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Biomedical subjects

E H Kass

Publications and source records attributed to E H Kass.

At least 19 recordsLinked to original sources

Prevention of preterm delivery and low birth weight associated with asymptomatic bacteriuria.

Since the first report of an association between asymptomatic bacteriuria and low birth weight (less than 2,500 g) in 1962, greater than 30 other studies on the same subject have been published. Some of these confirmed this association while others disputed it. Now, however, by using meta-analysis (a technique considered valid by many but not all statisticians) one may conclude with increased certainty that true associations between asymptomatic bacteriuria and preterm delivery (less than 37 weeks of gestation) and asymptomatic bacteriuria and low birth weight do exist. Because asymptomatic bacteriuria in pregnancy remains prevalent and preventable, a review of this important subject is relevant at this time.

Bacteriuria

Activation of in vitro proliferation of human T cells by a synthetic peptide of toxic shock syndrome toxin 1.

A 21-mer synthetic peptide (KGEKVDLNTKRTKKSQHTSEG), designated TSST-1(58-78), was constructed from the primary structure of the toxic shock syndrome toxin 1 (TSST-1). The peptide reacted with a panel of neutralizing monoclonal antibodies (MAbs) to whole TSST-1 in solid-phase immunoassays. TSST-1(58-78) promoted the in vitro proliferation of human peripheral blood mononuclear cells (PBMC) in a dose-dependent manner. Minimum dose required for stimulation (P less than or equal to .05 microM) was 0.75 microM peptide. This mitogenic effect was abrogated by incubation of the peptide with MAbs to whole TSST-1 before addition to PBMC. The ability of TSST-1(58-78) to stimulate the proliferation of highly purified resting human T cells was analyzed. Significant proliferation (P less than or equal to .01) was observed only in the presence of increasing populations of monocytes added to the cultures. Adherent human monocytes exposed to TSST-1(58-78) released tumor necrosis factor. Thus, some of the immunoregulatory properties attributed to TSST-1 are demonstrated by the region of the toxin represented by the peptide TSST-1(58-78).

Amino Acid Sequence

Influence of magnesium concentration on production of exoprotein and beta-lactamase by Staphylococcus aureus and Staphylococcus hemolyticus.

Earlier investigations demonstrated that production and secretion of toxic shock syndrome toxin-1 (TSST-1) and total exoprotein by strains of Staphylococcus aureus were maximal when magnesium ion was limiting and diminished when the concentration of magnesium increased. This investigation studied the influence of magnesium concentration on production of total exoprotein and beta-lactamase by strains of S. aureus and Staphylococcus hemolyticus, isolated from the genital tracts of women. These strains were resistant to penicillins. Each organism was incubated in chemically defined medium with various concentrations of magnesium, and total exoprotein production and beta-lactamase activity in supernatants were determined. In all strains, total exoprotein production and beta-lactamase activity per bacterial cell were markedly increased in the presence of low concentrations of magnesium. When the concentration of magnesium was elevated, production of total exoprotein and beta-lactamase was decreased. Therefore, magnesium-deficient strains of S. aureus and S. hemolyticus may secrete more exoproteins and be more resistant to beta-lactam drugs than when magnesium is not limiting.

Bacterial Proteins

Identification of functional antigenic segments of toxic shock syndrome toxin 1 by differential immunoreactivity and by differential mitogenic responses of human peripheral blood mononuclear cells, using active toxin fragments.

