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Biomedical subjects

A Weiss

Publications and source records attributed to A Weiss.

At least 325 records · Page 18Linked to original sources
PubMed1986

Synergy between the T3/antigen receptor complex and Tp44 in the activation of human T cells.

In addition to the T3/antigen receptor complex (T3/Ti), other T cell surface molecules participate in early events involved in human T cell activation. In this report we document that monoclonal antibody 9.3, which recognizes a 90,000 dalton homodimer expressed on human T cells, synergizes with ligands reacting with T3/Ti to activate purified T cells and Jurkat, a human T cell leukemic line. Unlike phorbol myristate acetate (PMA), 9.3 was able to synergize only with anti-T3 or anti-Ti if these antibodies were immobilized. Moreover, 9.3 failed to synergize with the calcium ionophore ionomycin. At high concentrations only, 9.3 could synergize with PMA in the activation of Jurkat and a T3/Ti negative mutant of Jurkat. At such high concentrations of 9.3, small transient increases in cytoplasmic free calcium ((Ca++)i) were detected in quin 2-loaded Jurkat cells. This increase in (Ca++)i was the result of release of internal stores of calcium. 9.3 induced the hydrolysis of polyphosphoinositides, albeit the magnitude of inositol phosphates generated in response to 9.3 was substantially less than that observed with anti-Ti. No effect on pkC translocation was observed in Jurkat cells stimulated with 9.3. Although the small increase in (Ca++)i induced by 9.3 may account for its synergy with PMA, this effect is unlikely to account for the more potent synergistic effect observed with 9.3 and phytohemagglutinin or immobilized anti-T3 and anti-Ti antibodies.

Antibodies, Monoclonal↗
PubMed1986

Psammomatoid ossifying fibroma.

Fibro-osseous lesions represent a variety of bone proliferations each characterized by different morphologic patterns of osteoid production. Psammomatoid ossifying fibroma (POF) is characterized histologically by numerous small round ossicles resembling psammoma bodies and is a locally invasive lesion of facial and cranial bones. Two cases of POF arising in the ethmoid sinus and involving the orbit are presented to emphasize the importance of complete surgical removal of involved bones. Histologically, portions of POF may demonstrate other patterns of osteoid production, which resemble fibrous dysplasia and Paget's disease of bone. The variation in radiodensity in POF on computed tomography is a function of the density of psammomatoid ossicles and of the coexistence of other "minor" forms of bone proliferation.

Child↗
PubMed1986

An epidemic of maternal thrombocytopenia associated with elevated antiplatelet antibody. Platelet count and antiplatelet antibody in 116 consecutive pregnancies: relationship to neonatal platelet count.

Twenty-eight (24%) of 116 pregnant women studied prospectively during an 8-month period in 1983 had platelet counts of less than 150,000/mm3 at least once during pregnancy. Thirteen of these were thrombocytopenic in both the prenatal and the peripartum period. Eighteen were restudied 3 to 12 months after delivery. One woman, who was pregnant again, had a platelet count of 140,000/mm3. In the others, platelet counts were in the normal range. Platelet-associated immunoglobulin G and serum antiplatelet antibody levels were elevated in 79% and 61%, respectively, of these 28 women on at least one occasion. However, 59% of 73 pregnant nonthrombocytopenic women had increased platelet-associated immunoglobulin G levels and 59% had positive serum antiplatelet antibody test results. Twenty women who had increased platelet-associated immunoglobulin G levels and positive serum antiplatelet antibody test results were normal 6 to 10 months after delivery. Of 105 infants studied, 10 were thrombocytopenic. Neonatal thrombocytopenia was not predicted by maternal platelet count, platelet-associated immunoglobulin G, or serum antiplatelet antibody. By the fall of 1984, the incidence of thrombocytopenia had dropped to two in 280 consecutive pregnancies. We conclude that (1) epidemics of thrombocytopenia can occur in pregnant women and (2) if a women is found to be thrombocytopenic for the first time during pregnancy, she should not be subjected to the measures advocated for the management of pregnancy in women with autoimmune thrombocytopenic purpura.

Adult↗
PubMed1986

A tissue culture system supporting cartilage cell differentiation, extracellular mineralization, and subsequent bone formation, using mouse condylar progenitor cells.

