Oligoclonal immunoglobulins in HIV infection

We tested 150 patients infected with human immunodeficiency virus (HIV) for the presence of oligoclonal bands in serum, prompted by reports that these abnormal proteins may have prognostic significance. Sixty HIV-negative individuals from "at-risk" groups were tested along with 80 HIV-negative, healthy blood donors for the presence of these bands. All sera were tested by isoelectric focusing, because it is more sensitive for this purpose than more-conventional electrophoretic techniques. In the HIV-positive group, 61% of the sera had oligoclonal bands; in the HIV-negative "at-risk" group, 36% had bands. No bands were detectable in sera from the healthy blood-donor group. Some patients were also followed for differing periods throughout their infection, and changes in their oligoclonal banding patterns could not be correlated with disease progression. The fact that oligoclonal bands were found to be present without HIV infection in a substantial number of individuals from within the "at-risk" groups leads us to conclude that the presence of oligoclonal bands in HIV infection is of limited prognostic significance.     

The use of quinacrine (Atabrine) in rheumatic diseases: A reexamination

Atabrine has been available for nearly 60 years. It has a variety of actions and has been administered to millions of individuals. Its antirheumatic properties have been well documented but have not been exploited optimally for a variety of reasons. The drug is generally quite safe and could be used in low doses in lupus and rheumatoid arthritis patients as a steroid-sparing agent or synergistically with hydroxychloroquine. Its bothersome side effects should not deter the clinician from using it, because they are easy to deal with or prevent (Table 5). Future studies should attempt to better characterize the immunosuppressive actions of this powerful drug, particularly in the treatment of lupus erythematosus and rheumatoid arthritis. Studies of the role of combination or single-agent antimalarial therapy in combination with other "remittive" drugs could be of great potential benefit.     

Inflammatory Bowel Disorders

Infiltration of leucocytes into the mucosa is a hallmark feature of a number of inflammatory bowel disorders, most notably Crohn's disease and ulcerative colitis. The interactions between circulating leucocytes and the vascular endothelium that permit leucocyte migration to a site of injury or infection are mediated via a variety of adhesion molecules. There is now ample evidence for alterations in adhesion molecule expression and function in inflammatory bowel disorders. This raises the possibility that adhesion molecules could be targets for novel therapies. Indeed, many existing anti-inflammatory drugs are capable of modulating adhesion molecule expression or function. Moreover, intensive research is under way to develop more selective and effective modulators of adhesion molecules, in the hope that they will be useful for treating various inflammatory disorders.     

Effects of intracerebral implants of steroid hormones on scent marking in the ovariectomized female gerbil (Meriones unguiculatus)

The effects of intracerebral implants of steroid hormones on scent marking in the female gerbil (Meriones unguiculatus) were studied in two experiments. In Experiment 1 various steroids were implanted alone or in combination into the preoptic and anterior hypothalamic area of ovariectomized females. Unilateral implants of testosterone + estrogen, estrogen, estrogen + progesterone, testosterone and testosterone + progesterone stimulated a significant level of marking when compared to controls. Experiment 2 utilized bilateral implants of estrogen dissolved in paraffin in order to explore the distribution hormone sensitive areas in the brain which might be important in the regulation of scent marking in the female gerbil. Pellets of estrogen-paraffin were implanted stereotaxically into either the anterior hypothalamus, preoptic area, septum, hippocampus, thalamus, amygdala or anterior olfactory nucleus of ovariectomized females. Total dosage of hormone implanted was 8.2–8.4 μg. A significant level of marking resulted in animals receiving implants into the anterior hypothalamus, preoptic area and septum when compared to controls. Marking appeared at about the same rate in each of these groups; however, the level of marking attained differed. By the last trial, anterior hypothalamic implanted animals were marking significantly more often than animals in either the preoptic or septum groups. Although there was no evidence of ieakage from the brain, the data suggested that some rapid diffusion of hormone, largely restricted to the brain, was taking place or that the three areas were differentially responsive to the hormone. The data do indicate that some localization of function does exist with respect to regulation of scent marking in the female.     

A2 adenosine receptors inhibit calcium influx through L-type calcium channels in rod photoreceptors of the salamander retina.

Presynaptic inhibition is a major mechanism for regulating synaptic transmission in the CNS and adenosine inhibits Ca(2+) currents (I(Ca)) to reduce transmitter release at several synapses. Rod photoreceptors possess L-type Ca(2+) channels that regulate the release of L-glutamate. In the retina, adenosine is released in the dark when L-glutamate release is maximal. We tested whether adenosine inhibits I(Ca) and intracellular Ca(2+) increases in rod photoreceptors in retinal slice and isolated cell preparations. Adenosine inhibited both I(Ca) and the [Ca(2+)]i increase evoked by depolarization in a dose-dependent manner with approximately 25% inhibition at 50 microM. An A2-selective agonist, (N(6)-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) (DPMA), but not the A1- or A3-selective agonists, (R)-N(6)-(1-methyl-2-phenylethyl)adenosine and N(6)-2-(4-aminophenyl)ethyladenosine, also inhibited I(Ca) and depolarization-induced [Ca(2+)]i increases. An inhibitor of protein kinase A (PKA), Rp-cAMPS, blocked the effects of DPMA on both I(Ca) and the depolarization-evoked [Ca(2+)]i increase in rods. The results suggest that activation of A2 receptors stimulates PKA to inhibit L-type Ca(2+) channels in rods resulting in a decreased Ca(2+) influx that should suppress glutamate release.     

Non-invasive and quantitative near-infrared haemoglobin spectrometry in the piglet brain during hypoxic stress, using a frequency-domain multidistance instrument

The frequency-domain multiple-distance (FDMD) method is capable of measuring the absolute absorption and reduced scattering coefficients of optically turbid media. Absolute measurement of absorption at two near-infrared (NIR) wavelengths makes possible the quantitation of tissue haemoglobin concentration and tissue haemoglobin oxygen-saturation (StO2). However, errors are introduced by the uncertainties of background absorption and the dissimilarities between real tissues and the simplified mathematical model on which these measurements are based. An FDMD-based tissue instrument has been used for the monitoring of tissue haemoglobin concentration and oxygenation in the brain of newborn piglets during periods of hypoxia and hyperoxia. These tissue haemoglobin saturation values were compared with arterial saturation (SaO2) and venous saturation (SvO2) measured by blood gas analyses. A linear correlation was observed between StO2 and the average of SaO2 and SvO2. However, StO2 is not equal to any fixed weighted average of SaO2 and SvO2 unless we introduce an effective background tissue absorption. The magnitude of the background absorption was about 0.08 cm(-1) at 758 nm and 0.06 cm(-1) at 830 nm, and it was nearly consistent between piglets. The origin of this 'effective' background absorption may be real, an artefact caused by the application of a simplified model to a complex sample, or a combination of factors.