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Biomedical subjects

M Fujiwara

Publications and source records attributed to M Fujiwara.

At least 613 records · Page 34Linked to original sources

Levels of neurokinin A, neurokinin B and substance P in rabbit iris sphincter muscle.

We investigated the contents of neurokinin A, neurokinin B and substance P in the rabbit iris sphincter muscle, combining HPLC and radioimmunoassay, as our previous reports indicated that a slow component of neurogenic contractions of this muscle is most probably mediated by such tachykinins. The concentrations of these tachykinins were 44.3 +/- 8.7 fmol/mg protein, 35.3 +/- 10.2 fmol/mg protein and 186.8 +/- 29.8 fmol/mg protein (N = 4), respectively. These results demonstrated that neurokinin A, neurokinin B and substance P are all present in the rabbit iris sphincter muscle.

Animals↗

Role of ammonia in the pathogenesis of brain edema.

The role of hyperammonemia in the pathogenesis of cerebral edema was investigated using mongrel dogs to develop a treatment for cerebral edema in acute hepatic failure. Intravenous infusion of ammonium acetate alone into dogs did not induce brain edema, although blood ammonia reached unphysiologically high levels. However, ammonium acetate infusion during mannitol-induced reversible (osmotic) opening of the blood-brain barrier (BBB) effectively induced cytotoxic brain edema. Pretreatment with a branched-chain amino acid (BCAA; valine, leucine and isoleucine) solution prevented an increase in intracranial pressure (ICP) and brain water content, and caused a decrease in brain ammonia content and an increase in brain BCAA and glutamic acid. The results suggest that ammonia plays an important role in the pathogenesis of cerebral edema during acute hepatic failure and that BCAAs accelerate ammonia detoxification in the brain.

Acetates↗

Detection of type V collagen-degrading enzyme activity in human liver.

Type V collagen-degrading enzyme activity was detected as a metalloprotease acting at neutral pH in the human liver. Type V collagen extracted from human placenta and labeled with [1-14C] acetic anhydride was used as the substrate in the assay. Four major degradation products with relatively high molecular weights were observed upon polyacrylamide gel electrophoresis of the incubation mixture of type V collagen and liver homogenate. The significance of the measurement of this enzyme activity was discussed in relation to the clarification of the mechanism of liver fibrosis.

Collagen↗

Assay procedures for cathepsin B, H and L activities in rat tissue homogenates.

Cathepsin B, H and L activities in small amounts of rat tissue homogenates corresponding to 10 micrograms protein were determined with 7-amino-4-methyl-coumarin conjugates as substrates. A new procedure for serum cathepsin H activity was also developed. High cathepsin B and H activities were found in kidney, spleen and liver. Liver cathepsin B, H and L activities in D-galactosamine-injured rats were decreased concomitantly with an increase in serum cathepsin H activity.

Animals↗

Mechanism of action of a polypeptide neurotoxin from the coral Goniopora on sodium channels in mouse neuroblastoma cells.

Goniopora toxin (GPT), a polypeptide toxin of 9700 Da isolated from coral, markedly slows inactivation of sodium currents recorded under voltage clamp in mouse neuroblastoma cells. The voltage dependence of sodium channel activation is shifted to more negative membrane potentials by 9.8 +/- 2.1 mV, and the voltage dependence of channel inactivation is shifted to more positive membrane potential by 6.0 +/- 2.5 mV. These actions of GPT are voltage dependent with an e-fold increase in K0.5 for toxin action for each 48.3-mV depolarization between -80 and +40 mV. GPT requires Na+ or another alkali metal cation in the extracellular medium for its effect on sodium channels. The relative effectiveness of the different cations tested is Na+ greater than K+ greater than Rb+ greater than Li+ greater than Cs+ much greater than choline+. Like other polypeptide neurotoxins that slow inactivation of sodium channels, GPT enhances persistent activation of sodium channels by veratridine. However, GPT does not block the binding of 125I-labeled Leiurus scorpion toxin to neurotoxin receptor site 3 on sodium channels at concentrations which effectively slow channel inactivation. Therefore, our results define a new site on the sodium channel at which specific effects on inactivation can occur.

