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With analysis methods using digital sweep integration of the absorbance function, linear current ramps can produce non-linear laser intensity and wavenumber functions from distributed feedback lasers. These non-linear functions produce offset and gain errors in mole fraction estimates on tunable diode laser gas analyzers. A method is described to synthesize polynomial current waveforms and laser intensity compensation functions to give linear wavenumber functions and to minimize the offset error. Quantitative and qualitative results are presented to evaluate reduction in mole fraction errors.

A fast response, open path tunable diode laser absorption spectroscopy H2O/CO2 gas analyzer suitable for eddy correlation concentration measurements in near surface turbulent environments is presented. The turbulent temperature characteristics, analysis theory, analysis methods, design structure and specifications of this dual laser analyzer are described. A fiber connected optical head with folded optical path is used to extend the resolution to ppb levels for H2O at 1.3964 microm and CO2 at 2.014 microm. The Fourier (discrete cosine) transform absorbance ratio analysis methods are outlined along with the modifications for temperature and pressure measurements in turbulent flows. Synthesis of the reference absorbance function using measured temperature, pressure and the Hitran parameters is extended with incorporation of the Hitran parameters n, gamma temperature exponent and E'', lower state energy. Additionally, the mole fraction equation developed for this Hitran model is presented and an absolute calibration technique is outlined along with methods of calibration retention. Simulation results on mole fraction estimations and errors are presented for synthetic temperature and laser noise processes and are used to verify the specifications.

Recent research has shown that a single undrugged prior experience of the elevated plus-maze produces significant behavioural changes upon 24-h retest in rats and mice. Typically, when reexposed to the maze, animals display an increased avoidance of the open arms and a corresponding preference for the enclosed sections of the apparatus. Using ethological analyses, the present series of experiments sought to further characterize this phenomenon in mice and to determine whether or not it involves cholinergic receptor mechanisms. Results confirmed that behaviour during Trial 2 is markedly different to that seen on initial exposure, and that such changes are independent of the duration of Trial 1 (2 vs. 5 min). Retest behavioural changes included reduced entry latencies, reduced open arm entries, less time on the open arms and centre platform, lower levels of exploratory head-dipping, and increased entries into and time spent in the closed arms. The importance to the retest phenomenon of the first few minutes of initial exposure was further suggested by min-by-min analyses of the behaviour of animals naive to the maze. Results showed that behaviour during the first min is characterized by high levels of risk assessment from the centre platform and relatively low, but equal, levels of open- and closed-arm exploration. From min 2 onwards, however, behaviour showed a marked change with increasing open arm/centre platform avoidance, increasing closed-arm preference, and decreasing levels of risk assessment and exploratory head-dipping. Thus, it would appear that this within-session aversive learning transfers between sessions to account for behavioural profiles on retest. Irrespective of the duration of Trial 1 (2 or 5 min), posttrial administration of the muscarinic antagonist, scopolamine (0.1-1.0 mg/kg), failed to significantly alter the behavioural changes seen between trials. Data are discussed in relation to the apparent sensitization of fear produced by plus-maze exposure, its possible relation to phobia acquisition, and the need for further research on underlying mechanisms.

Lens epithelial cells in culture can sometimes be induced to form spheroid aggregates termed lentoid bodies, composed of cells exhibiting various characteristics of the more highly differentiated lens fiber cells. However, lentoid bodies are often slow to form, and the ability to produce them declines with serial subculture. It was therefore of interest to establish and/or characterize lens epithelial cell lines capable of forming lentoid bodies. The differentiation state was assessed in lentoid bodies formed by each of two lens epithelial cell lines, the transformed alpha TN4 cell line from mouse and the nontransformed N/N1135A cell line from rabbit. Lentoid and monolayer cultures of each cell line were examined for transcripts of the lens-specific alpha A-crystallin ("alpha A"), gamma D-crystallin ("gamma D"; formerly gamma 1-crystallin) and MP26 genes. alpha TN4 lentoid bodies contained 2.5 times the alpha A RNA found in monolayer cells, but lacked detectable gamma D and MP26 RNA. None of the three markers were detected in either lentoid or monolayer N/N1135A cultures grown under the conditions described. Lentoid body formation alone, therefore, does not indicate the extent of differentiation occurring. At least some of the changes in cell adhesion occurring during lentoid body formation involve laminin-like and fibronectin-like interactions, and are reminiscent of those observed during embryonic lens formation. Finally, vascular endothelial growth factor mRNA was absent from the lens but present in alpha TN4 cells, suggesting a mechanism whereby the lens tumors of the founder mouse became vascularized.

