Biomedical subjects
Publications and source records attributed to N Murakami.
In the present study, we tried to examine whether the 2-deoxy-D-[14C]glucose (2-DG) technique is useful to investigate the metabolic activity of fetal rat brain in the maternal uterus. The result shows that metabolic mapping of the fetal brain was clearly obtained by means of the 2-DG technique.
We examined the adrenocorticotropic hormone-releasing activities of several human interleukin-1 beta analogues that have markedly reduced pyrogenic activities in rats. Among the analogues tested, [Gly4]-, [Leu93]- and [1-148]-interleukin-1 beta increased the plasma adrenocorticotropic hormone level to almost that induced by authentic human interleukin-1 beta. Modifications of the N-terminus of the authentic molecule, i.e., [7-153]- and [Des-Ala1, Asp4]-interleukin-1 beta, significantly reduced the hormone-releasing activity. These data suggest that the adrenocorticotropic hormone-releasing activity of human interleukin-1 beta resides in the N-terminal structure of the authentic peptide and can be separated from its pyrogenic activity.
Casein kinase II from bovine brain transfers about one mole of phosphate to a serine residue near the COOH terminus of the heavy chain of myosin isolated from bovine brain. We have purified and characterized a peptide that contains this phosphoserine. The peptide was generated by chymotryptic and thermolytic digestion and was isolated by gel filtration, Fe3+ affinity chromatography, and reverse-phase high pressure liquid chromatography. Its sequence, Leu-Glu-Leu-Ser(PO4)-Asp-Asp-Asp-Asp-Glu-Ser-Lys-Ala-Ser-(Xaa)-Ile-Asn-Glu-Thr- Gln-Pro-Pro-Gln, shows that the Ser(PO4) is in an acidic environment, as is typical for casein kinase II phosphorylation sites. The "hydrophobic repeat" typical of alpha-helical coiled-coils is absent, suggesting that the sequence is part of a non-helical "tail piece" of the heavy chain. A synthetic peptide corresponding to residues 1-9 is shown to be an effective substrate for casein kinase II.
This study was aimed at establishing the importance of routine monitoring of white blood cell counts in patients with Graves' disease receiving antithyroid drug treatment. In the 12-year period from 1975 to 1987, 15,398 patients with Graves' disease receiving treatment with antithyroid drugs were seen at our clinic. Of these, 55 (0.4%) were found to have agranulocytosis. Agranulocytosis was defined as a granulocyte count of 0.5 x 10(9)/L or less. In only 12 of the 55 patients was agranulocytosis detected after the occurrence of infection (symptomatic; classic agranulocytosis). The remaining 43 patients were asymptomatic when agranulocytosis was detected during routine white blood cell count monitoring. However, 14 of these 43 patients became symptomatic several days after withdrawal of antithyroid drug treatment despite antimicrobial treatment (asymptomatic to symptomatic). Twenty-nine patients who were treated appropriately had no symptom of infection throughout the course of the disease, despite the absence of or an extremely small number of granulocytes in circulation (asymptomatic). These results suggest that a "routine monitoring" of the white blood cell count could be the most effective way of predicting and detecting agranulocytosis due to antithyroid drug treatment.
We investigated the effect of intracarotid infusion of prostaglandin E2 (PGE2) on the single-unit activity of neurons in the preoptic and anterior hypothalamic (PO/AH) region. A total of 35 neurons in the PO/AH region were examined: 10 were warm-responsive neurons, 6 were cold-responsive neurons, and 19 were thermally insensitive neurons. In the warm-responsive neurons, the activities of 4 neurons were facilitated, while 3 neurons were inhibited and 3 neurons were not affected after intracarotid infusion of PGE2. In the cold-responsive neurons, the activities of 2 neurons were facilitated and 4 neurons were not affected by PGE2 infusion. Furthermore, 15 out of 19 thermally insensitive neurons were not affected by PGE2 infusion. These results suggest that thermoresponsive neurons of the PO/AH region respond well to intracarotid infusion of PGE2, compared with thermally insensitive neurons. However, the direction of neuronal response induced by intracarotid infusion of PGE2 could not be generally categorized based on the thermoresponsiveness of individual neurons.
