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Biomedical subjects

C Long

Publications and source records attributed to C Long.

At least 91 records · Page 5Linked to original sources

Immunomodulatory and therapeutic properties of alkyl lysophospholipids in mice.

This paper describes the immunomodulatory and therapeutic properties of the alkyl lysophospholipids [ALP; 1-O-octadecyl-2-O-rac-glycero-3-phosphocholine (ET-18-OCH3)]. ALP was able to activate macrophages both in vitro and in vivo as well as to act as an immunoadjuvant for syngeneic tumor vaccines. However, ALP appeared to be transferred, at least in part, to the macrophage membrane, and some of the tumoricidal macrophage-activating properties seem to be associated with the direct cytotoxic effect of membrane-released ALP. ALP also had some therapeutic activity for experimental and spontaneous metastases, requiring administration three but not two times weekly at near-toxic doses; this suggests that at least some of its therapeutic activity is due to direct cytotoxicity.

Animals↗

Lisinopril treatment of hypertension in patients with impaired renal function.

Lisinopril is a new, long-acting, nonsulfhydryl angiotension-converting enzyme (ACE) inhibitor that is excreted unchanged by the kidney. The antihypertensive efficacy and safety profiles of lisinopril were assessed in 24 patients (15 men, 9 women; mean age 52.3 years; range 21-75 years) with hypertension associated with impaired renal function (glomerular filtration rate GFR 60 ml/min or less), in an open study of 12 weeks' duration. Previous antihypertensive drugs were discontinued at entry into the study. Lisinopril was given orally once daily; the starting dose was 2.5 mg in patients with a GFR of less than 30 ml/min, and 5 mg in all other patients. The dosage of lisinopril was titrated upward to 40 mg daily according to BP response. A diuretic could then be added if hypertension was inadequately controlled. Twenty-three patients completed the study. Mean sitting BP was reduced from 177 +/- 21.2/106 +/- 9.1 mm Hg (mean +/- SD) at entry to the study to 145 +/- 21.4/88 +/- 8.3 mm Hg after 12 weeks of treatment (p less than 0.001). The median dose of lisinopril used was 10 mg (range 2.5-40 mg) and only 4 patients had a diuretic added to the lisinopril. Overall GFR was unchanged during the study: mean baseline value was 37 +/- 16.4 ml/min (range 10-60 ml/min) at the beginning of the study and 40 +/- 21.0 ml/min at the end. As in a previous pharmacokinetic study in similar patients, a tendency toward drug accumulation was noted only in those patients with the most severe renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A single-blind, comparative study of hydrochlorothiazide/amiloride ('Moduret' 25) and hydrochlorothiazide/triamterene ('dyazide') in elderly patients with congestive heart failure.

The efficacy and biochemical effects of two low-dose thiazide plus potassium-sparing diuretic preparations were compared in the treatment of elderly patients with stable, mild to moderate congestive heart failure. Sixty patients (mean age 80 years) were randomly allocated to treatment with 1 tablet daily of either 25 mg hydrochlorothiazide/2.5 mg amiloride or 25 mg hydrochlorothiazide/50 mg triamterene. The dose was increased to 2 tablets daily if necessary, after 2 weeks, for a further 6 weeks. Patients' response to treatment was assessed at 2, 4 and 8 weeks using a simple clinical scoring system for signs and symptoms of their condition, and routine biochemical analysis was carried out at baseline and the end of treatment. One patient was withdrawn from the study due to a rash which was probably related to hydrochlorothiazide/amiloride treatment. A further 11 patients were excluded from the analysis because of intercurrent illness or inadequate records. Analysis of the results from 48 patients showed that both treatments resulted in an improvement in clinical score and weight reduction, with more than three-quarters of the patients responding to treatment. No serious biochemical disturbances occurred; in particular, no new cases of hyponatraemia (serum sodium less than 130 mmol/l) developed. Both preparations, therefore, were effective and tolerated forms of treatment for mild to moderate congestive heart failure in the elderly and there were no significant differences between them.

Aged↗

Characterization of human interferon species using gel extraction and monoclonal antibodies: implications on clinical use of interferon preparations.

