significantly lower (P less than 0.01) than those in patients with transient hypocalcemia (1.59 +/- 1.59 mmol/mmol Cr) or those in control patients (1.27 +/- 0.70 mmol/mmol Cr). Preoperative concentrations of calcium and inorganic phosphate in serum and urine, and serum alkaline-phosphatase activities were also determined. However, there were no significant differences in these parameters between patients with prolonged and those with transient hypocalcemia. It is concluded that prolonged hypocalcemia is discriminated from the transient type by determining the urinary inorganic phosphate at the time of appearance of the initial symptoms for hypocalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[A clinicopathological study on 13 cases of motor neuron disease with dementia].

Thirteen patients suffering from motor neuron disease with dementia were studied to analyze the clinicopathological spectrum. The diagnosis of the disease was made on the basis of a clinical history of progressive dementia and motor neuron involvement. The mean age at onset of 11 sporadic cases was 54.9 years (range, 43 to 69 years), with a mean duration of disease of 25 months (range, 11 to 47 months). The initial symptoms were dementia in 7 cases, motor neuron involvement in 2 cases, and both dementia and motor neuron involvement in 2 cases. The clinical picture of motor neuron disturbance in sporadic cases represented bulbar-type of amyotrophic lateral sclerosis (ALS). Bulbar palsy was the initial symptom in 7 sporadic cases and all 11 patients developed bulbar palsy with advancing course of illness. Muscular wasting and fasciculation were more predominant in the upper limbs, shoulder girdle and anterior chest. Fasciculation was more extensively and frequently observed in those portions than that of classical ALS. In contrast, muscle strength in the lower limbs was well preserved so that all patients could walk even when respiratory failure developed. Hyperreflexia including jaw jerk was found in all cases and positive Babinski sign in 7 cases. Parkinsonism appeared in the initial stage in one sporadic case and in two familial cases. The type of dementia with uninhibited behavior and personality change closely mimicked that of Pick's disease. The degree of dementia was mild or moderate in 8 cases and severe in 3 cases. Language disorder was characterized by progressive reduction of speech output, leading finally to mutism in 5 cases. Perseveration was observed in 10 cases. Visuospatial disorder was absent even in the advanced stage. Mild memory disturbance was noted in the early stage in 10 cases. Pathological examination was performed in 7 cases including one familial case, revealing frontal atrophy in 3 cases, frontotemporal atrophy in 2 cases and temporal atrophy in 2 cases. On microscopic examination there were mild neuronal loss, gliosis, mild spongy state of the cortical superficial layers and fibrous gliosis in the frontotemporal white matter. The scattered senile plaques in one case did not justify a diagnosis of Alzheimer's type dementia. Neither circumscribed atrophy nor Pick body was found in any case. The nucleus basalis of Meynert showed no neuronal loss. The substantia nigra showed a mild to severe loss of nerve cells without Lewy bodies in all cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Determination and clinical significance of human hepatocyte growth factor in serum].

Hepatocyte growth factor (HGF) is the most potent mitogen for mature parenchymal hepatocytes in primary culture, and seems to be a hepatotrophic factor that acts as a trigger for liver regeneration after partial hepatectomy and liver injury. In the present study, we evaluated an enzyme-linked immunosorbent assay, using monoclonal antihuman HGF (h-HGF) antibody, for measuring serum h-HGF levels. Intra- and inter-assay coefficients of variation were 2.2-3.3% and 3.4-4.0%, respectively. Detection limit of this method was 0.1 ng/ml, determining by the dilution test. The substances tested did not interfere with this assay, except for high concentrations of hemoglobin. Furthermore, no interference was observed with plasminogen and lipoprotein (a), which show the structural homology to h-HGF, and with various kinds of cytokines. Reference ranges of serum h-HGF determined with 187 healthy subjects were 0.1-0.23 ng/ml. Serum h-HGF concentrations were increased in various kinds of liver diseases, in particular those were significantly higher in fulminant hepatic failure. Furthermore, prognosis of the patients with higher h-HGF values were strikingly worse than those with lower levels. We concluded that the determination of serum h-HGF plays important roles in the early diagnosis and prognosis of fulminant hepatic failure.

Antibodies, Monoclonal↗

Effects of repetitive administration of recombinant human interleukin-1 beta, an analog or corticotropin-releasing hormone combined with lysine vasopressin on rats with glucocorticoid-induced secondary adrenocortical insufficiency.

We investigated effects of corticotropin-releasing hormone (CRH), lysine vasopressin and interleukin (IL)-1 beta[1-148], a less pyrogenic analog of human IL-1 beta, on the hypothalamo-pituitary-adrenal axis in a rat model of secondary adrenocortical insufficiency. After 2 weeks of corticosterone 21-sodium succinate treatment, hypothalamic CRH, anterior pituitary adrenocorticotropic hormone (ACTH) and the adrenal weight of the rats decreased significantly and their plasma ACTH showed a significantly smaller response to ether stress, as did plasma corticosterone level. A mixed solution of CRH (10 micrograms) and lysine vasopressin (2 micrograms) or recombinant human IL-1 beta[1-148] (1 micrograms), administered to these rats for 7 days, apparently accelerated the recovery of the pituitary and adrenocortical responsiveness to ether stress and significantly increased the recovery rate of anterior pituitary ACTH contents and adrenal weight. The IL-1 beta analog also increased hypothalamic CRH. These data indicated that, in a rat model with glucocorticoid-induced adrenocortical insufficiency, synthesis and release of hypothalamic CRH, pituitary ACTH and adrenal glucocorticoid were all considerably affected. CRH combined with lysine vasopressin or a less pyrogenic IL-1 beta analog, when administered to these rats, accelerated the recovery of the pituitary and the adrenocortical functions significantly, suggesting the potential clinical usefulness of these peptides.

