Arachidonate 12-lipoxygenase.
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Amino Acid Sequence↗
Biomedical subjects
T Yoshimoto
Publications and source records attributed to T Yoshimoto.
Immunohistochemical demonstration of TGF-beta-receptor type II in human pituitary adenomas.
To investigate whether the signalling pathway of transforming growth factor-beta (TGF-beta) is active in human pituitary tumors, an antibody against TGF-beta-receptor type II (TGF beta-R-II) was prepared to demonstrate immunohistochemically TGF beta-R-II expression in 48 cases of human pituitary adenoma. Positive immunoreactivity for TGF beta-R-II was found in 26 adenomas: 1 of 2 somatotroph cell adenomas, 1 of 9 mammotroph cell adenomas, 0 of 3 mixed somatotroph and mammotroph cell adenomas, 5 of 9 corticotroph cell adenomas, 3 of 3 gonadotroph cell adenomas, 12 of 15 plurihormonal adenomas, and 4 of 7 null cell adenomas. Expression of TGF beta-R-II varied between histological types of adenomas and increased with decreasing grades of differentiation. It is concluded that TGF-beta-mediated signals may be passed via TGF beta-R-II in pituitary tumors.
Adenoma↗
Immunohistochemical demonstration of tenascin in human pituitary glands and adenomas.
The expression of tenascin in 8 cases of normal fetal and adult human pituitary glands and in 51 cases of human pituitary adenomas was investigated immunohistochemically with the use of polyclonal antibodies against human tenascin. The immunohistochemical study demonstrated that tenascin is expressed in both fetal and adult normal epithelial cells of the anterior lobe of pituitary glands and in tumor cells of pituitary adenomas, which suggests that tenascin is synthesized by normal pituitary cells as well as by pituitary adenoma cells. Plurihormonal pituitary adenomas, especially those producing 4 or 5 different hormones, tended to show the highest incidence of positive immunoreactivity for tenascin, suggesting that tenascin may be involved in the aggressive behaviour of plurihormonal adenomas.
Adenoma↗
Effect of phenytoin on cortical Na(+)-K(+)-ATPase activity in global ischemic rat brain.
Na(+)K(+)-ATPase activity, water content, and Na+/K+ concentrations in the parietal cortex were measured in untreated and phenytoin-treated rats following global cerebral ischemia. Inhibitory effects of phenytoin treatment on brain edema and changes in Na(+)-K+ concentration with ischemia or ischemia followed by recirculation of varying intervals were assessed. The cortical Na(+)-K(+)-ATPase activity increased in the phenytoin-treated group during and after ischemia. Based on these results, we conclude that phenytoin provides ischemic brain protection by activating cortical Na(+)-K(+)-ATPase activity and by reducing intracellular Na+ and water content.
Animals↗
IL-2 inhibits IL-4-dependent IgE and IgG1 production in vitro and in vivo.
Nippostrongylus brasiliensis (Nb) infection of mice induces IL-4 producing CD4+ T cells which stimulate polyclonal IgE and IgG1 production, providing a model system to study IL-4 action on B cells in vivo. B cell Ia expression and the proportion of IL-2R beta positive B cells were increased in Nb-inoculated mice, and B cells from these mice responded to IL-2 by prompt and marked cell growth. Injection of anti-IL-4 1 day after Nb inoculation substantially inhibited these responses, indicating that they were largely IL-4 dependent. Thus IL-4 acted as a polyclonal B cell activator in vivo and caused B cells to develop into IL-2 responsive cells. Furthermore, injection of IL-2 inhibited IgG1 and IgE production by Nb-inoculated mice. To understand the mechanism of this IL-2-mediated inhibition, we used an in vitro IgG1 and IgE induction system. B cells from Nb-inoculated mice displayed an increase in the capacity of IL-2 to inhibit lipopolysaccharide (LPS) plus IL-4-driven IgE and IgG1 production, indicating that B cells expressing IL-2R beta are highly sensitive to IL-2. This inhibition was principally dependent upon the direct action of IL-2 on B cells. However, partial abolition of IL-2 inhibitory action by anti-IFN-gamma treatment suggested that endogenous IFN-gamma released from IL-2-stimulated cells was also involved in this IL-2-mediated IgE and IgG1 inhibition. Northern blot analysis demonstrated that IL-2 inhibited IL-4 induction of germline and productive C epsilon transcripts in LPS-stimulated B cells. Digestion-circularization polymerase chain reaction analysis revealed IL-2 inhibited IL-4 induction of s mu-s gamma 1 rearrangement in LPS-stimulated B cells.
