Immunodiagnosis of sexually transmitted disease.

Methods for detecting microbial antigens in clinical specimens offer an alternative to culture in the diagnosis of some sexually transmitted diseases. Developers of the immunologic methods are faced with a number of problems in evaluating the new tests. Traditionally, these tests are compared to culture as the "gold standard." Unfortunately, culture for Neisseria gonorrhoeae or Chlamydia trachomatis--the two agents most commonly sought--is considerably less sensitive than 100 percent. Immunologic methods may appear to produce false positives when the paired specimens are actually false-negative cultures. Another source of discordant results is sampling variation. These considerations, however, will not account for all false-positive results. Even the best non-culture methods have a low rate of false-positive results. If a new test has a specificity of 97 percent, it, by definition, yields approximately 3 percent false-positive reactions. In low-prevalence settings this false-positive rate will create problems in interpreting the results. For example, in a population with 3 percent prevalence of infection, a positive result in a 97 percent specificity test could only have a predictive value of 50 percent. Most testing for STD agents is performed in low-prevalence settings. None of the currently available immunodiagnostic procedures has a performance profile that suggests it will be satisfactory for diagnostic use in the low-prevalence setting

Human pancreatic cancer cell lines do not express receptors for somatostatin.

The in vivo administration of somatostatin (SS) or its analogues is capable of suppressing the growth of pancreatic cancer in experimental animals. We examined the effects of SS-14 and its analogue RC-160 on the in vitro growth of two human pancreatic cancer cell lines MiaPaCa-2 and Panc-1 stimulated with epidermal growth factor (EGF) or insulin-like growth factor 1 (IGF-1). Neither SS-14 nor RC-160 inhibited the growth of either cell line. In contrast RC-160 did inhibit the EGF-stimulated growth of a rat pancreatic cancer cell line AR42J. Binding studies with 125I-Tyr11 somatostatin revealed the presence of a single class of high affinity binding sites with a Kd of 0.20 +/- 0.05 nM and a Bmax of 2.1 +/- 0.26 pmoles mg-1 protein on AR42J but not displaceable binding was observed on MiaPaCa-2 or Panc-1. We conclude that lack of receptors accounts for the failure of SS-14 and RC-160 to influence the growth of human pancreatic cancer in vitro. These results, taken together with other findings, lead us to question the therapeutic efficacy of somatostatin and its analogues as mono-therapy in the treatment of human pancreatic cancer

Inhibition of pancreatic cancer cell growth in vitro by the tyrphostin group of tyrosine kinase inhibitors.

Tyrphostins are a group of low molecular weight synthetic inhibitors of protein tyrosine kinases (PTK). The intracellular domains of the receptors for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), insulin-like growth factor 1 (IGF-1) possess PTK activity. Since EGF, TGF-alpha and IGF-1 are considered to play an important role in the proliferation of pancreatic cancer cells, we studied the effects of tyrphostins on the growth of three human pancreatic cancer cell lines (MiaPaCa-2, Panc-1 and CAV). The tyrphostins AG17, T23 and T47 all inhibited EGF and serum-stimulated DNA synthesis. AG17 was found to be the most potent of these agents and caused a dose-dependent but reversible inhibition of cell growth. Furthermore using an immunoblotting procedure we also found AG17 to inhibit EGF-induced tyrosine phosphorylation in the MiaPaCa-2 cell line. Tyrosine kinase inhibitors may prove to be useful agents for the treatment of pancreatic cancer

Pulmonary function evaluation during and following Skylab space flights

Previous experience during the Apollo postflight exercise testing indicated no major changes in pulmonary function. Although pulmonary function has been studied in detail following exposure to hypoxic and hyperoxic environments, few studies have dealt with normoxic environments at reduced total pressure as encountered during the Skylab missions. Forced vital capacity was measured during the preflight and postflight periods of the Skylab 2 mission. Initial in-flight measurements of vital capacity were obtained during the last two weeks of the second manned mission (Skylab 3). Comprehensive pulmonary function screening was accomplished during the Skylab 4 mission. The primary measurements made during Skylab 4 testing included residual volume determination, closing volume, vital capacity, and forced vital capacity and its derivatives. In addition, comprehensive in-flight vital capacity measurements were made during the Skylab 4 mission. Vital capacity was decreased slightly during flight in all Skylab 4 crewmen. No major preflight to postflight changes were observed in the other parameters

