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Biomedical subjects

C Casper

Publications and source records attributed to C Casper.

13 recordsLinked to original sources

Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes.

Change of HIV-1 coreceptor use has been connected to progression of disease in children infected with HIV-1, presumably subtype B. It has not been possible to discern whether the appearance of new viral phenotypes precedes disease development or comes as a consequence of it. We studied the evolution of coreceptor use in HIV-1 isolates from 24 vertically infected children. Their clinical, virological, and immunological status was recorded and the env V3 subtype was determined by DNA sequencing. Coreceptor use was tested on human cell lines, expressing CD4 together with CCR5, CXCR4, and other chemokine receptors. The children carried five different env subtypes (nine A, five B, four C, three D, and one G) and one circulating recombinant form, CRF01_AE (n = 2). Of the 143 isolates, 86 originated from peripheral blood mononuclear cells (PBMCs) and 57 originated from plasma, received at 90 time points. In 52 of 54 paired plasma and PBMC isolates the coreceptor use was concordant. All 74 isolates obtained at 41 time points during the first year of life used CCR5. A change from use of CCR5 to use of CXCR4 occurred in four children infected with subtype A, D, or CRF01_AE after they had reached 1.5 to 5.8 years of age. There was a significant association with decreased CD4+ cell levels and severity of disease but, interestingly, the coreceptor change appeared months or even years after the beginning of the immunological deterioration. Thus CXCR4-using virus may emerge as a possible consequence of immune deficiency. The results provide new insights into AIDS development in children.

Acquired Immunodeficiency Syndrome↗

Genetic analysis of a severe case of Netherton syndrome and application for prenatal testing.

Netherton syndrome (NS) is a rare autosomal recessive disease with variable expression. It is defined by a triad of symptoms: congenital ichthyosiform erythroderma, trichorrhexis invaginata and atopy. Recently, genetic linkage has been established to the SPINK5 gene locus on chromosome 5q32 encoding the serine protease inhibitor LEKTI. In this study, we present a recurrent homozygous mononucleotide deletion (153delT) resulting in a severe case of NS exhibiting exfoliative erythroderma with lethal outcome at the age of 4 months and its application in prenatal testing in a subsequent pregnancy of the mother.

Carrier Proteins↗

Mother-to-child transmission of HIV-1: the role of HIV-1 variability and the placental barrier.

The acquired immunodeficiency syndrome (AIDS), which is caused by the human immunodeficiency virus (HIV), was first described in the United States of America in 1981 [1]. The worldwide spread of HIV has soon been recognized and AIDS has become one of the most alarming infectious diseases of our days. Its impact has been tremendous, high morbidity and mortality has caused a reversal of socioeconomic gains previously recorded in several developing countries, especially those in Sub-Saharan Africa [2]. Epidemiological data about the HIV and AIDS pandemic are updated by the Joint United Nation Programme on HIV/AIDS, UNAIDS (http://www.unaids.org). Their latest report from December 2000 states that in year 2000 approximately 5.3 million people have become newly infected with HIV, of which 2.2 were women and 600,000 children younger than 15 years of age. The estimated number of people living with HIV/AIDS globally is 36.1 million, of which 16.4 million are women and 1.4 million are children younger than 15 years of age. Approximately 25.3 million (70%) of these HIV infected people live in Sub-Saharan Africa, 5.8 million in South- and South-East Asia (15%), and 1.4 million in Latin-America (5%). During year 2000, 3 million people died of AIDS (1.3 million women and 500,000 children younger than 15 years of age). This means that an estimated total of 21.8 million persons have died of AIDS since the beginning of the epidemic, including 4.3 million children younger than 15 years of age.

Adult↗

[Reduced mother-to-child transmission of HIV-1 infection. Exclusive breast feeding and weaning--a possible model in developing countries?].

Antiretroviral therapy with zidovudine during pregnancy, delivery, and to the newborn in combination with Cesarean section has markedly reduced the rate of mother-to-child transmission of HIV-1 in industrialized countries. These strategies are not realistic in the less developed world. Nevertheless, short-term antiretroviral therapy during delivery and shortly after birth has proven feasible as a means of reducing the rate of vertical transmission in less developed countries, in some studies even in combination with exclusive breast-feeding. The risks and benefits of breast-feeding among HIV-1 infected mothers are discussed.

