Structure and expression of Xenopus karyopherin-beta3: definition of a novel synexpression group related to ribosome biogenesis.

Karyopherin-beta3 is a nuclear transport receptor that appears to be involved in nuclear import of ribosomal proteins. Here we report on sequence and expression of karyopherin-beta3 in Xenopus. The differential distribution of karyopherin-beta3 mRNA during Xenopus embryogenesis is similar to that of several other protein import factors and of ribosomal proteins. These genes thus define a novel synexpression group in the context of ribosome biogenesis.

Characterization of a subfamily of related winged helix genes, XFD-12/12'/12" (XFLIP), during Xenopus embryogenesis.

The fork head domain family of genes defines a growing group of proteins that serve important regulatory functions in pattern-forming events of both invertebrates and vertebrates. Here we add three closely related, novel members to this family in Xenopus laevis, termed XFD-12, XFD-12' and XFD-12". All three genes reveal indistinguishable expression patterns during Xenopus embryogenesis. During gastrulation, XFD-12 type transcripts are detected exclusively in the superficial layer of cells within the Spemann organizer territory. In the open neural plate, XFD-12 type expression defines a row of cells located along the dorsal midline and destined to become the floor plate of the neural tube. After closure of the neural tube, XFD-12 type encoding mRNAs are only detected in the tailtip and a small area located at the midbrain/hindbrain boundary. Within the Spemann organizer and in the floor plate area, expression of XFD-12 type genes is only partially overlapping with XFD-1 expression.

Thyroid hormone economy in response to extreme cold exposure in healthy factory workers.

The effects of cold exposure on serum total T4 (TT4), total T3 (TT3), free T4 (FT4), free T3 (FT3), rT3, TSH, T4-binding globulin (TBG), and T3 resin uptake were investigated in 82 euthyroid factory workers. Twenty-five workers (group 1) were exposed intermittently (approximately 3.5 h daily) to extreme cold (-40 to -20 C) during the 8-h work shift, and 47 (group 2) were exposed to moderate cold (-10 to 8 C) for the entire 8 h. Ten individuals working at room temperature for the same period also were studied. After cold exposure, serum TT4 decreased in group 1 and did not change in group 2, whereas FT4 did not change in group 1 and increased in group 2. After exposure, serum TT3 and rT3 decreased significantly in both groups, while FT3 did not change in either. The basal serum TT4 levels in groups 1 and 2 were significantly lower than those in the control group, whereas those of FT4 and FT3 were higher. Thus, cold exposure had opposite effects on total thyroid hormones and their free fractions, consistent with a cold-induced decrease in thyroid hormone-binding capacity. A postexposure decrease in serum TBG was found in women in group 2, but not in men in either group 2 or group 1, suggesting that factors other than decreased TBG are also involved. The results suggest the possibilities that 1) decreased thyroid hormone-binding capacity is an adaptive response to cold exposure, and/or 2) increased free thyroid hormone levels in response to cold exposure result in a new higher equilibrium between extracellular and intracellular FT4 and FT3.

Treatment of reactive hypoglycemia with buformin.

The therapeutic effect of short-term buformin (l-butylbiguanide) treatment was investigated in 12 patients with reactive hypoglycemia. Eleven of them were classified as having idiopathic reactive hypoglycemia, nine obese and two nonobese. None of these patients had a degree of hyperglycemia during glucose tolerance tests which would indicate diabetes mellitus. In one patient reactive hypoglycemia was related to chemical diabetes. The diagnosis of reactive hypoglycemia was established on the basis of patient's hypoglycemic reaction and low blood glucose levels during 6-hour oral glucose tolerance tests. The patient's received 200 mg of buformin daily for 7 days and its therapeutic effectiveness was assessed by repeat testing. Buformin treatment resulted in significant increase of blood glucose values between 180 and 360 min after oral glucose challenge and in considerable improvement of hypoglycemia in nine obese patients with idiopathic reactive hypoglycemia and in the patient with chemical diabetes. Buformin also significantly reduced maximal insulin response and incremental insulin areas. In two nonobese patients hypoglycemic reaction was deteriorated after buformin therapy.

Relative increase of serum reverse T3 in patients with hypothyroidism.

In 17 hypothyroid patients serum T3: rT3 ratio was 7.5 /+- 1.1 which was significantly lower than in control subjects (12.2 /+- 0.6; p less than 0.001). The data suggest that in hypothyroidism the organism might shift conversion of T4 from biologically active T3 to biologically inactive rT3 which may not be a defense mechanism of the body, as it was found in chronic systemic illness.

[Children's health and their rights threatened by violence]. / A saúde e o direito da criança ameaçados pela violência.