Action Potentials↗

Effects of neurokinin A, substance P and electrical stimulation on the rabbit iris sphincter muscle.

A mammalian tachykinin, neurokinin A (NKA), and its analogs produced concentration-dependent contractions in the isolated rabbit iris sphincter muscle. Their potencies were slightly less than substance P (SP) but the maximal efficacies were much the same as seen with SP, except that the times required for the development of the contraction and for the recovery to the original level after washout were more rapid than in the case of SP. Although preceding exposure to SP reduced the subsequent responses to SP, NKA, carbachol, electrical stimulation and capsaicin, the exposure to NKA resulted in no such desensitization in the subsequent responses. Also, no reduction in the responses to NKA, SP and carbachol was observed in the preparations which had been exposed to capsaicin beforehand. The contractile responses to NKA and its analogs were more effectively inhibited by [D-Pro2, D-Trp7,9]-SP than was the response to SP. [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP also inhibited the responses to NKA and its analogs but had no effect on the response to SP. Both SP-antagonists inhibited the noncholinergic, nonadrenergic contractile response to electrical transmural stimulation. These results indicate that NKA and its analogs are potent contractile tachykinins in the rabbit iris sphincter muscle and that the mode of action differs somewhat from that seen with SP. We propose that noncholinergic, nonadrenergic contraction induced by electrical transmural stimulation is mediated predominantly by NKA rather than by SP, even though both these compounds are released concomitantly from the trigeminal nerve.

Amino Acid Sequence↗

Gastric mucosal erosion due to a mucosal ischemia produced by thromboxane A2-like substance in rats under water-immersion stress.

The involvement of a thromboxane (TX) A2-like substance in the decrease of mucosal blood flow (MBF) and occurrence of gastric erosions in rats under water-immersion stress was examined. MBF was estimated by aminopyrine clearance. Stress increased acid output without a parallel increase in MBF and caused erosions. OKY-046, an inhibitor of TXA2 synthesis, and ONO-11120, an antagonist of TXA2 receptors, increased MBF during stress in parallel with an increase in acid output, and erosions did not form. In another experiment, the effects of a TXA2-like substance on MBF during vagal stimulation were examined. Although vagal stimulation alone increased acid output, there were no erosions in the stomach, probably because MBF was increased in parallel with acid output. Intra-arterial administration of a TXA2-like substance formed by the metabolism of arachidonic acid in the blood reduced MBF during vagal stimulation. Intra-arterial administration of ONO-11113, an agonist of TXA2 receptors, also reduced MBF during vagal stimulation. Neither agent affected the elevated level of acid output during vagal stimulation, and erosions formed in the glandular part of the stomach. These results suggested that the gastric mucosal erosions induced by water-immersion stress in rats were due to mucosal ischemia produced by the presumed formation of a TXA2-like substance and to the increased secretion of acid.

Animals↗

A case of pneumocytoma (so-called sclerosing hemangioma) with lymph node metastasis.

A case of "sclerosing hemangioma" (pneumocytoma) of the lung with lymph node metastasis is reported. A 22-year-old Japanese man was found to have a well-defined round lesion in the right lung (S7), which increased in size slightly during a 2-year follow-up period. He underwent right lower lobectomy with a preoperative diagnosis of a benign lung tumor. The pulmonary tumor revealed histological features characteristic of "sclerosing hemangioma" of the lung, in addition to which there were many large polygonal foamy cells, forming tubular or papillary structures. These cells were found by electron microscopy to contain numerous cytoplasmic lamellar bodies and showed a positive reaction with anti-surfactant apoprotein antibody immunohistochemically. Therefore, they were considered to be cells differentiating toward type II pneumocytes. Review of 21 typical "sclerosing hemangiomas" disclosed a few or some such foamy cells in 10 cases. A single hilar lymph node was the site of microscopic metastases, which consisted of "large clear foamy cells" and smaller polygonal or round cells with slightly eosinophilic cytoplasm, both of which were components of the pulmonary "sclerosing hemangioma." This case supports the theory that "sclerosing hemangioma" is a neoplasm of type II pneumocyte lineage. Although it is said to be benign, rare cases apparently show metastatic potential.