When toxic shock syndrome toxin 1 was subjected to papain hydrolysis, two serologically active fragments of 16.3 kilodaltons (16K fragment) and 12.4 kilodaltons (12K fragment) were generated, whereas a third fragment of 9.7 kilodaltons (10K fragment) was inactive. The biologic activities of the fragments were evaluated in vitro by determining their ability to promote nonspecific proliferation of human peripheral blood mononuclear cells. The 12K fragment was significantly (P less than or equal to 0.013) more stimulatory than the 16K fragment. When human peripheral blood mononuclear cells were preincubated for a period of 24 h with various concentrations of the 16K fragment, followed by incubation with a constant amount (2 x 10(-2) ng/ml) of whole toxin, the level of DNA synthesis induced by the holotoxin was reduced by approximately 60% when compared with that of controls exposed to whole toxin alone. The 12K fragment did not demonstrate a similar blocking effect. Immunoblots of the toxic shock syndrome toxin 1 digest, which were exposed to monoclonal antibodies (MAbs) developed against native toxin, depicted the presence of two different antigenic regions (epitopes). One MAb, 8-5-7, which has been shown previously to inhibit the biologic activity of the holotoxin in vitro and in vivo, reacted primarily with the 12K fragment. A second MAb, 10-6-1, that did not neutralize interleukin-1 production reacted primarily with the 16K fragment. On the basis of the differential mitogenic responses and the identification of heterologous epitopes, it was concluded that the functional region of the holotoxin can be partitioned into at least two functional segments encompassed between amino acid residues 53 and 87 and between amino acid residues 88 and 194 on the polypeptide chain.

Antibodies, Bacterial

Low blood pressure in vegetarians: effects of specific foods and nutrients.

Strict vegetarians, who eat little if any animal products and lactovegetarians, who regularly eat dairy products, have lower blood pressures than the general population after adjustment for the effects of age, sex, and body weight. Controlled dietary trials were undertaken to determine the dietary basis for the differences in BP between vegetarians and nonvegetarians. Exchanging meat and eggs for vegetable products; increasing total dietary protein or replacing soy protein with dairy protein; exchanging saturated, monounsaturated, and polyunsaturated fatty acids; and changing the content of total dietary fat and carbohydrate all had no substantial effect on BP. Therefore, animal products, carbohydrate, and different types of fats do not appear to explain the low BP in vegetarians. Rather, modest intake of animal products may be a marker for a large intake of other potentially beneficial nutrients from vegetable products.

Age Factors

Effect of magnesium on production of toxic-shock-syndrome toxin-1: a collaborative study.

We performed a series of collaborative experiments to clarify the effect of Mg++ on production of toxic-shock-syndrome toxin-1 (TSST-1) in various culture media. TSST-1 production was enhanced by adding ethylenediamine-tetraacetic acid (EDTA) at appropriate concentrations to brain-heart infusion and beef-heart medium. The magnitude of this effect depended both on the number of bacteria used to inoculate the media and on the sampling time. Large inocula prepared in media containing high levels of Mg++ introduced sufficient Mg++ to the growth medium to influence subsequent bacterial multiplication and toxin production. Small inocula of bacteria washed in Mg++-deficient medium before inoculation did not, however, multiply or produce toxin in Mg++-deficient medium. Maximal toxin expression occurred during late logarithmic phase, regardless of Mg++ concentration, and Mg++ appeared to control when late logarithmic stage of growth would be achieved. The toxin-enhancing effect of EDTA was reversed by adding excess Mg++ to treated medium.

Bacterial Toxins

Structure-activity relationship of toxic-shock-syndrome toxin-1: derivation and characterization of immunologically and biologically active fragments.

Toxic-shock-syndrome toxin-1 (TSST-1), a 22-kilodalton (kDa) polypeptide, was proteolyzed by papain, generating three distinct fragments, identified as 16, 12, and 10 kDa (based on molecular masses estimated from the predicted amino acid sequence). The NH2-terminal sequence analysis of the fragments indicated that the peptide bonds between Tyr-52 and Ser-53 and between Gly-87 and Val-88 were cleaved. Functional activity, evaluated through enzyme-linked immunosorbent and inhibition assays, was demonstrated only with the 16- and 12-kDa fragments. The presence of homologous and heterologous antigenic determinants on the fragments was demonstrated by immunoblotting. In in vitro stimulation of human peripheral blood mononuclear cells, the 12-kDa fragment was significantly (P = .003) more active than the 16-kDa fragment. The former composed 75% of the latter and occupied the COOH-terminal portion of the holotoxin. The functional domains were located on two-thirds of the TSST-1 molecule, toward the COOH-terminal end, and mitogenicity apparently was separable from serological activity.

Amino Acid Sequence

Magnesium, Staphylococcus aureus and toxic shock syndrome.

In vitro studies led us to a new, coherent hypothesis for the pathogenesis of toxic shock syndrome (TSS). These studies show a hitherto unsuspected role of Mg in the pathogenesis of a serious microbial disease, and suggest one of several possible approaches to the prevention of the disorder.

