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Biomedical subjects

S Pillay

Publications and source records attributed to S Pillay.

14 recordsLinked to original sources
PubMed1998

8Cl-cAMP cytotoxicity in both steroid sensitive and insensitive multiple myeloma cell lines is mediated by 8Cl-adenosine.

We have examined the cytotoxic effects of cyclic adenosine-3', 5'-monophosphate (cAMP) derivatives on multiple myeloma cells lines and determined that the 8-Chloro substituted derivative (8Cl-cAMP) is one of the most potent. We report here that 8Cl-cAMP is cytotoxic to both steroid sensitive and insensitive myeloma cells with a half maximal concentration of approximately 3 micromol/L. 8Cl-cAMP toxicity in myeloma cells is dependent on phosphodiesterase activity in the serum of cell culture medium. A metabolite of 8Cl-cAMP, 8-Chloro-adenosine (8Cl-AD), kills myeloma cells as effectively as 8Cl-cAMP. Adenosine deaminase (ADA) converts 8Cl-AD into 8Cl-inosine and abrogates the cytotoxic effects of 8Cl-cAMP, 8Cl-AMP, and 8Cl-AD, as does 5-(p-Nitrobenzyl)-6-Thio-Inosine (NBTI), an inhibitor of nucleoside uptake. These data suggest that 8Cl-cAMP must be converted to 8Cl-AD and that 8Cl-AD is the compound that enters the cell. Contrary to glucocorticoid-mediated cell death in myeloma cells, the pathway of 8Cl-AD-mediated cell death appears to be independent of interleukin-6 (IL-6) actions. Although the exact mode of action for this agent is currently unknown, its ability to kill steroid sensitive and insensitive multiple myeloma cells in an IL-6 independent fashion may offer exciting new therapeutic options.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Correlation of the endoscopic and radiological anatomy of congenital obstruction of the posterior urethra and the external sphincter.

OBJECTIVE: To determine whether the external sphincter is distal to congenital occlusion of the posterior urethra in boys by correlating endoscopic video-recorded information with cysto-urethrographic observations and assessing the anatomy of the disease. PATIENTS AND METHODS: This study reviewed the endoscopic and radiographic findings in 42 boys (mean age 42 months, range newborn to 14 years), using material from a videotape library, and correlated these with the pre-operative cystogram. The nature of the obstructive lesion and its relationship to the verumontanum and the external sphincter was assessed. RESULTS: Of the 42 boys, 36 had the proximal extent of the external sphincter identified on the endoscopic video recording to be above the posterior urethral membrane; 22 of the membranes were obstructive. The proximal extent of the external sphincter was identified on the static cystogram images of only 31 of the 38 boys examined, but only ever above the posterior urethral membrane. CONCLUSION: The proximal extent of the external sphincter, i.e. that portion which is most prominent endoscopically, is proximal to the membrane in congenital obstruction of the posterior urethra.

Adolescent↗
PubMed1997

Cyclic adenosine-3',5'-monophosphate-mediated cytotoxicity in steroid sensitive and resistant myeloma.

Multiple myeloma is a neoplastic proliferation of plasma cells. Glucocorticoids are among the most effective agents against multiple myeloma, acting through the glucocorticoid receptor to induce programmed cell death. However, some patients do not respond to glucocorticoids, and those that do respond eventually develop resistance to this therapy. Alternative strategies using drugs that mediate cytotoxicity through complementary pathways have theoretical appeal. Cyclic adenosine-3',5'-monophosphate (cAMP) derivatives are cytotoxic to a number of cell lines of lymphocytic origin. cAMP analogues activate protein kinase A, affecting cell growth and differentiation. The cascade of events initiated by cAMP derivatives and glucocorticoid, although distinct, may share some distal molecular targets. We have found that pharmacological concentrations of 8-chloro-cAMP, dibutyryl-cAMP, and 8-bromo-cAMP are cytotoxic to multiple myeloma cells, enhance glucocorticoid effects, and can kill glucocorticoid-resistant clones. cAMP analogues induce apoptosis as demonstrated by the fragmentation of myeloma DNA chromatin in a distinctive ladder pattern. In contrast to glucocorticoids, cAMP growth inhibition cannot be reversed by exogenous interleukin 6. cAMP derivatives have activity against multiple myeloma and are appropriate candidates for clinical trials.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

A variant glucocorticoid receptor messenger RNA is expressed in multiple myeloma patients.

