Reflex sympathetic dystrophy. A review

Reflex sympathetic dystrophy is a syndrome of burning pain, hyperesthesia, swelling, hyperhidrosis, and trophic changes in the skin and bone of the affected extremity. It is precipitated by a wide variety of factors in addition to nerve injury. It occurs outside of dermatomal distributions and can spread to involve other extremities without new injury. The diagnosis is primarily clinical, but roentgenography, scintigraphy, and sympathetic blockade can help to confirm the diagnosis. The most successful therapies are directed toward blocking the sympathetic innervation to the affected extremity, in conjunction with physical therapy. The theories proposed to explain the pathophysiology of reflex sympathetic dystrophy include "reverberating circuits" in the spinal cord that are triggered by intense pain, ephaptic transmission between sympathetic efferents and sensory afferents, and the presence of ectopic pacemakers in an injured nerve.     

The expression of the Epstein-Barr virus nuclear antigen (EBNA-I) in oral hairy leukoplakia

OBJECTIVE: Oral hairy leukoplakia (OHL) is characterised by the presence of a replicative Epstein-Barr virus (EBV) in the superficial layers of the epithelium. There is some doubt, however, whether this reflects activation of a latent infection of the basal epithelial cells. EBV latency is associated with the expression of the viral gene product EBNA-I and the aim of this study was to investigate EBNA-I expression in OHL. METHODS: 22 biopsies of clinically suspicious OHL and three cases of normal mucosa were available as fresh frozen or paraffin embedded material. EBNA-I was detected immunocytochemically using a rat monoclonal antibody (IH4-I) following microwave irradiation. Lytic EBV infection was confirmed by the identification of the BZLF-I protein. RESULTS: 16 of the 22 cases displayed focal replicative EBV meeting the criteria for OHL, and in 13 of these, EBNA-I expression was restricted to the nuclei of epithelial cells in the upper layers of the epithelium. EBNA-I expression was absent from the basal cells in all cases and in the nine BZLF-I negative mucosal biopsies. CONCLUSION: These findings suggest that lytic EBV infection in OHL is not the result of activation of a latent infection of basal cells and suggests a role for EBNA-I, not only in latent EBV infection, but also in virus replication.     

Polymorphic human cytochrome P450 enzymes: an opportunity for individualized drug treatment.

Approximately 40% of human P450-dependent drug metabolism is carried out by polymorphic enzymes, which can cause abolished, quantitatively or qualitatively altered or enhanced drug metabolism. The latter situation is due to stable duplication, multiduplication or amplification of active genes, most likely in response to dietary components that have resulted in a selection of alleles with multiple non-inducible genes. Several examples exist where subjects carrying certain alleles suffer from a lack of drug efficacy due to ultrarapid metabolism or, alternatively, adverse effects from the drug treatment due to the presence of defective alleles. Knowledge in this field has grown rapidly and can now be applied to both drug development and clinical practice. This is facilitated by the recent development of high-throughput methods for mutation detection and oligonucleotide chips array technology for the identification of a multitude of mutations in the genes encoding drug-metabolizing enzymes. The outcome will allow for safer and more efficient drug therapies.     

Painful spondylolysis or spondylolisthesis studied by radiography and single-photon emission computed tomography

Planar bone scintigraphy (PBS) and single-photon emission computed tomography (SPECT) were compared in 19 adults with radiographic evidence of spondylolysis and/or spondylolisthesis. SPECT was more sensitive than PBS when used to identify symptomatic patients and sites of "painful" defects in the pars interarticularis. In addition, SPECT allowed more accurate localization than PBS. In 6 patients, spondylolysis or spondylolisthesis was unrelated to low back pain, and SPECT images of the posterior neural arch were normal. The authors conclude that when spondylolysis or spondylolisthesis is the cause of low back pain, pars defects are frequently heralded by increased scintigraphic activity which is best detected and localized by SPECT.     

