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Biomedical subjects

J Chin

Publications and source records attributed to J Chin.

At least 109 records · Page 6Linked to original sources

IL-1 binds to high affinity receptors on human osteosarcoma cells and potentiates prostaglandin E2 stimulation of cAMP production.

IL-1 is a potent bone resorbing agent. Its mechanism of action is unknown, but the presence of osteoblasts was shown to be necessary for IL-1 stimulation of bone resorption by isolated osteoclasts. This study examines the presence of IL-1R and IL-1 effects in osteoblastic cells from a clonal human osteosarcoma cell line, Saos-2/B-10. We found that the binding affinity and the number of binding sites increases substantially during the postconfluent stage. Scatchard and curve-fitting analysis revealed one class of high affinity binding sites, with Kd/Ki's of 40 +/- 17 pM (mean +/- SD) for IL-1 alpha (n = 5) and 9 +/- 7 pM for IL-1 beta (n = 5) and 2916 +/- 2438 (n = 6) receptors/cell. Incubation of the cells with 125I-IL-1 alpha (100 pM) at 4 degrees C, followed by incubation at 37 degrees C up to 4 h, revealed internalization of receptor-bound IL-1 alpha. Chemical cross-linking studies showed that the IL-1R in Saos-2/B-10 cells had a molecular mass of approximately 80 kDa. To assess the biologic effect of IL-1 in Saos-2/B-10 cells, we determined PGE2 content and adenylate cyclase activity. Although IL-1 had no effect on PGE2 synthesis, both IL-1 alpha and IL-1 beta enhanced PGE2 stimulation of adenylate cyclase two- to four-fold in a dose-dependent manner. The half-maximal effect for IL-1 alpha was seen at 8 to 10 pM and for IL-1 beta at 0.6 to 1.8 pM. IL-1 did not enhance basal adenylate cyclase or stimulation by parathyroid hormone, isoproterenol, or forskolin. IL-1 enhancement of PGE2-stimulated adenylate cyclase was detected between 1 to 2 h, was maximal at 4 to 5 h, was not prevented by cycloheximide treatment, and was seen in membranes from IL-1 pretreated cells. These data show effects of IL-1 on a human osteoblast-like cell line that are mediated by high affinity receptors. These IL-1 effects could contribute to the biologic action of IL-1 on bone.

Adenylyl Cyclases↗

Current and future dimensions of the HIV/AIDS pandemic in women and children.

The WHO estimates that during the first decade of the HIV/AIDS pandemic there were about 500,000 cases of AIDS in women and children, most of which have been unrecognised. During the 1990s, WHO estimates that the pandemic will kill an additional 3 million or more women and children world wide. HIV infection among heterosexual populations has been increasing throughout the world during the 1980s. AIDS has become the leading cause of death for women aged 20-40 in major cities in the Americas, Western Europe, and sub-Saharan Africa. In these cities, infant and child mortality could be as much as 30% greater than what would otherwise have been expected. During the 1990s, not only can hundreds of thousands of paediatric AIDS cases be expected, but also more than a million uninfected children will be orphaned because their HIV-infected mothers and fathers will have died from AIDS.

Acquired Immunodeficiency Syndrome↗

Methemoglobinemia induced by topical anesthetic (benzocaine).

Methemoglobinemia is a condition in which more than 2% of the hemoglobin of the blood has been oxidized to the ferric form, a molecule which is incapable of binding oxygen or carbon dioxide. Clinically, the patient appears lethargic, cyanotic, and does not respond to oxygen. We describe a patient with esophageal carcinoma who developed severe methoglobinemia following application of benzocaine in spray for local anesthesia prior to intraluminal irradiation. Review of the literature is presented.

Adenocarcinoma↗

Selective extraction of outer-membrane proteins from membrane complexes of Pseudomonas maltophila by chloroform-methanol.

An organic phase partitioning method is described for the selective purification of outer-membrane proteins (OMPs) from the total membrane complex of the opportunistic human and sheep pathogen, Pseudomonas maltophila. SDS-PAGE analysis confirmed that OMPs purified by chloroform-methanol treatment of the total membrane complex were not only identical to OMPs extracted from outer-membrane vesicles separated by sucrose gradient density centrifugation, but also possessed little or non-detectable levels of inner-membrane contaminants. Further analysis by enzyme linked immunosorbent assay (ELISA) and immunoblotting established that OMPs extracted by organic phase partitioning with chloroform-methanol retained antigenicity and serological activity indistinguishable from OMPs that were present in outer-membrane vesicles resolved by isopycnic sucrose density centrifugation of sarkosyl-treated membrane complexes.

