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Biomedical subjects

C W Smith

Publications and source records attributed to C W Smith.

At least 307 records · Page 17Linked to original sources

Isolation and characterization of native human renin derived from Chinese hamster ovary cells.

Transfection of Chinese hamster ovary (CHO) cells with a plasmid containing the cDNA for human preprorenin has provided cell lines that secrete 15 mg of native prorenin per liter of culture medium. Tryptic activation of the prorenin occurs by selective cleavage of the Arg66-Leu67 bond (numbering as in preprorenin). The renin product, purified in a single step and in high yield by affinity chromatography, is fully stable for as long as 8 months when stored in solution at 4 degrees C and pH 6.5. Purity of the renin was judged to be greater than 95% by gel electrophoresis, compositional and N-terminal sequence analyses, and specific enzyme activity. An important aspect of the present work is the development of a direct assay for renin which permits accurate and reproducible evaluation of enzyme units and kinetic parameters. Application of methods described herein, combined with appropriate scale-up fermentation capabilities, provides the means for generating gram quantities of human renin and its zymogen.

Animals↗

Specific absorption rate and tissue temperature in local hyperthermia.

Specific absorption rate (SAR) and tissue temperature were measured for a total of 83 treatments in 33 patients who received local hyperthermia treatment for cancer. The patients were grouped into three categories according to tumor size. Hyperthermia was induced by 13.56 MHz electromagnetic energy applied using capacitive coupling. A method is described for evaluating SAR from the tissue temperature traces at any time in the treatment when a step change is made in applied power. The method is possible only if the temperature traces are free from interference and the total power delivered to the patient is monitored. Mean values of SAR ranged from 4.6 to 89 W kg-1 depending on the treatment site. Satisfactory heating was achieved for superficial tumors, with temperatures greater than 42 degrees C being recorded in 69% of treatments. For axillary nodes only 4% of treatments exceeded 42 degrees C. For cervix tumors an idealized tumor model was used to estimate tumor temperature from the temperature and SAR measured in the adjacent normal tissue. From the model it appears necessary either to raise the systemic temperature to 40 degrees C or to increase the SAR by at least a factor of 4 to obtain a temperature of 42 degrees C in a typical tumor. Measurements of SAR and temperature are essential for feedback control of computer models which, in principle, could provide a complete distribution of temperature during a hyperthermia treatment. Furthermore, measured SAR provides a direct comparison of the power deposition from different treatment machines in a clinical environment. The data presented form a basis for comparison with the clinical use of other heating systems.

Absorption↗

The suicidal patient. The primary care physician's role in evaluation and treatment.

Evaluation of the suicidal patient involves careful consideration of risk factors, including attention to subtle clues from the history, and mental status examination. The most urgent decision for the physician to make is whether or not to insist on hospitalization. If the need for inpatient care is uncertain, a "no suicide" contract can be a helpful adjunct to management. Although suicidally depressed or psychotic patients require psychiatric consultation, many "suicidal" patients are simply experiencing a crisis and respond well to supportive crisis intervention counseling.

Adolescent↗

The postdate pregnancy. When to wait, when to induce labor.

The postdate pregnancy is a common and difficult problem for the physician, who must decide between risking premature delivery by inducing labor and waiting so long that post-maturity complications may be present. A normal contraction stress test with a postdate pregnancy is reassuring, and artificial labor promoted by an inducible cervix or an abnormal contraction stress test should attain the best result for both mother and baby.

Female↗

Medical students' attitudes to old people and career preference: a comparison of two universities.

Medical students' attitudes to old people were compared at broadly similar points in their education at two medical schools, one with a department of health care of the elderly (Nottingham), the other without such a university department (Leeds). The students were tested at both schools before their clinical training in care of the elderly, using a modified Rosencranz-McNevin semantic differential scale to measure general attitudes to old age, and a Likert scale to measure attitudes to medical care. Questions were also asked about career preferences. Both groups of students showed similar general attitudes to ageing. The Nottingham students showed more positive attitudes to care of old people, and this was reflected in career preferences.

Aged↗

Nurse-reported infections in a long term care facility.

350 nurse-reported infectious episodes over a two year period were studied in a nursing home population. Urinary tract infections were the most commonly reported, followed by respiratory and skin infections. Of these cases cultured, the most common urinary organisms were Proteus and E. Coli; the most common respiratory pathogen was Proteus; and the usual skin offender was Staph Aureus. Cultures were obtained more commonly for urinary than for skin and respiratory infections. Recurrent infections accounted for 38% of urinary, 39% of skin, and 24% of respiratory infections. These results provide further documentation about the problem of infections in the nursing home, and they may be helpful in designing preventive measures in this setting.

Humans↗

Adherence of neutrophils from dogs with diabetes mellitus.

Adherence of neutrophils from dogs with type I (insulin-dependent) diabetes mellitus controlled by insulin administration was compared with that from control dogs. Neutrophil adherence in whole blood decreased with increased serum glucose concentration, but was not different from normal cell adherence when isolated cells were examined. The decreased adherence in whole blood was considered to be the result of media factors and not dependent on altered neutrophil function.

Animals↗

Bundling of actin filaments by aorta caldesmon is not related to its regulatory function.

