A case report: Severe bone marrow suppression caused by 6-mercaptopurin in Crohn's disease patient]

A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and perianal abscess caused by Crohn's disease. After incision and drainage of the abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced. His white blood cell (WBC) count on day 12 after initiation of 6-MP was not decreased. However, on day 24 he was re-admitted because of severe myelosuppression (WBC: 300/microl), which was complicated by the recurrence of the perianal abscess. Myelosuppression was prolonged and required the administration of granulocyte colony stimulating factor (G-CSF). G-CSF was continued for 17 days to achieve recovery of his WBC count to a normal level.     

The effects of maternal ethanol exposure on neurotransmission and second messenger systems: a quantitative autoradiographic study in the rat brain.

The effects of maternal ethanol exposure on neurotransmission and second messenger systems were examined in rats using histochemistry and in vitro autoradiography. Thirty % ethanol was administered to pregnant rats from gestational day 7 to the day of delivery. Quantitative autoradiography was used to map muscarinic cholinergic, dopamine D2, adenosine A1, and inositol 1,4,5-trisphosphate binding sites, as well as to localize adenylate cyclase and protein kinase C. We found no difference in the patterns of staining with acetylcholinesterase and Timm's stain between control and prenatally ethanol-exposed rats on postnatal day (PN) 30. In the ethanol-exposed rats, [3H]forskolin binding sites were increased during early development in the CA1 subfield of the hippocampus and the occipital cortex; [3H]phorbol ester binding sites were increased in the cortex, striatum, and hippocampus; hippocampal muscarinic cholinergic sites were increased on PN4 and 30; adenosine A1 binding was reduced on PN10 in most regions examined, but was increased in the CA1 subfield on PN30; dopamine D2 receptor levels were significantly reduced on PN30 in the striatum; and IP3 receptors were decreased in most regions studied, but particularly in the cerebellum. Thus, some of these changes were transient and others were long-lasting. Although histopathological abnormalities were minimal, the alterations of binding sites in the cerebellum (the coordination center) and in the hippocampus (related to memory and learning) that were detected may contribute to the behavioral and mental deterioration seen in the fetal alcohol syndrome.     

Case of severe ulcerative colitis successfully treated with intravenous cyclosporine without high dose corticosteroid]

A 44-year-old women developed marked myopathy one year earlier, when she was treated with intravenous prednisolone for acute severe exacerbation of ulcerative colitis. When she was admitted to our hospital for another severe exacerbation, intravenous cyclosporine A was administered as monotherapy because she could not tolerate corticosteroid. The treatment was successful and she obtained complete remission. Cyclosporine A monotherapy is considered to be a valuable alternative to proctocolectomy for severe ulcerative colitis patients who cannot tolerate corticosteroid.     

Spontaneous spinal epidural hematoma diagnosed by MRI: a case report

Appropriate diagnostic procedure for spinal epidural hematomas has not been established yet. The authors reported a case of spontaneous epidural hematomas at the thoracic level, in which correct diagnosis was made with MRI and good results were obtained by surgery. A 63-year-old female experienced a severe back pain which appeared suddenly during a walk and was followed by motor weakness in both legs deteriorating quickly to paraplegia. The patient had no history of hypertension, trauma or bleeding tendency. The laboratory data were normal. On admission, neurological examination revealed flaccid paraplegia, total sensory loss below the level of Th 6 and urinary and fecal incontinence. Myelograms showed incomplete block at the Th 6 level and postmyelographic CT scan showed an isodense mass, which was suspected to be an epidural tumor located behind the spinal cord. Emergent MRI confirmed an epidural hematoma as a high intensity area extending from Th 3 through Th 11. Sixty-five hours after onset, laminectomy of Th 4 through Th 11 and the evacuation of epidural hematoma were performed without identification of the origin of the bleeding. Neither vascular malformation nor tumor was recognized during operation. Neither was it noticed on histological examination. The patient made favorable progress after the surgery. During the first two weeks in the postoperative period, she regained muscle strength enough to do standing exercise, and satisfactory improvement was made in sensory function including urination and defecation. We emphasize that MRI is indispensable to make a differential diagnosis of thoracic lesions. In the reported case, a correct diagnosis was made with MRI, and an extremely good result was obtained by an emergency operation.     

Intrarenal localization of receptors for alpha-rat atrial natriuretic polypeptide: an autoradiographic study with [125I]-labeled ligand injected in vivo into the rat aorta

We examined intrarenal localization of receptors for alpha-rat atrial natriuretic polypeptide (alpha-rANP) by injecting [125I]-labeled ligand in vivo into the rat aorta. We found that the receptors for alpha-rANP are distributed also on the vasa recta of the outer and inner medulla in addition to the previously reported sites, i.e., the renal arteries, renal pelvis, glomeruli, and inner medullary tissues including collecting tubules. In the vascular bundle of the outer medulla, the majority of grains was preferentially localized on the arterial vasa recta. The electron microscopic autoradiography of the glomerulus showed that the binding sites were mainly localized on the foot process of the podocyte. Since alpha-rANP injected into the aorta under physiological conditions was bound to the glomerulus and vasa recta in the kidney, the effect of ANP on these binding sites may be important in the mechanism of natriuresis.     