Animals↗

Extraction of membrane antigens from Brucella ovis and an assessment of their serological activity by immunoblotting.

The efficacy and selectivity of chaotropic and phase-partitioning procedures for the extraction of membrane proteins from Brucella ovis were compared with a standard Sarkosyl method. Major group 1, 2 and 3 outer-membrane proteins (OMPs) of B. ovis stained by Coomassie blue in SDS-PAGE gels had, respectively, apparent molecular masses of 81/82 kDa, 39-41 kDa and 30-32 kDa. The presence of these bands in the Sarkosyl extract of total membrane vesicles (TMVs) indicate that the procedure failed to selectively solubilize only inner-membrane proteins (IMPs). SDS-PAGE analyses also revealed the presence of OMPs and other additional bands following extraction of B. ovis TMVs by butanol phase-partitioning or with extraction solutions based on the chaotropic reagents potassium thiocyanate (KSCN), sodium salicylate (SSC) and lithium acetate (LAE). OMPs are therefore not selectively extracted by any one of these procedures. Based on the number and staining intensity of extracted membrane-associated polypeptides, the efficacy of different extraction procedures could be graded in decreasing order as follows: KSCN, SSC, butanol and LAE. Both butanol and SSC were particularly effective in extracting group 3 OMPs. Sera from chronic excretor rams were used to identify zones of seroreactivity in immunoblots. Essentially, two reactivity patterns were seen: strong antibody binding against polypeptides in zones A (46-85 kDa), C (28-32 kDa) and D (18-22 kDa) in one, and additional reactivity against zones B (34-44 kDa) and E (13-18 kDa) polypeptides in the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Projections of HIV infections and AIDS cases to the year 2000.

After the recognition of AIDS (acquired immunodeficiency syndrome) in the early 1980s, uncertainty about the present and future dimensions of HIV (human immunodeficiency virus) infection led to the development of many models to estimate current and future numbers of HIV infections and AIDS cases. The Global Programme on AIDS (GPA) of the World Health Organization (WHO) has developed an AIDS projection model which relies on available HIV seroprevalence data and on the annual rate of progression from HIV infection to AIDS for use in areas where reporting of AIDS cases is incomplete, and where scant data are available to quantify biological and human behavioural variables. Virtually all models, including the WHO model, have projected large increases in the number of AIDS cases by the early 1990s. Such short-term projections are considered relatively reliable since most of the new AIDS cases will develop in persons already infected with HIV. Longer-term prediction (10 years or longer) is less reliable because HIV prevalence and future trends are determined by many variables, most of which are still not well understood. WHO has now applied the Delphi method to project HIV prevalence from the year 1988 to mid-2000. This method attempts to improve the quality of the judgements and estimates for relatively uncertain issues by the systematic use of knowledgeable "experts". The mean value of the Delphi projections for HIV prevalence in the year 2000 is between 3 and 4 times the 1988 base estimate of 5.1 million; these projections have been used to obtain annual estimates of adult AIDS cases up to the year 2000. Coordinated HIV/AIDS prevention and control programmes are considered by the Delphi participants to be potentially capable of preventing almost half of the new HIV infections that would otherwise occur between 1988 and the year 2000. However, more than half of the approximately 5 million AIDS cases which are projected for the next decade will occur despite the most rigorous and effective HIV/AIDS prevention efforts since these AIDS cases will develop in persons whose HIV infection was acquired prior to 1989. The Delphi projections of HIV infection and AIDS cases derived from the WHO projection model need to be periodically reviewed and modified as additional data become available. These projections should be viewed as the first of many attempts to develop estimates for planning strategies to combat the HIV/AIDS pandemic in the 1990s.

Adult↗

International travel and HIV infection.

Although human immunodeficiency virus (HIV) infection is a worldwide problem, its prevalence and pattern vary from country to country. Accordingly, the risk to international travellers of acquiring HIV infection also varies widely in different parts of the world, and depends principally on their behaviour. The risk of sexual acquisition of HIV infection can be virtually eliminated by avoiding penetrative sexual intercourse with intravenous drug users and persons who have had multiple sexual partners (such as prostitutes) or reduced by the use of condoms. The risk of parenteral exposure to HIV can be reduced by avoiding parenteral drug use and behaviour that is likely to lead to injury (with its attendant risk of requiring blood transfusion) and by seeking medical facilities with adequate capabilities to screen blood donors for HIV and to sterilize instruments. HIV screening of international travellers is an ineffective, costly, and impractical public health strategy for limiting the worldwide spread of HIV infection. Travellers infected with HIV require specialized advice regarding health precautions, prophylactic medications, and immunization.

