Interactions between taste receptors in the frog tongue

Summary Receptors sensitive to stimulation with dilute CaCl₂ solutions and located in different fungiform papillae of the frog tongue are cross-connected via branches of the glossopharyngeal nerve fibers to form chemical sensory units comprising on average about 3 papillae; often one or more papillae were found to be common to different units.The receptor response observed when single papillae were individually stimulated increased, when the strength of the stimulus was raised, at a much lower rate than that obtained by stimulating the whole tongue surface. This proves that the antidromic impulses travelling in the cross-connections linking different papillae result in an evident depression of the receptor response to CaCl₂.The possible functional significance of mutual interaction between the receptors in the frog tongue is discussed.This study was supported by grants from the Consiglio Nazionale delle Ricerche (Impresa di Elettrofisiologia) of Rome, Italy.     

Interstitial Stress and Fluid Pressure Within a Growing Tumor

A solid tumor is composed of a population of cells that is expanding as a result of cell division. With dense cell packing, the solid matrix of the interstitial tissue is subject to residual stress. In addition, elevated interstitial fluid pressure (IFP) has been reported by researchers for a number of solid tumors. These features were incorporated into a mathematical model that predicts the mechanical response of a solid tumor within its host environment. A theoretical framework accounting for volumetric expansion, transvascular exchange and extravascular transport of fluids was developed using poroelastic theory, and applied to a spherical, vascularized, alymphatic tumor undergoing small growth increments. Simulations of tumor IFP were similar to those predicted by Jain and Baxter (Ref. 23), showing elevated IFP that is driven by microvascular fluid pressure. Tumor growth, tissue stiffness, and IFP contribute to the compressive stresses predicted in the solid tumor interior. Tensile and compressive stresses were predicted in adjacent host tissues corresponding to radial and circumferential directions, respectively. An application of this model includes a solid stress-based framework for predicting regions of vascular collapse within the tumor interior. © 2003 Biomedical Engineering Society. PAC2003: 8717Ee, 8710+e, 8719Rr, 8719Xx     

Coexpression of Aspartic Proteinases and Human Leukocyte Antigen-DR in Human Transplanted Lung

Aspartic proteinases have recently been shown to be implicated in antigen processing. We explored the expression of two aspartic proteinases, cathepsins E and D, and of human leukocyte antigen-DR (HLA-DR) molecules in a consecutive series of 80 transbronchial biopsies from transplanted lungs. For controls, we studied five normal donor lungs (not suitable for transplantation on account of thoracic trauma) and macroscopically normal areas of three cancer-affected lungs. Two of the five unsuitable donor lungs showed minimal inflammatory changes. Macroscopically normal samples from the three cancerous lungs showed mild and focal inflammatory infiltrates. In histologically normal lungs, HLA-DR expression was limited to professional antigenpresenting cells. Macroscopically normal lung samples with minimal inflammatory changes from both donor and cancer lungs showed variable HLA-DR expression by alveolar and bronchial epithelial cells and by endothelial cells. All transplanted lung biopsies showed HLA-DR expression by epithelial (alveolar and bronchial) and endothelial cells, with a trend for increased positivity in acute rejection. Cathepsin E was restricted to Clara and to rare bronchus-associated lymphoid tissue-related epithelial cells in histologically normal lung samples, whereas minimal de novo cathepsin E expression by rare alveolar pneumocytes was noted in control lung samples exhibiting minimal inflammatory changes. In all transplanted lung biopsies, cathepsin E was diffusely expressed de novo by hyperplastic alveolar epithelial cells, regardless of the presence or degree of rejection. Cathepsin D was expressed only by alveolar macrophages and by ciliated bronchial cells of normal, minimally inflamed, and transplanted lungs. In transplanted lung, Clara cells and several hyperplastic alveolar pneumocytes coexpressed HLA-DR and cathepsin E, whereas all alveolar macrophages and a few ciliated cells coexpressed cathepsin D and HLA-DR The present investigation suggests that the de novo expression of cathepsin E and HLA-DR by hyperplastic alveolar pneumocytes of transplanted lung may be crucial for antigen processing and presentation to recipient competent T cells, and thus for the triggering of the immune-inflammatory cascade that leads to rejection.     

TS/A: a new metastasizing cell line from a BALB/c spontaneous mammary adenocarcinoma

A metastasizing mouse cell line (TS/A), originated from a mammary adenocarcinoma which arose spontaneously in a BALB/c female retired breeder, has been established in vitro. It displayed a remarkable morphologic heterogeneity, which is evident in plastic adherent cultures (cell types ranging from epithelial-like to fibroblast-like) as well as in semi-solid agar cultures. The TS/A line exhibited the presence of specific cytoplasmic estradiol receptor, with a binding activity of 16 fmoles/mg cytosol protein. The in vivo growth pattern was as follows: (1) a s.c. inoculum of 105 cells caused a 100 per cent tumor take and kill in syngeneic animals; mean survival time was 54 + 1 days; (2) it did not show significant transplant immunogenicity in syngeneic animals; (3) it was able to give rise to both spontaneous lung metastases and artificial lung colonies; (4) it had a high capacity to grow in H-2 matched, minor histocompatibility antigen incompatible hosts (106 cells killed 100 per cent DBA/2 mice in 58 + 2 days). This line of spontaneous mammary tumor cells is proposed as a useful model for studies on the heterogeneity of the neoplastic population in relation to metastatic spread, on tumor immunogenicity, and on therapy of mammary neoplasia.     

