Thyroid-stimulating hormone (TSH) deficiency caused by a single base substitution in the CAGYC region of the beta-subunit.

Congenital isolated thyroid-stimulating hormone (TSH) deficiency is an autosomal recessive disease that manifests as hypothyroidism (cretinism), causing severe mental and growth retardations. Patients were found to have a single base substitution in the codon for the 29th amino acid of the TSH beta subunit gene. The alteration is in the center of the so-called CAGYC region, which consists of an amino acid sequence conserved among all of the known glycoprotein hormone beta subunits. No other nucleotide substitutions have been found in the gene thus far sequenced. Microinjection of the mutated beta mRNAs into Xenopus laevis oocytes led to the formation of conformationally altered beta polypeptides that could not associate with alpha subunits. The mutation created a new recognition site for the enzyme MaeI. Southern blot hybridization of genomic DNA digested with MaeI showed that the patients were homozygous and their parents were heterozygous for the mutation. This test was also used to examine other family members for the disease.     

Urinary iodide excretion measured with an iodide-selective ion electrode: studies on normal subjects of varying ages and patients with thyroid diseases

As a part of studies concerning clinical application of the measurement of urinary iodide with an iodide-selective ion electrode, we report here the reference values for the iodide content or concentration in morning spot urine specimens from normal subjects of varying ages and studies with patients with thyroid diseases in Japan. The number distribution of the iodide content or concentration in the morning specimens appeared logarithmic normal in adults, children and infants. Normal ranges found in 95 per cent of populations of healthy subjects were 5.3 to 62.0 mumoles/g Creatinine (Cr) for adults, 5.3 to 42 mumoles/g Cr for children, and 1.9 to 56 microM for infants, respectively. Urinary iodide concentrations in breast-fed infants varied widely compared with those in bottle-fed infants. Mean values were 16.4 microM for breast-fed infants and 8.6 microM for bottle-fed infants, and they were not statistically different. Urine samples from the infants with transient hypothyroidism, who had undergone amniofetography showed extraordinarily high iodide concentrations, even though they were measured at 20th, 29th and 30th days after birth. Although urinary iodide excretion in patients with simple goiter was within normal limits, the mean was statistically lower than that in normal controls (p less than 0.001). Because of the simplicity and rapidity of the electrode method, we strongly recommend it for use in examining iodide excretion in patients with various thyroid diseases.     

Relation of structural polarity to responses of cyclic 3', 5'-adenosine monophosphate accumulation and thyroid hormone release in cultured human thyroid follicles

The relationship of structural polarity to functional activities was examined in cultured human thyroid follicles, which were isolated from the thyroid gland of patients with Graves' disease by collagenase treatment. Structural polarity was examined morphologically by electron microscopy, while the functional response to bovine TSH was examined by measuring intracellular cAMP accumulation and T3 release. In freshly isolated thyroid follicles, structural polarity was normal and TSH induced significant cAMP accumulation but no significant release of T3. After culture for 5 days the structural polarity of thyroid follicles became inverted in the absence of thyroid stimulators, but normal polarity was retained in the presence of TSH or dibutyryl cAMP [Bu)2 cAMP). The response to TSH of cAMP accumulation increased markedly after culture in either the presence or absence of TSH, suggesting that cAMP accumulation in response to TSH is not related to structural polarity. In contrast, thyroid follicles cultured without thyroid stimulators showed no significant T3 release in response to TSH, whereas those cultured with TSH or (Bu)2 cAMP showed significant T3 release in response to TSH. These data indicate that in cultured human thyroid follicles, the responses to TSH of cAMP accumulation and T3 release are not always correlated. Among many other explanations, the results were at least compatible with the idea that normal structural polarity is necessary for thyroid hormone release in response to TSH.     

Transient hypothyroidism associated with increased anti-microsomal antibodies.

An unusual case of transient hypothyroidism during the course of chronic thyroiditis was reported. A 25 years old female noticed the remarkable enlargement of thyroid gland 3 months after paturition and was developed to be hypothyroidism with decreased blood thyroid hormone and increased serum TSH. The patient recovered to be euthyroid spontaneously in association with the decrement of goiter size. Anti-thyroid microsomal antibody increased concomitantly with hypothyroid period and decreased parallel with the recovery of thyroid function. The ratio of TSH potency estimated by bioassay to that by immunoassay changed during the course. Possible etiologic factors of this transient changes were discussed.     

