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B Lang

Publications and source records attributed to B Lang.

At least 37 records · Page 2Linked to original sources
PubMed2001

Differential expression of AMPA receptor subunits in dopamine neurons of the rat brain: a double immunocytochemical study.

We have examined the distribution of dopamine neurons expressing alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunits (glutamate receptors 1, 2/3 and 4) in the A8-A15 regions of the rat brain using double immunofluorescence. The distribution of glutamate receptor 1- or 2/3-like immunoreactive neurons completely overlapped that of tyrosine hydroxylase-like immunoreactive neurons in dopamine cell groups in the retrorubral field (A8), the substantia nigra (A9), the ventral tegmental area and the nucleus raphe linealis (A10), and the rostral hypothalamic periventricular nucleus (A14, A15). In the caudal hypothalamic periventricular nucleus (A11), arcuate nucleus (A12) and zona incerta (A13), the distribution was partially overlapping. Neurons double-labeled for tyrosine hydroxylase and glutamate receptor 1 or 2/3 immunoreactivities were, however, exclusively found in certain dopamine cell regions: in areas A14-A15, 85-88% of tyrosine hydroxylase-containing neurons expressed glutamate receptor 1 and 22-25% expressed glutamate receptor 2/3, while in areas A8-A10, 20-43% expressed glutamate receptor 1 and 63-84% expressed glutamate receptor 2/3. In contrast, the double-labeled neurons were hardly detected in the A11-A13 regions. No tyrosine hydroxylase-positive neurons displayed glutamate receptor 4 immunoreactivity, though a partially overlapping distribution of tyrosine hydroxylase- and glutamate receptor 4-immunopositive neurons was also seen in regions A8-10, A11 and A13. The present study has demonstrated the morphological evidence for direct modulation of dopamine neurons via AMPA receptors in rat mesencephalon and hypothalamus. This distribution may provide the basis for a selective dopamine neuron loss in neurodegenerative disorders, such as Parkinson's disease.

Animals↗
PubMed2001

Effects of light intensity, n-alcohols, water-soluble colorants, and solution viscosity on photoisomerization of sorivudine.

Effects of various factors, such as light intensity, polarizability of n-alcohol solvents, addition of colorants, and viscosity of solutions on the kinetics of the photoisomerization of therapeutically effective E-isomer of sorivudine to its less effective Z-isomer were studied. Solutions of known concentrations of E-isomer or Z-isomer in water or in a series of n-alcohols were directly exposed to ultraviolet (UV) A light, or visible light of 400 or 900 foot candles (fc). E-isomer solutions containing various colorants at 1% w/v, or in a series of poloxamer solutions of different viscosities, were also exposed to 400 or 900 fc light. Using the stability-indicating HPLC assay, which showed mass-balance between the starting isomer and the converting isomer, the kinetics of photoisomerization were monitored. The photoisomerization reaction, which takes place on the vinyl side chain, was found to be a first-order reversible reaction. In water, the rate of conversion of E-isomer to Z-isomer was faster than that of Z-isomer to E-isomer, since, E-isomer with higher extinction coefficient absorbed substantially more light than Z-isomer. The rate of photoisomerization increased with the intensity of the visible light and was very rapid in the presence of UV A light (300 to 400 nm), which is to be expected based on the 239 nm and 283 nm absorption maxima of sorivudine. Addition of water-soluble colorants retarded the photoisomerization process significantly, especially as the maximum absorption wavelengths (lambda max) of the colorants approached the UV region. The rate of photoisomerization increased with increasing polarizability (alpha s) of the n-alcohol solvents. Polarizable solvents such as alcohols could compensate for the electron density built up in the excited state, and thus facilitated the photoisomerization process. The rate of photoisomerization decreased as the viscosity of solution increased. This may be attributed to the fact that the twisting of the C=C bond in the excited state can be inhibited by the friction imposed by the viscous medium.

Alcohols↗
PubMed2001

Long term outcome in Lambert-Eaton myasthenic syndrome without lung cancer.

