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Biomedical subjects

A Zaidi

Publications and source records attributed to A Zaidi.

At least 55 records · Page 3Linked to original sources

Protection by lazaroids of the erythrocyte (Ca2+, Mg2+)-ATPase against iron-induced inhibition.

The calmodulin-stimulated (Ca2+, Mg2+)-ATPase (calmodulin-ATPase) of the erythrocyte membrane is susceptible to oxidative stress induced by heme and non-heme iron. There is a time-and concentration-dependent inhibition of the calmodulin-ATPase activity when the erythrocyte membranes are treated with either iron or hemin. In the present study, the calmodulin-ATPase has been used as a model system to evaluate the protective effects of a vitamin E analog (U83836E) and two 21-aminosteroids (U74500A and U74389G) against calmodulin-ATPase inhibition induced by iron and hemin. The drugs, lazaroids from Upjohn, can significantly protect the enzyme against iron-induced inhibition and also causes a decrease in the formation of thiobarbituric acid reactive species, with an IC50 of 0.4 microM for the drug U83836E and 4 microM for the drug U74500A. The 21-aminosteroid U74389G does not restore iron-inhibited calmodulin-ATPase activity under similar conditions. At higher concentrations (> 100 microM) all three drugs inhibit the calmodulin-ATPase activity. None of the drugs tested can restore hemin-inhibited calmodulin-ATPase activity.

Antioxidants↗

Heme as an optical probe for studying the interactions between calmodulin and the Ca(2+)-ATPase of the human erythrocyte membrane.

The heme group was used as an optical probe to study the interactions between calmodulin and its targets: the peptide melittin and the enzyme Ca(2+)-ATPase. As already reported, melittin when present in Tris buffer binds hemin-CN which quenches the tryptophan fluorescence. Addition of calmodulin restores the fluorescence significantly accompanied by a blue shift. We show here that the recovery of fluorescence is very slow and takes about 120 min to become constant. In a hydrophobic buffer, the fluorescence spectrum of melittin is already shifted with a peak at 335 nm and intensity almost 2-fold relative to a similar concentration of melittin in Tris buffer. The quenching of tryptophan fluorescence is lesser in this buffer and further addition of calmodulin fails to restore the fluorescence. This indicates the absence of binding of calmodulin to melittin in hydrophobic conditions. Under similar conditions of hydrophobicity, hemin-CN quenches about 35% of the tryptophan fluorescence of the Ca(2+)-ATPase. The subsequent addition of calmodulin restores about half of the quenched fluorescence. The interaction of calmodulin with the Ca(2+)-ATPase even under hydrophobic conditions suggests its high specificity for the enzyme which may be expected for a physiological target.

Calcium-Transporting ATPases↗

Sexual behavior, sexually transmitted diseases, and risk of cervical cancer.

To explore sexually transmitted diseases and sexual behavior as risk factors for cervical cancer, we analyzed data from a population-based case-control study of breast and cervical cancer in Costa Rica. Data from 415 cases of cervical carcinoma in situ, 149 cases of invasive cervical cancer, and 764 controls were included in the analysis. Multivariate analysis showed that lifetime number of sex partners, first intercourse before age 15 years, number of livebirths, herpes simplex virus type 2 seropositivity, and serologic evidence of previous chlamydial infection were predictors of carcinoma in situ. Serologic evidence of previous syphilis was not associated with carcinoma in situ. Predictors for invasive cervical cancer included lifetime number of sex partners, first intercourse before age 15 years, number of livebirths, serologic evidence of previous syphilis, herpes simplex type 2 infection, and chlamydial infection. Cigarette smoking, socioeconomic status, self-reported history of sexually transmitted diseases, and douching were not associated with either carcinoma in situ or invasive cervical cancer.

Adult↗

Studies on the differential morphological alterations in human and goat erythrocytes against ATP depletion and Ca(2+)-induced stresses.