Antibodies, Bacterial

Effect of linoleic and oleic acids on blood pressure, blood viscosity, and erythrocyte cation transport.

It has been proposed that dietary linoleic acid lowers blood pressure (BP) by being converted to arachidonic acid and prostanoids of the two-ene series. We tested the effects of linoleic acid on plasma arachidonic acid, blood pressure, blood viscosity, and RBC cation transport. Oleic acid, the major dietary monounsaturated fat and which is not a prostanoid precursor, was used as a control. Seventeen adults consumed 23 g/d of linoleic acid or oleic acid provided by genetic variants of safflower seed, each for 4 weeks in a double-blind crossover design. Linoleic and oleic acids were enriched significantly in the plasma cholesteryl esters, phospholipids and triglycerides during the respective periods of supplementation but there was no increase in arachidonate. Mean BP was 116.1/76.8 during ingestion of oleic and 113.6/74.6 during ingestion of linoleic acid (p = 0.09 systolic, p = 0.12 diastolic). The power of the study was over 75% for detecting a significant (p less than 0.05) effect of 4 mm Hg in systolic BP or diastolic BP. Whole blood and plasma viscosity, and RBC Li/Na countertransport, Na/K cotransport, and Na pump systems (Vmax) were unchanged during the protocol. Therefore, variations in dietary linoleic or oleic acids are unlikely to have major effects on BP or on several membrane-dependent erythrocyte functions related to hypertension.

Adult

Does prolonged exposure to antibiotic-resistant bacteria increase the rate of antibiotic-resistant infection?

The magnitude of the risk of acquiring infections due to antibiotic-resistant bacteria, as a consequence of prolonged contact with such bacteria, is unclear. We compared antibiotic resistance patterns of Escherichia coli isolated from the urine of bacteriuric female abattoir workers with resistance patterns of E. coli cultured from 190 poultry taken from the processing line. We found E. coli in 181 (95%) of the poultry cultures; 96% of the isolates were resistant to one or more antibiotics, and 87% were multiply resistant. Of the 649 women whose urine was cultured and who had not recently received antibiotic therapy, 69 (10.6%) had positive urine cultures, with E. coli accounting for 67% of the isolates. Of the 46 E. coli isolates, 8 (17.4%) were resistant to one or more antibiotics. All of the antibiograms of the urinary isolates were unique, and only one, a strain with resistance only to streptomycin, matched those of any of the poultry isolates. Of the women tested for bacteriuria, 74 had taken antibiotics within 3 months of culture, and these women were analyzed separately. Among the recent antibiotic users, six (8.1%) had positive urine cultures, all with E. coli. Four of these isolates were resistant to at least one antibiotic; all had patterns that matched at least one of the poultry isolates. Therefore, in a population of female abattoir workers who were not receiving antibiotic therapy, despite a high exposure to resistant microorganisms of animal origin, infections were infrequently caused by organisms with resistance patterns characteristic of the livestock to which the women were heavily exposed.

Abattoirs

Quantitative assessment of vaginal microflora during use of tampons of various compositions.

Although the effect of vaginal tampons on the microbial flora during menstruation has recently been studied by several investigators, quantitative effects attributable to particular tampon fibers have received less attention. The purposes of the present study were (i) to determine and then to compare the effects of polyacrylate rayon tampons and viscose rayon tampons on the normal vaginal flora, (ii) to compare quantitative bacterial counts obtained from these tampons with those obtained from concomitant vaginal swabs, and (iii) to determine whether either of these tampon types alters the vaginal microflora when compared with the microflora in the same women using all-cotton tampons or external catamenial pads. Tampon and swab samples were obtained at predetermined times from 18 women for an average of seven menstrual cycles. Samples consisting of swabs from women wearing menstrual pads were compared with swab and tampon samples taken at predetermined times during the menstrual cycle from women using cotton, polyacrylate rayon, or viscose rayon tampons. Samples were analyzed for total aerobic, facultative, and anaerobic bacterial counts. Statistical evaluation of the results indicated that, on the whole, total bacterial counts decreased during menstruation and that the numbers of bacteria in tampons tended to be lower than those in swab samples taken at the same time. The tampon type had little effect on the vaginal microflora.

