Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyadenylic-polyuridylic acid referred to as poly(A).poly(U) is a synthetic double-stranded RNA which has been shown to manifest both antitumoral and immunomodulatory activities. Here we used this agent to demonstrate its antiviral activity against the human immunodeficiency virus (HIV-1 and HIV-2). Treatment of cells with poly(A).poly(U) resulted in a significant delay in the development of the HIV-specific cytopathic effect characterized by the formation of syncytia and cell lysis. Furthermore, the production of virus measured by the concentration of the HIV major core protein was reduced by 90-95%. Under these experimental conditions, the synthesis of HIV proteins was reduced at least tenfold whereas the metabolism and proliferation of cells apparently were not affected. The inhibitory action of poly(A).poly(U) seems to be at the level of viral entry into cells. Combined treatment of infected cells with poly(A).poly(U) and azidothymidine (AZT) resulted in a 4-5-fold synergistic inhibitory effect. Previously, no toxicity has been observed in cancer patients with long-term treatment with poly(A).poly(U). In view of this and the significant anti-HIV effect, poly(A).poly(U) provides a potential candidate as a therapeutic drug in AIDS disease.
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PMID:Antiviral action of polyadenylic-polyuridylic acid against HIV in cell cultures. 154 Apr 14

The replication cycle of human immunodeficiency virus type 1 (HIV-1) consists of four distinct stages, each of which can be targeted for specific antiviral chemotherapy. The stages are (1) the attachment of virus to the CD4 receptor at the cell surface; (2) the uncoating of viral nucleic acid and its conversion via viral reverse transcriptase activity to DNA; (3) cellular multiplication, accompanied by the replication of integrated proviral DNA and production of viral RNA and proteins; and (4) the assembly and liberation of progeny virus from the cell and the potential reinitiation of the replication cycle in previously uninfected cells. Since each of these steps represents a potential target for anti-HIV chemotherapy, it is apparent that the rationale for the use of antiviral drugs is not dissimilar from the manner in which antineoplastic agents are targeted to specific stages in the replication cycle of tumor cells. As in the case of anticancer chemotherapy, it is hoped that combinations of drugs, which act against different steps in the viral replication cycle, might have synergistic potential. AZT or zidovudine is the most widely used drug to date to impede the replication of HIV-1; it is significant that this compound was designed initially with anticancer chemotherapy in mind. Although AZT therapy has been reasonably successful, this drug has had important toxic side effects. As in the case of many cancer chemotherapeutic agents, drug resistance to AZT is likely to be an important problem, and there have been several reports of the isolation of drug-resistant variants of HIV-1.
Cancer Invest 1992
PMID:Strategies in the treatment of AIDS and related diseases: the lessons of cancer chemotherapy. 155 Oct 24

Patients infected with the human immunodeficiency virus (HIV) are subject to infections and neoplasms, which frequently result in palpable or radiologically identified masses. Fine-needle aspiration (FNA) offers a rapid, simple, and cost effective approach for diagnosis of these masses. During a 2-yr period, 396 aspirates were performed on 362 HIV-infected patients within the LAC-USC Medical Center. Adequate material was obtained from 84% of the FNA, allowing the etiology of the mass to be determined in 90% of the cases by means of a combination of cytologic, microbiologic, and immunocytochemical procedures. Significant pathologic processes identified in these patients by means of FNA included reactive lymphoid proliferations (35%), abnormal lymphoid proliferations (12%), infections (12.5%), cystic (5.5%) and inflammatory processes (5%), nonlymphoid malignancies (4%), and salivary gland pathology (1%). We conclude that FNA is an appropriate initial diagnostic procedure in HIV positive patients presenting with mass lesions.
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PMID:A review of the fine-needle aspiration cytology findings in human immunodeficiency virus infection. 155 65

Ataxia-telangiectasia (A-T) is a progressive autosomal recessive disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation sensitivity and a highly increased proneness to cancer. A-T is ethnically widespread and genetically heterogeneous, as indicated by the existence of four complementation groups in this disease. Several "A-T-like" genetic diseases share various clinical and cellular characteristics with A-T. By using linkage analysis to study North American and Turkish A-T families, the ATA (A-T, complementation group A) gene has been mapped to chromosome 11q23. A number of Israeli Arab A-T patients coming from large, highly inbred families were assigned to group A. In one of these families, an additional autosomal recessive disease was identified, characterized by ataxia, hypotonia, microcephaly and bilateral congenital cataracts. In two patients with this syndrome, normal levels of serum immunoglobulins and alpha-fetoprotein, chromosomal stability in peripheral blood lymphocytes and skin fibroblasts, and normal cellular response to treatments with X-rays and the radiomimetic drug neocarzinostatin indicated that this disease does not share, with A-T, any additional features other than ataxia. These tests also showed that another patient in this family, who is also mentally retarded, is affected with both disorders. This conclusion was further supported by linkage analysis with 11q23 markers. Lod scores between A-T and these markers, cumulated over three large Arab families, were significant and confirmed the localization of the ATA gene to 11q23. However, another Druze family unassigned to a specific complementation group, showed several recombinants between A-T and the same markers, leaving the localization of the A-T gene in this family open.
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PMID:Ataxia-telangiectasia: linkage analysis in highly inbred Arab and Druze families and differentiation from an ataxia-microcephaly-cataract syndrome. 155 65