OBJECTIVES: To determine the prognosis in patients with Lambert-Eaton myasthenic syndrome (LEMS) without small cell lung cancer (SCLC), and to analyse longitudinal clinical, electrophysiological, and immunological data on each patient to establish prognostic factors for long term outcome. METHODS: The retrospective and part prospective study of 47 patients with LEMS was undertaken from data recorded during visits to a specialist neuromuscular clinic. Serial measurements of muscle strength score in shoulder abduction, elbow extension and hip flexion, compound muscle action potential (CMAP) amplitude, and postcontraction increment in abductor digiti minimi (ADM), and anti-P/Q-type voltage gated calcium channel (VGCC) antibody titre were made at each visit. RESULTS: Muscle strength scores were improved in 88% of patients after a median duration of immunosuppressive treatment of 6 years (range 1.3 to 17 years); anti-VGCC antibody titres fell in 52% after treatment; and mean resting CMAP amplitude improved from 2.7 mV initially to 8.8 mV after 2 years of treatment p<0.001). Initial pretreatment anti-VGCC antibody titre did not correlate significantly with either CMAP amplitude, CMAP increment, or clinical score: from serial measurements made during follow up, significant correlation between antibody titre and CMAP amplitude was seen in only two patients. Sustained clinical remission was achieved by 20 (43%) of whom only four remained in remission without the need for immunosuppression. Using a Cox proportional hazards model, the only independent predictor of sustained clinical remission was initial pretreatment clinical score (p=0.03). Lymphoma presented in three patients during the study. CONCLUSIONS: The prognosis in patients with LEMS without SCLC is favourable, although patients often need significant doses of immunosuppressive treatment to remain clinically stable. Only initial clinical muscle strength measurements and not anti-VGCC antibody titres or electrophysiological recordings are predictive of long term outcome.

Adolescent↗
PubMed2000

Autoantibody screening in subacute cerebellar ataxia.

In a retrospective study of 280 sera from patients presenting with cerebellar signs, seven of whom had proved positive for the typical paraneoplastic serum antibodies that were requested by the clinicians, raised concentrations of antibodies to voltage-gated calcium channels or to glutamic acid decarboxylase were detected in a further seven sera. Systematic screening for these and other antibodies in future cases should help in the diagnosis and management of the patients.

Autoantibodies↗
PubMed2000

Medium- and long-term functional outcomes in a multicenter cohort of children with juvenile dermatomyositis.

OBJECTIVE: To evaluate functional outcomes in a cohort of patients with juvenile dermatomyositis (DM). METHODS: A retrospective inception cohort of patients diagnosed as having juvenile DM between January 1, 1984 and January 1, 1995 was established at 4 Canadian tertiary care pediatric centers. Informed consent was obtained. Each subject was interviewed by telephone or in person. The primary outcome was physical function, as measured by the Childhood Health Assessment Questionnaire (CHAQ). Additional outcomes were educational and vocational achievement, growth, development of calcinosis, patient satisfaction with outcome, and development of other illnesses. Data regarding illness presentation, treatment, and disease course were obtained through chart review. RESULTS: Sixty-five of 80 patients (81%; 46 females and 19 males) could be contacted. The median followup time was 7.2 years (range 3.2-13.9 years), with a median age at followup of 13 years (range 7-26 years). Twenty-four patients (37%) had a monocyclic course, while the remaining 41 (63%) had a chronic continuous or polycyclic course. Sixty-two patients (95%) were treated with corticosteroids, while 41 (63%) received a second-line agent. Physical function was excellent, with a median CHAQ score of 0 (range 0-2.50). Eighteen patients had scores >0, and only 5 had moderate-to-severe disability, as defined by a CHAQ score >1.0. Females had higher CHAQ scores, and all but 1 of the patients with scores >0 were female (range 0-2.50; P = 0.015). Patients with a chronic continuous course also had higher CHAQ scores. Sixteen patients in the chronic continuous group had CHAQ scores >0 (range 0-2.50; P = 0.0009). Calcinosis developed in 22 patients (34%) and persisted to followup in 14. Development of calcinosis was not related to initial therapy, sex, or disease course, but was significantly associated with higher CHAQ scores (range 0-1.0 versus 0-2.5; P = 0.01). At the time of followup, 26 patients (40%) still had rash, 15 (23%) still reported weakness, and 23 (35%) continued taking medications, despite the fact that all were at least 3 years postdiagnosis. There was 1 death. CONCLUSION: In general, patients in this cohort had favorable outcomes. Most had CHAQ scores of 0, and only 8% met our definition of moderate-to-severe disability. However, many patients continued to have chronic disease, persistent rash, and continued taking medications >3 years after diagnosis. Further research is needed to improve outcomes for patients with juvenile DM.

