Dinucleotide repeat polymorphism of D15S10 in the Prader-Willi chromosome region (PWCR).
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Base Sequence↗
Biomedical subjects
A Smith
Publications and source records attributed to A Smith.
Ring chromosome 15 and 15qs+ mosaic: clinical and cytogenetic behaviour spanning 29 years.
A phenotypic female with mild mental retardation, minor facial anomalies, and short stature has been evaluated clinically and cytogenetically over 29 years. At age 59, she remains physically well and shows no signs of dementia. Cytogenetic analysis, performed on peripheral blood specimens on 10 occasions between 1961 and 1990, showed mosaicism with one cell line containing a large stable ring (15) chromosome and another cell line without the ring but with a 15qs+. The different cell lines remained constant. The case provides information on the natural history of the ring chromosome 15 syndrome.
Adult↗
Substrate and pH effects on glutamine synthesis in rat liver. Consequences for acid-base regulation.
Switching in acidosis of hepatic nitrogen disposal from urea synthesis to NH4+ and net glutamine production was demonstrated in the isolated perfused livers of starved male Wistar rats. Lactate was preferred to glucose as the substrate for the carbon skeleton of glutamine synthesized over the pH range 6.9-7.5. This is necessary if the switch away from a proton-producing process (ureagenesis) in acidosis is to constitute an acid-base regulating system intrinsic to the liver. Glutamine balance shifted with pH from marked net uptake to small net output under acidotic conditions (pH 7.5-6.9), an effect due solely to a decrease in glutamine uptake. NH4+ uptake by the liver had a linear relationship with pH, being markedly decreased in acidosis because glutamine synthesis was insufficient to compensate for the decreased incorporation into urea. Animals rendered chronically acidotic showed a lower central venous plasma urea concentration and a raised NH4+ concentration, but their livers synthesized no more glutamine when perfused at an acidotic pH than did normal livers. We conclude that perivenous hepatocytes may not be efficient scavengers of NH4+ ions, which must be partly disposed of elsewhere by non-proton-generating pathways if inhibition of ureagenesis is to represent a hepatic acid-base regulating system.
Acid-Base Equilibrium↗
Spontaneous echo contrast effect as an indicator of flow-limiting coronary stenosis.
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Aged↗
Crosslinking of hemin to a specific site on the 90-kDa ferritin repressor protein.
Incubation of a 90-kDa ferritin repressor protein (FRP) with small amounts of radiolabeled hemin resulted in the formation of a strong interaction between the two that was stable to SDS/PAGE. (We refer to this interaction as a "crosslink," without intending to imply knowledge as to its chemical nature.) Of seven other proteins tested individually, only apohemopexin and bovine serum albumin showed similar crosslinking ability, albeit to a much lower extent. [14C]Hemin specifically crosslinked to FRP in the presence of a 50-fold excess of total wheat germ proteins. Inclusion of catalase did not prevent the reaction of hemin with FRP, suggesting that H2O2 is not involved. The subsequent addition of a stoichiometric amount of apohemopexin did not reverse the reaction. Exhaustive digestion of the complex with Staphylococcus aureus V8 protease produced a major labeled peptide of 17 kDa. These results show the existence of a highly specific, uniquely reactive hemin binding site on FRP.
Binding Sites↗
The murine haemopexin receptor. Evidence that the haemopexin-binding site resides on a 20 kDa subunit and that receptor recycling is regulated by protein kinase C.
