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Biomedical subjects

M Sullivan

Publications and source records attributed to M Sullivan.

At least 343 records · Page 19Linked to original sources

Alpha 1 type IV collagen gene evolved differently from fibrillar collagen genes.

Type IV collagen is a major structural component in basement membranes. It is considerably different from the fibrillar collagens, types I-III. For example, unlike fibrillar collagens, the triple helical domain of type IV collagen is frequently interrupted by nonhelical regions. In this report, we demonstrate several overlapping genomic clones which cover most of the mouse alpha 1(IV) chain. Electron microscopic analysis of R-loops revealed that there were at least 28 exons within 35 kilobases of the gene segment. The sizes of six exons were determined by DNA sequence analysis to be 81, 178, 134, 73, 129, and 213 base pairs. These sizes do not appear to be related to the 54-base pair coding unit which is characteristic of fibrillar collagen exons, suggesting that the alpha 1 type IV collagen gene evolved differently from the fibrillar collagen genes.

Actin Cytoskeleton↗

In what sense is contemporary medicine dualistic?

Medicine's inability to humanely respond to the concerns of its patients has often been attributed to its Cartesian dualism of mind and body. More recently, this inability has been ascribed to medicine's penchant for isolating biological disease as its sole proper concern to the exclusion of experienced illness. This dualism of disease and illness is claimed to be an outgrowth of the Cartesian dualism but the differences and similarities between these two forms of dualism is not clear. This paper seeks to clarify their relationship through an examination of their historical origins. Disease is currently identified and characterized by a process of clinico-pathological correlation. By this means clinical impressions are corrected in light of autopsy findings. Our current mode of clinico-pathological correlation originated in Paris in the early nineteenth century with the work of Xavier Bichat and others. The theory of knowledge implicit within this clinico-pathological approach to the body is described and compared to that of Descartes. Though medicine does pursue certain Cartesian goals for knowledge, such as knowledge of the patient that does not rely upon his candor, it ultimately espouses neither a Cartesian theory of knowledge nor a Cartesian theory of the body. With pathological inquiry modeled after the autopsy as the final word in the identification and characterization of disease, the patient's capacity for self-knowledge and interpretation--not an entity called mind--is isolated away from his body. This approach to the body means that objective evidence of disease is valued to the exclusion of subjective evidence. If the shortcomings of modern biomedicine are to be effectively addressed, not only must the interdependence of disease and illness be acknowledged. The very canons of medical evidence must be revised. Subjective evidence must be rehabilitated and rejuvenated with better methods of subjective clinical investigation. Host factors relevant to the healing and knowing of sickness must be elucidated so that medicine may rediscover the sentience of its patients.

Communication↗

Computer analysis of exercise-induced changes in QRS duration in patients with angina pectoris and in normal subjects.

Exercise-induced changes in QRS duration were assessed in 25 normal subjects and in 17 patients with stable ischemic heart disease. None had bundle branch block or were taking medications, and all patients had angina pectoris induced during the test. QRS duration and ST60 amplitude were measured by computer during rest while standing, at a heart rate of 100 to 110 bpm during exercise, at peak heart rate for the angina patients (mean of 127 bpm), and at the corresponding matched heart rate and peak heart rate for the normals (mean of 174 bpm). As heart rate increased, the patients showed significant ST60 depression. In normal subjects, the QRS duration tended to increase initially but at the matched heart rate level and at peak heart rate it decreased significantly compared to rest (p less than 0.01). The QRS duration in the angina patients increased significantly at the heart rate level of 100 to 110 bpm (p less than 0.05). Of the eight patients who reached a peak heart rate above 127 bpm, six (75%) during that period further increased QRS duration compared to three (12%) of the 25 normal subjects (p less than 0.001). We conclude that a consistent increase in QRS duration during exercise, although subtle, may be a marker of ischemia and consequently a potential diagnostic tool.

Adult↗

Applications of experimental psychopathology in psychiatric rehabilitation.

Persons with schizophrenia show deficits in basic psychological functions such as attention, perception, and cognition. Remediation of these deficits by direct training may facilitate the effectiveness of neuroleptic medications, social skills training, and family therapy. In the vulnerability-stress model of schizophrenia, persons with schizophrenia may have lower thresholds for disorganization that contribute to vulnerability. Stress increases arousal, which brings many competing responses to the same strength, leading to intrusion of inappropriate responses. Interventions that reduce arousal and lower the strengths of competing responses should reduce psychological deficits. Arousal-reducing, attentional, and cognitive interventions are appropriate for the prodromal, acute, and chronic stages of schizophrenic disorders. Laboratory-based assessment and ongoing measurement of basic psychological deficits in schizophrenia are keys to the development and validation of multimodal psychiatric rehabilitation.

Adult↗

Physical, psychologic, and social function in chronic pain patients after epidural spinal electrical stimulation.

