Biomedical subjects
Publications and source records attributed to S Tani.
A 54-year-old man presented with symptoms of exertional syncope. Cardiac amyloidosis was diagnosed by endomyocardial biopsy. Exercise tolerance test revealed a failure of increased heart rate followed by sinus arrest, associated with syncope. Autopsy revealed amyloid deposits in the sinoatrial node.
Susceptibility of Apodemus sylvaticus and A. agrarius to infection with Acanthocheilonema viteae was compared with that of hamsters and jirds. Microfilaremia in A. sylvaticus was first noted on day 52 post-infection (p.i.) and lasted during the course of the study (up to day 150 p.i.). Maximum microfilaremic levels (female worm basis) of A. sylvaticus [mean +/- S.D. (n) = 690 +/- 1288(6)] were considerably higher than those of hamsters [16 +/- 18(6)] and jirds [51 +/- 25(5)]. Adult worm recovery in A. sylvaticus ranged from 2 to 40% of the number of infective larvae inoculated. Worm development in A. sylvaticus resembled that in hamsters and jirds. In contrast, microfilaremia was not detected in, nor adult worms recovered from A. agrarius throughout the study.
The effect of ethanol on pancreatic exocrine secretion was studied in isolated rat pancreatic acini. Ethanol caused a dose-dependent stimulation of amylase release, and a twofold increase of amylase release was observed with 600 mM ethanol. Ethanol inhibited cholecystokinin octapeptide (CCK-8)- and carbamylcholine-stimulated amylase release and similarly inhibited binding of [125I]CCK-8 and [N-methyl-3H]scopolamine to isolated rat pancreatic acini in a dose-dependent manner. The inhibitory effect of ethanol was fully reversible with respect to CCK-8-induced amylase release. On the other hand, ethanol potentiated secretin- and vasoactive intestinal peptide (VIP)-stimulated amylase release. Ethanol induced a small but significant increase in Ca2+ efflux, whereas CCK-8 induced an immediate and large increase, but ethanol significantly inhibited CCK-8-stimulated Ca2+ efflux. The present study clearly demonstrates the dual effects of ethanol on pancreatic exocrine function: stimulation and inhibition. We suggest that mobilization of intracellular Ca2+ may be involved in the mechanism of ethanol's action on isolated rat pancreatic acini.
Helodermin (HDM) belongs to the vasoactive intestinal polypeptide (VIP) family of polypeptides. Degradation of HDM in the tracheal tissue isolated from a guinea-pig and by an isolated enkephalinase was studied and compared with the degradation of VIP. The tracheal relaxing activity of VIP was potentiated by enkephalinase inhibitors, thiorphan and phosphoramidon, while the activity of HDM was not potentiated. On the other hand, bestatin, an aminopeptidase inhibitor, and captopril, an angiotensin converting enzyme inhibitor, did not influence the activity of VIP and HDM. The data suggests that the degradation of VIP but not HDM in the trachea was done by enkephalinase. Enkephalinase was then purified from the lung and the striatum membrane fraction through a DEAE-cellulose column, chromatofocusing column and hydroxyapatite column. The purified enkephalinase from the lung hydrolyzed VIP but not HDM. HDM and VIP were, however, hydrolyzed by the striatum enkephalinase. There was only a partial degradation of HDM by the striatum enkephalinase and the hydrolysis rate of HDM was slower than that of VIP. The degradation of VIP and HDM was inhibited by thiorphan. In conclusion, we found that VIP but not HDM was degraded by enkephalinase present in the respiratory system such as the trachea and the lung. Furthermore, enkephalinase, which hydrolyses HDM, was present in the brain.
A 53-year-old woman presented with symptoms of dyspnea on exertion and edema of lower extremities. Chronic cardiac tamponade caused by the rupture of the right atrial wall was diagnosed by two-dimensional contrast echocardiography. Autopsy findings revealed primary cardiac hemangiopericytoma.
