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Biomedical subjects

N Ueda

Publications and source records attributed to N Ueda.

At least 397 records · Page 22Linked to original sources

Purification of arachidonate 5-lipoxygenase from porcine leukocytes and its reactivity with hydroperoxyeicosatetraenoic acids.

Arachidonate 5-lipoxygenase was purified to near homogeneity from the 105,000 X g supernatant of porcine leukocyte homogenate by immunoaffinity chromatography using a monoclonal anti-5-lipoxygenase antibody. Reaction of the purified enzyme with arachidonic acid produced predominantly 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid with concomitant formation of several more polar compounds in smaller amounts. These minor products were identified as the degradation products of leukotriene A4, namely, 6-trans-leukotriene B4 (epimeric at C-12) and an epimeric mixture of 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acids. These compounds were also produced by reaction of the enzyme with 5-hydroperoxy-eicosatetraenoic acid. Association of the 5-lipoxygenase and leukotriene A synthase activities was demonstrated by several experiments: heat inactivation of enzyme, effect of selective 5-lipoxygenase inhibitors, requirements of calcium ion and ATP, and self-catalyzed inactivation of enzyme. The enzyme was also active with 12- and 15-hydroperoxy-eicosatetraenoic acids producing (5S,12S)- and (5S,15S)-dihydroperoxy acids, respectively. Maximal velocities of the reactions with these hydroperoxy acids as compared with that of arachidonic acid (100%, 0.6 mumol/3 min/mg of protein) were as follows: 5-hydroperoxy acid, 3.5%, 12-hydroperoxy acid, 22%, and 15-hydroperoxy acid, 30%.

Animals↗

Stereoselective hydrogen abstraction in leukotriene A4 synthesis by purified 5-lipoxygenase of porcine leukocytes.

Arachidonate 5-lipoxygenase purified from porcine leukocytes transformed arachidonic acid to 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid. By the leukotriene A synthase activity of the same enzyme the product was further metabolized to leukotriene A4 (actually detected as 6-trans-leukotriene B4, 12-epi-6-trans-leukotriene B4, and 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acids). The enzyme was incubated with [10-DR-3H]- or [10-LS-3H]-labeled arachidonic acid, and 6-trans-LTB4 and its 12-epimer were analyzed. More than 90% of 10-DR-hydrogen was lost while about 100% of 10-LS-hydrogen was retained, indicating a stereospecific hydrogen elimination from C-10 during the formation of leukotriene A4.

Animals↗

Cerebral blood flow and metabolism in experimental hydrocephalus.

Cerebral blood flow and metabolism were studied in experimental hydrocephalus which was produced by intracisternal injection of kaolin in cats, rabbits and rats. Measurements were carried out in varied stages of hydrocephalus. Local cerebral blood flow (l-CBF) was measured by the hydrogen clearance method. Assessment of cerebral metabolism was made biochemically in the brain tissues of various regions, including water content, Na, K, lactate, pyruvate, lipids, ATP, cyclic AMP, catecholamines and monoamine metabolites. Blood flow studies were performed in the cerebral cortex, periventricular white matter, thalamus and midbrain reticular formation in hydrocephalic cats. In all of these regions, l-CBF decreased to about half of the control in both acute and chronic stages of hydrocephalus. CO2 reactivity to CBF was impaired only in the acute stage, while autoregulation of CBF was preserved in the hydrocephalic brain. Water content of the brain tissue increased temporarily only within the periventricular white matter of hydrocephalic rabbits concomitant with increase in Na and decrease in K. Transient increase in the lactate and lactate/pyruvate ratios was also observed in the frontal lobe tissue. In hydrocephalic rats, decrease in phospholipids and cholesterol was observed parallel with the degree of ventricular dilatation. ATP and cyclic AMP decreased biphasically in both acute and chronic stages. On the other hand, increase in concentrations of norepinephrine, dopamine, homovanillic acid, and 5-hydroxyindoleacetic acid became evident in the chronic stage of hydrocephalus. From the above results, it is concluded that the hydrocephalic brain sustained considerable disturbance of metabolism in all modalities in association with decreased blood flow, which is sufficient to explain the clinical symptoms of hydrocephalus.

Adenosine Triphosphate↗

Sirenoid monopodia with defects of right abdominal wall and lower limb associated with chromosome abnormality.

We have experienced a case of sirenoid monopodia with extreme deformity, which was studied pathoanatomically and genetically. The pathoanatomical studies revealed complicated deformities such as absence of the right abdominal wall, sacrum, right side of the os coxae and lower extremity, etc., and a chromosome study revealed 46XX, t (1 p-, Xq+), -8, +M. Various authors have discussed the genetic factors of anomaly of vascular development and concluded that all cases except for a few familial types would appear to be sporadic. In the present paper we report on an extreme type of sirenoid monopodia with right lower limb defect associated with chromosome abnormality. It is supposed that impoverished blood supply to the right lower portion of the body may have been the cause of this case, but the involvement of genetic factors is still unknown.

Abdominal Muscles↗

Effect of dipyridamole treatment on proteinuria in pediatric renal disease.

The effect of dipyridamole on proteinuria was studied in 60 children with various renal diseases. A significant decrease in 24-hour urine protein excretion was observed within a few months after treatment in 32 (53%) of the patients with minimal or moderate mesangial proliferation. The effect was reproducible and parallelled by a reduction in plasma levels of beta-thromboglobulin. Renal function in patients significantly improved with the therapeutical effect. The appropriate dosage was 4-10 mg/kg daily and no serious toxicity was seen despite large dosage and even in long-term application. The data suggest that dipyridamole treatment appears safe and has a beneficial effect on proteinuria dependent on its effect on platelets in renal disease.

