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Biomedical subjects

N Wada

Publications and source records attributed to N Wada.

At least 145 records · Page 8Linked to original sources

Effect of oral administration of protease inhibitor on pancreatic exocrine function in WBN/Kob rats with chronic pancreatitis.

The effect of oral administration of protease inhibitor (camostat) on pancreatic morphology and exocrine function (conscious rat model) was investigated using WBN/Kob rats with spontaneous chronic pancreatitis. In nontreated WBN/Kob rats (2-12 months of age), pancreatic fibrosis and parenchymal destruction compatible with human chronic pancreatitis appeared at 3 months and advanced with each month. Pancreatic secretion was markedly impaired at all ages. In WBN/Kob rats fed diets containing camostat (from 2-3 or 4-5 months of age), the pancreas was hypertrophic and did not show any histological appearances compatible with chronic pancreatitis, and moreover, exocrine function was thoroughly restored with increased plasma cholecystokinin concentrations. Oral administration of protease inhibitor has both preventive and therapeutic effects on pancreatic lesions and dysfunction in an animal model of chronic pancreatitis, probably via endogenous cholecystokinin release.

Administration, Oral↗

Evaluation of nitric oxide formation from nitrates in pig coronary arteries.

To clarify the hypothesis that organic nitrates are converted to nitric oxide (NO) via nitrite ion (NO2-) by glutathione S-transferase, the metabolic conversion of four nitrates was examined in pig coronary arteries and compared with that in rat liver. Nitrates caused the relaxation of the artery muscles with the order of nitroglycerin > isosorbide dinitrate > nicorandil > or = nipradilol, whereas the order of NO formation in the arteries was nitroglycerin > isosorbide dinitrate > nipradilol > nicorandil. The same order of NO formation from the nitrates was also observed in liver cytosol. Nicorandil may cause more relaxation than nipradilol by both NO releasing and other (unknown) actions. Although the order of the potency in NO2- formation from the nitrates in liver cytosol was the same as that seen in NO formation, NO2- was not detected in pig coronary arteries. Thus NO2- formation from the nitrates correlated with NO formation in liver cytosol but not in pig arteries. When nonenzymatic and enzymatic NO formations from nitroglycerin were examined in the arteries, the enzymatic NO formation, which was not inhibited by glutathione S-transferase inhibitors, was 13% of the total NO. These results indicate that in pig coronary arteries, nitrates release NO mostly through a nonenzymatic manner, although there is a slight amount of enzymatically produced NO, and glutathione S-transferase may not contribute to the enzymatic NO formation.

Animals↗

Adrenocorticotropin-independent bilateral macronodular adrenocortical hyperplasia: immunohistochemical studies of steroidogenic enzymes and post-operative course in two men.

We treated two men with Cushing's syndrome due to adrenocorticotropin (ACTH)-independent bilateral macronodular adrenocortical hyperplasia (AIMAH). In both patients, plasma ACTH was low and plasma cortisol was not suppressed by a high dose of dexamethasone (8 mg) but was remarkably responsive to exogenous ACTH. The adrenal glands were extremely enlarged and contained multiple nodules composed of large clear cells and small compact cells. The immunoreactivity of P-450(17) alpha was predominant in the small compact cells, while that of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was observed exclusively in the large clear cells. Among various adrenocortical disorders, differential expression of 3 beta-HSD and P-450(17) alpha in clear and compact cells has heretofore been demonstrated only in AIMAH. Total adrenalectomy was done for one patient, and partial adrenalectomy for the other. In the former patient, the normal diurnal rhythm of plasma ACTH was restored 11 months postoperatively. In the latter patient, the normal dynamics in the hypothalamic-pituitary-adrenal axis became evident 15 months after surgery. Thus AIMAH is apparently a primary adrenocortical disorder and is not due to abnormalities of the hypothalamus or pituitary.

3-Hydroxysteroid Dehydrogenases↗

Efferents from the optic tectum to the brain stem in the Japanese quail (Coturnix japonica). Anterogradely biocytin method.

