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S B Horowitz

Publications and source records attributed to S B Horowitz.

At least 19 recordsLinked to original sources
PubMed1999

Thalidomide-induced toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) is a severe dermatologic disorder associated with mortality of up to 30%. Withdrawal of the causative agent is crucial in its management. Although thalidomide-induced dermatologic disorders rarely were reported before thalidomide was administered to patients positive for the human immunodeficiency virus, hypersensitivity reactions including rash are the agent's major dose-limiting toxicities in this population. As it is prescribed for other immunosuppressed patients, such as those with malignancies, the frequency of dermatologic reactions (including TEN) may increase. A 62-year-old woman developed TEN after approximately 5 weeks of thalidomide therapy for the treatment of a glioblastoma.

Angiogenesis Inhibitors↗
PubMed1997

A recommended occupational exposure limit for formaldehyde based on irritation.

In recent years, several regulatory agencies and professional societies have recommended an occupational exposure limit (OEL) for formaldehyde. This article presents the findings of a panel of experts, the Industrial Health Foundation panel, who were charged to identify an OEL that would prevent irritation. To accomplish this task, they critiqued approximately 150 scientific articles. Unlike many other chemicals, a large amount of data is available upon which to base a concentration-response relationship for human irritation. A mathematical model developed by Kane et al. (1979) for predicting safe levels of exposure to irritants based on animal data was also evaluated. The panel concluded that for most persons, eye irritation clearly due to formaldehyde does not occur until at least 1.0 ppm. Information from controlled studies involving volunteers indicated that moderate to severe eye, nose, and throat irritation does not occur for most persons until airborne concentrations exceed 2.0-3.0 ppm. The data indicated that below 1.0 ppm, if irritation occurs in some persons, the effects rapidly subside due to "accommodation." Based on the weight of evidence from published studies, the panel found that persons exposed to 0.3 ppm for 4-6 h in chamber studies generally reported eye irritation at a rate no different than that observed when persons were exposed to clean air. It was noted that at a concentration of 0.5 ppm (8-h TWA) eye irritation was not observed in the majority of workers (about 80%). Consequently, the panel recommended an OEL of 0.3 ppm as an 8-h time-weighted average (TWA) with a ceiling value (CV) of 1.0 ppm (a concentration not to be exceeded) to avoid irritation. The panel believes that the ACGIH TLV of 0.3 ppm as a ceiling value was unnecessarily restrictive and that this value may have been based on the TLV Committee's interpretation of the significance of studies involving self-reported responses at concentrations less than 0.5 ppm. The panel concluded that any occupational or environmental guideline for formaldehyde should be based primarily on controlled studies in humans, since nearly all other studies are compromised by the presence of other contaminants. The panel also concluded that if concentrations of formaldehyde are kept below 0.1 ppm in the indoor environment (where exposures might occur 24 h/d) this should prevent irritation in virtually all persons. The panel could not identify a group of persons who were hypersensitive, nor was there evidence that anyone could be sensitized (develop an allergy) following inhalation exposure to formaldehyde. The panel concluded that there was sufficient evidence to show that persons with asthma respond no differently than healthy individuals following exposure to concentrations up to 3.0 ppm. Although cancer risk was not a topic that received exhaustive evaluation, the panel agreed with other scientific groups who have concluded that the cancer risk of formaldehyde is negligible at airborne concentrations that do not produce chronic irritation.

Animals↗
PubMed1994

Membrane permeability changes during Rana oocyte maturation.

A transition from an open system to a closed one must occur during the complex process of meiotic maturation of the amphibian oocyte. Membrane permeability to urea in Rana oocytes following progesterone stimulation was determined, and the largest decrease was found to coincide with germinal vesicle breakdown. These findings suggest that the timing of the disappearance of membrane permeability correlates with developmental events that prepare the oocyte for a hostile environment.

Animals↗
PubMed1994

Setting health-protective soil concentrations for dermal contact allergens: a proposed methodology.