Measurement of nonlinear property of artery wall using remote cyclic actuation

Purpose For tissue characterization of the arterial wall, we developed a “phased tracking” method to measure the strain (change in wall thickness) and elasticity of the arterial wall. To improve the accuracy of tissue characterization, we are now attempting to measure other mechanical properties in addition to elasticity. Methods In this study, the change in elasticity during the cardiac diastole was measured with ultrasound by generating a change in internal pressure using remote cyclic actuation. Results From the measured change in elasticity during cardiac diastole, the nonlinear property in the stress–strain relationship of the artery wall was estimated. In basic experiments using a silicone rubber tube and in vivo experiments in human carotid arteries. Conclusion The proposal method enables the noninvasive measurement of the nonlinear mechanical property in addition to the elasticity of the arterial wall.     

Effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin on the dopaminergic and cholinergic receptors as evaluated by positron emission tomography in the Rhesus monkey

Summary The effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP) on the central cholinergic and dopaminergic systems in the Rhesus monkey brain were investigated by positron emission tomography (PET) with the muscarinic cholinergic receptor ligands (N-[¹¹C]methyl-benztropine) and dopaminergic receptor ligands selective for D₁ D₂, and D₃ subtypes ([¹¹C]SCH23390, N-[¹¹C]methyl-spiperone, and (+)[¹¹C]UH232, respectively). None of the doses (3, 10, and 30 mg/kg i.v.) of R-THBP used significantly affected the regional cerebral blood flow (rCBF as determined by Raichle's H₂ ¹⁵O method), and 10 mg/kg of R-THBP had little effect on the regional cerebral metabolic rate of glucose (rCMRglc) in the Rhesus monkey brain, as assessed by the graphical [¹⁸F]fluoro-deoxyglucose method. The effect of R-THBP on the muscarinic cholinergic system was dose dependent; while 3 mg/kg of R-THBP did not significantly alter the uptake ratio of N-[¹¹C]methyl-benztropine in several brain regions to that in the cerebellum, 10 and 30 mg/kg of R-THBP significantly reduced the uptake ratio in the thalamus, as well as in the frontal and temporal cortices. None of the doses (3, 10, and 30 mg/kg i.v.) of R-THBP tested affected [¹¹C]SCH23390 (dopamine D₁ receptor) binding. However, the k3 value for N-[¹¹C]methyl-spiperone (dopamine D₂ receptor) binding, which represents the association rate × B_max value, was significantly decreased in the striatum. The uptake ratio of (+)[¹¹C]UH232 (dopamine D₃ receptor) in the striatum to that in the cerebellum was also decreased by administration of R-THBP (3 and 30 mg/kg i.v.). These findings suggest that R-THBP acts on dopamine D₂ and D₃ receptors selectively without markedly affecting dopamine D₁ receptor binding. Furthermore, the changes in cholinergic and dopamine D₂ and D₃ receptors in vivo can not be attributed to a change in rCBF but may depend on the action of R-THBP.Abbreviations R-THBP 6R-L-erythro-5,6,7,8-tetrahydrobiopterin - PET positron emission tomography - rCBF regional cerebral blood flow - rCMRglc regional cerebral metabolic rate of glucose     

Molecular biological study of the rhodopsin gene in Japanese patients with autosomal dominant retinitis pigmentosa]

The author analyzed codon 347 of the rhodopsin gene using PCR (polymerase chain reaction) amplification and restriction enzymes in 19 unrelated Japanese families including 28 patients with autosomal dominant retinitis pigmentosa (ADRP). An allele of codon 347 mutation was found in a family (father and daughter). Sequence analysis shows that the mutation is from CCG to CTG. This mutation appears to be the cause of one form of ADRP, since it was also found in Japanese cases of ADRP which have a different racial background from families reported by Dryja et al.     

Reversal of alpha-methyltyrosine-induced hypoactivity by 6-(R)-5,6,7,8-tetrahydro-L-erythrobiopterin (R-THBP) in mice.

The effects of peripheral administration of 6-(R)-5,6,7,8-tetrahydro-L-erythrobiopterin dihydrochloride (R-THBP), a natural cofactor for tyrosine and tryptophan hydroxylases, were investigated in mice treated with a competitive inhibitor of tyrosine hydroxylase, alpha-methyltyrosine (alpha-MT). A subcutaneous dose of 250 mg/kg of alpha-MT decreased markedly both ambulatory activity and cerebral contents of norepinephrine, dopamine and their metabolites in mice. An intraperitoneal dose of 100 mg/kg of R-THBP, which did not alter ambulatory activities in normal mice, improved the hypoactivity in alpha-MT-treated mice. Moreover, R-THBP at intraperitoneal doses of 60 and 100 mg/kg inhibited the impairment of cerebral catecholamine metabolism induced by alpha-MT in mice. We suggest that the reversal of the alpha-MT effects by R-THBP might be due to reactivation of tyrosine hydroxylase in the central nervous system.