Anti-HIV Agents↗

Mapping of a mouse mammary tumor virus integration site by retroviral LTR--arbitrary polymerase chain reaction.

The de novo integration of retroviral genomes within the mammalian genome is believed to contribute to the tumorigenic process. Integration may result in the disruption or inappropriate transcription of key regulatory genes. We describe the application of an arbitrarily primed PCR method for the mapping and cloning of genomic integration sites of the mouse mammary tumor virus (MMTV). We have amplified DNA sequences between a selected retroviral MMTV-LTR and random sites in the 3' flanking DNA. Using this technique we were able to visualize several proviral integration sites present in a MMTV-induced mammary tumor derived cell line that were absent from the germ line. Cloning and sequencing of the PCR product corresponding to one site established its identification as an unique 3' flanking sequence.

Animals↗

The transcontinental transmission of tuberculosis: A molecular epidemiological assessment.

Many tuberculosis control activities are based on principles learned from studies of tuberculosis transmission. To date, these have largely been limited to outbreak investigations in confined geographical regions. In this report conventional and computerized DNA fingerprint- based approaches were integrated to demonstrate that the most widely prevalent strain of Mycobacterium tuberculosis from New York City was cultured from only 1 of 755 patients in San Francisco, Calif, who was a traveling salesman. Large-scale molecular epidemiologic studies may provide a better understanding of the dynamics of tuberculosis transmission between geographic regions and suggest rational measures to interrupt such transmission.

Adult↗

[In vitro diagnosis of coronary plaque morphology with intravascular ultrasound: comparison with histopathologic findings].

The aim of this study was to validate the accuracy of a commercially available intravascular ultrasound system in diagnosing plaque composition in human coronary arteries. Thirty-five coronary arteries of 18 human autopsy hearts were perfused with NaCl under a pressure of 100 mmHg and examined using a Diasonics ultrasound system and 4.8 F 20 MHz catheters. An ultrasound diagnosis was made of 139 coronary sections using previously published standard criteria and compared with histologic findings. In addition, the influence of the histologic pattern of lipid and calcific deposits on the accuracy of the ultrasound diagnosis was evaluated. Of the 25 sections with a histologically normal intima, 14 (56%) were correctly identified by ultrasound, whereas fibrotic thickening was diagnosed in the remaining 11 sections. There were 114 plaques by histology which were correctly visualized by ultrasound as plaques in all instances. Plaque calcification was correctly diagnosed in 54 of 63 (86%) sections, but massive calcifications were more reliably identified by ultrasound than small speckled calcifications (43/44 = 98% vs 11/19 = 58%, p < 0.001). Fibrosis was present in all 114 plaques and was correctly visualized by ultrasound in all instances. When lipid was diagnosed by ultrasound as a homogeneous zone of low signal intensity within a fibrous plaque as suggested in the literature, lipid accumulations were identified with a sensitivity of 26% (16/62) and a specificity of 92% (71/77). When lipids were diagnosed if more than a quarter of the plaque area showed lower signal intensity than the tissue surrounding the vessel, the sensitivity of ultrasound was improved to 73% (45/62) but specificity fell to 30% (23/77). The entire histologic composition of a section was correctly diagnosed by ultrasound in only 42% of the 139 sections. Further technical improvements are therefore mandatory before intracoronary ultrasound will be able to provide a reliable analysis of plaque composition, especially of the lipid content.

Adult↗

Stevens-Johnson syndrome-like exanthema secondary to methotrexate histologically simulating acute graft-versus-host disease.

A 61 year old male patient suffering from psoriasis vulgaris developed a severe skin reaction with toxic myelosuppression three days after administration of 20 mg methotrexate (MTX) p.o. per week and concomitant 100 mg acetylic salicylic acid (ASA) per day. The skin lesions simulated Stevens-Johnson syndrome with ulcerations of the oral mucosa and erythema multiforme-like target lesions. The histology of the epidermis resembled an acute graft-versus-host reaction. The increased toxic effect of MTX on keratinocytes in our patient was most likely caused by a lowered plasma binding capacity and reduced renal excretion of MTX due to concomitant administration of ASA. Thus in the treatment of severe forms of psoriasis with MTX, the combined administration of drugs aggravating MTX toxicity, particularly of ASA, should be carefully considered, due to the increased toxicity and risk of severe skin reactions.

Diagnosis, Differential↗