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Biomedical subjects

A Rees

Publications and source records attributed to A Rees.

At least 127 records · Page 7Linked to original sources

Binaural masking level difference effects in single units of the guinea pig inferior colliculus.

We have studied the masking effects of a binaurally presented noise on the responses to binaural signals recorded from low-frequency cells in the inferior colliculus of the guinea pig. The spike rates to the masker and signal + masker were compared to quantify masking at different interaural time delays of the noise. The signal was a 50-ms tone burst at best frequency or a 50-ms segment of a synthetic vowel presented at the best interaural delay of the unit tested. At each noise masker delay, the noise level was adjusted to obtain a criterion spike difference. In most cases, the level required was lowest at the best delay for the noise. The mean difference between maximum and minimum masked thresholds across the cell population was very similar to the human psychophysical masking level difference under the same signal and masker conditions. In another series of tests, we measured the effect of the noise masker on the temporal pattern of the discharge to the signal. The signal used was a 500-ms segment of the synthetic vowel. In virtually all cases the addition of a continuous noise masker reduced the discharge rate synchronized to the fundamental frequency of the vowel. The degree of this reduction was dependent on the interaural time delay of the noise masker. For most units, maximum reduction was seen when the vowel and noise had the same interaural time delay. The similarity between the masking which we have shown physiologically and the reported in a variety of human psychophysical experiments suggests that the processing at levels up to and including the inferior colliculus contributes to the psychophysical BMLD.

Acoustic Stimulation↗

Placental bed spiral arteries in the hypertensive disorders of pregnancy.

OBJECTIVE: The investigation of the histology of the placental bed spiral arteries in normal pregnancy and in pregnancies complicated by hypertension, with or without proteinura. DESIGN: An observational study, based on women having caesarean sections for clinical reasons. SUBJECTS: 17 normal pregnant women, 43 with gestational hypertension, of whom 39 had proteinuria, 17 with chronic hypertension, of whom 6 had proteinuria, and 5 with unclassified hypertension. INTERVENTIONS: Placental bed biopsies obtained during caesarean section. MAIN OUTCOME MEASURES: Histological appearance of sections stained with haematoxylin and eosin PAS and Lendrum's MSB. RESULTS: Biopsies containing spiral arteries were obtained from 6 normotensive and 44 hypertensive women. Trophoblastic invasion was present in 5 of the 6 normotensive biopsies but absent in the majority of those with hypertension. Subintimal proliferation was seen in all the normotensive biopsies but in only 8 of 28 from those with gestational hypertension and proteinuria. Other features seen predominantly or only in the hypertensive biopsies, in order of frequency, were medial hyperplasia, fibrin deposits, acute atherosis, endothelial vacuolation and thrombosis. CONCLUSION: Absence of physiological changes may not be peculiar to preeclampsia but may be associated or even a result of various forms of hypertension in pregnancy. Spiral arteries show a spectrum of changes in hypertensive pregnancies that do not appear to bear a clear-cut relation to the clinical signs.

Arteries↗

Molecular scanning of insulin-responsive glucose transporter (GLUT4) gene in NIDDM subjects.

We investigated the prevalence of mutations in the gene encoding the major insulin-responsive facilitative glucose transporter (GLUT4) in patients with non-insulin-dependent diabetes mellitus (NIDDM). All 11 exons of the GLUT4 gene from 30 British white subjects with NIDDM were amplified using the polymerase chain reaction and screened for nucleotide sequence variation using the single-stranded conformation polymorphism (SSCP) method. No variation between the study subjects was detected in exons 1-3, 4b-8, and 10. Variant SSCP patterns were detected in exons 4a and 9. SSCP variation in exon 4a was revealed by direct nucleotide sequencing to be due to a common silent polymorphism (AAC----AAT at Asn130). One NIDDM patient demonstrated a variant SSCP pattern in exon 9. This was caused by a point mutation (GTC----ATC) at codon 383, which leads to the conservative substitution of isoleucine for valine in the putative fifth extracellular loop of the transporter. Allele-specific oligonucleotide hybridization was used to examine the frequency of this mutation in 240 Welsh white subjects (160 with NIDDM and 80 controls). The Val----Ile383 mutation was found in the heterozygous state in two diabetic subjects and no control subjects. We conclude that mutations of the GLUT4 coding sequence are very uncommon in this population of subjects with typical NIDDM. Determining whether the Ile383 GLUT4 variant present in 3 diabetic subjects contributes in any way to their disease will require further study.

