Showing papers by "Jewish Hospital published in 1989"

Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release.

Abstract: In previous studies, we showed that blood monocyte elaboration of interleukin 1 (IL-1), a known stimulator of bone resorption, was higher in osteoporotic patients with rapid bone turnover than in those with slow turnover and in nonosteoporotic subjects. Since an acceleration of bone loss following menopause contributes to the risk of osteoporosis in women, we have studied the effects of menopause and ovarian steroid treatment on IL-1 release by monocytes obtained from nonosteoporotic and osteoporotic women. IL-1 activity in the monocyte culture medium derived from untreated postmenopausal women (nonosteoporotic and osteoporotic) was higher than in the medium derived from either untreated premenopausal or estrogen/progesterone-treated postmenopausal women. A significant negative correlation was found between IL-1 and years since menopause in both the healthy (r = -0.75; P less than 0.005) and the osteoporotic (r = -0.61; P less than 0.01) untreated postmenopausal women. The difference between the two slopes was significant at P less than 0.05. Premenopausal IL-1 levels were achieved within 8 years of menopause in the nonosteoporotic, but not in the osteoporotic, subjects in whom increases were evident as long as 15 years after menopause. IL-1 also correlated inversely with vertebral mineral density (r = -0.37; P less than 0.05), as measured by quantitative computed tomography. In prospective studies, treatment with estrogen/progesterone for 1 month caused a substantial highly significant decrease in IL-1 activity in each of three nonosteoporotic and five osteoporotic women, confirming the apparent effect of hormone therapy observed in the cross-sectional analysis. Although a cause-effect relationship has not been established, it is our hypothesis, based on these data, that alterations in IL-1 production may underlie the postmenopausal acceleration in bone loss and its inhibition by ovarian steroids. Persistent elevation of IL-1 secretion appears to be a feature of postmenopausal osteoporosis.

Extracellular protons acidify osteoclasts, reduce cytosolic calcium, and promote expression of cell-matrix attachment structures.

Abstract: Because metabolic acids stimulate bone resorption in vitro and in vivo, we focused on the cellular events produced by acidosis that might be associated with stimulation of bone remodeling. To this end, we exposed isolated chicken osteoclasts to a metabolic (butyric) acid and observed a fall in both intracellular pH and cytosolic calcium [( Ca2+]i). These phenomena were recapitulated when bone resorptive cells, alkalinized by HCO3 loading, were transferred to a bicarbonate-free environment. The acid-induced decline in osteoclast [Ca2+]i was blocked by either NaCN or Na3VO4, in a Na+-independent fashion, despite the failure of each inhibitor to alter stimulated intracellular acidification. Moreover, K+-induced membrane depolarization also reduced cytosolic calcium in a manner additive to the effect of protons. These findings suggest that osteoclasts adherent to bone lack functional voltage-operated Ca2+ channels, and they reduced [Ca2+]i in response to protons via a membrane residing Ca-ATPase. Most importantly, acidosis enhances formation of podosomes, the contact areas of the osteoclast clear zone, indicating increased adhesion to substrate, an early step in bone resorption. Thus, extracellular acidification of osteoclasts leads to decrements in intracellular pH and calcium, and appears to promote cell-matrix attachment.

Influence of cerebral hemodynamics on stroke risk: One‐year follow‐up of 30 medically treated patients

Abstract: The importance of hemodynamic factors in the pathogenesis and treatment of ischemic cerebrovascular disease is not clear. We have investigated the relationship between cerebral hemodynamics and the subsequent risk of stroke in 30 medically treated patients with symptomatic occlusion or greater than 75% intracranial stenosis of the carotid arterial system. Positron emission tomography (PET) was used to evaluate the regional hemodynamic status of the cerebral circulation. Clinical follow-up to 1 year post-PET was available for all patients. The incidence at 1 year of all strokes was 1/9 for patients with normal hemodynamics and 1/21 for patients with abnormal hemodynamics. The 1-year incidence of ipsilateral ischemic stroke was 1/9 for hemodynamically normal patients and 0/21 in the abnormal group. The 21 patients in the abnormal group fulfilled entry criteria for the Extracranial-Intracranial Bypass Trial. The 0/21 incidence of ipsilateral ischemic stroke at 1 year was compared with the 1-year rate of 0.109 for the 714 medically treated patients from the Bypass Trial. We were able to reject with better than 90% certainty (p = 0.089) the hypothesis that our sample of patients came from a population with an ipsilateral ischemic stroke rate of 0.109 or greater. Thus, in this small sample, we found no evidence that PET evidence of abnormal cerebral hemodynamics identifies a subgroup of patients at higher risk for early stroke if treated medically with antithrombotic drugs.

Activity of ion channels during volume regulation by clonal N1E115 neuroblastoma cells.