Animals↗
Protease II from Moraxella lacunata: cloning, sequencing, and expression of the enzyme gene, and crystallization of the expressed enzyme.
A gene coding for protease II (basic amino acid specific oligoendopeptidase) from Moraxella lacunata was cloned and expressed in Escherichia coli DH1. The transformant harboring a hybrid plasmid, pMPROII-12, with a 3.0-kbp insert at the PvuII-SacI site in pUC19, showed 23-fold higher enzyme activity than M. lacunata. The expressed enzyme from E. coli DH1/pMPROII-12 was purified by 40-80% ammonium sulfate fractionation, chromatography on DEAE-Toyopearl, and Sephadex G-150 gel filtration. The enzyme was most active at pH 6.5 and stable at pH 6.5-9.5. It had an optimum temperature of 35 degrees C for 5 min of reaction and was stable to up to 35 degrees C for 30 min at pH 7.0. Its molecular weight was estimated to be 80,000 by SDS-PAGE and gel-filtration analyses. It enzyme was inhibited by diisopropyl fluorophosphate (DFP) and classified as a serine endoprotease. Its amino acid sequence was 38% homologous to that of the E. coli protease II. By alignment with other members of the prolyl endopeptidase family, the amino acid residues involved in the catalytic triad were deduced to be Ser-534, Asp-619, and His-654. The enzyme was crystallized by the hanging drop vapor diffusion method using PEG 4000 as precipitant.
Amino Acid Sequence↗
Cushing's disease due to female gonadotroph adenoma of the pituitary.
A 39-year-old woman presented with amenorrhoea, hyperprolactinaemia and sellar mass. Bromocriptine normalized PRL levels but failed to suppress tumour growth. Subsequently, she developed clinical signs and elevated blood cortisol levels consistent with a diagnosis of Cushing's disease. A pituitary tumour was removed which was immunoreactive for ACTH. Electron microscopic examination, however, revealed a female gonadotroph adenoma indicating that adenoma cells regarded as gonadotrophs by ultrastructural analysis may occasionally secrete ACTH and cause Cushing's disease.
Adenoma↗
Gene expression of vascular natriuretic peptide receptor in the aorta of hypertensive rats.
1. To elucidate the pathophysiologic role of vascular natriuretic peptide (NP) receptor in hypertension, we determined NP-A and NP-B receptor mRNA levels by means of ribonuclease protection assay in aorta of three types of hypertensive rats. 2. The NP-A receptor mRNA level was higher in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and deoxycorticosterone acetate-salt hypertensive rats than that in their respective control rats. On the contrary, the NP-A receptor mRNA level was lower in NG-nitro-L-arginine-methyl ester (L-NAME)-induced hypertensive rats compared with that in the control. 3. The NP-B receptor mRNA level did not show any significant change in all three hypertensive rats compared with their respective controls. 4. The present study suggests that high blood pressure is not the major factor regulating the NP receptor gene expression and also that the receptor subtype is independently regulated from each other.
Animals↗
Effect of vagal stimulation on intractable epilepsy.
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Adult↗
Fatal cytomegalovirus myocarditis in a seronegative ALL patient.
Fatal cytomegalovirus (CMV) myocarditis occurred in a 2 year old boy with acute lymphoblastic leukemia (ALL) in remission. The patient showed mild hepatic dysfunction and a rapid progress of pancytopenia after complete remission had been achieved. At the fifth week of complete remission, he presented signs of heart failure such as tachycardia, S4 gallop on auscultation and decreased ejection fraction on echocardiography. However, no significant electrocardiographic changes were recognized. In addition to the cardiac dysfunction, the patient presented a marked tachypnea and dyspnea associated with hypoxemia. These were dramatically improved by methylprednisolone pulse therapy (30 mg/kg per day, for 3 days) and CMV high titer immunoglobulin (400 mg/kg per day, for 3 days). On the sixth day after signs of respiratory failure were improved, the patient suddenly presented a paroxysmal atrial tachycardia followed by a fatal ventricular fibrillation. Although we could detect neither a specific IgM antibody, a significant increase of IgG antibody, nor CMV genome by DNA hybridization techniques during the course of the illness, microscopic examination of necropsy specimens of the heart showed a marked disruption and disintegration of muscle bands associated with cytomegalic inclusion bodies. Polymerase chain reaction (PCR) yielded a 305 bp amplification product in the heart and lung tissues, supporting the view that myocarditis was caused by CMV.
