Inter-observer discrepancy in scoring signals on interphase FISH with an X library probe illustrated in a case of 47,XXX.
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Adolescent↗
Biomedical subjects
A Smith
Publications and source records attributed to A Smith.
Developmentally regulated sensitivity of Trypanosoma brucei brucei to the cytotoxic effects of human high-density lipoprotein.
The bloodstream developmental stages of the protozoan parasite Trypanosoma brucei brucei are lysed by normal human serum. The cytotoxic factor is a minor sub-class of human high-density lipoprotein termed trypanosome lytic factor (TLF). T.b. brucei rapidly develops resistance to TLF when incubated at 26 degrees C under conditions which allow differentiation to the procyclic, insect midgut developmental stage. This in vitro differentiation system allowed us to correlate loss of TLF sensitivity with other parameters of differentiation to the procyclic form. The onset of resistance to TLF occurs within 2 hr after shifting bloodstream forms to differentiation conditions. TLF resistance is correlated with a rapid but transient decrease in protein synthesis by the parasite, is acquired prior to cell division at 26 degrees C, and precedes the loss of variant surface glycoprotein. In addition, we found binding and uptake of TLF by established procyclic trypanosomes was reduced approximately fivefold relative to bloodstream trypanosomes and the TLF binding observed in procyclics was nonspecific. No TLF was bound to the procyclic flagellar pocket membrane and the procyclics failed to endocytose any of the surface-bound TLF. In contrast, bloodstream forms bind TLF via a flagellar pocket-localized protein and bound TLF is taken up by endocytosis. These findings suggest that resistance of procyclic T. b. brucei to TLF-mediated lysis is due to a reduction in the endocytosis of TLF by this developmental stage of the parasite.
Animals↗
Investigations with fluorescence in situ hybridization (FISH) demonstrate loss of the telomeres on the reciprocal chromosome in three unbalanced translocations involving chromosome 15 in the Prader-Willi and Angelman syndromes.
Two patients with classical features of Angel-man syndrome (AS) and one with Prader-Willi syndrome (PWS) had unbalanced reciprocal translocations involving the chromosome 15 proximal long arm and the telomeric region of chromosomes 7, 8 and 10. Fluorescence in situ hybridization (FISH) was used for the detection of chromosome 15(q11-13) deletions (with probes from the PWS/AS region) and to define the involvement of the telomere in the derivative chromosomes (with library probes and telomere-specific probes). The 15(q11-13) region was not deleted in one patient but was deleted in the other two. The telomere on the derivative chromosomes 7, 8 and 10 was deleted in all three cases. Thus, these are true reciprocal translocations in which there has been loss of the small satellited reciprocal chromosome (15) fragment.
Adult↗
Spatiotemporal stability and patterning of speech movement sequences.
In order to examine the stability and patterning of speech movement sequences, movements of the lip were recorded as subjects produced a phrase at normal, fast, and slow rates. Three methods of analysis were employed. First, a new index of spatiotemporal stability was derived by summing the standard deviations computed across amplitude- and time-normalized displacement records. This index indicated that normal and fast rates of speech production result in more stable movement execution compared to slow rates. In the second analysis, the relative time of occurrence of the peak velocity of the three middle opening movements of the utterance was measured. For each of the three peaks, the preservation of relative timing was assessed by applying Genter's (1987) slope test. The results clearly indicate that the relative timing of these events does not remain constant across changes in speech rate. The relative timing of the middle opening gestures shifted, becoming later as utterance duration increased. In a third analysis, pattern recognition techniques were applied to the normalized displacement waveforms. A classification algorithm was highly successful in sorting waveforms into normal, fast, and slow rate conditions. These findings were interpreted to suggest that, within a subject, three distinct patterns or movement templates exist, one for each rate of production. Speech rate appears to be a global parameter, one that affects the entire command sequence for the utterance.
Adult↗
An Mr 51,000 protein of mammalian spermatogenic cells that is common to the whole XY body and centromeric heterochromatin of autosomes.