Alleles↗

Rapid electrochemiluminescence assays of polymerase chain reaction products.

We demonstrate the first use of an electrochemiluminescent (ECL) label, [4-(N-succimidyloxycarbonylpropyl)-4'-methyl-2,2'- bipyridine]ruthenium(II) dihexafluorophosphate (Origen label; IGEN Inc.), in DNA probe assays. This label allows rapid (less than 25 min) quantification and detection of polymerase chain reaction (PCR)-amplified products from oncogenes, viruses, and cloned genes. For the PCR, we used labeled oligonucleotide primers complementary to human papiloma virus and the Ha-ras oncogene. These samples were followed by ECL analysis or hybridization with specific, Origen-labeled oligonucleotide probes. These studies demonstrate the speed, specificity, and effectiveness of the new ECL labels, compared with 32P, for nucleic acid probe applications. We describe formats involving conventional methodologies and a new format that requires no wash step, allowing simple and rapid sample analysis. These rapid assays also reduce PCR contamination, by requiring less sample handling. Improvements in ECL detectability are currently under investigation for use in DNA probe assays without amplification.

2,2'-Dipyridyl↗

An electrocardiographic midterm follow-up study after anatomic repair of transposition of the great arteries.

Prospective studies of rhythm and conduction, before and after 1-stage anatomic repair of simple transposition of the great arteries, were performed on 24 survivors. Pre- and postsurgical serial standard electrocardiograms were obtained on each patient. Fourteen patients underwent perioperative 24-hour electrocardiograms; all had follow-up 24-hour electrocardiograms. Rare atrial or occasional ventricular premature complexes were detected in 3 (11%) patients before operation. After surgery, 1 patient developed right bundle branch block. Two patients developed a left bundle branch block. One patient had a QS pattern in V6, which disappeared on follow-up electrocardiogram. Transient second-degree atrioventricular block was detected in 1 patient. A normal P-R interval and P-wave axis were present in all but 1 patient. Mild sinus bradycardia or rare atrial or ventricular premature complexes were detected in 4 of twenty-nine 24-hour electrocardiograms performed in the first 2 years after surgery. At 3 years after repair, 5 patients had a normal 24-hour electrocardiogram and 1 had low-grade ectopy (rare atrial and ventricular premature complexes). At 4 years, all 4 patients studied had normal 24-hour electrocardiograms. During a mean follow-up of 3 years, we have yet to document any symptomatic arrhythmias.

Arrhythmias, Cardiac↗

Interaural delay sensitivity to tones and broad band signals in the guinea-pig inferior colliculus.

We have measured the sensitivity of 243 low-frequency cells in the central nucleus of the guinea pig to the interaural time delay of best frequency (BF) tones, wideband noise and synthetic vowels. The highest rate of firing for the majority of cells occurred when the stimulus to the contralateral ear arrived 100-400 microseconds before that to the ipsilateral ear. The best delays for tones and noise measured in the same cell were highly correlated. In contrast to the tone delay functions, the majority of the delay functions obtained in response to wideband signals did not cycle, but were characterized by a single dominant peak or trough. The response frequency calculated from the delay functions to the vowel often did not correspond to the unit's BF, suggesting that the unit was responding to a component close to the first formant frequency (730 Hz) of the vowel. Phase-locked responses, on the other hand, only occurred to the fundamental frequency of the vowel (100 Hz) and not to higher frequency components. The responses to delayed tone and noise signals in the guinea pig are very like those obtained in the cat and other mammals. The similarity of the range of best delays for the guinea-pig with those reported for the cat, despite the difference in head size in these two species, suggests that the sensitivity to interaural delays reflects the properties of the binaural pathways rather than an adaptation to the delays normally experienced by the animal.

