Case 42-1994: Mycoplasma pneumonia and transverse myelitis.
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Adult↗
Biomedical subjects
S Ohta
Publications and source records attributed to S Ohta.
Association between sialyl Lewis(a) expression and tumor progression in melanoma.
Twenty-three primary and 27 metastatic melanoma lesions and 17 pigmented nevi lesions were tested utilizing the immunoperoxidase reaction with anti-sialyl Lewis(a) (sLea) and anti-sLex mAbs.sLea was expressed in 9, 25, and 5 and sLex was expressed in 6, 11, and 2 of these lesions, respectively. Expression of sLea in melanocytic tumors is associated with tumor progression. Serum levels of sLea and sLex were analyzed by a sandwich assay using mAbs in 25 melanoma patients. Only 2 patients at stage 4 showed higher levels of sLea and sLex than did normal control subjects. Moreover, sLea and sLex were expressed in 1 and 2 of 5 human melanoma cell lines, respectively, and expression of sLex and sLex was not modulated by cytokines. These findings suggest that the expression of sLea in melanocytic tumors is correlated with disease progression.
Antigens, Tumor-Associated, Carbohydrate↗
Adrenomedullin stimulates two signal transduction pathways, cAMP accumulation and Ca2+ mobilization, in bovine aortic endothelial cells.
The biological action of adrenomedullin, a novel hypotensive peptide, on bovine aortic endothelial cells, was examined. The specific binding of adrenomedullin to these cells was observed, and adrenomedullin was found to induce intracellular cAMP accumulation in a dose-dependent manner. EC50 for the cAMP accumulation was about 100 times lower than the apparent IC50 for the binding assay. Adrenomedullin also induced increase of intracellular free Ca2+ in endothelial cells in a dose-dependent manner. The Ca2+ response to adrenomedullin was biphasic with an initial transient increase due to the release from thapsigargin-sensitive intracellular Ca2+ storage and a prolonged increase by influx through the ion channel on the plasma membrane. This intracellular free Ca2+ increase resulted from phospholipase C activation and inositol 1,4,5-trisphosphate formation, and seemed to cause nitric oxide synthase activation by monitoring intracellular cGMP accumulation. Both cAMP accumulation and Ca2+ increased responses to adrenomedullin were mediated by cholera toxin-sensitive G protein, but the two signal transduction pathways were independent. Thus, the results suggest that adrenomedullin elicits the hypotensive effect through at least two mechanisms, a direct action on vascular smooth muscle cells to increase intracellular cAMP and an action on endothelial cells to stimulate nitric oxide release, with both leading to vascular relaxation.
Adrenomedullin↗
Effects of the antiprotease ulinastatin on mortality and oxidant injury in scalded rats.
BACKGROUND: Proteolysis and oxidant injury are important mechanisms of injury in thermal burns. The glycoprotein ulinastatin has antiprotease and free radical-scavenging properties and therefore could be useful in the treatment of these injuries. OBJECTIVE: To determine the free radical-scavenging effects of ulinastatin on rats with thermal injury. DESIGN: An experimental study. MATERIALS AND INTERVENTIONS: Sixteen rats with a 70% surface area immersion scald were treated intravenously for 3 hours; immediately after injury, the rats were treated with ulinastatin, 100,000 U/kg, in lactated Ringer's injection. Sixteen control rats were also scalded but were given only lactated Ringer's injection. Sixteen additional sham control rats were immersed in 37 degrees C water and given ulinastatin. MEASUREMENTS: Levels of malondialdehyde, superoxide dismutase, lactate, and pyruvate in skin, along with the water content of the skin, were measured before injury and at intervals thereafter in six rats from each group. RESULTS: The mortality rate was 50% at 72 hours and 90% at 14 days in scalded control rats, but it was 0% at 72 hours and 20% at 14 days in the treated rats (P < .01). Levels of malondialdehyde and superoxide dismutase in the skin and the lactate-pyruvate ratio all remained at the same values (as those before scalding) in treated rats but rose in the skin of scalded control rats (P < .05 for each). The water content of scalded skin gradually increased after injury in all groups, but at 3 hours, the scalded skin in treated rats contained less water than that in scalded control rats (P < .05). CONCLUSION: Ulinastatin may have a therapeutic role in treating thermal injuries.
Animals↗
Germ-line transcription of the T cell receptor delta gene in mouse hematopoietic cell lines.