This clinical research has been conducted to extend the understanding of pathophysiological mechanism involved in the tethered cord syndrome. In normal individuals, the filum terminale has elasticity similar to the rubber band. This allows cephalad or caudad movement of the lumbosacrococcygeal spinal cord while the spine is flexed or extended. This is based on the observation that the lowest pair of dentate ligaments spans from the T12 and L1 junction of cord segments to the dura between the dural exit of T12 and L1 nerve roots, and the spinal cord below T12 can freely ascends on flexion and descends in the spinal canal on extension of the spine. In 50 healthy human subjects, x-ray films of the thoracolumbosacral spine were studied. Lateral films of the spine were taken in the neutral, hyperextended and hyperflexed positions. The first group included 10 individuals whose ages ranged from 27 to 42 years. The distance between the middle of the T10 vertebra and L1-L2 interspace was measured. This distance was considered to represent the length of the lumbosacral cord segment (L1 through coccygeal cord segments). The second group included 40 individuals whose ages ranged from 17 to 50 years. The distance between the L1-L2 interspace and S1-S2 interspace was measured. The distance signified the distance between the caudal end of the spinal cord and attachment of filum terminale to the sacrum. There was a 3.5% (4.6mm by X-ray films) increase during hyperflexion in the distance measured in the first study.(ABSTRACT TRUNCATED AT 250 WORDS)
A 24-year-old housewife presented with weight gain of about 30 kg, constipation and pitting edema of extremity nine years after having a thyroidectomy. Hormonal examination revealed low levels of serum T3 and T4 and high levels of serum TSH and PRL. She also had enlarged pituitary gland (pituitary hyperplasia) with suprasellar extension on CT and MRI image. Thyroid replacement therapy and follow-up by MRI were performed without resort to surgery, because she had no visual disturbance. Within about 1 month after thyroid replacement therapy, serum TSH and PRL were normalized. And also thyroid function was normalized by thyronine (T3). Following this results, pituitary hyperplasia regression was seen on MRI image. About 1 year after thyroid replacement therapy, pituitary hyperplasia regression was more seen on MRI image. Prolonged hypothyroidism can result in hypertrophy of the pituitary thyrotropin-secreting cells and prolactin secreting cells. So, it can increase pituitary weight (pituitary hyperplasia). Radiological examination, abnormal sellar x-ray films suggesting intrasellar tumor are common in patients with primary hypothyroidism. Suprasellar extension of pituitary mass (pituitary hyperplasia) due to hypothyroidism was reported by radiological examination (PEG, CT and MRI image), and regression of pituitary hyperplasia was revealed by radiological examination after thyroid replacement therapy. The first choice of this type of pituitary hyperplasia is thyroid replacement therapy unless the patient has a visual disturbance. However, if this replacement therapy is not effective for diminution of the tumor, surgical removal of the tumor should be considered.
A case of solitary syringobulbia without syringomyelia diagnosed by MRI was reported. A 63-year-old female, who had a history of progressive gait disturbance for 9 months, was admitted to our department because of severe headache. Neurological examination revealed that the patient was suffering from right pyramidal sign as well as left deep sensory disturbance without apparent impairment of cranial nerves or nystagmus. The somatosensory evoked potential stimulated by the left median nerve showed delay in latency and low amplitude, however, the auditory brainstem response showed normal records bilaterally. A syringobulbia associated with platybasia, basilar impression, obstructive hydrocephalus and Arnold-Chiari malformation was diagnosed by the neuroradiological examinations including plain X-ray films of the skull, CT scan and MRI of the brain. Subsequent to the decompression around the cisterna magna by suboccipital craniectomy and laminectomy of the atlas, the opening of the Foramen Monro which was obstructed by a thick membrane was carried out, and prevention of communication between the fourth ventricle and the syrinx was accomplished by using a piece of muscle. This operative procedure was thought to be compatible with Gardner's operation for syringomyelia. The patient showed gradual improvement of gait disturbance as well as headache 3 months after surgery, and this neurological improvement was proved by decrease in the size of the known syringobulbia on MRI, and by normalized somatosensory evoked potential stimulated by the median nerve. Pathophysiology of the solitary syringobulbia with relatively acute onset of the neurological symptoms was assumed to have taken place in the following manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Tryptophan 248, located in the active site of tryptophanase from Escherichia coli, has been replaced with phenylalanine by site-directed mutagenesis. Judging from CD and fluorescence spectra, the global structure of the mutant enzyme was found to be the same as that of the wild-type enzyme. The binding affinity of the mutant enzyme for the coenzyme pyridoxal 5'-phosphate (PLP) was reduced tenfold compared to the wild-type enzyme. Kinetic analyses under PLP-saturated conditions indicated that the Km values of the mutant enzyme for substrates are the same as those of wild-type enzyme but the kcat values are decreased to about 85%, which accounts for the overall activity decrease. These findings suggest that tryptophan 248 interacts closely with PLP and plays an important role in the catalytic reaction.
The therapeutic effect and the mechanism of action of the synthetic trypsin inhibitor camostate were studied in a rat model of acute interstitial pancreatitis induced by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Rats with acute pancreatitis were given either 100 mg/kg body weight camostate or volume- and pH-adjusted water via an orogastric tube 30 min after the last cerulein injection. The elevation of serum amylase activity was significantly reduced by camostate treatment and the peak value was seen 1 hr earlier than that observed in the rats that did not receive camostate. Camostate also inhibited the reduction in pancreatic content of lipase and amylase seen during experimental pancreatitis. These effects were accompanied by alleviation of the histologic signs of acute pancreatitis such as cellular infiltration and acinar cell vacuolization. After oral administration, camostate and its metabolite were absorbed from the intestine and were detectable in plasma for more than 6 hr in concentrations high enough to have antiprotease activity. In addition, camostate in the duodenum was able to increase pancreatic juice flow and protein output and to stimulate endogenous secretin release. These results suggest that oral administration of camostate reduces the severity of cerulein-induced acute pancreatitis by releasing endogenous secretin and by its antiprotease activity.
