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S Mills

Publications and source records attributed to S Mills.

At least 73 records · Page 4Linked to original sources
PubMed1989

Modulation of IL-2-induced human B cell proliferation in the presence of human 50-kDa B cell growth factor and IL-4.

Several human T cell derived factors capable of stimulating human B cells to synthesize DNA have been previously described. One such factor exhibits an apparent m.w. of 50,000 Da and has been termed 50-kDa-B cell growth factor (BCGF). In this report, we show that a human B cell proliferation pathway based on the sequential action of anti-mu antibody, 50-kDa-BCGF and IL-2 is inhibited in the presence of human rIL-4. Although IL-4 itself is capable of triggering B cell DNA synthesis as measured at 72 h, this lymphokine inhibits, in a dose-related manner, the 50-kDa-BCGF driven response of B cells to IL-2 when such proliferation is determined after 144 h. This inhibition takes place at an early step of the B cell activation and does not require the presence of IL-4 during the whole culture period. Such inhibitory activity of IL-4 is specific to the IL-2-induced B cell proliferation because DNA synthesis measured in the presence of semi-purified human 12-kDa-BCGF is not affected by the presence of IL-4. Our results suggest that a particular pathway of human B cell activation leading to the proliferation of these cells in the presence of IL-2 could be either up- or down-modulated by 50-kDa-BCGF and IL-4, respectively.

Adjuvants, Immunologic↗
PubMed1989

Central nervous system mediated vasodepressor action of atrial natriuretic factor.

Administration of 20, 4 or 2.5 micrograms/kg of atriopeptin III (AT III) into the fourth ventricle of the brain of spontaneously hypertensive rats produced a 13, 14 and 7 mm Hg decrease in MAP respectively, while 1 microgram/kg had no effect on MAP and was significantly different from 20 or 4 micrograms/kg (p less than 0.025). In contrast, injection of AT III 20 micrograms/kg into the lateral ventricle did not produce a change in MAP. To examine an interaction of AT III with the opioidergic system, the opiate antagonist, naloxone HCl, 10 micrograms, was given by ICV injection 10 minutes prior to AT III, and significantly prevented the depressor response to AT III (p less than 0.025 compared with AT III alone). Injection of specific anti-sera to beta-endorphin failed to prevent the AT III-induced depressor response. Our results demonstrate that AT III can act within the central nervous system to decrease the MAP of rats, most likely at a locus in proximity to the fourth ventricle of the brain. Further, an interaction with the central opioidergic nervous system underlies the central effects of AT III.

Animals↗
PubMed1989

Hypomagnesemia in patients in postoperative intensive care.

In order to study the clinical consequences of postoperative hypomagnesemia, the serum magnesium (Mg) concentration was measured in samples of blood collected from 193 patients admitted to two postoperative ICUs. On admission to the ICU, 117 patients (61 percent) had hypomagnesemia (serum Mg less than 1.5 mEq/dl), 66 patients (34 percent) had normomagnesemia (1.5 to 2.0 mEq/dl), and ten patients (5 percent) had hypermagnesemia (greater than 2.0 mEq/dl). There were no correlations between the severity of illness score (r = 0.145) or the degree of hypoproteinemia (r = 0.01) and the postoperative serum Mg level. Patients with severe hypomagnesemia (serum Mg less than or equal to 1.0 mEq/dl) experienced hypokalemia more often (p less than 0.02) than the others in the study. Furthermore, those with severe hypomagnesemia had a higher mortality rate (7/17 or 41 percent) than the remainder of the population studied (22/176 or 13 percent) (p less than 0.02). Those with severe hypomagnesemia had received aminoglycosides more often (p less than 0.001) than those with normal serum Mg concentrations. The serum Mg level was not a sensitive (68 percent) or specific (37 percent) predictor of survival. Our conclusions were as follows: (1) hypomagnesemia is common in postoperative ICU patients; and (2) patients in the postoperative ICU who have severe hypomagnesemia have a higher mortality and more hypokalemia than similarly ill patients with normomagnesemia. Because of the association between aminoglycoside therapy and severe hypomagnesemia, we recommend measurement of this variable in those patients receiving aminoglycosides. Furthermore, Mg replacement therapy is recommended for those patients with serum Mg values of 1 mEq/dl or less.

