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Biomedical subjects

A H Saad

Publications and source records attributed to A H Saad.

At least 19 recordsLinked to original sources
PubMed2001

Cellular response to Schistosoma mansoni infection in Biomphalaria alexandrina strains selected for susceptibility and resistance.

Exposure of juvenile and adult Biomphalaria alexandrina to Schistosoma mansoni miracidia resulted, typically, in three susceptibility patterns: a) non-infected snails; b) normal infections, and c) retarded infections. Under laboratory conditions, a vigorous resistant-type cellular response to invading miracidia was seen in the histological sections of non-susceptible snails. Accordingly, they were classified as resistant snails. Data pertaining to the influence of host size on suceptibility to S. mansoni indicates that adult snails (i.e. 10-20 mm shell diameter) were significantly less likely to harbour sporocysts than juvenile ones (i.e. 5-10 mm shell diameter). Cellular reaction to the infection varied with sporocysts location and length of infection. At 2 days post-exposure (DPE), most sporocysts were viable. Approximately 8-12% of the sporocysts had elongated shaped transverse constriction and were categorized "normal", while those showing no elongation were categorized "retarded". All remaining sporocysts at 4 DPE were categorized "dead", while at 30 DPE, most sporocysts were "amorphous" with eosinophilic masses. Although encapsulation of sporocysts never occurred in susceptible snails, haemocyte aggregations could sometimes be observed in the proximity of well developed sporocysts. In resistant snails, this cellular response continued to increase and resulted in the encapsulation of the sporocysts. In susceptible snails, the nucleus of secretory cells of the albumen cytoplasm were different in susceptible and resistant snails.

Animals↗
PubMed1999

Possible role of Schistosoma mansoni infection in male hypogonadism.

Schistosomiasis has been suggested to decrease the reproductive potential or castrate both invertebrate and vertebrate hosts. Furthermore, schistosomiasis may cause anatomic anomalies of the reproductive organs responsible for permanent or reversible infertility. To specify the effect of schistosomiasis on gonadal functions, production of testosterone (TS), leutinizing hormone (LH) and estradiol (E2) in Egyptian men infected with schistosomiasis were studied. All participants were tested for the following parameters: Clinical examination and diagnostic, semen, haematological and liver function tests and blood level of IL-2. The mean TS levels were at the lowest limit of normal range for liver cirrhotic patients. Mean E2 levels were increased in all patients, but patients with liver cirrhosis-related schistosomiasis had higher E2 levels. Linear regression analysis showed that the sex hormone levels correlated best with the patient's liver function parameters. The present data suggest that a sex hormone imbalance plays a role in patients with liver cirrhosis due to the inhibitory effects of schistosomiasis on gonadal functions.

Animals↗
PubMed1996

Association of BCL-2 with membrane hyperpolarization and radioresistance.

The resting membrane potential of parental, neomycin control, and Bcl-2 transfected cells was measured, and the effect of membrane hyperpolarization or depolarization on radiosensitivity was studied. Bcl-2 transfected cells were significantly more radioresistant than control cells and were significantly hyperpolarized compared to parental and neomycin control transfected PW and HL60 cells. Hyperpolarization of the parental and neomycin control transfected cells by valinomycin significantly increased the radioresistance of these cells to such an extent that there was no longer a significant difference in the survival of the valinomycin treated and irradiated control cells compared to similarly irradiated Bcl-2 transfected cells. In contrast, depolarization of the Bcl-2 transfected PW and HL60 cells decreased the radioresistance of the Bcl-2 transfectants to a level similar to that of the control cells. The data presented here suggest that overexpression of Bcl-2 affects membrane potential and that this hyperpolarization is associated with increased radioresistance of cells that overexpress Bcl-2. Furthermore, Bcl-2 transfected cells were also less susceptible to the specific Na+/K(+)-ATPase inhibitor ouabain, suggesting that Bcl-2 may act at the level of the Na+/K(+)-ATPase pump.

Apoptosis↗
PubMed1996

Structural characterization of an Lyt-2/3 homolog expressed on Bufo regularis lymphocytes.