We performed a prospective study of all infections with Streptococcus pneumoniae documented during a 22-month period at our hospital. A total of 163 clinically significant strains of S. pneumoniae were isolated from 139 patients whose ages ranged from 8 days to 91 years (mean +/- SD, 42.6 years +/- 26.8 years). Twenty percent of the patients had cancer, and 18% were infected with the human immunodeficiency virus. Pneumococcal infection was nosocomially acquired in one-fourth of cases. One-third of patients had nonpneumonic disease. A wide range of serotypes were isolated, and 42.5% of all strains were nonsusceptible--i.e., showed either intermediate or high-level resistance--to penicillin. The rates of resistance to chloramphenicol, erythromycin, and tetracycline were 23%, 10.8%, and 48.2%, respectively. Twenty-two percent of the infected patients died, with a 15.8% mortality directly attributable to pneumococcal infection. Factors associated with infection by strains of S. pneumoniae not susceptible to penicillin included an age of less than or equal to 10 years, immunosuppression, the presence of a rapidly fatal underlying disease, previous antimicrobial therapy, and infection by serotypes 14 and 23. All clinically significant isolates of S. pneumoniae should be submitted for antimicrobial susceptibility studies, and, whenever a high prevalence of resistance to penicillin and macrolides is detected, the use of these well-established empirical therapeutic regimens should be reconsidered.
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PMID:Susceptibility of Streptococcus pneumoniae to penicillin: a prospective microbiological and clinical study. 155 28

Organ transplantation in the 1960s proceeded according to a "lifeboat" ethics formula with physicians acting as "gatekeepers." Selection of transplant recipients is now based on medical urgency and waiting time. Some candidates continue to be given low priority by virtue of psychological impairment. The three As--advanced age, acquired immune deficiency syndrome (or positive human immunodeficiency virus status), and alcoholism--also stand out as characteristics that tend to exclude candidates. Cancer is another relative or absolute contraindication to transplantation. This article focuses retrospectively on the psychosocial and medical aspects of the decision to include six patients at Massachusetts General Hospital who were selected for organ transplantation despite their borderline candidacy. The authors introduce four lines of thinking that decision-makers might use to either include or exclude marginal candidates (e.g., the physician's interpretation of what duty requires, the patient's or surrogate's wishes, cost-benefit considerations, or the need for research to improve our scientific understanding of transplantation issues) and discuss an ethical approach that supports each line of thinking. The authors conclude that not all of the ethical approaches lead practitioners and policymakers to the same conclusions regarding the optimum size of or who should be a part of the recipient pool. The future of who receives transplants and why depends at least in part on the underlying ethical considerations that are deemed appropriate as determinants of practice and policy.
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PMID:Reevaluation of organ transplantation criteria. Allocation of scarce resources to borderline candidates. 155 85

The histopathologic investigation of children with congenital immunodeficiency, and its relation to functional parameters and clinical data have been a major contribution to the present knowledge on the histophysiologic aspects of normal immune system function. Based on thorough knowledge in histophysiologic and dynamic aspects of lymphoid organs, the histopathologic evaluation in cases of suspected immunodeficiency today forms an integral part of the assessment of the immune status. Apart from conventional histologic techniques, advanced technology such as immunohistochemistry and in situ hybridization is applied. This enables analysis of the basic cellular components in various lymphoid tissue compartments, and evaluation of the consequences of the deficiency by the assessment of microorganisms and neoplasia. This review focuses on the histopathologic contribution to immunodeficiency evaluation. Sections deal with (1) the description of alterations in the various lymphoid tissues (bone marrow, thymus, lymph node, spleen, and gastrointestinal tissue); (2) histopathology of infection and malignancy; (3) pathology of some types of congenital immunodeficiency; (4) histopathologic methods and reagents; and (5) an autopsy protocol for immunodeficiency.
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PMID:Pathology of congenital immunodeficiencies. 156 87

Peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients is rarely caused by group B beta-hemolytic streptococcus species. We describe a 52-year-old man with chronic glomerulonephritis who developed a fatal peritonitis due to streptococcus group B in the absence of predisposing factors such as diabetes mellitus, malignancy, human immunodeficiency virus (HIV) infection, or liver disease. This report suggests that although beta-hemolytic streptococcus is a rare cause of peritonitis, the severity of the infection may be overwhelming and may rapidly lead to serious consequences and death.
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PMID:Fatal peritonitis due to group B beta-hemolytic streptococcus in a patient receiving chronic ambulatory peritoneal dialysis. 156 28

Freedom from infection is the result of many tiers of immune defenses that harmoniously interact to rid the body of microorganisms and their products, which are perceived as foreign. The ability to distinguish self from nonself is embodied in lymphocytes, which serve both effector and regulatory functions. Through the elaboration of cytokines and immunoglobulins, lymphocytes recruit nonspecific immune effectors, focus their activity, and modulate the intensity of the immune response. The phylogenetically more primitive complement system serves a similar function. Although congenital defects in immune function occur, by far the most common causes of immunodeficiency are acquired and occur in patients treated for cancer with myelosuppressive, cytolytic drugs and in transplant recipients treated with immunosuppressants. HIV infection and malnutrition are responsible for even larger numbers of immunocompromised patients worldwide. The nature and severity of infections that occur as a result of immunodeficiency vary as a function of the immune effector targeted and the degree to which it is dysfunctional. Granulocytopenia is well tolerated unless the absolute number of circulating cells falls below 500/mm3. Profound granulocytopenia and deficits of neutrophil function are often manifest as bacterial or fungal infections. Complement deficiency predisposes to infection with encapsulated bacteria such as pneumococci, meningococci, and Haemophilus influenzae. T cells play such a central role in the immune response that their derangement is associated with susceptibility to almost any potential pathogen. These patients often succumb to mortal opportunistic infections. Recent advances in hybridoma and recombinant DNA technology have provided us with immunologic reagents that enable us to manipulate the immune response. Anti-CD3 monoclonal antibody has permitted salvage of solid organ transplants in well-defined clinical settings. Monoclonal antibodies against TNF-alpha and lipopolysaccharide may alter the consequences of gram-negative sepsis. Alternatively, recombinant cytokines have been associated with clinically significant tumor regression in selected patients, presumably by enhancing the nascent antitumor immune response. The development of immunologic reagents such as these in concert with our growing understanding of the immune system may translate to improved care for immunocompromised patients.
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PMID:Immune function and dysfunction. A primer for the radiologist. 157 Mar 93

Causes of cellular immunodeficiency frequently associated with cancer remain poorly understood. One possible mechanism is tumor cell membrane shedding of immunosuppressive molecules, such as the sialic acid-containing glycosphingolipids, gangliosides. To explore this interesting hypothesis and establish structure-activity relationships, we examined the effects of a series of highly purified human gangliosides on T cell function. In all, ten individual molecular species of two major biosynthetic pathways were compared for their ability to inhibit human T cell proliferative responses. They include GM1, GD1a, GD1b, and GT1b (the predominant normal brain species), and GM4, GM3, GM2, GD3, GD2 and GQ1b. Strikingly, each HPLC-purified molecule, from the simplest monosialoganglioside to the most complex polysialoganglioside, had potent inhibitory activity; even the ganglioside with the most elemental carbohydrate structure (GM4, one sialic acid linked to a monosaccharide) strongly inhibits T cell proliferative responses to tetanus toxoid (ID90 = 1.5 microM). The data also reveal a complex interplay between elements of oligosaccharide structure in determining immunosuppressive activity. Sialic acid is critical to maximal activity, and (i) immunosuppression is most potent in gangliosides containing a terminal sialic acid. (ii) Total desialylation almost abolishes activity and (iii) partial alteration (lactone formation) reduces activity. (iv) Activity is generally but not always higher with higher numbers of sialic acid residues/molecule, and (v) some larger neutral glycosphingolipids retain measurable immunosuppressive activity. Overall, the potent inhibition by gangliosides supports the hypothesis that shedding of these molecules by tumors creates a highly immunosuppressive microenvironment around the tumor, thereby inhibiting the function of infiltrating host leukocytes and contributing to diminished T cell responses in cancer.
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PMID:Immunosuppression by human gangliosides: I. Relationship of carbohydrate structure to the inhibition of T cell responses. 157 61


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