Collagenous colitis responsive to octreotide therapy.
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Aged↗
Biomedical subjects
J R Green
Publications and source records attributed to J R Green.
Determining approximate estimates of inheritance parameters from sib-pair IBD proportions.
The use of IBD proportions from a large set of affected sib-pair data to estimate some or all of the main parameters describing the inheritance of a disease susceptibility gene is here considered. We assume there is no recombination present and neglect ascertainment bias, and assume that there are four distinct parental haplotypes present in each family.
Genetic Diseases, Inborn↗
Investigating a single facet of a multilocus model.
We consider looking a a single locus of a multilocus model, such as that for IDDM, in particular the use of the sib-pair method concentrating attention on the influence of HLA.
Chromosome Mapping↗
The ubiquitous VA68 isoform of subunit A of the vacuolar H(+)-ATPase is highly expressed in human osteoclasts.
The 67-kDa subunit A of the vacuolar-type H(+)-ATPase carries the high affinity ATP binding site and together with the 57-kDa subunit B forms the catalytic domain. Two isoforms of subunit A, VA68 and HO68, were cloned from an osteoclastoma cDNA library. We have analyzed their respective expression patterns in different tissues by RNAase A protection and in situ hybridization. The HO68 isoform was found to be present only in the tumor originally used to construct the cDNA library, whereas the ubiquitous VA68 RNA isoform was detected in large osteoclastic cells, as well as in brian and kidney, by RNAse protection assay. Furthermore, we localized the strong signal observed in osteoclastoma RNA to the large osteoclastic cell by in situ hybridisation. These findings suggest that the subunit A highly expressed in human osteoclasts is the ubiquitous isoform, VA68.
Alkaline Phosphatase↗
Cloning of a pea cDNA encoding a polypeptide of the light-harvesting complex associated with photosystem I using a monoclonal antibody.
A monoclonal antibody (MAb UB42) is described that binds to thylakoids in pea chloroplasts, as shown by EM-immunogold labelling. The antibody recognised proteins of ca. 23-29 kDa in western blots of a pea leaf homogenate. A cDNA library was prepared from pea epidermal cells in the vector lambda ZAP II, and immunoscreening of the library with UB42 led to the isolation of a clone, pUB42. This was sequenced and had an open reading frame of 269 codons encoding a predicted polypeptide of 28.9 kDa. The sequence showed extensive homology with three closely related polypeptides belonging to a family of chlorophyll a/b-binding proteins from the light harvesting complex of photosystem I (LHCI). Collectively, the results suggest that MAb UB42 recognises an epitope on the type II chlorophyll a/b-binding protein from LHCI and that clone pUB42 encodes this protein.
Amino Acid Sequence↗
Gastrointestinal calcium absorption and dietary calcium load: relationships with bone remodelling in vertebral osteoporosis.
Patients with vertebral osteoporosis have a wide range of bone loss rates, bone remodelling rates and capacities for gastrointestinal (GI) calcium absorption. To test the hypothesis that variations in GI absorptive capacity determine rates of bone loss or remodelling, we have sought relationships between calcium absorption or vitamin D metabolite levels on the one hand and rates of cancellous and cortical bone loss (measured by serial quantitative computed tomography in the radius; n = 25) or indices of bone remodelling in tetracycline-prelabelled transiliac biopsies (n = 41) on the other, in a sequential untreated group. Calcium absorption (net and true) was measured in 18-day balances and by a two-isotope deconvolution method (fractional absorption and maximum absorption rate, MAR). There was no significant seasonal effect on any of these four measures of calcium absorption (variance ratio, F = 0.52-1.61, p > 0.1) or on 1,25-dihydroxyvitamin D levels (F = 0.13, p > 0.1; range 11-69 pg/ml), notwithstanding the expected seasonal effect on 25-hydroxyvitamin D levels (mean 18.7 ng/ml, zenith mid July, semi-amplitude 7.5 ng/ml; F = 6.82, p < 0.01). Neither this metabolite nor 1,25-dihydroxyvitamin D correlated with any index of calcium absorption (p > 0.1). No measure of calcium absorption (or intake) had a significant relationship with radial cortical or cancellous bone loss (p all > 0.1) but cancellous bone loss was associated with the rate of endogenous calcium excretion (r = 0.50, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
Addition of metronidazole to omeprazole/amoxycillin dual therapy increases the rate of Helicobacter pylori eradication: a double-blind, randomized trial.
