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The plasma level of isosorbide dinitrate intraperitoneally administered to rats stressed by foot-shock was almost the same as that in non-stressed control rats. However, levels of its metabolites, 5-isosorbide mononitrate and 2-isosorbide mononitrate, were lower in stressed rats than in non-stressed rats, suggesting that stress may influence the metabolism and/or excretion of the metabolites.

We studied the effect of endogenous prostaglandin E2 (PGE2) on interleukin 1 (IL-1) production by peripheral blood monocytes from patients with rheumatoid arthritis (RA). IL-1 production by RA monocytes was not different from that of monocytes from normal controls, when the cells were either unstimulated or stimulated with lipopolysaccharide (LPS, 20 micrograms/ml), as measured by two different bioassays (thymocyte or fibroblast proliferation assay) and enzyme-linked immunosorbent assay. However, IL-1 production by LPS-stimulated monocytes from RA patients cultured in medium containing indomethacin, an inhibitor of PGE2 synthesis, was significantly greater than that of monocytes from normal controls. In addition, the levels of PGE2 in culture supernatants of unstimulated or LPS-stimulated monocytes from RA patients were higher than in culture supernatants of monocytes from normal controls. Moreover, the increase of in vitro IL-2 production by RA T cells stimulated by phytohemagglutinin (PHA) was observed when monocytes were removed from peripheral blood mononuclear cells. These results indicated that peripheral blood monocytes from RA patients could produce IL-1 in excess in vitro, but that in vivo IL-1 production by RA monocytes and IL-2 induction by RA T cells might be negatively regulated by endogenous PGE2.

Peptides and proteins in the extracellular space in the central nervous system were investigated in vivo using an intracerebral microdialysis probe. The molecular cut-off of the hollow fiber which was used for the probe was approximately 100 kDa. We examined recovery rates of several compounds in vitro. The recovery rates of proteins and peptides were between 7-28%, with the exceptions of substance P and insulin-like growth factor I. The recovery rates of monoamines and their metabolites were 22-40%. In in vivo studies, two major proteins with apparent molecular weights of 62 kDa and 12 kDa, and several minor proteins (28 kDa, 43 kDa, 52 kDa and 70 kDa) were detected by SDS-polyacrylamide gel electrophoresis in the dialysate from a probe implanted in the striatum of anesthetized rats. These results suggest that the newly developed, intracerebral microdialysis probe might be useful for investigating the dynamic changes of peptides and proteins in the central nervous system.

To select a suitable medium for serum-free primary culture of adult rat hepatocytes, ten commercially-available synthetic media were compared for their ability to maintain the cells under serum-free and serum-supplemented conditions with special reference to attachment, survival and albumin secretion. It was found that Williams' medium E and DM-160 medium were the best among the ten media for maintaining hepatocytes under serum-free conditions in primary culture.

A method for the simultaneous determination of hypotaurine and taurine was developed. The method consisted of the elimination of urea, which interfered with the determination of hypotaurine, by immobilized urease, and determination of hypotaurine and taurine with an amino acid analyzer. The analyzer equipped with a cation-exchange column was operated at 32 degrees C with 0.2 M sodium citrate buffer, pH 2.8. Using this method, the dynamics of hypotaurine and taurine in blood plasma of rats was studied after the intraperitoneal injection of L-cysteine. The concentration of cysteine reached the maximum 1 h after L-cysteine loading. The concentration of hypotaurine and taurine increased in parallel and reached the maximum 2 h after L-cysteine loading. These changes seem to indicate the precursor-product relationship of these substances and the rapid conversion of hypotaurine to taurine in vivo.

We studied the brains of two cases of amyotrophic lateral sclerosis with dementia. Bunina bodies were found in the motor neurons of cranial nerve nuclei (trigeminal, facial and hypoglossal nerves) as well as in the spinal motoneurons. They appeared mostly in the cytoplasm and occasionally in the neuronal processes. However, the present electron microscopic study disclosed clearly that Bunina bodies were present not only in the cell body but also in the dendrites. No Bunina bodies were observed in the axons. It is inferred that the Bunina bodies were degenerative products formed as a result of a protein metabolism disorder.

Capsaicin-sensitive and hexamethonium-insensitive contractile and relaxatory motor responses of circular muscle induced by mesenteric nerve stimulation were studied. Desensitization to substance P or to neurokinin A, or the substance P antagonist, spantide largely reduced the initial contractile response. Desensitization to calcitonin gene-related peptide moderately reduced the late prolonged relaxation response. These results indicate that both responses of the circular muscle to mesenteric nerve stimulation may be attributed to a release of neuropeptides evoked by the 'efferent' stimulation of capsaicin-sensitive sensory nerves.