In multiple myeloma cells resistant to glucocorticoids, we have previously identified a variant glucocorticoid receptor (GR) transcript (P. A. Moalli et al., Cancer Res., 53: 3877-3879, 1993). Here, we report a reverse transcription-PCR assay to assess whether this aberrant GR transcript is present in myeloma patients. We detected both the wild-type and variant GR transcripts in the patient isolate that was the source of our myeloma cell lines, in patients refractory to steroid treatment, and in healthy control subjects. Simultaneous amplification of wild-type and variant GR mRNAs indicates that the variant GR is more highly expressed in cells that are resistant to glucocorticoids. We hypothesize that the variant GR is a normal mRNA transcript that acts to modulate glucocorticoid responsiveness, and increased expression contributes to a resistant phenotype.

Base Sequence↗
PubMed1993

Alternatively spliced glucocorticoid receptor messenger RNAs in glucocorticoid-resistant human multiple myeloma cells.

Glucocorticoids are highly effective chemotherapeutic agents used in the treatment of hematological malignancies including multiple myeloma. However, the clinical usefulness of this class of drugs is limited by the problem of resistance. In the following study, we have isolated two alternatively spliced transcripts of the glucocorticoid receptor from a complementary DNA library generated from the glucocorticoid-resistant myeloma cell line MM.1Re. In each of the clones, specific exons of the hormone binding domain are precisely deleted. Our data implicate alternate splicing as a mechanism by which a cell generates different receptor isoforms and as a consequence evades the effects of hormone.

Alternative Splicing↗
PubMed1992

A mechanism of resistance to glucocorticoids in multiple myeloma: transient expression of a truncated glucocorticoid receptor mRNA.

Despite their widespread use, little is known of either the mechanism of action of glucocorticoids in the treatment of multiple myeloma or why patients ultimately become resistant to their therapeutic effects. Here, we address these issues by examining the direct effects of the glucocorticoid dexamethasone (DEX) on a hormone-sensitive clone (MM.1S) of a human multiple myeloma line and compare them with those of its hormone-resistant counterpart (MM.1R). MM.1S expresses approximately 50,000 glucocorticoid receptors (GR) per cell, the full-length 7.1-kb GR mRNA at high levels, and is lysed by DEX. DEX-induced cytolysis is effectively blocked by the glucocorticoid antagonist, RU 486, indicating the specificity of this response for the GR. In contrast to MM.1S, MM.1R is not lysed by hormone, has little hormone-binding activity, and expresses the 7.1-kb GR mRNA at low levels. Interestingly, we have found that two distinct phenotypes emerge from MM.1R with increasing periods of growth in culture. The first or "early" form, MM.1Re, expresses high levels of a variant GR mRNA of 5.5 kb that has a deletion in its 3' end. With further growth in the presence or absence of selective media, the expression of this transcript is repressed, resulting in the second or "late" phenotype characteristic of MM.1RL. No discernible differences in the organization of the genomic GR sequence in DEX-sensitive and -resistant cells were detectable by Southern analysis, suggesting that no gross deletions, rearrangements, or allelic variations in the genomic sequence account for the resistant phenotypes of MM.1R.

Adult↗
PubMed1992

The use of drug level measurements in adult patients receiving theophylline, anti-epileptic drugs and amikacin.

This prospective study was conducted to determine how frequently measurement of drug levels was used in the management of adult patients receiving theophylline, phenytoin, phenobarbitone, carbamazepine or aminoglycosides in a large hospital. Fifty consecutive outpatients with asthma and 40 with epilepsy were interviewed and their records reviewed to determine which drugs had been prescribed and whether a level of the appropriate drug had been measured in the previous six months. Also, the records of 40 in-patients who were currently receiving amikacin were studied to determine whether serum levels had been measured at any stage during therapy with this drug. Serum theophylline levels were measured in only four (eight pc) patients who were taking this drug and were below the target range in two patients. Serum levels had been measured in 21 (52.5 pc) of 40 patients who were receiving 45 anti-epileptic drugs and were within the target in only nine. Serum amikacin levels were measured in 15 (37.5 pc) patients; blood had been taken for both peak and trough levels in 10 patients and found to exceed the target range in two patients. This study revealed that measurement of serum concentrations of theophylline, anti-epileptic drugs and amikacin was underutilised in the management of adult patients receiving these drugs at this hospital.

Adult↗
PubMed1991

'Tru-Cut' needle biopsy of the liver: importance of the correct technique.