AIMS: To compare the efficacy, safety and tolerability of an omeprazole/amoxycillin (OA) dual therapy Helicobacter pylori eradication regimen with an omeprazole/amoxycillin/metronidazole (OAM) triple therapy regimen. METHODS: In this double-blind trial, conducted in 19 hospitals, 119 patients with symptomatic duodenal ulcer disease were randomized to receive either 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and placebo followed by a further 14 days' treatment with omeprazole 20 mg daily (n = 59) or 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s., followed by a further 14 days' treatment with omeprazole 20 mg daily (n = 60). H. pylori status was assessed by 13C-urea breath test at entry and at 4 weeks post-treatment. RESULTS: H. pylori infection was eradicated in 46% of the OA treated patients and in 92% of the OAM treated patients, a mean difference of 46% (P < 0.0001, 95% CI for the difference: +30 to +62). In only one patient was the duodenal ulcer not endoscopically healed after 4 weeks of treatment (OA 100%; OAM 98% healed). There were no significant differences in speed of symptom relief or improvement in symptoms between the two groups. Both regimens were well tolerated, with 96% of patients completing the course, and only one patient withdrawing due to an adverse event. The only side-effect with a significantly higher incidence in the OAM group was diarrhoea, which occurred in 36% of patients compared to 16% of patients in the OA group (P < 0.05). CONCLUSIONS: A regimen consisting of omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. for 14 days gives an appreciably higher H. pylori eradication rate than omeprazole and amoxycillin alone, with acceptable tolerability.
Administration, Oral↗
Combining event scores to estimate the ability of competitors.
Simulation was used to investigate the validities of nine measures of ability derived from scores of two or more competitive events. The measures were: raw means and least-squares means of raw scores, z scores, and normal scores; two measures derived from ranked scores; and the "personal-best" raw score. Simulations were performed for different numbers of competitors, events, and event entries, each for a range of validity of performance in a single event. A complete set of simulations was repeated for each of the following conditions: normal distribution of competitors' ability; skewed distribution of ability; event validity related to ability; validity, ability, and spread of scores differing between events; and events differing in difficulty. The raw mean of raw scores was generally the most valid measure. The personal best was comparable to the mean only when the number of entries approached one per competitor. The least-squares mean of raw scores had highest validity when events differed substantially in difficulty; it should therefore be used when events differ in length, or when event scores are affected by environmental conditions, judging bias, or by uneven matching of competitors in match-play sports.
Competitive Behavior↗
Heterogeneity of vacuolar H(+)-ATPase: differential expression of two human subunit B isoforms.
The catalytic domain of the vacuolar proton ATPase is composed of a hexamer of three A subunits and three B subunits. Here we describe the cloning and characterization of a cDNA isoform of subunit B, HO57, from an osteoclastoma cDNA library. HO57 is represented by three species of mRNA of 1.6, 2.6 and 2.8 kb and is expressed at low levels in a range of human tissues, but at significantly higher levels in brain, kidney and osteoclastoma, and is probably an ubiquitously expressed isoform. In contrast, the kidney-specific isoform has an mRNA of 2 kb and is specifically expressed at high levels only in kidney and, at a lower level, in placenta. Thus the HO57 isoform is integral to the vacuolar ATPase found in the general secretory system of all cells as well as in vacuolar-ATPase-rich sources such as neurones and osteoclasts, whereas both the kidney-specific isoform and HO57 are highly expressed in the kidney. Furthermore, we show by in situ hybridization that HO57 is the only isoform that is exclusively and highly expressed by osteoclasts.
Animals↗
Preclinical pharmacology of CGP 42'446, a new, potent, heterocyclic bisphosphonate compound.