Efferents from the optic tectum to the brain stem in the Japanese quail (Coturnix japonica) were studied with the anterogradely biocytin method. After injection of biocytin into the ipsilateral optic tectum, labeled terminals were seen in the rotund nucleus (Rt), neuropil part of the ventral lateral geniculate nucleus (GLnv), principal part of the dorsal lateral geniculate nucleus, lateral part of the dorsolateral thalamic nucleus, triangular nucleus (T), superficial parvocellular nucleus (SPC), pretectal nucleus, pretectal area (PA), subpretectal nucleus, central gray matter (GC), isthimo optic nucleus (ION), magnocellular and parvocellular parts of the isthimo nuclei (Imc and Ipc), semilunar nucleus (SLu), lateral and medial pontine nuclei and reticular formation (FRM) of the medulla, ipsilaterally. Labeled fibers were seen in the septomesencephalic tract nucleus, FRM, interstitio-paraetecto-subpraetectal nucleus, and the dorsal and ventral tectoreticular tracts (TRd and TRv). In the contralateral brain stem, labeled terminals were seen in the Rt, T. FRM, PA and paramedian nucleus. The contralateral terminals were remarkably fewer than those of the ipsilateral side. The present findings of the labeled terminals of the SPC and the GC at the level of the mesencephalic nucleus of the trigeminal nerve (MnT), and the topographic projection from optic tectum to the Rt in the thalamus, were original observations in the avian. The labeled terminals in the GLnv, Ipc, Imc and ION showed topographical projections from the optic tectum. Pathways to the contralateral brain stem were via the commissure posterior, ventral supraoptic decussation, and the predorsal bundle. The present results suggest that tectofugal impulses in the quail relate to various functions with special relation to the function of the GC at the level of the MnT as well as a visual function.

Animals↗

Endoscopic transpapillary bile duct biopsy without sphincterotomy for diagnosing biliary strictures: a prospective comparative study with bile and brush cytology.

OBJECTIVES: Endoscopic transpapillary bile duct biopsy has a high sensitivity for detection of malignant biliary strictures, but is commonly performed after endoscopic sphincterotomy. We performed transpapillary biopsy without sphincterotomy, using a recently developed, malleable biopsy forceps, and prospectively studied the usefulness of this diagnostic procedure, compared with that of bile and brush cytology. METHODS: We succeeded in transpapillary biopsy without sphincterotomy in 45 (87%) of 52 patients. In 43 patients with biliary strictures (31 malignant, 12 benign) who successfully underwent all endoscopic samplings by bile aspiration, brushing, and biopsy, the diagnostic value of these three sampling methods was compared. RESULTS: Transpapillary biopsy (81%) had a significantly higher level of sensitivity for malignancy than bile (32%) and brush (48%) cytology. Transpapillary biopsy was more sensitive for bile duct cancer (88%) than for pancreatic cancer (71%), as were cytology techniques. No false positives were found in any of the three sampling methods. No complications accompanied the endoscopic procedures. CONCLUSIONS: Transpapillary bile duct biopsy without sphincterotomy is a simple, safe, and effective technique for diagnosing biliary stricture. We recommend that this technique be performed routinely at initial endoscopic retrograde cholangiopancreatography for patients with a stricture or filling defect of the extrahepatic bile duct.

Adult↗

[Three cases with juvenile rheumatoid arthritis who showed hypocomplementemia related to disease activity].

We encountered three cases of juvenile rheumatoid arthritis which showed a depressed serum complement level during the clinical course. Circulating immune complex and increased secondary fibrinolysis were detected in all cases. The laboratory data suggested the presence of vesculitis. Cutaneous vasculitis was observed by biopsy in 2 cases and abnormal respiratory function in one cases. These 3 cases were in contrast to other 95 JRA cases treated in our department who showed normal serum complement levels. Estimation of serum complement may, therefore be useful to predict the vascular complication and refractoriness to therapy in JRA.

Adolescent↗

Polysynaptic pathways from high threshold muscle afferents innervating hindlimb muscles to tail motoneurons in the spinalized cat.

The postsynaptic potentials (PSPs) after stimulating hindlimb flexor (PBSt) and extensor muscle nerves (LGS) were recorded from 64 tail motoneurons innervating m. extensor caudae lateralis and m. flexor caudae longus in the spinalized cats. Postsynaptic potentials were produced after stimulating high threshold muscle afferent fibers (group II and group III) and the average central latencies of PSPs were distributed in a wide range between 4.5 and 15.1 ms. Opposite effects on tail motoneurons were observed between stimulation of flexor and extensor muscle nerves, or ipsilateral and contralateral muscle nerves.

Animals↗

Rhythmic discharges recorded from tail muscle nerves after injection of nialamide and L-DOPA solution in spinalized cats.