Adrenal Insufficiency↗

[Cerebrospinal fluid levels of 28 kDa calcium-binding protein in patients with neurological diseases].

Vitamin D-dependent calcium-binding protein (Calbindin-D: CaBP) (MW 28 kDa) is present in high concentrations in the central nervous system (CNS), especially in the cerebellum. In the cerebellum, CaBP is localized in Purkinje cells. By using an enzyme immunoassay method, we measured the cerebrospinal fluid (CSF) levels of CaBP in 96 neurological patients and 24 control subjects, and evaluated the clinical usefulness of determining CaBP, especially in the diagnosis of cerebellar damage. CSF CaBP levels were strikingly elevated in patients with cerebellar lesions, including primary spinocerebellar degeneration (SCD), subacute cerebellar degeneration with lung cancer, Wernicke-Korsakoff syndrome, as well as in patients with cerebrovascular disease (CVD) without involvement of the cerebellum. In these 2 groups, neuron-specific enolase (NSE) levels were determined. The ratio of CaBP to NSE (CaBP/NSE) in patients with cerebellar lesions was higher than that in CVD, reflecting differences in lesions between these 2 groups. In the SCD group, multiple system atrophy (MSA) showed higher CaBP levels than the other types of SCD. Probably it reflects remarkable damage of the Purkinje cells in MSA. In MSA, the CaBP levels decreased with the duration of illness. In myelopathy, neuropathy, meningitis, multiple sclerosis, and other degenerative diseases, the increase of CaBP was not remarkable. Our results suggested that CSF CaBP is considered to be a marker of cerebellar damage.

Adolescent↗

[Atrial septal defect associated with von Willebrand's disease--a case report].

Von Willebrand's disease is common hemorrhagic disorder that deserves particular attention in the patient undergoing open-heart surgery, because of perioperative unexpected bleeding. The present case is atrial septal defect associated with Willebrand's disease, affecting a 19-year-old female who has the past history of bleeding tendency with frequent subcutaneous bleeding. It is mandatory to maintain adequate levels of both factor VIII coagulation and ristocetin cofactor activities during the perioperative period. An infusion study of heat-treated evaluate the response and half-life of both factor VIII coagulation and ristocetin cofactor activities; and to calculate the effective dose and duration of the drug action as well as to formulate a protocol for patient's management in the perioperative periods in order for the surgical intervention to be performed uneventfully. Our case demonstrated that it is possible to perform an open heart surgery in patients with von Willebrand's disease without major bleeding as far as the levels of both factor VIII coagulation and ristocetin cofactor activities are maintained above 50% in the postoperative critical period.

Adult↗

[Anaphylactoid reactions to contrast media which occurred during cholecystectomy and subsequent disseminated intravascular coagulation--a case report].

A 67-year-old woman without any history of allergic episode developed severe hypotension (40 mmHg) without skin rash one minute after the administration of amidotrizoic acid for intraoperative cholangiography during thoracic epidural and light general anesthesia. Although ephedrine, methoxamine, dopamine and norepinephrine were administered, severe hypotension persisted for three hours and epinephrine was only effective. Marked elevations of serum levels of histamine, leukotriene D4 and leukotriene E4 were noted after the episode, suggesting the occurrence of the anaphylactoid reaction to amidotrizoic acid and the activation of the immunological complement system. After the recovery from the anaphylactoid reaction, the patient developed disseminated intravascular coagulation (DIC) and severe bleeding around the wound for which reoperation was needed. It is necessary to consider some prophylactic treatments against DIC when severe anaphylactoid reaction occurred.

Aged↗

[A clinicopathological study of two respirator-aided long-survival cases of amyotrophic lateral sclerosis].

We reported two respirator-aided 10-year-survival male patients with sporadic amyotrophic lateral sclerosis (ALS). Their ages at onset were 54 and 52, clinical features common in both cases, the durations to tracheotomy 32 months and 27 months respectively, and the durations for respiratory support over 8 years in both cases. There were normal external ocular movement, normal pelvic sphincter function, normal sensory system and no bed sores throughout 10 years of illness. The brain weighted 1,295 g in case 1 and 1,430 g in case 2, being normal macroscopically. The spinal cord was slightly wasted with atrophic anterior roots. The histopathological study demonstrated the typical pattern of ALS in spite of the prolonged survival with artificial respiration. Neuronal loss and gliosis of the motor nuclei in the spinal cord and brainstem were more striking than those of the natural course. Neither hypertrophic astrocyte, central chromatolysis nor neuronophagia was observed. This finding suggested inactive condition of the degeneration. The pattern of white matter degeneration in the cord indicated some pallor of anterior and lateral columns, severe pallor of pyramidal tracts and intact posterior column and spinocerebellar tracts. The giant pyramidal cells in the precentral gyrus were lost in both cases. Pyramidal degeneration was traceable up to the cerebral peduncles in the case 2 and undetectable in that portion in the case 1. On the other hand, the extraocular muscle nuclei, the Onuf's nuclei, the dorsal motor nucleus of the vagus nerve, intermediolateral and Clarke's nuclei were relatively preserved, though no cell count was done in Clarke's nuclei and Onuf's nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