We examined the effect of fasting on the course of experimental acute pancreatitis induced in rats by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Rats were either fasted from 24 hr before to 9 hr after the first cerulein injection or fed ad libitum throughout the experiment. Twenty-four hours of fasting reduced cerulein-induced increases in serum levels of amylase and anionic trypsin(ogen) to 50 and 70% of those in fed rats, respectively. Increases in pancreatic wet weight after cerulein injections were also less in fasted rats than in fed rats. Pancreatic content of trypsin was significantly decreased after a 24-hr fast, and no further changes were induced by cerulein injections. The histological signs of acute pancreatitis were greatly alleviated by fasting. However, 24 hr of fasting did not alter the sensitivity and responsiveness of the exocrine pancreas to cerulein in both in vivo and in vitro. Plasma CCK bioactivity and immunoreactive secretin concentration in 24-hr-fasted rats were significantly lower than those in fed rats. Administration of CCK receptor antagonist, loxiglumide, 12 hr prior to the induction of acute pancreatitis reduced the increase in serum amylase activity in fed rats to nearly the same levels as that in fasted rats and alleviated histological signs of pancreatitis to some extent. These present observations suggest that fasting lessens the severity of cerulein-induced acute pancreatitis by reducing endogenous CCK release.
We examined the biological and histologic characteristics of a new experimental model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. Rats were given a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine. At 12-24 hr after the arginine injection, serum levels of amylase, lipase, and anionic trypsin(ogen) reached respective peak values 2, 5, and 20 times those of control rats without arginine and returned to control levels after 24-48 hr. The contents of pancreatic protein, DNA, and digestive enzymes were markedly reduced after the arginine injection and reached their nadirs at 72 hr. After 14 days these levels were almost normal. Histologic examination revealed a number of small vesicles within acinar cells at 6 hr, which were identified as markedly swollen mitochondria by the electron microscope. Other intracellular organelles and nuclei also showed degenerative changes. At 12 hr interstitial edema appeared, and acinar cell necrosis was seen after 24 hr. The extent and severity of necrotic changes of pancreatic exocrine tissue with inflammatory cell infiltration were maximal at 72 hr. At seven days, pancreatic acinar cells began to regenerate, and pancreatic architecture appeared almost normal after 14 days. The present study has demonstrated that the administration of excessive doses of arginine induces a new, noninvasive experimental model of acute necrotizing pancreatitis.
An enzyme immunoassay (EIA) for human pancreatic amylase has been developed for the detection of human serum amylase content. Our monoclonal antibody is highly specific for human pancreatic amylase; it cross reacted negligibly with the salivary isoenzyme. We developed a solid phase enzyme immunoassay for determination of pancreatic amylase in human serum with this antibody. The assay required 20 microL of serum and the standard curve was linear to at least 1000 ng/mL of pancreatic amylase. Inter- and intra-assay CVs were less than 10%. The results obtained by the EIA correlated well with those determined by the conventional electrophoretic method. In normal subjects, the mean concentration of serum pancreatic amylase determined by the EIA was found to be 92.3 +/- 26.1 ng/mL (mean +/- SD). The EIA we describe is useful for directly determining pancreatic amylase in human serum. Specifically distinguishing pancreatic from salivary amylase may have considerable clinical value.
Plasma atrial natriuretic peptide (ANP) behavior was evaluated in 26 untreated essential hypertensives, 21 normotensives, and 20 normotensives with hypertensive heredity under normal sodium intake (120 mEq of Na+/day). All subjects were men, mean age 22.1 +/- 1.9 years. Plasma ANP was evaluated by radioimmunoassay on samples collected in supine position upon waking and again after 1 h of orthostatism. Resulting data showed that ANP in hypertensives (supine = 44.5 +/- 19.4 pg/mL, orthostatism = 24.1 +/- 11.6 pg/mL) was at higher levels than in controls (supine = 38.3 +/- 19.4 pg/mL, orthostatism = 19.9 +/- 10.6 pg/mL) or in normotensives with hypertensive heredity (supine = 42.1 +/- 16.8 pg/mL, orthostatism = 23.2 +/- 10.8 pg/mL). Mean ANP level was higher in the latter group than in the control group (supine = +9%; orthostatism = +14.2%). In conclusion, plasma ANP is raised in young essential hypertensives, resulting in slightly elevated levels in normotensives with hypertensive heredity.