Haemopexin receptors from mouse hepatoma (Hepa) cells were affinity-labelled by cross-linking to haem-125I-haemopexin complexes using two homo-[disuccinimidyl suberate (DSS) and 3,3'-dithiobis(succinimidyl propionate) (DTSSP)] and one hetero-[sulphosuccinimidyl 4-(p-maleimidophenyl)butyrate (sulpho-SMPB)] bifunctional cross-linking agents. Analysis of the cross-linked products by SDS/PAGE in the absence of reducing agents revealed that 125I-haemopexin was cross-linked specifically to a protein of apparent molecular mass 85-90 kDa. Upon reduction, haemopexin remained cross-linked to a protein of 20 kDa, suggesting that the murine haemopexin receptor has a subunit structure. Two subunits were identified: alpha (p65) and beta (p20). Furthermore, because haemopexin was cross-linked by all three agents to p20, the shortest cross-linker arm being 1.1 nm (11 A), we propose that the haem-haemopexin-binding site resides on this subunit. In addition, a cysteine residue of p20 is located near the haemopexin-binding site, since haemopexin, which has no free thiol groups, is cross-linked to this subunit by the hetero-bifunctional agent sulpho-SMPB. Exposure of Hepa cells to the tumour-promoting phorbol ester 4 alpha-phorbol 12-myristate 13-acetate (PMA) causes a rapid redistribution of haemopexin receptors from the cell surface to the cell interior. Within 2-4 min of incubation with 100 nM-PMA, there was an approx. 50% decrease in cell-surface haemopexin receptors, as judged by ligand binding at 0 degrees C and affinity labelling of the receptor. This time- and dose-dependent down-regulation was fully reversible within 60-90 min after removal of PMA, and the affinity of the remaining receptors was unaltered by PMA. The specificity of PMA was demonstrated by comparison with the non-tumour-promoter 4 alpha-phorbol, which did not affect any of the parameters examined. The amine H-7, a specific inhibitor of protein kinase C, antagonised the receptor redistribution effect of PMA, suggesting that the down-regulation of haemopexin receptors on the cell surface was a consequence of protein kinase C activation. The PMA-induced decrease in surface haemopexin receptors was due to a 2-fold increase in the rate of internalization (from 0.73 min-1 to 1.32 min-1), whereas the rate of exocytosis (0.6 min-1) was unchanged. PMA treatment, like binding of the natural ligand, haem-haemopexin, results in a lower steady-state level of surface haemopexin receptors independent of receptor synthesis, and the receptors were not degraded but were recycled back to the cell surface.
Animals↗
Comparison of nerve regeneration through different types of neural prostheses.
Rat sciatic nerve regeneration through three synthetic neural prostheses was compared with regeneration through nerve allografts. The synthetic prostheses were either nonpermeable nonabsorbable (Silastic), permeable absorbable (polyglactin mesh), or permeable nonabsorbable (polypropylene mesh). Animals were evaluated at 10, 24, and 90 days. Functional analysis of nerve regeneration was performed by noninvasive methods: electromyography and walking tracks. Nerve tissue was examined with routine histologic and immunofluorescent techniques. A compressive neuropathy developed with the use of the Silastic implant. A neutrophilic inflammatory infiltrate was consistently associated with implantation of the polyglactin mesh. A strong connective tissue response was noted around the polypropylene mesh. Early recovery of nerve function was seen with the Silastic implants, however, overall nerve function was best in the nerve allograft and polypropylene mesh groups. Polyglactin implantation increases the local inflammatory response and should not be used for nerve anastomoses. If Silastic entubulation is used, it should be removed between 24 and 90 days.
Animals↗
Post-mortem findings in a fetus with 48,XXY,+21.
A fetus with 48,XXY,+21 was detected on routine amniocentesis at 15 weeks for advanced maternal age. Fibroblast cultures from six different tissues were initiated after termination and each showed the same karyotype without any tissue limited mosaicism. The only phenotypic abnormality detected at post-mortem examination was bilateral clinodactyly of the fifth finger which had been detected on ultrasound. The maternal serum alpha-fetoprotein and the femur length were normal. Maternal age remains an essential criterion for prenatal diagnosis.
Adult↗
A de novo unbalanced reciprocal translocation identified as paternal in origin in the Prader-Willi syndrome.
Interstitial cytogenetic deletions involving the paternally derived chromosome 15q11-13 have been described in patients with the Prader-Willi syndrome (PWS). We report a child with PWS and a de novo unbalanced karyotype -45,XY,-9,-15,+der(9)t(9;15)(q34;q13). Molecular studies with the DNA probe pML34 confirmed that only a single Prader Willi critical region (PWCR:15q11.2-q12) copy was present. Hybridisation of patient and parental DNA with the multi-allelic probe CMW1, which maps to pter-15q13, showed that the chromosome involved in the translocation was paternal in origin. This is the first example of a paternally-derived PWCR allele loss caused by an unbalanced translocation that has arisen de novo.
Blotting, Southern↗
Comparative intraperitoneal pharmacokinetics of three platinum analogues.
The pharmakokinetic profiles of intraperitoneally infused platinum analogues were determined in 13 women exhibiting minimal residual disease following surgery and systemic chemotherapy for epithelial ovarian cancer or fallopian tube carcinoma by following the disposition of tracer doses of 195mPt radiolabel. Six patients received iproplatin, four were given cisplatin and three received carboplatin. The present data demonstrate no difference in the disposition of total platinum between these three analogues, but differences in the kinetics of free platinum may exist.