The purpose of this study is to analyze the follow-up of police reports concerning domestic violence against children aged 0-5, from 1990 to 1995, held in the city of Rio de Janeiro. Based on a descriptive study, initially, on a database, the accusations in general were characterized. Soon after, 18 police stations were visited to analyze the follow-up of the police reports. Out of 105 occurrences, only 25 were regarded as investigatory cases and just 01 was going to be analyzed in court. In sum, violence against child reflects cultural subjects.

Benefit of combined triiodothyronine (LT(3)) and thyroxine (LT(4)) treatment in athyreotic patients unresponsive to LT(4) alone.

Despite some reports, the usefulness of levothyroxine (LT(4)) and levotriiodothyronine (LT(3)) combination therapy in hypothyroidism remains controversial. The objective of this paper is to study a benefit of additional LT(3) in athyreotic patients who failed to normalize TSH on LT(4) alone even with hyperthyroid serum T(4) values. In a survey of 200 athyreotic patients treated between 2006 and 2009, about 7% failed to normalize serum TSH levels following treatment with LT(4), though serum T(4) values in the hyperthyroid range were achieved. These patients (characterized by serum T(4)≥160 nmol/L and TSH≥5.0 mIU/L), were additionally treated with 10 µg b. i. d LT(3). LT(3) and LT(4) combination therapy resulted in decreased serum TSH levels into the normal range (12.8 vs. 1.22 mIU/L; p<0.01) and reduced LT(4) dose (153.3 vs. 117.5 µg; p<0.01) required for normalization of serum T(4) values (170.6 vs. 123.3 nmol/L; p<0.01). Serum T(3) values were higher (1.3 vs. 2.26 nmol/L; p<0.01) than those during monotherapy with LT(4). Our results indicate a subpopulation of athyreotic patients that could significantly benefit from combined LT(4) + LT(3) therapy in restoring normal TSH and thyroid hormone patterns. Further research should be undertaken to provide a genetic basis for these findings.

Increased thyroidal T4 to T3 conversion in autonomously functioning thyroid adenoma: from euthyroidism to thyrotoxicosis.

AIM: The aim was to investigate whether the intrathyroid conversion of T4 to T3 in autonomously functioning thyroid adenoma (AFTA) tissue could influence serum T3 levels and suppression of TSH, especially in patients with borderline thyroid function. PATIENTS AND METHODS: In ten patients with AFTA, thyroidal conversion of T4 to T3 was investigated in nodular and paranodular, TSH-suppressed tissue. All patients had normal serum T4 and suppressed TSH. Serum T3 was normal in six, and borderline or slightly increased in four. AFTA and paranodular tissues were surgically removed and frozen at -70°C, then homogenized in a glass homogenizer, centrifuged at 100,000×g, and particulate fraction collected as a pellet. Analysis mixture consisted of thyroid enzyme suspension in 50 µmol/L TRIS buffer with 5 µmol DTT and 200 µL 1.3 µmol T4. Incubation was performed at 37°C and the generation of T3 measured after 5, 10, 20 and 40 minutes respectively. RESULTS: T3 production (pmol/mg protein) was significantly higher in AFTA than in paranodular tissues (8.8 1.2/Mean ± SE/vs. 1.8 ± 0.2; p<0.01), and excessively high (9.8, 14.1, 14.2 and 15.0) in four patients with borderline or slightly supranormal serum T3. A significant correlation was found between serum T3 concentrations and T3 generation (T4 conversion) in AFTA tissues. CONCLUSION: Results suggest that increased thyroidal T4 to T3 conversion in AFTA tissue could be involved in an increased delivery of T3, increased serum T3 and suppressed serum TSH, particularly in patients with the disease evolving from euthyroid to an early hyperthyroid phase.

Effect of fasting on posthyperglycemic glucose homeostasis in obesity--experimental model for reactive hypoglycemia.

The relationship between altered glucose-insulin interaction in the hyperglycemic period of oral glucose tolerance test (oGTT) and impaired posthyperglycemic glucose homeostasis was studied in 9 obese females. They underwent 6-hour oGTT following 72-96 hour total fast, and the results of blood glucose, insulin, growth hormone, cortisol, glucagon and free fatty acids were compared to those of the control test. Blood glucose values in the hyperglycemic period of oGTT were higher during the post-fasting than in the control study. Posthyperglycemic glucose levels following fast dropped below the control values and four patients showed subjective symptoms of reactive hypoglycemia. Mean maximum blood glucose irrespective of time was significantly higher, mean glucose nadir lower after fast than in the control experiment (138.4 +/- 7.1 mg/dl vs. 112.4 +/- 5.2 and 47.3 +/- 1.4 vs. 61.3 +/- 3.0, respectively). Insulin response following fast was significantly reduced in 0-2 h period with delayed maximum value obtained at 123.3 +/- 14.5 min vs. 60.0 +/- 10.0 min in the basal experiment. Post-fasting counter-regulatory cortisol response was higher when compared to control, but there was no difference in growth hormone and glucagon secretion. Basal and post-glucose values of free fatty acids were significantly higher after fast than in the control study. The data suggest that fasting-induced impairment of glucose-insulin interaction in the hyperglycemic period of oGTT decreases the ability of obese subjects to maintain posthyperglycemic glucose homeostasis and provokes reactive hypoglycemia in some of them. Examination of glucose metabolism in fasted subjects is a convenient experimental model for the investigation of reactive hypoglycemia.

