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Biomedical subjects

M McCarty

Publications and source records attributed to M McCarty.

At least 55 records · Page 3Linked to original sources

Bronchopulmonary Kaposi's sarcoma in patients with AIDS.

BACKGROUND: Kaposi's sarcoma is the most common secondary neoplasm to complicate HIV infection and may cause pulmonary disease. METHODS: A prospective study was carried out in 140 consecutive patients who were HIV seropositive and required bronchoscopy for new respiratory symptoms of at least two weeks' duration, with either a chest radiographic abnormality or abnormality of pulmonary function. The patients were classified into those with single local endobronchial lesions of Kaposi's sarcoma or generalised widespread lesions. Before bronchoscopy all patients had routine simple pulmonary function tests and chest radiography. RESULTS: Thirty nine (21%) patients had evidence of cutaneous Kaposi's sarcoma. Nineteen of the 39 were found to have endobronchial Kaposi's sarcoma lesions at bronchoscopy, but none of those who did not have cutaneous Kaposi's sarcoma. Respiratory symptoms of cough and breathlessness and radiographic abnormalities were attributed to Kaposi's sarcoma in this group, except in four patients who had concomitant pneumocystis pneumonia. Eight patients had local endobronchial Kaposi's sarcoma lesions and 11 had extensive lesions. Patients with extensive lesions had more widespread radiographic abnormalities; four of the patients with local endobronchial lesions had normal chest radiographs. All patients had reduced transfer factor for carbon monoxide and transfer coefficient, whereas patients with extensive endobronchial lesions also had reductions in forced expiratory volume in one second and forced vital capacity. Median survival (with palliative chemotherapy with vincristine and bleomycin) was only seven months. In three patients who needed further diagnostic bronchoscopy endobronchial lesions had regressed while they were having chemotherapy. CONCLUSIONS: This study suggests that endobronchial Kaposi's sarcoma is a relatively common finding in patients with AIDS and is particularly common in patients with cutaneous Kaposi's sarcoma who present with respiratory illness. Endobronchial Kaposi's sarcoma causes respiratory disease and abnormalities of pulmonary function. Pulmonary Kaposi's sarcoma should be considered as a possible cause for respiratory illness in any patient with cutaneous Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

Clinical Utility of cranial CT in HIV positive and AIDS patients with neurological disease.

An analysis was made of the clinical, pathological and radiological data relating to 117 requests for cranial CT on 83 patients who were HIV positive or had AIDS in one year at St Mary's Hospital. Central to the design was grouping of the patients according to clinical presentation. The aim was to establish whether there was evidence to support the view that, because of their immunocompromised state, these patients may commonly harbour serious, potentially treatable intracranial disease without the usual overt clinical signs. No patient who was only HIV antibody positive had treatable intracranial disease without focal neurological signs. In patients with AIDS, treatable or potentially treatable lesions were mainly confined to those with objective neurological signs or seizures. There is little evidence in this data to support the original hypothesis. While it would be inappropriate to advise that CT should never be carried out in the absence of focal signs or seizures, the results of this study should be useful in ascribing an appropriate degree of urgency to requests for cranial CT in these patients.

Acquired Immunodeficiency Syndrome↗

Radiological features of AIDS related cholangitis.

Cryptosporidial infection is one of the recognised causes of diarrhoea in AIDS patients. It may also produce biliary tract disease. Fifteen out of 250 (6%) AIDS patients seen at our hospital had Cryptosporidial enteritis and five of the 15 (2% total) had clinical evidence of biliary tract disease. The radiological findings in these five patients are presented. Ultrasound examination of all five patients showed abnormalities in the biliary tree; five had dilatation and irregularity of the intra- and extrahepatic bile ducts with focal strictures, four had gall-bladder wall thickening, two had thickening of the common bile duct wall, two patients showed areas of increased reflectivity in the periductal regions of the liver and two had pancreatic duct dilatation. ERCP in one patient confirmed the ultrasound findings and Cryptosporidium oocytes were isolated from the collected bile. We conclude that Cryptosporidial infection in the biliary tree can produce distinctive appearances on ultrasound which may well obviate the need for more invasive investigations such as ERCP.

Acquired Immunodeficiency Syndrome↗

Immunogenicity of liposome-bound hyaluronate in mice. At least two different antigenic sites on hyaluronate are identified by mouse monoclonal antibodies.

Hyaluronate (HA) was previously demonstrated to be immunogenic in rabbits. The immunogenicity of HA in mice was studied. Hyaluronidase-digested streptococcal HA (IA1) covalently linked to liposomes (IA1-liposomes) were produced for immunization. Mice immunized with IA1-liposomes developed measurable serum antibodies to IA1, while mice immunized with IA1 in Freund's adjuvant did not. mAbs produced by two stable hybridomas (10G6 and 5F11) from mice immunized with IA1-liposomes produced IgG antibody reactive with HA in ELISA. 10G6 had a much higher avidity for liposome-bound IA1 than free IA1, while 5F11 did not, suggesting that the mode of presentation of IA1 is important in HA immunogenicity and antigenicity. Both mAbs recognized terminal HA immunodeterminants exposed by hyaluronidase treatment. Sonication had no effect on HA reactivity for either mAb. However, ascorbic acid treatment significantly reduced the antigenicity of HA for mAb 5F11, but not 10G6. Only 10G6 was inhibited by glucuronic acid. Electrostatic forces appear to play a role in the binding site of 5F11, but not 10G6. 5F11 crossreacts with heparan sulfate and phosphorylcholine, while 10G6 did not crossreact with any glycosaminoglycans or phosphorylated compounds tested. These results confirm that HA is immunogenic. They suggest that the mode of presentation of HA is important for the induction of the immune response, and in HA antigenicity. At least two different antigenic sites on HA were demonstrated. 10G6 recognizes a terminal HA antigenic site expressed on IA1-liposomes that contains glucuronic acid in its immunodominant site. 5F11 recognizes an HA antigenic site in which electrostatic forces appear to play a role, is sensitive to ascorbic acid treatment, and is crossreactive with heparan sulfate. The use of mAbs should facilitate immunologic studies of HA.