Health-based cleanup goals for contaminated soils are typically established to protect potentially exposed individuals from increased incidences of cancer and serious noncancer effects. However, at least one regulatory agency has suggested that, for certain contact allergens such as hexavalent chromium, soil remedial goals should also consider the potential occurrence of allergic contact dermatitis (ACD) in sensitized individuals (NJDEPE, 1992). To date, appropriate risk assessment methods for setting ACD-based soil concentrations have not been addressed in the scientific literature. This paper defines and discusses the three key data needs for establishing ACD-based soil concentrations: (1) dose-response data from human patch-testing studies, in which the patch concentrations are reported in terms of mass of allergen per unit area of skin, (2) accurate estimates of the degree to which soil adheres to skin on a soil mass per unit area of skin basis, and (3) accurate estimates of the degree to which the allergen leaches from soil into human sweat. The requisite basis for each of these factors and suggested methods for obtaining and evaluating the necessary data are presented. In addition, two example calculations are presented for setting ACD-based goals for hexavalent and trivalent chromium in chromite ore-processing residues.

Chromium↗
PubMed1994

Urea transport in frog oocytes: effect of osmotic stress and vasopressin.

The transport of water and urea across biological membranes are considered to traverse separate channels or pores. While vasopressin responsiveness correlates with increased urea/water permeability in some epithelia, oocytes provide a single cell system to determine the coupling relationship. Urea transport under isotonic and hypotonic conditions are determined in full-grown frog oocytes in follicles. We found that urea reached equilibrium distribution (ratio of 14C-urea concentrations inside and outside of the oocyte) rapidly and remained equilibrated over 20 h period, independent of external urea concentrations. Thus, urea uptake is not via an active transport system. While hypotonicity caused oocytes to swell, vasopressin did not exert additional effect. Under hypotonic conditions, distribution ratios of water and urea changed in different ways supporting the view that distinguishable channels (pathways) were involved. It appeared that no correlated changes due to vasopressin occurred under osmotic challenge. The response pattern to vasopressin was different between renal epithelia and frog oocyte.

Animals↗
PubMed1993

Using human sweat to extract chromium from chromite ore processing residue: applications to setting health-based cleanup levels.

Chromite ore processing residue (COPR) containing measurable levels of hexavalent and trivalent chromium. [Cr(VI) and Cr(III), respectively] has been used to fill in low-lying areas in Hudson County, N.J. While it has been demonstrated that direct dermal contact with solutions containing Cr(VI) may elicit allergic contact dermatitis (ACD) in previously sensitized individuals, it is unknown to what degree skin moisture may solubilize Cr(VI) from COPR adhering to skin. An accurate estimate of this extraction potential is necessary to establish COPR concentrations of Cr(VI) and Cr(III) that are protective of eliciting ACD in sensitized individuals. The purpose of this study was to measure the extractable fraction of Cr(VI) and total chromium [Cr(III) and Cr(VI)] in soils impacted by COPR using human sweat as the extractant. Human sweat was collected from seven male volunteers. Samples of COPR material containing the following Cr(VI) and total chromium concentrations were collected: Cr(VI), 16, 136, and 1240 ppm; total chromium, 932 and 6660 ppm. The samples were sieved to obtain a uniform particle size < 500 microns. The samples were then mixed with human sweat at 30 degrees C for 12 h, after which the sweat was filtered and analyzed to determine the dissolved concentration of Cr(VI) and total chromium. The data from these analyses show that no detectable levels (limit of detection = 0.010 ppm) of Cr(VI) were leached from COPR containing 16 ppm Cr(VI). At Cr(VI) concentrations of 136 and 1240 ppm, less than 0.1% of the Cr(VI) present in the COPR sample was extracted into sweat, and sweat concentrations were 0.133 ppm Cr(VI) or less. Similarly, the amount of Crtotal extracted was 0.3% or less at COPR concentrations as high as 6600 ppm Crtotal, and sweat concentrations were 2.3 ppm Crtotal or less. If a minimum concentration of 10 ppm (Bagdon and Hazen, 1991) to 54 ppm (Paustenbach et al., 1992) Cr(VI) in sweat is required to elicit an ACD response in chromium-sensitive individuals, the current study results suggest that a COPR Cr(VI) concentration of at least 10,000-54,000 ppm would be required to elicit ACD. If 500 ppm (or greater) of solubilized Cr(III) is required to elicit an ACD response (NJDEPE, 1992a), then a COPR concentration of 250,000 ppm Cr(III) or greater would be required to elicit an allergic response. These results suggest that ACD is unlikely to occur as a result of environmental exposure to the COPR.

