[Effects of opiate and opioid peptides administered intrathecally on the pain threshold and micturition reflex in rats].
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Animals↗
Biomedical subjects
T Hisamitsu
Publications and source records attributed to T Hisamitsu.
Regulation of urinary bladder capacity by endogenous opioid peptides.
Naloxone administered to chloralose or ketamine anesthetized cats reduced urinary bladder capacity. Successive cystometrograms revealed that naloxone in doses of 0.5 microgram./kg. to 15 micrograms./kg. i.v. reduced the volume necessary to evoke micturition by 10 to 50 per cent, respectively. The effect was maximal within a few minutes, remained constant for about 1/2 hour and returned to control values over the next 2 to 3 hours. Following return to control, subsequent doses of naloxone produced no further effect on capacity. In chloralose anesthetized animals naloxone also increased the frequency and amplitude of low amplitude pressure waves on the tonus limb of the cystometrogram. Intrathecal administration of naloxone to the sacral spinal cord did not significantly reduce the volume necessary to evoke micturition even at large doses, but did increase the amplitude of micturition contractions. These data, along with previous reports, suggest that mu receptors in the brainstem alter urinary bladder capacity, while delta receptors in the spinal cord modulate the magnitude of bladder contractions. Pharmacological manipulation of these receptor systems could provide a tool for the management of neurogenic bladder dysfunction.
Animals↗
A sympathetic projection from sacral paravertebral ganglia to the pelvic nerve and to postganglionic nerves on the surface of the urinary bladder and large intestine of the cat.
Anatomical and electrophysiological experiments have demonstrated a prominent projection from the sacral sympathetic chain via the pelvic nerve to postganglionic nerves on the surface of the urinary bladder and the large intestine of the cat. Retrograde labeling studies revealed that the pelvic nerve, which is generally believed to carry primarily parasympathetic axons, has a considerable population of sympathetic fibers originating mainly from the S1-S3 paravertebral ganglia. The number of sympathetic neurons projecting to the pelvic nerve (2,100) was about 75% of that projecting to the pudendal nerve (2,900), a somatic nerve which would be expected to carry a large sympathetic fiber constituent. Sympathetic neurons projecting to the pudendal nerve were located primarily in the L6-S2 ganglia. Electrophysiological studies confirmed the presence of a sympathetic pathway from the paravertebral ganglia to the pelvic viscera. Electrical stimulation (thresholds 1.5-3 V) of the lumbar sympathetic chain evoked firing in the pelvic nerve and in postganglionic nerves on the surface of the colon and bladder at latencies of 60-150 msec. The responses were unaffected by cutting the chain one segment rostral to the site of stimulation, but were abolished by the administration of a ganglionic-blocking agent (tetraethylammonium). The responses on the colon and bladder postganglionic nerves were also abolished by transection of the pelvic nerve. The conduction velocity in the sympathetic postganglionic axons was approximately 1 m/second. In summary, these studies indicate that the pelvic nerve, like somatic nerves, receives a prominent projection from the sympathetic chain ganglia. The function of this sympathetic paravertebral pathway and its relationship with prevertebral innervation of the pelvic organs remains to be established.
Adrenergic Fibers↗
The inhibitory effect of opioid peptides and morphine applied intrathecally and intracerebroventricularly on the micturition reflex in the cat.