Normal insulin secretagogues, including glucose, usually have little influence on insulin secretion from insulinomas. Therefore, insulinomas typically cause fasting hypoglycemia with relative hyperinsulinemia. This report describes a patient with hyperinsulinemia due to an islet cell adenoma with microadenomatosis, which, upon provocative in vivo testing, was found to be profoundly responsive to hypoglycemic and hyperglycemic stimuli. A 72 hr fast followed by brisk exercise resulted in a gradual reduction of serum glucose and insulin concentrations, but did not provoke symptomatic hypoglycemia. Oral glucose tolerance testing resulted in a prompt 10-fold increase in serum insulin accompanied by a mildly symptomatic and gradual fall in serum glucose to 30 mg/dl 90 minutes after glucose ingestion. An intravenous glucose challenge caused an acute increase in serum insulin to more than 1200 microU/ml with a resulting serum glucose of 11 mg/dl 25 minutes later, associated with loss of consciousness. Although a prolonged fast has proven to be the best diagnostic test for insulin secreting tumors, many other provocative tests that use normal insulin secretagogues have been somewhat useful in this regard. The patient in this report supports the concept that insulinomas vary widely in their response to a number of normal physiologic regulators of insulin secretion, including the serum glucose concentration. A variety of provocative tests may be needed to fully evaluate the rare patient in whom there is a strong clinical suspicion of insulinoma but who has a nondiagnostic prolonged fast.

Studies were conducted to explore the tissue- and cell-specific regulation of cellular retinoic acid-binding protein (CRABP) expression in the rat. Two studies were carried out. The first explored the regulation of CRABP mRNA levels in selected rat tissues by dietary retinoid status, and the relationship between CRABP mRNA and protein levels in different tissues. The second examined the cellular localization of CRABP expression in the testis. In order to conduct these experiments, a cDNA encoding CRABP was isolated and characterized. The DNA sequence of the coding region had 96% identity with that of the mouse CRABP cDNA and encodes a protein identical to mouse and bovine CRABP. CRABP mRNA and protein levels were quantified in five tissues from normal, retinoid-deficient, and retinol-repleted rats. Tissue CRABP and CRABP mRNA levels were highly correlated (P less than 0.01) indicating that inter-tissue variability of CRABP levels mainly results from regulation of CRABP mRNA levels. Neither CRABP protein nor mRNA levels were affected by retinol deficiency, in marked contrast with results previously demonstrated with cellular retinol-binding protein (CRBP) (J. Lipid Res. 1990. 31: 821-829). 35S-labeled CRABP cRNA probes were used to localize CRABP mRNA within the testis of adult rats by in situ hybridization. CRABP mRNA was localized selectively in the periphery of the seminiferous tubules, primarily in type A spermatogonia. The localization of CRABP mRNA differs from that of CRABP protein, which is known to be enriched in maturing and more mature germinal cells. This difference suggests that CRABP in germ cells may be highly stable, remaining in the maturing germ cells without degradation long after CRABP mRNA levels have declined to very low levels. The specific localization of CRABP mRNA and protein presumably reflects the biological roles of retinoic acid in the development and/or later function of germinal cells.

We examined the effects of elevated thyrotropin-releasing hormone (TRH) levels on the gonadotropin response to gonadotropin-releasing hormone (GnRH) in 16 healthy men. A TRH infusion, which was begun 15 minutes before and continued for 120 minutes after the bolus administration of GnRH, was compared with a saline infusion. During the TRH infusion the gonadotropin responses to acute GnRH stimulation were higher than in the saline control period but, although statistically significant, the differences were small in magnitude and were similar to the intraindividual coefficient of variation in gonadotropin responses determined under control conditions. They did not appear to be of clinical significance. TRH significantly lengthened the interval between GnRH administration and the appearance of peak gonadotropin levels. These results indicate that a brief TRH infusion, producing mild elevations of thyrotropin and prolactin, causes slight alterations predominantly in the timing of GnRH-stimulated gonadotropin secretion.

