The effects of thermochemotherapy using cyclophosphamide plus hyperthermia on the malignant pleural mesothelioma in vivo

The human malignant pleural mesothelioma is related to the use of asbestos in the majority of cases. Though the use of asbestos has been prohibited since the 1990s, the incidence of pleural mesothelioma is still increasing because of a latency period of at least 20 years. This study investigated the benefit of single therapy with cyclophosphamide or hyperthermia or the combination of both on cells of a human pleural mesothelioma cell line, xenotransplanted subcutaneously in the paw of mice. A CONTROL group received the same volume of physiological saline. The oxygenation of tumours was measured, tumour growth was followed over 3 weeks, immunohistochemical studies and a light and electron microscopic evaluation were performed. Chemotherapy or hyperthermia alone was only temporarily effective. The greatest benefit was achieved using combined thermochemotherapy consisting of cyclophosphamide plus hyperthermia: 50% of this group had partial remissions, and 67% responded to this therapy. After 3 weeks tumours grew again. Superior effects could be achieved by performing additional cycles of chemotherapy or adding another drug or radiation for instance. This study shows promising results in the treatment of malignant pleural mesothelioma.     

Detection of capsid antigen of human papillomavirus (HPV) in benign lesions of female genital tract using anti-HPV monoclonal antibody.

We established a murine monoclonal antibody (K1H8) to human papillomavirus (HPV) using alkaline-disrupted virions of HPV type 1 (HPV-1) as the immunogen. K1H8 recognized a 57 kD capsid protein of HPV-1 and detected the antigen in paraffin sections of formalin-fixed tissue. With K1H8, we examined immunohistochemically 68 biopsy specimens obtained from the female genital tract. The specimens were histologically condyloma acuminatum or koilocytotic lesions with or without dysplasia and each specimen was found to harbour a single type of genital HPV, such as types 6, 11, 16, 18, 31, 33, 42, 51, 52, 56, and 58, by Southern blot hybridization analysis. The antigen was localized in the nuclei and occasionally in the cytoplasm of squamous cells showing koilocytotic changes. Eighty-four per cent of the specimens (57 cases) showed positivity for the antigen, indicating that K1H8 is a broadly-reactive antibody to various genital HPVs. The results suggest that benign mucosal lesions of the female genital tract are more frequently associated with viral production and are a potential source of transmission.     

Immune Abnormalities Induced by Human Endogenous Retroviral Peptides: With Reference to the Pathogenesis of Systemic Lupus Erythematosus

P15E is a specific sequence among the envelope gene (env)-encoded transmembrane proteins of exogenous and endogenous retroviruses. A synthetic peptide (CKS-17) that shows homology to this p15E region in several species of retrovirus is known to induce immune abnormalities. In this study, we examined the effect of a synthetic peptide derived from a region of human endogenous retrovirus (HERV) clone 4-1 ( 4-1) similar to sequences of CKS-17 on the induction of systemic lupus erythematosus (SLE)-related immune abnormalities. Our results indicated that this peptide could induce T-cell activation and anergy in normal peripheral blood mononuclear cells, and the peptide could also promote the production of interleukins IL-6 and IL-16. These phenomena are representative immune abnormalities observed in SLE patients. Thus, our findings support the possibility that HERV acts as a pathogen in human SLE.     

重组人免疫缺陷病毒Ⅰ型逆转录酶的纯化及其动力学性质

目的纯化重组人免疫缺陷病毒Ⅰ型逆转录酶（ＨＩＶ－１ＲＴ），筛选新的ＨＩＶ－１ＲＴ抑制剂。方法在适宜的培养条件下诱导工程菌Ｅ．ｃｏｌｉＪＭ１０９（ＰＫＲＴ２）可高效表达重组人免疫缺陷病毒Ⅰ型（ＨＩＶ－１）逆转录酶（ＲＴ）。应用ＤＥＡＥ－纤维素和磷酸纤维素离子交换柱层析法从细菌裂解液中分离、纯化重组ＲＴ。结果１升细菌培养液可得到１．１ｍｇ产物。ＳＤＳ－聚丙烯酰胺凝胶电泳分析显示所纯化的重组ＲＴ为由两个分子量分别为６６ｋＤ和５１ｋＤ的亚基组成的杂二聚体。酶活性测定结果表明，经纯化的重组ＲＴ具有很高的逆转录酶活性（比活力为１．４×１０４ｕｍｇ）。结论本文通过对ＲＴ反应条件的研究，优化了ＲＴ反应系统，并测定了磷甲酸钠（ＰＦＡ）对重组ＲＴ的抑制效应，结果表明ＰＦＡ对重组ＲＴ的抑制反应动力学机制与天然ＲＴ相同，从而进一步说明用此法纯化的重组ＲＴ可直接用于抗ＨＩＶ药物的筛选与评价。     

原位PCR技术检测石蜡包埋脑组织中人巨细胞病毒DNA

应用原位聚合酶链反应（ＩＳＰＣＲ）技术检测了２５例尸检畸形胎儿石蜡包埋脑组织中人巨细胞病毒（ＨＣＭＶ）ＤＮＡ，并与普通ＰＣＲ及原位杂交（ＩＳＨ）进行了比较。ＩＳＰＣＲ、ＰＣＲ及ＩＳＨ检测阳性率分别为４４％，３６％及２０％。与ＩＳＨ相比较，ＩＳＰＣＲ不仅检出阳性率高，而且信号强度增强。研究结果提示，ＩＳ－ＰＣＲ是诊断ＨＣＭＶ感染的快速、敏感、特异的实用方法。     