Antineoplastic Agents↗
The run-down and closure of a psychiatric hospital. Effects on patients' behaviour.
The run-down and closure of psychiatric hospitals can be stressful for both staff and patients. Interviews with approximately 50% of over 100 long-stay psychiatric patients during an 18 month period preceeding a hospital closure show them to be generally ill-informed as to reasons for closure and future plans for their care. However, repeat measures of behavioural functioning (CAPE and REHAB) during this running-down period show no significant changes in patients' behaviour.
Activities of Daily Living↗
Further characterization of structural determinants of rabbit hemopexin function.
To further identify structural features of the hemopexin molecule important for its heme transport function, a fragment of the heme-binding domain (residues 1-213, Mr 35 kD, domain I) of rabbit hemopexin was obtained after digestion with subtilisin. Both apo- and heme-domain I were cleaved by subtilisin, and the subtilisin-digested form of domain I (called SD-DI) was shown by microsequencing to have been cleaved at Asp 22 forming a 30 kD subfragment lacking the conserved histidine residue at position 7 and the N-linked oligosaccharide at Asn 9. The 5 kD peptide cleaved from domain I is not disulfide linked to domain I and can be removed by membrane ultrafiltration. SD-DI retains the ability of domain I to bind heme, to associate with the other functional domain of hemopexin (domain II), and to interact with the hemopexin receptor on mouse Hepa cells. Moreover, although the heme complex of SD-DI is less thermostable than native heme-domain I, like heme-domain I, heme-SD-DI is stabilized to a large extent when associated with domain II. These results show that the conserved His 7 residue is not involved in heme binding by hemopexin and that residues 1-22 of hemopexin and the N-linked oligosaccharide at Asn 9 are not essential for either receptor binding or interdomain interactions. Nevertheless, these N-terminal residues of hemopexin do contribute significantly to the overall stability of the hemopexin molecule and the interdomain interactions necessary for receptor recognition.
Amino Acid Sequence↗
Helicobacter pylori in children with peptic ulcer and their families.
Little is known about the source and spread of Helicobacter pylori, but transmission from infected family contacts has been suggested. We have therefore investigated 15 children with peptic ulcer and their first-degree relatives for H. pylori. Serum anti-H. pylori IgG, pepsinogen I, and gastrin levels were measured. Endoscopy was carried out on the children and relatives, and biopsies were taken from the gastric antrum for histology, microbiology, and urease testing. Six of 11 children with duodenal ulcer (55%) and two of four children with gastric ulcer (50%) were positive for H. pylori. Fourteen of 16 parents (87%) and eight of 13 siblings (61%) of H. pylori-positive children with peptic ulcer were also infected compared with eight of 14 parents (57%) and none of four siblings of H. pylori-negative children with peptic ulcer (P less than 0.10, greater than 0.05, and NS, respectively). The children with H. pylori-negative peptic ulcer and negative siblings combined were younger than positive children with peptic ulcer and positive siblings (P less than 0.001). The reliability of serum anti-H. pylori IgG level as a screening test for infection was confirmed. These findings call into question a pathogenetic role for H. pylori in some childhood peptic ulceration, but do suggest that person-to-person spread of infection occurs.
Adolescent↗
The myth of the aortic annulus: the anatomy of the subaortic outflow tract.
Surgical repair of the small aortic root is limited in part by the very structure of the outflow tract from the left ventricle. The root is not constructed on the basis of a ringlike annulus supporting the leaflets of the aortic valve. The only truly circular structure within the outflow tract is the junction of the aortic wall with the underlying ventricular structures, themselves partly muscular and partly fibrous. This circular ventriculoarterial junction is crossed by the semilunar attachments of the leaflets of the aortic valve, producing an interlinking arrangement between the expanded aortic sinuses and three triangles of fibrous tissue placed beneath the apexes of the commissures between the valve leaflets. The triangles form extensions of the left ventricle that are related, in part, to the pericardial cavity surrounding the heart. The arrangements of the attachment of the leaflets in malformed valves with two (or only one) effective leaflets are highly abnormal, although these valves are usually produced on the template of three aortic sinuses. The valve with two leaflets rarely gives problems during childhood. In valves producing "critical stenosis", there is usually only one effective leaflet, a condition due to incomplete liberation of two of the anticipated three commissures. Detailed study shows that, in these malformed hearts, the attachment of the leaflets is much more annular than in normal valves, with inadequate formation of the fibrous triangles.