We report an intraventricular cyst in a 2-year-old boy who had myoclonic jerks of the extremities. The cyst had no communication with the ventricular system or subarachnoid space. Total removal of the cyst adhering to the choroid plexus was accomplished. The glial cyst wall was lined in part by flattened or cuboidal epithelium. The preoperative and postoperative computed tomographic scans and magnetic resonance images are presented, and congenital benign cysts in the lateral ventricle are reviewed and discussed.
Effects of dietary iodine on the induction of thyroid carcinoma using N-nitrosobis(2-hydroxypropyl)amine (BHP) were studied. Male Wistar rats were fed with an iodine-adequate diet (IAD group), an iodine-rich diet (IRD group) and an iodine-deficient diet (IDD group), respectively, until the time of sacrifice. From the 2nd experimental month, animals were injected with BHP once a week for 10 weeks. In the IAD and IRD groups, benign nodules and papillary carcinoma were found. The incidence of rats with benign nodules was 100% in both groups and animals with papillary carcinoma in the IAD and IRD groups comprised 33% and 29%, respectively. The area of the thyroid gland occupied by nodular lesions was much narrower in the IRD group than in the IAD group. In the IDD group, the thyroid showed marked enlargement due to multiple nodular proliferation of follicle cells. The incidence of rats with carcinoma was 100%, and not only papillary but also follicular carcinoma and one pulmonary metastasis were found. As the iodine content of the diet decreased, the nodular lesions increased in width and number, and the incidence of carcinoma in rats became higher. These effects of dietary iodine are probably related to the goitrogenic and/or promoting effects of TSH.
The effects of monensin on subcellular structure, release of thyroglobulin (TG) and peroxidase (PO) activity were investigated using primary cultures of thyroid cells obtained from patients with Basedow's disease (Basedow's cells). TG concentration in the culture medium was measured by a sandwich enzyme immunoassay and the amount of TG in cultured cells was measured with an identical sandwich enzyme immunoassay after lysis of the cells with Triton X-100. PO activity of cultured cells was measured by a biochemical method. Addition of TSH (10 mU/ml/day) to the culture medium increased the synthesis and release of TG. When monensin (1 micron/l) was added to the medium on the last day of a 3-day incubation with TSH, the Golgi complex showed vacuolative change ultrastructurally, and the amount of intracellular TG was increased, whereas the amount of TG in the culture medium and PO activity became lower than those in the control group. These results suggest that in cultured Basedow's cells, TG is secreted through the Golgi complex, and that the activity of PO is elevated after processing in the Golgi complex.
We observed one case of ectopic nesidioblastosis. A solitary nesidioblastoma was observed in the anterior wall of the duodenum. Ectopic nesidioblastosis has not been previously reported, but our experience suggests the necessity of examination for ectopic pancreas in cases of SIDS or its near-miss.
1. We investigated the effect of intravenous, intracerebroventricular and intrapreoptic injections of human recombinant granulocyte colony stimulating factor (GCSF) on body temperature and acute phase responses in the rabbit, including changes in the plasma concentration of iron, zinc, copper and fibrinogen and in circulating leucocyte count. 2. Neither intravenous nor intracerebroventricular injection of GCSF had any effect on the body temperature. 3. Both the intravenous and the intracerebroventricular injections of GCSF induced a dose-dependent increase in the circulating leucocyte count but neither affected the plasma concentration of iron, zinc, copper and fibrinogen. Furthermore, intrapreoptic injection of GCSF produced leucocytosis but had no effect on the red blood cell count. 4. The present results suggest that GCSF induces leucocytosis through its action on both the peripheral target organs and the central nervous system.
