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Biomedical subjects

J W Clark

Publications and source records attributed to J W Clark.

At least 163 records · Page 9Linked to original sources

Epidemiology of human lymphotrophic retroviruses: an overview.

The discovery of HTLV-I opened the way for the subsequent recognition of other human retroviruses. HTLV-I is linked to an aggressive T-cell cancer. The availability of a marker for the AIDS agent, HTLV-III, has substantially enhanced our ability to define the nature of the AIDS epidemic, its clinical and subclinical manifestations, and the spectrum of disease outcomes associated with this exposure. Of particular interest is the fact that there is substantial risk for AIDS and AIDS-related outcomes in virally infected individuals as detected by antibody positivity. The preliminary data from these well defined cohorts provide a basis for estimating the enormity of the AIDS epidemic as it is starting to emerge and provide an opportunity for the forward thinking health strategies necessary for dealing with a pandemic of such proportions.

Acquired Immunodeficiency Syndrome↗

Type-I HTLV antibody in urban and rural Ghana, West Africa.

The prevalence of antibodies against the newly described human T-cell lymphoma virus, type I (HTLV-I) in two communities in Ghana, West Africa, is described. There was no difference by community (urban, 3.6% and rural, 4.0%). Prevalence increased with age, being 5.9% among persons greater than 10 years old, but did not differ by sex. There was no difference when data were analysed by housing status or crowding. Non-confirmed reactions in the assay system were frequent and correlated with both prevalence and titer of antibody against malaria. Possible explanations include vector-borne transmission like that of malaria, but the relationship is more probably due to a polyclonal stimulation of B cells, enhancing the potential for detecting reactivity in the assay. Because assay systems vary and because most laboratories do not routinely use a confirmation assay, results presented by different groups must be interpreted cautiously.

Adolescent↗

Karyotypic differences between primary cultures and cell lines from tumors with the human T-cell leukemia virus.

Chromosome abnormalities were studied in primary cultures and in established T-cell lines from patients with human T-cell leukemia virus (HTLV)-positive leukemia or lymphoma. The present findings, and data from other laboratories, indicated that primary cultures of the HTLV-positive neoplastic cells nearly always showed a chromosomally abnormal clone, whereas most established cell lines had an apparently normal karyotype. These differences included circumstances in which the same blood specimen was used for both types of culture or in which separate specimens were obtained within a short time span. These observations indicated that many cell lines from HTLV-positive leukemia or lymphoma may be derived from nonneoplastic T-cells that were transformed in vitro by the leukemia virus; human T-cells newly infected with HTLV were suggested to have an in vitro growth advantage over the HTLV-infected tumor cells.

Cell Line↗

The epidemiology of ovarian cancer.

Although no unequivocally effective ovarian cancer prevention strategies have emerged, epidemiologic studies have identified high-risk populations. The striking international variation (apparently a fivefold difference) can probably be explained on the basis of differential parity, differing classification measures, and differences in the underlying population age distribution. United States age-adjusted mortality has increased slightly in the past 30 years, and the cancer remains predominantly a disease of older adult white women of northern European extraction. The increases in age-specific mortality and age-adjusted mortality over time may be related to a decrease in average family size. Pregnancy, especially pregnancy before age 25 years, and use of oral contraceptives are protective; the risk of ovarian cancer increases with increasing years of ovulation. A positive family history is also associated with a substantial increase in ovarian cancer risk. Survivors of ovarian cancer are more susceptible to cancers of the breast, endometrium, and colon than are similarly-aged normal women, most probably because all four cancers share some common risk factor(s). Various alkylating agents are clearly leukemogenic in survivors of ovarian cancer, an observation that suggests caution in the use of adjuvant chemotherapy in women at relatively low risk of relapse.

Adolescent↗

HTLV: epidemiology and relationship to disease.

With the discovery of the human retrovirus class, an important turning point in the understanding of the process by which cancer is caused and develops in humans has been achieved. As summarized here, clinical and epidemiologic studies have documented the close association of human T-cell leukemia virus (HTLV-I) to a particular form of T-cell malignancy, adult T-cell leukemia/lymphoma (ATL). Yet to be understood is the process involved in translating virus infection into malignant lymphoproliferation. Epidemiologic data suggest that this may involve a relatively long latent period between primary HTLV-I infection and subsequent malignancy risk. Presumably, identifiable co-factors will emerge to explain the trigger for malignant transformation. However, the restricted pattern of tumor phenotype suggest that this process is tightly linked to cells for which HTLV-I has a particularly strong infectious trophism. Interdisciplinary studies are currently under way in a number of laboratories to elucidate the molecular interactions in the HTLV-I associated malignant transformation process in order to correlate these with the epidemiologic data. Thus, lessons are likely to be learned from these molecular and epidemiologic studies which may provide new and important etiologic insights applicable to the prevention and therapy of cancer. Furthermore, with the recent discovery of HTLV-III, a cytopathic form of this class of human retrovirus, the likely cause of acquired immunodeficiency syndrome (AIDS) has been discovered. This has enormous public health implications for the detection, treatment, and prevention of this major medical epidemic. Epidemiologic studies are currently under way to identify what factors associated with virus exposure result in the full-blown AIDS syndrome. In addition, the malignancy potential of this new type of retrovirus is currently the subject of intensive investigation.

