Bilateral hip replacements in a man with cystic fibrosis and episodic arthritis.
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Adult↗
Biomedical subjects
S M Jones
Publications and source records attributed to S M Jones.
Expression of the cutaneous lymphocyte antigen and its counter-receptor E-selectin in the skin and joints of patients with psoriatic arthritis.
We have investigated whether the skin-homing T lymphocytes identified by the cutaneous lymphocyte antigen (CLA) are increased in the synovial membrane of patients with psoriatic arthritis. Twenty-six synovial samples (13 psoriatic arthritis, seven rheumatoid arthritis, six osteoarthritis) were obtained from involved knees. Lesional skin biopsies were taken from nine of the patients with psoriatic arthritis and six patients with psoriasis alone. All samples were single- and dual-stained for CLA and CD3 (to identify T lymphocytes) using HECA-452 (anti-CLA) and anti-CD3 monoclonal antibodies. E-selectin expression was also determined. The percentage of dual-stained lymphocytes was significantly greater in psoriatic skin than in synovium (P < 0.001) and similar between psoriatic and rheumatoid synovium. There was no significant difference in the percentages of CLA-positive cells in psoriatic skin in patients with psoriatic arthritis compared with psoriasis alone. The intensity of endothelial E-selectin expression was significantly greater in skin psoriasis than in synovium (P < 2 x 10(-5)), and rheumatoid synovium had significantly greater expression than psoriatic synovium (P < 0.05). However, there was no significant correlation between E-selectin expression and the percentages of CLA-positive lymphocytes. This study provides further evidence that the CLA antigen is enriched on skin-homing lymphocytes. Conversely, the link between skin and joint inflammation in psoriatic arthritis does not seem to be explained by increased trafficking of CLA T cells to psoriatic synovium.
Adult↗
Evidence for alternative splicing in hepatic alpha 1B-adrenergic receptor gene expression.
The interactions of catecholamines with alpha 1B-adrenergic receptors (alpha 1B-AR) located on the surface of many cell types are responsible for physiologic and pathologic functions in mammalian systems. Transcription of the alpha 1B-AR gene leads to the expression of multiple alpha 1B-AR mRNAs that are distributed in a tissue-specific fashion. The purpose of this study was to define the 5'-untranslated regions of the multiple alpha 1B-AR gene transcripts. Evidence for a previously unidentified intron in the alpha 1B-AR gene upstream of the receptor open reading frame was obtained via rapid amplification of cDNA ends. A product was amplified and was found to be missing the nucleotide interval from -708 to -194, (+1 is the start of translation). Evidence for tissue-specific alternative intron splicing was obtained from ribonuclease protection assays and RT-PCR experiments. Using an RNA probe extending from -240 to +93 and including 45 nucleotides into the putative intron, a single protected fragment was detected in heart RNA while two protected fragments were detected in liver RNA. RT-PCR amplification of the region spanning the intron resulted in detection of two PCR products in liver RNA and no detectable product in heart RNA. These findings emphasize the complexity of alpha 1B-AR gene regulation and suggest that multiple alpha 1B-AR mRNAs with different 5'-UTRs may play a role in regulating alpha 1B-adrenergic responsiveness.
Alternative Splicing↗
Physicians need more education about inherited cancer predisposition.
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Curriculum↗
Human microtubule-associated protein 1a (MAP1A) gene: genomic organization, cDNA sequence, and developmental- and tissue-specific expression.