A case of hepatocellular carcinoma is reported in which the main tumor, intrahepatic metastases and a tumor thrombus in the portal vein were necrotized completely after Lipiodol chemoembolization. In this case, the tumor thrombus seemed to act as a portal embolus. This phenomenon is interesting because Lipiodol chemoembolization alone usually can not necrotize intra- or extra-capsular invasion, intrahepatic metastasis or tumor thrombus in the portal vein. This case is considered to be suggestive of a possible therapy for hepatocellular carcinoma.

The excretion of 3-mercaptolactate-cysteine mixed disulfide [S-(2-hydroxy-2-carboxyethylthio)-L-cysteine, HCETC], sulfate and taurine in the urine of normal adults was investigated before and after oral administration of L-cysteine and related sulfur-containing amino acids. Before the loading of amino acids, the excretion (mean +/- SD) per kg of body weight per day of HCETC, free sulfate and taurine was 0.096 +/- 0.042, 305.7 +/- 66.1 and 31.9 +/- 8.7 mumols, respectively. After the loading of L-cysteine (800 mumols/kg of body weight), the average excretion in the 24-h urine of HCETC increased 2-fold and that of taurine increased 1.6-fold. The average excretion of free sulfate after the L-cysteine loading was 989.4 +/- 145.1 and 388.8 +/- 51.6 mumols/kg per day in the first and second 24-h urine, respectively, indicating that the sulfur corresponding to 85% of the L-cysteine loaded was excreted as free sulfate in 24 h. Administration of L-cystine (400 mumols/kg) resulted in similar results. The increase in HCETC after L-cysteine or L-cystine administration indicates that L-cysteine is metabolized in part through the transamination pathway (3-mercaptopyruvate pathway) and that an equilibrium exists between the intake and excretion of sulfur in humans.

In the extrinsically denervated smooth muscle esophagus of the hen anesthetized with urethane (1 g/kg, i. m.), it was studied whether peptidergic neurons in the intramural plexus are involved in the intrinsic reflex. Ascending and descending contractions, and descending relaxation were induced by electrical stimulation of a narrow segment of the esophagus. Naloxone (1 microM), desensitization to substance P (0.3 microM) and spantide (20 microM) inhibited the ascending and descending contractions, respectively. The degree of the inhibition of the contractile response by a combination of naloxone and substance P was nearly the same as that by a single administration of naloxone or substance P. The ascending and descending contractions were reduced to one-third of the control by hexamethonium (100 microM) and abolished by atropine (10 microM). The descending relaxation was abolished after desensitization to vasoactive intestinal peptide (0.3 microM). Taken together the results suggest that in the hen's esophagus, opioid- and substance P-containing neurons in the intramural plexus may act as preganglionic neurons of cholinergic motor neurons in the ascending and descending excitatory pathways and that vasoactive intestinal peptide-containing neurons are involved in the descending inhibitory pathway.

<p>Tissue contents and urinary excretion of taurine were studied in rats after the administration of L-cysteine and its derivatives. Average taurine content in the liver of rats fed a 25% casein diet for 7 days increased 2-fold 2h after the intraperitoneal administration of 5 mmol of L-cysteine per kg of body weight, whereas that in rats fed a 5% casein diet for 2 days increased only slightly. The difference in the liver taurine contents between these two groups was discussed in relation to cysteine dioxygenase. Taurine contents in the heart, brain and blood did not differ significantly between these two groups or between the control and the group of rats which received L-cysteine. The increase in liver taurine concentrations after L-cysteine administration was much higher than that after L-cystine administration, suggesting a difference in their absorption. The intraperitoneal administration of 5 mmol/kg of L-2-oxothiazolidine-4-carboxylate (OTCA) resulted in a 3-fold increase in liver taurine content. The average increase in taurine excretion in the 24-h urine after OTCA administration corresponded to about 6.0% and that in the next 24-h urine to about 2.6% of OTCA administered, suggesting that nearly 10% of OTCA was metabolized to taurine and excreted in the urine.</p>

Progenitor cells in the bone marrow and the spleen of mice, whether infected with Schistosoma japonicum or not, formed cell clusters and colonies when incubated with culture supernatant fluid of spleen cells incubated with soluble egg antigen (SEA). The egg extract, up to a concentration of 250 micrograms/ml protein, did not directly stimulate progenitor cell proliferation in the bone marrow. Eosinophilia in mice infected with S. japonicum may be mediated indirectly by egg antigen-stimulated immune lymphocytes and not directly by the egg antigen.

We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH), 1 micrograms/kg growth hormone releasing hormone (GRH), 500 micrograms thyrotropin-releasing hormone (TRH), 100 micrograms luteinizing hormone releasing hormone (LH-RH), and a relatively small dose (5 mU/kg) of lysine vasopressin (LVP). In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH) induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH), prolactin (PRL) and follicle-stimulating hormone (FSH) responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function.