Abstract: When exposed to a hypotonic bathing solution, clonal N1E115 neuroblastoma cells initially swell and then undergo a regulatory volume decrease (RVD). Using cell-attached patch-clamp recording, we have found that the activity of a stretch-sensitive, nonselective cation [C+(SA)] channel increases shortly after the onset of osmotically induced cell swelling; this depolarizes the cells as much as 30 mV. Shortly thereafter, and roughly coincident with the onset of RVD, two types of voltage-dependent channels open at the new resting potential; these are (i) a delayed-rectifier type K+ [K+(DR)] channel and (ii) a large-conductance anion channel. We suggest that opening of the C+(SA) channel may contribute to the volume "sensor" mechanism, while the depolarization-induced opening of the K+(DR) and anion channels may constitute a significant K+ salt exit pathway, operating in RVD.

Techniques and results in the management of anal and perianal Crohn's disease.

Abstract: We reviewed our experience with 73 patients who had Crohn's disease and underwent local anorectal surgical procedures for perianal suppurative disease during a ten year period. All but one of these patients had intestinal granulomatous disease. The average length of follow-up study was 4.6 years. By using conservative, local anorectal surgical procedures and intensive medical treatment, we were able to establish adequate drainage of abscesses, reduce the inflammatory process and relieve symptoms. Extensive drainage procedures were avoided to preserve the anal sphincter. A sliding endorectal flap repair provided satisfactory results for rectovaginal fistulas and anterior anal fistulas. Proctectomy was eventually necessary in nine patients, the primary indication being severe perianal disease in five. By performing complete excision of the perineal disease at the time of proctectomy, we were able to achieve primary healing of the perineal wound in eight of these patients. Patients were classified according to five categories of results: healed after initial local treatment, eight patients; healed after more than one local treatment, 30 patients; incomplete healing with acceptable condition, 17 patients; healed after fecal diversion, nine patients, and required proctectomy, nine patients. The majority of patients with Crohn's disease and anal and perianal suppurative disease can be managed by meticulous drainage of sepsis and preservation of the anal sphincter.

Severe hypophosphatemia following the institution of enteral feedings.

Abstract: Although severe hypophosphatemia has been recognized in refeeding syndromes, it is not a commonly reported complication of enteral nutrition. The present study was designed to identify cases of severe hypophosphatemia (less than 0.32 mmol/L [less than 1.0 mg/dL]) related to the administration of carbohydrates via the enteral route. Serum phosphorus levels were evaluated at the time of admission of 25 patients to two midwestern teaching hospitals and during their postoperative enteral support in the surgical intensive care unit. The initial serum phosphorus levels ranged from 0.77 to 1.55 mmol/L (2.4 to 4.8 mg/dL), serum calcium levels ranged from 1.80 to 2.44 mmol/L (7.2 to 9.8 mg/dL). From two to five days following the initiation of isotonic enteral feedings, the serum phosphorus level decreased to 0.16 to 0.39 mmol/L (0.5 to 1.2 mg/dL). Serum phosphorus levels were corrected within two to ten days with oral supplementation only. Patients with high metabolic demand may have a higher daily requirement for phosphorus than that available in routine isotonic enteral formulas.

Contractile properties of human prostate adenomas and the development of infravesical obstruction.

Abstract: The contractile response of human prostate adenomas to KCl, phenylephrine (alpha 1 adrenergic agonist), UK 14304 (alpha 2 adrenergic agonist), and carbachol (muscarinic cholinergic agonist) was evaluated in tissue specimens obtained from men with symptomatic and asymptomatic BPH. Prostate specimens were obtained from 5 men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). Quantitative symptom score analysis and urinary flow rate determination documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The magnitude of the contractile response (Emax) and the potency of phenylephrine-induced contractions (EC50) in prostatic preparations obtained from men with symptomatic and asymptomatic BPH were similar. The IC50 for the inhibition of phenylephrine-induced contractions by prazosin was 3.2 nM, confirming that phenylephrine-induced contraction in the human prostate is mediated by the alpha 1 adrenoceptor. The contractile responses of prostate adenomas to muscarinic cholinergic and alpha 2 agonists were negligible. This study demonstrates that the development of bladder outlet obstruction in men with BPH is not related to alterations in the functional response of the smooth muscle component of the prostate adenoma.