T cell receptor (TCR) genes are initially activated in hematopoietic stem cells that have been committed to the T cell lineage during ontogeny. We have established cell lines derived from hematopoietic organs which express truncated TCR delta mRNA (1.3 kbp). In this study, cDNA clones of this mRNA were analyzed to characterize TCR delta gene activation in early T cell development. Transcription started from an intron between D delta 2 and J delta 1, 72 bp upstream from J delta 1, and continued to J delta 1 and C delta exons, which were directly spliced to J delta 1. Thus, the truncated mRNA expressed by the cell lines was determined to be a germ-line transcript. The promoter activity of the DNA fragment between D delta 2 and J delta was assessed by its ability to drive the transcription of a reporter gene linked to it in the cell line expressing the TCR delta germ-line transcript. TCR delta germ-line transcription was found not only in these cell lines but also in fetal liver and thymus cells. These findings indicate that the TCR delta germ-line transcription is a naturally occurring event in developing T cells. The significance of germ-line transcription of TCR delta genes is unknown, but it may be an event that follows T-lineage commitment or, at least, may be closely associated with this commitment.
Animals↗
Cold stability of pyruvate, orthophosphate dikinase of Flaveria brownii.
The nucleotide sequences of the complementary DNA of pyruvate, Pi dikinase (PPDK) from Flaveria bidentis, a C4 plant which possesses a cold-sensitive form of PPDK, and Flaveria brownii, a 'C4-like' plant which possesses a cold-tolerant form of PPDK, were determined. PPDK was isolated from the leaves of both Flaveria species and purified and the N-terminal amino acid sequences characterised. Together with a maize PPDK cDNA, cDNA inserts which code for the mature form of PPDK of F. bidentis and of F. brownii were expressed in bacteria and the cold sensitivity of the expressed PPDK studied. The cold sensitivity of the PPDK expressed in bacteria mimics the cold sensitivity of PPDK found in vivo in all three plant species. This study indicates that the cold sensitivity of plant PPDK is controlled by the primary structure of the enzyme.
Amino Acid Sequence↗
Spontaneous resolution of symptoms in an infant with a congenital dural caroticocavernous fistula.
We report a 5-week-old boy with a congenital dural caroticocavernous fistula (CCF). He had gradually progressive proptosis, dilated conjunctival veins, chemosis, abducens nerve palsy and an objective bruit. Angiography of the right common carotid artery revealed fistulous communication in the cavernous sinus (CS) region. The CS was fed by the middle meningeal artery and drained through the superior ophthalmic vein and the superior petrosal vein. The child's symptoms and signs disappeared within a few weeks and did not recur over 11 months. At that time, however, angiography still showed a small communication between the right external carotid artery and the CS.
Arteriovenous Fistula↗
Possible mechanism to induce protein kinase C-dependent arterial smooth muscle contraction after subarachnoid haemorrhage.
A possible mechanism for the induction of protein kinase C (PKC)-dependent vascular contraction independent to the increase of intracellular Ca++ was investigated in the pathogenesis of cerebral vasospasm in the double subarachnoid haemorrhage (SAH) model. The level of 1,2-diacylglycerol (DAG), which is an intrinsic PKC activator, significantly increased from days 4 to 7 in the basilar artery after the initial SAH, and the continuous administration of 1,2-bis(nicotinamido)-propane (AVS), a novel free radical scavenger, not only lowered the concentration of lipid peroxides in the CSF but also successfully suppressed the basilar arterial wall in the same model. It was suggested that lipid peroxides generated in the subarachnoid clot affect the DAG content of the cerebral artery. Analysis of hydroxy-eicosatetraenoic acids (HETEs) with high performance liquid chromatography (HPLC) revealed the production of relatively large amount of 12-HETE in the subarachnoid clot. To examine the potential effect of exogenous 12-HETE on the DAG content of the cerebral artery, the basilar artery was incubated with 12-HETE in vitro. 12-HETE induced a concentration-dependent slow increase in DAG content in the arterial wall after 6 hours of incubation. Under conditions in which DAG formation was facilitated by the Ca(++)-ionophore, DAG accumulation in the basilar artery was enhanced in the presence of 12-HETE. It was suggested that 12-HETE generated in the subarachnoid clot, induced DAG accumulation in the arterial wall by inhibition of DAG metabolism, resulting in the induction of prolonged PKC-dependent smooth muscle contraction in the pathogenesis of cerebral vasospasm.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Successful management of infantile hepatic hilar hemangioendothelioma with obstructive jaundice and consumption coagulopathy.
A 4-month-old boy with benign hemangioma of the porta hepatis is described. Obstructive jaundice and consumption coagulopathy developed, which were treated by percutaneous transhepatic drainage (PTHD), without resection of the tumor or bypass surgery. Because of tumor regression, the patient has remained free of symptoms even after the PTHD tube was removed. Because juvenile hemangioma is a benign tumor and occasional spontaneous regression is known to occur (as in our case and other reports), it is suggested that complete resection or bypass surgery is not necessary for juvenile hemangioendothelioma, even with obstructive jaundice, if bile drainage is adequately maintained.
