Effect of Topical Preparation of Mycophenolic Acid on Experimental Allergic Contact Dermatitis of Guinea-pigs Induced by Dinitrofluorobenzene

Abstract— The effects of a topical preparation of mycophenolic acid on the experimental allergic contact dermatitis induced by dinitrofluorobenzene was investigated. Visual assessment of skin reactions showed significant efficacy of a topical preparation of mycophenolic acid. This efficacy appeared from the early stage and endured up to 3 days. Morphological changes in the epidermis and dermis layers of animals treated with a mycophenolic acid cream were moderate compared with that in animals treated with vehicle only. In particular, hyperkeratosis was strongly suppressed. Since suppression of inflammatory cell infiltration was also observed, this efficacy might reach to the epidermis and dermis layer.     

Microheterogeneity of serum transferrin in the diagnosis of hepatocellular carcinoma

Heterogeneous reactivity of human serum transferrin (Tf) with lectins was analysed using patient sera to determine whether it can be used to distinguish patients with hepatocellular carcinoma (HCC) from those with liver cirrhosis (LC). Microheterogeneity of Tf was analysed by crossed immunoaffinity electrophoresis (CIAE) with concanavalin A (Con A) and Lens culinaris agglutinin (LCA). Sample sera from 58 patients with HCC, 43 patients with LC and 10 normal controls were used in this study and the results were evaluated statistically. The increments of Con A-non-reactive (C1) and -weakly reactive (C2) species of Tf were observed in HCC compared with those of LC and Norm. Significant increase in the combined percentage of Con A- C1 + C2 species was also revealed in HCC (35.5 ± 8.5%, mean ± s.d.) compared with those of LC (29.1 ± 6.8%; P < 0.001) and normal controls (17.1 ± 2.3%; P < 0.001). The elevation of LCA-reactive (L2) species of Tf was recognized in HCC (8.2 ± 3.8%) in comparison with those of LC (4.8 ± 3.1%; P<0.001) and normal controls (1.3 ± 1.7%; P < 0.001). The increment of C1+C2 species and/or L2 species of Tf was observed in 78% (sensitivity) of patients with HCC. The specificity, the positive predictive value and the overall accuracy were 81, 88 and 72%, respectively. Positive ratio of C1+C2 and/or L2 species was 77 and 70% in alpha-fetoprotein low and -high producing HCC patients, respectively. These results indicate that the microheterogeneity analysis of human serum Tf is useful for distinguishing patients with HCC from those with LC and normal controls.     

Effect of chronic ipsapirone treatment on the density of 5-HT1A receptors and 5-HT1A receptor mRNA in discrete regions of the rat brain

Abstract There is increasing evidence that the 5-hydroxytryptamine (HT)_1A partial agonist ipsapirone is an effective anxiolytic/antidepressant agent, although its mechanism of action is not clear. In this study, we investigated the effects of chronic ipsapirone treatment (5 or 10 mg/kg; twice daily, 3 weeks) on 5-HT_1A receptor density 8-hydroxy-2-(di-n-propyl amino) tetralin (80H-DPAT) binding and the level of its mRNA ( in situ hybridization) in various regions of the rat (male Wistar 250 g) brain. Receptor density was reduced in the frontal cortex, but did not change significantly in the hippocampus and dorsal raphe nucleus. The level of receptor mRNA was unchanged in each of these brain regions. The present results suggest that the clinical anxiolytic effects of ipsapirone may be mediated partly by postsynaptic action on serotonergic transmission in the frontal cortex, but not in the hippocampus or dorsal raphe nuclei.     

Intravenous Adenosine Triphosphate Disodium: Its Efficacy and Electrophysiologic Effects on Patients with Paroxysmal Supraventricular Tachycardias

We studied the electrophysiologic effects of intravenous adenosine triphosphate disodium (ATP-2Na) on 17 patients with paroxysmal supraventricular tachycardias (PSVTs). One patient had sinus node (SN) reentry, two had intraatrial (IA) reentry, 7 patients had AV nodal reentry and seven had atrioventricular reentrant tachycardias (AVRTs) with accessory pathways (APs). ATP-2Na was injected during ventricular pacing in patients with AV nodal reentry and AVRTs with APs. A bolus injection of ATP-2Na terminated all the PSVTs within 50 s except for one case of IA reentry (case 2). The sites of block at termination were the atrium in SN reentry and IA reentry, between A and H (AH) or between H and A (HA) in AV nodal reentry, and AH block in all the PSVTs with APs. The sites of action on the patients with AV nodal reentry were both the antegrade and retrograde pathways, while the modes of block were Mobitz type I and type II, respectively. ATP-2Na during ventricular pacing in patients with AV nodal reentry produced Mobitz type II ventriculoatrial block (VAB) in four of seven cases. ATP-2Na during ventricular pacing in patients with AVRTs with APs produced changes of atrial activation sequences in two patients, induction of PSVT in two patients, and Mobitz type II VA block in three patients. The former two phenomena suggested a retrograde AV nodal block and raised the possibility of a simple test for retrograde atrial fusion during ventricular pacing in patients with WPW syndrome. Chest discomfort of short duration was most commonly noted after ATP-2Na administration.     