Adult↗

Biochemical characterization of alpha-adrenergic receptors in human brain and changes in Alzheimer-type dementia.

Using ligand binding techniques, we studied alpha-adrenergic receptors in brains obtained at autopsy from seven histologically normal controls and seven patients with histopathologically verified Alzheimer-type dementia (ATD). Binding of the alpha-adrenergic antagonists [3H]prazosin and [3H]yohimbine to membranes of human brains exhibited characteristics compatible with alpha 1- and alpha 2-adrenergic receptors, respectively. Binding of both ligands was saturable and reversible, with dissociation constants of 0.15 nM for [3H]prazosin and 5.5 nM for [3H]yohimbine. [3H]Prazosin binding was highest in the hippocampus and frontal cortex and lowest in the caudate and putamen in the control brains. [3H]Yohimbine binding was highest in the nucleus basalis of Meynert (NbM) and frontal cortex and lowest in the caudate and cerebellar hemisphere in the control brains. Compared with values for the controls, [3H]prazosin binding sites were significantly reduced in number in the hippocampus and cerebellar hemisphere, and [3H]yohimbine binding sites were significantly reduced in number in the NbM in the ATD brains. These results suggest that alpha 1- and alpha 2-adrenergic receptors are present in the human brain and that there are significant changes in numbers of both receptors in selected regions in patients with ATD.

Aged↗

Dissociation between acid secretion and mucosal blood flow after treatment of rats with reserpine.

The correlation between acid secretion and mucosal blood flow in the gastric mucosa after administration of reserpine to rats was determined in an attempt to define the etiology of reserpine-induced gastric erosions. Although gastric acid output was increased gradually by administration of reserpine, mucosal blood flow was not significantly affected. The increase in acid output induced by reserpine was completely prevented by pretreatment with atropine. Reserpine-induced increase in acid secretion may have been mediated by the vagus nerves, probably as a result of central and/or peripheral diminution in noradrenergic inhibitory mechanisms. The dissociation between mucosal blood flow and acid secretion, resulting in a relative ischemic state in the gastric mucosa, may have occurred in part from reduced cardiac function after treatment with reserpine. Vagal stimulation induced a parallel increase in both acid secretion and mucosal blood flow in control rats. 6-Hydroxydopamine-induced sympathectomy did not increase mucosal blood flow to a degree corresponding to the increase in acid output by vagal stimulation. In animals treated with 6-hydroxydopamine, gastric erosions occurred. We conclude that reserpine increases acid output but without a parallel increase in the mucosal blood flow and that the erosions which occur are probably due to the relative ischemic state of the gastric mucosa.

Animals↗

Low incidence of post-transfusion hepatitis in patients with liver cirrhosis.

A study has been undertaken to determine the incidence of post-transfusion hepatitis in 57 patients with liver cirrhosis (non-B type) and 93 cases without liver disease, who received blood transfusion during major surgery. A significantly lower incidence of post-transfusion hepatitis (5.3%) was found in patients with liver cirrhosis than in those (17.2%) without liver disease. Two out of three cirrhotic patients with post-transfusion hepatitis progressed to the clinical state of hepatic failure.

Adolescent↗

Evaluation of different preparations of aggregated human IgG for use as a standard in the assays of circulating immune complexes.

Comparative studies were carried out with regards to different preparations of aggregated human IgG (AGHG) to be used as the standard protein in the assays to estimate the amounts of circulating immune complexes. 5 different preparations of AGHG were used, in which WHO reference AGHG and glutaraldehyde-polymerized AGHG were included. These AGHG preparations were measured by the 4 different binding assays. Glutaraldehyde-polymerized AGHG, though weaker than heat-denatured AGHG in the binding activities, showed apparent dose-dependent curves in the 4 assays. It was also shown that molecular size of AGHG affect the binding activities: the smaller the molecular size, the weaker the binding activities. These results are considered to provide invaluable information for the standardization of the preparation of AGHG.

Antigen-Antibody Complex↗

[Quantitative integrated backscatter characteristics in the normal and infarcted canine myocardium].