Adult

Qualitative assessment of vaginal microflora during use of tampons of various compositions.

The effect of vaginal tampons on the microbial flora during menstruation has recently been studied by several investigators. However, little information regarding the qualitative effects attributable to particular tampon fibers is available. The purpose of the present study was to compare the effects of polyacrylate rayon tampons and cotton-viscose rayon blend tampons on the qualitative bacterial counts obtained from tampons and concomitant vaginal swabs and to determine whether either of these tampon types alters the qualitative makeup of the vaginal microflora when compared with the microflora in the same women using all-cotton tampons or external catamenial pads. Tampon and swab samples were obtained as described previously (A. B. Onderdonk, G. R. Zamarchi, M. L. Rodriguez, M. L. Hirsch, A. Muñoz, and E. H. Kass, Appl. Environ. Microbiol. 53:2774-2778). The genus and species of the six dominant bacterial species in each sample were identified, if possible. A statistical evaluation of the qualitative makeup of the microflora revealed that the same numerically dominant phenotypes were present regardless of sample type, sample time, or catamenial product. Predictable changes in total numbers among the dominant species were also noted when the data were evaluated by day of menstrual cycle. The correlation between the total numbers of each dominant species present was evaluated by day of cycle, and the findings are discussed.

Adult

Absence of significant cellulase activity in microbial flora of the female genital tract.

It has been postulated that toxic shock syndrome may be mediated by the hydrolysis of certain tampon fibers by bacteria of the female genital tract, leading to the release of glucose that would in turn serve as a substrate for the multiplication of staphylococci producing the toxic shock marker protein (TSST-1). We sought cellulolytic organisms among microorganisms isolated from the female genital tract throughout the menstrual cycle. A total of 288 aerobic and facultative vaginal isolates from 13 healthy female volunteers, aged 18 to 25, and 57 anaerobes from the same sources were screened for cellulase activity. No evidence of production of glucose or degradation of cellulose was found; hence, none of the strains could be described as cellulolytic. A total of 44 organisms (12.7%) showed weak endoglucanase activity as evidenced by minimal changes in the viscosity of the cellulose substrate, but this activity was not reproducible in all of the strains and was inconstantly observed on repeated examination. Five strains of Staphylococcus aureus isolated from cases of toxic shock syndrome also showed no cellulase activity. Cellulase activity does not appear to be a frequent or regular feature of the microflora of the human female genital tract.

Adolescent

Nonproduction of toxic shock syndrome toxin 1 by coagulase-negative staphylococci.

We tested 187 strains of coagulase-negative staphylococci (CNS) for the production of toxic shock syndrome toxin 1 (TSST-1). A total of 111 CNS strains were isolated from the tampons of menstruating women and 74 were isolated from unused tampons. Two strains were isolated from the genital tract of a patient with toxic shock syndrome. Strains were cultivated by the membrane-over-agar method to enhance production of TSST-1, and culture supernatants were tested by two exquisitely sensitive enzyme-linked immunosorbent assays. None of the 187 CNS strains produced TSST-1. We conclude that CNS colonizing the genital tracts of menstruating women and unused tampons produce TSST-1 infrequently, if ever, and are unlikely to play a role in toxic shock syndrome.

Bacterial Toxins

History of the specialty of infectious diseases in the United States.

Infectious diseases in the United States were for generations so integral to health and medicine that a special interest in the field, except for investigative purposes, could hardly be contemplated. With declining mortality and morbidity from infections, and the advent of major antimicrobial drugs, interest in infectious disease flagged in clinical and microbiological departments. Several factors have caused a new interest in infectious disease, including the appearance of newly recognized infectious disease syndromes; advances in microbiologic, immunologic, virologic, and epidemiologic understanding; increased societal interest; proliferation of effective therapeutic and preventive agents; and the general thrust toward specialization. This interest led to the formation of societies, subspecialty boards, and journals, and accounts for the prominence of infectious disease in clinical departments and in national thought. Similar developments are taking place at various rates in other countries, with renewed attention to the toll of infectious diseases in developing countries.

Anti-Bacterial Agents