The Evolution of Thyroid Function Tests

No AbstractKeywords: Evolution, Thyroid Function Test

Characterization of a Full-Length Endogenous Beta-Retrovirus, EqERV-Beta1, in the Genome of the Horse (Equus caballus)

Information on endogenous retroviruses fixed in the horse (Equus caballus) genome is scarce. The recent availability of a draft sequence of the horse genome enables the detection of such integrated viruses by similarity search. Using translated nucleotide fragments from gamma-, beta-, and delta-retroviral genera for initial searches, a full-length beta-retrovirus genome was retrieved from a horse chromosome 5 contig. The provirus, tentatively named EqERV-beta1 (for the first equine endogenous beta-retrovirus), was 10434 nucleotide (nt) in length with the usual retroviral genome structure of 5′LTR-gag-pro-pol-env-3′LTR. The LTRs were 1361 nt long, and differed approximately 1% from each other, suggestive of a relatively recent integration. Coding sequences for gag, pro and pol were present in three different reading-frames, as common for beta-retroviruses, and the reading frames were completely open, except that the env gene was interrupted by a single stopcodon. No reading frame was apparent downstream of the env gene, suggesting that EqERV-beta1 does not encode a superantigen like mouse mammary tumor virus (MMTV). A second proviral genome of EqERV-beta1, with no stopcodon in env, is additionally integrated on chromosome 5 downstream of the first virus. Single EqERV-beta1 LTRs were abundantly present on all chromosomes except chromosome 24. Phylogenetically, EqERV-beta1 most closely resembles an unclassified retroviral sequence from cattle (Bos taurus), and the murine beta-retrovirus MMTV

Toxic cannabis psychosis is a valid entity

One hundred black men admitted to hospital with acute psychiatric symptoms were investigated for the presence of urinary cannabis metabolltes in order to delineate the psychiatric role played by 'dagga', the potent South African cannabinol, in the study population and to determine the diagnostic value of the entity 'toxic psychosis (dagga)'. Cannabinoids were present in 29% of patients, and 31% were discharged with a diagnosis of toxic psychosis (dagga). Clinical and demographic material was gathered for all patients and no consistent differences were found between dagga-posItlve and dagga-negative patients or toxic dagga psychotic patients and 'functional' psychotics other than a history of recent dagga use and the dagga screening test result. The latter measure was found to be both more sensitive and more specific than the history of dagga use alone. The findings support the routine use of a simple screening test for dagga in the sample population studied. The study demonstrated the heterogeneous nature of the toxic dagga psychosis syndrome by documenting a variety of different clinical presentations, which included schizophrenia (42%), paranoia (26%), maniform psychosis (16%) and organic psychosis (16%)

Identifying HIV-1 dual infections

Transmission of human immunodeficiency virus (HIV) is no exception to the phenomenon that a second, productive infection with another strain of the same virus is feasible. Experiments with RNA viruses have suggested that both coinfections (simultaneous infection with two strains of a virus) and superinfections (second infection after a specific immune response to the first infecting strain has developed) can result in increased fitness of the viral population. Concerns about dual infections with HIV are increasing. First, the frequent detection of superinfections seems to indicate that it will be difficult to develop a prophylactic vaccine. Second, HIV-1 superinfections have been associated with accelerated disease progression, although this is not true for all persons. In fact, superinfections have even been detected in persons controlling their HIV infections without antiretroviral therapy. Third, dual infections can give rise to recombinant viruses, which are increasingly found in the HIV-1 epidemic. Recombinants could have increased fitness over the parental strains, as in vitro models suggest, and could exhibit increased pathogenicity. Multiple drug resistant (MDR) strains could recombine to produce a pan-resistant, transmittable virus

Evaluation of point-of-care tests for detecting microalbuminuria in diabetic patients

Background: Microalbuminuria, the presence of low levels of albumin in the urine, indicates renal damage and is recognised as a risk factor for the progression of renal and cardiovascular disease. Several international scientific bodies recommend microalbuminuria screening. Point-of-care testing (POCT) of microalbuminuria allows immediate identification of risk, and monitoring of treatment effects. In this study, two POCT instruments were evaluated as microalbuminuria screening methods. Method: Spot urine specimens from diabetic patients were analysed with the quantitative HemoCue® urine albumin analyser (n = 245), and the semiquantitative Clinitek® microalbumin urine dipstick (n = 204). These results were compared to the respective data for laboratory-determined albumin (nephelometry), creatinine (modified Jaffe) and albumin-to-creatinine ratio (ACR). Results: Linear regression analysis demonstrated a good correlation for the HemoCue® urine albumin with the laboratorydetermined albumin concentration (y = 0.8557x + 0.2487y, r = 0.97). The sensitivities for the HemoCue® and Clinitek® POCT systems were 79.6% and 83.8%, and the specificities 97.1% and 93.8% respectively. Positive and negative predictive values for the HemoCue® were 95.6% and 85.8%, and were 88.6% and 91.0% the Clinitek®. The repeatability of both instruments was excellent. Both instruments are easy to use, and more cost-effective than the laboratory methods for albumin and ACR. Conclusion: Both the HemoCue® and the Clinitek® microalbumin POCT systems for albuminuria are easy to use and inexpensive, and are adequately accurate as a screening method. Although the HemoCue® POCT system measures only urine albumin concentration, its sensitivity and specificity compared well with that of the Clinitek® POCT system, which determines the ACR.Keywords: microalbuminuria, point-of-care testing, HemoCue®, Clinitek®, urinary albumin excretio