1. Febrile responsiveness of rabbits and rats to intravenous (I.V.) or intracerebroventricular injection of human recombinant interleukin-1 alpha (IL-1 alpha), human recombinant interleukin-1 beta (IL-1 beta) and prostaglandin E2 was examined. 2. The I.V. injection of both IL-1 alpha and IL-1 beta produced dose-dependent fever over a range of 0.05-2.0 micrograms/kg. A small dose of IL-1 alpha (0.5 micrograms/kg) or IL-1 beta (0.5 micrograms/kg) produced a monophasic patterned fever in both rabbits and rats. A large dose (2.0 micrograms/kg) of IL-1 alpha or IL-1 beta produced a biphasic fever in rabbits, but monophasic fever in rats. Febrile responses in rabbits induced by I.V. injection of IL-1 alpha or IL-1 beta were significantly greater than those in rats induced by these same injections. Furthermore, in both species, the pyrogenicity of I.V. IL-1 beta was greater than that of IL-1 alpha. 3. The intracerebroventricular injection of both IL-1 alpha and IL-1 beta produced dose-dependent fever over a range of 0.2-20 ng. In rabbits and rats, the ventricular injections of IL-1 alpha and IL-1 beta produced fever with almost the same pattern--monophasic, regardless of injection doses. Although febrile responsiveness of rabbits to ventricular injection of IL-1 alpha was greater than that of rats, responsiveness to IL-1 beta was almost the same in both species. Pyrogenicity of ventricular IL-1 beta was greater than that of IL-1 alpha. However, febrile responses in rats induced by ventricular injections of several doses (2-2000 ng) of prostaglandin E2 were greater than those in rabbits. 4. The present results show that febrile responsiveness of rabbits to I.V. IL-1 is significantly greater than that of rats. However, fever sensitivity within the central nervous system (CNS) of rats is not lower compared with that of rabbits. Therefore, we considered that between the two species there exist structural differences in the organum vasculosum laminae terminalis (OVLT), which is currently believed to be the pathway of pyrogen to the CNS and/or the site of production of pyrogenic prostaglandins. 5. Histological examinations showed that the rabbit's OVLT has two vascular components with capillaries, one in the layer near the third ventricle and the other in the layer near the subarachnoideal space. However, the rat's OVLT only has a single component, in the layer near the subarachnoideal space.(ABSTRACT TRUNCATED AT 400 WORDS)
1. Intravenous (I.V.) human recombinant interleukin-1 beta (IL-1 beta) in high doses caused biphasic fever in rabbits. In lower doses it produced only the first phase of fever. 2. Intracerebroventricular (I.C.V.) or intrapreoptic-anterior hypothalamic (IPOAH) injection of IL-1 beta produced a rather rapid and marked increase in rectal temperature. 3. Subcutaneously administered indomethacin partly reduced the first phase and more substantially the second phase of the biphasic fever induced by high doses of I.V. IL-1 beta. The first phase may thus be prostaglandin independent at least in part. 4. In the fever induced by I.C.V. injection of IL-1 beta, subcutaneous indomethacin reduced the elevation of the rectal temperature considerably and delayed the onset of fever. Administration of indomethacin (I.C.V.) caused marked inhibition of the fever induced by a lower I.C.V. dose of IL-1 beta, but with a high dose the onset of the fever was delayed for about 1 h, without the total rise being affected. 5. It is concluded that the first phase of biphasic fever is caused by IL-1 beta acting via an extravascular component of the organum vasculosum laminae terminalis (OVLT) or the circumventricular organs accessible from only the blood side, to release arachidonate metabolites, presumably prostaglandin E2 (PGE2), and the second phase by IL-1 beta acting via the blood-brain interface accessible both from the blood side and the brain side, to release metabolites other than PGE2.
1. We investigated the effect of physical training on febrile and acute-phase responses induced in rats by intravenous (I.V.) injection of bacterial endotoxin or human recombinant interleukin-1 beta (IL-1). Physical training was performed by swimming for 1 h per day, 5 days a week. After four weeks of training, animals were used in the experiments. 2. The I.V. injection of endotoxin produced a febrile response in the trained group but not in the control group. However, there were no statistically significant differences between febrile responses induced by the I.V. injection of IL-1 in the control and trained groups. 3. The I.V. injection of endotoxin significantly decreased the plasma concentration of iron and zinc and increased the plasma fibrinogen concentration in both the control and the trained groups. However, the decreases in the plasma iron and zinc concentrations in the trained group were significantly greater than those in the control group. The I.V. injection of endotoxin increased the circulating leucocyte count in the only trained group. 4. The I.V. injection of IL-1 significantly decreased the plasma concentration of iron and zinc and increased the plasma fibrinogen concentration and the circulating leucocyte count in both the control and the trained groups. However, between the two groups, no significant differences in the values of acute-phase reactants were observed. 5. The present results suggest that the ability to produce cytokine(s) to induce febrile and acute-phase responses is enhanced by physical training. However, physical training has no effect on the febrile and acute-phase responses induced by IL-1.