During mammalian male meiotic prophase the sex chromosomes form a structure called the XY body or sex vesicle. This structure is characterized by differential condensation of chromatin and transcriptional inactivity. The reasons and mechanisms for the allocyclic behaviour of sex chromosomes with respect to autosomes are largely unknown. In order to gain insight into the process of XY-body formation we are involved in the characterization of proteins associated with meiotic sex chromosomes by immunological approaches. Here we report on the identification of an Mr 51,000 protein (p51) that is homogeneously distributed in the XY body of rodents as shown by immunocytochemistry with the novel monoclonal antibody 4EC. Interestingly, in germ line cells the antibody also labelled the centromeric heterochromatin of autosomes. We speculate that p51 may be a component of the mechanisms that lead to wide chromosome regions becoming inaccessible for transcription and/or recombination events.
Animals↗
Experience with the iodine-123 and technetium-99m labelled anti-granulocyte antibody MAb47: a comparison of labelling methods.
Four different methods of radiolabelling the anti-granulocyte monoclonal antibody MAb47 were compared and their influence on diagnostic value studied. The best clinical images were obtained following labelling with iodine-123 by the Iodogen method and direct labelling with technetium-99m after tris-(carboxyethyl)-phosphine treatment of MAb47 to achieve disulphide bridge reduction. 99mTc labelling using a specific ligand (MAb47-mtp), or a second method involving direct reduction with mercaptoethanol, led to an increased background activity in clinical studies, thus impeding the diagnosis of chronic disease. Fresh infections were clearly localized by all four preparations. The elimination of the activity from the blood was slower in the case of the iodinated MAb47, while the collected urine samples showed an excretion of about 10% of the injected activity per day independent of the labelling method. The results in terms of sensitivity and specificity were rather similar for all labelling methods and ranged from 90% to 99%.
Abscess↗
Effect of (-)-DS 121 and (+)-UH 232 on cocaine self-administration in rats.
The novel dopamine autoreceptor antagonists (-)-DS 121 and (+)-UH 232 were tested for their ability to alter cocaine self-administration behavior in rats reinforced on a progressive ratio (PR) schedule. (-)-DS 121 (15 mg/kg) and (+)-UH 232 (30 mg/kg) produced significant decreases in breaking point. (-)-DS 121 produced variable results on rate of cocaine intake on an FR1 schedule, indicating that rate may on occasion be insensitive to changes in cocaine reinforcement. In animals previously trained to self-administer cocaine, (-)-DS 121 failed to maintain responding when substituted for cocaine. This profile suggests that (-)-DS 121 is a promising new candidate for the treatment of cocaine abuse.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Oral self-administration of sweetened nicotine solutions by rats.
Oral self-administration of sweetened nicotine solutions in rats was studied in two ways. In the first experiment, one group had continuous access to a water bottle containing a sucrose solution and nicotine (10 micrograms/ml), while another group had access to an identical sucrose solution without nicotine. All rats had continuous access to water. While consumption of nicotine increased with increasing concentrations of sucrose, consumption of the sucrose+nicotine solution never exceeded the intake of sucrose alone. In subsequent experiments, the delivery of the solutions was made contingent upon an operant response. The sucrose+nicotine solution was found to maintain responding to higher response/reinforcer ratios than the sucrose only solution. These data demonstrate that rats will self-administer sweetened nicotine solutions and that sucrose+nicotine solutions are more reinforcing than sucrose solutions alone. Free access consumption is not a good predictor of the response maintaining properties of nicotine solutions.
Administration, Oral↗
Optimising the radioimmunotherapy of malignant disease: the broadening choice of carrier and effector moieties.
The treatment of cancer by radioimmunotherapy remains an experimental approach successful only in a limited number of selected disease conditions. One ground for optimism over the future of radioimmunotherapy lies in the fact that where cures have been obtained it has been despite the design of the immunoconjugate rather than because of it. As the choice of available functional components for conjugate construction increases, the process of evaluation and optimisation is underway. The replacement of the commonly used 131I with radionuclides possessing radiation characteristics more suited to particular disease states, and tailored to the behaviour of the carrier vehicle, should bring improved energy deposition within tumour while reducing whole body radiation burden. Similarly, the introduction of chemically or genetically engineered targeting molecules in place of conventional antibodies may bring improved pharmacokinetic characteristics and higher tumour accumulation. Optimisation of the therapeutic and carrier moieties employed in radioimmunotherapy should bring distinct improvements in clinical efficacy.