Intrathecal (i.t.) and intracerebroventricular (i.c.v.) administration of enkephalins and enkephalin analogs inhibited reflex contractions of the urinary bladder and firing in vesical parasympathetic postganglionic nerves. Leucine- and methionine-enkephalin (L-Enk and M-Enk, mean threshold doses: 110 micrograms, i.t. and 17 micrograms, i.c.v.) elicited short-lasting inhibition (3-30 min), whereas D-Ala2-leucine- and D-Ala2-methionine enkephalinamide (mean threshold dose 23 microgram, i.t.), produced more prominent and prolonged inhibition (1.5-3 h). DSLET , a delta selective opiate receptor agonist, blocked bladder activity when injected i.c.v. or i.t. (mean threshold doses 0.08 microgram and 13 micrograms), whereas morphine, which has greater affinity for mu opiate receptors, was effective by i.c.v. and intravenous (i.v.) injection (mean threshold doses, 5 micrograms and 300 micrograms/kg), but not by i.t. injection (200-400 micrograms). Thiorphan (50-200 micrograms, i.t., i.c.v.) enhanced the responses to L-Enk, whereas naloxone (10-50 micrograms, i.t., i.c.v., i.v.), blocked the responses to all opioid substances. In untreated animals thiorphan depressed and naloxone enhanced bladder reflexes. With i.t. administration naloxone (10-200 micrograms) increased the duration and magnitude of bladder contractions, whereas with i.c.v. injections, the drug increased the frequency and reduced the amplitude of the contractions. Large doses of naloxone i.t., but not i.c.v., produced sustained bladder contractions and versical efferent firing. These results indicate that bladder reflexes are controlled by tonic enkephalinergic inhibitory mechanisms in both the brain and spinal cord. In the brain enkephalinergic inhibition which was mediated by delta and mu opiate receptors, seems to control the frequency of bladder contractions and micturition threshold, whereas in the spinal cord, inhibition is mediated by delta receptors and seems to control the magnitude of bladder contractions.
Animals↗
Clinicopathological features of hepatocellular carcinoma--comparison of hepatitis B seropositive and seronegative patients.
Clinicopathological features were studied in 113 non-alcoholic patients with histology-proven hepatocellular carcinoma, of whom 35 were positive for hepatis B virus surface antigen (HBsAg), 23 were negative for all seromarkers for hepatitis B virus, and 55 were negative for HBsAg, but positive for anti-HBs and/or anti-core antibody (anti-HBc) with low titers. It was found that the age of the patient at the time of diagnosis was significantly lower in HBsAg cases than in the other two groups. Serum alpha-fetoprotein levels were often normal or below 100 ng/ml in the seronegative cases, and its measurement less frequently served as a diagnostic clue. Otherwise, clinically there was no difference between the three groups except for more frequent liver disease within the second degree of kinship in the HBsAg patients. Histopathological study of the livers showed that there were more expanding type hepatocellular carcinomas in the seronegative cases as compared with the HBsAg positive cases. There was no autoimmune chronic liver disease in these patients. These observations and data seem to indicate that there are certain differences between HBsAg positive and seronegative hepatocellular carcinomas. Since most patients had progressive liver disease, it is likely that many of these seronegative cases had chronic non-A, non-B viral disease, which is very common in Japan. It may be inferred further that non-A, non-B hepatitis virus is less carcinogenic as compared with hepatitis B virus.
Adult↗
Quantification of individual serum bile acids in patients with liver diseases using high-performance liquid chromatography.
Using high-performance liquid chromatography combined with a column of immobilized 3 alpha-hydroxysteroid dehydrogenase, 15 bile acids, i.e., cholate, chenodeoxycholate, deoxycholate, lithocholate, ursodeoxycholate, and their five taurine conjugates and five glycine conjugates, were clearly separated and quantified in 38 patients with various hepatobiliary diseases and 9 normal controls. The serum levels of bile acids, both primary and total, were elevated in patients with liver disease, but did not differentiate between parenchymal disease and cholestasis. The ratio of cholate/chenodeoxycholate was significantly increased in cholestasis as compared with parenchymal liver injury. In primary biliary cirrhosis, the ratio of total glycine/taurine conjugates was decreased, with a marked increase of taurochenodeoxycholate. The bile acid pattern was distinctly different between extrahepatic cholestasis and primary biliary cirrhosis, which mainly reflects intrahepatic cholestasis. In acute hepatitis, there was a quick normalization of major taurine and glycine conjugates in the convalescent stage. Most of the major taurine and glycine conjugated bile salts were significantly elevated in cirrhosis, and the elevation of taurochenodeoxycholate was particularly marked in the decompensated state. Furthermore, the quantitative relationship between taurocholate and taurochenodeoxycholate in cirrhosis was reversed from that in acute hepatitis. These changes in absolute and relative concentrations of bile acids in various liver diseases perhaps reflect differing pathology and metabolism, and may prove diagnostic. Measurement of individual bile salts is easily and quickly done with this method, and may lend itself clinical application.