Microtubule-associated proteins (MAPs) regulate microtubule stability and play critical roles in neuronal development and the balance between neuronal plasticity and rigidity. MAP1a (HGMW-approved symbol MAP1A) stabilizes microtubules in postnatal axons. We describe human MAP1a's genomic organization and deduced cDNA and amino acid sequences. MAP1a is a single-copy gene spanning 10.5 kb. MAP1a coding sequence is contained in five exons. Translation begins in exon 3. Human MAP1a contains 2805 amino acids (predicted molecular weight 306.5 kDa) and is slightly larger than rat MAP1a (2774 amino acids). Like rat and bovine MAP1a, human MAP1a contains conserved tubulin binding motifs in the amino-terminal region. The carboxy-terminal portion contains a conserved pentadecapeptide that is present in the light chain portion of rat and bovine MAP1a/LC2 polyprotein. We show that human MAP1a gene expression occurs almost exclusively in the brain and that there is approximately 10-fold greater gene expression in adult brain compared to fetal brain. Strong, interspecies conservation between human and rat MAP1a cDNA and amino acid sequences indicates important relationships between MAP1a's function and its primary amino acid sequence.
Adult↗
The management and outcome of critical limb ischaemia in diabetic patients: results of a national survey. Audit Committee of the Vascular Surgical Society of Great Britain and Ireland.
It is generally considered that the outcome from critical limb ischaemia (CLI) in people with diabetes is inferior to that in non-diabetic patients. However, excellent results have been reported in diabetic people with the use of bypass surgery to pedal arteries. Data from a prospective national survey on CLI have been analysed to compare surgical practice and outcome from CLI in diabetic and non-diabetic populations. Of 679 limbs included in the survey, 204 (30%) were in diabetic patients. Thirty-seven (18%) of diabetic limbs were treated by primary amputation compared to 43 (9%) in non-diabetics (p = 0.0013). Revascularization was the primary treatment intention in 127 (62.3%) of diabetic limbs compared to 342 (72%) in non-diabetics (p = 0.01). Bypass to pedal arteries was reported in only 2 (1%) diabetic patients. The limb salvage rate in diabetic patients was 60%, compared to 72.5% for non-diabetic patients (p = 0.0013). The mortality rates were 15% and 12% in diabetic and non-diabetic patients, respectively (NS). These results confirm that in the UK and Ireland diabetic patients with CLI fare considerably worse than do people without diabetes. The results may be improved if more pedal artery reconstructions were performed.
Adult↗
L-arginine minimizes reperfusion injury in a low-flow, reflow model of liver perfusion.
A low-flow, reflow model of liver perfusion was used in the rat to investigate the effects of L-arginine on reperfusion injury in the absence of blood elements. In contrast to in vivo studies, L-arginine cannot minimize hypoxia by improving the microcirculation under these special conditions, but rather can only increase oxygen delivery upon reflow. During reflow, lactate dehydrogenase (LDH) release reached a new steady-state value of 35 +/- 3 U/g/h in livers perfused in the absence of L-arginine. L-Arginine (0.1 mmol/L) significantly reduced LDH release during reflow to 14 +/- 1 U/g/h; higher concentrations (1.0-3.0 mmol/L) were less effective and the arginine analogue Nomega-nitro L-arginine methyl ester (L-NAME, 0.3 mmol/L) reversed the protective effect completely. Infusion of the biologically inactive isomer D-arginine (0.1 mmol/L had no effect on the observed reperfusion injury. Malondialdehyde (MDA) release during reflow averaged 92 +/- 10 nmol/g/h and was decreased significantly to 47 +/- 13 nmol/g/h with L-arginine (0.1 mmol/L). Oxygen uptake during reflow was not significantly altered by L-arginine, although the time required to reach steady state values upon reflow was reduced significantly (about twofold), indicating improved microcirculation. Trypan blue distribution time, which is used to index the hepatic microcirculation, was decreased significantly from 330 +/- 17 to 227 +/- 31 seconds by L-arginine, an effect also blocked by L-NAME. Additionally, L-arginine, significantly increased both the rate of entry and exit of fluorescein-dextran, a dye confined to the vascular space, by approximately 50%, also reflecting improved microcirculation. Collectively , these findings indicate that L-arginine protects against hypoxia/reoxygenation injury in a blood-free perfusion model specifically during the reoxygenation period. It is likely that L-arginine rapidly removes substrates for free radical generation by improving the microcirculation.