Acquired Immunodeficiency Syndrome↗

A mathematical model of the vagally driven primary pacemaker.

Information regarding the electrical behavior of cells in the sinoatrial (SA) node of the heart is by no means complete; yet sufficiently detailed information is available in the literature to allow the formulation of a reasonably quantitative model of the membrane of the primary pacemaker cell (P-cell) and its parasympathetic innervation. In a previous study [Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H207-H218, 1982], the well-known McAllister-Noble-Tsien model of the cardiac Purkinje fiber is modified to account for the electrical activity of the SA node. In the present study, the effects of vagal activity on sinus rhythm are considered by adding a special acetylcholine-sensitive "muscarinic channel" to the membrane model for the P-cell. The resulting model mimics published data quite well and is capable of characterizing the free-running SA node cell as well as its responses to electrotonic and vagal stimulation.

Acetylcholine↗

A mathematical model of primary pacemaking cell in SA node of the heart.

Application of voltage-clamp techniques to cardiac primary pacemaker tissue is currently a subject of considerable interest in cardiac electrophysiology. Information regarding the electrical behavior of this type of membrane is by no means complete, yet sufficiently detailed information is available in the literature that would allow the formulation of a reasonably quantitative model to represent the electrical activity of primary pacemaker tissue. In this study the well-known McAllister-Noble-Tsien (MNT) model of the cardiac Purkinje fiber is modified to account for the electrical activity of the primary pacemaking cell (P-cell) of the sinoatrial (SA) node in the heart. Modification is accomplished by appropriately deleting (or inactivating) selected inward- or outward-current channels in the MNT model and adjusting the range of voltage dependence of the various channel-gating variables. Wherever possible, this is accomplished by taking into account voltage-clamp and other electrophysiological data from experiments on the SA node. The resultant model mimics published data quite well and is capable of characterizing the free-running behavior of the primary pacemaker as well as its response to injected currents.

Action Potentials↗

Antitussive effect of guaifenesin in young adults with natural colds. Objective and subjective assessment.

The efficacy of guaifenesin in reducing cough frequency in young adults with acute respiratory disease was evaluated by both an objective cough counting system and a questionnaire. A guaifenesin cough preparation and the syrup vehicle were administered in a double-blind manner. Coughs were recorded on tape over a 24-hour baseline evaluation period and a 36-hour treatment period for 42 patients. A pronounced diurnal variation in cough frequency was observed. The evaluation of efficacy was based upon comparisons between equivalent six-hour time periods of successive days. No antitussive effect of guaifenesin was demonstrated. The questionnaire was administered to 65 patients, including the 42 whose coughs were recorded. Of 26 patients with productive cough receiving guaifenesin, 25 (96 percent) reported a decrease in sputum thickness compared to 13 (54 percent) of 24 patients receiving the vehicle (p = 0.01, Fisher exact test). Twenty-three of 26 (88 percent) patients receiving guaifenesin also reported reduction in sputum quantity compared to 15 of 24 (62.5 percent) receiving the vehicle (p = 0.07, Fisher exact test). The diurnal variation in cough frequency measured by the tape recording was not apparent from the subjective cough frequency estimates obtained by the questionnaire.

Adolescent↗

Interpretation of multigated Fourier functional images.

First-harmonic Fourier analysis is currently used to aid in the interpretation of multigated cardiac studies. Its intrinsic inaccuracies are not generally appreciated. This study investigates the characteristics and magnitudes of the errors of this technique. The study analyzes computer-generated phantoms that isolate the various motions of the ventricles (contraction, translation, and rotation) with the first-harmonic approach. The first-harmonic output is compared with a more accurate fitting scheme using multiple terms of the Fourier expansion. Significant artifacts of the inaccuracy of the first harmonic appear in the phantom studies and are observed in patient examples. We conclude that caution is needed in interpreting first-harmonic phase and amplitude images, and particularly in associating them with parameters like the onset of contraction and the stroke volume.

Computers↗