Cholestasis↗
Opioid receptor interaction and adenylyl cyclase inhibition of dihydroetorphine: direct comparison with etorphine.
To find out the reason of weak addiction property of dihydroetorphine, we compared the affinities of dihydroetorphine to the type selective opioid receptor and inhibition effect on the adenylyl cyclase activity with those of etorphine. Dihydroetorphine and etorphine have almost the same binding affinities to all types (mu, delta, and kappa) of opioid receptors and antagonist binding sites, and have similar inhibition activities to forskolin stimulated adenylyl cyclase. However, dihydroetorphine showed significantly smaller value of DTNB-index compared with that of etorphine. This differentiation may explain partly the high analgesic with low dependence properties of dihydroetorphine.
Adenylyl Cyclase Inhibitors↗
Comparative studies on bioaccumulation of PCDDs and PCDFs in C57BL/6 and DBA/2 mice treated with a mixture by oral administration.
To determine the cause of the extremely high accumulative potency of OCDD in human tissues, EROD activity and accumulation of 2,3,7,8-chlorine substituted PCDDs and PCDFs in liver of C57BL/6 and DBA/2 mice administered these chemicals orally were measured during a period of 28 days. Consequently, in both C57BL/6 mice with high EROD induction and DBA/2 mice with low EROD induction, there was no high accumulation of OCDD similar to that observed in human tissues. In addition, the C57BL/6 mice accumulated larger amounts of these chemicals in their liver than did the DBA /2 mice.
Administration, Oral↗
Pollution by PCDDS and PCDFS in sediment from freshwater fish culture ponds near incineration sites for metal reclamation in Wan-Li, Taiwan, Republic of China.
Sediment samples from nine culture ponds for freshwater fish at and near waste incineration sites for metal reclamation in Wan-Li, southern Taiwan, Republic of China were analyzed for PCDDs and PCDFs by HRGC-HRMS. Four of nine samples were heavily polluted by PCDDs and PCDFs, indicating the latter to be dominant. The total TEQ concentrations of PCDDs and PCDFs in the four samples were in the range of 257 to 12200 pg/g dry weight. In addition, the levels corresponded to those of surface soil samples from the same waste combustion areas.
Animals↗
Tumor-associated glycoantigen, sialyl Lewis(a) as a target for bispecific antibody-directed adoptive tumor immunotherapy.
The KM231 mAb recognizing sialyl Lewis(a) (sLe(a)) epitope of glycoprotein or glycolipid expressed on various human cancers was used to prepare bispecific antibody (BSAb) containing anti-CD3 x anti-sLe(a) mAb. The effect of anti-CD3 x anti-sLe(a) BSAb on the induction of cytotoxicity by activated T cells was investigated. The activated CD3+ T cells expressing CD8 or CD4 were induced from human peripheral blood mononuclear cells by culture with recombinant IL-2 plus immobilized anti-CD3 mAb. The activated CD8+ and CD4+ T cells showed marginal cytotoxicity against tumor cells by themselves. However, addition of anti-CD3 x anti-sLe(a) BSAb resulted in a great augmentation of their cytotoxicity against gastrointestinal tumor cells. The BSAb also triggered IL-2 production of CD4+ helper/killer T cells during lysis of tumor cells. Moreover, the BSAb was demonstrated to have a potent in vivo antitumor activity against human colon cancer implanted in nude mice by combination with CD4+ helper/killer cells. These results demonstrated that sLe(a) antigen might be a good target molecule for BSAb-directed adoptive tumor immunotherapy.
Animals↗
Development of near-field optic/atomic force microscope for biological materials in aqueous solutions.
This paper reports improvements of optical fiber cantilevers and the scanning near-field optical microscopy imaging of biological materials in liquid. In our scanning near-field optical/atomic-force microscope (SNOAM), the scanning of an optical fiber cantilever over the specimen was controlled by dynamic mode AFM to reduce damage to the probe and soft specimens. The typical resonant frequency of the optical fiber cantilever was 19.5 kHz, while it was 23.0 kHz in air. The Q-factor of the cantilever depended on the vibration amplitude and was typically 260-600 in air and 40-240 in water. The relationship between the vibration amplitude and the average sample-probe separation indicated that the cantilever worked in the non-contact mode in water, while it worked in the cyclic-contact mode in air. Cultured cells in aqueous solutions were visualized by the SNOAM, indicating that the SNOAM is suitable to observe soft specimens.
