Diagnostic value of dengue virus-specific IgA and IgM serum antibody detection.

The diagnostic value of dengue virus (DV)-specific immunoglobulin A (IgA) serum antibody detection, by an indirect immunofluorescence assay (IFA) was evaluated. For this study, the kinetics of DV-specific IgA serum antibodies was analysed in two experimentally immunised macaques, paired samples from 35 patients suspected of a primary or secondary DV infection, paired sera from patients with high levels of IgA specific antibodies against influenza virus (n = 15), sera from patients with other viral infections (n = 40) and healthy blood donors (n = 10), which served as controls. The presence of DV-specific IgA serum antibodies in humans and in monkeys was compared with that of DV-specific IgM demonstrated in a capture enzyme-linked immunosorbent assay (ELISA). The development of DV-specific IgA and IgM antibodies in macaques proved to be similar to that observed in humans with a DV infection. In sera obtained from suspected primary DV patients during the acute phase and convalescent phase, DV-specific IgA was detected in 1/6 (17%) and 6/6 (100%), whereas IgM was detected in 4/6 (67%) and 5/6 (83%), respectively. In sera from suspected secondary DV patients during the acute phase and convalescent phase, DV-specific IgA was detected in 18/29 (62%) and 28/29 (97%), whereas IgM was detected in 20/29 (69%) and 28/29 (97%), respectively. The control group consisted of five paired serum samples from yellow fever vaccinated individuals and a patient with acute tick-borne encephalitis, 15 paired serum samples from patients with high levels of IgA antibodies specific for influenza virus and 40 serum samples from patients with specific IgM antibodies against other viruses. Ten serum samples from healthy blood donors were included. Among the control serum samples, in one patient, both DV-specific IgA and IgM antibodies were present, and in three sera DV-specific IgM antibodies could be demonstrated. These data suggest that detection of DV-specific IgA serum antibodies by IFA may have additional value for the diagnosis of DV infection.

[Seroprevalence of human T-cell lymphotropic virus type I in Curaçao and predictive variables for that infection]. / Seroprevalentie van humaan T-cellymfotroop virus type I op Curaçao en voorspellende variabelen voor die infectie.

OBJECTIVE: To determine the seroprevalence of human T-cell leukaemia virus (HTLV) type I and predictive variables in Curaçao. DESIGN: Descriptive. SETTING: St. Elisabeth Hospital, Curaçao. METHODS: A total of 2531 sera were randomly collected from a total population of approximately 145,000 over a period of three months (of seven the sex was not known). An initial ELISA test was performed to detect anti-HTLV-I antibodies. If this test was positive an ELISA re-test (in duplicate) was performed. If one of these re-tests was found positive a western blot confirmation test was performed. The association with age, sex, social class and history of syphilis were analysed with multiple logistic regression models and adjusted for confounding. RESULTS: The estimated prevalence of HTLV-I was 1.9% (49/2524). No significant sex differences were observed (odds ratio (OR): 1.13; 95% confidence interval (95% CI): 0.62-2.05). Increasing age (p for trend = 0.0003) and lower social class (OR: 1.86; 95% CI: 1.03-3.38) were important predictive factors for HTLV-I infection. Members of the lower social classes and persons 50 years or older were at relatively high risk (OR: 3.91; 95% CI: 2.21-6.94). CONCLUSION: HTLV-I infection is endemic in the island of Curaçao, as in other Caribbean islands. The estimated prevalence is 1.9%. Age and lower social class were important predictive factors for HTLV-I infection.

HIV registration in the Netherlands Antilles 1985-1996 - abstract

The objectives of this paper are to describe the HIV/AIDS epidemiology in the Netherlands Antilles over the last decade and the problems attached to the registration of these cases in a country that is spread over five islands. Some of the problems are that the total number of persons tested for HIV are not recorded, there is a lack of concensus on what case-definition to use in AIDS cases and when to start with administration of drugs. These problems in registration and the ensuing deficiences in the current data give further rise to underestimating the HIV/AIDS epidemic. Since HIV/AIDS has profound impication on demographic, economic and social aspects of a society; and considering the fact that there is still no cure for the disease, it is important to understand and to have a clear picture of the epidemilogy and the consequences of HIV infection and AIDS for the population. From 1985 until the third quarter of 1996 the cumulative total of known HIV -infected persons in the Netherlands Antilles was 793. Most of them are between the ages of 25 and 44 years. From 1991 and 1993 the leading cause of death of in Curacao for people between 25 to 44 years was AIDS. HIV/AIDS accounted for 14 percent of all deaths in this age group in 1991-1993. Curacao and Saint Maarten account for 97.5 percent of the known HIV-infected for the Netherlands Antilles. Recommendations are made for improving the HIV/AIDS registration in the Netherlands Antilles. (AU)

Dengue in Curacao: an analysis of available data from 1993, 1995 and 1996 - abstract