Secretion of growth hormone and cortisol in obese subjects with asymptomatic reactive hypoglycemia.

Secretion of growth hormone and cortisol during 6-hour glucose tolerance test was investigated in obese subjects with asymptomatic reactive hypoglycemia (n = 27), obese controls (n = 22) and nonobese individuals (n = 18). Asymptomatic reactive hypoglycemia was defined as the presence of blood glucose value(s) of 40 mg/dl and below in the posthyperglycemic period of the test with no related symptoms. Growth hormone and cortisol levels following glucose nadir were significantly higher in obese asymptomatic hypoglycemics than in obese controls. Specific post-nadir increment (delta growth hormone) was higher in hypoglycemic (6.41 +/- 0.48/Mean +/- SE/) than in nonhypoglycemic obese subjects (1.04 +/- 0.28 ng/ml). Similar difference was found for delta cortisol (8.48 +/- 1.1 vs. -0.81 +/- 0.63 microgram/dl). In contrast to growth hormone, significant inverse proportion was found between delta cortisol and blood glucose nadir (i.e. the lower glucose nadintrols. Cortisol response seems to be more important in the diagnosis of previous hypoglycemic condition. Results suggest that obese subjects with asymptomatic reactive hypoglycemia are similar to manifest reactive hypoglycemics.

Glucose-insulin interaction in obese individuals with asymptomatic reactive hypoglycemia.

The interrelationship of glucose and insulin was investigated in obese nondiabetic subjects with asymptomatic reactive hypoglycemia. Results were compared to those obtained from obese control subjects and normal individuals. The diagnostic criteria for asymptomatic reactive hypoglycemia were the appearance of blood glucose values of 40 mg/dl and below during the postabsorptive phase of a 6-h OGTT and the absence of related symptoms. The blood glucose nadir occurred earlier in obese hypoglycemics than in obese controls. Maximum insulin response was similar in both obese groups, but occurred significantly later in obese hypoglycemics than in obese subjects without hypoglycemia and normal subjects. In obese hypoglycemics the blood glucose nadir was inversely proportional to the time of the insulin peak (i.e. the later the insulin peak the lower the blood glucose nadir) but correlated poorly to maximum insulin values. Delayed insulin response was found to be the major abnormality in asymptomatic reactive hypoglycemia and a probable cause of the decreased ability to maintain post-hyperglycemic glucose homeostasis. Decreased glucose tolerance in some obese hypoglycemics pre-treated with prednisolone suggests that asymptomatic reactive hypoglycemia could be the manifestation of an early diabetic stage.

The urinary iodide excretion in subjects on different diets.

The urinary iodide excretion in hospital subjects on regular and different restrictive diets was investigated. In subjects on a regular diet the average urinary iodide (microgram I-/g creatinine; mean +/- SD) was 104.7 +/- 36.7. In subjects on a low caloric diet the urinary iodide content was 101.1 +/- 24.2; in subjects starving for weight-reduction the mean value was 63.2 +/- 23.9, significantly different from the controls (p less than 0.005). In subjects on a high-caloric diet the urinary iodide was 145 +/- 45.4, in those on a hepatoprotective diet 96.8 +/- 18.8, respectively. The iodide excretion in subjects on an ulcer-protective diet was on the average 76.4 +/- 22.3 which was significantly different from those on a regular diet (p less than 0.01).

Relationship between T4, T3 and T4/T3 ratio in thyroid tissue, thyroid and peripheral veins in patients with nontoxic nodular goiter.

