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.     

Skin Cancer Risk Associated with Immunosuppressive Therapy in Organ Transplant Recipients

The aim of this review is to summarise the available literature regarding the epidemiology and proposed mechanisms of skin cancer development in organ transplant recipients who are receiving lifelong treatment with immunosuppressive therapy and to review the different strategies for managing complications in this group of patients. Organ transplantation is complicated by an increased incidence of certain cancers, of which non-Hodgkin's lymphoma, Kaposi's sarcoma and squamous cell carcinoma are the most common. The most important risk factor for these cancers is immunosuppressive therapy. The relative importance of different immunosuppressive therapy regimens in relation to the development of skin cancer is still unclear. Immunosuppression per se may play the most important role, but other mechanisms, which are independent of host immunity and which may be different for the various agents used, may also be of importance for the increased risk of cancer. Apart from immunosuppressive therapy, exposure to sunlight and infection with human papillomaviruses are believed to be the most important risk factors for the development of cutaneous squamous cell carcinoma in organ transplant recipients. Human papillomaviruses, no doubt, benefit considerably from immunosuppression, as is indicated by the large number of warts found in these patients, but many questions remain unanswered about their significance in cutaneous oncogenesis. The E6 protein from a range of cutaneous human papillomavirus types effectively inhibits apoptosis in response to ultraviolet light damage. It is, therefore, conceivable that the development of skin cancer in organ transplant recipients is the result of a complex interplay between exposure to ultraviolet radiation, human papillomavirus infection and genetic predisposition. Measures for protection from the sun are important for reducing the risk of skin cancer in organ transplant recipients. Regular surveillance of patients with skin problems and easy access to a dermatologist for these patients is advised. Changing the immunosuppressive regimen from azathioprine to cyclosporin or vice versa does not seem to relieve the skin problems. Tapering the immunosuppressive therapy to the lowest possible dose may be of some advantage. Oral retinoids, e.g. acitretin, have some effect in reducing the number of keratotic skin lesions and in the prevention of skin cancer in organ transplant recipients. Resurfacing the back of the hand can be a successful treatment for patients with multiple skin cancers on the back of the hand and can be used prophylactically in patients with severely actinically damaged skin.     

肝素酶和碱性成纤维细胞生长因子与非小细胞肺癌转移和预后的关系

目的 探讨肝素酶(heparanase)和碱性成纤维细胞生长因子(bFGF)在人非小细胞肺癌(NSCLC)组织中表达的临床意义及其与肺癌转移和预后的关系。方法 采用免疫组织化学、原位杂交和Western blot方法,检测115例人NSCLC石蜡切片和45例新鲜肺癌及对应癌旁正常组织中肝素酶和bFGF的表达情况。采用χ^2检验、t检验、生存曲线和Cox比例风险回归等方法分析肝素酶和bFGF分别表达及共表达的意义。结果 免疫组织化学染色证实肝素酶(91／115)和bFGF(89／115)主要表达在癌细胞质和(或)细胞膜中,在正常肺泡上皮和支气管上皮中则呈阴性表达。Western blot也证实肝素酶在肺癌中的表达明显增高(P=0．041)。统计分析结果显示：肝素酶和bFGF的表达具有明显的一致性(P：0．0001),二者单独表达和共表达均与肺癌的分期、血管侵袭、淋巴结转移、微血管密度和预后有关,其中,二者共表达时与分期和微血管密度的相关性更显著;另外,bFGF还与肺癌的分化程度有关。多因素分析结果显示,肺癌的分化程度、血管浸润、淋巴结转移和bFGF的表达可以作为判断肺癌预后的危险因素,但肝素酶不是影响预后的独立因素。结论 肝素酶和bFGF均与肺癌的转移、血管生成和预后密切相关。     

Enhanced responsiveness of human extravisual areas to photic stimulation in patients with severely reduced vision

Lesions in the primary visual cortex induce severe loss of visual perception. Depending on the size of the lesion, the visual field might be affected by small scotomas, hemianopia, or complete loss of vision (cortical blindness). In many cases, the whole visual field of the patient is affected by the lesion, but diffuse light-dark discrimination remains (residual rudimentary vision, RRV). In other cases, a sparing of a few degrees can be found (severely reduced vision, SRV).In a follow-up study, we mapped visually induced cerebral activation of three subjects with SRV using functional magnetic resonance imaging. We were especially interested in the visual areas that would be activated if subjects could perceive the stimulus consciously although information flow from V1 to higher visual areas was strongly reduced or virtually absent. Because subjects were only able to discriminate strong light from darkness, we used goggles flashing intense red light at a frequency of 3 Hz for full visual field stimulation. Besides reduced activation in V1, we found activation in the parietal cortex, the frontal eye fields (FEF), and the supplementary eye fields (SEF). In all patients, FEF activation was pronounced in the right hemisphere. These patterns were never seen in healthy volunteers. In a patient who recovered completely, we observed that extrastriate activation disappeared in parallel with the visual field restitution. This result suggests that damage to the primary visual cortex changes the responsiveness of parietal and extravisual frontal areas in patients with SRV. This unexpected result might be explained by increased stimulus-related activation of attention-related networks.     