Erythrocyte membranes obtained from goat exhibited Ca2+/calmodulin-insensitive (Ca(2+)-Mg2+)-ATPase activity and the activity levels were significantly lower as compared to those obtained from human erythrocyte membranes. Although Ca2+/ionophore A23187 -treatment enhanced the intracellular Ca2+ levels in both the freshly collected human and goat erythrocytes, negligible loss of ATP was noticed in goat erythrocytes under such conditions. Also, fluoride, a known metabolic inhibitor, caused a lesser ATP depletion in goat erythrocytes compared to that of human. Goat erythrocytes showed remarkable rigidity to shape change and unlike human erythrocytes, did not undergo echinocytic formation as a result of metabolic depletion and Ca2+/ionophore A23187-treatments. These studies suggest the participation of (Ca(2+)-Mg2+)-ATPase -independent mechanism(s) for Ca(2+)-extrusion.

Adenosine Triphosphate↗

Modulation of the osteoclast Ca2+ receptor by extracellular protons: possible linkage between Ca2+ sensing and extracellular acidification.

We report a sensitivity of the osteoclast cell surface Ca2+ receptor to extracellular protons. Freshly isolated rat osteoclasts were exposed to the known agonists of the Ca2+ receptor, Ca2+ and Ni2+, in extracellular solutions set at different pH values. Decreasing the extracellular pH from 7.8 to 4.0 units markedly potentiated the cytosolic Ca2+ signals elicited in response to Ca2+ receptor activation by either Ni2+ (50 microM, 500 microM or 5 mM) or Ca2+ (5 mM). Each response consisted of a rapid and usually transient elevation of cytosolic [Ca2+]. Maximal cytosolic [Ca2+] responses were obtained at pH values of 6.6 (for 5 mM-[Ni2+]) and 4.0 units (for 5 mM-[Ca2+]). Finally, the effects of extracellular pH persisted in Ca(2+)-free, EGTA-containing solutions, suggesting a modulation of intracellular Ca2+ release.

Animals↗

Quantitative studies on the effect of prostacyclin on freshly isolated rat osteoclasts in culture.

Prostaglandins exert marked but transient inhibitory effects on bone resorption. The present study examines the effects of prostacyclin (0.15 to 25 microM) on the morphology of freshly disaggregated rat osteoclasts. An area descriptor, rho, represented changes in total cell spread area, and a motility descriptor, mu, represented overall changes in cell motility. The application of prostacyclin intercepted the trend of an increasing cell spread area with time and produced a transient reduction of rho, an R effect. Its magnitude depended upon concentration and was marked at 25 microM prostacyclin. The subsequent recovery (+0.8/min) of rho at this concentration resembled the persistent spreading seen in the absence of the agonist. There was also a sustained decrease in mu to approximately 60% of its pretreatment value (a Q effect) following the application of 25 microM prostacyclin. The extracellular application of 20 mM [Ca2+] produced a similarly transient cell retraction preceded by a rise of cytosolic [Ca2+], but without a corresponding decrease in mu. In contrast, prostacyclin did not elevate cytosolic [Ca2+], suggesting the triggering of an alternative transduction pathway. A fully reversible retraction together with incomplete quiescence may explain the transience characteristic of the antiresorptive action of prostacyclin.

Animals↗

Ca(2+)-induced alterations in the activity of membrane (Ca(2+)-Mg2+)-ATPase of human and rat erythrocytes.

Effect of intraerythrocyte Ca2+ elevation on human and rat erythrocyte membrane (Ca(2+)-Mg2+)-ATPase along with that of incubation of the erythrocyte ghosts in their own hemolysates enriched with Ca2+ has been studied. While the membrane (Ca(2+)-Mg2+)-ATPase levels of Ca(2+)-loaded human erythrocytes showed an initial increase and subsequent decline, membranes incubated in their own hemolysate showed a consistent decrease in the enzyme activity. Calmodulin sensitivity was retained by the preparations in contrast to the earlier observations made with washed erythrocyte membranes. Similar changes in (Ca(2+)-Mg2+)-ATPase activity but of greater magnitude were observed in response to Ca2+ in the calpain-rich rat erythrocytes. Considerable crosslinking and proteolysis was observed in case of human and rat erythrocytes exposed to high Ca2+ concentrations. The Ca(2+)-activable transglutaminase, however, did not play any role in the activation of the (Ca(2+)-Mg2+)-ATPase.

