Nonmitogenic anti-CD3F(ab')2 fragments inhibit lethal murine graft-versus-host disease induced across the major histocompatibility barrier

We have investigated the in vivo administration of nonmitogenic anti-CD3F(ab')2 fragments for the prevention of lethal graft-vs-host disease (GVHD) in irradiated recipients of fully allogeneic bone marrow cells plus splenocyte (BMS) inocula. Recipients of anti-CD3F(ab')2 fragments administered for 1 mo post-bone marrow transplantation (BMT) had 100% survival without clinical or histopathological evidence of GVHD. Controls given saline injections succumbed by 39 days post-BMT. Similar results were obtained in groups of recipient mice given BMS in which T cells were depleted by in vitro anti-Thy-1.2 plus C' treatment. Further studies were undertaken to define mechanistic differences in the two approaches. Using Ly-5 congenic sources of donor bone marrow and spleen, we determined that anti-CD3F(ab')2 fragments induced TCR modulation and T cell depletion. Mature splenic-derived CD4+ cells were depleted to a greater extent than CD8+ cells. Early post-BMT, recipients receiving injections with control saline had the highest number of CD4+ and CD8+ cells (which may cause GVHD) followed by recipients of anti-CD3F(ab')2 fragments, with the fewest CD8+ cells observed in the anti-Thy-1.2 + C' treated group. CD3+CD4-CD8- cells (which may suppress GVHD generation) were present in higher numbers early post-BMT in recipients given anti-CD3F(ab')2 fragments as compared to recipients given anti-Thy-1.2 + C'-treated BMS. In long term survivors, a mononuclear T cell containing infiltrate without evidence of destruction was observed in sites of GVHD (lung and liver), consistent with a "Quilty" effect, which was not observed in either of the other two groups. Although survivors were tolerant of donor skin grafts and rejected third party grafts, recipients given anti-CD3F(ab')2 fragments but not anti-Thy-1.2 + C'-treated BMS had vigorous anti-host proliferative responses. These results demonstrate that although in vitro anti-Thy-1.2 + C' treatment of BMS (which is highly depletionary) and in vivo administration of anti-CD3F(ab')2 fragments (which is modulatory and less depletionary) are both effective strategies for GVHD, the cellular events involved in achieving GVHD prevention are indeed different.     

Frequency dependence of MR relaxation times. I. Paramagnetic ions

T1 and T2 of paramagnetic ions in free and chelated form were measured over the range of clinical magnetic resonance imaging field strengths (0.02-1.5 T). T1 values agreed with published data; however, to our knowledge, the field dependence of T2 has not been systematically studied before Mn2+, Cr3+, and Fe3+ all showed T2 reduction at high field strengths, although reduction due to Fe3+ was minimal. This is believed to be due to "contact" interactions, which have been previously noted for manganese. No such T2 reduction was seen in the chelates, except that dysprosium chelate (but not free ion) showed an anomalous decrease in T2 at high field strengths, which may possibly be explained by a dephasing effect caused by the large magnetic moment of Dy3+.     

Sodium metabisulfite and SO2 release: an under-recognized hazard among shrimp fishermen

Since the introduction of sodium metabisulfite as a food preservative, it has been associated with several idiosyncratic reactions (eg, bronchospasm, oculonasal symptoms, and urticaria/angioedema) in sulfite-sensitive individuals. The pathogenic mechanism of these reactions is not yet understood. We report the case of two crewmen on a shrimp trawler who were found dead in the ship's hold. Their deaths had occurred while they were applying dry sodium metabisulfite, referred to as "shrimp dip" in the shrimping industry. Postmortem examinations showed diffuse pulmonary edema consistent with death secondary to asphyxia. Associated findings were visceral congestion. Although it is possible to measure death from sodium metabisulfite with available records, its potential morbidity cannot be estimated. It is known that sodium metabisulfite can react with acids and water, releasing toxic sulfur dioxide (SO2) gas. In addition, SO2 gas reacts with respiratory tissue forming sulfureous acid, and inducing a pulmonary reaction causing hypoxemia. Furthermore, sodium metabisulfite, compared with sodium bisulfite, has a much greater propensity to release SO2 gas. We conclude that there is a need for improved education regarding the potential side effects of sodium metabisulfite, thus eliminating needless occupational morbidity and mortality.     

The clinical assessment of cancer tests: a statistical approach to the prediction of "false positive" rates from controls

As the sensitivity of the new in vitro cancer detection techniques increases, a larger number of "false positive" results can be expected from control populations apparently free from malignant disease at the time of the test. An attempt is made to predict the number of unexplained positives, together with the expected age and sex distribution, using published cancer registration statistics. The predicted numbers are compared with the observed numbers of unexplained positives in two clinical trials of the MEM test.     

Imported measles. A potential control problem

From Dec 23, 1978, through Jan 31, 1979, an outbreak of five laboratory-confirmed cases and four clinical cases of measles occurred in a Vietnamese refugee population living in a single housing complex in Albuquerque, NM. The index cases were in two refugee siblings in whom measles was incubating on arrival in the United States. Despite spread through three subsequent generations of disease transmission within the Vietnamese population, there was no additional spread into the general Albuquerque population. Responsible factors included the age distribution of susceptible persons, the social isolation of the refugee population, and the physical structure of the housing complex. There is a need to identify the problem of imported measles in "ethnic islands" in need of vaccination.     