Adult↗
PubMed1989

Gonadotropin stimulates oocyte translation by increasing magnesium activity through intracellular potassium-magnesium exchange.

We previously showed that gonadotropin increases the K+ activity in Xenopus oocytes and that this is a signal for increased translation. However, K+ need not act to control synthesis directly but may act through an unidentified downstream effector. Using microinjection to vary the salt content of oocytes and concomitantly measuring [3H]leucine incorporation, we found that small changes in Mg2+ greatly affect translation rates. (Ca2+ had little influence.) By measuring intracellular ion activities, we found that oocyte cations existed in a buffer-like (ion-exchange) equilibrium in which K+ and Mg2+ are the preponderant monovalent and divalent cations. Hence, increasing cellular K+ activity might increase translation by causing Mg2+ activity to rise. If so, the increased translation rates produced by hormone treatment or K+ injection would be prevented by EDTA, a Mg2+ chelating agent. This prediction was tested and confirmed. We conclude that, when gonadotropin increases K+ activity, the cell's internal ion-exchange equilibrium is altered thereby increasing Mg2+ activity and this up-regulates translation.

Animals↗
PubMed1988

Potassium salt microinjection into Xenopus oocytes mimics gonadotropin treatment.

Gonadotropin stimulates protein synthesis and growth in ovarian oocytes. The hormone is also known to modify transfollicular K+ fluxes and is now shown to cause increased intraoocytic K+ activity (aK). The hormone's effect on aK was duplicated by microinjecting K+ salts into oocytes which were incubated in paraffin oil. This treatment mimicked the influence of gonadotropin on both the rate of protein synthesis and the synthesis of specific polypeptides. These findings suggest that gonadotropin-stimulated oocyte growth is attributable largely to the hormone's influence on transfollicular K+ fluxes. They support the hypothesis that the K+ flux and aK changes observed during cell activation are critical in causing subsequent increases in protein synthesis and growth.

Animals↗
PubMed1988

A function that relates protein synthetic rates to potassium activity in vivo.

A newly developed experimental system allows the controlled alteration of intracellular K+ activity (aK) and the measurement of amino acid incorporation rates in a single cell, the Xenopus oocyte. We found that as aK is increased by microinjecting a K+ salt, [3H]leucine incorporation (R) varies over a 100-fold range, first stimulated and then inhibited as it passes through four response regions (A-D). In region A (aK approximately 60-100 mM), R is at a nongrowth or maintenance level and is stimulated weakly by increasing aK. In region B (aK approximately 100-130 mM), R is stimulated intensely by increasing aK, roughly tripling with every 10 mM increase. In region C (aK approximately 130-160 mM), R is inhibited intensely by increasing aK. Finally, in region D (aK greater than 160 mM), R is inhibited weakly as aK increases. Collectively, the four response regions constitute the oocyte's R/aK response function. The function provides a comprehensive description of how K+ activity influences the rate of protein synthesis in an intact cell. In the subsequent discussion, we compared the oocyte response function with the K+ response determined in cell-free translational systems. While in vivo and in vitro functions are similar, differences exist that may be important in a cellular control system. We then considered the relevance of the oocyte R/aK response function to "normal" processes in the oocyte and in somatic cells, i.e., those in which aK is varied by physiological changes in the plasma membrane. We concluded that the intensely stimulatory region B is importantly involved in hormonal action and other growth-activating processes and that the entire R/aK response function may play a role in control of protein synthesis during the cell cycle.

Animals↗
PubMed1986

Intracellular compartmentalization of adenosine triphosphate.

The intracellular distribution and diffusivity of adenosine triphosphate (ATP) was studied by cryomicrodissection of individual Rana pipiens oocytes. We measured ATP concentrations in the nucleus, in animal and vegetal hemisphere cytoplasm, and in an intracellular reference phase (iRP, a microinjected gelatin "organelle") which samples diffusive ATP. Regional concentrations were not equal: nucleus much greater than animal ooplasm greater than vegetal ooplasm. ATP binding and water availability (as solvent) were determined by plotting nuclear and cytoplasmic ATP concentrations as a function of reference phase ATP concentrations (isothermal analysis). The nucleus/iRP isotherm for ATP was an equimolar line, showing that nucleoplasm resembles iRP gelatin (and consequently a simple aqueous solution) in its solvent properties. Cytoplasm/iRP isotherms were more complex, having slopes much less than unity and ordinal intercepts above the graph's origin. They demonstrate the presence in cytoplasm of mechanisms that are capable of excluding and binding ATP. These mechanisms are responsible for the inhomogeneity in ATPs intracellular distribution. In addition, exclusion and binding have different and opposing effects on ATP concentrations in the cell's "soluble space," and hence on ATP availability to enter into cellular reactions. It follows that these phenomena must be considered in attempts to model ATPs role in metabolism.