Defective Aspergillus killing by neutrophil leucocytes in a case of systemic aspergillosis.

A persistent defect of Aspergillus killing was observed in the neutrophils of a 6-year-old patient with a systemic A. fumigatus infection which was highly refractory to anti-mycotic therapy. Aspergillus phagocytosis in vitro was normal, but nearly 80% of the ingested organisms (versus 30% in the controls) survived intracellularly during the 2-hr assay period. The patient's neutrophils showed a subnormal frequency of nitroblue tetrazolium reduction and a subnormal hexose monophosphate shunt activation in response to phagocytosis. The metabolic responsiveness, however, was clearly superior to that of chronic granulomatous disease neutrophils tested for comparison. The immune status of the patient and the following properties of his neutrophils were found to be normal: random and chemotactic motility, killing of S. aureus and C. albicans, and the contents of several granula enzymes. Our findings suggest the existence of neutrophil factors or functions which are required for killing Aspergillus, but not S. aureus and C. albicans.     

Viral determinants and host immune responses in the pathogenesis of HBV infection

Hepatitis B virus (HBV) is a virus that infects about 350,000,000 people worldwide with a clinical spectrum of acute hepatitis, the healthy carrier state, cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is the result of complicated viral-host interactions. As in other infections with non-cythopatic viruses, the immune response is thought to play a crucial role in disease pathogenesis but there is increasing evidence that a variety of viral mechanisms, some depending on the function of virally encoded proteins, have a profound impact on the infected hepatocytes, the liver microenvironment, and host anti-viral responses. Indeed, the virus has evolved multiple mechanisms to ensure its success in infecting a susceptible host. The essential aspects of the life cycle of HBV and the host immune response are reviewed and recent new developments in the molecular virology of HBV, including experimental animal models, in the role of accessory viral proteins in disease pathogenesis and HCC development and in the characterisation of the T cell response in the control of HBV infection, are highlighted.     

Hypomethylation of the human HLA-DRα gene in breast carcinomas and autologous metastases

The methylation pattern of the human HLA-DR gene was analyzed in normal breast tissues, breast primary tumors and lymphonodal metastases isolated from patients carrying breast carcinomas. In breast adenomas and also in normal tissues (including breast, muscle, brain, sperm and T- and B-lymphocytes), the HLA-DR gene is hypermethylated at the CCGG and GCGC sites. In all tissues studied, the only constantly unmethylated region is located in the 5 portion of the gene, near the promoter sequence. Further, the results indicate that the HLA-DR gene is hypomethylated in carcinomas and in the relative metastatic lymph nodes. It is suggested that hypomethylation of the human HLA-DR gene could be proposed as a molecular marker of malignant breast tumors.     

Cervical muscle response to trunk flexion in whiplash-type lateral impacts

The purpose of this study was to determine the response of the cervical muscles to increasing low-velocity, whiplash-type lateral impacts when the occupant is seated out of the recommended driving position (neutral posture). Twenty healthy volunteers were subjected to left lateral impacts of 4.1, 7.7, 10.5, and 13.7 m/s² acceleration, with their trunk flexed by 45° and laterally flexed to the right and left also by 45° at the time of impact. Bilateral electromyograms of the sternocleidomastoids, trapezii, and splenii capitis were recorded. Under these conditions of trunk-flexed postures, in a left lateral impact, muscle responses were of generally low magnitude with the trunk flexed to either the left or right. Even at the highest acceleration of 13.7 m/s², all muscles generated less than 37% of their known maximal voluntary contraction electromyogram. Also, in these left lateral impacts, the right splenius capitis showed a greater EMG response than the left splenius capitis regardless of whether the subject was flexed to the right or left at the time of impact. The right splenius capitis (the one contralateral to the left lateral impact direction) was more active than its counterpart. Compared to what is known for EMG responses with an occupant in the neutral posture, the right sternocleidomastoid (usually the most active muscle in a left lateral collision) was significantly less-active with trunk flexion than with neutral posture conditions (P<0.01). In the absence of bodily impact, the flexed trunk posture does not produce a biomechanical response that would increase the likelihood of cervical muscle injury in low velocity lateral impacts, and may lessen the risk of injury for some muscles.     

HLA antigens in ulcerative colitis: a study in the Sicilian population

HLA antigens were investigated in 41 Sicilian patients with ulcerative colitis and in 151 healthy controls. Frequencies of HLA-B5 and DR2 were increased in the group of patients with ulcerative colitis whereas the DR3 antigen frequency was decreased. However the corrected p values were not significant. Thus, present results indicate that in ulcerative colitis HLA linked genetic factors play a marginal role, if any.