The overall function, pain, and mood disturbance of 54 patients with benign chronic pain were studied as to their response to epidural spinal electrical stimulation (ESES) more than 12 months after the implantation of ESES electrodes. Both responder (n = 23) and nonresponder (n = 31) pain patients demonstrated extensively worse physical and psychosocial function on the Sickness Impact Profile (SIP) and worse self-rated mood disturbance on the Mood Adjective Check List (MACL) than a control population sample. Responders to ESES were insignificantly less impaired in physical functions of daily life than nonresponders, but clearly less inhibited in the social pattern of contact. Self-rated pain sensation differed 36% between responders and nonresponders, and the pain measures of all pain patients correlated with total mood disturbance on the MACL and with its dimensions for depression and fatigue. Social characteristics, sex, diagnoses, comorbidity, and duration of pain did not discriminate. In a supplementary prospective short-term study, pain ratings had improved by 30% 3 weeks after implantations. The night sleep and general psychic balance (SIP category emotional behavior) were then also significantly improved. A shortened SIP version of 8 items optimizing responder-nonresponder differences and 12 items of mood disturbance are suggested to supplement pain ratings for overall assessment of chronic pain patients. A wider usage of ESES is recommended for pain patients who can comply to the regimen, because the surgical technique is now simple and safe.

Activities of Daily Living↗

The acute effects of exercise on prolactin and growth hormone secretion: comparison between sedentary women and women runners with normal and abnormal menstrual cycles.

Acute exercise may stimulate PRL secretion, which, in turn, may contribute to exercise-associated menstrual dysfunction. We compared the response of PRL secretion in sedentary women and women runners with normal and abnormal menstrual cycles. We also studied the GH response to acute exercise, as GH may bind to lactogenic receptors. Five nonrunning women, 5 eumenorrheic running women, four oligomenorrheic running women, and six amenorrheic running women were studied on 2 consecutive days. On day 1, the women cycled on a bicycle ergometer against an increasing workload until total exhaustion. Serum PRL and GH increased several-fold in response to acute exercise in all three groups of running women. On day 2, the women simulated a daily training run by enduring a designed submaximal exercise regimen. In response to submaximal exercise, no group had a significant elevation of PRL or GH. Therefore, a threshold of exercise intensity exists that must be achieved before a significant increase in PRL or GH secretion occurs in women runners; serum PRL and GH in the nonrunning group did not increase significantly even in response to acute maximal exercise. The transient elevations in PRL and GH in women runners probably do not contribute to their menstrual dysfunction unless individual hypersensitivity of the hypothalamic-pituitary-ovarian axis to such intermittent elevations is present.

Adult↗

Sonographic characterization of carotid plaque: detection of hemorrhage.

By careful evaluation of the sonographic characteristics of carotid plaques, two patterns can be identified: a homogeneous pattern containing uniform echoes corresponding to dense fibrous tissue and a heterogeneous pattern containing mixed echoes and anechoic areas that represent intraplaque hemorrhage pathologically. A prospective study was conducted of 50 patients to determine the accuracy of identifying these different forms of plaque. The patients' carotid arteries were examined by a high-resolution duplex scanner before carotid endarterectomy. The plaques were evaluated carefully by vascular surgeons and pathologists for the presence of intraplaque hemorrhage. In this study, the accuracy of identifying the presence or absence of intraplaque hemorrhage with sonography was 90% (48 of 54); sensitivity, 94% (17 of 18); and specificity, 88% (27 of 31). High-resolution sonography appears to be an accurate means of identifying intraplaque hemorrhage and may ultimately be useful in identifying patients at risk for embolic disease.

Aged↗

Measuring health in rheumatic disorders by means of a Swedish version of the sickness impact profile. Results from a population study.

A technique for assessing the overall consequences of disease is introduced, comprising a Swedish version of a behaviour-based measure, the Sickness Impact Profile (SIP). Measurement characteristics of the profile are defined in an epidemiological study of 147 women with rheumatic disorders. The drop-out rate was 7.5%. Cross-cultural evidence of the validity of the SIP was obtained in this study. Test-retest reliability was substantial. A high level of validity of the Swedish version was demonstrated, as assessed by hypothesized significant relationships with selected functional, psychological, and social correlates. The profile was able to describe the various sickness impacts in a specific and sensitive manner. In the epidemiological setting, the subscales representing Ambulation, Body care and movement, Emotional behaviour, Social interaction, Sleep and rest, Home management and Recreation and pastimes, all showed discriminatory capacity. The categories Mobility, Alertness behaviour, Communication, Work, and Eating discriminated less well. The response pattern was recognizably related to rheumatic complaints, emphasizing a broader applicability of this scale in rheumatology.

Activities of Daily Living↗

Desensitization of the mammalian beta-adrenergic receptor: analysis of receptor redistribution on nonlinear sucrose gradients.