Human interferons from various sources have been characterized using sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by electrotransfer onto nitrocellulose and reaction with specific polyclonal and monoclonal antibodies. When gel slices were extracted, alpha-interferon subspecies possessed antiviral activity predominantly in the 18.6-19.7K region bands, the beta-interferon in the 22.1K band, and gamma-interferon in the 16.5-18.0K bands. Three of the monoclonal antibodies (Ab 138, Ab 126, Ab 098) reacted with a characteristic triplet of biologically active bands (18.6K, 19.1K, 19.7K) obtained using the Namalwa cell interferons, while two (Ab 194 and Ab 232) reacted only with the 18.6K band and Ab 523 reacted with the 19.7K band. With the human leukocyte interferons, Ab 098, Ab 194, and Ab 232 reacted with the active 18.6K band. The Ab 138, Ab 126, and Ab 523 reacted specifically with certain lower molecular weight active bands (13K region). A comparison of the antiviral activity and reactivity towards monoclonal and polyclonal antibodies presents a differentiation of the subspecies of interferons in the wide array of closely related proteins in interferon preparations packaged for clinical use.

Antibodies, Monoclonal↗

Immunomodulatory and therapeutic properties of bestatin in mice.

In this report, we describe the immunomodulatory properties and therapeutic efficacy of bestatin. Macrophage activation, but not natural killer cell augmentation, was observed both in vitro and in vivo. Immunostimulation of T-cell activity was observed in assays of allogeneic mixed lymphocyte response, but cytotoxic effector cells did not develop after an allogeneic mixed lymphocyte-tumor cell culture. Bestatin also had T-cell adjuvant activity when it was admixed with a suboptimal vaccine composed of irradiated tumor cells. We observed significant therapeutic activity against preexisting experimental and spontaneous metastases when bestatin was administered at high doses per animal for 4 weeks.

Adjuvants, Immunologic↗

Cardiac and renal hyperplasia in newborn genetically hypertensive rats.

Newborn spontaneously hypertensive rats (SHR), compared with Wistar-Kyoto (WKY) controls, usually show cardiac and renal hyperplasia. To determine whether these anomalies are common to genetically hypertensive rats, we examined newborn rats from models of essential hypertension (Kyoto, Montreal, Dunedin and Lyon strains of hypertensive rats), renal hypertension (Milan strain of hypertensive rats) and experimental hypertension [deoxycorticosterone acetate (DOCA)-salt hypertensive Wistar rats]. The hearts, kidneys and livers of these newborns were collected on site at various centres and sent to Montreal for protein and DNA determinations. The results showed that protein and DNA, corrected for body weight in models of essential hypertension, were increased in the heart and kidney, and normal or decreased in the liver at birth. This pattern differed in offspring of the Milan strain (renal hypertension) and of DOCA-salt hypertensive animals (experimental hypertension). Since cardiac and renal hyperplasia associated with the hypertensive trait in four different genetic models of spontaneous hypertension was distinct from that observed in renal and experimental hypertension, it is conceivable that a specific cardiovascular growth pattern is a reflection not of a simple linkage or consequence, but of a causal association with spontaneous hypertension.

Animals↗

The BRMP IL-2 reference reagent.

The BRMP has established an interim IL 2 Reference Reagent. Unitage was assigned after a collaborative, 7 laboratory study. The standard has been distributed to over 350 investigators to date.

Indicators and Reagents↗

Two fatalities resulting from Tessalon (benzonatate).

Two fatal cases involving Tessalon (benzonatate) were quantitated by ultraviolet (UV) and high performance liquid chromatography (HPLC). The first case involved an infant found choking; Tessalon perles were found with the child. The second case involved a successful suicide of an 18-year-old that consumed a "handful" of phenytoin and benzonatate and expired within 1 hr of the ingestion. Blood, brain and kidney concentrations are reported. These are believed to be the first two reported cases involving this compound.

Adolescent↗

Biochemical characterization and purification of human B cell stimulatory factor (BSF).

B cell stimulatory factor (BSF) activity was generated over a period of five days by phytohemagglutinin-stimulated E rosette-positive peripheral blood lymphocytes. This activity was subjected to a multistep purification procedure including ammonium sulfate precipitation, anion-exchange chromatography, gel filtration, procion red-agarose chromatography and reverse phase high performance liquid chromatography (RP-HPLC). The last purification step dissected BSF activity into two active fractions, one corresponded to the interleukin 2 (IL 2) activity whereas the other active fraction was free of IL 2 activity. Preparative isoelectric focusing analysis defined isoelectric points of pH 7.2 for both BSF and IL 2. Molecular weight analysis of BSF was carried out by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. BSF activity was eluted from gel strips corresponding to a molecular mass of 16 and 17 kDa. The 16-kDa fraction was free of IL 2 activity whereas the 17-kDa fraction overlapped with IL 2. Since recombinant IL 2 was capable of exhibiting significant BSF activity in anti-IgM or Staphylococcus aureus Cowan strain I-dependent assay systems, it cannot be excluded that IL 2 itself is a BSF. Nevertheless these studies demonstrate the existence of a BSF free of IL 2 activity.

Antibodies, Anti-Idiotypic↗

The effect of glycerol on cochlear function and ionic concentration.