Effects of dietary fish oil supplementation on membrane fluidity and enzyme activity in rat small intestine

Abstract: Rats were fed either a fat-free diet supplemented with 10% menhaden oil or a control diet for four months. Intestinal brush border membranes were isolated; phospholipid fatty acid analysis revealed that the membranes from the fish-oil fed animals had higher levels of palmitoleic (C16:1) and eicosapentaenoic (C20:5) acids and lesser levels of stearic (C18:0) linoleic (C18:2) acids compared with controls. The membranes from the fish-oil fed animals had increased levels of alkaline phosphatase activity compared with controls but disaccharidase levels were equivalent in the two groups. Rocket immunoelectrophoresis studies revealed that the increase in alkaline phosphatase activity was due to an increase in the specific activity of the enzyme rather than an increase in the amount of enzyme. Membrane fluidity was assessed by fluorescence anisotropy using diphenylhexatriene and 12-anthroyl stearate as fluorescent probes. The anisotropy of both probes was similar in the two membranes. These studies indicate that fish-oil supplementation alters the fatty acid composition of the intestinal brush border membrane and increases alkaline phosphatase activity without affecting membrane fluidity. Thus the effects of changes in membrane lipid composition on alkaline phosphatase activity appear to result from changes in the local lipid environment of the enzyme rather than from changes in the biophysical characteristics of the membrane.

Effects of Histoplasma capsulatum on murine macrophage functions: inhibition of macrophage priming, oxidative burst, and antifungal activities.

Abstract: Histoplasma capsulatum yeast cells fail to trigger an oxidative burst response in normal murine macrophages. The results of this study, in which an in vitro assay of macrophage antifungal effects was used, extend these findings. During 18 h of incubation, unprimed elicited murine macrophages inhibited H. capsulatum growth only when macrophages were present in great excess. Gamma interferon (IFN-gamma)-primed macrophages showed enhanced fungal growth inhibition but a similar requirement for an excess of phagocytes. Macrophages containing heat-killed H. capsulatum exhibited diminished antifungal effects toward viable H. capsulatum and Saccharomyces cerevisiae cells. Parallel experiments showed no comparable effect of ingested latex particles on macrophage antifungal activity. Using chemiluminescence as a measure of the oxidative burst, we found that macrophages primed in vitro with IFN-gamma alone failed to exhibit a significant response to triggering by H. capsulatum yeast cells unless a second priming agent (tumor necrosis factor alpha or bacterial lipopolysaccharide) was added to IFN-gamma. Furthermore, macrophage priming with single agents was blocked by the prior ingestion of heat-killed H. capsulatum. These studies provide evidence that ingestion of H. capsulatum yeast cells can induce a prompt and enduring deactivation of murine macrophages.

IL-1 activates the Na+/H+ antiport in a murine T cell.

Abstract: One of the early events following growth factor exposure is elevation of intracellular pH, a process mediated by the Na+/H+ antiport. We studied the effects of human rIL-1 alpha (HrIL-1 alpha) on intracellular pH (pHi) and calcium ([Ca2+]i) in a murine T cell line (MD10 cells), which proliferates in response to IL-1 alone. By using the intracellularly trapped fluorescent dyes (2(1),7(1)-bis-2-carboxyethyl)-5(and -6) carboxyfluorescein) and indo-1, we monitored immediate to early changes of pHi and [Ca2+]i in response to HrIL-1 alpha. Exposure to HrIL-1 alpha (120 pM) leads to an early, sustained intracellular alkalinization (delta pH = + 0.09 +/- 0.03) that plateaus within 20 min. Lower concentrations of the monokine (12 pM, 1.2 pM) have a positive but not statistically significant effect on pHi. These effects parallel the degree of MD10 IL-1R saturation predicted by the KD (49 pM) as assessed by 125I-HrIL-1 alpha binding by MD10 cells (Bmax = approximately 1300). Both the MD10 IL-1 receptor KD and the HrIL-1 alpha concentration required to induce early measurable alkaline pH shifts, however, exceed by three orders of magnitude the HrIL-1 alpha ED50 (50 fM) required for MD10 proliferation. The IL-1-induced rise in pHi is both sodium dependent and amiloride sensitive, indicative of activation of the Na+/H+ antiport. Additionally, PMA (100 nM) and IL-2 (2 nM) alkalinize MD10 cells, with the rise in pHi as a result of PMA exceeding the maximal IL-1 effect (delta pH = + 0.13 +/- 0.04). Furthermore, although PMA alkalinizes cells previously exposed to HrIL-1 alpha, the monokine does not alter the pHi of PMA-treated MD10 cells. Importantly, intracellular alkalinization induced by either HrIL-1 alpha or PMA is inhibited by staurosporine (1 mu iM). Finally, HrIL-1 alpha does not change MD10 [Ca2+]i, in either an acute or sustained fashion. These results indicate that IL-1 activates the Na+/H+ antiport in T cells by a mechanism that is unrelated to changes in [Ca2+]i but may involve protein kinase C activation.

Use of sulfated polysaccharides to decrease cholesterol and fatty acid absorption

Abstract: This invention encompasses a method and compositions which inhibit pancreatic cholesterol esterase and triglyceride lipase and hence, lower cholesterol and triglycerides in the blood stream.

New fluorescence assay for the quantitation of fungi.

