Human cytomegalovirus open reading frame TRL11/IRL11 encodes an immunoglobulin G Fc-binding protein.

Several herpesviruses encode Fc receptors that may play a role in preventing antibody-mediated clearance of the virus in vivo. Human cytomegalovirus (HCMV) induces an Fc-binding activity in cells upon infection, but the gene that encodes this Fc-binding protein has not been identified. Here, we demonstrate that the HCMV AD169 open reading frame TRL11 and its identical copy, IRL11, encode a type I membrane glycoprotein that possesses IgG Fc-binding capabilities.

Molecular cloning of a human Vent-like homeobox gene.

We have isolated a previously unknown human homeobox-containing cDNA, VENT-like homeobox-2 (VENTX2), using PCR with a bone marrow cDNA library and primers designed from the VENTX1 (alias HPX42) homeobox sequence. Here we describe the molecular cloning, chromosomal localization to 10q26.3, and functional analysis of this gene. The 2.4-kb human VENTX2 cDNA encoded a protein with a predicted molecular weight of 28 kDa containing a homeodomain with 65% identity to the Xenopus laevis ventralizing gene Xvent2B. VENTX2 antisera detected a 28-kDa protein in cells transfected with a VENTX2 expression construct, in a human erythroleukemic cell line and in bone marrow samples obtained from patients in recovery phase after chemotherapy. The similarity of the homeodomains from VENTX2 and the X. laevis Vent gene family places them in the same homeodomain class. Consistent with this structural classification, overexpression of VENTX2 in zebrafish embryos led to anterior truncations and failure to form a notochord, which are characteristics of ventralization.

Regulation of quorum sensing in Vibrio harveyi by LuxO and sigma-54.

The bioluminescent marine bacterium Vibrio harveyi controls light production (lux) by an elaborate quorum-sensing circuit. V. harveyi produces and responds to two different autoinducer signals (AI-1 and AI-2) to modulate the luciferase structural operon (luxCDABEGH) in response to changes in cell-population density. Unlike all other Gram-negative quorum-sensing organisms, V. harveyi regulates quorum sensing using a two-component phosphorylation-dephosphorylation cascade. Each autoinducer is recognized by a cognate hybrid sensor kinase (called LuxN and LuxQ). Both sensors transduce information to a shared phosphorelay protein called LuxU, which in turn conveys the signal to the response regulator protein LuxO. Phospho-LuxO is responsible for repression of luxCDABEGH expression at low cell density. In the present study, we demonstrate that LuxO functions as an activator protein via interaction with the alternative sigma factor, sigma54 (encoded by rpoN). Our results suggest that LuxO, together with sigma54, activates the expression of a negative regulator of luminescence. We also show that phenotypes other than lux are regulated by LuxO and sigma54, demonstrating that in Vibrio harveyi, quorum sensing controls multiple processes.

A genetic analysis of the functions of LuxN: a two-component hybrid sensor kinase that regulates quorum sensing in Vibrio harveyi.

The bioluminescent marine bacterium Vibrio harveyi controls light production using two parallel quorum-sensing systems. V. harveyi produces two autoinducers (AI-1 and AI-2), which are recognized by cognate membrane-bound two-component hybrid sensor kinases called LuxN and LuxQ respectively. Under conditions of low cell density, in the absence of autoinducer, the hybrid sensors are kinases, and under conditions of high cell density, in the presence of autoinducer, the sensors are phosphatases. These activities allow LuxN and LuxQ to modulate the level of phosphorylation of the response regulator protein LuxO. LuxO, in turn, controls the transcription of the genes encoding luciferase. The phosphorelay protein LuxU is required for signalling to LuxO. In this report, we present a genetic analysis of the activities of the AI-1 sensor LuxN. Point mutations and in frame deletions were constructed in luxN and recombined onto the chromosome of V. harveyi for in vivo phenotypic analysis. We show that the conserved histidine (H471) in the sensor kinase domain of LuxN is required for kinase activity but not for phosphatase activity. In contrast, the conserved aspartate (D771) in the response regulator domain of LuxN is required for both activities. Furthermore, the LuxN phosphatase activity is localized to the response regulator domain. Our results indicate that the LuxN kinase activity is regulated by the presence of AI-1, whereas the LuxN phosphatase activity is constitutive. We also show that signalling from the two V. harveyi quorum-sensing systems is not equivalent. AI-1 and LuxN have a much greater effect on the level of LuxO phosphate and therefore Lux expression than do AI-2 and LuxQ.

Morphologic and molecular characterization of new Cyclospora species from Ethiopian monkeys: C. cercopitheci sp.n., C. colobi sp.n., and C. papionis sp.n.

In recent years, human cyclosporiasis has emerged as an important infection, with large outbreaks in the United States and Canada. Understanding the biology and epidemiology of Cyclospora has been difficult and slow and has been complicated by not knowing the pathogen s origins, animal reservoirs (if any), and relationship to other coccidian parasites. This report provides morphologic and molecular characterization of three parasites isolated from primates and names each isolate: Cyclospora cercopitheci sp.n. for a species recovered from green monkeys, C. colobi sp.n. for a parasite from colobus monkeys, and C. papionis sp.n. for a species infecting baboons. These species, plus C. cayetanensis, which infects humans, increase to four the recognized species of Cyclospora infecting primates. These four species group homogeneously as a single branch intermediate between avian and mammalian Eimeria. Results of our analysis contribute toward clarification of the taxonomic position of Cyclospora and its relationship to other coccidian parasites.