Animals↗
Somatic cell mutation frequency at the HPRT, T-cell antigen receptor and glycophorin A loci in Cockayne syndrome.
Skin fibroblasts of patients with Cockayne syndrome (CS) are hypersensitive to the lethal or mutagenic effect of ultraviolet light, which may cause genetic instability. Up to now, however, no systematic study of in vivo somatic cell mutation in CS cells has been reported. This article describes our investigation of the mutation frequencies (Mfs) at three different loci, i.e. hypoxanthine-guanine phosphoribosyl transferase (HPRT), T-cell antigen receptor (TCR) and glycophorin A (GPA), in six patients with CS. Mfs at the HPRT and TCR loci were found to be within the normal range as determined in age-matched controls. In the GPA locus of two patients, there was a slight increase, but it was much smaller than that reported in other DNA repair deficient syndromes. The frequency of spontaneous HPRT mutation in Epstein-Barr virus transformed B-lymphoblastoid cells derived from CS patients was similar to that in cells from normal children. The molecular characterization of the representative HPRT mutant T cell clones from CS patients did not show any structural alterations. These results may explain, at least in part, why CS is not associated with predisposition to cancer.
Adolescent↗
Phase II study of infusional cisplatin in combination with etoposide in the treatment of small cell lung cancer.
The efficacy of a 5 day continuous infusion of cisplatin, 25 mg/m2/day, in combination with a bolus infusion of etoposide, 100 mg/m2/day over 2 h for 3 days (PiE therapy), was evaluated in a phase II study of previously untreated patients with small cell lung cancer (SCLC). There were 39 evaluable patients, of whom 17 had limited disease (LD) and 22 extensive disease (ED). The overall response rate was 92% (LD, 100%; ED, 86%). The complete response rate was 21% (LD, 41%; ED, 5%). The median survival time was 45.6 weeks (LD, 123.2 weeks; ED, 28.8 weeks). The major side-effects were grade 3 or 4 leucopenia (55%), neutropenia (88%) and thrombocytopenia (20%). There were no episodes of bleeding, severe infection or treatment-related deaths. PiE therapy was associated with significant myelosuppression, but was effective, with an especially encouraging response rate and survival for LD patients.
Adult↗
A computer program for the analysis of chromatograms used in pharmacokinetic studies.
An analog/digital (A/D) converter and software written in BASIC language have been developed for the analysis of chromatographic data which are needed for pharmacokinetic (PK) studies in humans and in experimental animals such as dogs and rats. Using an A/D converter, widely sold personal computers produced by NEC or EPSON are applicable to both high-performance liquid-chromatography (HPLC) data analysis and PK analysis. When chromatographic data is taken up by the computer and treated as a variable, a maximum of 12,000 data points are saved by the computer. As 10 digital data points are taken up by the computer per second through the A/D converter, the maximum run time of a chromatogram is 20 min. For the purpose of HPLC analysis, however, five digital data points per second are usually enough for routine analysis. In this software, the program is written to take and save five digital data points/s. Therefore, the maximum run time of this software increased to 40 min per chromatogram. All the digital data through the A/D converter are saved into the data file on a floppy disk or hard disk. For the chromatogram analysis, both automatic peak identification and manual peak identification, which must be selected with the use of the mouse driver, are available. All the data, peak area, peak height, etc. are also saved into the data file. After a calibration curve is produced, following the input of peak analysis data of known spiked samples, the drug concentration for each sample is estimated. These concentration-time data are also saved into the data file.(ABSTRACT TRUNCATED AT 250 WORDS)
Analog-Digital Conversion↗
1-Benzyl-1,2,3,4-tetrahydroisoquinoline as a parkinsonism-inducing agent: a novel endogenous amine in mouse brain and parkinsonian CSF.
1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) was detected as a novel endogenous amine in mouse brain and parkinsonian CSF by using the gas chromatography-selected ion-monitoring method. The level of 1BnTIQ was very high in CSF of some parkinsonian patients compared with that of controls with other neurological diseases, the mean value being three times higher (parkinsonians: 1.17 +/- 0.35 ng/ml of CSF, n = 18; vs. controls: 0.40 +/- 0.10 ng/ml of CSF, n = 11; mean +/- SEM, not significantly different). The pole test, a toxicological examination to evaluate behavior abnormalities related to Parkinson's disease, was used to examine the pharmacological effect of 1BnTIQ in mice. Repeated administration of 1BnTIQ induced behavior abnormalities, which pretreatment with 1-methyl-1,2,3,4-tetrahydroisoquinoline could prevent. We suggest that 1BnTIQ may be related to the idiopathic Parkinson's disease.
Animals↗