Undifferentiated progenitor cells of mandibular condyles of neonatal mice were kept in a tissue culture system for up to 9 days. After 2 days in culture, new chondroblasts developed within the explants, whereas the peripheries of the latter were occupied by undifferentiated cells undergoing mitosis. By 4 days in culture, many of the cartilage cells showed signs of hypertrophy, while the matrix revealed positive reactivity for type II collagen and matrix metachromasia. The process of maturation of cartilage cells appeared to have reached its final stages after 6 days in culture, at a time when the initial loci of matrix mineralization could be easily identified. Concomitantly, peripheral areas bordering the cartilaginous core, as well as portions of the cartilage, reacted positively for type I collagen and fibronectin. Light microscopy examination showed signs of new bone formation after 9 days in culture. The extracellular matrix at the upper portion of the explant, facing the medium-air interface, reacted intensely with antibodies against type I collagen and fibronectin, but not with antibodies against type II collagen. Further, the newly formed osteoid was found to have undergone mineralization, thus forming an expanded layer of new bony tissue. A close spatial association was found between mature, mineralized cartilage and new bone. Hence, we hereby introduce a new in vitro system serving as an experimental model for studies related to the differentiation of progenitor cells into chondroblasts, which in turn promote ossification.

Animals↗
PubMed1986

Structural and metabolic changes characterizing the aging of various cartilages in mice.

It is well documented that various organs and tissues in the body show a differential, non-homogeneous pattern of development and aging. The present study evaluates some of the morphological and metabolic changes characterizing the aging of different types of cartilages in normal male mice. Representatives of hyaline, fibrous, articular and elastic types of cartilage were obtained from animals ranging from 1 week to 1 year of age. Our determinations included the following: total body and organ weights, proteins and DNA concentrations, [3H]leucine and [35S]sulfate uptake. The biochemical assays were accompanied by morphological examinations of corresponding tissue specimens. This investigation clearly indicates that the growth and maturational activities of the various cartilages examined attained their completion at a very early stage of life (1-3 months postnatally). Thereafter, a phase of steady state prevails, followed by a gradual but continuous decline in the various metabolic activities. The morphological findings illustrate the nature of the age-related structural changes. The present findings indicate that a skeletal tissue such as cartilages of various types, tends to age early during the lifespan of the animal.

Aging↗
PubMed1986

Effect of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--I. Growth hormone.

In this report the effects of various receptor blockers on desimipramine (DMI)-induced growth hormone (GH) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker: methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). DMI-induced GH stimulation was not significantly different after DMI i.v. alone (n = 12) than after three days' pretreatment with 12 mg methysergide p.o. in another group of subjects (n = 12). Following combined administration of DMI and propranolol (15 mg i.v.), GH secretion was significantly increased by 25 mg DMI (p less than 0.05) and 50 mg DMI (incomplete block design, n = 18). GH secretion was significantly lower (p less than 0.01) after DMI in combination with 60 mg phentolamine i.v. compared to that after administration of DMI alone in the same group (n = 12). Following 10 mg yohimbine i.v. in combination with DMI (n = 6), the DMI-induced GH increase was also significantly less (p less than 0.05) than that after DMI alone. The DMI-induced GH increase following DMI plus 1 mg prazosin p.o. (n = 12) was comparable to that after DMI alone. The results indicate that the GH-stimulating effect of DMI is primarily related to the ability of DMI to inhibit noradrenaline (NA) reuptake. Should serotonergic receptors be involved in the DMI-induced GH secretion at all, they transmit a positive stimulus. The alpha-1 receptors are most likely not (or not essentially) involved, whereas alpha-2 receptors affect the DMI-induced secretion positively, and beta receptors have an inhibitory effect.

Adolescent↗
PubMed1986

Effects of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--II. Prolactin.

In this report the effects of various receptor blockers on desimipramine (DMI)-induced prolactin (PRL) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker: methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). Following administration of methysergide (12 mg p.o., n = 12), a significantly lower (p less than 0.01) DMI-induced PRL secretion compared to DMI alone in another group of subjects (n = 12) was observed. Combined administration with propranolol (15 mg i.v.) significantly enhanced the DMI-induced PRL secretion compared to DMI 50 mg i.v. alone (n = 18, incomplete block design) (p less than 0.01). Neither combined administration with phentolamine (60 mg i.v., n = 12), yohimbine (10 mg i.v., n = 6), nor prazosin (1 mg p.o., n = 12) significantly influenced the DMI-induced PRL secretion compared to DMI alone in the same subjects. The results of the present study, especially the inhibitory effect on DMI-induced PRL secretion of methysergide, indicate that the primarily noradrenaline (NA) and lesser serotonin (5-HT) reuptake inhibiting antidepressant DMI stimulates PRL secretion via 5-HT neurons. Furthermore, the significantly enhanced PRL release following combined administration of DMI and propranolol suggests that a noradrenergic inhibitory effect also may be involved in the transmission of the PRL stimulus.