Adolescent↗
Segmental distribution and central projections of renal afferent fibers in the cat studied by transganglionic transport of horseradish peroxidase.
The segmental and central distributions of renal nerve afferents in adults cats and kittens were studied by using retrograde and transganglionic transport of horseradish peroxidase (HRP). Transport of HRP from the central cut ends of the left renal nerves labelled afferent axons in the ipsilateral minor splanchnic nerves and sensory perikarya in the dorsal root ganglia from T12 to L4. The majority of labeled cells (85%) were located between L1 and L3. A few neurons in the contralateral dorsal root ganglia were also labeled. Labeled cells were not confined to any particular region within a dorsal root ganglion. Some examples of bifurcation of the peripheral and central processes within the ganglion were noted. A small number of preganglionic neurons, concentrated in the intermediolateral nucleus, were also identified in some experiments. In addition, many sympathetic postganglionic neurons were labeled in the renal nerve ganglia, the superior mesenteric ganglion, and the ipsilateral paravertebral ganglia from T12 to L3. Transganglionic transport of HRP labeled renal afferent projections to the spinal cord of kittens from T11 to L6, with the greatest concentrations between L1 and L3. These afferents extended rostrocaudally in Lissauer's tract and sent collaterals into lamina I. In the transverse plane, a major lateral projection and a minor medial projection were observed along the outer and inner margins of the dorsal horn, respectively. From the lateral projection many fibers extended medially in laminae V and VI forming dorsal and ventral bundles around Clarke's nucleus. The dorsal bundle was joined by collaterals from the medial afferent projection and crossed to the contralateral side. The ventral bundle extended into lamina VII along the lateroventral border of Clarke's nucleus. Some afferents in the lateral projection could be followed ventrally into the dorsolateral portion of lamina VII in the vicinity of the intermediolateral nucleus. In the contralateral spinal cord, labeled afferent fibers were mainly seen in laminae V and VI. These results provide the first anatomical evidence for sites of central termination of renal afferent axons. Renal inputs to regions (laminae I, V, and VI) containing spinoreticular and spinothalamic tract neurons may be important in the mediation of supraspinal cardiovascular reflexes as well as in the transmission of activity from nociceptors in the kidney. In addition, the identification of a bilateral renal afferent projection in close proximity to the thoracolumbar autonomic nuclei is consistent with the demonstration in physiological experiments of a spinal pathway for the renorenal sympathetic reflexes.
Animals↗
Commonly responsive neurons in the periaqueductal gray matter and midbrain reticular formation of rabbits to acupuncture stimulation, inversion, pressure on body parts and morphine.
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Acupuncture Therapy↗
A prospective study on the development of hepatocellular carcinoma from liver cirrhosis with persistent hepatitis B virus infection.
We made a prospective study on the development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis with hepatitis B virus infection from April, 1973 to December, 1977. Seven out of 30 patients (23%) with hepatitis B surface antigen (HBsAg)-positive cirrhosis developed HCC. On the other hand, only 5.9% of the patients with HBsAg-negative liver cirrhosis developed HCC. These patients were classified into three groups according to their anti-HB core (anti-HBc) titers. When the anti-HBc titer, expressed as a dilution of serum, was 2(10) or more (Group I), 20-24% of the liver cirrhosis patients developed HCC either with or without a detectable amount of HBs Ag present in the sera. When the anti-HBc titer was 2(9) or less (Group II), only 0-5.7% developed HCC. There was no significant difference between this and the anti-HBc and HBsAg-negative group (Group III), which was 4.4%. In five individual cases from group I, HBsAg was detected in serum, and in biopsies of liver cells, before HCC could be detected by angiography and/or rising levels of alphafetoprotein (AFP). In all of these cases, the anti-HBc titer was higher than 2(10) throughout the observation period, even before the development of HCC. These findings indicate that active virus proliferation in chronic hepatitis B virus infection precedes the development of HCC as indicated by a higher anti-HBc titer. Therefore we have prepared these studies to show the pathogenic role of hepatitis B virus in the development of hepatocellular carcinoma.