Two alloantisera and a monoclonal antibody (mAb 53-6.7) of proven specificities to the murine Lyt-2/3 macromolecule labeled, in indirect immunofluorescent assays, a distinct lymphocyte population in the toad, Bufo regularis. Lyt-2/3 antigenic activities expressed by B. regularis lymphocytes have been solubilized and purified by mAb 53-6.7 affinity chromatography and found to be associated with a single 67 kDa macromolecule in SDS-PAGE. Upon reduction, this macromolecule resolved into 38 kDa, 34 kDa and 28 kDa subunits corresponding to the alpha, alpha' and beta subunits of the murine Lyt-2/3 complex. Comparisons based on the S delta Q index of differences in amino acid compositions of HPLC-purified alpha- and alpha'-subunits of the amphibian Lyt-2/3 molecule indicated a significant structural relatedness to their murine counterpart as well as to the human CD8 polypeptide. Our observations point to an early phylogenetic emergence of Lyt-2/3 as an important component of the T cell cytolytic apparatus during vertebrate evolution.

Amino Acids↗
PubMed1995

Ovarian activity during follicular-phase down regulation in in vitro fertilization is associated with advanced maternal age and a high recurrence rate in subsequent cycles.

PURPOSE: Previous reports have suggested that the ovarian response to leuprolide acetate is predictive of in vitro fertilization pregnancy rates. This study evaluated the outcome of in vitro fertilization cycles complicated by elevated estradiol levels during leuprolide acetate down regulation and the outcome of subsequent cycles in the same patients. METHODS: Two hundred fifty-two in vitro fertilization cycles were initiated utilizing leuprolide acetate down regulation beginning on cycle day 1. RESULTS: Seventy-four of these cycles had an elevated estradiol level at the time of the baseline scan (28%). This group of patients had a higher maternal age, a higher cycle cancellation rate (27.5 vs 16.3%), and a high rate of recurrence on subsequent cycles (63%). CONCLUSIONS: The pregnancy rate per retrieval was equivalent in the two groups. This suggests that patients with advanced maternal age or a history of failure to suppress in a previous cycle may benefit from alternate regimens of superovulation.

Adult↗
PubMed1995

Characterization of Biomphalaria alexandrina-derived lectins recognizing a fucosyllactose-related determinant on schistosomes.

Two novel lectins that bind selectively to a schistosome-associated fucosyllactose-related determinant have been characterized and purified from the hemolymph of Biomphalaria alexandrina, the snail vector of Schistosoma mansoni. Both lectins were purified by affinity chromatography on a column of equimolar mixture of D- and L-glucose coupled to epoxy-activated Sepharose 6B and sequential elution by D-glucose (designated BaSI) and L-fucose (designated BaSII). Assessment of the structural characteristics, by one- and two-dimensional polyacrylamide gel electrophoresis, indicated that BaSI and BaSII were structurally distinct, and exist in their native forms as multimers of non-covalently associated subunits, that were of different sizes in BaSI and of equal size in BaSII. Removal of N-linked glycans by Endo-beta-N-acetylglucosaminidase F resolved the heterodisperse pattern of BaSI subunits into two spots of 13.2 kDa (pI 7.2) and 10.1 kDa (pI 5.8), and collapsed the acidic charge microheterogeneity of the BaSII subunit into a single spot that corresponded in terms of molecular weight and pI to the basic 13.2-kDa subunit of BaSI. In miracidial binding and inhibition assays with different sugars, both lectins exhibited selectivity towards a fucosyllactose sequence, but BaSII had a higher binding preference to fucose moieties. BaSII-Sepharose 4B affinity chromatography and analysis on two-dimensional gels indicated that multiple copies of the fucosyllactose-related determinant were expressed by heterogeneous, acidic glycoproteins in the miracidial stage of S. mansoni.

Animals↗
PubMed1995

Seasonal distribution and hormonal modulation of reptilian T cells.