In 22 decapitated and high spinalized cats, rhythmic discharges were recorded from the nerves supplying the tail muscles, m. extensor caudae lateralis (ECL) and m. flexor caudae longus (FCL) after intravenous injection of Nialamide and L-DOPA solution. In 15 out of 22 cats, stable rhythmic discharges were recorded from tail muscle nerves. Two different discharge patterns were observed. The predominant pattern consisted of an alternating activation between left and right tail muscle nerves and a synchronous activation of ECL and FCL nerves on one side. The second pattern consisted of synchronous activity involving all four tail muscle nerves.

Animals↗

Descending pathways from the medial longitudinal fasciculus and lateral vestibular nucleus to tail motoneurons in the decerebrate cat.

Responses of motoneurons supplying two tail muscles (m. extensor caudae lateralis [ECL] and m. flexor caudae longus [FCL]) to stimulation of the medial longitudinal fasciculus (MLF) and lateral vestibular nucleus (LVN) were studied using intracellular recording in the decerebrate cat. Stimulation of the MLF and the LVN produced mainly excitatory postsynaptic potentials (EPSPs) or mixed PSPs (EPSP/IPSPs), but inhibitory postsynaptic potentials (IPSPs) were also observed in a few motoneurons. The segmental latencies of early PSPs produced by MLF or LVN stimulation were distributed over a wide range, and PSPs with a segmental latency of mono- or disynaptic origin were observed in ECL and FCL motoneurons. The spatial facilitation technique indicated convergence of the descending pathways from MLF and LVN on a common interneuron.

Animals↗

Adrenoleukodystrophy indicated by abnormal electro-encephalography.

An 8 year old boy with adrenoleukodystrophy and his asymptomatic brother, both with abnormal electro-encephalography as the initial sign of adrenoleukodystrophy, are reported. After suffering from aseptic meningitis caused by Echo virus 30, the first case was suspected of having a complication of meningitis because of persistent abnormal electro-encephalography (i.e. slow wave bursts in the occipital region). This patient was finally diagnosed as having adrenoleukodystrophy because of the increased level of very long chain saturated fatty acids, and typical occipital lesions demonstrated by magnetic resonance imaging and computed tomography. Dietary therapy was tried, but the course was progressive. The brother's electro-encephalography was also abnormal and so was diagnosed as having asymptomatic adrenoleukodystrophy because of an increased level of very long chain saturated fatty acids, although brain magnetic resonance imaging was normal. Abnormal electro-encephalography can therefore be an initial sign of adrenoleukodystrophy even if magnetic resonance imaging shows no abnormality in the brain.

Adrenocorticotropic Hormone↗

Location of motoneurons supplying tail muscles in the domestic fowl.

The distribution of motoneurons innervating the tail muscles, levator caudae, depressor caudae, pubocaudalis externus, pubocaudalis internus, lateralis caudae and flexor cruris, in the adult domestic fowl was examined by retrograde transport of horseradish peroxidase Labeled motoneurons supplying tail muscles were distributed in longitudinal column in the spinal cord below sacral spinal segment 3 and average diameters of cell bodies ranged from 27 to 59 microns. Each motor pool was localized in a characteristic position in the ventral horn.

Animals↗

Polysynaptic neural pathways from low threshold trunk cutaneous afferents to tail motoneurons in the spinalized cat.

Postsynaptic potentials (PSPs) after stimulating the cutaneous nerves of the trunk, dorsal cutaneous nerve (DC) and ventral cutaneous nerve (VC) were recorded from alpha-motoneurons innervating two tail muscles, the m. extensor caudae lateralis (ECL) and m. flexor caudae longus (FCL) in 22 spinalized (T10) cats. Stable recordings were obtained from 33 ECL and 42 FCL motoneurons. Stimulation of cutaneous nerves at 1.5-5 times threshold typically produced three types of synaptic effects in ECL and FCL motoneurons: predominant excitation (EPSP), or predominant inhibition (IPSP), or mixed effects characterized chiefly by early excitation followed by inhibition (EPSP/IPSP). The average central latencies of PSPs were distributed over a wide range (4.5-15.6 ms). Latency measurements indicated that most neural circuits from the trunk cutaneous afferents to the tail muscle motoneurons were oligosynaptic pathways via intraspinal slow-conducting fibers or polysynaptic pathways.

Afferent Pathways↗

Transcription stimulation of the Fas-encoding gene by nuclear factor for interleukin-6 expression upon influenza virus infection.