Animals↗
A prevalence study of ear problems in school children in Kiambu district, Kenya, May 1992.
Information on the prevalence of hearing impairment and related ear pathologies in children in sub-Saharan Africa is scarce. A pilot study for a clinical trial of simple treatments for chronic suppurative otitis media (CSOM) in school children in Kiambu district, Kenya, provided information on the prevalence of hearing impairment and ear pathologies. Five-thousand-three-hundred-sixty-eight children from 57 randomly chosen primary schools in Kiambu district were examined. Simple otoscopy was performed by clinical officers with specialty training in ENT, and hering testing was performed by trained nurses, using a hand held field audiometer. Microbiological specimens were obtained from those children with CSOM. Five-point-six percent of the children had a hearing impairment of > 30 dB HL in one or both ears, with 2.2% having bilateral hearing impairment. Two-point-four percent had at least one perforated tympanic membrane, and 1.1% had CSOM. Eight-point-six percent of the children had wax obstructing the tympanic membrane. There is evidence of a relationship between hearing impairment and both CSOM and wax obstructing the tympanic membrane. The most common organisms found were Pseudomonas spp. (34%), Proteus spp. (34%) and Eschericia coli (19%). These results are comparable with other studies in Africa and indicate a considerable burden of ear disease in Kiambu district, Kenya.
Adolescent↗
The alpha-Ca2+/calmodulin kinase II: a bidirectional modulator of presynaptic plasticity.
The alpha-Ca2+/calmodulin kinase II (alpha CaMKII) is required for long-term potentiation in the CA1 region of the hippocampus. Here, we report that this kinase also has a crucial role in presynaptic plasticity. Paired-pulse facilitation is blunted in the CA1 region of mice heterozygous for a targeted mutation of alpha CaMKII, confirming that this kinase can promote neurotransmitter release. Unexpectedly, field and whole-cell recordings of posttetanic potentiation show that the synaptic responses of mutants are larger than those of controls, indicating that alpha CaMKII can also inhibit transmitter release immediately after tetanic stimulation. Thus, alpha CaMKII has the capacity either to potentiate or to depress excitatory synaptic transmission depending on the pattern of presynaptic activation.
Animals↗
Obstetric complications and severity of illness in schizophrenia.
A history of obstetric complications (OCs) is common in schizophrenia and may lead to a severe form of the disorder. In order to test this possibility, three questions were identified: (1) Is a history of OCs in schizophrenia common in patients with a severe form of illness? (2) Do patients with OCs have more impaired function, greater severity of illness, and poorer treatment outcome than those with no identified OCs? (3) Are OCs associated with an early age at onset of illness? Obstetric history, clinical indices of functioning, and illness severity were obtained for 83 severely ill patients with schizophrenia. The proportion of patients with a history of OCs was greater in this study than has been reported previously. Subjects with a history of OCs had better functioning than those with no OCs at the time of admission but no group differences were found at discharge. No difference in age at onset of illness was found between patients with and without an OC history.
Activities of Daily Living↗
Development of a simple and selective separation of 67Cu from irradiated zinc for use in antibody labelling: a comparison of methods.
A procedure for the production and separation of Cu isotopes from irradiated Zn was developed. Following a comparison of methods based on extraction, electrolysis and ion-exchange chromatography, a technique for the separation of Cu employing three ion-exchange matrices was developed which was simple, reproducible and hot cell-compatible. The specific activity of the final product was 37 MBq 67Cu/microgram Cu at EOB. The level of impurities was so low that no interference with antibody labelling was observed.
Antibodies↗
The surgical anatomy of coronary venous return in hearts with isomeric atrial appendages.