Characterization of a novel CYP2A7/CYP2A6 hybrid allele (CYP2A6*12) that causes reduced CYP2A6 activity

The human CYP2A6 enzyme metabolizes certain drugs and pre-carcinogens and appears to be the most important enzyme for nicotine metabolism. At present, more than 10 different allelic variants are known that cause abolished or decreased enzyme activity. Genetic polymorphism in this gene might be of particular importance for an individual's need for nicotine and for susceptibility to lung and/or liver cancer. We have identified a new CYP2A6 allele (CYP2A6*12) which carries an unequal crossover between the CYP2A6 and CYP2A7 genes in intron 2. This results in a hybrid allele where the 5' regulatory region and exons 1-2 are of CYP2A7 origin and exons 3-9 are of CYP2A6 origin, resulting in 10 amino acid substitutions compared to the CYP2A6(*)1 allele. Phenotyping with the CYP2A6 substrate coumarin indicates that it causes reduced CYP2A6 activity in'vivo. Furthermore, when expressed in mammalian COS-1 cells, the enzyme variant catalyzed 7-hydroxylation of coumarin at a rate approximately 60% of that of the wild-type enzyme. The CYP2A6(*)12 allele was present at an allele frequency of 2.2% among Spaniards, but was absent in Chinese.     

The progressive rise in the expression of alpha crystallin B chain in human endometrium is initiated during the implantation window: modulation of gene expression by steroid hormones

Human endometrium undergoes sequential changes during the menstrual cycle and becomes receptive to implantation during a defined period in the secretory phase. We attempted to identify the genes expressed during this period by representational difference analysis (RDA). When the cDNAs of a proliferative endometrium were used as the driver and the cDNAs of a post-ovulatory day 5 endometrium were used as the tester, a number of bands were identified by RDA. DNA of the cloned RDA products revealed that the majority of the clones contained a fragment of a cDNA identical to that of a crystallin B chain. Northern blot analysis showed that the expression of the alpha crystallin B chain mRNA was absent during the proliferative phase. The expression of the mRNA of alpha crystallin B chain first appeared in the secretory phase, progressively increased during this phase and peaked in the late secretory endometria. The pattern of expression of alpha crystallin B chain mRNA in the endometrium of mature cycling baboons (Papio anubis) was similar to that seen in human endometrium. As revealed by Western blot analysis, the expression of the alpha crystallin B chain protein in human endometrium followed a pattern of expression similar to its mRNA. At the cellular level, the immunoreactive protein first appeared in the surface epithelial cells of human endometrium within the implantation window without significant immunoreactivity in the underlying glandular cells. During the mid- and late secretory phases, the intensity of staining in the epithelial cells was enhanced and an intense immunoreactivity was developed in the glandular epithelium, alpha crystallin B chain was virtually an epithelial product and no immunoreactivity for this protein was detectable in the stromal cells, endothelial cells or lymphoid cells. The expression of alpha crystallin B chain could be regulated, by medroxy progesterone acetate as well as by oestrogen withdrawal, in human endometrial carcinoma cells (EnCa- 101), transplanted to nude mice. Based on the data presented here, the known function of alpha crystallin B chain and its distinct pattern of expression in human endometrium, we suggest that this protein is an important factor within the molecular repertoire that makes endometrium receptive to implantation.      

A locus for autosomal dominant posterior polar cataract on chromosome 1p

Autosomal dominant congenital cataract is a clinically and genetically heterogeneous lens disease. Here we report the linkage of a locus for autosomal dominant posterior polar cataract (CPP) to the distal short arm of chromosome 1. To map the CPP locus we performed molecular genetic linkage analysis using microsatellite markers in a three- generation pedigree. After exclusion of 13 known loci and candidate lens genes for autosomal dominant cataract, we obtained significantly positive LOD scores for markers D1S508 (Z = 3.14, theta = 0) and D1S468 (Z = 2.71, theta = 0). Multipoint analysis gave a maximum LOD score of 3.48 (theta = 0.07) between markers D1S508 and D1S468. From haplotype data, however, CPP probably lies in the telomeric interval D1S2845- 1pter, which includes the locus for the clinically distinct Volkman congenital cataract (CCV). This study provides the first evidence for genetic heterogeneity of autosomal dominant posterior polar cataract for which a locus had been linked previously to chromosome 16q.      

