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Beneficial effects of oral zinc supplementation on the immune response of old people.

Zinc is known to have beneficial effects on the immune response. In an attempt to modify age-associated immune dysfunction, supplemental zinc was administered to 15 subjects over 70 years of age (220 mg zinc sulfate twice daily for a month). As compared to 15 controls, matched for age and sex, there was a significant improvement in the following immune parameters in the treated group: (1) number of circulating T lymphocytes; (2) delayed cutaneous hypersensitivity reactions to purified protein derivative, Candidin and streptokinase-streptodornase; (3) immunoglobulin G (IgG) antibody response to tetanus vaccine. Zinc treatment had no influence on the number of total circulating leukocytes or lymphocytes, or on the in vitro lymphocyte response to three mitogens: phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM). The data suggest that the addition of zinc to the diet of old persons could be an effective and simple way to improve their immune function.

Adult↗

Capping of the surface OKT3 binding molecule prevents the T-cell proliferative response to antigens: evidence that this molecule conveys the activation signal.

The human T-lymphocyte receptor for antigen appears to have been localized to a cluster of associated surface glycoprotein molecules, among which is the OKT3 binding molecule. We have tested the hypothesis that selective removal of the OKT3 binding molecule eliminates the cellular immune response to antigens by clearing the surface of the molecule that conveys the activation signal. Enriched T cells were obtained from donors immune to purified protein derivative (PPD), streptokinase-streptodornase (SK-SD), or keyhole limpet hemocyanin (KLH). T-3 molecules were cleared from the cell surface by capping with OKT3 and F(ab')2 goat anti-mouse IgG. Regeneration of surface molecules was prevented by culturing the T-3 capped cells with OKT3 625 ng/ml. The capacity of capped T cells to proliferate in culture with antibody in response to antigens, alloantigens, and the mitogens, PHA and ionophore A23187, was compared to uncapped cells pretreated with media and to capped cells permitted to regenerate the OKT3 binding molecule. T-3 capped cells cultured in the presence of antibody failed to proliferate to antigens or alloantigens. However, T-3 capped cells cocultured with antibody also did not significantly proliferate to PHA, but did respond to A23187. In contrast, both media-treated T cells and cells which had regenerated the OKT3 binding molecule proliferated to mitogens, antigens, or alloantigens. The requirement for the OKT3 binding molecule was determined by utilizing T-1, T-4, and T-8 capped cells. T-1, T-4, or T-8 capped cells cultured in the presence of OKT1, OKT4, or OKT8 proliferated in response to antigens, alloantigens, and mitogens. These results demonstrate that in the absence of the OKT3 binding molecule, antigens, alloantigens, and PHA failed to induce a significant cellular proliferative response. In the absence of this molecule, PHA cannot bind to its carbohydrate moiety, and therefore cannot activate T cells to proliferate. These data support the concept that the molecule binding OKT3 conveys the transmembrane signal resulting in cellular activation.

Adult↗

Prolonged impairment of cell-mediated immunity after major abdominal surgery in malnourished patients.

The effect of the nutritional status on postoperative impairment of the immune response was studied in adults undergoing major abdominal surgery. The immune function was evaluated by measuring in vitro the lymphocytic response to phytohaemagglutinin (PHA), concanavalin A (Con A) and the purified protein derivative of tuberculin (PPD) in whole blood cultures, and in vivo delayed skin hypersensitivity to candida, mumps, streptokinase-streptodornase and PPD. Nutritional assessment was carried out by evaluating recent weight loss, the weight for height index and by measuring the arm muscle circumference (AMC), triceps skinfold thickness (TSF), the creatinine-height index (CHI) and the serum concentration of albumin and prealbumin. The patient was considered malnourished, if at least three of these criteria were abnormal. The immune parameters were measured preoperatively, at the end of the surgery and five days after operation. Before the operation both malnourished and well-nourished patients had normal lymphocytic responses, but the malnourished patients had a slower recovery of immune responses after the operation and they had an increased number of postoperative complications. No significant differences in the incidence of anergy were observed between the well and malnourished patients pre or postoperatively.

Journal Article↗

Purification and some properties of streptococcal NAD-glycohydrolase.