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.     

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.     

Accumulation of very long-chain fatty acids does not affect mitochondrial function in adrenoleukodystrophy protein deficiency

X-linked adrenoleukodystrophy (X-ALD, OMIM 300100) is a severe inherited neurodegenerative disease, associated with the accumulation of very long-chain fatty acids (VLCFA). The recent unexpected observation that the accumulation of VLCFA in tissues of the Abcd1-deficient mouse model for X-ALD is not due to a deficiency in VLCFA degradation, led to the hypothesis that mitochondrial abnormalities might contribute to X-ALD pathology. Here, we report that in spite of substantial accumulation of VLCFA in whole muscle homogenates, normal VLCFA levels were detected in mitochondria obtained by organellar fractionation. Polarographic analyses of the respiratory chain as well as enzymatic assays of isolated muscle mitochondria revealed no differences between X-ALD and control mice. Moreover, analysis by electron microscopy, revealed normal size, structure and localization of mitochondria in muscle of both groups. Similar to the results obtained in skeletal muscle, the mitochondrial enzyme activities in brain homogenates of Abcd1-deficient and wild-type animals also did not differ. Finally, studies on mitochondrial oxidative phosphorylation in permeabilized human skin fibroblasts of X-ALD patients and controls revealed no abnormalities. Thus, we conclude that the accumulation of VLCFA per se does not cause mitochondrial abnormalities and vice versa-mitochondrial abnormalities are not responsible for the accumulation of VLCFA in X-ALD mice.     

Pulmonary endocrine cells in various species in the Himalaya

The numbers, morphology and distribution of pulmonary endocrine cells in goats, sheep and the yak and its interbreeds with cattle, dzos and stols, were studied after their demonstration by means of the peroxidase-antiperoxidase technique with a polyclonal antiserum raised in the rabbit to human neuron-specific enolase, a marker for neuroendocrine cells. The numbers, morphology and distribution were related to species and not to residence at high altitude. Pulmonary endocrine cells were common and mainly distributed as solitary cells in the epithelium of the bronchial tree in sheep. They were much less common and found mainly as clusters in the alveolar capillary walls in goats and in the yak and its interbreeds with cattle.     

The effect of tyrphostin AG-556 on intimal thickening in a mouse model of arterial injury

BACKGROUND: Inflammation has been shown to play an important role in promoting the response to arterial injury and proinflammatory cytokines, such as tumor necrosis factor (TNF) alpha, are candidate mediators. AG-556 is a tyrosine kinase inhibitor proven to be effective in a model of multiple sclerosis-like syndrome in mice due to its immunomodulating effect. In the current study, we investigated the effect of the tyrphostin AG-556 on neointimal thickening and cytokine profile in a model of arterial injury in the mouse. METHODS: Injury was induced by external cuff placement on the left femoral artery of wild-type C57BL/6 mice. AG-556 dissolved in DMSO was injected intraperitoneally daily to the injured mice in a dosage of 2 mg/mouse. Control mice received DMSO injections. Histological analysis was carried out to assess neointimal formation. Splenocytes were cultured in the absence and presence of a mitogen for evaluation of thymidine incorporation and cytokine production. RESULTS: AG-556 treatment significantly attenuated intimal thickening (43,000+/-17,000 microm2; n=11) when compared to DMSO administration (286,000+/-127,000 microm2; n=10; P<0.05). Basal interferon-gamma production by splenocytes from AG-556-treated mice was increased by approximately 20-fold in comparison with levels in DMSO-treated animals, whereas Con-A induced secretion of the cytokine was similar between both groups. Levels of TNF-alpha, IL-4 and IL-10 in the culture supernatant from treated and non-treated animals did not differ significantly. CONCLUSION: The tyrosine kinase inhibitor AG-556 may have a role in the reduction of intimal thickening. The effect could be mediated via an immune modulating effect involving a significant increase in the smooth muscle cell inhibitory cytokine IFN-gamma.