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Biomedical subjects

G Nuki

Publications and source records attributed to G Nuki.

At least 19 recordsLinked to original sources
PubMed1992

The point mutation of hypoxanthine-guanine phosphoribosyltransferase (HPRTEdinburgh) and detection by allele-specific polymerase chain reaction.

The change in DNA responsible for partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency in three brothers has been determined by polymerase chain amplification and sequencing. An A-to-G substitution at base 155 in exon 3 predicts a change in aspartic acid 52 to glycine. Allele-specific polymerase chain amplification verified the presence of the mutation in genomic DNA and provides a means of direct diagnostic assay.

Adolescent↗
PubMed1992

Systemic and mucosal antibodies to Klebsiella in patients with ankylosing spondylitis and Crohn's disease.

Whole gut lavage fluid is a useful source of material for the study of intestinal immunity and inflammation in humans. Systemic and mucosal antibodies to Klebsiella pneumoniae were measured by enzyme linked immunosorbent assay (ELISA) in serum samples and whole gut lavage fluid from 14 patients with ankylosing spondylitis, 14 with Crohn's disease, and 16 immunologically normal controls. As the concentration of IgG in whole gut lavage fluid reflects disease activity in Crohn's disease, this approach was used to detect intestinal inflammation in patients with ankylosing spondylitis who also had disease activity and use of non-steroidal anti-inflammatory drugs (NSAIDs) recorded. Small intestinal permeability to cellobiose and mannitol was also studied. In serum samples, levels of IgA antibody to klebsiella were high in patients with Crohn's disease and in patients with active ankylosing spondylitis, and were significantly correlated with the erythrocyte sedimentation rate in patients with ankylosing spondylitis. Levels of IgG antibody to klebsiella were also high in patients with Crohn's disease. Studies of whole gut lavage fluid showed similar levels of IgA antibody to klebsiella in the three study groups, but levels of whole gut lavage fluid IgM and IgG antibodies to klebsiella were high in patients with Crohn's disease. Levels of IgG in whole gut lavage fluid were high in patients with Crohn's disease but in only one patient with ankylosing spondylitis, though the cellobiose/mannitol permeability ratio was abnormal in eight of 13 patients with ankylosing spondylitis. It is concluded that high levels of serum IgA antibody to klebsiella are not specific to ankylosing spondylitis, and that there is no evidence of an abnormal intestinal IgA antibody response to klebsiella in patients with ankylosing spondylitis.

Adult↗
PubMed1992

Multicentric reticulohistiocytosis with arthritis and cardiac infiltration: regression following treatment for underlying malignancy.

The case is reported of a 63 year old man presenting with a rapidly destructive symmetrical polyarthritis and widespread papular nodular skin lesions, confirmed by a biopsy to be due to multicentric reticulohistiocytosis. Biventricular cardiac failure developed secondary to extensive myocardial infiltration with multicentric reticulohistiocytosis, a complication of this disease which has not previously been reported. The joint, skin, and cardiac manifestations of multicentric reticulohistiocytosis substantially regressed following resection of an associated squamous cell carcinoma. This report adds to the small amount of published work which suggests that multicentric reticulohistiocytosis can be a paraneoplastic disease that may respond to treatment directed at the underlying tumour.

Arthritis↗
PubMed1992

Response of plasma membrane to applied hydrostatic pressure in chondrocytes and fibroblasts.

Effects of applied hydrostatic pressure on transmembrane potentials were investigated in sheep articular chondrocytes and human skin fibroblasts in non-confluent monolayer cultures. Resting potentials in chondrocytes (about -12 mv) and in fibroblasts (about -15 mV) were increased and decreased respectively by over 40% after pressure was applied cyclically (0.33 Hz, 120 mm Hg, 20 minutes). Continuous pressure (120 mm Hg, 20 minutes) caused deplorization in both cell types. Low frequency pressure application (less than 0.08 Hz) caused depolarization in chondrocytes and hyperpolarization in fibroblasts. Quinidine (2 x 10(-5) M) blocked and verapamil (10(-5) M) reduced hyperpolarization responses, suggesting involvement of Ca(2+)-dependent K+ channels. A23187 (1.9 x 10(-6) M) caused hyperpolarization in chondrocytes, augmented further by subsequent pressure application (0.33 Hz). Tetrodotoxin (10(-6) M) blocked depolarization responses indicating that these were due to Na+ influx. Blockade of histamine H1 receptors by chlorpheniramine maleate (5.1 x 10(-6) M), H2 receptors by cimetidine (7.9 x 10(-6) M) and beta-adrenoreceptors by sotolol (1.3 x 10(-4) M) had no effect on hydrostatic pressure-induced hyperpolarization in chondrocytes. Cytochalasin B (2 x 10(-5) M and at 4 x 10(-6) M) abolished pressure-induced hyperpolarization in chondrocytes; in contrast, applied cyclical hydrostatic pressure to cytochalasin-treated fibroblasts caused hyper-polarization, suggesting that cytoskeletal changes were involved.

Animals↗
PubMed1991

Resonant frequency at the wrist in hypermobile women.