To develop ultrasonic cardiac tissue characterization, serial changes in intensity of backscattered ultrasound from the normal and infarcted myocardium were studied in vitro, with frequency-domain analysis. As an index of backscattered signal intensity, quantitative integrated backscatter [(10 X log-S2/S1)] (dB), S1 and S2 = areas of power spectra of digitized (sample rate = 100 MHz, 8 bits) ultrasonic signals from a perfect reflector and good specimens) were calculated for 60 regions of the myocardium (N = 20, MI = 40) excised from 10 dogs 3 days, 1, 2, and 4 weeks after coronary artery ligation in 2, 3, 3, and 2 dogs, respectively. The myocardial specimens and a stainless steel reflector were mounted at the focal distance of a newly-developed wide-band transducer having a center frequency of 4.0 MHz, in a water bath filled with degassed physiological saline. Tissue concentrations of hydroxyproline (HP) were also established using a HPLC (Hitachi amino acid analyzer model 835). The results obtained were as follows: 1. No significant changes in the integrated backscatter of the normal myocardium were observed throughout the experimental period (3 days = -52.5 +/- 0.7, one week = -53.6 +/- 1.8, two weeks = -51.6 +/- 0.8, four weeks = -52.8 +/- 1.4 (dB) (mean +/- SE). 2. Integrated backscatter of the infarcted myocardium [3 days = -47.3 +/- 0.6, one week = -49.2 +/- 1.3, two weeks = -40.7 +/- 1.3, four weeks = -39.6 +/- 2.0 (dB)] was significantly increased compared with the integrated backscatter of the normal myocardium in the early stage of myocardial infarction, before tissue concentrations of hydroxyproline increased, as well as in the chronic stage of myocardial infarction. 3. Results of histological examinations suggest that minute changes in structure, such as interstitial edema or neovascular proliferations, may be the cause of an early increase in integrated backscatter. The results suggest that quantitative integrated backscatter is a sensitive parameter for detecting both early and old myocardial infarction by cardiac tissue characterization.

Animals↗

[Study on cefotiam in the perinatal period].

Cefotiam (CTM), a new cephem antibiotic with high activity against Gram-positive and Gram-negative bacteria, has been investigated for use in 60 mothers in perinatal period, and following results were obtained. The concentration of CTM in maternal serum was 38 micrograms/ml at 0.5 hour after an intravenous administration of 1 g. A good transport of CTM into umbilical cord serum and amniotic fluid was observed after the intravenous administration into the mother. No adverse effect appeared in the neonates. The CTM is highly useful antibiotic in perinatal infections, and the safe dose of CTM to the mother in perinatal period is considered to be 1-2 g per day.

Abortion, Induced↗

Elevation of plasma glucagon-like immunoreactivity (GLI) in patients with liver cirrhosis.

Plasma glucagon-like immunoreactivity (GLI) levels were increased in patients with liver cirrhosis. The levels were not significantly correlated with plasma glucagon immunoreactivity (GI) and serum insulin levels. None of the conventional liver function tests were correlated with the GLI levels, although plasma GI levels were high in cirrhotics with hyperammonemia. A significant correlation between plasma GLI and amino acid levels was not observed in these cases. The oral glucose tolerance test (OGTT) showed a significant decrease of plasma GI levels in cirrhotics but no change of plasma GLI concentrations: cirrhotic patients with diabetes mellitus or total gastrectomy showed marked increases of GLI levels. Glucagon (Glucagon Novo) injection at a dose of 10 micrograms/kg body weight to cirrhotic patients produced marked increases of both GI and GLI levels rapidly, though the mechanism of GLI elevation could not be clearly explained.

Adult↗

[A study on ceftazidime in the perinatal period].

Ceftazidime (CAZ), a new cephem antibiotic with high activity against Gram-negative bacteria, has been investigated for use in mothers in perinatal period, and the results obtained are summarized below. Into maternal serum, umbilical cord serum and amniotic fluid, CAZ showed good transfer after intravenous administration of 1 g or 2 g into mothers, and no adverse effect appeared in their neonates. The CAZ is a very useful antibiotic for the prophylaxis and the treatment of perinatal infections at a dose level of 1-2 g per day.

Bacterial Infections↗