Ca2+-sensitive thin filaments from vascular smooth muscle were disassembled into their constituent proteins, actin, tropomyosin and caldesmon. Caldesmon bound to both actin and to actin-tropomyosin and inhibited actin-tropomyosin activation of skeletal muscle myosin MgATPase. It also promoted the aggregation of actin or actin-tropomyosin into parallel aligned bundles. Quantitative electron microscopy measurements showed that with 1.1 microM actin-tropomyosin, 1.6 +/- 0.5% (n = 3) of the filaments were in bundles. At 0.073 microM, caldesmon inhibited MgATPase activity by 50%, whereas bundling was 3.0 +/- 1.3% (n = 4). At 0.37 microM caldesmon, MgATPase inhibition was 83% while 28.1 +/- 6.9% (n = 4) of filaments were in bundles. Experiments at 4.4 microM in which MgATPase and bundling were measured in the same samples gave similar results. Small bundles of 2-3 filaments showed the most frequent occurrence at 1.1 microM actin. At 4.4 microM actin the most common bundle size was 3-5 filaments, with the occasional occurrence of large bundles consisting of up to 120 filaments. The incidence of bundling was the same in the presence and absence of tropomyosin. Thus caldesmon can induce the formation of actin bundles but this property bears no relationship to its inhibition of MgATPase activity.

Actins↗

Disassembly and reconstitution of the Ca2+-sensitive thin filaments of vascular smooth muscle.

The Ca2+-sensitive thin filaments of aorta smooth muscle have been, disassembled into their constituent proteins, actin, tropomyosin and a 120-kDa protein. The 120-kDa protein bound to aorta actin-tropomyosin and inhibited its ability to activate myosin MgATPase. This inhibition correlated with the binding of one 120-kDa protein molecule per 29 actin monomers. Upon the addition of calmodulin to the actin-tropomyosin-120-kDa protein complex, the inhibition was relieved in 10(-4) M Ca2+ but not 10(-9) M Ca2+. The full release of inhibition was not accompanied by a full release of 120-kDa protein binding to actin-tropomyosin. A fully active, Ca2+-sensitive aorta thin filament has thus been reconstituted from just four components: actin, tropomyosin, 120-kDa protein and calmodulin.

Actins↗

The thin filaments of smooth muscles.

Contraction in vertebrate smooth and striated muscles results from the interaction of the actin filaments with crossbridges arising from the myosin filaments. The functions of the actin based thin filaments are (1) interaction with myosin to produce force; (2) regulation of force generation in response to Ca2+ concentration; and (3) transmission of the force to the ends of the cell. The major protein components of smooth muscle thin filaments are actin, tropomyosin and caldesmon, present in molar ratios of 28:4:1 respectively. Other smooth muscle proteins which may be associated with the thin filaments in the cell are filamin, vinculin, alpha-actinin, myosin light chain kinase and calmodulin. We have reviewed the structural and functional properties of these proteins and where possible we have suggested what their function and mechanism of action may be. We propose that actin and tropomyosin are involved in the force producing interaction with myosin, and that this interaction is controlled by a Ca2+-dependent mechanism involving caldesmon, tropomyosin and calmodulin. Vinculin, alpha-actinin and filamin appear to be involved in the attachment of the thin filaments to the cell membrane and their spatial organization within the cell. We conclude that the filaments of smooth muscles share many common properties with those from skeletal muscle, but that they are also quite distinct in terms of both their caldesmon based regulatory mechanism and their mode of organization into a contractile apparatus.

Actinin↗

Hyperventilation syndrome. Bridging the behavioral-organic gap.

Hyperventilation syndrome is frustrating to patient and physician alike. This common condition can be managed successfully if the primary care physician understands the pathophysiology of symptoms and takes a persistent, supportive approach to the patient. Invasive testing and psychiatric referral are less effective and more costly than an ongoing relationship with a primary care physician. Positive results are most likely to derive from frequent office visits marked by reassurance and repetition of instructions on how to cope with anxiety and its attendant symptoms.

Adolescent↗

Smith-McGuckin spot.

Direct inspection of the tympanic membrane, especially with the help of the microscope, continues to be an important part of the examination of the patient suffering from ear disease. Accurate assessment of the varied appearances can be helpful in anticipating the prognosis in SMOM and may give information about the pathology of CSOM and cholesteatoma. The Smith-McGuckin spot was first described 20 years ago (Smith 1964, R Thomas 1965, personal communication) and its significance is reviewed. Further evidence of the relationship between skeletal disorders such as Turner's syndrome and persistent SMOM is described. It is suggested that bone resorption in the deep meatus, outer attic wall and ossicles may result from chronic hyperaemia rather than sepsis or avascular necrosis. The part played by cholesteatoma in bone erosion is questioned.

Bone Diseases↗

Cardiovascular effects of a renin inhibitor in relation to posture in nonhuman primates.

Orthostatic cardiovascular reflexes were evaluated in conscious cynomolgus monkeys during interruption of the renin-angiotensin system with the renin inhibitor: RIP (Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr-Lys-OH). RIP was synthesized via solid phase techniques and purified to homogeneity. In vitro studies indicated that it exhibited classical competitive inhibition of renin with a KI of 2.3 microM. In vivo, RIP at 2 mg/kg per min inhibited renin and angiotensin I pressor responses indicating that it was not a specific renin inhibitor at this dose. However, in spite of the nonspecificity, RIP did not affect the supine blood pressure of sodium-replete monkeys, but did evoke hypotension in supine sodium depleted monkeys. RIP did not elicit significant orthostatic hypotension in either sodium-replete or sodium depleted monkeys. The cardiovascular effects of RIP described in this study appear to be due to inhibition of the renin-angiotensin system.

Angiotensin I↗