Biomarkers, Tumor↗
[Imported hepatitis: problems with imported infectious diseases].
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Adult↗
Clinicopathologic features of encapsulated hepatocellular carcinoma: a study of 26 cases.
The clinicopathologic features of 26 cases of hepatocellular carcinoma (HCC) surrounded by a grossly distinct capsule-like fibrous tissue were studied. The frequency of this type was 10.3% among autopsy cases of HCC. The mean age of the patients was 64.1 years, which was significantly older compared with that of 143 cases of nonencapsulated HCC. Hepatitis-B surface antigen in serum was positive in 18.7% of the cases studied, the positivity rate being lower than that of HCC in general. Histologically, the tumor was relatively well differentiated and the capsule was the product of slow expanding growth. Intravenous tumor invasion was less frequent compared with other types of HCC. Clinically, celiac angiography proves to be a most useful diagnostic method; a thick capsule may be demonstrated as a thin radiolucent rim around the mass. The clinical course from the early stage is protracted and, if detected early, this type of HCC may be removed surgically.
Adult↗
[Liver cirrhosis associated with peptic ulcer].
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Adult↗
Clinical observations during a relatively early stage of hepatocellular carcinoma, with special reference to serum alpha-fetoprotein levels.
Five cases of hepatocellular carcinoma in whom diagnosis was made when the tumor was relatively small, are described. In 2 cases, serum alpha-fetoprotein (AFP) strted to rise sharply, which enabled early detection and surgical removal of the tumor. Serum AFP was below 100 ng per ml, but above the upper normal limit by radioimmunoassay, and was unfluctuating for a considerable period of time before it began to rise in 2 cases. It was negative throughout in 1 case, who lived more than 4 years after the tumor had reached a detectable size. In 4 of 5 cases, the tumor seemed to have evolved during a stage of chronic hepatitis or its transition to cirrhosis. In 1 case with chronic schistosomiasis and advanced mixed macro- and micronodular cirrhosis, a 1.5-cm tumor was detected by celiac angiography. These observations on time relationship of oncogenesis may be generalized to modify the cirrhotic liver. Necessity is emphasized for the early detection of this type of carcinoma to monitor serum AFP in chronic hepatitis patients, particularly in those with unfluctuating, mildly abnormal levels of AFP.
Aged↗
[Diagnosis of mild cases of liver dysfunction].
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Adult↗
The role of neuropeptides in the sacral autonomic reflex pathways of the cat.
Immunohistochemical and pharmacological studies were conducted to examine the origin and function of peptidergic nerves in the sacral autonomic system of the cat. Leucine-enkephalin (L-Enk) immunoreactivity was identified in nerve terminals in peripheral ganglia on the surface of the urinary bladder and in the parasympathetic nucleus in the sacral spinal cord. In colchicine-treated animals L-Enk was also detected in sacral preganglionic neurons (sPGN) identified by retrograde transport of a fluorescent dye. L-Enk terminals in bladder ganglia are believed to arise from sPGN since the terminals were eliminated by transection of the sacral ventral roots. Pharmacological studies indicated that exogenous as well as endogenously released enkephalins have an inhibitory action at both ganglionic and spinal sites in the sacral outflow to the urinary bladder. Peptides were also associated with afferents nerves in the sacral autonomic system. The distribution of substance P, VIP and cholecystokinin in the sacral dorsal horn paralleled the distribution of visceral afferent projections as demonstrated with HRP techniques. Dye labeling combined with immunohistochemistry revealed that some dorsal root ganglion cells projecting to the pelvic viscera contain substance P or VIP.
