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Biomedical subjects

S S Shapiro

Publications and source records attributed to S S Shapiro.

At least 19 recordsLinked to original sources
PubMed1992

Tumor necrosis factor-alpha modulation of glycoprotein Ib alpha expression in human endothelial and erythroleukemia cells.

Glycoprotein Ib alpha (GpIb alpha) is a platelet membrane Gp that binds von Willebrand factor and mediates platelet adhesion to subendothelium. We have found both GpIb alpha mRNA and protein in human umbilical vein endothelial cells (HUVEC). In previously published work we reported that combined treatment with interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) markedly increased the GpIb alpha mRNA level in HUVEC. We have now documented that TNF-alpha alone induces GpIb alpha mRNA and protein expression, studied the kinetics of this response, and investigated potential mechanisms of the TNF-alpha effect. GpIb alpha mRNA induction by TNF-alpha is detectable as early as 2 hours after exposure to this cytokine, and reaches a maximal level after 20 to 24 hours. Using a nuclear run-on assay we found that GpIb alpha gene transcription is increased approximately 10-fold after 2 hours of TNF-alpha treatment. Furthermore, using two monoclonal antibodies that recognize different epitopes of GpIb alpha, we found that the protein expression in endothelial cells is markedly increased by TNF-alpha. Interleukin-1 (IL-1) and the phorbol ester phorbol myristate acetate, which mimic many effects of TNF-alpha on endothelial cells, have no effect on endothelial or human erytholeukemia (HEL)-cell GpIb alpha mRNA. TNF-alpha treatment for 24 hours increases the HEL cell GpIb alpha mRNA level approximately fourfold, showing a time- and dose-dependent effect similar to that seen in HUVEC. TNF-alpha-induced GpIb alpha mRNA and protein synthesis may play a role in mediating platelet or other cell interaction with activated endothelium. Unlike other endothelial pro-thrombotic and pro-adhesive proteins induced by TNF-alpha, GpIb alpha is not induced by IL-1 treatment, which suggests a novel pathway for induction of this protein.

Blotting, Western↗
PubMed1992

Longitudinal study of semen quality in Wisconsin men over one decade.

To determine whether there has been a time-related change in semen quality, we examined a Wisconsin population of men over a 10-year period. The semen quality of potential sperm donors was assessed between the years 1978 and 1987. The semen analyses included sperm concentration, motility, and morphology. No significant changes over time were observed for sperm concentration or motility. The percentage of morphologically abnormal sperm rose sharply between 1982 and 1983. This, however, coincided with a change in criteria used to identify abnormal sperm, and was, therefore, due to a procedural artifact. In summary, we found no evidence of a decline in semen quality in our Wisconsin population over a 10-year period.

Humans↗
PubMed1991

Ultrastructural effects of UVB radiation and subsequent retinoic acid treatment on the skin of hairless mice.

The ultrastructure of hairless mouse skin exposed to UVB radiation and followed by retinoic acid treatment was studied to identify alterations induced in both epidermis and dermis. Female mice were irradiated 3 times weekly for 5-6 months; a group of these mice was then treated topically 3 times weekly for 10 weeks with either 25 micrograms all-trans-retinoic acid dissolved in acetone or with acetone alone. Age-matched, unexposed, untreated mice served as controls. Cutaneous changes induced by UVB radiation included keratinocyte mitochondrial inclusions often accompanied by damaged cristae, duplication of basement membrane, increased number of dermal fibroblasts, inflammatory cells and elastic fibers, and abnormal elastic fibers. Subsequent retinoic acid treatment resulted in more prominent mitochondrial inclusions which sometimes coalesced to form irregular contoured bodies. Also observed were lipid droplets in the stratum corneum, glycogen deposits in keratinocytes and granular material in dilated keratinocyte endoplasmic reticulum. Poorly differentiated epidermis with necrotic or apoptotic cells was present in some specimens. Elastic fibers were fewer and usually morphologically normal. Skin exposed to UVB and treated with vehicle appeared similar to control except for the presence of excess basement membrane and occasional small mitochondrial inclusions. Because of the heightened concern regarding UV radiation-induced damage to the human skin and the current topical use of retinoids, the cutaneous changes described are considered worthy of attention.

Animals↗
PubMed1990

Cytokine-enhanced expression of glycoprotein Ib alpha in human endothelium.