Animals↗
The response of gamma delta T cells to Plasmodium falciparum is dependent on activated CD4+ T cells and the recognition of MHC class I molecules.
Peripheral blood gamma delta T cells from non-exposed individuals respond to antigens of the malaria parasite, Plasmodium falciparum, in vitro. This response, largely caused by T cells bearing the V gamma 9+ chain of the T-cell receptor, is stimulated by components of the parasite expressed on the schizont stage and released at schizont rupture. The response of V gamma 9+ T cells to parasite components is inhibited by antibodies to major histocompatibility complex (MHC) class I and class II. However, the inhibition by anti-MHC class II antibodies can be overcome by the addition of interleukin-2 (IL-2) to the cultures, suggesting that gamma delta T cells themselves do not recognize MHC class II molecules but require an MHC class II-dependent response taking place in the culture. In contrast, the inhibition by anti-class I antibodies cannot be reversed by addition of IL-2. Since an accompanying CD4+ T-cell response occurred in peripheral blood mononuclear cells cultured with P falciparum antigens, it was considered that these cells provide the cytokines necessary for the subsequent activation and expansion of V gamma 9+ T cells recognizing components of the parasite and MHC class I molecules. This was confirmed by reconstituting the response of enriched gamma delta T cells to P falciparum schizont extract by addition of purified CD4+ T cells.
Animals↗
Effects of bromocriptine on lactation and plasma progesterone in Bettongia gaimardi, a Tasmanian macropodid marsupial.
Many macropodids exhibit lactational quiescence during which an embryo produced at post-partum mating is retained as a blastocyst in utero while a pouch young is sucking. The sucking stimulus maintains secretion of prolactin which may in some species inhibit the activity of the corpus luteum and, hence, the development of the embryo. When the sucking frequency decreases, the blastocyst resumes development. In the present study, the dopamine agonist bromocriptine, which in many mammals results in decreased secretion of prolactin from the pituitary gland, was administered to the Tasmanian bettong (Bettongia gaimardi) at two different doses (12.5 mg kg(-1) and 5 mg kg(-1)). Although lactation was affected by both doses, as evidenced by slower growth of the pouch young or their loss, in only two cases did the quiescent blastocyst activate at the time of injection. This occurred with the highest dose of bromocriptine and was reflected by earlier changes in plasma progesterone concentrations. It is concluded that the Tasmanian bettong is unusual in its lack of sensitivity to bromocriptine.
Animals↗
Comparison of a rapid readout biological indicator for steam sterilization with four conventional biological indicators and five chemical indicators.
OBJECTIVE: In this study, we compare a new biological indicator that provides results within 3 hours with four conventional, 48-hour biological indicators and five chemical indicators. DESIGN: Biological indicators tested included the conventional Attest 1262, Proof Plus, Assert, and Biosign, and the new Attest 1292 Rapid Readout biological indicator. Chemical indicators tested included Comply, Propper, Chemdi, Sterigage, and Thermalog S. Spore survival following 121 degrees C in a gravity displacement sterilizer was measured by media color change after incubation for 24 and 48 hours at 56 degrees C for the conventional biological indicators, fluorescence at 3 hours for the Attest 1292 Rapid Readout biological indicator, and color change for the chemical indicators. Each exposure time was replicated 12 times with 5 samples of each indicator per run (ie, 60 replicates per indicator). RESULTS: At 48 hours, the conventional biological indicators Attest 1262, Proof Plus, Assert, and Biosign showed 100%, 95%, 88%, and 93% spore survival at 5 minutes' exposure 0%, 0%, 0% and 8% at 10 minutes; and all showed 0% survival at 15 minutes' exposure. Following a 3-hour incubation, the Attest 1292 Rapid Readout biological indicator showed fluorescence at 100%, 72%, and 0% at 5, 10, and 15 minutes, respectively. The chemical indicators Comply, Propper, Chemdi, Sterigage, and Thermalog S revealed sterilization failure rates of 100%, 100%, 100%, 100%, and 100% at 5 minutes' exposure; 0%, 0%, 0%, 92%, and 100% at 10 minutes; and 0%, 0%, 0%, 3%, and 27% at 15 minutes' exposure, respectively. CONCLUSIONS: The sensitivity of the Attest 1292 Rapid Readout biological indicator parallels that of conventional biological indicators. These data suggest that a 3-hour rapid readout biological indicator is equivalent to a standard 48-hour biological indicator. Some chemical indicators (eg, Thermalog S) failed to indicate adequate sterilization at 15 minutes' exposure. These chemical indicators have the potential of causing unnecessary recall of adequately sterilized items.
