Downregulation of plasma membrane expression/cytoplasmic accumulation of beta-catenin predicts shortened survival in non-small cell lung cancer. A clinicopathologic study of 100 cases

The E-cadherin-catenin complex proteins function in cell-cell adhesion and have been reported to be dysregulated in various human malignancies. Beta catenin is a cytoplasmic protein that associates with tyrosine kinase receptors and modulates cytoskeletal dynamics. It also plays a role in the Wnt signaling pathway. During neoplastic transformation, the phosphorylation of beta-catenin causes a loss of intercellular adhesions resulting in increased tumor cell motility and invasiveness. Tissue sections from 100 cases of non-small cell lung cancer (NSCLC) were immunostained with a monoclonal beta-catenin antibody. There were 47 squamous cell carcinomas (SCC) and 53 adenocarcinomas (AC) in the study group. Plasma membrane/cytoplasmic beta-catenin immunoreactivity was scored for intensity and distribution and correlated with tumor stage, grade and survival. Plasma membrane/cytoplasmic immunoreactivity for beta-catenin protein was observed in 71 (71%) of 100 NSCLC. 44 (94%) of 47 SCC and 27 (51%) of 53 AC expressed beta catenin. On univariate analysis, loss of beta catenin expression correlated with high tumor stage (p = 0.025), large tumor size (p = 0.02) and decreased patient survival (p = 0.04). The loss of beta catenin expression associated with high grade NSCLC reached near significance (p = 0.07). On multivariate analysis, the loss of beta catenin expression independently predicted shortened overall patient survival in NSCLC (p = 0.05). Beta catenin expression loss is associated with advanced tumor stage and is an independent predictor of shortened patient survival in NSCLC.     

Functional organization of enhancer (ENII) of hepatitis B virus.

A new enhancer ENII, located in the X open reading frame and immediately upstream of the core gene promoter, has recently been identified in the genome of hepatitis B virus. We have studied the functional constituents of this new enhancer in different cell lines. ENII can be divided into two functional elements, A and B, corresponding to two major binding sequences for nuclear protein factors. Element A alone gave very low activity; however, it was a modulatory element important for cell-type specificity. Element B was shown to be the basic functional element of ENII, which retained about 70% of the enhancer activity of the complete ENII in HepG2 cells. Element B can be further dissected into three subunits, B1, B2, and B3, which act synergistically. A 52-bp sequence is identified as the core sequences of element B. A model for the mechanism of ENII function is proposed.     

Dipeptidyl peptidase IV activity in cells of T-lymphoid origin is decreased in cultures with 12-0-tetradecanoylphorbol-13-acetate (TPA)

Dipeptidyl peptidase IV (DPP IV) is a specific enzyme for cells of T-lymphocytic lineage. It has been attempted to induce DPP IV activity in DPP IV negative T-lymphoid leukaemias by 12-o-tetradecanoylphrobol-13-acetate (TPA). Isolated cells from peripheral blood of 6 healthy blood donors and 22 patients with various types of leukaemia were cultivated in RPMI-1640 medium with 20% fetal calf serum alone (control) or supplemented with 20% human placenta conditioned medium (HPCM) or with 16 nmol/l TPA for 3 days. The percentage of DPP IV positive lymphocytes from blood donors remained unchanged in control and HPCM cultures, but decreased significantly in TPA cultures. Leukemic cells from three DPP IV positive cases of acute T-lymphoblastic leukaemia (T-ALL) reacted to the TPA treatment in a similar manner. Leukaemic cells of two DPP IV negative T-ALL cases remained negative in all three types of cultures, thus no induction of DPP IV activity was found. Other normal blood cells as well as leukaemic cells of 7 null-ALL, 1 preB-ALL, 3 B-CLL and 6 AML patients were DPP IV negative before and after cultivation in all types of culture. These findings showed that DPP IV is specifically expressed in cells of T-lymphocytic lineage even after short-term cultivation. HPCM was found to have no effect on DPP IV activity in T-lymphoid cells.     

A fluorescence histochemical and biochemical evaluation of the effect of p-chloroamphetamine on individual serotonergic nuclei in the rat brain.

The serotonin (5-hydroxytryptamine) content of eight raphe nuclei was measured 9 days after injection of p-chloroamphetamine. 5-Hydroxytryptamine levels were reduced in only the B-9 cell group.The histofluorescence of serotonergic neurons in the B-9 cell group was also studied at two time intervals after a single injection of p-chloroamphetamine. Nine days after the administration of p-chloroamphetamine there was a small decrease both in the intensity of fluorescence and in the number of yellow fluorescent serotonergic cells. After 2 months the drug caused a more marked decrease in the number of viable serotonergic cells. The results are discussed in relation to the mechanism of action of p-chloroamphetamine.It is suggested that following the administration of p-chloroamphetamine retrograde destruction may occur in the B-9 cell group, in contrast to those of the other raphe nuclei, whose cell bodies may possess a sufficient number of collateral processes to resist the slow neurotoxic destruction of their cell bodies.     