Platelet glycoprotein Ib is a major platelet membrane protein composed of two disulfide-linked chains, termed the alpha and beta chains. The larger alpha chain (GpIb alpha), a platelet receptor for von Willebrand factor, plays a major role in mediating platelet adhesion to the subendothelium. Our laboratories have previously reported synthesis of a protein in human endothelial cells that is immunoprecipitated with polyclonal and monoclonal antibodies to platelet GpIb alpha. Lopez et al. (Lopez, J. A., Chung, D. W., Fujikawa, K., Hagan, F. S., Papayannopoulou, T., and Roth, G. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5615-5619) have reported the cloning of GpIb alpha from a human erythroleukemia (HEL) cell cDNA library. Using this clone as probe, we have isolated two partial GpIb alpha clones from a human umbilical vein endothelial cell lambda gt11 cDNA library. These clones were localized within HEL-derived GpIb alpha cDNA by sequence and restriction enzyme analysis. Additionally, they detected the same message species in HEL and tonsilar RNA that was detected with the HEL GpIb alpha cDNA. Low level GpIb alpha mRNA expression was detected in cultured human umbilical vein endothelial cells, which was increased by treatment of the cells with tumor necrosis factor-alpha. This effect was enhanced by pretreatment with interferon-gamma. Additionally, localization of GpIb alpha in endothelium of fresh tonsilar tissue was demonstrated by immunohistochemistry and in situ hybridization. GpIb alpha may play a role in mediating platelet or other effector cell adhesion to activated endothelium.

Cloning, Molecular↗
PubMed1990

Retinoid effects on sebocyte proliferation.

The human sebocyte model offers several advantages over the current animal models. Foremost among these is the correlation of in vitro activity with clinical results, which was not true for arotinoids in the animal models. It is also possible to study several parameters (total cell number, [3H]thymidine uptake, protein and lipid composition/synthesis, hormone response, receptor regulation, etc.) in the same system. The proliferation of isolated sebocytes is inhibited by retinoids, such as isotretinoin and tretinoin, which are known to be clinically active in human acne. Sebocytes are not responsive to the arotinoid temarotene, which is active in the aforementioned animal models and against dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma but inactive clinically in acne. Additionally, this model is not responsive to etretinate, a compound known to be active in psoriasis but inactive in acne. The in vitro model is, therefore, more predicative of clinical efficacy than the animal models alone.

Cell Division↗
PubMed1990

Retinoid effects on photodamaged skin.

The effects of retinoid treatment on wrinkling in the hairless mouse can be understood in the context of the repair of the dermal elastosis. The two isomers of retinoic acid do not differ qualitatively in their effects on the histological appearance of the tissue or on the wrinkling patterns produced. The all-trans isomer is slightly more potent in this system than the 13-cis isomer but substantially more irritating, which may limit the maximum degree of repair attainable. The "reconstructed" dermis is thickened, it contains new collagen as a result of the stimulation of gene expression, and the tangled, disorganized elastin is packed into a thin layer in the lower dermis. Thus, the framework within which a wrinkle had been established is eliminated, and the skin assumes a normal state, as observed. That the effacement is apparently permanent is additional evidence of the relationship between the integrity of the elastic fiber network and the surface appearance. The only difference in the repaired skin is the absence of filamentous surface features. The thickening effect of UVB and subsequent retinoid treatment on the epidermis does not contribute substantially to the overall thickness of the repaired skin. Nevertheless, despite having a minor role in the effacement of deep wrinkles, these epidermal changes evidently preclude the formation of fine surface features. The model is a valid one for the repair of photodamaged skin. From what is known about the role of elastin in maintaining skin integrity and from the association of wrinkling with excessive sun exposure, it is encouraging to observe the dual effect of retinoic acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Relative efficiency of therapeutic donor insemination using a luteinizing hormone monitor.

A prospective randomized study was performed to evaluate the use of a urinary luteinizing hormone (LH) detection kit with 1 insemination as compared with 2 alternate day inseminations with timing based on previous cycle length and basal body temperature changes. The study involved 60 patients who underwent a total of 264 therapeutic donor insemination cycles using cryopreserved semen specimens. Patients alternated LH-kit timed cycles with cycles timed by non-LH methods for a total of 6 cycles or until pregnancy was achieved. Fecundability rates were 12.3% for LH-kit cycles and 5.3% for non-LH method cycles. The difference in outcome was not statistically significant. However, when the LH kit plus 1 insemination was compared with 2 inseminations timed by conventional methods, there appeared to be a distinct monetary and time expenditure advantage. These findings suggest that sufficient advantage may be derived from use of an LH kit to recommend its use on a routine basis for the timing of therapeutic donor insemination.