Acquired Immunodeficiency Syndrome↗

Public health surveillance of AIDS and HIV infections.

The general methods used for public health surveillance of acquired immunodeficiency syndrome (AIDS) cases and of human immunodeficiency virus (HIV) infections are no different from those used for other diseases and infections. However, the methods used must be adapted to the unique epidemiology, wide variation in prevalences, and the very long incubation period of HIV infections. In addition, the severity of AIDS and the extreme social and personal implications of identifying HIV-infected persons make surveillance of AIDS cases and HIV infections much more difficult and place paramount importance on issues such as anonymity and confidentiality. Information on the occurrence of AIDS cases is essential for planning and developing the clinical and laboratory facilities needed for treatment and care of patients with the disease. However, surveillance of AIDS cases is of limited value for assessing the magnitude and future trends of the pandemic because the number of such cases detected, diagnosed, and reported reflect HIV infections that were acquired many years previously. In addition, there are significant problems associated with the accuracy, completeness, and timeliness of most AIDS case-reporting systems. Routine HIV surveillance systems are being developed worldwide. Such systems must be adapted to the prevailing epidemiological situation; and the sampling methods used in populations where the prevalence of infection is very low must necessarily differ from those where it is moderate to high. Large-scale population serosurveys are very costly, and the results from such surveys may also be of limited accuracy because of serious problems of selection and participation bias. Furthermore, they may become outdated rapidly in areas where a high incidence of HIV infection occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Serodiagnosis↗

An outbreak of hepatitis B associated with jet injections in a weight reduction clinic.

From January 1984 through November 1985, 31 clinical cases of hepatitis B occurred among attendees of a weight reduction clinic (clinic 1). Before the onset of illness, each case-patient had received a series of injections of human chorionic gonadotropin administered by jet injectors at clinic 1. Clinical history, risk factor assessment, serologic evaluation, and review of clinic injection records were obtained on 287 (84%) of 341 persons who had attended clinic 1 in the first 6 months of 1985. Of this cohort, 21% (60/287) had evidence of acute infection with hepatitis B virus (either documented clinical cases or antibody to hepatitis B core antigen, IgM positive). Of persons who had been given human chorionic gonadotropin at the clinic during the period studied, 24% (57/239) of those receiving human chorionic gonadotropin only by jet injector experienced acute hepatitis B virus infection. None of the 22 persons who had received injections only by syringe experienced hepatitis B virus infection. Stopping the use of the jet injectors on July 2, 1985, at clinic 1, was associated with the termination of this outbreak. This investigation demonstrated that jet injectors can become contaminated with hepatitis B virus and then may be vehicles for its transmission.

Adult↗

The immunosuppressant FK506 selectively inhibits expression of early T cell activation genes.

FK506, a neutral macrolide with immunosuppressive properties, was shown to selectively and rapidly inhibit the accumulation of IL-2 mRNA, as well as the mRNAs of other early (E) phase T cell activation genes such as IL-3, IL-4, GM-CSF, TNF alpha, IFN-gamma, and c-myc in activated human peripheral blood T cells. The activity of FK506, when compared to Cyclosporin A, another immunosuppressant, was 10 to 100x more potent in its ability to inhibit IL-2 mRNA synthesis. FK506 inhibited IL-2 mRNA accumulation in Con A, Con A plus PMA, Ionomycin plus PMA, anti-CD3, and anti-CD3 plus PMA activated T cells. Transcripts from other T cell gene classes such as the immediate early (IE) phase gene, c-fos, the late phase (L) genes, transferrin receptor, IL-2R alpha-chain, and TNF-beta, and the constitutive class genes glyceraldehyde-3-phosphate dehydrogenase and class I MHC HLA-B7 were not affected by FK506. The macrolide Rapamycin, which is structurally related to FK506, had no inhibitory effect on IE, E, L, or constitutive class mRNAs, but it appeared to increase the levels of the E-phase transcripts that were inhibited in FK506 treated T cells. The effect of FK506 on inducible genes in non-T and non-lymphoid human cells was studied in LPS-induced monocytes and PMA or IL-1 activated synovial fibroblasts. FK506 did not affect expression of the mRNAs for IL-1 alpha or IL-1 beta in human monocytes, or of stromelysin, collagenase, or TIMP in synovial fibroblasts. Nuclear run-off transcription studies indicate that FK506 inhibits transcription of the IL-2 gene. These studies suggest that Cyclosporin A and FK506 may effect a common early event in the T cell activation pathway.