Adenosine Triphosphate↗
PubMed1984

Water, potassium, and sodium during amphibian oocyte development.

Water, K+, and Na+ were measured in Rana pipiens oocytes during growth and prematurational development using low-temperature microdissection. Whole oocytes were analyzed during previtellogenic and vitellogenic growth. Ooplasm and germinal vesicle (nucleus) were analyzed at the onset and conclusion of vitellogenic growth. In previtellogenic oocytes (less than 40 micrograms), water, K+, and Na+ concentrations resembled those in somatic cells and were independent of cell size. With the onset of yolk deposition, water and K+ concentrations progressively decreased and Na+ progressively increased. These changes were restricted to ooplasm, the site of yolk deposition. In full-grown oocytes, vegetal ooplasm, with greater yolk density than animal ooplasm, contained less water and K+ and more Na+ than animal ooplasm. Collectively, the data indicate that yolk is poorer in water and K+ and richer in Na+ than yolk-free ooplasm (cytoplasm) or nucleoplasm. Yolk concentrations were estimated to be approximately 32%, water, approximately 69 meq K+/liter H2O, and approximately 94 meq Na+/liter H2O. Several nonyolk parameters, such as cation activities and nucleoplasmic binding, also appear to change during oogenesis.

Animals↗
PubMed1984

Regional water changes during oocyte meiotic maturation: evidence of ooplasmic segregation.

Cryomicrodissection was used to measure the intraoocytic distribution of water before and during meiotic maturation in Rana pipiens oocytes. Animal ooplasm contained about 10% more water in matured than in ovarian oocytes. The increase was not dependent on the uptake of extracellular water, occurring even when oocytes were matured in a paraffin oil medium. Rather, animal ooplasm hydration appeared to be due to an increase in the volume fraction occupied by cytoplasm (reduced yolk density) through: (1) migration of cytoplasm from the vegetal to animal hemisphere and (2) mixing of ooplasm with nuclear sap during germinal vesicle breakdown (GVBD). Cytoplasmic migration (or ooplasmic segregation) began prior to GVBD, probably within an hour of exposure to progesterone and appeared to continue through the period of GVBD. The volume of cytoplasm that moved significantly reduced water concentrations in vegetal ooplasm at 6 hr postprogesterone and offset any subsequent water gain due to the mixing of nuclear sap and vegetal ooplasm at GVBD. The findings suggest that segregational movements are among the early maturational changes entrained by progesterone. Ooplasmic segregation is considered in the context of theories of cytomatrix movement in which control resides in regional Ca2+ activity gradients. We address the problem of the vegetal----animal directionality of movement and suggest that the annulate lamellae play a role.

Animals↗
PubMed1984

Artifacts caused by cell microinjection.

The effects of microinjection on Rana pipiens oocytes were determined using cryomicrodissection to measure Na, K, water, and injected radiolabeled sucrose (in gelatin) in the nucleus, animal, and vegetal ooplasm and injected bolus (reference phase, RP). The results point to potential problems in the interpretation of microinjection experiments. When oocytes were injected and incubated in Ringer's solution, nucleus, ooplasm, and RP lost K and sucrose and gained Na. Patterns of loss and gain were complex but were consistent with continuous solute leakage at the injection site causing artifactual intracellular diffusion gradients. In spite of leakage, oocytes completed scheduled meiotic maturation when exposed to progesterone. When oocytes were microinjected and incubated in paraffin oil (a medium in which polar solutes cannot exchange), nuclear and ooplasmic Na, K, and water concentrations remained identical to those in uninjected cells. Neither microinjection per se nor the injected bolus affected intraoocytic solute distributions. These findings imply that, after microinjection in aqueous media, metabolites are lost from and redistribute in cells, and that these artifactual changes are inadequately reflected in the ability of the cell to carry out a complex process. They also show that injection artifacts can be avoided by injecting and incubating cells under paraffin oil.