Animals↗

Seroepidemiological characterization of a syphilis epidemic in the Republic of the Marshall Islands, formerly a yaws endemic area.

The annual numbers of reported cases of syphilis in the Republic of the Marshall Islands (RMI) increased from none in 1983 to more than 600 in 1989, suggesting a large outbreak of syphilis. Much of the increase resulted from expanded serological screening. The apparent outbreak of syphilis, therefore, may have been partly the result of increased surveillance or, since the RMI was formerly a yaws endemic area, possibly due to a resurgence of yaws. To address this problem and better characterize the epidemic, we analysed results from a 1989/90 Ministry of Health Services mass serological screening on Majuro Atoll, the main population centre. Serum specimens from 9160 people (86% of residents aged 15-44 years) on Majuro were screened with the rapid plasma reagin (RPR) card test; we repeated the RPR and performed a confirmatory microhaemagglutination assay for Treponema pallidum-specific antibodies (MHA-TP) on a sample of serum specimens. To estimate the seroprevalence of syphilis, we also tested a sample of RPR nonreactive specimens by MHA-TP. Among people less than 45 years of age, total (11.5%) and high-titre (5.2%) seropositivity rates were highest in the 20-24 year age group, as was MHA-TP seroprevalence (15.9%). These results suggested that a large outbreak of syphilis was responsible for the observed seroreactivity. Cumulative incidence modelling and comparisons with the results of a previous serosurvey conducted in 1985 suggested that the duration of the syphilis epidemic was approximately 10 years and that incidence had not increased appreciably since 1985.

Adolescent↗

Goat erythrocyte calmodulin is not abnormal.

Calmodulin was purified from goat erythrocyte hemolysate using heat treatment and Sephadex G-100 gel filtration chromatography. The molecular weight and Stokes, radius of the purified calmodulin was determined. The goat erythrocyte calmodulin stimulated (Ca(2+)-Mg2+)-ATPase but not (Mg2+)-ATPase and (Na(+)-K(+)-Mg2+)-ATPase. The (Ca(2+)-Mg2+)-ATPase of the erythrocyte membrane derived from human, rat, rabbit and pig were significantly stimulated.

Animals↗

A time series analysis of gonorrhea surveillance data.

Gonorrhea is the most frequently reported communicable disease in the United States. In response to rapidly rising rates in the late 1960s, the Public Health Service instituted a gonorrhea control programme. An important component of the programme is the screening of women for gonococcal infections. We use a time series intervention model to estimate the initial increase in reporting of cases in women associated with the control programme. From the middle 1970s to the middle 1980s, a regular seasonal pattern in the data is conspicuous. We use a second time series model to quantify the seasonal variation during this period and to construct forecasts.

Data Interpretation, Statistical↗

Time series analysis of injuries.

We used time series models in the exploratory and confirmatory analysis of selected fatal injuries in the United States from 1972 to 1983. We built autoregressive integrated moving average (ARIMA) models for monthly, weekly, and daily series of deaths and used these models to generate hypotheses. These deaths resulted from six causes of injuries: motor vehicles, suicides, homicides, falls, drownings, and residential fires. For each cause of injury, we estimated calendar effects on the monthly death counts. We confirmed the significant effect of vehicle miles travelled on motor vehicle fatalities with a transfer function model. Finally, we applied intervention analysis to deaths due to motor vehicles.

Accidents, Traffic↗

Abnormal development of the testis after administration of the Leydig cell cytotoxic ethylene-1,2-dimethanesulphonate to the immature rat.

Male rats were injected with 50 mg ethylene-1,2-dimethanesulphonate/kg from Day 5 to Day 16 after birth and control rats received injections of the same volume of vehicle. Testes were studied at various times from Day 6 to Day 108 using histochemistry, light and electron microscopy. Fine structural degenerative changes were observed in the Leydig cells and seminiferous tubules of EDS-treated animals as early as Day 6. By Day 11 no Leydig cells could be detected and the interstitia of EDS-treated testes contained large numbers of fibroblast-like cells which formed peritubular collars 3-5 cells thick; the tubules contained Sertoli cells with heterogeneous inclusions and large numbers of lipid droplets. A small number of Leydig cells was found at Day 14 and their numbers increased so that, in animals of 28 days and older, large clusters of Leydig cells were present between severely atrophic tubules. These tubules contained Sertoli cells with few organelles; germinal cells were not observed after 28 days in EDS-treated animals. These results show that EDS destroys the fetal population of Leydig cells postnatally and this mimics the well documented effect of EDS on adult Leydig cells. The seminiferous tubules were permanently damaged by EDS in the present experiments. Tubular damage could have been due to a direct cytotoxic effect of multiple injections of EDS on the tubule before the blood-testis barrier develops or due to withdrawal of androgen support secondary to Leydig cell destruction.

