The human calcitonin gene generates 2 distinct mature mRNAs by alternative RNA processing, encoding calcitonin (CT) in thyroid C-cells or a neuropeptide (CGRP) in the brain. We evaluated quantitatively by in situ hybridization the expression of the CT gene in tissue section of 5 MTCs (2 sporadic and 3 familial forms). The primary tumor of one MTC was compared to a brain metastasis. In situ hybridization was carried out with tritiated cDNA probes coding for CT and CGRP mRNA. After autoradiography the number of silver grains was counted in 400 cells by computerized analysis of digitized images and expressed as the labelling level (L.L. = grain area/cell area per day of autoradiographic exposure). This was used to calculate the relative abundance per cell of the specific messengers studied, which depends on the autoradiographic efficiency and the specific activity of the probe used. The CT mRNA content was 3.25-6.55 10(-10) micrograms equivalents in the 3 familial forms of MTC and 4.95-9.25 10(-10) micrograms equivalents for the 2 sporadic forms. The levels of CT mRNA in the brain metastasis and in the primary tumor were identical (4.10 10(-10) micrograms equivalents). CGRP mRNA expression was weaker in the sporadic and in the familial thyroid tumors (0.60-1.65 10(-10) micrograms equivalents). The content of mRNA CGRP in the brain metastasis (0.60 10(-10) micrograms equivalents) was lower than that in the primary tumor (1.05 10(-10) micrograms equivalents).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Is carbamazepine associated with NAG elevations suggestive of renal disease?

Elevations of urinary N-acetyl-beta-glucosaminidase (NAG) were found in previous studies of epileptic patients using carbamazepine. Since NAG can be a sensitive indicator of urinary tract problems, it was postulated that carbamazepine could be causing urinary tract damage. To explore this issue further, 27 mood disorder patients who were taking carbamazepine were compared to 171 mood disorder patients who were not using carbamazepine. There were no significant differences in NAG levels between the two groups. A hypothesis is presented which states that the elevated NAG levels found in some seizure patients could be associated with abnormalities of serotonin metabolism.

Acetylglucosaminidase↗

PubMedDate not supplied

Modulation of cytokeratin and actin gene expression and fibrillar organization in cultured rat hepatocytes.

Intermediate filaments of rat hepatocytes are composed of cytokeratins 8 and 18 (CK8 and CK18, respectively). Recent work from our laboratory has indicated a close relationship between the synthesis of these cytokeratins, their organization into intermediate filaments, and the promotion of growth and differentiation of cultured rat hepatocytes by insulin, epidermal growth factor, and dexamethasone. In the present study, we examined the mRNA expression, level of protein synthesis, and fibrillar distribution of cytokeratins 8 and 18 and actin in hepatocytes, isolated from normal and dexamethasone-injected rats and cultured as monolayers or spheroids in the presence of insulin, or from normal rat hepatocytes, cultured as monolayers in the presence of dexamethasone, insulin, and dimethyl sulfoxide. The CK8 mRNA level was lower in hepatocytes isolated from noninjected rats and cultured as either monolayers or spheroids, than in those from dexamethasone-injected rats. However, the CK18 mRNA level varied in a manner that was different from that of CK8 mRNA, showing that the modes of expression of the two genes were independent. The various changes in hepatocyte culture conditions led to variations in albumin mRNA levels that largely followed those observed in CK8 mRNA levels. In the case of actin, the amount of mRNAs varied from relatively high levels in hepatocyte monolayers to extremely low levels in hepatocyte spheroids, even though in both cases the cells were isolated from dexamethasone-injected rats. These changes in mRNA levels did not necessarily correlate with changes in the synthesis of cytokeratins 8 and 18, and actin. Changes in culture conditions induced a major reorganization in the distribution of cytokeratin intermediate filaments and actin filament between the region near the surface membrane and the cytoplasm. The most divergent patterns in cytokeratin intermediate filaments and actin filament distributions were observed between hepatocytes cultured as spheroidal aggregates and as monolayers in the presence of dimethyl sulfoxide. The former condition resulted in patterns of cytokeratin and actin gene expression and fibrillar organization that best matched those in situ. In the latter condition, inappropriate patterns were obtained, in spite of the fact that dimethyl sulfoxide treated hepatocytes are known to exhibit survival and functional activities equivalent to that of hepatocyte spheroids. These results demonstrate for the first time that the survival and functional activity (i.e., albumin production) of rat hepatocytes in vitro is not necessarily correlated with a particular pattern of cytokeratin and actin gene expression and fibrillar arrangement.

Actin Cytoskeleton↗

PubMedDate not supplied

[Recommendations for the standardization of growth hormone assays].

The diagnosis of growth hormone (GH) deficiency is based on the GH biological response to pharmacological stimulation tests. The cut-off value defining normality is the same whatever the GH assay used. In a group of the French Society for Clinical Biology (SFBC), we have evaluated whether differences between the GH concentrations obtained with the 9 commercial GH assays available in France exist or not. The study samples consisted of 72 serum pools and serial dilutions of the recombinant GH 22 kDa international standard, IS 98/574. These dilutions were performed by using 3 different diluents: the specific diluent provided by the manufacturers and thus different from one assay to another, serum without GH and heparin plasma without GH. Despite being calibrated against the same international standard, the different assays proposed variable conversion factors between microg and mIU, and we decided to express the results in mIU. The GH concentrations obtained for the 72 serum pools with the 9 assays were highly correlated, but absolute concentrations were significantly different from one assay to another. In particular, the ratio between the concentrations measured with both assays giving the lowest and highest concentration in the same sample respectively was about 50%. In the recovery test executed by adding the international standard, the slope of the regression curve describing the relationship between expected and measured concentrations was different of 1 in all but one assay. Furthermore, for a given assay and a given expected concentration, the measured values were sometimes different by up to 30% depending on the diluent used. These results led us to advise the manufacturers to calibrate their assays against the recombinant GH international standard, IS 98/574, to take into account the matrix effect detected in our study and to use the official conversion factor of 3 mIU/microg. Waiting for this new calibration, it is recommended that the results should be expressed in mIU/L and that serum samples should be used for the measurement of GH instead of plasma samples.

Blood Chemical Analysis↗

PubMedDate not supplied

[Epidemic of pulmonary histoplasmosis after visiting a cave in New Caledonia].

We report an epidemic of acute pulmonary histoplasmosis which occurred in February 1994 among a group of 24 persons after they had once or twice visited a cave in New Caledonia. This study describes the physical and laboratory findings, which lead to the diagnosis of histoplasmosis. Each test was evaluated. All members of the group had a physical examination, early and late serological tests, pulmonary X-rays (including CT) and some had mycological examination of bronchoalveolar washes. Mycological investigations were made on samples collected from the cave. Histoplasmic skin testing was not possible. We defined a case as a person who visited the cave in January 1994, had evocative radiological features and at least four symptoms among the following: weakness, fever, headache, arthralgia, thoracic pains, dyspnea, cough and nausea. Of the 24 exposed persons, 7 cases were considered as severe, 8 cases as moderate, and 6 cases as mild, for a total of 21 cases and an attack rate of 87.5%. There was no progression towards disseminated histoplasmosis and no recorded death. The incubation period lasted from 5 to 17 days. The symptoms were divided into three groups. In the first group, the symptoms of fever, headache and arthralgia were common and nonspecific. In the second group, the symptoms of chest pain, cough, and dyspnea which often occurred later, were less common and more specific. In the third group, the symptoms of vomiting, diarrhea and dizziness were less common. The chest X-ray showed abnormalities in 100% of the cases, and in 11 of the 21 cases the characteristic finding was a miliary.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