Equipment Contamination↗
Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature.
The true incidence of sarcoidosis in common variable immunodeficiency (CVID) is unknown. We report here 8 cases of sarcoidosis among 80 patients with CVID followed in our clinics, along with 22 well-documented cases reported in the literature. Sarcoidosis, therefore, represents an important entity to consider among patients with CVID who exhibit clinical, radiographic, laboratory, and biopsy findings compatible with sarcoidosis. Conversely, the diagnosis of CVID should be considered in patients with sarcoidosis who do not exhibit the characteristic hypergammaglobulinemia and who have a history of recurrent infections. Although many features of sarcoidosis are similar in patients with CVID to those in patients with sarcoidosis alone, there are many important differences. Patients with CVID in whom sarcoidosis develops present with hypogammaglobulinemia rather than hypergammaglobulinemia and have a higher prevalence of recurrent infections, thrombocytopenia, and splenic involvement. Steroids, in most cases, appeared helpful in reducing adenopathy and splenomegaly, improving uveitis, lowering serum alkaline phosphatase, and reversing hematologic abnormalities. The underlying pathophysiology responsible for the association of these 2 disorders in the same patient remains obscure. However, as more patients are identified, it may be possible to gain a better understanding of the immunologic defect responsible for the dual presentation of these 2 relatively uncommon diseases.
Adult↗
Hereditary spastic paraplegia linked to chromosome 15q: Analysis of candidate genes.
We previously reported an extended kindred with autosomal dominant uncomplicated hereditary spastic paraplegia (HSP) and found close linkage between the disorder and microsatellite polymorphisms on chromosome 15q. Multipoint linkage analysis reached a maximum LOD score (10.16) between D15S128 and D15S156, a region that includes genes encoding alpha5 and beta3 subunits of GABAA receptor. Theoretically, abnormal GABA-mediated neurotransmission could produce spasticity and possibly other changes of HSP. We used genetic linkage analysis to evaluate these two HSP candidate genes and observed obligate recombinants for polymorphisms immediately adjacent to (or within untranslated regions of) genes encoding alpha5 and beta3 GABAA receptor subunits. Although these genes are linked tightly to the HSP locus, our findings conclusively exclude these genes from being responsible for HSP in this kindred.
Adult↗
The association between basal body temperature, plasma progesterone and the oestrous cycle in a marsupial, the Tasmanian bettong (Bettongia gaimardi).
Basal body temperature, quantitative changes in vaginal smears and plasma concentrations of progesterone were measured during a number of oestrous cycles in Tasmanian bettongs (Bettongia gaimardi). These methods of monitoring the reproductive cycle were compared in an attempt to find a technique that allowed non-stressful assessment of the reproductive condition of the bettongs. Telemetric measurement of basal body temperature showed that there was a diurnal variation of 1.3 degrees C, typical of a nocturnal animal. During the oestrous cycle, there was a small, but not significant, peak in basal body temperature at oestrus (day 0) followed by a significant trough on day 2. There was a significant increase on day 3 and the temperature remained raised until day 10, during which time plasma progesterone concentrations are also high; the temperature then fell 2 days before oestrus. This fall corresponds to a decrease in concentration of plasma progesterone and in the numbers of leucocytes in vaginal smears. Telemetric measurement of body temperature may be useful as a non-stressful method of monitoring the oestrous cycle in bettongs.
