Thyroid hormones inhibit frog corticotropin-releasing factor-induced thyrotropin release from the bullfrog pituitary in vitro

Due to the lack of a radioimmunoassay (RIA) system for amphibian thyrotropin (TSH), no direct evidence that thyroid hormone suppresses the release of TSH from the amphibian pituitary has been obtained. However, we recently developed an RIA for bullfrog (Rana catesbeiana) TSH and thus were able to study the effect of thyroid hormone on the release of TSH from the bullfrog pituitary. Enzymatically dispersed pituitary cells of larval, juvenile, and adult bullfrogs were cultured in the absence or presence of 100 nM corticotropin-releasing factor of bullfrog origin (fCRF), which is known to be a potent stimulator of the release of TSH. The amount of spontaneously released TSH was higher in late prometamorphic and climactic tadpoles than in early prometamorphic larvae and juvenile and adult frogs. Pituitary cells from tadpoles at metamorphic climax responded to fCRF to release much more TSH than those from early and late prometamorphic tadpoles and juvenile and adult frogs. In all cases, the fCRF (100 nM)-induced, but not the basal, release of TSH was significantly suppressed by 1 nM triiodothyronine (T(3)) and 1000 nM thyroxine (T(4)), when examined using adult pituitary cells. The suppressive effect of thyroid hormones was revealed to be dependent on their concentrations.     

Clinical and virological characteristics of untreated patients with chronic hepatitis C who develop serum alanine aminotransferase flare-up

Among patients with chronic hepatitis C virus (HCV) infection, serum alanine aminotransferase (ALT) rarely increases above 500 IU/L. We examined the clinical and virological features of untreated patients with serum ALT > or = 500 IU/L. One thousand seven hundred and sixty adult patients with chronic HCV infection were followed-up. Among these patients, 22 developed ALT flare-up (M:F=13:9, median age, 50.5 years). We evaluated liver function tests, genotype, and viral titer in these patients and 44 randomly selected age- and sex-matched control without ALT flare-up. In four patients with ALT flare-up, we examined changes in viral loads and sequential changes in amino acid sequences of the core region, hypervariable region 1 (HVR1), and interferon sensitivity determining region (ISDR) before and after ALT flare-up. Multivariate analysis identified genotype 2 as the only significant determinant of ALT flare-up. ALT flare-up occurred in three of four patients without increase in viral load. Several alterations in amino acids were noted in HVR1 before and within 6 months of ALT flare-up. One or two alterations in the core region and many alterations in HVR1 were noted after ALT flare-up in some patients. Genotype 2 is an important factor for ALT flare-up. However, we could not directly relate ALT flare-up to these alterations in amino acids of the core region, HVR1, and ISDR.     

Probability of axillary lymph node metastasis when sentinel lymph node biopsy is negative in women with clinically node negative breast cancer: a bayesian approach

BACKGROUND: Although sentinel lymph node biopsy(SLNB)is highly accurate in predicting axillary nodal status in patients with breast cancer, it has been shown that the procedure is associated with a few false negative results. The risk of leaving metastatic nodes behind in the axillary basin when SLNB is negative should be estimated for an individual patient if SLNB is performed to avoid conventional axillary lymph node dissection(ALND). METHODS: A retrospective analysis of 512 women with T1-3N0M0 breast cancer was conducted to derive a prevalence of nodal metastasis by T category as a pre-test(i.e., before SLNB)probability and to examine potential confounders on the relationship between T category and axillary nodal involvement. Probability of nodal metastasis when SLNB was negative was estimated by means of Bayes' theorem which incorporated the pre-test probability and sensitivity and specificity of SLNB. RESULTS: Axillary nodal metastasis was observed in 6.1% of T1a-b, 25.1% of T1c, 28.7% of T2, 35.0% of T3 tumors. Point estimates for the probability of nodal involvement when SLNB was negative ranged from 0.3-1.3% for T1a-b, 1.6-6.3% for T1c, 2.0-7.5% for T2, and 2.6-9.7% for T3 tumors with representative sensitivities of 80%, 85%, 90% and 95%, respectively. The risk may be higher when the tumor involves the upper outer quadrant of the breast, while it may be lower for an underweight woman. CONCLUSIONS: The probability of axillary lymph node metastasis when SLNB is negative can be estimated using a Bayesian approach. Presenting the probability to the patient may guide the decision of surgery without conventional ALND.     

Effects of mononuclear phagocyte system modulating agents on Fc and C3 receptors of adherent cells.

Agents which modulate the mononuclear phagocyte system (MPS) were examined for their effects on Fc and C3 receptors of adherent cells (A-cells) as judged by rosette formation. Dextran sulphate, carrageenan, and immune complexes, known as MPS suppressants, reduced the percentage of receptor-positive A-cells, while levamisole, known as a MPS-activator, increased the percentage in vitro. The changes in the percentage of Fc receptor were parallel to those of the C3 receptor in vitro. The effects of these agents were also examined in vivo.     

Subectodermal microfibrillar bundles are organized into a distinct parallel array in the developing chick limb bud

In this study, a unique fiber system in the subectodermal mesenchyme of the chick limb bud was visualized immunohistochemically with the use of a novel monoclonal antibody termed "FB1." This antibody stained a subset of extracellular fibers in the embryonic mesenchyme. Among the fibers visualized, those running perpendicularly to the limb bud ectoderm became progressively prominent in their thickness and length, and organized into a parallel array in the subectodermal region. This fiber system was distinct from that of major collagens, fibronectin, or tenascin. A molecule immunoprecipitated with FB1 comigrated with JB3 antigen, or chicken fibrillin-2. The fibers visualized immunohistochemically by FB1 and JB3 were indistinguishable from each other, and ultrastructurally appeared to be bundles composed of tubular-like microfibrils that originated directly from the ectodermal basal lamina. They lacked the amorphous deposits that are characteristic of elastin. A similar array of subectodermal fibers was also found in the developing axilla and some truncal regions, again well before the development of a definitive dermis. These findings suggest that a parallel array of subectodermal FB1-positive fibers constitutes a precocious fiber system in the presumptive dermis prior to the substantial formation of collagenous fibers. These fibers could be developmentally linked to oxytalan fibers, which are known to be present in the papillary dermis in mature cutaneous tissue.     

Correlation of p53 protein expression with apoptotic incidence in colorectal neoplasia

The wild-type p53 gene suppresses cell proliferation and induces apoptosis when it is transfected into human colon cancer cell lines. Therefore, mutation of the p53 gene, which correlates closely with p53 protein overexpression, would be predicted to activate cell proliferation and limit apoptosis. We tested this hypothesis by correlating p53 protein expression with cell proliferation and apoptosis in 70 neoplasms (29 adenomas and 41 carcinomas) using p53 and Ki-67 immunohistochemical staining and DNA nick end labelling. The p53 immunoreactivity was independent of the Ki-67 positivity. The apoptotic incidence was less frequent (P<0.005) in tumours with diffuse p53 protein overexpression than in those with the sporadic overexpression, defined as p53 staining of isolated or scattered expression. In addition, apoptotic incidence only correlated directly (P<0.05) with Ki-67 positivity in tumours with sporadic p53-protein expression. These results indicate that p53 protein that is expressed sporadically in colorectal neoplasms is probably wild-type protein and induces apoptosis in response to active cell proliferation. In contrast, diffusely overexpressed p53 protein in colorectal neoplasms is probably mutant and correlates with a reduction in apoptotic cell death independently of cell proliferation.