The resonant frequency of the wrist has been measured in sixteen hypermobile and nine normal women at ten levels of peak torque. At the lowest level the results were identical but at the others the hypermobile values were lower. Damping and thixotropy appeared to be normal. In another group the grip strength of hypermobile subjects was similar to that of controls. The possibility that the connective tissue of the musculature of hypermobile subjects is of enhanced compliance is discussed.

Adult↗
PubMed1990

Pain control and the use of non-steroidal analgesic anti-inflammatory drugs.

Rheumatic complaints, particularly associated with osteoarthritis, are responsible for about one third of all General Practice consultations in people over the age of 65 and non-steroidal anti-inflammatory drugs (NSAIDs) are used on a vast scale for pain relief. Although the individual risk to life is small NSAIDs are the major cause of serious adverse reactions (ADRs) reported to drug regulatory authorities and ADRs are more common and more serious in the elderly. Gastric ulceration, haemorrhage and perforation are the major concern but fluid retention, renal and hepatic failure, asthma, skin reactions, bone marrow suppression and a host of drug interactions can occur. NSAIDs are responsible for a fifth of all admissions to hospital with bleeding or perforated peptic ulcer and thousands of deaths worldwide. Strategies for minimising the risks of ADRs are discussed and emphasis is placed on using minimal analgesic, rather than anti-inflammatory, doses of short-acting NSAIDs and where possible avoiding their use in high risk patients. For the future cytoprotection with prostaglandin analogues may have a role to play.

Aged↗
PubMed1990

A multicentre double-blind comparison of auranofin, intramuscular gold thiomalate and placebo in patients with psoriatic arthritis.

The efficacy and safety of the oral gold compound auranofin and intramuscular gold thiomalate have been compared in a placebo-controlled, double-blind, four-centre trial in 82 patients with psoriatic arthritis requiring remittive drug therapy. There were statistically significant falls in Ritchie articular index, visual analogue pain score and ESR at 12 and 24 weeks following i.m. gold but no significant changes in the auranofin group. Intramuscular gold was safe and more effective than auranofin as a second-line, suppressive antirheumatic agent for patients with psoriatic arthritis when followed for 6 months.

Adult↗
PubMed1989

Hypoxanthine-guanine phosphoribosyltransferase deficiency in three brothers with gout: characterization of a variant, HPRTEdinburgh, having altered isoelectric point, increased thermal lability and normal levels of messenger RNA.

Three brothers who developed acute gouty arthritis at ages 16, 20 and 26 years were found to have increased plasma urate. Erythrocyte hypoxanthine phosphoribosyltransferase (HPRT) activity was less than 1% of normal and adenine phosphoribosyltransferase (APRT) activity was increased 2-3-fold. This variant, HPRTEdinburgh, was further studied using lymphoblast lines established from these patients and the following observations are consistent with a mutation involving a single amino acid substitution. Lymphoblasts from these patients had 0.9-1.6% of control HPRT activity which was 8-fold more labile than control activity at 75 degrees C. Isoelectric focusing of the variant protein in polyacrylamide gels indicated a pI of 6.5-6.7 which is more basic than normal HPRT, pI 6.0-6.3. The Michaelis constants were increased: 10-fold for hypoxanthine from 1.3 to 13 mumol/L, and 5-fold for PP-ribose-P from 6 to 30 mumol/L, for control and variant respectively. The Ki for product inhibition by GMP was marginally increased in the variant. Northern blot analysis of variant lymphoblast RNA indicated normal amounts of the expected 1.6 kilobase messenger RNA.

Adolescent↗
PubMed1989

Biodynamics of the wrist in rheumatoid arthritis--the enigma of stiffness.

The wrist has been moved rhythmically in the horizontal plane by sinusoidal torques provided by a printed motor. Measurements have been made on normal subjects and subjects with rheumatoid arthritis. Both groups exhibited a resonance, the oscillations being greatest when the applied torque was of certain frequency. In both groups the resonant frequency fell to approximately the same constant value when the torque was raised. While the main relationships were similar a somewhat lower torque resulted in the lowering of resonant frequency in the patients. The relationship between applied torque and peak velocity at resonance was also studied. For a given torque the motion was greater in the patients. No objective signs of increased viscous or elastic stiffness were demonstrable at the wrist in patients with rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1988

Tumour necrosis factor in synovial exudates.

The actions of tumour necrosis factor (TNF) include resorption of bone and cartilage, suggesting a potential role in the pathogenesis of arthritis. TNF activity was looked for in synovial fluids from 137 patients with different rheumatic diseases. Unfractionated samples were tested in the L929 bioassay. Significant TNF activity that was neutralised by monoclonal antibody to TNF alpha occurred in 13 (30%) of 44 samples. Raised TNF levels were not associated with any particular disease type or routine laboratory markers of inflammation but were related to disease duration in osteoarthritis. The finding of biologically active TNF in symptomatic joints of arthritic patients supports the idea that it may contribute to the pathogenesis of joint damage in chronic rheumatic diseases.

Biological Assay↗
PubMed1987

Interleukin 1 (IL 1) as a mediator of crystal arthritis. Stimulation of T cell and synovial fibroblast mitogenesis by urate crystal-induced IL 1.