Animals↗
Prevalence of primary sclerosing cholangitis and other liver diseases in Japanese patients with chronic ulcerative colitis.
An association between primary sclerosing cholangitis (PSC) and chronic ulcerative colitis (CUC) is well known in Western countries, but there have been no reports on this association in Japan. We reviewed 163 consecutive CUC patients (91 males and 72 females) diagnosed from 1984 to 1990 at Tokyo Women's Medical College. Abnormal liver function tests were found in 42 patients with CUC (25.8%), but chronic liver disease was only diagnosed in seven patients (4.3%). Among these seven patients, there were four with PSC, one with small-duct PSC, one with transfusion-associated chronic hepatitis and one with Type B liver cirrhosis. No relationship was found between the documented colonic manifestations of CUC and the presence of PSC. The four PSC patients did not have a longer history of CUC at the time of diagnosis of PSC than CUC patients without PSC. At the time of PSC diagnosis, two patients were asymptomatic, one presented with right upper quadrant pain, and the other had fatigue. Three patients were diagnosed as having CUC before the onset of PSC (range 2-13 years), and the other patient had both diseases simultaneously. All four had a good prognosis. Thus PSC was the most common chronic liver disease associated with CUC in our series, and it was present in all our CUC patients with alkaline phosphatase levels exceeding twice the upper limit of normal and mild transaminase elevation.
Adolescent↗
Emission of extremely strong magnetic fields from the head and whole body during oriental breathing exercises.
This article reports the result of an experiment that was designed to measure the biomagnetic field emanating from two individuals who were practising traditional Oriental Qi Gong breathing exercises. The biomagnetic field was measured with differential coils wound 80,000 turns, a magnetic needle compass and a digital electromagnetic wave detection device. It was found that an extremely strong magnetic field was emitted from the two individuals. One subject emitted a magnetic field at the level of 200-300 mT (2-3 mGauss) and the other at 0.13 mT (1.3 mGauss). In both cases, moreover, the magnetic needle compass rotated 30 degrees (this was tested 32 times). When the rotation of the needle occurred, a reproducible magnetic field of 800-1500 mT (8-15 mGauss) was indicated on the digital measuring device (this was tested 12 times). It is concluded that traditional Oriental Qi Gong breathing appears to stimulate an unusually large biomagnetic field emission.
Breathing Exercises↗
Production of hydrogen peroxide in cancerous tissue by intravenous administration of sodium 5,6-benzylidene-L-ascorbate.
We investigated whether the antitumor action of sodium 5,6-benzylidene-L-ascorbate (SBA) is mediated via oxidation-involved mechanism, in three different systems: 3'-methyl-4-dimethylaminoazobenzene (DAB)-induced rat hepatocellular carcinoma (in vivo), its homogenate (semi in vivo), and cultured cells (in vitro). Oral intake of DAB irreversibly produced hepatocellular carcinoma in rats, with a maximum incidence of carcinogenesis after 4 months. Intravenous administration of SBA induced vacuolar, eosinophilic degeneration and nuclear debris, producing greater amounts of ESR signal of ascorbate radical and hydrogen peroxide (H2O2)-derived chemiluminescence (CL) (H2O2-CL) in the cancerous tissue than in the normal tissue. When SBA was directly added to the homogenates, higher amounts of ascorbate radical and H2O2-CL were generated in cancerous tissues. When SBA was added to the RPMI1640 medium supplemented with 10% fetal bovine serum, methionine was oxidized to methionine sulfoxide and H2O2 was produced in amounts that sufficiently induce apoptotic cell death in human promyelocytic leukemic HL-60 cells. Cytotoxic activity of SBA was significantly reduced by catalase. These data suggest that antitumor activity of SBA in vivo might at least in part be due to H2O2, produced from SBA.
Animals↗