Dengue is endemic in most countries of the Americas. The presentation of the disease can range from an undifferentiated fever to a more life-threatening form, ie., the dengue shock syndrome. Four serotypes of the viruses are distinguished: the most common ones in the American regon are types 2 and 4. It is transmitted primarily through the Aedes aegypti, a vector widely found in the region. Dengue is also a health problem in Curacao, where since 1973 endemicity has been established. The objective of the present study is to describe the dengue situation in Curacao with regards to the prevalence, surveillance system and vector control, as well as the evaluation of these. This was done on laboratory-based surveillance data of the years 1993, 1995 and 1996. Cases were either confirmed by laboratory results or classified as probable cases based on clinical information, using the case definition of the Pan American Health Organization. Results of the surveys on larval indices of the same years are presented. The surveillance data show that there was an outbreak in the first few months of 1993. One death was reported in February. During this outbreak, dengue types 2 and 4 were isolated. In 1995, there were two outbreaks, one in March/April and another one later in the year during the year during the months October/November. At the beginning of 1996 the last cases of the 1995 outbreak were detected, but in the second half of the year no confirmed cases were reported. Both the curent surveillance system and the vector surveys hae provided valuable data. Nevertheless, the prevalence of the disease in 1995 shows that the availability of information is not enough for the prevention of disease if not combined with a defined plan of action. (AU)

The melanoma growth stimulatory activity receptor consists of two proteins. Ligand binding results in enhanced tyrosine phosphorylation.

The human melanoma growth-stimulatory activities (MGSA alpha, beta, gamma/GRO) are products of immediate early genes coding for cytokines that exhibit sequence similarity to platelet factor-4 and beta-thromboglobulin. MGSA/GRO alpha has been demonstrated to partially complete for binding to the approximately 58-kDa neutrophil receptor for another beta-thromboglobulin-related chemotactic protein, IL-8. We demonstrate that when [125I]MGSA/GRO alpha was cross-linked to receptors/binding proteins from human placenta, there were two major [125I]MGSA cross-linked bands of approximately 64,000 and approximately 84,000 Mr. Because [125I]MGSA exists primarily in monomer and dimer forms at the concentrations used here, it is not clear whether the receptor/binding proteins represented by the cross-linked bands are approximately 50,000 and approximately 70,000 or approximately 58,000 and approximately 78,000 Mr. Ligand binding to the receptor proteins is associated with enhanced tyrosine phosphorylation of a number of substrates, including proteins in the same Mr range as the MGSA/GRO receptor/binding proteins.

Effects of MGSA/GRO alpha on melanocyte transformation.

In the work described here we demonstrate that the clonal cell line Mel-a-6, produced by transfection of mouse Melan-a cells with human MGSA, had an increased ability to form large colonies in soft agar and increased ability to form tumors when injected into nude mice as compared to cells transfected with the neomycin resistance gene alone. This effect appeared to be dependent on the levels of MGSA produced since another transfected clone, Mel-a-l, produced only a low level of MGSA transgene mRNA, formed only minimal large colonies in soft agar and had a tumorigenic rate equal to that of neomycin resistant controls. The histology of the Mel-a-6 tumors is compatible with features normally exhibited by melanoma tumors. The cells do not stain for melanin, and they are positive for the neural crest marker protein S-100 as well as the HMB 45 melanoma specific antigen. Immunohistochemical studies revealed expression of the human MGSA in tumor cells from tissues, excised from animals injected with cells from clone Mel-a-6. Whereas DNA ploidy analysis suggests that in vitro the Mel-a parent cell line, control Mel-a-neo, Mel-a-1 and Mel-a-6 cells show no evidence of aneuploidy, the nuclei isolated from the tumors from animals injected with Mel-a-6 do exhibit aneuploidy. These data suggest that over-expression of MGSA in immortalized melanocytes contributes to transformation.

Recombinant expression, biochemical characterization, and biological activities of the human MGSA/gro protein.

Melanoma growth stimulatory activity (MGSA) is a mitogenic protein secreted by Hs294T melanoma cells that corresponds to the polypeptide encoded by the human gro gene. The MGSA/gro cDNA has been expressed in mammalian cells and the secreted recombinant factor has been purified. Biochemical and biological characterization shows that the recombinant protein is identical with the natural protein and is devoid of posttranslational glycosylation, sulfation, and phosphorylation. The two C-terminal amino acids are proteolytically removed from the mature recombinant MGSA, indicating a length of 71 instead of the predicted 73 amino acids. The recombinant MGSA is mitogenically active on the Hs294T melanoma cells. The purified MGSA competes with interleukin 8 for binding to neutrophil receptors and exhibits neutrophil chemotactic activity equivalent to that of interleukin 8.

Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin.

Melanoma growth stimulatory activity (MGSA) is a mitogenic polypeptide secreted by Hs294T human melanoma cells. Comparison of the N-terminal sequences of the 13 and 16 kd MGSA species with the cDNA sequence revealed that the mature form of human MGSA is maximally 73 amino acids long. Expression of the cDNA in mammalian cells results in the secretion of this peptide with mitogenic activity. MGSA is structurally related to the platelet-derived beta-thromboglobulin and to several other polypeptides. These factors may constitute a family of growth factors. MGSA mRNA was detected in a variety of cell types. The level of MGSA mRNA in melanoma cells is strongly elevated by treatment with MGSA. MGSA is the gene product of a recently detected gene gro. The gene was mapped to chromosome 4 (region q13----q21). This same region also contains genes for two of the structurally related factors, for c-kit, a receptor for an as yet unidentified ligand, and for 'piebald trait', an inherited skin pigmentation disorder.