We reported before that monosodium urate (MSU) crystals were potent stimulators of endogenous pyrogen (EP) production from human and rabbit mononuclear phagocytes, and proposed that this property of MSU crystals may be important in the pathogenesis of gout. EP activity is now attributed to interleukin 1 (IL 1) peptides but IL 1 is not the only pyrogenic monocyte-derived cytokine, since both interferon-alpha (alpha-IFN) and tumor necrosis factor (TNF) are also pyrogenic in rabbits. Using a T cell comitogenic assay based on a murine helper T cell clone that does not respond to IFN or TNF, we now report the release of IL 1 activity from human blood monocytes and synovial fluid mononuclear cells (MNC), following stimulation with MSU crystals. MSU-induced supernatants with IL 1 activity were neutralized with rabbit antiserum to human IL 1 and also stimulated the growth ([3H]thymidine incorporation) of long-term fibroblast-like cell lines derived from human synovial rheumatoid exudate. Two other crystals associated with articular inflammation were tested: hydroxyapatite was a much less potent stimulus compared with MSU crystals, and calcium pyrophosphate dihydrate did not stimulate IL 1 release from human monocytes or synovial fluid MNC. As a model for the inflammatory consequences of acute and chronic overproduction of IL 1, gout is the only sterile inflammatory disease where the local and systemic pathology is compatible with such overproduction; raised IL 1 levels have been found at the site of inflammation, and a necessary etiologic agent, crystalline urate, has been shown unequivocally to be a direct activator of mononuclear IL 1 release.

Adsorption↗
PubMed1987

A method for the determination of 5-phosphoribosyl 1-pyrophosphate concentrations in erythrocytes using high-performance liquid chromatography.

A method for the measurement of erythrocyte 5-phosphoribosyl 1-pyrophosphate (PP-ribose-P) using HPLC is described. Inosinic acid formed from the enzyme-catalyzed reaction of hypoxanthine and PP-ribose-P using partially purified hypoxanthine-guanine phosphoribosyltransferase is measured after chromatography on an ion-exchange column (Partisil 10 SAX). The average recovery of PP-ribose-P added to erythrocytes was 96.6%. Normal values found were 1.3 +/- 0.6 nmol PP-ribose-P/ml packed RBC (20 individuals). Replication experiments gave a coefficient of variation of 4.4%. Elevated levels in the range 4.4-7.9 nmol PP-ribose-P/ml packed RBC were found in four patients with gout and partial deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase.

Chromatography, High Pressure Liquid↗
PubMed1987

Non-secretion of ABO blood group antigens as a host susceptibility factor in the spondyloarthropathies.

Gram negative bacteria precipitate reactive arthritis and may be concerned in the pathogenesis of ankylosing spondylitis and other spondyloarthropathies. Susceptibility to many infectious agents is associated with ABO blood group or secretor state, or both. The distribution of the ABO blood group or secretor state, or both, was therefore determined in 87 patients with ankylosing spondylitis and 32 with other forms of spondyloarthropathy. The prevalence of non-secretors was significantly increased in the total patient group (54/114; 47%) and in the subgroup with ankylosing spondylitis (41/84; 49%) compared with local controls (89/334; 27%) (p less than 0.001). Other subgroups of patients showed a similarly increased prevalence of non-secretion (33-47%). The distribution of ABO blood groups did not differ between patients and controls. The association between non-secretor state and ankylosing spondylitis strengthens the hypothesis that ankylosing spondylitis is a form of reactive arthritis. It also suggests several pathogenic mechanisms which may be relevant to the initial hostparasite interaction in ankylosing spondylitis.

ABO Blood-Group System↗
PubMed1987

Ligand-binding and idiotypic cross-reactions between anti-DNA antibodies and antibodies to Klebsiella K30 polysaccharide in patients with systemic lupus erythematosus or rheumatoid arthritis.

Antibodies to DNA and K30p were purified by affinity procedures and tested for their ability to cross-react with K30p and DNA, respectively. Anti-ssDNA antibodies were shown to react with solid-phase K30p and be inhibited in a dose-dependent manner by soluble ssDNA and K30p. Conversely, anti-K30p antibodies were found to bind immobilized ssDNA and be inhibited with soluble inhibitor. These results show that certain subpopulations of anti-ssDNA and anti-K30p antibodies overlap in their ligand-binding specificities. Idiotypic (Id) analysis showed that anti-K30p antibodies did not react significantly with an anti-Id reagent directed against a common anti-DNA framework Id (AM Id), thus clearly separating K30p-binding anti-DNA antibodies into an AM Id-negative population. When anti-DNA antibodies were probed with an anti-Id reagent directed against a framework Id present on anti-K30p antibodies (SP Id), substantial reactivity was found. Thus the SP Id identifies a subpopulation of antibodies capable of binding both K30p and DNA. These results show that a subset of anti-ssDNA antibodies cross-react with K30p antigen and are idiotypically related to a subset of antibodies reactive with K30p.

Antibodies, Anti-Idiotypic↗