NAD-glycohydrolase (NADase) was purified from culture supernatant fluids of group C streptococci by adsorption on silica gel, chromatography on hydroxyapatite and ion exchange on Mono S column. After inactivation of a chymotrypsin-like protease, a homogeneous enzyme was isolated with an N-terminal sequence of VSGKEGKKSDVKYEMTKVMEANATSSKEDKHVMHTLDKVM. According to serological methods, the purified enzyme of group C streptococci was identical to the group A enzyme showing a specific activity of 10 000 000 U mg-1. It did not attack NADH, NADP or NADPH. In addition, a streptodornase was isolated having an N-terminal sequence of KTVSVNQTYGE.

Amino Acid Sequence↗

Pharmacotherapy in complicated parapneumonic pleural effusions and thoracic empyema.

Parapneumonic pleural effusions (PPE) and pleural empyema (PE) present a frequently diagnostic and therapeutic challenge in clinical practice. Although pleural diseases have received increased attention during the past decade, there are still many unanswered questions concerning the diagnosis and treatment of PPE and PE. A lack of controlled studies concerning the management of PPE and PE was noted in recent guidelines. The use of fibrinolytics intrapleurally appears to enhance intercostals tube drainage, reducing the requirement for subsequent surgical mechanical debridement. Recently, there has been interest in other intrapleural agents including combination drugs consisting of streptokinase and streptodornase-alpha, Dnase. Factors to be considered in evaluating whether or not intrapleural instillation of fibrinolytics is effective include an assessment of clinical responses. This review discusses the use of fibrinolytic agents as a novel therapeutic options for treating the various stages of parapneumonic effusions and empyemas.

Debridement↗

Outcome of asbestos exposure (lung fibrosis and antinuclear antibodies) with respect to skin reactivity: an 8-year longitudinal study.

Two hundred seventy asbestos workers were examined during an 8-year period. During this time five consecutive surveys were completed. Skin tests with streptokinase-streptodornase (SK-SD), tuberculin (PPD), and phytohemagglutinin (PHA) were performed in the middle of this period. The results of these tests were related to X-ray chest film results and the appearance of antinuclear antibodies (ANA). In all surveys, except the first, X-ray films with small irregular opacities with a profusion greater than or equal to 1/1 belonged more frequently to asbestos workers who did not respond to SK-SD or PHA. Thirty-one cases of asbestosis were diagnosed at that time, 23 of them became asbestotic after the skin tests were performed. Asbestotic cases contributed more frequently to the group with anergy as compared to asbestos workers lacking asbestosis. Furthermore, asbestosis was correlated with lack of response to second strength of SK-SD in males and PHA in both sexes. Lack of response to these activators was predictive of asbestosis. Asbestos workers with ANA frequently displayed a lack of response to the first strength of SK-SD, PPD, and PHA. This was partly due to the presence of asbestotic cases in the group. However, low responders to all these activators were found more frequently in the group with ANA independent of the presence of asbestosis.

Adult↗

Antigen-specific suppressor cells in subclinical leprosy infection.

A two-stage in-vitro culture system was used to assay cells which suppress the lympho-proliferative response to Mycobacterium leprae (ML). Responses to ML, purified protein derivative of tuberculin, and streptokinase-streptodornase were preferentially suppressed by mitomycin-treated cells which had been primed with the same antigen in a 7-day primary culture. Healthy subjects exposed to leprosy for more than 3 years showed strong suppression of the response to ML antigens (11 of 12 showed more than 40% suppression), whereas those exposed for 3 months to 3 years showed much less suppression (12 of 15 showed less than 40% suppression). The in-vitro generation of strong ML-specific suppression may reflect the maturation of a well-regulated and protective immune response. However, premature induction and in-vivo activation of these suppressor cells could predispose to disseminated (lepromatous) forms of leprosy. With this assay it would be possible to assess the ability of proposed leprosy vaccines to engage strongly the regulatory network controlling the immune response to ML in the same way as long-term exposure to the natural infection.

Adolescent↗

Effects of preoperative parenteral nutrition on cell-mediated immunity in malnourished patients.