The relationship between T4, T3 and T4/T3 ratio in thyroid nodules/paranodular tissues, thyroid and peripheral veins has been investigated in 26 patients with nontoxic nodular goiters; eleven of them were treated with l-thyroxine 150 micrograms daily. A significant correlation between iodothyronine concentrations and T4/T3 [corrected] ratio in paranodular thyroid tissues and thyroid effluents was found in both groups of patients. By contrast, the correlation between these parameters in the nodule and thyroid veins was poor, which implies that the thyroid hormone pattern in the thyroid veins on the side of nodular lesion is predominantly controlled by the release of the hormones from paranodular healthy tissue. A close dependence of the serum T4/T3 ratio on the values of iodothyronines and their ratio in thyroid tissues and thyroid veins was observed in nontreated, but not in treated patients. Conversely, in the latter group, the thyroidal T4/T3 ratio in paranodular tissue, but not in the nodule, was found to be dependent on the serum T4/T3 ratio, suggesting that paranodular thyroid tissue more readily responds to 1-thyroxine-inhibited TSH secretion. The results demonstrate that 1. the serum thyroid hormone pattern under physiological conditions is dependent on the intrathyroidal T4/T3 ratio, and 2. minor alterations in the serum thyroid hormones may secondarily change the thyroidal T4/T3 ratio, presumably by their effect on TSH secretion.

Low thyroidal T3 in nodular goitrous tissue.

Six nodular tissues of non-treated and four of treated patients (suppressive treatment with thyroid hormones from three months to two years until the operation) with nodular non-toxic goitre contained low T3 (less than 1 ug/g w.w.). The results of iodothyronines and thyroglobulin (Tg) were compared with respective tissues containing T3 greater than 1 ug/g w.w. In non-treated patients, nodular tissues with low T3 and very high T4/T3 ratio showed T4 and Tg concentrations not different from the tissues with T3 greater than 1 ug/g w.w. In the goitres with low T3 of treated patients, T4 was also reduced but disproportionately to T3. Microscopically, nodular goitres with low T3 were characterized with gross fibrous infiltration and diffuse haemorrhage which was substantially different from histological findings in nodular goitres with T3 greater than 1 ug/g w.w. High T4/T3 ratio in the tissues with low T3 is similar to increased T4/T3 ratio in paranodular tissues of autonomously functioning adenomas. The results suggest that low T3 and high T4/T3 ratio in nodular goitrous tissue could be due to grossly impaired thyroid function or due to suppressed secretion of TSH.

Exogenous and endogenous suppression of thyroid-stimulating hormone induces similar effects on thyroidal iodothyronines.

Thyroidal concentrations of T4 and T3 and the T4/T3 ratio were analyzed in the nodular and paranodular tissues from two groups of patients with suppressed TSH secretion. The first group consisted of 17 patients with nontoxic nodular goitre (NG), 8 of whom received long-term levothyroxine therapy to suppress TSH, while remaining 9 were untreated. The second group consisted of 10 patients with autonomously functioning thyroid adenoma (AFTA), in whom TSH secretion was suppressed due to the adenoma-induced increase in thyroid hormone concentrations. In nodular tissues of NG patients, thyroidal T4 and the T4/T3 ratio were significantly higher in treated than in untreated patients (0.34 +/- 0.05 vs. 0.15 +/- 0.02 mol T4/mol of thyroglobulin (Tg) and 10.9 +/- 1.2 vs. 5.2 +/- 0.7 respectively). Analysis of paranodular tissues of NG patients also revealed a higher T4/T3 ratio in treated patients (16.0 +/- 2.1 vs. 6.9 +/- 0.9), although thyroidal T3 and T4 concentrations in treated and untreated patients were similar. In AFTA patients, both T3 and T4 concentrations were higher in the adenoma than in paranodular tissues (0.14 +/- 0.04 vs. 0.02 +/- 0.005 mol T3/mol Tg and 1.08 +/- 0.32 vs. 0.26 +/- 0.06 mol T4/mol Tg), whereas the T4/T3 ratio was significantly higher in paranodular tissues (23.2 +/- 5.9 vs. 9.3 +/- 1.8). These results indicate that suppression of TSH induced either exogenously or endogenously results in an increase in the thyroidal T4/T3 ratio that reflects an increase in T4 and/or a decrease in T3 concentrations. These findings also support the notion that TSH preferentially stimulates thyroidal T3 production.

Increased thyroidal T4/T3 ratio in nodular and paranodular tissues of nontoxic goiter following suppressive treatment with thyroid hormones.

The effect of suppressive treatment with thyroid hormones on thyroidal iodothyronines and T4/T3 ratio in nodular and paranodular tissues was investigated in 12 patients with nontoxic goiter. Results were compared to those from 11 nontreated patients. Continuous thyroid hormone administration produced a significant increase in thyroidal T4 and T4/T3 ratio in nodular tissues while T3 remained unchanged. In paranodular tissues a significant rise of T4/T3 ratio, an insignificant increase in T4 and a decrease in T3 were observed following the administration of thyroid hormones. The results are very similar to those obtained in paranodular tissue of autonomously functioning thyroid nodule, and are probably the consequence of suppressed TSH secretion, as TSH predominantly stimulates the synthesis of T3 and/or thyroidal T4 monodeiodination.