Adolescent↗
PubMed2000

Autonomic neuropathy in patients with HIV: course, impact of disease stage, and medication.

The purpose of this article is to examine the prevalence, degree, and natural course of pupillary neuropathy (PANP), cardiovascular autonomic neuropathy (CANP), and sensorimotor neuropathy (SNP) and to study the impact of disease stage and medication on neuropathy in 61 consecutive patients with HIV. PANP, CANP, and SNP were assessed by standardized test procedures. Overall prevalence of PANP, CANP, and SNP were 66%, 15%, and 15%, respectively. The maximal pupillary area (pupillary measure, p <0.0001) and the lying-to-standing ratio (cardiovascular measure, p <0.0001) were abnormal as compared with control subjects. The changes in CD4+ T-lymphocytes and respiratory sinus arrhythmia percentile during 2 years of follow-up correlated significantly (r = 0.758, p = 0.007). Patients with CANP were more often in an advanced disease stage than patients without CANP (p = 0.004). SNP, but not PANP or CANP, was associated with the intake of the neuropathogenic drugs dideoxycytidine, dideoxyinosine, and 2',3' didehydro-2',3' dideoxythymidine (p <0.05). Autonomic and sensorimotor neuropathy are frequent in patients with HIV, and progression of CANP may put patients at risk for unexpected cardiorespiratory arrest.

Adult↗
PubMed2000

Serotonin potentiates the response of neurons of the superficial laminae of the rat spinal dorsal horn to gamma-aminobutyric acid.

Employing the Nystatin-perforated whole-cell patch-clamp recording technique, the modulatory effects of serotonin (5-HT) on gamma-aminobutyric acid (GABA)-activated whole-cell currents were investigated in neurons acutely dissociated from the superficial laminae (laminae I and II) of the rat spinal dorsal horn. The results showed: (1) GABA acted on GABA(A) receptors and elicited inward Cl(-) currents (I(GABA)) at a holding potential (V(H)) of -40 mV; (2) 5-HT potentiated GABA-induced Cl(-) current without affecting the reversal potential of I(GABA) and the apparent affinity of GABA to its receptor; (3) alpha-methyl-5-HT, a selective agonist of 5-HT(2) receptor, mimicked the potentiation effect of 5-HT on I(GABA), whereas ketanserine, an antagonist of 5-HT(2) receptor, blocked the potentiation effect of 5-HT; (4) Chelerythrine, an inhibitor of protein kinase C, reduced the potentiation effect of 5-HT on I(GABA). The present results indicate: (1) The potentiation of 5-HT on I(GABA) is mediated by 5-HT(2) receptor and through a protein kinase-dependent transduction pathway; (2) The interactions between 5-HT and GABA might play an important role in the modulation of nociceptive information transmission at spinal cord level.

Animals↗
PubMed2000

Molecular targets for autoimmune and genetic disorders of neuromuscular transmission.

The neuromuscular junction is the target of a variety of autoimmune, neurotoxic and genetic disorders, most of which result in muscle weakness. Most of the diseases, and many neurotoxins, target the ion channels that are essential for neuromuscular transmission. Myasthenia gravis is an acquired autoimmune disease caused in the majority of patients by antibodies to the acetylcholine receptor, a ligand-gated ion channel. The antibodies lead to loss of acetylcholine receptor, reduced efficiency of neuromuscular transmission and muscle weakness and fatigue. Placental transfer of these antibodies in women with myasthenia can cause fetal or neonatal weakness and occasionally severe deformities. Lambert Eaton myasthenic syndrome and acquired neuromyotonia are caused by antibodies to voltage-gated calcium or potassium channels, respectively. In the rare acquired neuromyotonia, reduced repolarization of the nerve terminal leads to spontaneous and repetitive muscle activity. In each of these disorders, the antibodies are detected by immunoprecipitation of the relevant ion channel labelled with radioactive neurotoxins. Genetic disorders of neuromuscular transmission are due mainly to mutations in the genes for the acetylcholine receptor. These conditions show recessive or dominant inheritance and result in either loss of receptors or altered kinetics of acetylcholine receptor channel properties. Study of these conditions has greatly increased our understanding of synaptic function and of disease aetiology.