We have investigated the pharmacologic effects of a new bisphosphonate compound, CGP 42'446 [2-(imidazol-1-yl)-1-hydroxyethylidene-1,1-bisphosphonate], on bone metabolism. The compound exhibited potent inhibitory activity on the bone resorption induced by 1,25-dihydroxyvitamin D3 both in vivo in the thyroparathyroidectomized rat (ED50 0.072 microgram/kg SC) and in vitro in mouse calvarial cultures (IC50 0.002 microM). A comparison of the in vivo and in vitro inhibitory potencies of a total of nine bisphosphonates revealed an excellent correlation between the two assays (r = 0.97). CGP 42'446 also potently inhibited calvarial bone resorption induced by parathyroid hormone (1-34), parathyroid hormone-related protein (1-34), and recombinant human interleukin-1 beat. Short-term treatment of growing rats with CGP 42'H446 dose-dependently increased the radiographic density of the tibial proximal metaphysis (ED50 1.7 micrograms/kg SC) as well as increasing the calcium and hydroxyproline content of femoral trabeculae (ED50 values 0.17 and 1.1 micrograms/kg SC, respectively), but there was no detectable effect on cortical bone. On a molar basis in this range of in vivo screening assays, CGP 42'H446 was between 940-fold (thyroparathyroidectomized rat) and 87-fold (rat femoral trabecular calcium content) more potent than pamidronate. It is concluded that CGP 42'446 is a promising new, highly potent bisphosphonate for the suppression of the increased bone resorption associated with various diseases.
Animals↗
A comparison of omeprazole and ranitidine in the prevention of recurrence of benign esophageal stricture. Restore Investigator Group.
BACKGROUND/AIMS: Dilatation combined with subsequent pharmacological control of gastroesophageal reflux represents a logical but poorly documented approach to the management of benign esophageal stricture. This large trial (366 patients) aimed to assess whether omeprazole as the most effective available medication for gastroesophageal reflux disease prevents recurrent stricture formation. METHODS: Patients (n = 366) were randomized in a double-blind study to undergo either omeprazole (20 mg once daily; 180 evaluable patients) or ranitidine therapy (150 mg twice daily; 185 evaluable patients) for 1 year after dilatation to 12-18-mm diameter (36-54F gauge). Subsequently, endoscopy and dilatation were performed when clinically indicated and endoscopy on completion. Symptoms were assessed at clinic visits every 3 months and using weekly diary cards. RESULTS: Fewer patients undergoing omeprazole therapy required redilatation compared with those on ranitidine (43 of 143 [30%] vs. 66 of 143 [46%] by 12 months; P < 0.01), and patients in the omeprazole group needed fewer redilatations during the year (0.48 vs. 1.08; P < 0.01). On completion, symptom relief favored omeprazole: 76% of patients in the omeprazole group were free of dysphagia (compared with 64% in the ranitidine group; P < 0.05); 83% were able to accept a normal diet (69%; P < 0.01); and 65% were completely asymptomatic (43%; P < 0.001). CONCLUSIONS: Omeprazole, 20 mg once daily, was more effective than ranitidine, 150 mg twice daily, as prophylaxis against stricture recurrence and in providing symptom relief.
Adult↗
Modification of macrophage -T cell interaction during infection of mice with Mesocestoides corti (Cestoda).
Peritoneal macrophages from Mesocestoides corti-infected mice showed a marked and progressive loss of ability to act as accessory cells for syngeneic Con A-stimulated mesenteric lymph node lymphocytes. The same effect on the macrophages could be induced by intraperitoneal injection of M. corti culture supernatant, despite a concurrent increase in numbers of peritoneal adhesive macrophages. The findings are used to compare and contrast the known immunomodulatory effects of M. corti and taeniid metacestodes, the latter differing chiefly in their potential for modifying T-cell as well as macrophage behaviour.
Animals↗
Disease susceptibility genes and the sib-pair method: a review of recent methodology.
