Cell biology and possible therapeutic applications of anti-CD3-activated killer-T cells (review)

Polyclonal T lymphocyte populations can be stimulated with anti-CD3 antibody to proliferate, secrete cytokines, and mediate MHC-unrestricted cytotoxic activity against a wide range of tumor target cells. Because anti-CD3-activated killer-T (AK-T) cells may be useful in the immunotherapy of human cancers, it is important to understand the signaling pathways and cell-surface structures involved in the induction and tumoricidal effector function of AK-T cells. Studies in the mouse model system have characterized the cytokines, signal transduction pathways, and costimulatory molecules involved in AK-T cell development. The recognition/adhesion and subsequent signaling events which lead to tumoricidal activity by mouse AK-T cells have also been defined. These findings, providing they translate accurately to the human system, may allow for the design of effective strategies to use AK-T cells for the treatment of human cancers. However, to date, the encouraging results obtained with anti-CD3 antibody/AK-T cell-based immunotherapies in mouse models of cancer have not been duplicated in clinical trials. The most likely explanation for this dis-appointing result is that tumor-reactive T lymphocytes in long term tumor-bearers fail to function correctly in the tumor microenvironment due to tumor-induced immune suppression and defects in key signal transduction molecules. It is clear that a detailed understanding of the inhibitory effect of established tumors on host T cells and the means to overcome tumor-induced immunosuppression are needed before anti-CD3 antibody/AK-T cell-based immunotherapies can be expected to succeed in the clinical setting.     

Confirmation that Thiobacillus halophilus and Thiobacillus hydrothermalis are distinct species within the gamma-subclass of the Proteobacteria

BACKGROUND: There is controversy regarding the most appropriate investigation for suspected colorectal carcinoma. We offered these patients same-day flexible sigmoidoscopy (FS) and double-contrast barium enema (DCBE). METHODS: We reviewed the results of 117 consecutive adult patients. All patients underwent FS followed by DCBE on the same day. The radiographs were reviewed by two of the authors who were blinded to the clinical information, flexible sigmoidoscopy reports, and the original DCBE report. RESULTS: One hundred seventeen patients made up the study population. Thirty-four of the 117 patients had polyps and/or carcinoma. Three malignant tumours were detected by DCBE; one of these was also seen on FS, and the other two cancers were out of FS range. Fifty-three polyps were found by FS; nine were removed by biopsy prior to the enema examination. Of the 44 remaining polyps, DCBE failed to detect 87% of the 0-9-mm group and 67% of the >9-mm group. Ten polyps were seen only on DCBE; seven of these 10 were beyond the range of the sigmoidoscope, and the three remaining polyps were less than 5 mm. CONCLUSION: DCBE is insensitive in the detection of rectosigmoid polyps. FS should continue to be used as a complementary examination to DCBE in the investigation of suspected colorectal carcinoma.     

Study of the pulsation method for the hygienic treatment of underwear

Hygienic processing of the underwear in a device combining mechanical treatment, forced pumping of the washing solution and wringing by compressed air can be used under special conditions. The basic parameters of the engineering process have been determined, viz.: the number of washing baths, temperature of the water, time of processing, etc.     

Biological impact of small air ions

The thrust of the experimental data presented here is that small air ions are biologically active. There is convincing evidence that both negative and positive ions (i) inhibit growth of bacteria and fungi on solid media; (ii) exert a lethal effect on vegetative forms of bacteria suspended in water when opportunity is provided for contact of cells and ions; and (iii) reduce the viable count of bacterial aerosols. Through physical action, ions of either charge upset the stability of aerolosized bacterial suspensions and, in addition, have a direct lethal effect which is more prominent with negative ions than with positive ions. With regard to the serotonin hypothesis of air ions action, the situation is more complex. The essential fact is that mice and rats display a charge-related metabolic response to air ions and this phenomenon also occurs in humans. Because serotonin is such a potent hormone, the ultimate functional changes incident to air ion action are impressive and account for the signs of symptoms of the sharav syndrome. Alterations in the cumulative mortality rate with three experimental respiratory disease in the mouse also are charge-dependent, positive ions routinely exercising a detrimental effect. Further, in the case of mice infected with influenza virus, ion-deprivation increases the cumulative mortality rate. Since ion depletion is a constant concomitant of modern urban life, one reasonably may speculate about comparable inimical effects on humans.     