Animals↗
Paroxysmal dystonic choreoathetosis: tight linkage to chromosome 2q.
Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at rest both spontaneously and following caffeine or alcohol consumption. We analyzed a Polish-American kindred with autosomal dominant PDC and identified tight linkage between the disorder and microsatellite markers on chromosome 2q (maximum two-point LOD score 4.77; recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant PDC on distal chromosome 2q. The fact that three other paroxysmal neurological disorders (periodic ataxia with myokymia and hypo- and hyperkalemic periodic paralysis) are due to mutation in ion-channel genes raises the possibility that PDC is also due to an ion-channel gene mutation. It is noteworthy that a cluster of sodium-channel genes is located on distal chromosome 2q, near the PDC locus. Identifying the PDC locus on chromosome 2q will facilitate discovery of the PDC gene and enable investigators to determine whether PDC is genetically homogeneous and whether other paroxysmal movement disorders are also genetically linked to the PDC locus.
Athetosis↗
Management of varicose veins according to reason for presentation.
Of 229 newly referred patients with varicose veins, untoward symptoms were the most frequent reason for presentation (38%). Cosmetic concerns were significantly more common in women than in men (33% vs 8%, P < 0.001). Sclerotherapy was offered to 20 patients (8.7%). Surgical operation was offered in 113 (49.3%), mostly for symptoms. No invasive treatment was indicated in 96 patients (42%), more than half of whom had presented because of inappropriate fears of deterioration or with symptoms unrelated to their veins. We advocate that careful evaluation of the reasons for presentation should be used as a guide to the efficient management of varicose veins.
Adolescent↗
Cross-cultural considerations in health care delivery: Chinese viewpoints.
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Asian↗
VCAM-1 expression on endothelium in lesions from cutaneous lupus erythematosus is increased compared with systemic and localized scleroderma.
The cutaneous lesions in systemic sclerosis (SSc) and lupus erythematosus (LE) are pathologically distinct and may display separate cell adhesion receptors. We have scored lesional skin for the presence of cell adhesion molecules that may influence inflammatory and fibrotic processes in five patients with LE, six patients with diffuse scleroderma and four patients with morphoea. The immunohistological distribution, and the number and intensity of cells staining, were recorded for VCAM-1, ICAM-1, E-selectin, alpha 2 to alpha 6 and beta 2 integrins and HLA-DR. VCAM-1 staining intensity was increased on endothelium from lesions in LE compared with SSc (P = 0.05). Low-level VCAM-1 and E-selectin expression was present on endothelium from uninvolved skin including that from patients with morphoea. HLA-DR expression was increased on infiltrating mononuclear cells (P < 0.05) and keratinocytes in LE (P < 0.05) and the number of fibroblasts staining for ICAM-1 was increased in lesions from patients with SSc, although this did not reach statistical significance. Overall, with respect to endothelial adhesion events, our findings support an important role for VCAM-1 in sustaining chronic inflammation in cutaneous LE.
Adult↗
Transcranial magnetic stimulation: cortical motor maps in acute spinal cord injury.
This investigation examined the motor pathways of four, C5-6 spinal cord injured (SCI) patients within 6-17 days of injury. Mapping of the motor cortex was achieved by transcranial magnetic stimulation (TMS) applied to the scalp. Motor evoked potentials were recorded from target muscle groups (Biceps brachii and Abductor pollicis brevis m.). Evidence of an expanded cortical map of the preserved contralateral biceps muscle was demonstrated in these patients as early as 6 days. These findings suggested that early motor re-organization may occur following acute cervical spinal cord injury in man.
Adult↗