Sex-related differences in thermoregulatory responses while wearing protective clothing

This study examined the thermoregulatory responses of men (group M) and women (group F) to uncompensable heat stress. In total, 13?M [mean (SD) age 31.8 (4.7) years, mass 82.7 (12.5)?kg, height?1.79?(0.06)?m, surface area to mass ratio 2.46?(0.18)?m²?·?kg^?1?·?10^?2, Dubois surface area 2.01 (0.16)?m², %body fatness 14.6 (3.9)%, V˙O_2peak 49.0?(4.8)?ml?·?kg^?1?·?min^?1] and 17 F [23.2 (4.2) years, 62.4 (7.7)?kg, 1.65 (0.07)?m, 2.71 (0.14)?m²?·?kg^?1?·?10^?2, 1.68 (0.13)?m², 20.2 (4.8)%, 43.2 (6.6)?ml?·?kg^?1?·?min^?1, respectively] performed light intermittent exercise (repeated intervals of 15?min of walking at 4.0?km?·?h^?1 followed by 15?min of seated rest) in the heat (40°C, 30% relative humidity) while wearing nuclear, biological, and chemical protective clothing (0.29?m²?·°C · W^?1 or 1.88 clo, Woodcock vapour permeability coefficient 0.33?i _m). Group F consisted of eight non-users and nine users of oral contraceptives tested during the early follicular phase of their menstrual cycle. Heart rates were higher for F throughout the session reaching 166.7 (15.9) beats?·?min^?1 at 105?min (n?=?13) compared with 145.1 (14.4)?beats?·?min^?1 for M. Sweat rates and evaporation rates from the clothing were lower and average skin temperature ( ) was higher for F. The increase in rectal temperature (T _re) was significantly faster for the F, increasing 1.52 (0.29)°C after 105?min compared with an increase of 1.37?(0.29)°C for M. Tolerance times were significantly longer for M [142.9?(24.5)?min] than for F [119.3?(17.3)?min]. Partitional calorimetric estimates of heat storage (S) revealed that although the rate of S was similar between genders [42.1?(6.6) and 46.1?(9.7) W?·?m^?2 for F and M, respectively], S expressed per unit of total mass was significantly lower for F [7.76?(1.44)?kJ?·?kg^?1] compared with M [9.45?(1.26) kJ?·?kg^?1]. When subjects were matched for body fatness (n?=?8?F and 8?M), tolerance times [124.5?(14.7) and 140.3?(27.4)?min for F and M, respectively] and S [8.67?(1.44) and 9.39?(1.05)?kJ?·?kg^?1 for F and M, respectively] were not different between the genders. It was concluded that females are at a thermoregulatory disadvantage compared with males when wearing protective clothing and exercising in a hot environment. This disadvantage can be attributed to the lower specific heat of adipose versus non-adipose tissue and a higher percentage body fatness.     

Recombinant human acid alpha-glucosidase: high level production in mouse milk, biochemical characteristics, correction of enzyme deficiency in GSDII KO mice

Glycogen storage disease type II (GSDII) is caused by lysosomal acid alpha-glucosidase deficiency. Patients have a rapidly fatal or slowly progressive impairment of muscle function. Enzyme replacement therapy is under investigation. For large-scale, cost-effective production of recombinant human acid alpha-glucosidase in the milk of transgenic animals, we have fused the human acid alpha-glucosidase gene to 6.3 kb of the bovine alphaS1-casein gene promoter and have tested the performance of this transgene in mice. The highest production level reached was 2 mg/ml. The major fraction of the purified recombinant enzyme has a molecular mass of 110 kDa and resembles the natural acid alpha-glucosidase precursor from human urine and the recombinant precursor secreted by CHO cells, with respect to pH optimum, Km, Vmax, N-terminal amino acid sequence and glycosylation pattern. The therapeutic potential of the recombinant enzyme produced in milk is demonstrated in vitro and in vivo. The precursor is taken up in a mannose 6-phosphate receptor-dependent manner by cultured fibroblasts, is converted to mature enzyme of 76 kDa and depletes the glycogen deposit in fibroblasts of patients. When injected intravenously, the milk enzyme corrects the acid alpha-glucosidase deficiency in heart and skeletal muscle of GSDII knockout mice.