Adult↗
PubMed1990

Mitochondrial inclusions in keratinocytes of hairless mouse skin exposed to UVB radiation.

Mitochondrial inclusions were observed in keratinocytes during an ultrastructural investigation of the skin of hairless mice exposed to UVB radiation. Mice were irradiated 3 times a week for 5-6 months with sunlamps at individual doses seldom exceeding 0.06 J/cm2. Strips of dorsal skin were processed for electron microscopic examination; blocks were sectioned to include both epidermis and dermis. Mitochondrial inclusions were observed in keratinocytes of the basal, spinous and granular layers. They were spherical in shape and of moderate and homogeneous electron density. Mitochondria toward the upper regions of the epidermis were swollen and had fragmented cristae; mitochondria in the lower areas of the epidermis usually contained smaller and less dense inclusions and intact or partially disrupted cristae. Because mitochondria are essential in providing the energy for cellular function, keratinocyte mitochondrial damage induced by UVB radiation may have serious pathological consequences. Possible mechanisms involved in mitochondrial inclusion formation are suggested.

Animals↗
PubMed1990

Pregnancy outcome, health of children, and family adjustment after donor insemination.

We evaluated the pregnancies of 427 women who conceived through artificial insemination by donor (AID) at our clinic over a 12-year period. Initial phone contact was followed by a questionnaire. Outcome was known for 594 of the 606 pregnancies, with a total of 502 live-born children including 15 sets of twins. The spontaneous abortion rate was 16.5%, with no difference between fresh- and frozen-semen pregnancies. Significant correlations were found between spontaneous abortion rate and maternal age (P less than .001) and spontaneous abortion rate and cycle of conception (P less than .025). Follow-up was completed on 481 children, among whom the following were found: one chromosomal anomaly, 22 major congenital anomalies, four children with possibly syndromic conditions, and 38 with minor congenital anomalies. Of the school-aged children, 5.8% had recognized learning disabilities and 10.5% were considered gifted by their schools. We also investigated the psychological impact of AID on each family. The majority of couples (71.7%) informed their obstetricians of the AID. Half of the couples did not tell any family or friends. Many couples did not (47%) or probably did not (14%) plan to tell their children of their origins. The divorce rate among those with AID children was 7.2%, which was significantly less (P less than .01) than that in a matched population. Psychological counseling specifically related to AID was sought by 2.8% of the couples. We conclude that AID children are at similar risk for congenital anomalies as normally conceived children, but they experience lower rates of family dissolution.

Abortion, Spontaneous↗
PubMed1989

Successful treatment in two women with antiphospholipid antibodies and refractory pregnancy losses with intravenous immunoglobulin infusions.

In two women with antiphospholipid antibodies and recurrent fetal losses refractory to usual treatments, therapy consisting of aspirin, heparin, and intravenous gamma-globulin infusions was successful. Production of antiphospholipid antibodies was not suppressed. The transient decrease in anticoagulant activity noted in one case was not reproduced in vitro and was probably not physiologically important.

Abortion, Habitual↗
PubMed1989

Effect of dietary lipids on hepatic and plasma beta-carotene and vitamin A levels in rats fed beta-carotene.

Diets low in carotenoids have been associated with greater risks of developing certain cancers. Diets high in fats, especially unsaturated fats, have also been associated with increased risks of developing cancer. This study was undertaken to evaluate the effect of fat type on the beta-carotene status in a rat model. Rats were fed diets containing 2 g/kg beta-carotene or placebo and either 10% lard or corn oil for 13-16 weeks. Plasma vitamin A was unaffected by the dietary regimes. Liver vitamin A levels were significantly increased in the beta-carotene groups and were greater in the lard-fed animals. No detectable level of plasma beta-carotene was found in the rats fed placebo diets. In animals given dietary beta-carotene, plasma beta-carotene levels were significantly reduced in the group fed corn oil compared to the group fed lard. Liver beta-carotene levels were higher in the groups fed corn oil. The results suggest that the type of dietary fat can significantly affect the circulating and tissue levels of beta-carotene.

Animals↗
PubMed1989

Progesterone altered amino acid accumulation by human endometrium in vitro.