Blood Glucose↗
PubMed1986

Effects of receptor blockers (methysergide, propranolol, phentolamine, yohimbine and prazosin) on desimipramine-induced pituitary hormone stimulation in humans--III. Hypothalamo-pituitary-adrenocortical axis.

In this report the effects of various receptor blockers on the desimipramine (DMI)-induced cortisol (ACTH) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker, i.e. methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). In addition, the effect of prazosin on DMI-induced ACTH stimulation was examined. DMI-induced cortisol stimulation was not significantly different after DMI alone (n = 12) from that after three days pretreatment with methysergide (12 mg p.o.) in another group of subjects (n = 12). Neither the combination of DMI plus propranolol (15 mg i.v. n = 18, incomplete block design) nor that of DMI plus phentolamine (60 mg i.v. n = 12) had a significant influence on DMI-induced cortisol secretion. Following combined administration with yohimbine (10 mg i.v.), cortisol secretion was higher compared to that after DMI alone in the same group (n = 6). DMI-induced cortisol secretion was significantly lower (p less than 0.01) following combined administration with prazosin (1 mg p.o. n = 12), as was DMI-induced ACTH secretion (p less than 0.05) in these subjects. The findings of these trials, especially those of the prazosin trial, indicate that DMI-induced stimulation of cortisol and ACTH secretion is attributable to the noradrenaline (NA) reuptake inhibiting effect of DMI, and that the stimulus is transmitted with the aid of noradrenergic alpha-1 receptors. Alpha-2 receptors possibly exert a negative influence on this effect.

Blood Glucose↗
PubMed1986

Traumatic retinoschisis in battered babies.

Five infants who were victims of physical abuse had extensive bilateral retinal hemorrhages on initial evaluation and subsequently developed signs of permanent retinal damage. None showed external evidence of trauma to the eyes. Vitreous hemorrhage developed after a delay of several days or more in three cases that were followed closely from the time of the traumatic incident. In several eyes, apparent intraretinal blood-filled cavities were seen acutely in the macular region and elsewhere. Late scarring of the macula typically had a cystic or crater-like configuration. Electroretinography showed loss or reduction of the positive B-wave with preservation of the negative A-wave in every case. We propose that splitting of the retina resulting from the direct mechanical effects of violent shaking was responsible for all of these findings.

Child Abuse↗
PubMed1986

Expression of T3 in association with a molecule distinct from the T-cell antigen receptor heterodimer.

The T-cell antigen receptor consists of a disulfide-linked heterodimer (Ti) that is associated with another set of three nonpolymorphic, noncovalently linked peptides termed "T3." The cell surface expression of T3 has been thought to depend upon association with Ti. In this study, we demonstrate that T3 can be expressed in the absence of an associated Ti molecule on a T-cell leukemic line, PEER. Instead, on this cell line, T3 appears to be expressed in association with a 55- to 60-kDa glycoprotein that has a peptide backbone of 29 kDa. PEER fails to express Ti alpha-chain transcripts but does express Ti beta- and gamma-chain transcripts. Using a monoclonal antibody that reacts with nonpolymorphic epitopes expressed on Ti, WT31, we demonstrate that PEER fails to react with this antibody but does react with three independently derived anti-T3 antibodies. Moreover, a small subpopulation of T3-positive peripheral blood lymphocytes, like PEER, fails to express the antigenic determinants recognized by WT31. These results suggest that, on these normal lymphocytes, T3 may likewise be associated with a non-Ti molecule. The possibility that the 55- to 60-kDa molecule expressed on PEER, termed "Tp55-60," represents the protein product of the previously identified Ti gamma-chain gene is discussed.

Antibodies, Monoclonal↗
PubMed1986

The role of the T3/antigen receptor complex in T-cell activation.

The role of the T3/antigen receptor complex is summarized by the diagram presented in Figure 4. Signals transmitted through T3/Ti activate a phosphodiesterase. This enzyme acts on its substrate PIP2 to generate two important mediators, IP3 and diacylglycerol. IP3 mobilizes calcium from bound intracellular stones. This increase in [Ca2+]i is one intracellular signal which, in conjunction with others, induces expression of lymphokine genes by influencing pretranslational, presumably transcriptional, events. Several problems remain. Which of the five molecules in the T3/Ti complex serves as the effector molecule in the transmembrane signaling process is not known. Which molecules serve to link T3/Ti to the phosphodiesterase enzyme is under investigation. The role diacylglycerol protein kinase C and other mediators play in signalling activation is not established. Finally, for those events occurring after the early events pictured in Figure 4 that result in gene activation, the sequence is a black box. Approaches to address each of these questions are available, and answers should be forthcoming.