SIVdrl detection in captive mandrills: are mandrills infected with a third strain of simian immunodeficiency virus?

A pol-fragment of simian immunodeficiency virus (SIV) that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus) was detected in two mandrills (Mandrillus sphinx) from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely to be hybrids. Their mitochondrial haplotype suggested that they descended from founder animals in Cameroon or northern Gabon, close to the habitat of the drill. SIVdrl has once before been found in a wild-caught mandrill from the same region, indicating that mandrills are naturally infected with a SIVdrl-like virus. This suggests that mandrills are the first primate species to be infected with three strains of SIV: SIVmnd1, SIVmnd2, and SIVdrl

Effect of desferrioxamine on reperfusion damage of rat heart mitochondria

Ischaemia of the myocardium leads to necrosis unless oxygen supply is restored but it has only recently been realised that reperfusion is not without danger. The greatest rate ofmyocardial damage, as measured by mitochondrial function, occurred during the first 5 minutes of reperfusion in rat hearts subjected to normothermic ischaemic cardiac arrest. Addition of desferrioxamine to the perfusate after 5 minutes of reperfusion did not reverse the mitochondrial damage. It is therefore concluded that desferrioxamine prevents mitochondrial damage caused by ischaemia-reperlusion but does not reverse the damage already present

Retroviral superinfection resistance

The retroviral phenomenon of superinfection resistance (SIR) defines an interference mechanism that is established after primary infection, preventing the infected cell from being superinfected by a similar type of virus. This review describes our present understanding of the underlying mechanisms of SIR established by three characteristic retroviruses: Murine Leukaemia Virus (MuLV), Foamy Virus (FV), and Human Immunodeficiency Virus (HIV). In addition, SIR is discussed with respect to HIV superinfection of humans. MuLV resistant mice exhibit two genetic resistance traits related to SIR. The cellular Fv4 gene expresses an Env related protein that establishes resistance against MuLV infection. Another mouse gene (Fv1) mediates MuLV resistance by expression of a sequence that is distantly related to Gag and that blocks the viral infection after the reverse transcription step. FVs induce two distinct mechanisms of superinfection resistance. First, expression of the Env protein results in SIR, probably by occupancy of the cellular receptors for FV entry. Second, an increase in the concentration of the viral Bet (Between-env-and-LTR-1-and-2) protein reduces proviral FV gene expression by inhibition of the transcriptional activator protein Tas (Transactivator of spumaviruses). In contrast to SIR in FV and MuLV infection, the underlying mechanism of SIR in HIV-infected cells is poorly understood. CD4 receptor down-modulation, a major characteristic of HIV-infected cells, has been proposed to be the main mechanism of SIR against HIV, but data have been contradictory. Several recent studies report the occurrence of HIV superinfection in humans; an event associated with the generation of recombinant HIV strains and possibly with increased disease progression. The role of SIR in protecting patients from HIV superinfection has not been studied so far. The phenomenon of SIR may also be important in the protection of primates that are vaccinated with live attenuated simian immunodeficiency virus (SIV) against pathogenic SIV variants. As primate models of SIV infection closely resemble HIV infection, a better knowledge of SIR-induced mechanisms could contribute to the development of an HIV vaccine or other antiviral strategies

Of Mice and Men: On the Origin of XMRV

The novel human retrovirus xenotropic murine leukemia virus-related virus (XMRV) is arguably the most controversial virus of this moment. After its original discovery in prostate cancer tissue from North American patients, it was subsequently detected in individuals with chronic fatigue syndrome from the same continent. However, most other research groups, mainly from Europe, reported negative results. The positive results could possibly be attributed to contamination with mouse products in a number of cases, as XMRV is nearly identical in nucleotide sequence to endogenous retroviruses in the mouse genome. But the detection of integrated XMRV proviruses in prostate cancer tissue proves it to be a genuine virus that replicates in human cells, leaving the question: how did XMRV enter the human population? We will discuss two possible routes: either via direct virus transmission from mouse to human, as repeatedly seen for, e.g., Hantaviruses, or via the use of mouse-related products by humans, including vaccines. We hypothesize that mouse cells or human cell lines used for vaccine production could have been contaminated with a replicating variant of the XMRV precursors encoded by the mouse genome