Biological and Clinical Implication of Neuron-Specific Enolase and Creatine Kinase BB in Small Cell Lung Cancer

The specificity of neuron-specific enolase (NSE) and creatinekinase BB (CK-BB) for small cell lung cancer (SCLC) was determinedby biological and immunohistochemical procedures in lung cancertissues and cultured cell lines. Average values of extractableNSE and CK-BB of SCLC tissues were significantly higher thanthose of non-SCLC and normal lung tissues. A large amount ofNSE and CK-BB was demonstrated in SCLC cell lines. Immunohistochemical examination showed positive staining forNSE and CK-BB in most cases of SCLC and in a few cases of non-SCLC.From these data NSE and CK-BB should be considered to be highlyspecific for SCLC. In a clinical study serum values exceeding 10 ng/ml for NSEand 1.5 ng/ml for CK-BB were set as positive for the enzymes.Positive rates in SCLC were 71.4% for NSE and 65.3% for CK-BB,which were significantly higher than those in non-SCLC. Allpositive cases were in an advanced stage. Consecutive dailyNSE determinations during induction chemotherapy showed transientelevation immediately after the initiation of drug administration(tumor lysis syndrome), followed by a decline to the normalrange in responders. This phe nomenon seems to indicate tumorsensitivity to cytotoxic drugs. NSE positive non-SCLC was assensitive to cytotoxic drugs as SCLC. These findings indicatethat lung cancer with elevated serum NSE and CK-BB levels atdiagnosis should be strongly suspected of being SCLC in theadvanced stage.     

Small Cell Lung Carcinoma with Ectopic Adrenocorticotropic Hormone and Antidiuretic Hormone Syndromes: A Case Report

This report describes a 63-yr-old man with lung cancer accompanyinghypertension, hyperpigmentation, muscle weakness, psychosis,hypokalemia, hyperglycemia, hyponatremia, massive naturesisand lower serum osmolality than urine osmolality. Elevated levelsof plasma and urine corticosteroids and of plasma immunoreactiveadrenocorticotropic hormone (ACTH) were not altered by the administrationof large amounts of dexamethasone. Elevated plasma antidiuretichormone (ADH) values were also demonstrated. Postmortem examinationsrevealed small cell lung carcinoma with extensive metastasis,bilateral adrenocortical hyperplasia and Crooke's degenerationof the pituitary gland. Immunoradiological and immunohistochemicalstudies demonstrated the presence of immunoreactive ACTH, ADHand gastrin-releasing peptide in the tumor tissue. Beta-melanocyte-stimulatinghormone, calcitonin and carcinoembryonic antigen were also detectedby one of the methods. Hence, this is a rare case of lung cancerwith multiple hormone production and clinical and laboratoryevidence of both the ectopic ACTH and ADH syndromes. ^* Present address: Department of Internal Medicine, Keio UniversitySchool of Medicine, Tokyo, Japan     

INTRACELLULAR LOCALIZATION OF TYROSINASE INHIBITOR IN AMELANOTIC AND MELANOTIC MALIGNANT MELANOMA

Summary.— Intracellular distribution of the tyrosinase inhibitor in malignant melanoma cells has been investigated in order to elucidate the defect of melanization in the pigment cell cytoplasm and premelanosomes of amelanotic melanoma. We have found that the tyrosinase inhibitor has its highest activity in the cytoplasmic soluble fraction for both amelanotic and melanotic melanomata. However, inhibitor assay of melanoma subfractions reveals a distinct difference between the inhibitor activity of amelanotic and melanotic melanomata. Premelanosome-containing subfractions of amelanotic melanomata contain much higher inhibitor activity than those of melanotic malignant melanomata. A high concentration of inhibitor seen in subfraction 3 which contains most of the total succinoxidase activity is found to be contained in the premelanosomes of this subfraction.
It is suggested that the absence of melanization in the non-premelanosomal cytoplasm of pigment cells and in the premelanosomes of tyrosinase containing amelanotic melanomata is directly related to the concentration of tyrosinase inhibitor in these compartments of the cells.     

INCREASED IN VITRO RADIO-SENSITIVITY OF MALGNANT MELANOMA INDUCED BY THE IN VIVO ADMINISTRATION OF CHLORPROMAZINE

Summary.— In vitro x-ray irradiation with 3000 R of strips of Fortner's melanotic melanoma was found to have no effect on the rate of successful transplantation of these strips in hamsters. However, when the hamsters bearing; the melanomata from which the strips were obtained had been treated with 3·5 mg chlorpromazine before irradiation, the incidence of melanoma transplantability was reduced to 33%. Chlorpromazine-treated melanomata which did grow after irradiation grew at a greatly reduced rate. It is postulated that chlorpromazine may increase the radio-sensitivity of melanized cells by masking the free radical nature of melanin.