Antibodies, Viral↗
Visual disturbances in patients with pituitary adenoma.
INTRODUCTION: To clarify the relationship between visual disturbances caused by pituitary adenomas and the degree of chiasmal compression, MRI (1.5T) findings were assessed two dimensionally. MATERIAL AND METHODS: 50 cases of pituitary adenomas and 17 control cases were studied. The position of the optic chiasm was measured by the distance from the line of the frontal base and posterior clinoid process on the sagittal T1 weighted image, and from the upper surface of the bilateral internal carotid artery on the coronal T1 image. RESULT: Visual disturbances appeared when the chiasm was displaced to more than 8 mm above the aforesaid reference level on the sagittal image and more than 13 mm above on the coronal image. There was a good correlation between the appearance of visual field defects and the degree of chiasmal compression. CONCLUSION: The degree of chiasmal displacement measured by MRI two dimensionally can provide useful information for predicting the appearance of visual disturbances.
Adenoma↗
Interleukin-2 therapy of Langerhans cell histiocytosis.
A 20-month-old girl was diagnosed with Langerhans cell histiocytosis on the basis of a seborrheic skin rash, multiple punched out bony lesions, and skin biopsy findings. Combination therapy including alpha-interferon, vincristine, vindesine, cyclophosphamide, etoposide, cisplatin, betamethasone, THP-adriamycin, cytarabine and methotrexate was ineffective. Because cyclophosphamide enhanced lesion growth within the skull, we administered an intravenous infusion of interleukin-2 with remarkable efficacy. The reduction in lesion size with interleukin-2 treatment paralleled the increase in the percentage of CD16-positive natural killer cells in the peripheral blood.
Antineoplastic Combined Chemotherapy Protocols↗
Immunocytochemical localization of platelet-type arachidonate 12-lipoxygenase in mouse blood cells.
Arachidonate 12-lipoxygenase is an enzyme that oxygenates the 12 position of arachidonic acid to produce its 12-hydroperoxy derivative. We were interested in the tissue distribution and subcellular localization of the platelet-type 12-lipoxygenase, which is distinguished from the leukocyte type by several criteria. Antiserum was raised in rabbits against purified recombinant arachidonate 12-lipoxygenase of human platelets. When mouse bone marrow cells and lung were immunostained and observed by light and electron microscopy, the positively stained cells were platelets, megakaryocytes, and eosinophils. 12-Lipoxygenase was localized in the cytoplasm of platelets but was hardly detectable in the plasma membrane and intracellular organelles. The enzyme was found in the cytoplasm of immature megakaryocytes with kidney-shaped nuclei and a few profiles of demarcation membranes, as well as in the mature form with well-developed demarcation membranes. These results indicated the expression of 12-lipoxygenase at an early stage in the course of megakaryocytopoiesis.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Modulation of vascular natriuretic peptide receptor gene expression in hypertensive and obese hyperglycemic rats.
Receptors for natriuretic peptide (NP) consist of three subtypes: NP-A, NP-B, and NP-C. Recent studies in cultured aortic cells have suggested a phenotype-related switching of the vascular NP receptor from NP-A to NP-B. To ascertain the biological significance of the phenomenon in vivo, we developed a sensitive and reproducible ribonuclease protection assay and determined each receptor messenger RNA (mRNA) level in the vascular vessels of stroke-prone spontaneously hypertensive rats, deoxycorticosterone acetate-salt hypertensive rats, and genetically hyperglycemic. Wistar fatty rats and in cultured aortic smooth muscle cells. The aortic NP-A receptor mRNA level was significantly up-regulated in both types of hypertensive rats, whereas the NP-B receptor mRNA level did not show any significant change. Both NP-A and NP-B receptor mRNA levels were significantly up-regulated in Wistar fatty rats compared with the control values. There was no significant up-regulation of NP-A receptor mRNA in the inferior vena cava of the stroke-prone spontaneously hypertensive rats. Although the NP-A receptor was always the predominant subtype in rat aortic tissue, NP-B receptor was the predominant subtype in aortic smooth muscle cells in culture. These findings suggest that up-regulation of the NP-A receptor, but not the subtype switching, is the major modulation of receptor gene expression in both hypertensive and diabetic rats.