Cell-mediated immunity was studied in 19 malnourished patients admitted for major abdominal surgery. Nine of them received total parenteral nutrition (TPN) before operation (the TPN group), while ten (the control group) were operated on without a period of TPN. In vitro lymphocyte proliferative responses to phytohaemagglutinin (PHA), concanavalin A (Con A) and purified protein derivative of tuberculin (PPD), were measured in whole blood cultures preoperatively, at the end of surgery and 5 days after operation. In vivo delayed skin hypersensitivity to candida, mumps, streptokinase-streptodornase and PPD was studied preoperatively and 5 days after operation. Complications in both groups were observed and recorded. Nutritional assessment was carried out by evaluating the extent of recent weight loss, the weight for height index and by measuring the arm muscle circumference (AMC), triceps skinfold thickness (TSF), the creatinine-height index (CHI) and serum albumin and prealbumin concentrations. The patient was considered to be malnourished and was included in the study, if at least three of these criteria were abnormal. In the TPN group changes in mitogen induced lymphocyte proliferative responses caused by surgery were not significant. By contrast, responses in the control group decreased significantly (P < 0.01) during surgery and most of these responses differed from the preoperative values even at the fifth postoperative day. Anergy was equally common in both groups before and after surgery. The number of infectious complications was lower in the TPN group.

Journal Article↗

Immunodeficiency in non-tuberculous mycobacterial disease.

T-cell immunity was investigated in eight patients with non-tuberculous mycobacterial disease, to see whether impaired immune function might be the explanation for their infection. Cellular immune function was evaluated in vitro by measuring the proliferation of peripheral blood mononuclear cells in response to both non-specific mitogens (phytohaemagglutinin and pokeweed mitogen) and specific recall antigens (streptokinase-streptodornase and purified protein derivative from Mycobacterium tuberculosis), and in vivo, by measuring the skin test response to a panel of recall antigens. Functionally relevant T-lymphocyte sub-populations (CD4, CD8, activated CD3 and gamma/delta T-cells) were enumerated by two-colour flow cytometry. The results were compared with those for a group of patients with pulmonary tuberculosis, with groups of controls matched for age and smoking habit, and with a patient group receiving steroid treatment. The patients with non-tuberculous mycobacterial disease had poor or absent skin test responses; in vitro, their response to recall antigens was depressed, although their response to mitogens was normal. The patients had significantly raised levels of CD8 lymphocytes and activated T-cells, but lacked any circulating gamma/delta T-cells. There were also differences between the various control groups. In conclusion, this study demonstrates a deficiency in the cellular immune system of these patients, which is most readily detectable by skin testing, or by measuring lymphocyte proliferative responses to recall antigens. However, the study also shows changes in cellular immune responses in controls matched for age and smoking and in patients on steroid treatment, and underscores the need for matched controls. Further work needs to be done to ascertain whether the cellular immune deficiency is a cause of, or is caused by, the mycobacterial infections, and also to investigate the pathological significance of the alterations in T-cell sub-populations.

Adult↗

An investigation of the general immune status and specific immune responsiveness to retinal-(S)-antigen in patients with chronic posterior uveitis.

Immunological abnormalities in endogenous posterior uveitis are widely reported but difficult to verify. We have therefore studied several immunological parameters in 14 patients with chronic posterior uveitis and compared the results with 14 healthy controls. Both the general immune status and the specific immune responsiveness to retinal S-antigen have been investigated. Results for the patient group as a whole were not significantly different from the control group. However the patients with severe eye disease (n = 4) had a reduced proliferative response to streptokinase-streptodornase antigen and two further individuals showed a general deficiency in functional cell mediated immunity. Circulating T-helper cells were marginally but not significantly reduced in patients. Responsiveness to bovine retinal S-antigen varied to a similar degree in both the patient and control groups. These findings indicate that, although severe uveitis may be associated with functional defects in cellular immunity in certain cases, in general the measurement of immune responsiveness of peripheral blood lymphocytes is unlikely to aid in the diagnosis or management of chronic posterior uveitis.

Adolescent↗

A case of cryofibrinogenaemia responsive to stanozolol.

Cryofibrinogen is a plasma protein complex whose presence in the peripheral blood is generally asymptomatic, but may sometimes cause multiple thromboembolism in the skin, lung and myocardium. The pathological manifestations associated with cryofibrinogenaemia have been treated with plasmapheresis and fibrinolytic drugs such as streptokinase, streptodornase and/or urokinase. Good results have recently been reported with stanozolol. This prompted us to treat a patient suffering from cryofibrinogenaemia with this androgenic hormone. The patient was a 66-year-old woman with rapidly evolving leg ulcers. Stanozolol was orally administered at 4 mg b.i.d. for 5 months and then gradually reduced. Plasma cryofibrinogen disappeared after 45 d from the start of therapy and cutaneous ulcers healed in 5 months.