We previously found that the level of Fas, a cell surface receptor for an apoptosis signal, increases at the mRNA level in influenza virus-infected HeLa cells prior to their death by apoptosis. Here we investigated the mechanism of activation of the Fas-encoding gene expression upon influenza virus infection. Nucleotide sequences for the binding of nuclear factor for interleukin-6 expression (NF-IL6), also known as CCAAT/enhancer-binding protein beta, were repeated 8 times in the 5'-end region of the human FAS gene, spanning from -1360 to +320. This region directed the expression of a downstream marker gene when introduced into HeLa cells and the activity of the FAS gene promoter was stimulated about 2-fold upon influenza virus infection. Gene expression driven by the FAS promoter was activated when human NF-IL6 was overproduced in a DNA when human NF-IL6 was overproduced in a DNA co-transfection study. Moreover, the DNA-binding activity of NF-IL6 increased after infection with the virus, whereas the amount of NF-IL6 seemed unchanged. The results suggest that NF-IL6 is activated upon influenza virus infection through post-translational modification and that the modified factor stimulates the transcription of the human FAS gene.

Antigens, Surface↗

High K-ras mutation rates in goblet-cell-type adenocarcinomas of the lungs.

Adenocarcinomas of the lungs show a variable histology. We have subclassified such lesions into five cell types: hobnail, columnar, polygonal, mixed and goblet cell types, and investigated their relationships with K-ras mutations. Codons 12, 13 and 61 of the K-ras gene in 120 surgically resected pulmonary adenocarcinomas were examined by the mutation-allele-specific amplification method. Point mutations were observed in 10% of the adenocarcinomas limited to K-ras codon 12 and the commonest base substitution (nine cases) was a G to T transversion. Of the five types, goblet cell lesions demonstrated the highest mutation index, which at 100% (6/6) was significantly different from that of all other cell types. No relationship between K-ras mutation and cigarette smoking was observed. From these findings, it appears that development of goblet-cell-type adenocarcinomas of the lung may involve different carcinogenic mechanisms from adenocarcinomas of other subtypes.

Adenocarcinoma↗

Acute hepatitis in an adult with acquired rubella infection.

We report a case of acute hepatitis in a 28-year-old male with acquired rubella infection. Serological tests revealed acute rubella virus infection and ruled out infection by other common viruses, including type A and type B hepatitis viruses. The patient showed not only marked increase of lactate dehydrogenase (LDH) activity, with only slight liver dysfunction, but also platelet and kidney injury, suggesting systemic rubella virus infection. Because the liver dysfunction was slight, liver biopsy was not performed. When a patient has mild, transient hepatitis accompanied by high LDH activity in comparison with both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, we should take a common viral infection such as rubella into consideration when making a diagnosis.

Acute Disease↗

Management of recurrent hyperthyroidism in patients with Graves' disease treated by subtotal thyroidectomy.

If the aim of surgical treatment for Graves' disease is not permanent hypothyroidism, it is difficult to avoid recurrent hyperthyroidism completely. The management of recurrent hyperthyroidism, however, is neither easy nor obvious. Improvement in the sensitivity of TSH assay has allowed the diagnosis of latent hyperthyroidism. Little is known about the clinical course of latent hyperthyroidism. We studied the management and outcome of recurrent hyperthyroidism in patients with Graves' disease treated by subtotal thyroidectomy. Between January 1988 and August 1991, 1115 patients with Graves' disease were treated by surgery. Postoperative thyroid function was evaluated by free T3, free T4 and TSH measurements. One hundred seventy-five patients with suppressed TSH secretion for at least 6 months were categorized as having recurrent hyperthyroidism. Eighty patients (45.1%) also had elevated thyroid hormone levels, (group 1). The remaining 95 patients (54.9%) had normal thyroid hormone levels with suppressed TSH values (group 2). In group 1, 58 patients were treated with antithyroid drug (ATD), 12 with iodine and 10 with radioiodine (RI). Remission of Graves' disease was obtained in 22 patients (11 by ATD, 1 by iodine and 10 by Ri). On the other hand, patients in group 2 were followed up without medication, and spontaneous remission was observed in 21 of theln (22.1%). It was difficult to induce remission of overt recurrent Graves' disease by ATD or iodine. In contrast spontaneous remission could be obtained in some patients with postoperative latent hyperthyroidism.

Adolescent↗