Although thyroidal uptake of gallium-67 has been described in several thyroid disorders, gallium-67 scanning is not commonly used in the evaluation of thyroid disease. Thyroidal gallium-67 uptake has been reported to occur frequently with subacute thyroiditis, anaplastic thyroid carcinoma, and thyroid lymphoma, and occasionally with Hashimoto's thyroiditis and follicular thyroid carcinoma. A patient is described with progressive systemic sclerosis who, while being scanned for possible active pulmonary involvement, was found incidentally to have abnormal gallium-67 uptake only in the thyroid gland. Fine needle aspiration cytology of the thyroid revealed Hashimoto's thyroiditis. Although Hashimoto's thyroiditis occurs with increased frequency in patients with progressive systemic sclerosis, thyroidal uptake of gallium-67 associated with progressive systemic sclerosis has not, to our knowledge, been previously described. Since aggressive thyroid malignancies frequently are imaged by gallium-67 scintigraphy, fine needle aspiration cytology of the thyroid often is essential in the evaluation of thyroidal gallium-67 uptake.

Two patients are presented who developed autonomous thyrotoxicosis following a diagnosis of primary hypothyroidism. In one of these patients, antibodies to the TSH receptor were typical of Graves' disease when measured as thyrotropin binding inhibitor immunoglobulins (TBII) and as human thyroid adenylate cyclase stimulating (HTACS) activity, while a needle biopsy of the thyroid gland was consistent with lymphocytic thyroiditis. Twenty-one other reported cases of this unusual sequence found in the literature are reviewed. This occurrence is more common than is generally appreciated.

Hypothyroidism results in decreased platelet aggregation and has unique effects on the development of atherosclerosis and angina pectoris. Because prostacyclin and thromboxane A2 profoundly influence platelet function and vascular tone and are thought to be important in the development of atherosclerosis and angina pectoris, we studied the effects of hypothyroidism in rats on the in vitro elaboration of prostacyclin passively by aortic tissue and of thromboxane A2 by thrombin-stimulated whole blood. Hypothyroidism induced by iodine 131 (given at age 7 weeks) persistently caused a mild decrease in platelet count (P less than 0.01) and 30% decrease in immunoreactive thromboxane B2 (the hydrolysis product of thromboxane A2) generation per platelet (P less than 0.01) compared with age-matched euthyroid rats. Between 20 and 23 weeks of age immunoreactive 6-ketoprostaglandin F1 alpha (the hydrolysis product of prostacyclin) generation decreased by 30% in euthyroid rats. In hypothyroid rats less than 23 weeks of age, 6-ketoprostaglandin F1 alpha production was the same as that of age-matched euthyroid rats. With further aging, 6-ketoprostaglandin F1 alpha production did not decrease as it did in euthyroid rats. Hypothyroid rats more than 20 weeks old had, therefore, significantly greater 6-ketoprostaglandin F1 alpha production than age-matched euthyroid rats (P less than 0.005). L-Thyroxine given daily for 28 days to 23-week-old hypothyroid rats caused a rapid increase in platelet count and a delayed normalization of the thromboxane synthetic abnormality. 6-Ketoprostaglandin F1 alpha production transiently increased in response to L-thyroxine, but decreased to the euthyroid level after 28 days of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The rate of transcription and translation of the leu-2 gene of Neurospora crassa was measured after induction by alpha-isopropylmalate. Little message of enzyme was found before inducer addition but transcription in the lower eukaryote was found well underway within five minutes after inducer addition, followed in a minute or two by the appearance of functional enzyme. The timing was close to the limit set by RNA synthesis and ribosome procession. As a consequence, it seems unlikely that traversal of the cell and/or nuclear membranes by the inducer and message involves intermediate synthetic reactions and that the leu-3 positive regulatory element is fully available for participation in the induction process before the inducer is added. A significant overshoot in message synthesis was found early in the induction process. This is discussed with respect to previously observed effects of the inducer on general RNA synthesis.