Aged↗

Invasive M1T1 group A Streptococcus undergoes a phase-shift in vivo to prevent proteolytic degradation of multiple virulence factors by SpeB.

A globally disseminated strain of M1T1 group A Streptococcus (GAS) has been associated with severe infections in humans including necrotizing fasciitis and toxic shock syndrome. Recent clinicoepidemiologic data showed a striking inverse relationship between disease severity and the degree to which M1T1 GAS express the streptococcal cysteine protease, SpeB. Electrophoretic 2-D gel analysis of the secreted M1T1 proteome, coupled with MALDI-TOF mass spectroscopy, revealed that expression of active SpeB caused the degradation of the vast majority of secreted GAS proteins, including several known virulence factors. Injection of a SpeB+/SpeA- M1T1 GAS strain into a murine subcutanous chamber model of infection selected for a stable phase-shift to a SpeB-/SpeA+ phenotype that expressed a full repertoire of secreted proteins and possessed enhanced lymphocyte-stimulating capacity. The proteome of the SpeB-in vivo phase-shift form closely matched the proteome of an isogenic speB gene deletion mutant of the original M1T1 isolate. The absence or the inactivation of SpeB allowed proteomic identification of proteins in this M1T1 clone that are not present in the previously sequenced M1 genome including SpeA and another bacteriophage-encoded novel streptodornase allele. Further proteomic analysis of the M1T1 SpeB+ and SpeB- phase-shift forms in the presence of a cysteine protease inhibitor demonstrated differences in the expression of several proteins, including the in vivo upregulation of SpeA, which occurred independently of SpeB inactivation.

Animals↗

Role of streptococcal infection in the acute pathology of lymphatic filariasis.

Growing evidence suggest that secondary bacterial, mainly streptococcal, infections contribute significantly to recurrent episodes of acute adenolymphangitis (ADL) of filarial origin. We examined the role of group A streptococci in the progression of lymphedema in Polynesian patients with filariasis-related ADL (22 cases) or chronic pathology (10 cases), or with erysipela (10 patients) and, as controls, in 20 healthy adults. Antistreptolysin O (ASLO) and anti-streptodornase B (ASDB) titers were systematically determined in parallel to parasitological and biochemical tests. ASLO and ASDB assays were positive in 100% of erysipela, 75% of filarial ADL as compared to 50% of chronic pathology and 39% of healthy controls. Interestingly, by opposition to ASLO titers which were not significantly different between the four groups, ASDB titers were higher in ADL (p = 0.019) and erysipela (p = 0.002) than in controls. These results support the hypothesis that recurrent streptococcal infections may have an important role in the pathogenesis of ADL in lymphatic filariasis.

Adult↗

[Prevention of postoperative adhesions--animal experiment study].

Standardised lesions were placed on both uterine horns and on the abdominal wall of seventy-five female rabbits. The animals were divided into five groups consisting of 15 animals each. Before closure of the peritoneum the following drugs were applied in the peritoneal cavity: Group I received NaCl (control), Group II received 10 ml poly-(1-vinyl-1-pyrrolidone)-iodine complex (Betaisodona), Group III received 100 000 I. U. streptokinase and 25 000 I. U. streptodornase (Varidase), Group IV received 100 000 KIE approtinine (AntagosanA) and Group V received triamcinolone acetonide (Volon A-Haftsalbe). Two weeks after surgery the animals were relaparotomised and the situs was inspected. Quality and extent of the adhesions were assessed and documented. The results obtained in group II did not differ from controls, while the remaining groups showed significantly fewer adhesions. The best results were obtained in animals receiving Volon A-Haftsalbe (Group V) where 86% fewer adhesions were observed.

Abdomen↗

Host defense mechanisms in elective and emergency vascular surgery: predicting septic-related mortality.