Although absence of the coronary sinus is widely recognized in hearts with isomerism of the right atrial appendages, little attention has been paid to the fashion of the venous return from the heart itself. In this study, the arrangement of coronary venous return was investigated in 99 specimens with isomeric right and 49 with isomeric left appendages. In the normal heart, the coronary veins consist of a circumflex component within the atrioventricular groove and longitudinal components on the ventricular mass. The circumflex venous system was seen in 44 hearts with isomerism of left appendages (90%), but 23 of these hearts lacked the anatomic features of the coronary sinus. Circumflex veins were entirely lacking in the other 10% of hearts with isomeric left appendages and in all those with isomeric right appendages. In these hearts, longitudinal veins drained independently into the atria in three patterns. The first was a direct connection, with the venous orifice opening between the trabeculations of the atrial wall immediately having crossed the atrioventricular groove. The second was a crooked return, with the vein running an intramural course along the atrioventricular groove. The third was a distant connection, reaching superiorly to the smooth-walled atrial component after running an intramural course. Intramural courses were seen in 19% of the longitudinal veins, such veins being found in 62% of all hearts with no circumflex venous system. These findings, which to the best of our knowledge have never previously been recognized in detail, almost certainly have potential surgical significance.
Coronary Vessel Anomalies↗
Left ventricular structures in atrioventricular septal defect associated with isomerism of atrial appendages compared with similar features with usual atrial arrangement.
In patients with isomeric atrial appendages, regurgitation of atrioventricular valves is recognized clinically as one of the risk factors that militate against successful achievement of definitive repairs. To determine whether this reflected anatomic features, we investigated 91 specimens with atrioventricular septal defect that had a common atrioventricular valve and biventricular atrioventricular connections. Of these specimens, 35 had isomeric right appendages, 23 showed isomeric left appendages, and 33 had usual atrial arrangement. We measured either the size or location of the supporting papillary muscles and the circumference of the mural leaflet within the morphologically systemic ventricle, as well as the length of outlet, inlet, and so-called scooped dimensions of the muscular ventricular septum. Presence of a solitary papillary muscle, or deviation of the attachments of the papillary muscles, was more frequent in hearts with isomeric right appendages. Values for the diameter and lengths of the papillary muscles were significantly smaller in hearts with isomeric right appendages compared with those with usual atrial arrangement (p < 0.001), as were the distances between the papillary muscles (p < 0.002) and the circumference of the mural leaflet (p < 0.001). The proportional length of ventricular outlet was longer in the setting of isomeric right appendages than in the other groups (p < 0.001), whereas the extent of septal scooping showed no differences among these three groups. We conclude that these structural features could be factors in the known insufficiency of the common atrioventricular valve and the ventricular dysfunction in patients with isomeric right appendages.
Heart Atria↗
The role of support group facilitator: ensuring success.
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Counseling↗
Does it matter where you live? Treatment variation for breast cancer in Yorkshire. The Yorkshire Breast Cancer Group.
Over 27,000 patients with breast cancer were identified from cancer registry data from 1978 to 1992 and differences in treatment practice across the 16 districts of Yorkshire studied. A total of 50 surgeons treated more than an average of ten cases a year. Surgeons who expressed an interest in breast cancer were more likely to treat a greater number of patients than those who had no special interest in the disease and offered patients chemotherapy, hormone therapy and radiotherapy more often. The average regional mastectomy rate fell from 70% to 44% over this period, but the rate varied between districts from 13% to 87%, with those at the extremes occupying these positions year on year. The rate of uptake of radiotherapy varied between districts from 13% to 58% over the period 1978-92. The use of adjuvant chemotherapy increased from 5% to 19% and hormone therapy from 19% to 80% over this time period. An audit of the facilities available within each district carried out in early 1994 also showed considerable variation, although all districts now have access to a nurse specialist. There were wide variations in treatment offered to patients with breast cancer. Patients in some districts were denied access to chemo- and and radiotherapy despite published guidelines showing these modalities to be useful. It is recommended that patients are referred to units with an interest in breast cancer rather than to general surgical out-patients.
Breast Neoplasms↗
Investigation of the redox state of recombinant horseradish peroxidase produced in inclusion bodies and factors affecting the efficiency of refolding.
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Cloning, Molecular↗