Aortic Valve↗
Predisposing factors in bladder calculi. Review of 100 cases.
One hundred patients, aged twenty to ninety-two years, underwent 111 procedures for removal of bladder calculi. Most patients (88) had some type of bladder outlet obstruction. Two types of stones were identified: those that had apparently formed in the upper tract and been trapped in the bladder (17 cases) and those that appeared to have formed in the bladder in the presence of various types of outlet obstruction. Stone analysis revealed uric acid stones in 50 percent, calcium oxalate stones in 19 percent, and stones of mixed composition in 31 percent. Five patients had metabolic abnormalities predisposing to stone formation; in 2 cases, these abnormalities were discovered during the evaluation for stone disease. Treatment depended on stone characteristics, associated pathology, and the general health of the patient. A review of the literature with regard to the morbidity and mortality of combining treatment of vesical calculi and bladder outlet obstruction secondary to prostatic obstruction is included.
Adult↗
A rapid solid-phase rosette-inhibition assay for the detection of Fc receptor (FcRII)-blocking alloantibodies [corrected].
A procedure for the detection of FcR-blocking alloantibodies is described which uses human B lymphocytes immobilised on plastic by poly-L-lysine. Antibodies which inhibited rosette formation between B lymphocytes or Daudi cells and ox erythrocytes coated with rabbit antibodies (EA) were detected in 10 out of 10 sera containing anti-HLA A2 antibodies and 3 out of 3 sera containing anti-HLA class II antibodies. Inhibition of rosette formation (EAI activity) was mediated by protein G-separated IgG. Analysis of rosette formation using these 13 sera and lymphocytes from 39 donors revealed that the degree of inhibition was bimodal; most sera were either clearly inhibitory or non-inhibitory in the assay. However, there was no correlation between inhibition of rosette formation (EAI activity) and lymphocytotoxicity. Four pairs of sera showed similar patterns of reactivity (r greater than 0.6, p less than 0.01; 2 x 2 chi-square test), and cells from 2 donors showed antithetical reactions with 12 of 13 sera (r = -0.86, p less than 0.001). These data suggest that the solid-phase rosette inhibition assay is a rapid and reproducible means of detecting antibodies reactive with non-HLA class I or class II antigens on human B cells.
B-Lymphocytes↗
Developmental and age-related changes in reflexes of the human jaw-closing system.
Reflex responses of the jaw-closing system to innocuous mechanical stimulation of the tongue and palate were examined in a group of 25 girls aged 7-8 years and in a group of 25 women aged 70-80 years. Responses were measured both as changes in background biting force and from bilateral recordings of masseter EMGs. For comparative purposes, results from an earlier study of 35 young adult women (aged 18-25 years) were available. Compared to younger groups of subjects, reflex responses of the elderly were reduced in numbers and amplitude, were characterized by fewer initial excitatory component responses, and had longer latency to onset. Analyses of responses of the children indicated that age 7-8 years is a transitional period. Some children show adult-like responses, while others display responses that appear to represent earlier forms or transitional responses. These results suggest that oral-motor reflexes are not fixed response patterns upon which more complex motor skills, such as speech, are built. Rather, oral reflex development appears to occur in concert with the acquisition of complex motor skills. Systematic changes in reflex responses also occur in the period from young adulthood to seventh decade of life. This result indicates a continuous evolution of oral sensorimotor systems throughout the human life span.
Adult↗
Influences of meal size on post-lunch changes in performance efficiency, mood, and cardiovascular function.
This study examined the effects of the size of the meal on post-lunch changes in attention, mood, blood pressure and pulse. Thirty-five females subjects were tested before and after lunch. One group (n = 12) were than given a normal-sized lunch, another (n = 11) were given a lunch designed to contain 40% more energy than their individual requirement and the third group (n = 12) had a lunch with an energy content 40% less than the estimated requirement. After lunch all groups of subjects reported that they felt more feeble, dreamy and bored, and less alert, excited, clear-headed, energetic, quick-witted, friendly, sociable and elated. However, the size of the meal did not alter the extent of the pre/post-meal differences. Similarly, there was no effect of meal size on pulse rate or blood pressure, although pre/post-meal differences were observed. In contrast, subjects who had a larger lunch than normal made more errors on focussed attention and search tasks (especially the search task) than those who had a normal-sized lunch or one which was smaller than normal.
Adult↗