Search PubMed⌕ Search

Biomedical subjects

S Kelley

Publications and source records attributed to S Kelley.

51 records · Page 3Linked to original sources

Transdermal clonidine therapy in elderly mild hypertensives: effects on blood pressure, plasma norepinephrine and fasting plasma glucose.

Twenty patients aged 60-74 years entered a study on the effect of transdermal clonidine (Catapres-TTS) as monotherapy for mild hypertension [diastolic blood pressure (DBP) 90-104 mmHg]. Seventeen patients (85%) had a positive therapeutic response (DBP reduced to less than 90 mmHg or by greater than or equal to 5 mmHg). Patient acceptance was high and side effects mild; however, one-quarter of the patients experienced localized skin reactions. A slight increase in fasting plasma glucose level (mean delta = 20 mg/dl) was consistently observed. Transdermal clonidine led to a sustained decline in plasma catecholamine levels although this effect did not seem to be closely related to the observed decreases in blood pressure. Three out of four evaluable patients had a blood pressure 'overshoot' upon discontinuation of therapy to levels above pretreatment values. Transdermal clonidine appears to be effective and generally well tolerated in the treatment of mild hypertension in the elderly; however, more studies designed to investigate effects on glucose tolerance and the possible existence of a rebound syndrome are needed.

Administration, Topical↗

Stimulation of natural killer cell activity and inhibition of proliferation of various leukemic cells by purified human leukocyte interferon subtypes.

One of several human leukocyte interferon subtypes A (LeIF-A), obtained in purified form from a gene cloned in Escherichia coli, stimulated human peripheral blood natural killer cell activity, whereas another human leukocyte interferon subtype D (LeIF-D) had no effect with the use of K562 as target cells. With Daudi as target cells, both LeIF-A and LeIF-D stimulated natural killer cell activity. A hybrid human leukocyte interferon, NH2-terminal 61 amino acids and COOH-terminal 104 residues of LeIF-A and LeIF-D, respectively (LeIF-AD) showed greater stimulation than did LeIF-A, but the stimulation did not exceed that of natural buffy coat interferon. A mixture of equal antiviral units of LeIF-A and LeIF-D was no more effective than was LeIF-A alone. The cloned interferon subtypes showed differential effects on the proliferation of three human leukemic cell lines: Daudi (B-cell lymphoblastoid leukemia); BALL 1 (B-cell acute lymphoblastic leukemia); CCRF-HSB-2 (T-cell acute lymphoblastoid leukemia). Growth of Daudi cells was generally most sensitive to all the interferons tested, LeIF-A, -D, -AD, and a buffy coat preparation; no viable cells remained after 120-hr exposure to 1000-unit/ml doses of the interferons. BALL 1 was relatively resistant to the interferon subtypes tested including LeIF-AD, but this cell lines was very sensitive to a preparation of natural buffy coat interferon. CCRF-HSB-2 showed some sensitivity to all the interferons with greatest sensitivity to LeIF-A (10% of the viable cells were detected after 1000 units/ml exposure for 120 hr). In contrast to the leukemic cell lines tested, human amnion cells (WISH) and the human erythroid leukemia, K562, were resistant to the antiproliferative activity of the interferons.

Cell Division↗

Hybrid clones of rat liver and hamster ovary cells as targets for carcinogen screening.

Many short-term carcinogen-screening assays use transformed cells which require exogenous metabolizing systems to activate carcinogens. We have sought untransformed target cell-lines with a high mitotic index and the intrinsic ability to metabolize carcinogens. Hybrid cell clones were established by fusing an untransformed rat liver cell-line (with a normal diploid karyotype, epithelial morphology and carcinogen-metabolizing capacity) and a Chinese hamster ovary cell-line (with a high mitotic index, ability to grow in soft agar, a characteristic of transformed cells, and which cannot metabolize most carcinogens). A number of such clones were characterized with respect to their morphology, karyology, growth properties and the ability to metabolize 7,12-dimethylbenz[a]anthracene. Selected hybrid clones were found to respond to several types of carcinogen, using the induction of sister chromatid exchange as the criterion. A significant increase in the induction was observed in cloned hybrid cell-lines compared with the hamster ovary cell line. Moreover, the same hybrid clones can be used repeatedly without an exogeneous activating system, which makes this test system very practical.

Animals↗

Induction of sister chromatid exchanges by carcinogens mediated through cultured rat liver epithelial cells.

A cloned, untransformed rat liver cell-line, LNRL (with the normal diploid karyotype and epithelial morphology) was tested for use as the metabolizing component in a co-cultivation system for carcinogen-screening using sister chromatid exchanges (SCE) as the criterion. The well characterized early cultures of LNRL cells were co-cultivated with Chinese hamster ovary (CHO) cells, the target commonly used for the induction of SCE, and exposed to different concentrations of various chemicals for 24 h. Two polycyclic hydrocarbons, 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene did not produce any SCE in CHO cells cultured alone, but produced a significant number of SCE in CHO co-cultivated with LNRL. The aromatic amine, 2-acetylaminofluorene, and the potent carcinogenic mycotoxin, aflatoxin B1, induced SCE to a limited extent even in CHO cells cultivated alone, but in the presence of liver cells the SCE frequency was greatly increased. Aflatoxin G2, the least potent of the aflatoxins, also produced a response in the co-cultivation system. These results indicate that cultured liver cells can be used as the metabolizing cells in co-cultivation systems for carcinogen-screening. The advantages of this assay over those employing liver microsomal fractions are discussed.