The use of glycerol continues to be a popular clinical test for diagnosing reversible hearing loss in patients with Meniere's disease, although its mechanism of action remains obscure. The purpose of this investigation was to study experimentally the alterations in the ionic composition and function of the cochlea which occur following glycerol administration. Immediate decreases in inner ear pressure and increases in AP threshold were seen. Delayed decreases in the endocochlear potential with increases in inner ear electrolytes occurred. However, we were unable to find any substantial changes in inner ear oxygen concentrations. Our findings support the concept that the principal action of glycerol is in osmotic reduction of inner ear pressure.

Action Potentials↗

Psychological factors and outcome of electrode implantation for chronic pain.

The utility of using psychological assessments as a basis for predicting pain relief after electrode implantation is examined. Two raters independently reviewed the functional pain protocols of chronic pain patients who were candidates for deep brain (n = 13) or spinal cord (n = 17) electrode implants and predicted whether each would have a good or poor treatment response. At follow-up, five deep brain (39%) and four spinal cord (24%) patients were classified as having good responses to treatment. Predictions of outcome based on psychological data were accurate for 80% of the patients. These results suggest that functional pain assessment is useful as a part of preimplantation screening and emphasize the importance of psychological factors in the outcome of treatment for chronic pain.

Electrodes, Implanted↗

Hyporesponsiveness to augmentation of murine natural killer cell activity in different anatomical compartments by multiple injections of various immunomodulators including recombinant interferons and interleukin 2.

Augmentation of natural killer (NK) cell activity has been observed after the single administration of a wide variety of biological response modifiers (BRM); however, multiple injections of BRM have resulted in hyporesponsiveness to NK augmentation in both preclinical and clinical studies. In these studies, hyporesponsiveness to augmentation of NK cell activity occurred after multiple injections of interferon (IFN recombinant human IFN-alpha A/D and recombinant IFN-gamma) and interleukin 2 and was found to be systemic (lungs, liver, blood, and spleen). In contrast, hyporesponsiveness to augmentation by multiple injections of maleicanhydride divinyl ether (MVE-2) or Propionibacterium acnes was limited to the spleen and peripheral blood lymphocytes, with continued augmentation of NK cell activity in the peritoneum, lungs, and liver. Despite the hyporesponsiveness to augmentation of NK activity by multiple IFN injections, NK activity could still be augmented by a single injection of another BRM. The NK cell hyporesponsiveness induced in the spleen by MVE-2 was also reversed by a single administration of IFN or polyinosinic-polycytidylic and poly-L-lysine solubilized by carboxymethyl cellulose but not by OK-432 or P. acnes. These results demonstrate that the nature of the hyporesponsiveness to NK augmentation, which is induced by multiple treatments with BRM, varies with the type of agent. The noncytokine BRM that were studied induced hyporesponsiveness only in specific lymphoid compartments but not in major nonlymphoid organs, whereas cytokine BRM induced a systemic hyporesponsiveness. The hyporesponsive state induced by the different types of BRM, also varied in regard to the pattern of susceptibility to augmentation of NK activity by unrelated BRM.

Adjuvants, Immunologic↗

Preparation and characterization of monoclonal antibodies directed at epitopes of human IFN-gamma.

Five monoclonal antibodies (A7, B24, I14, L12, and M2) recognizing different epitopes of the human natural IFN-gamma were prepared by immunizing BALB/c mice with a highly purified human natural IFN-gamma preparation (10(7) U/mg). All five antibodies had high IFN-gamma-binding activity but exhibited differential IFN-gamma-neutralizing activities. Furthermore, none of them neutralized the antiviral activity exhibited by either IFN-alpha or IFN-beta preparations, indicating thus their specificity for IFN-gamma. The A7, L12, M2, and I14 monoclonal antibodies, but not the B24, blocked the augmentation of natural killer cytotoxicity, mediated by peripheral blood monocyte-depleted lymphocytes, by Escherichia coli-derived IFN-gamma or natural IFN-gamma but not by IFN-alpha 2. All five monoclonal antibodies precipitated an identical molecular complex containing two major protein components with molecular weights of 20,000 (20 kD) and 25,000 (25 kD) and two minor components with molecular weights of 17,000 (17 kD) and 45,000 (45 kD). Treatment of the immunoprecipitated IFN-gamma molecule with endoglycosylase F led to a stepwise removal of the carbohydrate portions on both the 25 and 20 kD chains, which resulted in the appearance of both 16 kD and 18 kD chains. The hereby reported monoclonal anti-IFN-gamma antibodies will prove useful as probes for purification and for rapid assay of human IFN-gamma molecule.

Animals↗