Long-acting narcotic antagonist complexes

We evaluated the ability of close to 100 organic acids to form water-soluble salts with methadone, cyclazocine, naloxone, naltrexone and, more recently, diprenorphine. About half the acids yielded insoluble salts. Polybasic acids affording insoluble salts were evaluated for their ability to form drug:acid:metal complexes with the polyvalent metal ions, Zn++, Al+++, Mg++ and Ca++. Optimum conditions for forming complexes have been developed and the consistency of their composition has been established. Salts were analyzed spectrophotometrically for drug content, and complexes were analyzed for drug and metal content. The in vitro degree of dissociation at equilibrium was measured for the preparations suspended in a simulated physiological buffer, pH 7.3. Preparations of the narcotic antagonist drugs showing relatively low degrees of dissociation in vitro, since it early appeared that a high degree of dissociation contraindicated a prolonged duration of pharmacological action, were evaluated in mice after intramuscular administration at several dose levels by the mouse tail-flick test for the potency and duration of their morphine antagonist activity. Our most promising preparations to date, showing the most prolonged durations of action without evidence of gross toxicity, are naltrexone zinc tannate and naltrexone aluminum tannate. These are undergoing detailed evaluation as potential clinical candidates. Thus far, the most useful of several dosage forms studied is a suspension in an aluminum monostearate gel.     

Phenomenon of life span instability in Drosophila melanogaster: I. Nonrandom origin of life span variations in successive generations

The dynamics of life span (LS) and fecundity in Drosophila melanogaster, strain D-32, were analyzed in a series of successive generations. Highly reliable variations in both fitness components were found. On initial inspection the variations would be characterized as random or irregular wherein mean values differed up to threefold. The variance in longevity is greater in females than in males. By use of mathematical procedures we have shown a scale regularity in LS distributions for all generations. Such regularity, in spite of considerable differences in absolute values (mean and maximum LS), suggested that the origin of LS instability is nonrandom.     

Molecular genetic investigations of autism

Genetic factors are likely to play a major role in the etiology of autism. The genetics of the disorder is however complex, probably involving the action of several genes. In an attempt to identify autism susceptibility loci we are currently undertaking a systematic screening of the whole human genome using multiplex families. We describe the resources and the methods needed to achieve such a task, including extensive collection of family data, semiautomated genotyping technology, and specialized statistical approaches for linkage analysis of complex traits.     

Edema associated with I-125 or Pd-103 prostate brachytherapy and its impact on post-implant dosimetry: an analysis based on serial CT acquisition

PURPOSE: To characterize the magnitude and duration of post-implant edema following the implantation of I-125 or Pd-103 seeds into the prostate and to investigate its effect on the CT-based calculation of the total dose delivered by the implant. MATERIALS AND METHODS: A pre-implant CT scan and 3 to 5 serial post-implant CT scans were obtained on 10 patients who received either I-125 or Pd-103 seed implants. None of the patients received hormone therapy. The magnitude and duration of edema were determined from the change in the spatial distribution of the implanted seeds as the edema resolves. Dose volume histograms were compiled to determine the percentage of the prostate volume that received a dose equal to, or greater than, the prescribed dose. RESULTS: The magnitude of the edema, expressed as the ratio of the post- to pre-implant volume on the day of the procedure, ranged from 1.33 to 1.96 (mean 1.52). The edema decreased exponentially with time; however, the edema half-life (time for the edema to decrease by 1/2) varied from 4 to 25 days (mean 9.3 days). As the edema resolved, the percentage of the prostate that received a dose equal to or greater than the prescribed dose increased by at least 7% in 7 of the 10 patients and increased by more than 15% in 2. In those patients in whom dose coverage was unaffected by the resolution of edema, more than 90% of the prostate was covered by the prescribed dose in the initial CT scan. CONCLUSION: Post-implant edema increased the prostate volume by factors which ranged from 1.33 to 1.96 (mean: 1.52). The edema resolved exponentially with an edema half-life which varied from 4 to 25 days (mean: 9.3 days). Edema had a significant effect on the post-implant dosimetry in 7 of 10 cases. Factors that affect the impact of edema on the dosimetry are the magnitude of the edema and the planned margin between the prescribed isodose line and the periphery of the prostate.     

Visualization of vortex shedding at the proximal side-to-end artery-graft anastomosis

The motion of guanine particles was recorded by video to visualize transitional flow phenomena in models of a proximal side-to-end anastomosis. Close examination of successive video fields revealed that above a critical Reynolds number, particles were periodically shed into the graft from a vortex situated near the anastomosis heel, and this disturbed the flow patterns in the graft causing vortex shedding to occur near to the toe of the anastomosis. The images clearly demonstrated that periodic flow structures propagated distally along the graft for over 15 tube diameters from the proximal anastomosis. The frequency of the vortex shedding was found to increase with Reynolds number. Under pulsatile conditions, the primary vortex at the heel of the anastomosis became unstable during the deceleration phase of the flow cycle and particles were shed downstream into the graft. Although it was possible briefly to observe the characteristic banded structure in the bypass graft, the flow patterns were highly three-dimensional and were quickly broken up by the accelerating flow. Dynamic flow visualization using guanine particles was found to be a complementary technique to particle tracer flow visualization and was highly effective in identifying transitional flow phenomena and the mass transport mechanisms associated with them.