Binding Sites↗
PubMed2000

The adrenal steroid status in relation to inflammatory cytokines (interleukin-6 and tumour necrosis factor) in polymyalgia rheumatica.

OBJECTIVES: To determine the correlation between inflammatory cytokines and adrenal hormones in patients with polymyalgia rheumatica (PMR) and to compare the ratio of serum cortisol and androstenedione (ASD) or dehydroepiandrosterone sulphate (DHEAS) in normal subjects with PMR patients. METHODS: In 102 patients with PMR (32 beginning and 70 chronic disease) and 31 age-matched and sex-matched healthy subjects, ASD, cortisol, DHEAS, interleukin-6 (IL-6), and tumour necrosis factor (TNF) were measured by immunometric assays. RESULTS: Serum levels of IL-6 were elevated in patients with PMR as compared with normal subjects (10.0 +/- 1.6 vs 2.1 +/- 0.1 pg/ml, P = 0.01), which was not found for TNF. In PMR patients, serum levels of IL-6 were positively correlated with serum levels of ASD (P < 0.001), cortisol (P < 0.001), and DHEAS (P = 0. 038) irrespective of corticosteroid treatment. Serum levels of cortisol in relation to IL-6 were significantly lower in patients with chronic disease and long-standing corticosteroid administration as compared with patients with recent onset of the disease and without corticosteroid therapy (P < 0.01). CONCLUSIONS: In PMR, as expected, there was an increase in IL-6 serum levels that was associated with elevated serum levels of ASD, DHEAS, and cortisol which was more marked in patients with recent-onset disease and without corticosteroids. However, serum levels of cortisol in patients with and without corticosteroids were lower than expected by considering the inflammatory status (increased IL-6). This may indicate a change in the hypothalamic-pituitary-adrenal (HPA) axis responsiveness to inflammatory stimuli such as IL-6 during chronic disease. Furthermore, there seems to be a shift of biosynthesis to cortisol in relation to DHEAS or ASD in chronic disease.

Adrenal Glands↗
PubMed2000

Call us first--we'll fix it. How a day case unit plays a vital role through teamwork.

Clinical effectiveness can be defined as 'the extent to which specific clinical interventions, when deployed in the field for a particular patient or population, do what they are intended to do ... maintain health and secure the greatest possible health gain from the available resources.' (NHS Executive 1996) 3M/NATN Award winner for 1999 Bobbie Lang describes how her Day Case Unit has become the central focus for the co-ordination of such procedures--offering clinical effectiveness for a particular patient group.

Abortion, Incomplete↗
PubMed2000

Detection of activated complement complex C5b-9 and complement receptor C5a in skin biopsies of patients with systemic sclerosis (scleroderma).

OBJECTIVE: Upregulated matrix synthesis is a hallmark of systemic sclerosis (SSc). There are indications that growth factors such as platelet derived growth factor (PDGF) are involved in proliferative pathways in SSc lesions. As activated complement releases PDGF from endothelial cells, we searched for activated complement and the complement receptor for C5a (C5aR) in skin biopsies of patients with SSc. METHODS: Snap frozen sections of 8 patients with early SSc and 5 patients with longterm SSc were examined. Using monoclonal antibodies against activated complement complex C5b-9 and the C5aR, skin biopsies derived from both clinically involved and non-involved skin were examined by APAAP immunohistochemistry. RESULTS: A pattern of activated complement C5b-9 and the CSaR could be detected in SSc microvasculature. Eleven of the 13 patients (7/8 patients with early SSc) showed positive staining for C5b-9. The CSaR was detected in 6 of the 8 patients with early SSc. In 3 patients with longterm disease, C5aR expression could also be detected in non-involved skin. CONCLUSION: Activated complement and complement receptors could be detected in early and late stages of SSc skin lesions. The presence of complement receptors in non-involved skin may indicate preclinical activation of pathways resulting in growth factor dependent matrix synthesis.