Interaction between radiation and drug damage in mammalian cells. II. The effect of actinomycin-D on the repair of the sublethal radiation damage in plateau phase cells

The effect of actinomycin-D (AMD) on radiation damage repair was studied in plateau phase V79 Chinese hamster cells. Sublethal radiation damage repair, as demonstrated by survival fluctuations following two x-ray exposures separted by time, was observed in our plateau phase cells. Plateau phase cells exposed to 0.01-0.04 mug/ml AMD (a nontoxic regimen to 8 hours) between x-ray exposures were less able to repair sublethal damage. If plateau phase cells were plated at low dilutions into fresh medium (conditions for resuming exponential growth) immediately after the first x-ray dose, and exposed to 0.01--0.04 mug/ml AMD until the second dose, inhibition of sublethal damage repair and additional cell killing were observed particularly at 0.04 mug/ml AMD. It is suggested that radiation-drug damage interactions should be studied in plateau phase cells and in cells resuming exponential growth after plateau phase (possibly analogous to "recruitment"), as well as in exponential phase cultures.     

Histochemical light microscopic study of catecholamine containing paraganglia in the human pelvis

Histological and histochemical techniques have been employed to determine the structure and autonomic innervation of paraganglia located in the human pelvis. In foetal and early postnatal tissues, paraganglia formed rounded cellular masses which were frequently in company with the autonomic nerves and ganglia of the urinary bladder and other pelvic viscera. The constituent cells contained only small amounts of cholinesterase and were unrelated to enzyme positive autonomic nerves; acetylcholinesterase containing nerves were occasionally observed in the capsule and the fibrous septa of the pelvic paraganglia. In early postnatal specimens, pelvic paraganglia frequently contained single or multiple "pacinian-like" corpuscles, each possessing a central region which was rich in both acetyl and pseudocholinesterase. These structures were rarely observed within autonomic ganglia and were absent 4 1/2 years post partum. By means of a histochemical technique, pelvic paraganglia were found to contain catecholamine which was attributed to the presence of relatively large quantities of noradrenaline. These observations have been discussed with particular reference to the results of other studies on the autonomic innervation of paraganglia.     

The heroin epidemic in San Francisco: estimates of incidence and prevalence

Much attention has recently been focused on the question of the extent of heroin use in America. In a worthwhile effort to call public attention to the problem, many estimates of its size have evidenced a tendency toward exaggeration and aggrandizement. This paper presents methods of estimation of the extent of heroin addiction which, when carefully employed, should effectively correct such distorted estimates. Two general types of estimation are employed, incidence and prevalence. Incidence estimates are concerned with new cases of heroin addiction that occur in a specific population within a given amount of time. These estimates are based upon self-report data from addicts regarding date of first addiction. When corrected for the "lag phase" (that period of time between onset of first addiction and eventual visit to a treatment program), these data permit accurate retrospective charting of incidence trends. Prevalence estimates focus on all known cases of heroin addiction in a specific population within a given amount of time. Three separate types of prevalence estimates from three separate sources are outlined in this article: estimates based on overdose death data, estimates based on crime statistics, and estimates of "unknown" addicts. In outlining these methods, this article describes the fluctuations in heroin addiction in one major American city, San Francisco, California. After analyzing data gathered from a sample of 2,367 addicts contacted over a 3-year period, this study suggests that the incidence of heroin addiction seems to have declined after 1970. Possible factors underlying this apparent decline in heroin addiction are then discussed, including the post-1970 maturation of the "population at risk," the effectiveness of antidrug media messages, the changing drug fashions in the heroin subculture, and the gradual deterioration of the quality and potency of street heroin.     

Community intervention with the elderly: a social network approach

A technique is described for using the advantages of a social systems approach when working with elderly persons in psychiatric distress. The technique is based on the assumption that the solution to a variety of human predicaments lies within the collective instrumental and affective resources of the client's social network. The vehicle for accomplishing this objective is the "Network Session" during which a mental health professional meets with the elderly person and members of his/her social network to help resolve the difficulty. A case report demonstrating use of the technique is included.     

A model for the stimulation of taste receptor cells by salt

A taste cell mucosal surface is regarded as a planar region containing bound anionic sites and openings to ionic channels. It is assumed that the bulk aqueous properties of the exterior phase are not continuous with the surface but terminate at a plane near the surface. The region between the (Stern) plane and the membrane is regarded as having a lower dielectric constant than bulk water. This fact admits the possibility of ion pair formation between fixed sites and mobile cations. Mobile ion pairs entering the region may also bind to a fixed anionic site. Thus, it is assumed that mobile cations and ion pairs are potential determining species at the surface. Binding cations neutralizes surface charges, whereas binding mobile ion pairs does not. This competition accounts for the observed anion effect on stimulation of tast receptors by sodium salts. The potential profile is constructed by superimposing the phase boundary potentials with an ionic diffusion potential across the membrane. The model accounts for the anion effect on receptor potential, pH effects, the reversal of polarity when cells are treated with FeCl3, and the so-called "water reponse," depolarization of the taste cell upon dilution of the stimulant solution below a critical lower limit. The proposed model does not require both bound cationic and anionic receptors, and further suggests that limited access to a Stern-like region continuous with membrane channels may generally serve to control transport of ions.