Development of an auxotrophic oral live Shigella flexneri vaccine

An oral live attenuated Shigella flexneri vaccine candidate strain was constructed by making it auxotrophic and dependent on aromatic metabolites not available in mammalian tissues. An aroD gene of Escherichia coli K12 strain NK 5131, inactivated by insertion in it of the Tn 10 transposon, was transduced using phage P1 into a virulent S. flexneri serotype Y strain (Sfl 1) isolated from a patient with bacillary dysentery. One of the transductant strains Sfl 114 was found to invade HeLa cells in vitro, to cause plaque formation in HeLa monolayers (i.e. maintain intracellular multiplication in vitro), but to be unable to cause keratoconjunctivitis in guinea-pig eyes. When the strain was fed to Macacca fascicularis monkeys it was well tolerated, excreted for 1-4 days, and found to elicit a local intestinal sIgA and serum IgA, IgM and IgG responses. Monkeys challenged with 100 ID50 dose (1 X 10(11) bacteria) of the virulent parent Sfl 1 strain were completely protected from development of diarrhoea. Coloscopy of the monkeys and the sampling of intestinal biopsies showed that the vaccine protected against the surface epithelial erosions and ulcerations seen in unimmunized monkeys. Killing of invading virulent shigellae apparently took place intracellularly in the mucosa suggesting that cellular immune mechanisms played a role in the elicited host defence. The constructed S. flexneri Sfl 114 strain has the properties of a promising shigella vaccine and will next be the subject of studies with human volunteers.     

Behaviors and attitudes associated with eating disorders: perceptions of college athletes about food and weight

This study surveyed male and female athletes from 22 midwesterncolleges and universities regarding behaviors and attitudesassociated with anorexia nervosa and bulimia nervosa. The responserate was 66% (N= 695) and the findings indicated that the bodyimage of some athletes may be distorted; one-seventh perceivedthemselves as fat even though they were not. Many athletes seemedpreoccupied with food and weight; almost one-third reportedroutinely thinking about food and weight and more than one-thirdreported dramatic annual weight fluctuations (9 lb or greater)related to bingeing and fasting. Athletes also did not feelin control when they ate and their habits related to food consumptionappeared to be extreme; one-tenth reported a lack of controlwhen they ate, more than one-third binged, one-twentieth ateuntil they were physically ill, and a similar proportion preferrednot to eat in the presence of others. In addition, it was foundthat as many men as women athletes reported these perceptionsbut significant sex differences were noted for specific items.It was suggested that behaviors and attitudes be viewed on acontinuum with normals at one end, eating disordered individuals at the other end,and college athletes in between. Health education that focuseson behaviors and attitudes as symptoms of eating disorders wasrecommended for athletes and those working closely with athletes.Future research was suggested to determine reasons for the undesirablebehaviors and attitudes and to study the onset, development,long-term effects and whether these behaviors and attitudeslead to an eating disorder.     

Sodium sensitivity: a determinant of essential hypertension

The epidemiologic correlation of chronic dietary salt intake among populations with the prevalence of hypertension has resulted in the concept that sodium plays an etiologic role in the development of essential hypertension (EH). However, the association of sodium intake with blood pressure in individuals within populations has been difficult to demonstrate. The differing human responses to sodium intake are dependent upon the individual level of sodium sensitivity or sodium resistance. Factors associated with sodium sensitivity are race, age, and other dietary factors. More recent investigations have pursued the interaction of sodium intake with other physiologic parameters including neurogenic activity, vascular structure, renal function, and other cations such as potassium and calcium. The observations that some humans demonstrate very little increase in blood pressure despite high levels of sodium intake supports the concept that a high sodium intake alone is not a single causal factor in hypertension. Sodium intake appears to interact with renal excretory capacity and vascular compliance. These varying physiologic functions must be delineated to characterize sodium sensitivity.     