Using PNA and anti-Thy-1 fluorescent binding assays, T lymphocytes of the lizard, Chalcides ocellatus were phenotypically distinguishable into four subpopulations (PNA+ Thy-1-, PNA+ Thy-1+, PNA- Thy-1+ and PNA-Thy-1-), which seemed to be affected independently by endogenous steroid levels. Indeed, the size of PNA+ thymocytes is maximal and coincides with the low level of circulating cortisol during spring through summer and decreases gradually with the elevation of the cortisol level. On the other hand, as the endogenous testosterone (TS) level begins its physiological rise, lympholysis of Thy-1+ thymic cells begins in spring with gradual increase in size and with the decrease in TS levels. Among splenocytes and bone marrow lymphocytes, seasonal-dependent alterations in the size of both lymphocyte subpopulations seemed to correlate in part with the status of the thymus. Direct support of this observation was derived from subsequent in vitro studies with exogenous hydrocortisone (HC) and testosterone propionate (TP) treatments in spring and autumn. In all incidents, the data were indicative of the selective susceptibility of the PNA+ Thy-1- subpopulation to HC in the thymus and not in the periphery, and the susceptibility of the PNA- Thy-1+ subpopulation to TP in all three lymphoid organs tested. In vivo studies with a purified fraction of thymosin alpha 1 (T alpha 1) suggested that the PNA+ Thy-1- subpopulation in the different organs was the selective target for the action of T alpha 1. Finally, the dual treatment with T alpha 1 in vivo followed by TP or HC in vitro confirmed that TP-sensitivity was confined to the PNA- Thy-1+ and HC to PNA(+)-Thy-1- subpopulations in any of the three lymphoid organs.

Animals↗
PubMed1995

Identification of peanut agglutinin-binding glycoproteins on lizard lymphocytes.

The expression of PNA-binding glycoproteins on lizard lymphocytes was investigated by studying the reactivity of FITC-PNA towards lizard lymphocytes obtained from the different lymphoid organs. Direct immunofluorescence assays have demonstrated that the majority of lizard thymocytes (70%) and only a fraction of lymphocytes in the spleen, peripheral blood and bone marrow were PNA-positive. This positivity was selectively inhibited by galactose as well as lactose, indicating the specificity of binding. Putative PNA receptors were purified from lizard thymocytes and splenocytes by affinity chromatography on a PNA-Sepharose 4B column and resulted in fractions enriched 1,792-fold and 3,141-fold for the PNA-binding component expressed on lizard thymocytes and splenocytes, respectively. Analysis on reducing and non-reducing SDS-PAGE revealed that both thymic and splenic PNA-binding glycoproteins migrated as a single component of 35 KDa, with no evidence for the association into higher multimers in both tissues. Analyses for amino acid and carbohydrate compositions indicated that the thymic and splenic glycoproteins have similar amino acid composition and differed in the content of neutral and amino-sugars as well as sialic acid. The content of the latter residue was relatively higher in the splenic form of the receptor compared to its thymic counterpart, and was inversely correlated with the content of galactosyl residues in both forms of the receptor. The functional significance of PNA-binding glycoproteins during vertebrate evolution is discussed.

Amino Acids↗
PubMed1994

Modulation of potassium channels by protein tyrosine kinase inhibitors.

Exposure of non-excitatory cells to the tyrosine kinase (PTK) inhibitors, genistein, herbimycin A, and tyrphostin, induced at least two families of K+ currents. The first, a TEA-insensitive slow-inactivating K+ current, is induced within 3 min following treatment with 140 mM genistein or 100 nM herbimycin A. The second current, a TEA-sensitive delayed rectifier, is induced within 30 min following treatment with 50 mM genistein or 10 nM herbimycin A. Currents with similar biophysical and pharmacological characteristics are induced in these cells following exposure to ionizing radiation. The radiation-induced currents are inhibited by pretreatment with the free radical scavenger, N-Acetyl L-Cysteine, or by pretreatment with the protein kinase C inhibitor, staurosporine; those induced by PTK inhibitors are not. The latter, therefore, do not appear to be mediated through free radicals or require serine/threonine phosphorylation for activation. Once the channels are activated by the PTK inhibitors, phosphorylation of the channel at serine/threonine residues results in slower inactivation of the induced current. We propose that protein tyrosine phosphorylation of the K+ channel protein itself or of a factor that interacts with it maintains the K+ channels of non-excitatory cells in a closed state. Following exposure to ionizing radiation, free radical-induced activation of serine/threonine kinase(s) results in phosphorylation of the channel and/or inactivation of a tyrosine kinase that in turn leads to activation of the K+ channels.

Acetylcysteine↗
PubMed1994

Mutagenesis in mammalian cells can be modulated by radiation-induced voltage-dependent potassium channels.