Abstract: Quantitative determination of fungal mass is easily achieved with a new procedure that detects particle epifluorescence. Fungi are detected after exposure to a fluorescent stain (Fungiqual; CIBA-GEIGY Corp., Summit, N.J.) by using a fluorescence particle concentration analyzer. This report describes a simple fluorescence method for quantitation of either yeast or mycelial forms of fungi. The nature of the staining reaction was studied, and a practical application of this procedure for determination of fungal susceptibility to an antifungal agent is presented.

Use of sulfated polysaccharides to inhibit pancreatic cholesterol esterase

Abstract: This invention encompasses a method and compositions which inhibit pancreatic cholesterol esterase and triglyceride lipase and hence, lower cholesterol and triglycerides in the blood stream.

Multiorgan failure from the inadvertent intravenous administration of enteral feeding.

Abstract: Nasogastric tube-feeding was inadvertently administered parenterally to a 65-year-old woman with chronic lymphocytic leukemia. Administration was discontinued after approximately 8 hr of infusion. The patient manifested acute renal failure, respiratory failure, hepatic insufficiency, and high-output septic shock requiring invasive hemodynamic monitoring, peritoneal dialysis, mechanical ventilation, and broad spectrum intravenous antibiotics. Blood cultures were positive for alpha-hemolytic Streptococcus, Staphylcoccus epidermidis, and Enterobacter cloacae while cultures of the enteral solution grew alpha-hemolytic Streptococcus, S. epidermidis, Pseudomonas vesiculare and unidentifiable coliforms. Aggressive management resulted in hospital discharge, although she eventually died of recurrent pneumonia and septicemia 111 days after the infusion. It is of paramount importance to be cognizant of this potential complication in any patient receiving enteral feeding who presents with the clinical picture of high...

Tolerance induced by physiological levels of secreted proteins in transgenic mice expressing human insulin.

Abstract: We have used transgenic mice to study immune tolerance to autologous, non-MHC encoded proteins that are expressed at physiological levels in the circulation. The transgenic mice used in these studies express the human preproinsulin gene and synthesize human proinsulin. Human and mouse insulin are secreted from the pancreatic islets of transgenic mice in response to normal physiological stimuli, such as glucose. Our data demonstrate that the transgenic mice have acquired tolerance to human insulin. The repertoire of T cells specific for exogenous antigens is shaped by the acquired tolerance to autologous proteins since pork but not beef or sheep insulin is also nonimmunogenic in the transgenic mice. We also found that the transgenic mice were tolerant to human proinsulin, the intracellular precursor of insulin. Unresponsiveness to human proinsulin most likely results from tolerance of insulin-specific and proinsulin-specific T cells that recognize the secreted enzymatic cleavage products of proinsulin, insulin and C-peptide.

The Post-Infectious Chronic Fatigue Syndrome

Abstract: In the past few years, a syndrome of extreme persistent fatigue and associated symptoms, often including myalgia and/or disturbances of cognitive function, has been increasingly studied in a number of countries. In 1988, Holmes et al. established a working definition (Table 1) for this syndrome, referred to as chronic fatigue syndrome (CFS), in order to provide a starting point for various investigators to compare their results more meaningfully. CFS is apparently a heterogeneous collection of illnesses, emphasized by the number of names attributed to this constellation of symptoms in the literature (Krueger, see below). Since Epstein-Barr virus (EBV) has been implicated as one cause of post-infectious chronic fatigue syndrome (PICFS) (Tobi et al., 1982; Jones et al., 1985; Straus et al., 1985) and chronic EBV (CEBV) infection has become a widely diagnosed illness, a re-evaluation of CFS appears appropriate for the Third International Symposium on Epstein-Barr Virus and Associated Diseases.

Alpha adrenergic antagonists for the treatment of symptomatic BPH.

Abstract: Benign prostatic hyperplasia (BPH) describes a benign enlargement of the prostate gland that develops in the aging male population. Approximately 50% of 60-year-old men have histologic evidence of BPH. The clinical manifestations of BPH are related entirely to the obstruction of urinary outflow. Benign prostatic hyperplasia produces obstruction to urinary flow by static and dynamic factors. The dynamic component of infravesical obstruction presumably is mediated by the tone of the prostate smooth muscle. Pharmacologic agents that cause relaxation of the prostate may represent an effective therapeutic approach for symptomatic BPH. Organ bath contractile studies have indicated that the contractile properties of prostate adenoma are mediated by alpha1 adrenoceptors. Ten clinical trials evaluating the efficacy of alpha adrenergic blockers for the treatment of symptomatic BPH have been performed in Europe during the past 11 years. Clinical efficacy was observed in 9 of the 10 clinical trials. Randomized, placebo controlled, multicenter clinical trials are currently in progress in the United States to evaluate the efficacy of alpha blockers for the treatment of BPH. Rationale and the clinical experience of alpha adrenergic blockers for the treatment of symtomatic BPH is reviewed in this article.