When human endometrium is exposed to progesterone, the rate of amino acid incorporation into its protein pool is altered. Accumulation into specific proteins has been evaluated by one-dimensional polyacrylamide gel electrophoresis. Comparison of steroid-exposed and nonexposed tissue has revealed a change in the rate of radiolabeled amino acid uptake into a few stained protein bands. To further characterize the effect of progesterone on endometrial protein metabolism, we have examined the one-dimensional electrophoretic band that undergoes the greatest change in leucine accumulation using two-dimensional gel and monoclonal antibody technologies. The band of interest results from altered amino acid uptake into a single protein spot on two-dimensional gels. This particular protein has an approximate size of 50 kDa and pI of 5.8. It exists in a monomeric form under nondenaturing conditions. During organ culture of proliferative endometrium exposed to 0.1 micrograms/ml progesterone, there is a sixfold increase in the rate of methionine uptake into this protein. The rate of amino acid accumulation is maximal after 24 h of culture in medium containing progesterone. Partial purification provided a product enriched 120-fold for this specific protein and facilitated development of a monoclonal antibody that was used to identify the protein in several human tissues besides endometrium. Antibody-antigen complex could not be detected in medium from secretory endometrium, suggesting that this protein resides in the cytosol without being secreted by the tissue.

Adult↗
PubMed1989

Diagnosis and resection of an oral contraceptive-suppressible Sertoli-Leydig cell tumor with preservation of fertility and a 7-year follow-up.

A 21-year-old white woman presented with virilization, hirsutism, and acne of 1.5 years' duration. Endocrine testing demonstrated complete suppression of serum testosterone, from 5.3 to 0.6 ng/mL, and serum androstenedione, from 4.7 to 1.7 ng/mL, after oral administration of 50 micrograms of mestranol and 1 mg of norethindrone for 21 days. No suppression of either steroid was produced by dexamethasone, whereas serum dehydroepiandrosterone sulfate was suppressed from 5.2 to 1.9 micrograms/mL. A left salpingo-oophorectomy was performed for a 3 x 4-cm Sertoli-Leydig cell tumor of intermediate differentiation. Intraoperative studies demonstrated that the tumor secreted testosterone, androstenedione, 17 alpha-hydroxyprogesterone, and estradiol, but not dehydroepiandrosterone sulfate. These findings support the thesis that hormonal manipulation tests cannot differentiate between adrenal and ovarian virilizing tumors. Nor does the oral contraceptive suppression of testosterone secretion exclude an ovarian malignancy. The patient remains free of recurrence after 7 years.

Adult↗
PubMed1988

Human monocytes generate basophil histamine-releasing activities.

Human peripheral blood monocytes generated activities during 24-h culture that were capable of triggering histamine release from 17 of 18 human basophil donors. Monocytes and their in vitro transformed macrophages continued to elaborate these basophil histamine-releasing activities for at least 3 wk in culture. In the 18 basophil donors tested, maximum histamine release induced by monocyte supernatants was 33.8 +/- 5.9% (mean +/- SEM) of total basophil histamine content; optimum anti-IgE-induced release was 38.8 +/- 6.2%. Basophil histamine release in response to monocyte activities was optimal at 37 degrees C and at calcium concentrations of 2 to 5 mM. Release was greater than 90% complete 1 min after challenge and was inhibited by anti-allergic drugs. The mechanism of release appeared to be independent of IgE binding. Gel filtration of supernatants derived from both day 1 (monocyte stage) and day 14 (macrophage stage) cultures demonstrated activity peaks with approximate m.w. of 12,000 and 30,000. In contrast to the marked responsiveness of basophils, only 2 of 10 human lung mast cell preparations responded; release in those preparations was low: 3% and 13% histamine release, respectively. Thus, monocytes produce potent histamine-releasing activities with differential actions on basophils and mast cells.

Basophils↗
PubMed1988

Freezing of mammalian embryos without the aid of a programmable freezer.

A simple, inexpensive and repeatable method of freezing/thawing (F/T) mammalian concepti was developed with the use of 2-cell mouse embryos. Cryoprotectants, length of exposure to protectants, and subzero holding times before liquid nitrogen (LN2) exposure were examined in an effort to obtain an effective freezing protocol. Sequential examination of these variables provided data suggesting that 3.5 M dimethyl sulfoxide (DMSO) plus 0.25 M sucrose exposure for 5 minutes at room temperature, followed by a -30 degrees C environment for 90 minutes, best prepared embryos for LN2 storage. After thawing and culture, 48 of the 93 (52%) embryos developed to the blastocyst stage.

Animals↗