In mammalian cells, little is known about the initial events whose ultimate consequence is mutagenesis or DNA repair. The role the plasma membrane may play as an initiator of such a pathway is not understood. We show, for the first time, that membrane voltage-dependent potassium (K+) currents, activated by ionizing radiation (Kuo et al., 1993), play a significant role in radiation mutagenesis. Specifically, we show that the frequency of mutation at the HGPRT locus is increased as expected to 37.6 +/- 4.0 mutations per 100,000 survivors by 800 cGy of ionizing radiation from a spontaneous frequency of 1.5 +/- 1.5. This increase, however, is abolished if either K+ channel blocker, CsCl or BaCl2, is present for 2 h following irradiation of the cells. RbCl, chemically similar to CsCl but known not to block K+ channels, is ineffective in reducing the mutation frequency. Treatment of cells with CsCl or BaCl2 had no effect on radiation-induced cell killing.

Animals↗
PubMed1993

Potassium-channel activation in response to low doses of gamma-irradiation involves reactive oxygen intermediates in nonexcitatory cells.

Active oxygen species are generated during pathophysiologic conditions such as inflammation and ionizing radiation exposure. We tested the hypothesis that an early cellular event in response to these species involves regulation of ion channels. We exposed cells to gamma-irradiation or treated them with hydrogen peroxide, xanthine/xanthine oxidase, or [3H]thymidine and then monitored channel activity by the technique of whole-cell voltage clamping. Recordings showed that both normal and tumor cells exhibit an increase in K+ currents after treatment with radiation, H2O2, and xanthine/xanthine oxidase but not with high specific activity [3H]thymidine, suggesting that the signal for K+ channel activation originates at the cell membrane. A single noncytotoxic dose of 10 cGy induced measurable levels of K+ currents, suggesting that the induction of currents regulates biochemical changes in response to stress. To test whether channel activity is sensitive to active oxygen species, we pretreated cells with N-acetyl-L-cysteine (NAC) to increase cellular pools of free radical scavengers before radiation. In NAC-pretreated cells, K+ channel activation by gamma-irradiation was abolished. It has previously been shown that protein kinase C (PKC) is activated by ionizing radiation and can regulate K+ channels in some cells. However, the effect of radiation on induction of K+ channel activity was independent of PKC, since cells chronically exposed to phorbol esters still produced K+ currents after radiation. These results suggest that an early cellular response to oxidative stress is the activation of K+ channels.

Acetylcysteine↗
PubMed1993

Activation of potassium channels by hypoxia and reoxygenation in the human lung adenocarcinoma cell line A549.

Active oxygen species are generated in cells during pathophysiologic conditions such as inflammation and postischemic reperfusion. If oxygen radical scavengers are added before reperfusion, then the magnitude of injury is reduced. We investigated whether free radicals generated following exposure to hypoxia and reoxygenation activate voltage-dependent K+ ion channels in tumor cells in vitro. Using the technique of whole cell voltage clamping, we recorded currents from two families of potassium (K+) channels that were activated following reoxygenation. One of these groups possessed the electrophysical characteristics of a tetraethylammonium (TEA)-sensitive delayed rectifier channel and the other possessed characteristics of a Tea-insensitive slow inactivating channel. We present evidence which suggests that K+ channels are activated following reoxygenation but not during the hypoxia phase. The K+ currents decayed with time following reoxygenation. The decay characteristics of the K+ currents depended on the duration and level of hypoxia to which the cells were exposed. To determine whether activation of K+ channels by reoxygenation was initiated by free radicals, we pretreated cells with N-Acetyl L-Cysteine (NAC), a free radical scavenger, and found that this pretreatment abolished the currents induced by reoxygenation. We also present evidence that free radicals do not directly act on the channel itself, but activate a protein kinase which, in turn, activates the K+ channels. Taken together, these results indicate that one of the early responses to oxidative stress is the activation of K+ currents.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Thymus histogenesis in the lizard, Chalcides ocellatus.

Different stages of thymus morphogenesis and thymocyte differentiation have been studied at the ultrastructural level in the lizard, Chalcides ocellatus. On stage 36 of embryonic development, the thymus primordium was composed principally of undifferentiated epithelial cells and some lymphoid stem-cells. From stage 37 to 38, the lymphoid stem-cells differentiate into lymphoblasts and then transform into typical lymphocytes. A clasmotosis phenomenon seems to be involved in this transformation. In the developing cortical regions, lymphoblasts accumulated rapidly, stretching the epithelial cells which become stellate in shape. From stage 39 to 40, a phase of intense proliferation occurs and numerous lymphocytes die in the thymic tissue and are phagocytosed by macrophages. On stage 41, the presence of interdigitating cells in the medullary area completed cortico-medullary differentiation. On neonatal and juvenile lizards, small cortical thymocytes differentiated and the thymus possessed all characteristic of an adult thymus. Thus, at birth, the histogenesis of the lizard thymus was achieved and the only further modification consisted in a gain of weight.