Antigens, CD↗
PubMed2000

A 30 year history of panniculitis.

The differential diagnosis of panniculitis may be challenging due to the uniform clinical presentation of different panniculitis subsets. We describe a 45-year-old woman with a 30 year history of panniculitis, who had repeatedly failed to fulfill diagnostic criteria for various panniculitis subsets. Finally, erythema induratum was diagnosed and she was successfully treated with antituberculous chemotherapy. The wide spectrum of histological alterations of chronic erythema induratum as well as the sensitivity of polymerase chain reaction for Mycobacterium tuberculosis in erythema induratum lesions is discussed.

Antitubercular Agents↗
PubMed2000

IgG from "seronegative" myasthenia gravis patients binds to a muscle cell line, TE671, but not to human acetylcholine receptor.

Antibodies to acetylcholine receptor (AChR) are found in 85% of patients with myasthenia gravis (seropositive MG [SPMG]) and are thought to be pathogenic; but in 15% of MG patients, the standard immunoprecipitation test for anti-AChR is negative (seronegative MG [SNMG]). Here, we used a novel approach, fluorescence-activated cell sorting analysis, to measure binding of SPMG and SNMG IgG antibodies to rhabdomyosarcoma cell lines that express human adult (TE671-epsilon) or fetal (TE671-gamma) AChR, and to human embryonic kidney (HEK) fibroblasts that express adult human AChR (HEK-AChR). We found that whereas most SPMG antibodies bind to all three cell lines, IgG from 8 of 15 SNMG sera/plasmas bind to the surface of both TE671 cell lines but not to HEK-AChR cells. These results indicate that SNMG antibodies bind to a muscle surface antigen that is not the AChR, which strongly supports previous studies that suggest that SNMG should be considered a distinct subtype of MG.

Adult↗
PubMed1999

Kinesin-like protein CENP-E is upregulated in rheumatoid synovial fibroblasts.