Animals↗

Inhibition of testicular and somatic development after treatment of the postnatal rat with the Leydig cell cytotoxic ethylene dimethanesulphonate.

The Leydig cell cytotoxic ethylene dimethanesulphonate (EDS) was administered s.c. daily (50 mg/kg) to male rats aged 5-16 days. Apart from loss of weight and that the eyelids unfused earlier, no gross toxicity was observed during treatment. On day 17 testis weights, serum testosterone concentrations, testicular serum testosterone content and 125I-labelled human chorionic gonadotrophin (hCG) binding to testicular homogenates were reduced. Serum LH and FSH concentrations were elevated. The testes did not recover from EDS treatment and at 63 and 120 days were minute (less than 2% of control), and the prostate and seminal vesicles were small although not completely atrophied. In addition, body weights were substantially reduced. Serum and testicular testosterone and 125I-labelled hCG binding to testicular homogenates were reduced but not absent. Serum LH and FSH concentrations were increased. Light microscopy of the adult testes showed that EDS treatment inhibited the development of the seminiferous tubules. Most of the tubules were devoid of germ cells and Sertoli cells were rare. Occasionally tubules also contained spermatogonia and spermatocytes but no signs of spermiogenesis. The testes were composed mainly of closely packed interstitial tissue with no lymphatic space. The interstitial cells resembled Leydig cells and stained for 3 beta-hydroxysteroid dehydrogenase. Histochemically identified Leydig cells were absent during treatment but reappeared when treatment was withdrawn.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mechanisms of vessel injury during percutaneous transluminal angioplasty of saphenous vein bypass grafts and coronary arteries.

Three patients were studied in whom percutaneous transluminal angioplasty (PTA) was attempted in stenotic saphenous vein bypass grafts. In two cases, large splits were present in the thick fibrotic intima of the vein grafts, accompanied by rupture of atherosclerotic plaques or hemorrhage into atherosclerotic plaques. Both cases required emergency coronary artery bypass surgery. In the third case, a vein graft failed to dilate after multiple attempts. Only small splits were present in that fibrotic intima. Two other patients were studied in whom coronary artery PTA was attempted. In both cases, laceration of a nonatherosclerotic segment of the artery occurred. Combined with our previous report, these observations indicate that PTA results in lacerations of atherosclerotic plaques, fibrotic intima, and otherwise normal vessel walls and that laceration is the mechanism of both successful dilation and serious complications.

Angioplasty, Balloon↗

Balloon rupture during coronary angioplasty.

Out of a total of 1,500 percutaneous coronary angioplasties (PTCA), 55 (3.6%) were associated with balloon rupture. Lesion calcification was noticed in 7 of these 55 patients (12.7%). Balloon rupture occurred at a mean pressure of 10.7 atmospheres. All balloons were retrieved without difficulty. Intimal tears were noted in 18 (32.7%) cases. Three patients required bypass surgery. In 29 patients restudied angiographically, the restenosis rate was 38%. Balloon rupture during PTCA does not seem to be associated with detrimental consequences.

Adult↗

Serological response to syphilis treatment. A new analysis of old data.

One important aspect of the posttreatment evaluation of patients with early syphilis is assessment of serological test results. Using information previously collected from 818 patients in the Early Syphilis Study, we evaluated the seroresponse of people treated for primary or secondary syphilis. We generated curves describing the VDRL titer declines with time. The VDRL titer declined approximately fourfold at three months and eightfold at six months. These observations will allow clinicians to identify treatment failures or reinfections at the earliest possible time during their follow-up.

Antibodies, Bacterial↗