Ankle injuries and the family physician

In transmitting the body's weight, the ankle is subject to frequent static and dynamic injury due to concentrated stresses during standing and movement. The frequency of athletic ankle injuries ranges from 10 to 90 percent, with the highest rate occurring in basketball players. There is prolonged disability and recurrent instability for months to years for 25 to 40 per cent of these patients. Because most of this trauma is handled by primary care physicians, this review presents the mechanism of injury, relevant anatomy, physical examination, and appropriate therapeutic intervention in the acute and rehabilitative phases.     

Theoretical and practical considerations in the doubly-labelled water (2H2(18)O) method for the measurement of carbon dioxide production rate in man

In the doubly-labelled water (2H2(18)O) method for the measurement of carbon dioxide production rate in man, single exponential disappearance curves for 2H2O and H2(18)O in body water are used; the precision with which the slopes and intercepts of the curves are estimated determines the precision of the estimate of carbon dioxide production rate. In studies with infants, and in computer simulations, the effect of different experimental regimes on the overall precision of the carbon dioxide production estimate was investigated. When the number of data points used was progressively reduced by shortening the total observation period from 7 d (about 3 biological half-lives for the isotopes) to 1 d there was a deleterious effect on precision and in the infants there was an upward bias in the values for carbon dioxide production. When the number of data points was reduced by removing points from the middle of the exponential curves with the maintenance of the 7-d experimental period, precision was also reduced but by less than in the former procedure and there were no consistent trends in the average values for carbon dioxide production.     

Chorioretinal folds and a macular hole secondary to craniofacial surgery

Chorioretinal folds have been reported as a result of many intraocular and extraocular inflammatory processes or tumors. Visual loss is usually secondary to a combination of the underlying process and chorioretinal folds involving the macula. We report a patient who developed decreased vision, metamorphopsia, chorioretinal folds, and a lamellar macular hole secondary to global compression by a bone fragment. The chorioretinal folds regressed and his vision stabilized following surgical decompression. Chorioretinal folds and lamellar macular hold formation are previously unrecognized complications of reconstructive craniofacial surgery.     

Phase I evaluation of diaziquone in childhood cancer

Summary We conducted a phase I clinical study of aziridinylbenzoquinone (Diaziquone, AZQ) given as a 4 hour infusion weekly × 4. Forty-five children with recurrent acute leukemia and 33 children with various advanced solid tumors participated. Severe myelosuppression was the dose limiting toxic effect, occurring in all patients at the upper dose levels. Gastrointestinal and hepatic toxicities were infrequent and not severe. No allergic reactions occurred. Objective tumor regression was noted in 3 of 25 patients with a CNS tumor and in 6 of 45 patients with acute leukemia. For phase II trials the recommended dosage of Diaziquone given by this schedule is 18 mg/M²×4 for patients with a solid tumor, and is 30 mg/M²/week × 4 for children with acute leukemia.     

Development of a protein phosphatase-based assay for the detection of phosphatase inhibitors in crude whole cell and animal extracts

Diarrhetic shellfish poisoning (DSP) is a serious and globally widespread phytoplankton-related seafood illness. Although DSP is rarely life-threatening, it causes incapacitating diarrhea and vomiting with no known medical treatments. In addition, phytoplankton producing DSP toxins have been identified in temperate coastal waters worldwide, and their numbers may be increasing as a result of coastal eutrophication. The toxic effects of the major DSP toxins, okadaic acid and dinophysistoxin-1 (35-methylokadaic acid), appear to originate from their inhibitory activity against a family of structurally related serine/threonine protein phosphatases (PSPases). In particular, the inhibition of essential PSPases (e.g. PP1 and PP2A) has catastrophic consequences in most eukaryotic cells. Exploiting the potent inhibitory property of the DSP toxins, we have developed an enzyme-based assay (PP2A assay) capable of detecting both okadaic acid and dinophysis- toxin-1 in nanogram amounts. The assay employs purified PP2A, which has an extremely high affinity for both DSP toxins. This provides the PP2A assay with a level of sensitivity comparable to, or surpassing, that of most monoclonal antibody probes. To evaluate the PP2A assay as a means of detecting contaminated shellfish, a series of spike recovery experiments was conducted. The findings from these studies suggest that the PP2A assay has the potential for development into a rapid and relatively simple method for detecting PSPase inhibitors in crude extracts produced from shellfish.