In order to determine which technique would provide adequate tissue for histological examination when the 'Tru-Cut' needle is used for liver biopsy, the livers of cadavers were biopsied by a single operator, under direct vision, using a 'Tru-Cut' needle. The modified breast biopsy technique either preceded or followed one of two alternative methods, one of which was recommended by the manufacturer, in a random manner. Thereafter, the biopsies were repeated using the alternative sequence. The mean length of the liver biopsy specimens that were obtained using the modified breast biopsy technique was 16.3 mm (range: 8-20 mm). The corresponding figures for the manufacturerer's method were 7.7 mm (range: 2-14 mm) and for the third technique were 2.7 mm (range: 0.5-8 mm). Three of the 40 specimens (7.5%) obtained using the latter technique fragmented when placed in formalin; this did not occur in any of the 40 specimens taken using the modified breast biopsy technique. This investigation indicates that the modified breast biopsy technique should be used when 'Tru-Cut' needle biopsy of the liver is performed. This provides specimens which are adequate for histological diagnosis. In addition, the safety of liver biopsy, which is compromised by poor technique, is improved. The alternative methods, including that recommended by the manufacturer, must be avoided.

Biopsy, Needle↗
PubMed1991

Circulating CA-195 in hepatocellular carcinoma and metastatic hepatic carcinoma.

This study was conducted to determine the role of a relatively new tumor marker, CA-195, in the diagnosis of hepatocellular carcinoma and metastatic hepatic carcinoma, and in distinguishing between these two conditions. CA-195 levels were measured using a commercially available immunoradiometric assay (Tandem-R CA-195) in 30 black inpatients with hepatocellular carcinoma, 15 metastatic carcinoma, 10 with amoebic liver abscess, 10 with cirrhosis and 10 normal individuals at King Edward VIII Hospital, Durban. A cutt-off value of 10 u/ml was used. The sensitivity and specificity of CA-195 in hepatocellular carcinoma and metastatic carcinoma was 60% and 22%, and 87% and 42% respectively. False positive results occurred in 5 (50%) patients with amoebic liver abscess, 10 (100%) with cirrhosis and 2 (20%) normal individuals. These results indicate this tumor marker as of limited value in the diagnosis of hepatocellular carcinoma and metastatic carcinoma, and in distinguishing between these conditions.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1987

The prevalence of sexually transmitted disease agents in pregnant women in Suva.

Routine testing of 440 women (257 Fijians, 183 Indians) at the first antenatal attendance identified Chlamydia trachomatis in 50% of Fijians and 38% of Indians; the seropositivity rates for syphilis were 14.2% and 1.7% respectively, and the isolation rates for N. gonorrhoeae were 3.1% in Fijians and 1.1% in Indians.

Adult↗
PubMed1982

The change in fetal activity periods in diabetic and nondiabetic pregnancies.

Fetal active and quiet periods of behavioral activity were determined at 28 and 32 weeks' and 36 to 40 weeks' gestational age in insulin-dependent diabetic pregnancies and in normal pregnancies resulting in infants with weights appropriate for gestational age. Fetal active and quiet periods were based on observations of fetal movements and long-term fetal heart rate variability. The number of fetal active-quiet periods, the average duration of fetal quiet periods, and the average duration of fetal active periods were the three parameters evaluated. In the normal pregnancy groups, with increasing fetal gestational age from 28 to 32 weeks to 36 to 40 weeks there was an increase in the length of the active and quiet periods with fewer active-quiet cycles per hour. The fetuses of the diabetic women had findings similar to those of the normal group at 28 to 32 weeks; these findings were essentially unchanged at 36 to 40 weeks. These findings suggest delayed development of the active-quiet cycles in these diabetic pregnancies.

Behavior↗
PubMed1982

Correlation between gestational age and fetal activity periods.

Cyclic patterns of active and quiet fetal activity were evaluated in 36 clinically normal gravidas between 27 and 42 weeks of gestation. All infants were subsequently delivered between 37 and 42 weeks of gestation, were clinically normal and of appropriate weight for gestational age. Active-quiet cycles occurred less frequently and were of longer duration with increasing gestational age. Regression analysis of the number of active-quiet cycles with gestational age yielded a correlation coefficient of 0.52 (p less than 0.01). The similarity of fetal active-quiet cycles and active and quiet sleep cycles observed after birth is noted.

Female↗
PubMed1981

A comparison between maternal, tocodynamometric, and real-time ultrasonographic assessments of fetal movement.

Fetal movements were simultaneously studied with maternal perception, tocodynamometry, and real-time ultrasonography. A comparison between these three modalities demonstrated good agreement. The percentage of agreement improved with increasing duration of fetal movements. For fetal movements lasting longer than 3 seconds, the agreement between ultrasonography and tocodynamometry was 95.6%. These findings suggest that tocodynamometry is a sensitive method for studying fetal movements.

Female↗