Animals↗
PubMed1984

Solvent properties of ground substance studied by cryomicrodissection and intracellular reference-phase techniques.

Water, sodium, potassium, ATP, amino acids, and sugars are not uniformly distributed in Rana pipiens oocytes. Concentration differences exist between nucleus (germinal vesicle) and ooplasm and between animal and vegetal ooplasmic regions. The mechanisms responsible for these differences were investigated using intracellular reference-phase (iRP) analysis. The iRP is an artificial "organelle" that has the solvent properties of a dilute salt solution and is in diffusional equilibrium with water and solutes present in other cellular compartments. Ooplasm/iRP solute distributions show that ooplasm differs from ordinary aqueous solutions--exhibiting both solute exclusion and solute binding. Yolk platelets are an important cause of this behavior, largely because their proteins are present as hydrate crystals, which are rich in anionic sites and which interact intensely with associated water. Because of yolk's abundance, it obscures the solvent and binding properties of ooplasmic ground substance. The oocyte nucleus is yolk and organelle free and the nuclear envelope is readily permeable. Consequently, nucleus/iRP solute concentration differences reflect the binding and solvent properties of nuclear ground substance. Nucleoplasm binds approximately 19 meq of potassium. Furthermore, the monosaccharides, 3-O-methylglucose, L-glucose, and D-xylose, are selectively excluded, their nucleus/iRP concentration ratios averaging about 0.7; ratios for other solutes studied are unity. We interpret monosaccharide exclusion to mean that nuclear ground substance water is different in its "instantaneous" structure from ordinary saline water. Because of this difference, hydrogen bond interaction between nuclear water and certain sterically restricted solutes, of which ringed monosaccharides are examples, is reduced. Some implications of modified ground substance water and selective solute exclusion are discussed.

3-O-Methylglucose↗
PubMed1983

Protein loss during nuclear isolation.

Cryomicrodissection makes possible the measurement of the entire in vivo protein content of the amphibian oocyte nucleus and provides a heretofore missing baseline for estimating protein loss during nuclear isolation by other methods. When oocyte nuclei are isolated into an aqueous medium, they lose 95% of their protein with a half-time of 250 s. This result implies an even more rapid loss of protein from aqueously isolated nuclei of ordinary-size cells.

Animals↗
PubMed1981

Intracellular monosaccharide and amino acid concentrations and activities and the mechanisms of insulin action.

Current amino acid and monosaccharide transport models are based on an assumption which equates the intracellular chemical activity of a solute with its concentration. This assumption was tested for alpha-aminoisobutyric acid and 3-O-methylglucose in a giant cell, the amphibian oocyte, by using recently developed cryomicrodissection and internal reference phase techniques. We found the following. (i) alpha-Aminoisobutyric acid and 3-O-methylglucose activities were much greater in cytoplasm than was suggested by concentration data; i.e., activity coefficients were higher than in ordinary water solutions. This is attributable to the inaccessibility of considerable water as solvent (solute exclusion). (ii) Solute concentrations varied regionally as follows: nucleus > > animal cytoplasm > vegetal cytoplasm. Insulin increased the nucleus/cytoplasm concentration asymmetry, apparently by increasing cytoplasmic solute exclusion. (iii) Nuclear activity coefficients more closely resembled those of ordinary saline solutions so that nucleus/ extracellular concentration ratios reflected transmembrane activity gradients better than did cytoplasm (or whole cell)/extracellular ratios. (iv) Mediated passive alpha-aminoisobutyric acid and 3-O-methylglucose transport were constituent oocyte membrane properties. Membrane active transport was initiated with time (in the presence of substrate) and by insulin. (v) Increased temperature mimicked insulin in enhancing transmembrane alpha-aminoisobutyric acid activity gradients and increasing the nucleus/cytoplasm concentration asymmetry. These results indicated that concentration data are a misleading measure of cellular amino acid and monosaccharide activity; some consequences of this observation were explored. A model is proposed in which cell water has reduced solvent capacity or is compartmentalized (considered less likely) and is susceptible to physiological modulation. The model accounts for many observations in small cells, suggesting generality of the exclusion phenomenon and a previously unrecognized metabolic control mechanism.

3-O-Methylglucose↗