Calcium↗
PubMed1989

Effect of adenosine triphosphate depletion in vivo on renal function in the rat with and without ischemia.

To investigate the importance of renal tissue concentrations of adenosine triphosphate (ATP) in maintaining normal renal functions as well in the recovery from ischemic injury in vivo, fructose was administered without ischemia as well as in the setting of an ischemic insult. In nonischemic as well as kidneys recovering from 30 min of clamp ischemia, fructose caused a 50% reduction in the tissue concentration of ATP which persisted for over 1 h. In nonischemic animals, fructose had no effect on renal function as assessed by inulin clearance and sodium reabsorption and showed no evidence of histologic injury 24 h after administration. In animals subjected to 30 min of ischemia, animals given fructose showed no worsening of functional or histologic injury as compared to controls. We conclude from these data that reductions in the tissue concentration of ATP in the range observed does not adversely affect normal renal functions or recovery from a reversible ischemic insult.

Adenine Nucleotides↗
PubMed1988

Expression of CD23 antigen is not necessary for human 12-kDa B cell growth factor-mediated B cell proliferation.

In an attempt to understand the relationship between the CD23 antigen and the human 12-kDa B cell growth factor (BCGF) receptor, we have undertaken studies to define the biological efficacy of 12-kDa-BCGF on CD23+ (Raji) and CD23- (P3HR1) human Burkitt B cell lines. Our results show that recombinant 12-kDa-BCGF can induce efficient [3H]thymidine incorporation and proliferation in cells of either phenotype. These results strongly suggest that a functional receptor for the 12-kDa-BCGF may exist independently of the CD23 molecule.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1988

An evaluation of the relation between food consumption rate and equilibrium body-weight in male rats.

1. Two experimental approaches were employed to assess the relation between food consumption rate and maintenance requirements in male weanling rats. The first approach involved restricting food intake in rats previously given free access to food from weaning to 59 d of age. The second approach involved restriction of food intake to various levels after weaning. Maintenance requirements (g food/d per g body-weight (W] were estimated by dividing the rate of food consumption by the resulting equilibrium W (EBW) for each animal. In addition, food consumption was partitioned into growth-independent (maintenance) and growth-dependent (gain) components by alternately setting W and specific growth rate (W') to zero in an equation relating food intake rate to W and W'. Coupling coefficients representing maintenance consumption (g food/d per g W) and gain consumption (g food/g gain) were estimated for each animal by least squares. 2. Both techniques for estimating maintenance consumption provided similar estimates within and across experiments, and regardless of when food restriction was imposed or its severity, consumption for maintenance was about 5% W/d. 3. The EBW to which animals in each treatment group aspired was directly proportional to that group's food intake rate. 4. Coventional measures of growth efficiency were also related to food intake; efficiency decreased with decreasing food intake. Partitioning food consumption into maintenance and gain components revealed that as the rate of food intake decreased, the proportion of total intake consumed for maintenance increased. The results suggest that growth efficiency declines during food intake restriction because proportionately more of total intake is used for maintenance, leaving less available for gain.

Animals↗
PubMed1988

Liver structure and function in print workers exposed to toluene.

An unresolved controversy is whether exposure to organic solvents in the workplace causes hepatotoxicity. From a medical surveillance study of 289 printing factory employees who were exposed primarily to toluene, we identified eight workers who had persistently abnormal serum transaminase and/or alkaline phosphatase values. The eight men were generally healthy and gave no history of taking medications or of drinking ethanol to excess. None was obese or diabetic. Six patients had hepatomegaly based on physical examination. All eight had mild elevations (less than 2 to 3 times the upper value of normal) of serum transaminases [alanine (ALT) and aspartate aminotransferase (AST)]. However, there was a marked increase in the ratio of ALT/AST (mean = 1.61). In each case, liver biopsy revealed mild, pericentral fatty change. Our results, consistent with those previously published by some others, suggest that pericentral fatty liver with mild "reactive hepatitis" is the most likely diagnosis in workers exposed to solvents for whom common causes of mild liver test abnormalities have been excluded. An increased ALT/AST ratio may represent a convenient, previously unrecognized indicator of this condition.