Human papovavirus in a routine urine specimen of a four-year-old boy

Cellular changes produced by viruses can be readily identified using light microscopy and Papanicolaou stain of a fixed specimen. These findings can then be confirmed by viral culture and/or electron microscopy studies. Human polyomavirus, common in transplant recipients or otherwise immunocompromised patients, is one virus that can be identified using these methods. The following is a case study of a 4-yr-old boy with no known immune impairment who exhibited human papovavirus (polyomavirus) on a routine urine examination. The diagnosis was confirmed by electron microscopy.     

Functional expression and properties of the human skeletal muscle sodium channel

Full-length deoxyribonucleic acid, complementary (cDNA) constructs encoding the-subunit of the adult human skeletal muscle Na⁺ channel, hSkM1, were prepared. Functional expression was studied by electrophysiological recordings from cRNA-injectedXenopus oocytes and from transiently transfected tsA201 cells. The Na⁺ currents of hSkM1 had abnormally slow inactivation kinetics in oocytes, but relatively normal kinetics when expressed in the mammalian cell line. The inactivation kinetics of Na⁺ currents in oocytes, during a depolarization, were fitted by a weighted sum of two decaying exponentials. The time constant of the fast component was comparable to that of the single component observed in mammalian cells. The block of hSkM1 Na⁺ currents by the extracellular toxins tetrodotoxin (TTX) and -conotoxin (CTX) was measured. The IC₅₀ values were 25 nM (TTX) and 1.2 M (CTX) in oocytes. The potency of TTX is similar to that observed for the rat homolog rSkM1, but the potency of CTX is 22-fold lower in hSkM1, primarily due to a higher rate of toxin dissociation in hSkM1. Single-channel recordings were obtained from outside-out patches of oocytes expressing hSkM1. The single-channel conductance, 24.9 pS, is similar to that observed for rSkM1 expressed in oocytes.     

Molecular mechanisms of virus-induced carcinogenesis: the interaction of viral factors with cellular tumor suppressor proteins

Accumulating evidence indicates that tumor viruses represent a major etiological factor in a significant portion of human cancers. These cancers include human papillomavirus induced anogenital cancers, hepatitis B and C virus associated hepatocellular carcinomas, nasopharyngeal carcinomas and lymphomas linked to Epstein-Barr virus infection, and human T cell leukemia virus associated adult T cell leukemias. This review summarizes the recent progress made in understanding the molecular mechanisms of viral carcinogenesis, with a particular focus on the interaction of viral factors with cellular tumor suppressor proteins. The functional inactivation of tumor suppressor proteins may represent a common strategy by which several tumor viruses contribute to malignant cell transformation.Abbreviations EBV Epstein-Barr virus - E6AP E6-associated protein - HBV Hepatitis B virus - HCC Hepatocellular carcinoma - HPV Human papillomavirus - HTLV Human T cell leukemia virus - pRb Retinoblastoma protein - RB Retinoblastoma - SV40 Simian virus 40     

Responses to eccentric rotation in two space-bound subjects

Summary Two subjects were rotated eccentrically in the manner described previously. In contrast to a normal control group, settings of a luminous line to the subjective vertical were almost unrelated to the gravitoinertial vector before, and totally so shortly after, space flight. Only 3 days postflight did a clear relation to the gravitoinertial vector re-establish itself in the one subject who actually flew. The correspondence became normal 5 days after the flight. Since there were no clinical abnormalities evident in the subjects, it is suggested that both subjects suppressed their vestibular information, presumably as an effect of vestibular deconditioning training before the flight. In addition, as a consequence of the flight experience one subject continued to ignore it several days after the flight.Abbreviations DARA Deutsche Agentur für Raumfahrtangelegenheiten - DLR Deutsche Forschungsanstalt für Luft-und Raumfahrt - ESA European space agency - ESTEC European space research and technology centre - G _z G-Units (9.81 m/s²) in z-axis direction - L-xx Launch minus xx days - R+xx Return - VESTA ESA Neurovestibular experiment facility     

Somatotopic organization along the central sulcus, for pain localization in humans, as revealed by positron emission tomography

Regional cerebral blood flow was measured with positron emission tomography (PET) in six healthy volunteers at rest and during experimentally induced, sustained cutaneous pain on the dorsum of the right hand or on the dorsum of the right foot. Pain was inflicted by intracutaneous injection of capsaicin, providing a mainly C-fibre nociceptive stimulus. Statistical analysis showed significant activations along the central sulcus (SI) area when comparing pain in the hand to pain in the foot. Separate comparison of both pain states to a baseline revealed different locations along the central sulcus for hand pain and foot pain. The encountered differences are consistent with what is previously known about the somatotopics of non-painful stimuli. When comparing painful stimuli to baseline, the contralateral anterior cingulate gyrus, the ipsilateral anterior insular cortex and the ipsilateral prefrontal cortex were implicated. The results are consistent with an involvement of SI in the spatial discrimination of acute cutaneous pain. Received: 17 October 1996 / Accepted: 12 May 1997