The influence of physical exercise on the urinary excretion of proteins was examined in 17 male high school baseball players. Their urine was collected before and after exercise to determine the concentrations of total protein, albumin, beta 2-microglobulin and creatinine along with the activity of N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30). Concentrations of total protein, albumin, beta 2-microglobulin and creatinine increased significantly (p less than 0.01) after exercise, while N-acetyl-beta-D-glucosaminidase activity did not increase. Similar results were obtained when the concentrations of these urinary components were calculated on the basis of a urinary density of 1.024, and when they were expressed relative to the amount of creatinine. Positive correlations were seen among total protein, albumin, beta 2-microglobulin and creatinine concentrations, but not between the beta 2-microglobulin concentration and N-acetyl-beta-D-glucosaminidase activity. Isoenzyme activities of N-acetyl-beta-D-glucosaminidase in the urine were determined by electrophoresis on cellulose acetate plates. After exercise, the A-form increased slightly, and the B-form decreased slightly, but these changes were not statistically significant.

A rare gastrointestinal tract neoplasm, primary non-Hodgkin's B-cell lymphoma in a 39-year-old, asymptomatic woman is described. The tumor was originally localized in the rectum without evidence of any other lymphoma-involved organ and treated by curative surgical procedure associated with postoperative chemotherapy.

The effects of salt loading and adrenalectomy on arginine vasopressin (AVP) mRNA levels in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus were studied by semiquantitative in situ hybridization histochemistry, using a synthetic oligonucleotide probe and a computer-assisted image analysis system. Salt loading (2% NaCl) for 7 days produced marked increases in AVP mRNA levels in the magnocellular neurons of the PVN, SON, and accessory nuclei. Adrenalectomy caused an increase in AVP mRNA expression in the magnocellular part of the PVN and the expansion of hybridization signals into its medial parvocellular region, where the cell bodies of corticotropin-releasing hormone (CRH) neurons are located. No apparent alteration of AVP mRNA levels was observed in the SON following adrenalectomy. These results indicate that hyperosmotic stimulation and the loss of circulating glucocorticoids had differential effects on AVP gene expression in the PVN and SON, and that the magnocellular PVN and SON neurons responded in different manners to the loss of feedback signals.

Effects of mesenteric nerve (MN) stimulation on the electrophysiological behavior of myenteric neurons in the guinea pig ileum were investigated with intracellular recording techniques in the myenteric flaps innervated with mesenteric nerves. MN stimulation at 0.11-6 Hz evoked fast excitatory postsynaptic potentials (EPSPs) in 6 myenteric neurons (2 Type 2/AH, 3 NS and 1 Type 1/S cells) and rarely evoked antidromic soma spike potentials in 3 myenteric neurons. Fast EPSPs were abolished by hexamethonium. Slow EPSPs evoked by MN stimulation (Takaki and Nakayama (1988) Brain Res., 442, 351-353) were also obtained in 5 Type 2/AH neurons and were irreversibly abolished by superfusion with capsaicin 10 microM. It is, therefore, likely that fast EPSPs mediated by nicotinic cholinergic receptors are due to stimulation of the vagus nerve and slow EPSPs are mediated by a release of substance P at axosomatic synapses due to antidromic activation of the capsaicin-sensitive sensory nerves.

To clarify the relationship between the catalase activity in mouse organs and the amounts of metallic mercury exhaled, normal, homozygous hypocatalasemic and acatalasemic mice were injected with mercuric chloride. The cumulative amount of metallic mercury exhaled by mice was evidently expressed in the descending order of acatalasemic, hypocatalasemic, and normal mice. Statistically significant differences in the cumulative exhaled metallic mercury levels were observed between acatalasemic and hypocatalasemic mice, between normal and hypocatalasemic mice, and between acatalasemic and normal mice using the method of one way analysis of variance (ANOVA). A linear relationship was obtained through logarithm of catalase activity in the lungs or the blood, and logarithm of the cumulative amount of the exhaled mercury.

A rare case of variant Philadelphia (Ph1) chromosome positive [46, XX, t (9; 22) (q34; q11), inv (9) (9q22; 22q13)] chronic myelocytic leukemia (CML) was described. The patient, 73 years old female, was hospitalized to our hospital because of leukocytosis. Hematological findings corresponded to those of CMLs. However, this case lacked hepatosplenomegaly. Southern blot analysis using a 3 breakpoint cluster region (bcr) probe revealed a bcr rearrangement. The patient has been in the chronic phase for sixteen months without treatment. Clinical and chromosomal changes are under observation in order to get accumulate data for a pathophysiological analysis of variant Ph1 positive CMLs.