Adult↗
PubMed1988

Atrial natriuretic factor-induced vasodepression occurs through central nervous system.

To characterize the blood pressure and heart rate effects of atrial natriuretic peptide (ANP) in the brain, we administered 20 micrograms/kg of atriopeptin III in 5 microliters of 0.9 normal saline into the fourth ventricle of awake, freely moving, spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. ANP produced a 13 +/- 1 mmHg decrease in mean arterial blood pressure (MAP) in the SHR (P less than 0.001 vs. base line or saline control, n = 10) and a 9 +/- 2 mmHg decrease in the WKY (P less than 0.02). Heart rate did not change significantly in response to ANP. To determine whether an interaction with the adrenergic nervous system played a role in the effects of ANP, we administered 100 ng yohimbine HCL, an alpha 2-antagonist, by intracerebroventricular injection, 45 min before ANP and completely prevented the ANP-induced decrease in MAP. In contrast, 100 ng intracerebroventricular prazosin, an alpha 1-adrenergic antagonist, had no significant influence on the MAP effect induced by ANP. A third group of SHR was pretreated with intracerebroventricular 6-OH dopamine to deplete central catecholamines or with saline. The rats pretreated with 6-OH dopamine (n = 6) had no significant response to ANP, which was administered 9 days later. This was significantly different from the saline-pretreated control group (n = 6), which responded with a 19 +/- 3 mmHg decrease in MAP (P less than 0.025). These studies indicate that the administration of ANP into the fourth ventricle of the brain decreases the MAP of rats through an interaction with the central alpha 2-adrenergic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Studies of the penetration of the blood brain barrier by atrial natriuretic factor.

The atrial natriuretic factors (ANF) have been detected in various areas of the brain. To determine whether circulating blood borne ANF could contribute to the ANF content in the central nervous systems we examined the ability of ANF-99-126 or ANF-102-126 to penetrate the blood brain barrier. Carotid artery injections of [3H] inulin with [125I] ANF in anesthetized rabbits resulted in a comparably minimal brain uptake index (BUI) for each labeled substance as measured in cerebral cortex extracts. Injection of [3H] HOH and [125I] ANF resulted in a mean BUI in cortex of 4.9 +/- .6 (SEM)% for ANF relative to triated water; this low uptake was not significantly saturable. The BUI ratio for ANF/HOH in olfactory bulb was somewhat higher though still low, at 7.0 +/- 9%, possibly reflecting the high density of ANF receptors in this structure. Infusion of [125I] ANF into the carotid artery of anesthetized rabbits resulted in little radioactivity being detected in the cerebrospinal fluid. Infusion of unlabeled ANF, which raised plasma levels as high as 26.3 ng/ml, resulted in little change in CSF levels. Our results demonstrate that the uptake of ANF into the brain is minimal and supports the idea that local synthesis of ANF predominantly accounts for the brain pool of this peptide.

Animals↗
PubMed1987

Pharmacokinetics of oral and intramuscular methotrexate in children with acute lymphoblastic leukaemia.

Repeated methotrexate absorption studies were performed under standard conditions in 127 children receiving either oral or intramuscular methotrexate for acute lymphoblastic leukaemia. There was marked variability in peak concentration, area under the serum concentration curve and clearance both between patients and in repeated studies on the same patient. Although the intramuscular route produced higher serum concentrations and AUC than the oral route, variability within and between patients was considerable and was most marked at higher concentrations. Neither age or sex could account for variation in methotrexate absorption or clearance. Intramuscular methotrexate, although producing higher serum concentrations and AUC, does not reduce the variability observed with oral administration. Prediction of subsequent methotrexate concentrations from the knowledge of one absorption profile is not possible.

Administration, Oral↗
PubMed1986

Modified Capizzi maintenance regimen in children with relapsed acute lymphoblastic leukaemia.