Adolescent↗

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↗

Granular cell tumor of the orbit.

An 18-year-old woman had a 3-month history of increasing proptosis and visual loss secondary to an inferior orbital mass. Surgical exploration revealed an encapsulated mass in the orbit. After this mass was excised good vision was restored. The diagnosis of granular cell tumor was made as a result of various microscopic studies. The location of the tumor within the orbit is unusual and its histologic origin is uncertain. Immunohistochemistry by peroxidase-antiperoxidase method revealed that this tumor had S-100-protein-positive cells and negative results for lysozyme and alpha-1-antitrypsin. This fact suggests that the origin of the granular cell tumor may be due to the Schwann cell.

Adolescent↗

Prostaglandins enhance trigeminal substance P-ergic responses in the rabbit iris sphincter muscles.

Contractile responses due to substance P released from the trigeminal nerve were observed after electrical transmural stimulation or exogenous application of bradykinin in the isolated rabbit iris sphincter muscle. Prostaglandins, particulary prostaglandin E1, enhanced and indomethacin inhibited these substance P-ergic responses. Since the responses to exogenously applied substance P were neither affected by prostaglandins nor indomethacin, it was suggested that prostaglandins acted presynaptically to enhance the release of substance P from the trigeminal nerve terminals.

Animals↗

Chromosome aberrations in epithelial cells of the digestive tract of rats induced by 1-methyl-3-nitro-1-nitrosoguanidine.

The effect of a gastrointestinal carcinogen, 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), on chromosomes of rat digestive tract epithelial cells was studied. A blind loop of colorectal segment was surgically produced and the epithelial cells of this loop were treated twice with 0.5% and 0.1% MNNG solutions, respectively (5 ml each). After the first treatment, the mucosa revealed severe damage, and repair and mitoses upon regeneration were maximal on days 4-6. Chromosomal aberrations were studied 3-48 hr after the second treatment. Cells with chromosomal aberrations increased progressively from 6 hr on, reaching their maximum level at 15 hr, and gradually returned to the original level at 48 hr. Chromosomal aberrations consisted of gaps, breaks, and exchanges. The above results indicate that gastrointestinal carcinogens induce chromosomal aberrations in target epithelial cells.

Animals↗

Nonchromaffin paraganglioma in the nose and paranasal sinuses.

Nonchromaffin paraganglioma occurring in the nose and paranasal sinuses are extremely rare. The authors have experienced a case of nonchromaffin paraganglioma of nasal cavity which extended to the epipharynx. To our knowledge, this reported case is the fourth case that has appeared in the world literature. The patient, a 31-year-old female, had complained of a right nasal obstruction and mucopurulent rhinorrhea for two years. The right nasal cavity was filled with a polypoid mass showing no bleeding tendency or necrosis. Radiographs revealed a homogeneous shadow which occupied the entire nasal cavity and paranasal sinuses. Histopathological studies revealed that the tumor showed typical findings of nonchromaffin paraganglioma and neurosecretory granules in cytoplasm were observed by electron microscopic study. Subsequently, the tumor recurred at on the posterior epipharyngeal wall after a duration of one year and three months, and was removed completely. Since then, there was no recurrence of the tumor until the present time.

Adult↗

Creutzfeldt-Jakob disease. An autopsy case of the panencephalopathic type and a review of the literature.

This is a case report of a purported panencephalopathic type of Creutzfeldt-Jakob (C-J) disease in a 61-year-old Japanese farmer. He died nine months after the onset of clinical symptoms. This variety of C-J disease was named and reported in 1981 by Mizutani. The characteristic feature is extensive degeneration of cerebral white matter not related to cortical damage in addition to the spongiform changes in the cortical gray matter. The case was diagnosed clinically and at post mortem marked neural loss, astrocytic macrogliosis, and degeneration of subcortical white matter were found. Senile plaques and neurofibrillary tangles were virtually absent. Degeneration of the white matter is uncommon in C-J disease, and when it occurs is usually mild, and limited in distribution.

Brain↗

Dual effects of dynorphin-(1-13) on cholinergic and substance P-ergic transmissions in the rabbit iris sphincter muscle.

In the rabbit iris sphincter muscle, transmural electrical stimulation produces cholinergic and substance P-ergic responses. In the present work, the effects of dynorphin-(1-13), an endogenous ligand of the kappa opioid receptor, on these two neurogenic responses were examined pharmacologically and the data compared to findings in case of other opioid agonists. Dynorphin-(1-13) (10(-7) to 10(-6) M) enhanced the cholinergic responses and attenuated the substance P-ergic response, in a concentration-dependent manner, and these actions of dynorphin-(1-13) were more apparent in the case of low-frequency stimulation. These effects of dynorphin-(1-13) were antagonized by naloxone (10(-5) M). Dynorphin-(1-13) had no effects on the responses to exogenously applied acetylcholine, carbachol and substance P. The augmenting effect on the cholinergic transmission was unique in kappa agonists, as the cholinergic responses were also augmented by other kappa agonists such as dynorphin-(1-17) and ethylketocyclazocine, but attenuated by other opioid agonists (Met-enkephalin, beta-endorphin and morphine) and not affected by SKF-10,047 and nalorphine. On the other hand, the substance P-ergic response was attenuated by all the opioids used. These results suggest that dynorphin-(1-13) presynaptically increases the release of acetylcholine from the parasympathetic postganglionic nerves and reduces the release of substance P from the trigeminal nerve, mediated by kappa type of opioid receptors.

Acetylcholine↗