We examined the inhibitory effect of L-364,718, a nonpeptide cholecystokinin (CCK) antagonist, on CCK stimulation of pancreatic exocrine and endocrine secretion in both the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, L-364,718 inhibited CCK octapeptide (CCK-8)-stimulated amylase release and binding of 125I-CCK-8 in a dose-dependent manner without appreciable effects on the basal amylase secretion. L-364,718 also inhibited amylase release in response to caerulein and gastrin I, but had no effect on amylase release stimulated by other secretagogues or by agents bypassing receptors. Similarly, binding of N-methylscopolamine to pancreatic acini was not inhibited by L-364,718. In the isolated perfused pancreata, L-364,718 inhibited CCK-8-stimulated pancreatic exocrine secretion and insulin release. The inhibitory effects of L-364,718 were more potent for insulin release than for exocrine secretion and persisted even after the removal of L-364,718 infusion. These results clearly demonstrate that L-364,718 is a specific, potent, and prolonged antagonist of CCK's stimulatory actions on pancreatic acinar and B cells.
We evaluated the effects of a new cholecystokinin (CCK) receptor antagonist, loxiglumide, in a model of mild pancreatitis induced by repeated injections of cerulein and in a severe necrotizing form of pancreatitis induced by retrograde ductal injection of sodium taurocholate (NaTc) in rats. A single subcutaneous injection or oral administration of 50 mg/kg of body weight of loxiglumide almost completely reduced the increases of serum amylase activity and pancreatic wet weight, and caused histologic improvements of the cerulein-induced acute pancreatitis when given 30 min before the first cerulein injection. Loxiglumide was also effective in reducing the elevated serum amylase activity, pancreatic wet weight, and histologic alterations even when administered after the induction of acute pancreatitis. However, loxiglumide offered no apparent beneficial effects when given 30 min before and 3 h after the induction of acute pancreatitis by NaTc as determined by changes in serum amylase activity, pancreatic wet weight, and histology. These results do not necessarily suggest that CCK is not important in the pathogenesis of pancreatitis, but do suggest that the sole blockade of peripheral CCK receptors is ineffective against NaTc-induced severe necrotizing pancreatitis.
The effects of proglumide-related cholecystokinin (CCK) receptor antagonists CR 1409 and CR 1392 on CCK-octapeptide (CCK-8)-stimulated immunoreactive insulin (IRI) release and exocrine secretion were examined simultaneously in the isolated perfused rat pancreas. The CR 1409, at concentrations of 10-100 nM, significantly inhibited CCK-8 (100 pM) stimulation on IRI release but failed to inhibit the stimulatory effect of CCK-8 on both pancreatic juice flow and protein secretion. Increasing concentrations of CR 1409 inhibited both CCK-8-stimulated IRI release and exocrine secretion. Half-maximal inhibition was observed with approximately 2 nM for IRI release and 1 microM for protein secretion. When a higher dose (1 nM) of CCK-8 was used, the inhibitory effect of 10 nM CR 1409 on CCK-8-stimulated IRI release was abolished, whereas 10 microM CR 1409 retained significant inhibitory effect. Furthermore, 1 microM carbachol-induced IRI release was not altered by the addition of 10 microM CR 1409. The CR 1392 also had an inhibitory effect on both CCK-8-stimulated IRI release and exocrine secretion. The concentration of CR 1392 that caused half-maximal inhibition of CCK-8-stimulated IRI release was 300 times lower than that of exocrine secretion. In addition, 1 microM carbachol-stimulated IRI release was not altered by 100 microM CR 1392. Thus, the inhibitory effects of CR 1409 and CR 1392 on IRI release were mediated through the interaction at the CCK receptor and were more potent than those on juice and protein secretion. This study suggests, therefore, that CCK receptors on B cells might be different from those on acinar cells in terms of their relative affinities for antagonists.
The effect of aclatonium napadisilate, a newly synthesized choline ester, on pancreatic exocrine function was compared with that of the muscarinic agonist carbamylcholine in isolated rat pancreatic acini. Both compounds increased amylase release and 45Ca2+ efflux in a dose-dependent fashion, and similarly decreased the binding of [N-methyl-3H]scopolamine to isolated rat pancreatic acini. While aclatonium napadisilate was 20-30 times less potent than carbamylcholine in stimulations of amylase release and 45Ca2+ efflux, the potency of aclatonium napadisilate in inhibiting [N-methyl-3H]scopolamine binding was nearly the same as that of carbamylcholine. These results indicate that aclatonium napadisilate stimulates pancreatic exocrine secretion via muscarinic receptors and Ca2+ mobilization, and its intrinsic activity is less than carbamylcholine in the isolated rat pancreatic acini. Since aclatonium napadisilate is known to increase motility and peristalsis of the gastrointestinal tract, stimulatory effects of aclatonium napadisilate, shown in the present study, on digestive enzyme secretion from the pancreas may provide additional benefit of aclatonium napadisilate in the treatment of various gastrointestinal disorders.