Acoustic Stimulation↗

The Apo(a) gene: structure/function relationships and the possible link with thrombotic atheromatous disease.

The last 25 years have witnessed an exponential increase of interest in the lipoprotein Lp(a). The structure of the gene encoding for its unique apo protein, Apo(a) has been determined resulting in possible structure/function relationships which may explain the close association between elevated levels of Lp(a) and atheromatous vascular disease. These findings may have profound therapeutic implications for the future treatment of the hyperlipidaemias and hypercholesterolaemia in particular.

Apolipoproteins A↗

Allelic variants at insulin-receptor and insulin gene loci and susceptibility to NIDDM in Welsh population.

A cohort of 132 well-documented White Welsh non-insulin-dependent diabetic (NIDDM) subjects were genotyped for 5 restriction-fragment-length polymorphisms (RFLPs) at the insulin-receptor gene (IRG) locus and a polymorphic locus 5' to the insulin gene. There was no significant difference in RFLP frequencies between the NIDDM subjects and a group of 87 matched White control subjects. Paired haplotype analysis of the IRG RFLPs suggested a difference between NIDDM and control groups for the endonuclease combinations Bgl II-Rsa I and Bgl II-Xba I. Analysis of implied haplotypes defined by the endonucleases Bgl II, Rsa I, and Xba I revealed one haplotype to be more prevalent in the NIDDM group; whereas, another haplotype was associated with the control group (P less than 0.02). Subset analysis within the NIDDM cohort compared the metabolic response of NIDDM subjects with the differing IRG haplotypes to a standard meal tolerance test. Both groups showed equivalent basal and postprandial glucose excursions, but one group revealed a significantly exaggerated plasma insulin response compared with the other (P less than 0.05). This may reflect the influence of genetic variation at the IRG locus on insulin sensitivity in patients with NIDDM.

Adult↗

Intracardiac extension of Wilms' tumor.

Three cases of right-sided Wilms' tumor with direct intracardiac extension are described. Wilms' tumor is one of the most common intraabdominal tumors of childhood. Primary cardiac tumors that arise from myocardium are extremely rare. Metastasis to the heart or pericardium is usually a late complication in the course of a malignancy. In Wilms' tumor cardiac manifestations may be the presenting symptoms at the time of diagnosis. The prognosis for Wilms' tumor with intracardiac extension of the tumor is poor. A thorough cardiovascular examination and a metastatic workup should be done for abdominal masses presumptive of Wilms' tumor. Two-dimensional echocardiography is a noninvasive diagnostic tool, and the information obtained by its use not only allows planning of surgical intervention, chemotherapy, or local radiation therapy, but also is beneficial for long-term follow-up. Aggressive surgery, chemotherapy, and radiation therapy has increased the survival figures of these children.

Child, Preschool↗

Neuronal responses to amplitude-modulated and pure-tone stimuli in the guinea pig inferior colliculus, and their modification by broadband noise.

Neuronal responses were recorded to pure and to sinusoidally amplitude-modulated (AM) tones at the characteristic frequency (CF) in the central nucleus of the inferior colliculus of anesthetized guinea pigs. Temporal (synchronized) and mean-rate measures were derived from period histograms locked to the stimulus modulation waveform to characterize the modulation response. For stimuli presented in quiet, the modulation gain at low frequencies of modulation (approx less than 50 Hz) was inversely proportional to the neuron's mean firing rate in response to both the modulated stimulus and to a pure tone at an equivalent level. In 43% of units the mean discharge rates in response to the AM stimuli were greatest for those modulation frequencies that generated the largest temporal responses. These discharge-rate maxima occurred at signal intensities corresponding to the steeply sloping part of the neuron's pure-tone rate-intensity function (RIF). The change in mean-rate response to modulated stimuli, as a function of intensity, was qualitatively similar to the pure-tone RIF. Adding broadband noise to the modulated stimulus increased the neuron's temporal response to low modulation frequencies. This increase in modulation gain was correlated with mean firing rate in response to the modulation but did not bear a simple relationship to the noise-induced shift in the RIF measured for a pure tone.