Animals↗
Magnetic resonance imaging of titanium anterior cervical spine plating systems.
Magnetic resonance imaging (MRI) of titanium anterior cervical plating systems and their effect on postoperative images were evaluated ex vivo and in vivo. The Synthes and Caspar plating systems were examined by 0.5- or 1.5-T MRI scanners. A phantom study of these implants showed that in spin-echo modes, the plates and screws were seen as areas of signal loss accompanying a marginal hyperintense band, which was more obvious in higher tesla magnetic fields. Distortion of the magnetic field was more prominent in T2-weighted images. In gradient echo mode, the plate and screws were seen as areas of signal loss larger than the size of the metal because of the magnetic susceptibility effect. Postoperative MRI produced images of the implants similar to those observed ex vivo. The Synthes plating system did not interfere with the evaluation of the spinal cord, and the Caspar screw (which penetrated the posterior cortex of the vertebral body) caused a small artifact to be present at the anterior aspect of the spinal cord. In addition to being able to provide fixation of the cervical spine, titanium anterior cervical plates allow superior MRI of the postoperative spine.
Artifacts↗
Spinous process-splitting laminoplasty with an extended foraminotomy for cervical myelopathy.
We present the surgical results of a laminoplasty with an extended foraminotomy for cervical myelopathy. We chose spinous process-splitting laminoplasty, because it gave us the opportunity to perform bilateral foraminotomies through the same exposure. An extended foraminotomy means that root decompression is performed as far laterally as possible, using the surgical microscope. We performed this method in 18 patients and experienced favorable clinical results. Neuroradiological evaluations revealed good decompression of the spinal cord postoperatively. Although the operation time needed was longer compared with the original method, the average blood loss was 430 ml and blood transfusion was necessary in five patients. This method can be considered when cervical myelopathy is treated by a posterior approach.
Cervical Vertebrae↗
Partial purification and characterization of an esterase acting on the anticancer pro-drugs, 7-ethylcamptothecin derivatives.
A hydrolytic enzyme which catalyzes hydrolysis of the ester-linkage of a series of 17-O-acyl derivatives of 7-ethylcamptothecin-21-(2-dimethylamino)ethylamide [acyl derivatives of 22E] was purified from rat liver and its properties were characterized. It hydrolyzed the ester-linkage of all 22E derivatives tested as well as p-nitrophenyl acetate at pH 8-9 but had no effect on 7-ethyl-10-[4-(piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11: irinotecan), unlike CPT-11 converting carboxylesterase, which was previously purified from rat serum [Tsuji T. et al., J. Pharmacobio-Dyn., 14, 341 (1991)]. The enzyme had no effect on either acetyl choline or butyrylcholine. It was inhibited by several organophosphorous compounds such as diisopropyl fluorophosphate (DFP), bis-(p-nitrophenyl)phosphate and paraoxon, but was insensitive to inhibitors specific for choline esterases. These results indicate that this liver esterase is clearly distinct from choline esterase and serum CPT-11 converting enzyme and is able to convert pro-drugs, O-acyl derivatives of 22E, to an antitumor agent.
Animals↗
Prolidase from Xanthomonas maltophilia: purification and characterization of the enzyme.
Prolidase (iminodipeptidase, EC 3.4.13.9) was purified from an extract of Xanthomonas maltophilia, by ammonium sulfate fractionation and sequential chromatographies on DEAE-Toyopearl, Toyopearl HW65C, FPLC-Hiload Superdex 200 pg, and FPLC-Hitrap Q columns, which an activity recovery of 2.3%. The enzyme was the most active at pH 7.5 with Leu-Pro as substrate. It was stable between pH 6.0 and 8.5 for 60 min at 37 degrees C and retained half of activity after 60 min at 37 degrees C. The isoelectric point of the enzyme was 3.7. Its molecular weight was estimated to be 100,000 by gel filtration on FPLC-Hiload Superdex 200 and 51,000 by SDS-PAGE, suggesting that it is a dimer. It hydrolyzed dipeptides only if proline is located at the carboxyl terminal position. The enzyme was inhibited by PCMB and o-phenanthroline, and was activated by Mn2+.
Chromatography, Ion Exchange↗