Focus on Adoptive T Cell Transfer Trials in Melanoma

Adoptive Cell Transfer (ACT) of Tumor-Infiltrating Lymphocytes (TIL) in combination with lymphodepletion has proven to be an effective treatment for metastatic melanoma patients, with an objective response rate in 50%–70% of the patients. It is based on the ex vivo expansion and activation of tumor-specific T lymphocytes extracted from the tumor and their administration back to the patient. Various TIL-ACT trials, which differ in their TIL generation procedures and patient preconditioning, have been reported. In the latest clinical studies, genetically engineered peripheral T cells were utilized instead of TIL. Further improvement of adoptive T cell transfer depends on new investigations which seek higher TIL quality, increased durable response rates, and aim to treat more patients. Simplifying this therapy may encourage cancer centers worldwide to adopt this promising technology. This paper focuses on the latest progress regarding adoptive T cell transfer, comparing the currently available protocols and discussing their advantages, disadvantages, and implication in the future

Characterization of the Horizontal and Vertical Sexual Transmission of Chlamydia Genital Infections in a New Mouse Model.

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide, and there is a need to control this epidemic. So far there is no established animal model in which both the horizontal and the vertical transmission of Chlamydia can be studied. To implement a horizontal sexual transmission model, male mice were inoculated in the meatus urethra with Chlamydia muridarum and they were caged with naive female mice. Urine and vaginal swab specimens were collected for culture. To study vertical transmission, newborns were euthanized and specimens were cultured. As controls, females were mated with sham-infected male mice. All C. muridarum-inoculated male mice had positive urine cultures. As determined by serology, all females caged with C. muridarum-inoculated males became infected, and 93% of them had positive vaginal swab specimen cultures. More females mated with C. muridarum-infected male mice (35%) than females mated with sham-infected male mice (0%) were infertile (P < 0.05). Also, C. muridarum-infected females delivered significantly fewer pups (3.8 ± 3.2/mouse) than control females (6.3 ± 1.6/mouse) (P < 0.05). Of the newborn mice, 32% were C. muridarum positive either in the lungs or in the intestines. Female mice housed with sham-infected males had no positive vaginal swab specimen cultures or C. muridarum-positive pups. This new mouse model of horizontal and vertical sexual transmission of Chlamydia closely parallels C. trachomatis sexual transmission in humans and may be a good model system to better understand the pathogenesis of these infections

Radio Luminosities and Classificatory Criteria of BL Lacertae Objects

Using the sample of radio selected BL Lacertae objects (RBLs) and X-ray selected BL Lacertae objects (XBLs) presented by Sambruna et al. (1996), we calculated the luminosities of radio, optical and X-ray of each source and made the statistical analysis among the luminosities at different wave-bands, broad-band spectral indices from radio to X-ray ($\alpha_{\rm rx}$) and peak frequencies ($\nu_p$). Our results are as follows: (i) there is a positive correlation between radio luminosity $L_{\rm r}$ and $\alpha_{\rm rx}$ and a negative correlation between $L_{\rm r}$ and $\nu_p$. High-energy peak BL Lacs (HBLs) and low-energy peak BL Lacs (LBLs) can be distinguished very well, the dividing lines are probably those of $\log {L_{\rm r}}=43.25$ (erg/sec) and $\alpha_{\rm rx}>$(or $\leq$)0.75 for $L_{\rm r}$ - $\alpha_{\rm rx}$ plot and those of $\log {L_{\rm r}}\leq 43.25$ (erg/sec) and $\log {\nu_p}>14.7$ for the $L_{\rm r}$ - $\nu_p$ plot; (ii) there is a weak positive correlation between optical luminosity $L_o$ and $\alpha_{\rm rx}$ and a negatively weak correlation between $L_{\rm o}$ and $\nu_p$; (iii) there is no correlation between X-ray luminosity $L_X$ and $\alpha_{\rm rx}$ or between $L_X$ and $\nu_p$. From our analysis, we find that synchrotron radiation is the main X-ray radiation mechanism for HBLs while inverse Compton scattering for LBLs.Comment: 9 pages, 3 figures. Submitted to A&