Aging↗
PubMed1992

Activation of potassium channels: relationship to the heat shock response.

We examined the possibility that whole cell currents are involved and possibly trigger the response of mammalian cells to heat shock. Heat-sensitive cells from a radiation-induced fibrosarcoma (RIF-1) and heat-resistant variants (TR-4, TR-5) were heated at 45 degrees C for 3-30 min. We observed induction of voltage-dependent currents after heating in the heat-resistant cells. These currents decayed to nonmeasurable levels over a period of 6 h. In RIF-1 cells, however, voltage-dependent currents were detectable during heating only; these currents then decayed rapidly. Tetraethylammonium (TEA) cations blocked the currents; changing the concentration of extracellular K+ modified the current-voltage (I-V) relationship. These currents, therefore, resulted from the activation of voltage-dependent K+ channels. Addition of TEA during heating sensitized TR-4 cells to heat but had no effect on the heat response of the RIF-1 cells. Continuous exposure of the RIF-1 cells to 2% (vol/vol) dimethyl sulfoxide (DMSO) for 7 days induced the expression of additional functional, voltage-dependent K+ channels; these gave rise to currents that were measurable after heating. In parallel, these cells became heat resistant. Addition of TEA to DMSO-treated cells blocked channels and returned the heat response almost to the pre-DMSO levels. Our data show a correlation between heat resistance and expression of K+ channels. Because resistance to heat very likely relates to the heat shock response, our data suggest that activation of channels may be a very early event in initiation of the heat shock response.

Animals↗
PubMed1992

Ultrasound-enhanced effects of adriamycin against murine tumors.

Earlier studies from our and other laboratories have demonstrated that ultrasound (US) enhances the cytotoxicity in vitro of the antitumor agent Adriamycin (Adr) (Harrison et al. 1991; Loverock et al. 1990; Saad and Hahn 1987, 1989; Yang et al. 1991; Yumita et al. 1987, 1989). We have now tested the possibility that this additional cytotoxicity can be translated into antitumor activity in vivo. Mice, bearing either a fibrosarcoma (RIF-1) or a melanoma (B-16) on their thighs, were injected with a single dose of Adr (10-20 mg/kg). The tumors were then heated locally to 41 degrees -43 degrees C for 30 min, either by insonation with US or by immersion of the animals' limbs into hot water baths. Antitumor efficacy was scored two ways: by serial measurements of tumor volume to determine the time for the tumor to double in size, or by determining the X-ray dose required to sterilize 50% of the tumors (TCD50) after the Adr-hyperthermia treatment. Both assays gave similar results. Ultrasound-induced hyperthermia was substantially more effective in enhancing Adr activity than was hyperthermia induced by the water bath. The mean-doubling time was 13 days for tumors treated with the combination of Adr and US and 6 days for tumors heated with a water bath immediately after injection of Adr. The TCD50 was 21.2 +/- 0.8 Gy for the combination of US and Adr and 36.1 +/- 0.9 Gy for the water bath heating and Adr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Reptilian thymus gland: an ultrastructural overview.

Like in higher vertebrates, the thymus gland of reptiles consists of lymphoid cells within epithelial framework and characteristic myoid cells. Mammalian-like Hassall's corpuscles are absent. Secretory cells, secretory and degenerative cysts as well as phagocytic cells, and plasma cells can be observed. Interdigitating cells and some characteristic features of thymic innervation and vascular system are also described in the reptilian thymus gland.

Animals↗
PubMed1991

Testosterone induces lymphopenia in turtles.

Owing to the possible role of sex steroids in the immune-neuroendocrine interactions found in lower vertebrates, we attempted to delineate the effect of testosterone propionate on peripheral blood (PB) and the lymphoid organs of the turtle Mauremys caspica. A single intraperitoneal injection of 200 micrograms/g body weight produced thymic involution and intense lymphopenia in the spleen and, less severely, in the PB compartment. It is suggested that lymphocyte redistribution may occur among the various compartments of the body as the main effect of hormone-induced lymphocyte redistribution, although the mechanism in reptiles and mammals is not yet understood.

Animals↗