Effects of synthetic ovine corticotropin-releasing factor (CRF) on plasma ACTH and cortisol in 31 normal human males

Responses of plasma ACTH and cortisol to corticotropin-releasing factor (CRF) were evaluated in 31 normal human males. 1.0 micrograms/ks of sterilized synthetic ovine CRF was administered to the subjects, aged 19 to 53 yr and weighing 50 to 78 kg, at between 9:30 a.m. and 10:30 a.m. as an intravenous bolus injection after an overnight fast. Blood specimens were drawn before and 15, 30, 60, 90 and 120 min after injection for later determination of plasma ACTH and cortisol concentrations by radioimmunoassays. Plasma ACTH and cortisol levels for all subjects rose significantly (p less than 0.001) from the basal level (mean +/- SEM, 26.8 +/- 4.5 pg/ml and 12.6 +/- 0.9 micrograms/dl) to peak levels (58.4 +/- 5.5 pg/ml and 22.9 +/- 1.0 micrograms/dl) at 30 min and at 60 min, respectively. Although the plasma concentrations of ACTH and cortisol thereafter declined gradually, the levels at 120 min (43.4 +/- 5.2 pg/ml and 18.9 +/- 0.9 micrograms/ml, respectively) were still significantly higher than the basal levels (p less than 0.001). Significant inverse correlations were observed between the basal levels of each hormone and the ratio of the peak level to the basal level (p less than 0.01), and the increases in plasma ACTH and cortisol concentrations were either not significant or much smaller for the individuals in whom the basal levels were higher than 65 pg/ml and 17.0 micrograms/dl, respectively. No serious subjective symptom was observed during the experimental period in any of the subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diffusive and hydraulic transfer of solutes through homogeneous membranes

Rates of hydraulic transport of water, solute permeabilities, and sieving coefficients of homogeneous kappa-carrageenan and bovine serum albumin membranes were measured. These values increased with the water content of membranes. The data show good agreement with the predictions based on the pore model.     

Sequence analysis of full-length cDNA of sex chromosome-linked novel gene 2d-2F9 in Gallus gallus

We obtained two novel W chromosome-linked chick genes by the use of female-male subtraction macroarrays, one of which, 2d-2F9, (recorded as AB188527 in DDBJ) did not have sufficient length (776 bp) to reveal its real form or characteristics. Hence, we obtained full-length Z-linked and W-linked 2d-2F9 genes of 2596 bp and 2589 bp respectively by the oligo-capping and RACE methods.Sequence analysis of these genes not only revealed that there is a counterpart of the W-linked 2d-2F9 gene on the Z chromosome, but also that there is a low homologous area at 5'-UTR between the W- and Z-kinked genes. Using this information, we designed a set of primers to identify sex and to select clones having the Z and W-linked gene (named 2d-2F9-Z and 2d-2F9-W), and also prepared two sets of primers for RT-PCR. These genes were found to be expressed constitutively and ubiquitously from the early embryo to the hatched chick, and they were assigned to the AAA ATP-superfamily.     

Neurofeedback using real-time near-infrared spectroscopy enhances motor imagery related cortical activation

Accumulating evidence indicates that motor imagery and motor execution share common neural networks. Accordingly, mental practices in the form of motor imagery have been implemented in rehabilitation regimes of stroke patients with favorable results. Because direct monitoring of motor imagery is difficult, feedback of cortical activities related to motor imagery (neurofeedback) could help to enhance efficacy of mental practice with motor imagery. To determine the feasibility and efficacy of a real-time neurofeedback system mediated by near-infrared spectroscopy (NIRS), two separate experiments were performed. Experiment 1 was used in five subjects to evaluate whether real-time cortical oxygenated hemoglobin signal feedback during a motor execution task correlated with reference hemoglobin signals computed off-line. Results demonstrated that the NIRS-mediated neurofeedback system reliably detected oxygenated hemoglobin signal changes in real-time. In Experiment 2, 21 subjects performed motor imagery of finger movements with feedback from relevant cortical signals and irrelevant sham signals. Real neurofeedback induced significantly greater activation of the contralateral premotor cortex and greater self-assessment scores for kinesthetic motor imagery compared with sham feedback. These findings suggested the feasibility and potential effectiveness of a NIRS-mediated real-time neurofeedback system on performance of kinesthetic motor imagery. However, these results warrant further clinical trials to determine whether this system could enhance the effects of mental practice in stroke patients.     

Are folliculo-stellate cells in the anterior pituitary gland supportive cells or organ-specific stem cells?

Folliculo-stellate cells (FS-cells) in the anterior pituitary gland are star-shaped cells and form tiny follicles. FS-cells are positive for S-100 protein and produce many cytokines or growth factors, such as interleukin-6 (IL-6), leukemia inhibitory factor (LIF), basic fibroblastic growth factor (bFGF) and vascular endothelial cell growth factor (VEGF). Therefore, it is generally accepted that FS-cells regulate endocrine cells through these growth factors. FS-cells also exhibit a phagocytotic activity and are known to work as scavenger cells. In addition to these functions, FS-cells are considered to have some unknown functions. In order to reveal the biological significance of FS-cells in the anterior pituitary gland, we performed a morphological study and obtained some new findings. First, we were interested in the colloid formation in the senescent porcine pituitary gland. We analyzed the colloids and found that clusterin is a major protein in them. We also found that the accumulation of clusterin in the colloids is related to the phagocytotic activity of FS-cells. In our next study, we found that FS-cells have the potential to differentiate into striated muscle cells. From FS-cells show multi-potent cell character and other cytological evidence, we propose that FS-cells are candidate of organ-specific stem cells in the anterior pituitary gland.