2-Acetylaminofluorene↗

Transformation of BALB/c-3T3 cells by tsA mutants of simian virus 40: effect of transformation technique on the transformed phenotype.

Simian virus 40 tsA-transformed BALB/c-3T3 cells isolated as foci of overgrowth in liquid medium were compared with those isolated as colonies in soft agar. Efficiencies of transformation were equivalent in the two procedures. Cells isolated as foci were able to grow in agar and vice versa. No difference in temperature sensitivity of the transformed phenotype was detected when tsA transformants selected in agar were compared with those selected as foci. The use of the two different transformation procedures, then, did not form the basis for generation of different transformed phenotypes, and transformants generated in both ways were dependent upon expression of the A gene for maintenance of the transformed state.

Agar↗

The complement fixation test and African trypanosomiasis. II. The complement fixation test as an aid for assessing therapy.

Complement-fixing antibody titres decline after successful treatment of trypanosoma infected cattle during a fixed period. For investigating the practicability of the resulting double test procedure in the field, cattle under controlled drug regimes were tested at treatment and again 3 weeks later. Alternatively, the results from groups of treated and untreated animals from the same area were compared. Both serological and parasitological test results indicated an insuffieicnt effectiveness of therapy in the area under investibation.

Animals↗

Experiments on the Babesia bigemina carrier state in East African buffalo and eland.

Three captive East African buffalo (Syncerus caffer) were injected with 5 x 109 bovine erythrocytes with Babesia bigemina pathogenic for cattle. None of the buffalo showed signs of disease, but Babesia were found in blood smears for four days indicating their multiplication. The carrier state of Babesia bigemina was established in two buffalo for 28 and 147 days respectively by sub-inoculation into splenectomized calves, while no parasites were demonstrated 28 days after injection in the third buffalo. Two buffalo shot in Kenya did not appear to be carriers of Babesia gibemina, as shown by sub-inoculation of blood in splenectomized calves. Two captive eland (Taurotragus oryx) were inoculated and their blood investigated as with the experimental buffalo. Neither eland appeared to harbour Babesia bigemina 28 days after injection, even though one was splenectomized. The experimental data indicate that the East African buffalo can be a carrier of Babesia bigemina for at least 5 months, while this parasite did not survive in eland. Buffalo may play a role in the epidemiology of babesiosis in cattle, while eland most likely do not.

Animals↗

Overview of phase I trials of 2',3'-dideoxyinosine (ddI) conducted on adult patients.

Ninety-two adult patients with AIDS or severe AIDS-related complex were treated with 2',3'-dideoxyinosine (didanosine; ddI) at dosages ranging from 0.8 to 66.0 mg/(kg.d) for at least 6 weeks in phase I trials. Potentially beneficial changes in weight (40% of patients), clinical signs or symptoms (40% of patients), CD4+ cell counts (25% of patients), and serum levels of HIV p24 antigen (50% of antigen-positive patients) were reported. Response rates tended to be higher among patients with AIDS-related complex and among those who had not received prior zidovudine therapy. A major response (improvement in at least one clinical parameter and in at least one laboratory marker) occurred in 29% of patients, and rates of major response tended to be higher in patients receiving higher dosages. The primary dose-limiting toxicity observed was peripheral neuropathy, which was observed with increasing frequency in patients receiving greater than 20 mg/(kg.d). Of the other adverse effects, pancreatitis was possibly dose-dependent and hyperuricemia (without clinical gout) occurred only at high doses. Dosages of 250 mg and 375 mg of ddI twice daily will be used in extended phase II/III studies.

AIDS-Related Complex↗

Synostosis of the ring-small finger metacarpal in Apert acrosyndactyly hands: incidence and treatment.

SUMMARY: This study reports on the incidence of a synostosis between the ring-small metacarpal bases in patients with Apert syndrome and describes a technique to resect the synostosis and insert silicone sheets to improve hand function. Records of 9 patients (18 hands) were evaluated. Average age at follow-up was 9.5 years. Three relationships between the ring-small metacarpals were observed. Type I hands (22%) had no abnormal interconnections; type II hands (33%) possessed a synostosis since birth; type III hands (44%) did not possess a synostosis at birth, but one later developed at average age of 79 months. Total incidence of synostosis was 77%. Five patients underwent excision of the synostosis. At an average of 16 postoperative months, 4 of these patients experienced improvement in hand prehension. In patients with Apert syndrome, resection of abnormal interconnections between the ring-small metacarpals is highly recommended to improve hand prehension based on the high incidence of a synostosis in this region.

Acrocephalosyndactylia↗