An increase in hookworm infection temporally associated with ecologic change.

This report describes a significant increase in the prevalence of hookworm infection in an area of Haiti where intestinal parasites are common, but hookworm has not been common. Changing environmental conditions, specifically deforestation and subsequent silting of a local river, have caused periodic flooding with deposition of a layer of sandy loam topsoil and increased soil moisture. We speculate that these conditions, conducive to transmission of the infection, have allowed hookworm to reemerge as an important human pathogen.

Dying in palliative care units and in hospital: a comparison of the quality of life of terminal cancer patients.

A comparison of the quality of life of terminal cancer patients in two palliative care units with that of those in a general hospital is reported here. Quality of life was considered as a multidimensional concept. It was assessed for the 182 patients by applying content analysis scales to transcripts of their responses to part of a standardized interview. A personal construct model of dying provided the specific hypotheses about differences in quality of life. Patients in specialized palliative care units were, as predicted, found to differ from those dying in hospital, showing less indirectly expressed anger but more positive feelings. They also reported more anxiety about death but less anxiety about isolation and general anxiety, and fewer influential and nonspecified shared relationships. Against prediction, the patients in the two specialized units were also found to differ from each other, those in the smaller unit showing more directly expressed anger and helplessness than those in the larger unit.

Time trends and occupational differences in cancer of the testis in New Zealand.

The findings are reported from a New Zealand Cancer Registry-based case-control study involving 427 male patients with testicular cancer registered during the period 1979-1983 and aged 20 years or more at time of registration. Controls were also males chosen from the Cancer Registry with two controls per case, matched on age and year of registration. It was found that, as in other countries, persons in the upper social class groupings were at increased risk of testicular cancer. Persons in professional occupations were also at increased risk, but the odds ratio of 1.09 was much smaller than found in other studies. The previously reported excess risks for farmers, food and beverage workers, forestry workers, and pulp and paper workers were not supported by the New Zealand data. On the other hand, the previously reported excess risk for sales and service workers including members of the armed forces was supported, to some extent, by the New Zealand data with odds ratios of 1.38 (95% confidence limits 0.98-1.93) and 2.15 (95% confidence limits 0.80-5.79), respectively. Other groups with elevated risk include: physicians (odds ratio = 6.50, 95% confidence limits 1.29-32.6); production supervisors (odds ratio = 2.85,95% confidence limits 1.00-8.13); and motor vehicle mechanics (odds ratio = 2.02, 95% confidence limits 0.93-4.42). However, the New Zealand data generally does not suggest that occupational factors (or lifestyle factors associated with occupation) are of major direct importance in the etiology of testicular cancer. The incidence of testicular cancer has a bimodal age distribution in New Zealand and has risen markedly during the period 1948-1979. The New Zealand data differed from patterns observed in other countries in that the relative increase was approximately uniform across age groups rather than being stronger in the younger age groups.

Leukemia among New Zealand agricultural workers. A cancer registry-based study.

Mortality studies have indicated that workers in agriculture and forestry may be at increased risk of leukemia. Findings are reported from a New Zealand Cancer Registry-based case-control study involving 546 male leukemia patients registered during 1979-1983 and aged 20 years or more at time of registration. Controls were also males chosen from the Cancer Registry with four controls per case, matched on age and year of registration. The case group contained an excess of the occupational category involving agriculture and forestry (odds ratio (OR) = 1.24, 95% confidence interval (CI) = 0.95-1.61) with the greatest relative risk being for livestock farmers (OR = 3.00, 95% CI = 1.23-7.32). There was also an excess of electrical workers (OR = 1.72, 95% CI = 0.92-3.20). The agricultural excess was greatest in patients aged 65 years or more at time of registration (OR = 1.29, 95% CI = 0.94-1.78), particularly in patients with acute myeloid leukemia (OR = 1.55, 95% CI = 0.90-2.67) or acute monocytic leukemia OR = 10.38, 95% CI = 1.99-54.29), although the latter excess only involved five cases. Acute myeloid leukemia was also elevated in meat workers (OR = 2.51, 95% CI = 1.19-5.30).

Mortality among New Zealand Maori and non-Maori Mormons.

Mortality rates for New Zealand Maori and non-Maori Mormons in the period 1970-77 have been compared with those for non-Mormons in the census year 1976 to measure the impact of the Mormon lifestyle on differences in mortality between Maoris and non-Maoris. Maori mortality was much lower among Mormons than non-Mormons suggesting that environmental, rather than genetic factors, play a predominant role in the relatively high overall Maori mortality. However the prevalence of smoking among Maori Mormons was not much lower than for the general Maori population. Reasons for the relative mortality advantage of Maori Mormons were therefore not clear, although attitudes to health and health services utilization, and the influence of strong social support networks, might be involved. Paradoxically, non-Maori Mormon mortality rates were similar to those for non-Mormons. A combination of factors appeared to contribute to this finding including the fact that 26% of non-Maori Mormons were of Pacific Island origin, non-Maori Mormons were of lower socioeconomic status than other non-Maoris, and part Maoris probably constitute a high, but unknown, proportion of Mormons classified as non-Maoris.