Animals↗
PubMed1986

Differential effect of cyclosporin A on activation signaling in human T cell lines.

Different T cell lines, which can be induced to secrete interleukin 2 (IL-2) in vitro, were used to dissect the effect of cyclosporin A (CsA). The T leukemia cell Jurkat requires an increase in cytoplasmic calcium concentration ([Ca++]i) and phorbol myristate acetate (PMA) for the induction of IL-2 production, which is completely blocked by CsA. Another T cell line, HUT 78, also produces IL-2 in response to a rise in [Ca++]i and PMA; however, in HUT 78, PMA alone induces low levels of IL-2 production that is not blocked by CsA. After treatment with 5-azacytidine, HUT 78 cells produced maximal levels of IL-2 in response to PMA alone without requiring [Ca++]i increasing stimuli. In these cells no inhibitory effect of CsA on PMA-induced activation could be demonstrated. In addition, CsA does not inhibit PMA-induced translocation of protein kinase C. These data suggest that CsA does not globally inhibit IL-2 gene expression, but rather interferes with signaling events of T cell activation.

Azacitidine↗
PubMed1986

A transferrin receptor antibody represents one signal for the induction of IL 2 production by a human T cell line.

We previously demonstrated a two-signal requirement for the activation of the human T cell lines Jurkat and HUT 78. Interleukin 2 (IL 2) production by these lines can be induced by phytohemagglutinin (PHA), T3 antibodies, or calcium ionophores, but only in combination with phorbol myristate acetate (PMA). To obtain further information about surface structures involved in T cell activation, we produced a monoclonal antibody that could substitute for PMA in the activation of HUT 78. This antibody, designated J64, induced IL 2 secretion by HUT 78 in combination with PHA, T3 antibodies, or calcium ionophores, however not by itself. J64 also had other PMA-like effects on HUT 78, such as an increase in IL 2 receptor expression and an inhibition of cell growth. J64 was shown to immunoprecipitate the transferrin receptor (TfR). However, it bound to an epitope different from those recognized by other TfR antibodies and different from the transferrin-binding site. In addition, other previously described TfR antibodies did not, like J64, function as activating stimuli for HUT 78. Possible mechanisms for activation signaling in T cells involving the TfR are discussed.

Animals↗
PubMed1986

Effects of systemic glucocorticoids on the degradation of glycosaminoglycans in the mandibular condylar cartilage of newborn mice.

This investigation studied the early in vivo effects of triamcinolone hexacetonide, a potent fluorinated analogue of cortisol, on the degradation of sulfated proteoglycans in condylar cartilage of newborn mice. While determining the rate of [35S]sulfate release in test and control specimens, it became evident that in hormone-treated animals there was a dose-dependent retardation of the isotope clearance. Further, triamcinolone was found to have increased the half-life of condylar glycosaminoglycans (GAGs) from 16 h in control animals to 31.4 h in hormone-treated ones. Dexamethasone, another fluorinated analogue of cortisol, and progesterone evoked a similar effect. On the other hand, hydrocortisone and cortisone induced a much milder effect, whereas the non-glucocorticoid steroid deoxycorticosterone did not affect the turnover of radiosulfate in this tissue. Clearance of the isotope from the serum was faster in the hormone-treated animals. Further, the hormone led to a decrease in the overall content of GAGs, a feature that lasted for 24 h. These data tend to imply that, concomitant with the inhibitory effects of glucocorticoids on proteoglycan synthesis in cartilage, they also induce a transient depressive effect upon the degradation of proteoglycans and thereby interfere with the normal growth and development of this cartilage.

Animals↗
PubMed1986

[Vasoconstrictor effects on isolated vessel segments determined by pressure-volume measurements].

A method for pressure-volume measurement in isolated segments of dog saphenous veins and femoral arteries is described. Its applicability was shown by means of the vasoconstrictor effects of noradrenaline and serotonin. By this method changes in intravascular pressure were measured in dependence upon the in- and outflowing volume of liquid. The pressure-volume diagrams allowed to estimate the intravascular pressure, work, resistance and compliance of the vascular segments. From the diagrams differences in the responses of veins and arteries to the biogenic amines could be demonstrated. The concentration-response relationships of the venous segments for noradrenaline and serotonin corresponded to those obtained in helically cut venous strips.

Animals↗