The distribution of beta-adrenergic receptors in lysates from several mammalian cell lines was analyzed on nonlinear sucrose density gradients before and after desensitization by isoproterenol. On the nonlinear gradients, the receptors in lysates from untreated HeLa, A431, S49 cyc- and C6 cells were well resolved into light and heavy density membrane fractions. In contrast, with the former three cell lines, there was very poor or no separation of the two peaks of receptors on linear sucrose gradients. With C6 cells, resolution was better on the nonlinear than on the linear gradient. In all cases, successful separation of the two density fractions of the receptor was achieved only when cells had been treated with concanavalin A prior to lysis. Adenylate cyclase activity cosedimented with the heavy membrane fraction of the receptor, and no activity was detected with the light fraction. After desensitization of adenylate cyclase by isoproterenol, there was a redistribution of the receptors to the light density fraction. This shift of receptors, but not desensitization, was prevented when cells were pretreated at 37 degrees C with concanavalin A prior to exposure to isoproterenol. Thus, sequestration of beta-adrenergic receptors away from the plasma membrane and adenylate cyclase to a lighter density membrane fraction appears to accompany, but may not be a prerequisite for desensitization in mammalian cells. This receptor redistribution, however, can be readily detected on nonlinear sucrose gradients.

Adenylyl Cyclases↗

Structure of the human interleukin-2 receptor gene.

The gene encoding the human interleukin-2 (IL-2) receptor consists of 8 exons spanning more than 25 kilobases on chromosome 10. Exons 2 and 4 were derived from a gene duplication event and unexpectedly also are homologous to the recognition domain of human complement factor B. Alternative messenger RNA (mRNA) splicing may delete exon 4 sequences, resulting in a mRNA that does not encode a functional IL-2 receptor. Leukemic T cells infected with HTLV-I and normal activated T cells express IL-2 receptors with identical deduced protein sequences. Receptor gene transcription is initiated at two principal sites in normal activated T cells. Adult T cell leukemia cells infected with HTLV-I show activity at both of these sites, but also at a third transcription initiation site.

Amino Acid Sequence↗

Can patients with coronary artery disease receiving beta blockers obtain a training effect?

Fifty-nine male volunteers with stable coronary artery disease underwent 1 year of supervised exercise and were compared with 69 similar control patients. Both groups underwent exercise tests initially and at 1 year to determine maximal oxygen uptake. Initial and 1-year tests were performed with patients off all cardiac medications including beta blockers. Although patients had been randomized to exercise intervention, administration of beta blockers was at the prerogative of their physicians. Thirty-seven percent of the trained group and 39% of the control group were taking beta blockers during the year of study. Regardless of whether or not beta blockers were administered, patients in the exercise intervention group had a significant increase in aerobic capacity and improvement in the other hemodynamic markers of training compared with control subjects. Of the trained patients, those on beta blockers were able to comply with the exercise regimen as well as those not taking beta blockers.

Adrenergic beta-Antagonists↗

Structure of the promoter of the rat type II procollagen gene.

We have isolated several overlapping genomic clones which contain the 5' terminal portion of the rat pro-alpha 1 (II) chain gene. These clones span about 20 kilobases (kb) of contiguous DNA containing 15 kb of the gene and 5 kb of the 5' flanking sequence. Electron microscopic analysis of mRNA-DNA hybrids by R-looping shows that collectively these clones contain 16 exons which code for approximately one-third of the pro-alpha 1 (II) chain. The sizes of the exons are small, except for the first exon which is relatively large. The nucleotide sequence of the first exon and the 1000 base pairs (bp) preceding it was determined. The first exon contains a 150-bp untranslated segment and an 85-bp sequence coding for the signal peptide and a part of the NH2-terminal propeptide of type II collagen. The segment preceding the transcription initiation site contains the "TATA" box and several G + C-rich stretches, whereas the "CAT" box is not evident between -70 and -120. The hexanucleotide sequence 5'-GGGCGG-3' is found in three different places between -200 and the TATA box. The inverted complement sequence of this hexanucleotide, 5'-CCGCCC-3', is located around both -220 and -450. The hexanucleotide and its inverted sequence have been found previously in the promoter region of the tk gene of herpes virus. These sequences are known to function in a mutually dependent manner as transcription signals for the tk gene; thus, they may play a role in determining the level of transcription of this cartilage gene. The hexanucleotide, 5'-CCGCCC-3', is also found in the 21-base pair repeats of the SV40 promoter and the promoter region of hydroxymethylglutaryl-CoA reductase gene. The sequence 5'-GTGGTTAGA-3' located around -280 is identical to the "core" sequence that has been reported as enhancer element in both viral and cellular genes. These unusual structures may be related to the tissue-specific expression of this gene.

Animals↗