Animals↗

Induction of antibodies to hyaluronic acid by immunization of rabbits with encapsulated streptococci.

The immunogenicity of hyaluronic acid was investigated. Rabbits were immunized with encapsulated group A and C streptococci. Intact long-chain hyaluronate was conjugated to BSA for use as antigen in an ELISA. Antibodies to the hyaluronate-BSA conjugate were detected in peak immune sera. The specificity of the antibodies for both mammalian and streptococcal hyaluronate was shown by inhibition studies. To further confirm the presence of antihyaluronate antibodies, hyaluronidase-digested streptococcal hyaluronate was conjugated to biotin and used as an antigen in the ELISA. A clear immunization effect was shown for each rabbit by the study of preimmune and postimmunization bleedings. Titers for each rabbit increased by greater than 32 - 256 - fold. Inhibition studies using hyaluronidase-digested hyaluronate and periodate-treated hyaluronate showed that the immunodominant site of antibody reactivity was a terminal glucuronic acid residue. Further studies showed that the carboxyl group of the terminal glucuronide was the major immunoreactive site. Both mammalian and streptococcal hyaluronate inhibited the immune rabbit sera reaction to streptococcal hyaluronate, demonstrating crossreactivity of these molecules. Thus, hyaluronate was shown to be immunogenic in rabbits.

Agglutination Tests↗

Can dietary selenium reduce leukotriene production?

The leukotrienes, prominent mediators of immediate hypersensitivity and inflammation, are derived from the major product of leukocyte lipoxygenase activity, 5-HPETE. An alternative pathway for 5-HPETE metabolism is reduction to 5-HETE. I hypothesize that, in analogy to its established role in platelet lipoxygenase metabolism, the selenium-dependent glutathione peroxidase mediates this reduction. If so, supplementary selenium may decrease leukotriene production, and thus have value as a nutritional adjuvant in the management of asthma and various other inflammatory disorders.

Animals↗

High-chromium yeast for acne?

Many dermatologists have reported that insulin and tolbutamide are therapeutically effective in acne. This rationalizes a recent observation that high-chromium yeast appears to have value as an acne treatment.

Acne Vulgaris↗

Immunochemical analysis of streptococcal group A, B, and C carbohydrates, with emphasis on group A.

Streptococcal group A, B, and C carbohydrates were analyzed by counterimmunoelectrophoresis, immunoelectrophoresis, and inhibition of immunoprecipitation. Extracts of streptococci group A or C were shown by counterimmunoelectrophoresis to contain both anodic and cathodic migrating components. In immunoelectrophoresis, group A and C substances formed a continuous precipitation line stretching from the anode to the cathode, suggesting a heterogeneous population of molecules with immunochemical identity. This identity was confirmed by inhibition of immunoprecipitation, in which both anodic and cathodic immunoprecipitates were inhibited by the same constituent sugars: group A-anti-A was inhibited by N-acetylglucosamine, and group C-anti-C was inhibited by N-acetylgalactosamine. Extracts of group B showed only anodic migration in counterimmunoelectrophoresis and a narrow, anodic arc in immunoelectrophoresis. The group B-anti-B reaction was inhibited by rhamnose. Carbohydrates of variant strains of group A streptococci were also analyzed by the same methods. The results suggest that the heterogeneity of group A carbohydrate may have resulted from attachment of various amounts of N-acetylglucosamine to the polyrhamnose backbone.

Acetylgalactosamine↗

Nutritionally variant streptococci from patients with endocarditis: growth parameters in a semisynthetic medium and demonstration of a chromophore.

Nutritionally variant streptococci have been characterized in the past by their growth as satellite colonies and by their nutrient requirements of cysteine or vitamin B6 for growth in complex media. To further understand the growth characteristics of these strains, we studied fresh isolates from patients with endocarditis by using chemically defined medium enriched with 2% Todd-Hewitt dialysate. Under anaerobic conditions, growth yields of the strains in this medium were comparable to those obtained from a complex medium supplemented with vitamin B6, whereas under aerobic conditions, most of the strains had higher growth yields in the semisynthetic medium. Furthermore, the requirement for cysteine and vitamin B6 in the semisynthetic medium was no greater than that of other Streptococcus species. Electron microscopic studies demonstrated normal cell wall structures in organisms grown in the semisynthetic medium as compared with abnormal and irregular cell wall thickening in organisms grown in supplemented complex medium. Finally, these strains appeared to contain a common component when grown in the semisynthetic medium as demonstrated by the appearance of a chromophore after boiling the bacteria at pH 2. Therefore, the demonstration of a medium which permits adequate growth with a normal ultrastructure of nutritionally variant streptococci will permit the further study of this group of important streptococci.

Culture Media↗

Thioproline.

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Benzaldehydes↗