There is now a considerable body of literature which describes and analyses various methods of testing for the presence of disease susceptibility genes by examining the degree of HLA haplotype sharing of parental haplotypes over random expectations amongst affected siblings. We here survey a number of improvements, generalizations and extensions of the earlier reported methods with the aim of bringing them to the attention of those who are collecting HLA or other haplotype data on familial disease.
Family↗
The distribution of Q: a powerful sibship test of association.
Non-random inheritance of the two parental haplotypes among siblings affected by certain diseases has long been used to provide evidence of the presence of disease susceptibility genes. The distribution of a powerful test, called Q, based on haplotype concordance and discordance, is derived under the null hypothesis of random inheritance of haplotypes by affected siblings. The presence of a disease gene possibly linked to one of the haplotypes causes a change in the distribution of these haplotypes in the affected siblings. This distribution is found to be that of the sum of two independent variates contributed by the two parents in all parental types except one where both parents are heterozygous for the disease allele; which is dealt with separately. For comparison, the tables showing the powers of the test along with those of another well-known test, the N-test of haplotype concordance, are given. This is because Q is a modification of N to deal with the case when information on unaffected siblings is also available.
Genetic Diseases, Inborn↗
Glycoprotein domains and their role in gamete recognition in Fucus.
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Fertilization↗
Use of a bisphosphonate (pamidronate) to modulate fracture repair in ovine bone.
Bisphosphonates influence the morphology and mechanical properties of bones in growing rats, but their effects on fracture repair are not well documented. This study tests the hypothesis that bisphosphonates will modulate the remodelling phase of fracture repair, influencing the mechanical properties of healing bone. The effects of a bisphosphonate (pamidronate, Aredia) on the healing of a 3 mm osteotomy gap in the mid-diaphysis of the tibia, under rigid unilateral external fixation, were evaluated using 2 groups of 6 skeletally mature sheep. The repair process was evaluated weekly for 12 weeks using conventional radiographs, dual photon absorptiometry, and fracture stiffness measurements. The animals were then killed and the torsional stiffness and strength of the tibiae measured. More prolific callus formation, with an associated rise in the rate of bone mineral content, was observed in the treated group. There were no differences in in vivo fracture stiffness or postmortem torsional stiffness between the 2 groups, but torsional strength was greater in the treated group. Callus remodelling was reduced but not arrested in the treated group. Bisphosphonates act to reduce callus remodelling, leading to an increased amount of bridging callus and therefore strength. This study indicates that pamidronate has no adverse effects on the restoration of the mechanical integrity of a long bone after fracture.
Animals↗
Cloning and tissue distribution of subunits C, D, and E of the human vacuolar H(+)-ATPase.
The vacuolar proton ATPase (V-ATPase) translocates protons into intracellular organelles or across the plasma membrane of specialised cells such as osteoclast and renal intercalated cells. The catalytic site of the V-ATPase consists of a hexamer of three A subunits and three B subunits which bind and hydrolyse ATP and are regulated by accessory subunits C, D and E. cDNAs encoding subunits C, D, and E were cloned from human osteoclastoma, a tissue highly enriched in osteoclasts, as a first step in the characterisation of the V-ATPase used by the osteoclast. By Northern blot analysis only one mRNA species were detected for each of these subunits, which is consistent the constant transcription level in all tissues irrespective of the presence of specialised cells highly enriched in V-ATPases.
Amino Acid Sequence↗
A study of the quality of impressions for anterior crowns received at a commercial laboratory.
A report is presented of a study which was carried out to investigate the standard of impressions for anterior crowns received at a commercial dental laboratory in Great Britain. Aspects examined were the type of tray and its suitability to the impression technique used, fixation of the impression to the tray, the method of storage in transit, contamination, defects on the preparations and defects elsewhere affecting the occlusion. The quality of the actual preparation was not examined in this study. Similar details were noted for the opposing impression. Of the 50 cases examined only 12 were recorded as totally satisfactory, with 26 cases being recorded as not being of an acceptable standard for the construction of an adequate restoration. The results are presented with the conclusion that in this survey the general quality of impression was unacceptable.
Cross Infection↗