Improved survival of children with acute lymphoblastic leukaemia who relapse during therapy has been reported using the Capizzi maintenance regimen. We have treated ten such patients, without histocompatible donors, with this regimen, which consisted of fortnightly doses of vincristine (1.5 mg/m2) and an escalating dose of intravenous methotrexate (90-470 mg/m2) followed 24 hours later by asparaginase (15,000 units). Remission of disease had been successfully achieved in all patients using conventional therapy prior to the start of maintenance treatment. Cerebrospinal fluid concentrations of methotrexate were estimated serially in several patients but remained relatively low despite dose escalation. It appears that additional intrathecal chemotherapy is therefore necessary. Treatment was generally well tolerated but there is concern about the incidence of neurotoxicity in patients who had previously received cranial irradiation and intensive intrathecal therapy. The median duration of bone marrow remission was only 35 weeks (range 18-50). Two patients who had not been receiving IT therapy had early isolated CNS relapses. In conclusion, it appears that contrary to early expectations this treatment approach is unlikly to offer a significantly better outlook for these patients, in whom the chance of early marrow relapse remains high.

Adolescent↗
PubMed1986

Endogenous opioid modulation of pancreatic hormone secretion: studies in dogs.

The role of endogenous opioid peptides in the modulation of secretion of hormones from the endocrine pancreas was studied in dogs. In response to insulin-induced hypoglycemia, plasma glucagon secretion significantly increased, followed by an increase in plasma somatostatin immunoreactivity. Pretreatment with the opiate antagonist, naloxone, prevented the somatostatin response but had no effect on the augmented glucagon secretion. Neither the degree of hypoglycemia nor recovery from the induced glucose nadir were affected by naloxone. Arginine Hcl administration resulted in prompt increases in immunoreactive glucagon and insulin secretion, as well as a rise in serum glucose. Pretreatment with naloxone failed to affect any of these responses. Our results suggest that endogenous opioid peptides mediate the somatostatin response following hypoglycemia-induced glucagon secretion.

Animals↗
PubMed1985

Calcium transport in canine renal basolateral membrane vesicles. Effects of parathyroid hormone.

The effects of parathyroid hormone were studied on Ca2+ fluxes in canine renal proximal tubular basolateral membrane vesicles (BLMV). Efflux of Ca2+ from preloaded BLMV was found to be stimulated by an external Na+ gradient, and this was inhibited by the Na+ ionophore, monensin, and enhanced by intravesicular negative electrical potentials, which indicated electrogenic Na+/Ca2+ exchange activity. There was a Na+ gradient independent Ca2+ flux, but membrane binding of Ca2+ was excluded from contributing to the Na+ gradient-dependent efflux. The Na+ gradient-dependent flux of Ca2+ was very rapid, and even 2- and 5-s points may not fully represent absolute initial rates. It was saturable with respect to the interaction of Ca2+ and Na+ with an apparent (5 s) Km for Na+-dependent Ca2+ uptake of 10 microM, and an apparent (5 s) Vmax of 0.33 nmol/mg protein per 5 s. The Na+ concentration that yielded half maximal Ca2+ efflux (2 s) was 11 mM, and the Hill coefficient was two or greater. Both Na+ gradient dependent and independent Ca2+ efflux were decreased in BLMV prepared from kidneys of thyroparathyroidectomized (TPTX) dogs, and both were stimulated by parathyroid hormone (PTH) infusion to TPTX dogs. BLMV from TPTX dogs exhibited significantly reduced maximal stimulation of Na+ gradient-dependent Ca2+ uptake with an apparent (5 s) Vmax of 0.23 nmol/mg protein per 5 s, but the apparent Km was 8 microM, which was unchanged from normal. The Na+ gradient independent Ca2+ uptake was also reduced in BLMV from TPTX dogs compared with normal. Thus, PTH stimulated both Na+/Ca2+ exchange activity and Na+ independent Ca2+ flux. In vivo, the latter could result in an elevation of cytosolic Ca2+ by PTH, and this might contribute to the observed decrease in solute transport in the proximal tubule.

Adenosine Triphosphate↗
PubMed1984

Fibrous defect (nonossifying fibroma) of the mandible.

Two cases of fibrous defect (nonossifying fibroma) of the mandible are presented. Each case occurred in the mandibular ramus of an 11-year-old girl. The usual fibrous defect of bone is an intraosseous fibrous, nonneoplastic, reactive lesion which appears as a well-delineated defect in the metaphysis of long bones. This report reviews the literature, histopathology, and classification of the fibrous defect of bone.

Child↗