UNLABELLED: Articular destruction by invading synovial fibroblasts is a typical feature in rheumatoid arthritis (RA),. Recent data support the hypothesis that key players in this scenario are transformed-appearing synovial fibroblasts at the site of invasion into articular cartilage and bone. They maintain their aggressive phenotype toward cartilage, even when first cultured and thereafter coimplanted together with normal human cartilage into severe combined immunodeficient mice for and extended period of time. However, little is known about the upregulation of genes that leads to this aggressive fibroblast phenotype. To inhibit this progressive growth without interfering with pathways of physiological matrix remodelling, identification of pathways that operate specifically in RA synovial fibroblasts is required. In order to achieve this goal, identification of genes showing upregulation restricted to RA synovial fibroblasts is essential. AIMS: To identify specifically expressed genes using RNA arbitrarily primed (RAP)-polymerase chain reaction (PCR) for differential display in patients with RA. METHODS: RNA was extracted from cultured synovial fibroblasts from 10 patients with RA, four patients with osteoarthritis (OA), and one patient with psoriatic arthritis. RAP-PCR was performed using different arbitrary primers for first-strand and second-strand synthesis. First-strand and second-strand synthesis were performed using arbitrary primers: US6 (5'-GTGGTGACAG-3') for first strand, and Nuclear 1+ (5'ACGAAGAAGAG-3'), OPN28 (5'GCACCAGGGGG-3'), Kinase A2+(5'-GGTGCCTTTGG-3') and OPN24 (5'AGGGGCACCA-3') for second strand synthesis. PCR reactions were loaded onto 8 mol/l urea/6% polyacrylamide-sequencing gels and electrophoressed. Gel slices carrying the target fragment were then excised with a razor blade, eluated and reamplified. After verifying their correct size and purity on 4% agarose gels, the reamplified products derived from the single-strand confirmation polymorphism gel were cloned, and five clones per transcript were sequenced. Thereafter, a genbank analysis was performed. Quantitative reverse transcription PCRj of the segments was performed using the PCR MIMIC technique. In-situ expression of centromere kinesin-like protein-E (CENP-E) messenger (m)RNA in RA synovium was assessed using digoxigenin-labelled riboprobes, and CENP-E protein expression in fibroblasts and synovium was performed by immunogold-silver immunohistochemistry and cytochemistry. Functional analysis of CENP-E was done using different approaches (eg glucocorticoid stimulation, serum starvation and growth rate analysis of synovial fibroblasts that expressed CENP-E). RESULTS: In RA, amplification of a distinct PCR product suitable for sequencing could be observed. The indicated complementary DNA fragment of 434 base pairs from RA mRNA corresponded to nucleotides 6615-7048 in the human centromere kinesin-like protein CENP-E mRNA (GenBank accession No. emb/Z15005). The isolated sequence shared greater than 99% nucleic acid (P=2.9e(-169)) identify with the human centromere kinesin-like protein CENP-E. Two base changes at positions 6624 (A to C) and 6739 (A to G) did not result in alteration in the amino acid sequence, and therefore 100% amino acid identity could be confirmed. The amplification of 10 clones of the cloned RAP product revealed the presence of CENP-E mRNA in every fibroblast culture examined, showing from 50% (271.000 +/- 54.000 phosphor imager arbitrary units) up to fivefold (961.000 +/- 145.000 phosphor image arbitrary units) upregulation when compared with OA fibroblasts. Neither therapy with disease-modifying antirheumatic drugs such as methotrexate, gold, resochine or cyclosporine A, nor therapy with oral steroids influenced CENP-E expression in the RA fibroblasts. Of the eight RA fibroblast populations from RA patients who were receiving disease-modifying antirheumatic drugs, five showed CENP-E upregulation; and of the eight fibroblast populations from RA patients receiving steroids, four showed CENP-E upregulation. Numerous synovial cells of the patients with RA showed a positive in situ signal for the isolated CENP-E gene segment confirming CENP-E mRNA production in rheumatoid synovium, whereas in OA synovial tissue CENP-E mRNA could not be detected. In addition, CENP-E expression was independent from medication. This was further confirmed by analysis of the effect of prednisolone on CENP-E expression, which revealed no alteration in CENP-E mRNA after exposure to different (physiological) concentrations of prednisolone. Serum starvation also could not suppress CENP-E mRNA completely. DISCUSSION: Since its introduction in 1992, numerous variants of the differential display method and continuous improvements including RAP-PCR have proved to have both efficiency and reliability in examination of differentially regulated genes. The results of the present study reveal that RAP-PCR is a suitable method to identify differentially expressed genes in rheumatoid synovial fibroblasts. The mRNA, which has been found to be upregulated in rheumatoid synovial fibroblasts, codes for a kinesin-like motor protein named CENP-E, which was first characterized in 1991. It is a member of a family of centromere-associated proteins, of which six (CENP-A to CENP-F) are currently known. CENP-E itself is a kinetochore motor, which accumulates transiently at kinetochores in the G2 phase of the cell cycle before mitosis takes place, appears to modulate chromosome movement and spindle elongation,and is degraded at the end of mitosis. The presence or upregulation of CENP-E has never been associated with RA.The three-dimensional structure of CENP-E includes a coiled-coil domain. This has important functions and shows links to known pathways in RA pathophysiology. Coiled-coil domains can also be found in jun and fos oncogene products, which are frequently upregulated in RA synovial fibroblasts. They are also involved in DNA binding and transactivation processes resembling the situation in AP-1 (Jun/Fos)-dependent DNA-binding in rheumatoid synovium. Most interestingly, these coiled-coil motifs are crucial for the assembly of viral proteins, and the upregulation of CENP-E might reflect the influence of infectious agents in RA synovium. We also performed experiments showing that serum starvation decreased, but did not completely inhibit CENP-E mRNA expression. This shows that CENP-E is related to, but does not completely depend on proliferation of these cells. In addition, we determined the growth rate of CENP-E high and low expressors, showing that it was independent from the amount of CENP-E expression. supporting the statement that upregulation of CENP-E reflects an activated RA fibroblast phenotype. In summary, the results of the present study support the hypothesis that CENP-E, presumably independently from medication, may not only be upregulated, but may also be involved in RA pathophysiology.

Adult↗