Base Sequence↗

Bovine brucellosis: evaluation of field sera by a competitive and superimposable ELISA utilising a monoclonal antibody against Brucella abortus lipopolysaccharide.

With the aid of a horseradish peroxidase (HRP) tagged monoclonal antibody against smooth lipopolysaccharide from Brucella abortus (Bruce 1), a competitive and superimposable ELISA test procedure for bovine brucellosis has been evaluated for its ability to discriminate between Strain 19-vaccinated (S19-Vacc) and Biotype 1-infected (B1-Inf) cattle. In the competitive assay, all sera from S19-Vacc animals competed effectively against HRP-Bruce 1 (low HRP activity), while 10 out of 40 B1-Inf animals competed less effectively with Bruce 1 (high HRP activity). Successful competition by cattle antibodies would result in an increased proportion of cattle Igs binding to the assay antigen. This was confirmed by superimposing an alkaline phosphatase conjugated rabbit anti-cattle Ig after the competitive ELISA had been completed. With the superimposable assay, alkaline phosphatase activity was correspondingly high for S19-Vacc animals, and low for 36 out of 40 B1-Inf animals. The superimposable ELISA had therefore improved the discriminatory capabilities of the assay procedure from 75% to 90%.

Animals↗

Guidelines for rapid estimation of the direct and indirect costs of HIV infection in a developing country.

The economic impact of AIDS may be especially severe in developing nations because of the additional burden on scarce health care resources and the potential loss of human capital. We describe a methodology for estimating the direct and indirect costs of HIV infection. Our approach is designed for the typical environment of international economic consulting, where time is short, and data sparse. We focus on HIV rather than AIDS because the only way now known to prevent AIDS is to prevent HIV infection.

Acquired Immunodeficiency Syndrome↗

Identification of a monocyte specific pre-interleukin 1 beta convertase activity.

Interleukin 1 (IL-1) is a lymphokine secreted by monocytes in response to a variety of inflammatory stimuli. IL-1 beta, the predominant form of IL-1 produced by human monocytes, is synthesized as an inactive precursor of 31 kDa and is cleaved at Asp116-Ala117 to yield a 17.5-kDa extracellular form. The exact cellular site of cleavage and mechanism of secretion is at present unknown. We have prepared cell-free postnuclear extracts from freshly isolated human monocytes as well as THP.1 cells, a human monocyte-like cell line, and various blood lymphocytes and fibroblast cell lines. Using pre-IL-1 beta synthesized by in vitro transcription and translation, we have shown that only extracts derived from human monocytes and THP.1 cells were capable of cleaving precursor IL-1 beta to authentic mature IL-1 beta. Subcellular fractionation of the extracts suggested that the processing activity is found in the cytosol of monocytes or monocyte-like cell lines. The cleavage product of this protease is identical to authentic IL-1 beta as shown by mobility on SDS/PAGE and amino acid sequence analysis of the [3H]leucine-labeled product. The cleavage product is also capable of binding to the IL-1 receptor found on fibroblast membranes. Finally, mutation of Asp116----Ala116 rendered the IL-1 beta precursor resistant to cleavage by the processing activity. We conclude that a protease activity found only in monocytes will specifically process IL-1 beta to an active form.

Caspase 1↗

The global epidemiology and projected short-term demographic impact of AIDS.

This paper summarizes the natural history, surveillance, and global patterns of infections with the human immunodeficiency virus (HIV), the etiologic agent of AIDS The focus is primarily on HIV-1 because surveillance of HIV-2, which has recently been recognized as a separate type of the virus, is only just beginning. The natural progress of the disease is described, from acute infection through asymptomatic phase to the clinical illness phase. Available evidence on the speed of progression from infection to AIDS and possible co-factors in that progression are reviewed. The 3 patterns of AIDS which are described characterize the experience of different regions according to the types of transmission ( i.e., homosexual versus heterosexual, contaminated blood, drug use) and demographic characteristics of the affected persons. An epidemiologically based short-term forecasting model for AIDS cases is presented and used to project the demographic impact of AIDS in a hypothetical central African country. In that hypothetical setting, the impact of AIDS is shown to be disproportionately felt in urban areas, where the projected increase in population will decrease by 30% due to AIDS deaths by 1997; the growth rate of the rural population will be only slightly affected. In conclusion, the global prevalence of the disease, and prospects and implications for the future are discussed. Without effective drugs for treatment and no vaccine for prevention of HIV infections, the short-term outlook is not good. HIV/AIDS is expected to be an increasing public-health problem in the next 2 decades.

Acquired Immunodeficiency Syndrome↗