This study examines host defense mechanisms in vascular surgery patients when admitted to the hospital to determine the frequency of abnormal host defense and the predictability of this information for septic-related mortality in affected patients. Sixty-four patients undergoing elective surgery (indications: 35 with aneurysms, 27 with aortoiliac disease, and two with renovascular disease) and nine patients undergoing emergency operation (indications: two with ruptured aneurysms, seven with aortoenteric fistulas) were skin tested when admitted to the hospital with five ubiquitous antigens (Candida, mumps, tuberculin, Trichophyton, and streptokinase-streptodornase [Varidase]) and read at 24 and 48 hours. Patients were anergic with none, relatively anergic with one, or reactive with two or more antigen responses (induration 5 mm). Eighty-nine percent of elective surgery patients were reactive, 5% were relatively anergic, and 6% were anergic. This compared with 64% reactive, 13% relatively anergic, and 17% anergic patients in a separate concurrent study of 565 surgical patients with gastrointestinal malignancies (p less than 0.001, chi 2). There were two septic-related deaths in the elective surgery group and both patients were anergic at admission, which resulted in a mortality rate of 50%. Two deaths not related to sepsis occurred in two reactive patients (4%). Logistic regression analysis predicted 3.9 deaths in the elective surgery group and four deaths were observed. Both patients with ruptured aneurysms were unreactive and both died of septic-related complications. Only one of seven patients admitted with an infected graft was reactive. All had surgery. Using the admission data of these seven patients, we predicted 2.3 deaths. Two deaths were observed 21 and 48 days after operation. Both patients were anergic and scored high probabilities of mortality (more than 0.6) at admission. The remaining emergency procedure patients scored lower probabilities of mortality (less than 0.4) at admission and none died.2+.

Adult↗

Virulence control in group A Streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling.

Two-component gene regulatory systems composed of a membrane-bound sensor and cytoplasmic response regulator are important mechanisms used by bacteria to sense and respond to environmental stimuli. Group A Streptococcus, the causative agent of mild infections and life-threatening invasive diseases, produces many virulence factors that promote survival in humans. A two-component regulatory system, designated covRS (cov, control of virulence; csrRS), negatively controls expression of five proven or putative virulence factors (capsule, cysteine protease, streptokinase, streptolysin S, and streptodornase). Inactivation of covRS results in enhanced virulence in mouse models of invasive disease. Using DNA microarrays and quantitative RT-PCR, we found that CovR influences transcription of 15% (n = 271) of all chromosomal genes, including many that encode surface and secreted proteins mediating host-pathogen interactions. CovR also plays a central role in gene regulatory networks by influencing expression of genes encoding transcriptional regulators, including other two-component systems. Differential transcription of genes influenced by covR also was identified in mouse soft-tissue infection. This analysis provides a genome-scale overview of a virulence gene network in an important human pathogen and adds insight into the molecular mechanisms used by group A Streptococcus to interact with the host, promote survival, and cause disease.

Animals↗

Immunocompetency in anorexia nervosa.

Twenty-two consecutively admitted patients diagnosed for anorexia nervosa were evaluated for cellular immune functioning by means of an anergy panel to test delayed hypersensitivity. The panel included candida, streptokinase-streptodornase, and mumps antigen administered by a standard protocol. A standard nutritional profile including current weight, usual weight, total protein, albumin, total iron-binding capacity, white blood cell count, total lymphocyte count, triceps skinfold, and arm muscle circumference was concurrently compiled on these subjects. Six of 22 patients studied were anergic. Visceral protein measures were generally within normal limits even in the most depleted patients. Malnutrition as measured by severity of weight loss and triceps skinfolds was significantly related to anergy, whereas visceral protein indicators (serum albumin, total iron binding capacity, transferrin) were not correlated with anergy. Anergy appeared to be related more strongly to anthropometric indices of malnutrition than to visceral protein values. Cellular immunity was generally preserved until weight loss was far advanced.

Adult↗

Immunomodulating properties of dimethylglycine in humans.

Dimethylglycine (DMG), a tertiary amino acid, has had wide acceptance as a nonfuel nutrient; presumably it enhances oxygen utilization by tissue and complexes free radicals. Its potential as an immunoadjuvant has also been suggested by a study of an analog of DMG, calcium pangamate. A double-blind study in 20 human volunteers showed a fourfold increase in antibody response to pneumococcal vaccine in those receiving DMG orally as compared with controls (P less than 0.01). Production of leukocyte inhibitory factor in response to concanavalin A was similar in the two groups, but those taking DMG tablets had a significantly highr mean response of leukocyte inhibition factor to streptokinase-streptodornase (P less than 0.001). The in vitro responses of lymphocytes from patients with diabetes and those with sickle cell disease to phytohemagglutinin, convanavalin A, and pokeweed mitogen were increased almost threefold after addition of DMA. These results suggest that DMG enhances both humoral and cell-mediated immune responses in humans.

Adjuvants, Immunologic↗