An autolytic substance in an axenic cyanobacterium, Phormidium tenue, was identified as a mixture of fatty acids, by use of cultured cells in the laboratory. Among them, linoleic acid and linolenic acid were potent growth inhibitors.
Effects of novel aldose reductase inhibitors, M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) and M16287 (1-(3-chlorobenzo[b]furan-2-ylsulfonyl)hydantoin), on galactose-induced cataract formation in rats were investigated. Rats fed a 30% galactose diet developed lenticular opacity in the peripheral region by the 6th day of galactose feeding and showed gradual progression of opacity from the equator to the center of lenses. Histological study on the 15th day showed apparent lens fiber swelling and vacuolation predominantly in the equatorial and anterior cortical regions. Biochemical changes such as accumulation of galactitol, depletion of myo-inositol and decrease in glutathione (GSH) content in lenses preceded the appearance of opacity. Remarkable increase in NADPH content and decrease in NADP+ content, in addition to elevation of the ratio of Na+/K+, in lenses were also observed on the 15th day. Both M16209 and M16287 (10, 30 and 100 mg/kg/day, p.o.) dose-dependently ameliorated these morphological and biochemical changes except that restoration of myo-inositol content was incomplete. These results indicate that M16209 and M16287 can prevent galactose-induced cataract formation through amelioration of metabolic disorders and thus have high potential for clinical use in the treatment of some diabetic complications.
In order to clarify the effect of thyroid hormone on the plasma atrial natriuretic peptide (ANP) concentration, 14 patients with Graves' disease and 6 normal control subjects were studied. They were all under constant sodium intake because dietary sodium is known to affect the amount of plasma ANP. Sodium intake remained constant at 171 mEq daily for five consecutive days at which time the ANP concentration was measured. Graves' disease patients were tested both before and after surgery. The preoperative, hyperthyroid ANP level concentration in Graves' disease patients was 6.7 +/- 2.3 fmol/ml compared to a significantly lower level of 4.2 +/- 1.4 fmol/in normal control subjects. Seven days after surgery when Graves' disease patients became euthyroid their ANP markedly decreased to 4.2 +/- 2.9 fmol/ml. In the present study we were able to confirm that under a constant sodium diet, high plasma ANP in patients with Graves' disease was reduced after surgery when they became euthyroid. Results also suggest that high circulating ANP might play an important role in sodium and water metabolism and hemodynamic changes in hyperthyroidism.
A fragment of human genomic DNA containing the entire pro-opiomelanocortin (POMC) gene was introduced by transfection into the rat glial cell line C6. Blot analysis using poly(A)-rich RNA from the transformed C6 cells showed several hybridization bands. One band was similar in size (1.2 kb) to the POMC mRNA of human pituitary, while two were larger (2.6 and 2.2 kb) and the fourth smaller (800 bp). S1 nuclease mapping revealed that the POMC transcripts in transformed C6 cells were similar to those in non-pituitary tissues. Immunoreactive ACTH (ir-ACTH) was measurable in both the culture medium and cells. Gel chromatography showed that ir-ACTH in the medium eluted at a position identical to that of so-called big ACTH (approximately 40 kDa) which is found in the plasma of patients with ectopic ACTH syndrome. The human POMC gene could thus be expressed in the non-pituitary rat glial cell line C6, although the transcripts and translation products in C6 cells differ from those in the human pituitary. These results suggest that the transformed C6 cell may be a useful tool for studying the regulation of human POMC gene expression in non-pituitary cells.
After rats were chronically exercised by endurance swimming, an augmentation of succinic dehydrogenase (SDH) activity in the diaphragm and the EDL muscle was observed. In addition, endurance training induced a decrease in the percentage of myosin heavy chain (MHC) IIb in the diaphragm, and a decrease in the percentage of HCIIb concomitant with an increase in the percentage of HCIId in the EDL muscle. These results indicate that endurance training induced not only an increase of the oxidative capacity but also an alteration in the expression of an MHC phenotype in the diaphragm and skeletal muscle.