Acoustic Stimulation↗

Combined septal perforation and cardiac rupture after myocardial infarction. Clinical features and surgical considerations of a correctable condition.

The combination of septal perforation and cardiac rupture after myocardial infarction has rarely been reported. This article describes two cases of successful surgical repair of this condition and reviews another three cases previously reported in the literature. The important clinical features were as follows: (1) acute occlusion of a single dominant coronary artery; (2) renewed chest pain before perforation or rupture; (3) electromechanical dissociation at the time of frank rupture; (4) rupture through the left ventricular free wall; (5) in three patients both complications occurred within 3 days of the infarction, and in the other two patients they developed within three weeks. The main surgical considerations are as follows: (1) femoral cannulation to prevent exsanguination before instituting cardiopulmonary bypass; (2) electrically induced fibrillation to avoid systemic embolism; (3) a left ventricular approach to repair the septal perforation followed by infarctectomy; (4) concomitant revascularization was unnecessary. In conclusion, combined septal perforation and cardiac rupture after myocardial infarction is a potentially correctable condition that requires early diagnosis and prompt surgical intervention.

Acute Disease↗

AIDS: who to treat?

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Acquired Immunodeficiency Syndrome↗

Specificity of proliferative response of human CD8 clones to mycobacterial antigens.

Human CD8 T lymphocyte clones (TLC) were generated from the pleural effusion of patients with tuberculosis using a protocol that required, in addition to antigen, coculture of purified CD8+ T cells, accessory cells, interleukin 2 (IL2) and anti-CD3-Sepharose. The TLC obtained were stimulated by mycobacterial soluble extracts in an IL2-dependent and MHC class I-restricted manner. When antigen-responsive TLC were screened with extracts from the recombinant mycobacterial library they were found to respond to either the Y3125 (100-kDa) or the Y3111 (71-kDa) lambda gt11 clones. Polyacrylamide gel immunoblot analysis demonstrated that the CD8 TLC responded to fractions with the molecular mass range 27-45 kDa in the Y3125 lysogen and 60-90 kDa in the mycobacterial soluble extract. The specificity of TLC reactive with the Y3111 clone was confirmed using the 71-kDa antigen purified from the same lysogen. These TLC recognized sequences common to the 71-kDa protein derived from mycobacteria, E. coli or a human cell line. Studies of three TLC using antigen-presenting cells of known genetic haplotype indicated that stimulation with both the Y3125 and the 71-kDa antigens were restricted by determinants encoded by HLA-B8.

Antigens, Bacterial↗

The incidence of immunosuppression-related skin disease in long-term transplant patients.

One hundred and twenty-one patients who had received a renal allograft between 4 months and 21 years previously (mean +/- SD, 71 +/- 62 months) were studied. Seventy-two patients were conventionally immunosuppressed with azathioprine and prednisolone, and 36 had been exposed to the current regime of cyclosporine, azathioprine, and prednisolone. Forty-five patients had viral warts, of whom 20 had more than 10 warts. The presence of viral warts was significantly associated with pale skin type, excess sun exposure, and with duration of allograft. Viral warts were significantly more common in those on conventional immunosuppressive therapy, but this could be solely a reflection of the difference in duration of transplant between the 2 groups. Twelve patients were found to have developed dysplastic or neoplastic skin lesions since transplantation. The incidence of dysplasia increased with increasing age and was significantly associated with pale skin type, excess sun exposure, and duration of allograft. Despite the shorter duration of treatment in those on the new treatment regime, there was no difference between the 2 groups in the proportion of patients with dysplastic skin lesions. Immunosuppression-related skin disease may be a significant problem in allograft recipients in this country, and we suspect that patients taking cyclosporine will have similar problems to those on conventional immunosuppressive drugs alone. Immunosuppressed patients should be advised to avoid sun exposure, to use sunscreens, and should be monitored carefully for the development of dysplastic lesions.

Dermatomycoses↗