Serum and lymph-node collagenase in sarcoidosis. Comparison with angiotensin-converting enzyme.

Serum collagenase was significantly elevated in stage II, but not stage I sarcoidosis, in contrast to elevation of serum angiotensin-converting enzyme in stages I and II. Neither serum collagenase nor angiotensin-converting enzyme was elevated in active tuberculosis. Elevated serum collagenase and angiotensin-converting enzyme levels were decreased with steroid therapy. Serum collagenase and angiotensin-converting enzyme were significantly correlated but did not vary identically. Collagenase was not elevated in lymph nodes in sarcoidosis, in contrast to marked elevation of angiotensin-converting enzyme. The results suggest that serum angiotensin-converting enzyme is a more sensitive index of sarcoidosis activity than serum collagenase, which may have an ancillary role in assessment of the disease.     

HIV-1 p24 antigen testing in blood banks: results from Saudi Arabia

HIV-1 p24 antigen testing was introduced to increase sensitivity in the early detection of HIV infection in blood donors. Since the introduction of HIV-1 p24 antigen testing in Saudi Arabia, we have failed to detect a single positive case. Over a three-year period, only four indeterminates were detected out of 24,654 blood donors. All four proved negative by confirmatory testing. Based on this experience, we believe that resources would be better directed to pooled nucleic acid testing and that p24 serological testing should be abandoned.     

A new haplogroup pattern displayed in Fujian Han in China

Human Y-chromosomal binary polymorphisms have been considered to preserve the paternal genetic legacy and provide evidence on human evolution and the genetic relationships among and demographic history of different populations. To reveal the genetic origin and immigration of the Fujian Han, 13 binary markers on the Y chromosome were used to screen Fujian Han by allele-specific polymerase chain reaction. The results indicated that the M₉G marker was highly prevalent (96.20%), suggesting a significant genetic drift. In addition, M₁₂₂C frequency was only 22.78%, and M₄₅A and M₁₀₃T were default. The distinctive haplogroup frequencies (H₁, H₅, and H_6/7/8) imply that the haplogroup pattern is a relatively ancestral and interim type. Received: October 13, 2001 / Accepted: December 3, 2001     

Primary culture of prostatic adenocarcinoma: a model for studies of stromal-epithelial interactions

Primary culture of prostatic adenocarcinoma is obtained from surgical material after radical prostatectomy. Typing of the obtained culture with antibodies to vimentin and cytokeratins has shown that the proportion of basic cell components--stromal and epithelial--in vitro correlates with such in the initial tumor tissue. In cultivation in different media active migration and proliferation of all cell types in the presence of embryonal serum and suppression of the stromal component in the medium where the serum was replaced for bovine hypophysis extract were observed. A comparative immunohistochemical analysis registered a release into culture of alpha SMA-positive myofibroblasts and active expression of TGF beta-1 in the medium containing serum. Design of dynamic mixed cell systems may serve a convenient model for investigation of stromal-epithelial interactions and their changes in cancer progression.     

The sensory innervation of the rat rhinarium

The present study documents the characteristics of innervation of the rhinarium or hairless rat snout skin by light and electron microscopy. The outer glabrous surface is covered with a stratified squamous epithelium that forms both rete pegs and rete ridges, the latter on the inferior border near the philtrum. The glabrous skin contains numerous presumptive epidermal and dermal free nerve endings (FNE's), Merkel terminals at the base of the rete ridges and pegs, and simple, nonencapsulated corpuscles. A second region of dense innervation, found on an elevation of the inner wall of the vestibule, contains similar components of innervation, with the exception that no Merkel terminals were identified. Since no Merkel terminals were present in this area of the vestibule, intraepidermal as well as dermal FNE's could be identified with certainty. This skin is covered by a thin squamous epithelium overlying dense connective tissue. The simple corpuscles are similar to those in the rhinarium, as well as resembling those described in other species. FNE's were frequently observed intimately associated with simple corpuscles. Several examples of large FNE's with two to three layers of cytoplasmic lamellae were found, suggestive of transitional forms between FNE's and simple corpuscles. Thus, the pattern of sensory innervation in the glabrous rat snout skin is similar to that found in other furred species described to date, but in addition, the sensory innervation of ridged skin in the rat also resembles that of epidermis organized into rete pegs. This dense sensory innervation may be correlated with whisking behavior of the predominantly nocturnal rat.     

Gm allotypes in blacks with systemic lupus erythematosus

Serum samples were collected from 328 healthy American Blacks and from 61 American Blacks with systemic lupus erythematosus (SLE). Sera were typed for the Gm1,2,3,5,6,13,17, and 21 allotypes as well as for the Km(1) allotype. The frequency of Gm phenotype 1,17;5,6,13 was significantly increased in the SLE patients (p = 0.0001, RR = 3.19, EF = 0.29). Our data suggest the existence of at least two immunoglobulin allotype associated genes that somehow interact to increase susceptibility to SLE in Blacks. To our knowledge, this is the first report of an association of Gm and SLE in Blacks.