Biomedical subjects

I Husain

Publications and source records attributed to I Husain.

At least 19 recordsLinked to original sources

PubMed1998

An epidemiologic study of cystitis among Muslim women attending an out-patients clinic in Karachi.

Cystitis is considered to be one of the most common infections afflicting women of all age groups. It has been suggested that personal hygiene customs may influence the prevalence of cystitis. In this study, 130 women of child bearing age attending the out-patients clinic were interviewed in order to determine the frequency of cystitis and its associated risk factors including personal hygiene practices. Twenty seven percent of the women reported suffering from cystitis atleast once in the past, comparable to reported studies from the United States but higher than reported from other Muslim countries. Sixty-three percent of women reported their first episode during pregnancy and a significant relationship was observed between parity and cystitis (p value < 0.000). However, personal hygiene practices following micturition or sexual intercourse bore no significant association with cystitis. Cystitis, commonly reported among Pakistani married women, occurs primarily during pregnancy. Preventive measures during pregnancy are suggested.

Adult↗

PubMed1995

Specific inhibition of DNA polymerase beta by its 14 kDa domain: role of single- and double-stranded DNA binding and 5'-phosphate recognition.

DNA polymerase beta (beta-polymerase) has been implicated in short-patch DNA synthesis in the DNA repair pathway known as base excision repair. The native 39 kDa enzyme is organized into four structurally and functionally distinct domains. In an effort to examine this enzyme as a potential therapeutic target, we analyzed the effect of various beta-polymerase domains on the activity of the enzyme in vitro. We show that the 14 kDa N-terminal segment of beta-polymerase, which binds to both single- and double-stranded DNA, but lacks DNA polymerase activity, inhibits beta-polymerase activity in vitro. Most importantly, the 8, 27 and 31 kDa domains of beta-polymerase do not inhibit beta-polymerase activity, demonstrating that the inhibition by the 14 kDa domain is specific. The inhibition of beta-polymerase activity in vitro is abolished by increasing the concentrations of both of the substrates (template-primer and deoxynucleoside triphosphate). In contrast, an in vitro base excision repair assay is inhibited in a domain specific manner by the 14 kDa domain even in the presence of saturating substrates. The inhibition of beta-polymerase activity by the 14 kDa domain appears specific to beta-polymerase as this domain does not inhibit either mammalian DNA polymerase alpha or Escherichia coli polymerase I (Klenow fragment). These data suggest that the 14 kDa domain could be used as a potential inhibitor of intracellular beta-polymerase and that it may provide a means for sensitizing cells to therapeutically relevant DNA damaging agents.

Base Sequence↗

PubMed1995

Purification and characterization of DNA ligase III from bovine testes. Homology with DNA ligase II and vaccinia DNA ligase.

Mammalian cell nuclei contain three biochemically distinct DNA ligases. In the present study we have found high levels of DNA ligase I and DNA ligase III activity in bovine testes and have purified DNA ligase III to near homogeneity. The high level of DNA ligase III suggests a role for this enzyme in meiotic recombination. In assays measuring the fidelity of DNA joining, we detected no significant differences between DNA ligases II and III, whereas DNA ligase I was clearly a more faithful enzyme and was particularly sensitive to 3' mismatches. Amino acid sequences of peptides derived from DNA ligase III demonstrated that this enzyme, like DNA ligase II, is highly homologous with vaccinia DNA ligase. The absence of unambiguous differences between homologous peptides from DNA ligases II and III (10 pairs of peptides, 136 identical amino acids) indicates that these enzymes are either derived from a common precursor polypeptide or are encoded from the same gene by alternative splicing. Based on similarities in amino acid sequence and biochemical properties, we suggest that DNA ligases II and III, Drosophila DNA ligase II, and the DNA ligases encoded by the pox viruses constitute a distinct family of DNA ligases that perform specific roles in DNA repair and genetic recombination.

Amino Acid Sequence↗

PubMed1995

The aetiological and clinical pattern of childhood urolithiasis in Saudi Arabia.

The clinical and aetiological pattern in 85 stone-forming children presenting to an integrated nephrourological service in Riyadh is reviewed. All patients were below the age of 15 years, the male to female ratio being 2:1. Only 2 children presented with bladder calculi. The remaining all had upper tract stones and, in 12 cases, these were bilateral. Of 34 calculi recovered for analysis, one-third was predominantly calcium oxalate and a further third was composed of uric acid or urate. Four patients had cysteine stones and the remaining 7 presented mixed calcium stones, 6 (17.6%) being struvite and infection-related. Of the 85 patients 55 were treated successfully with extracorporeal shock wave lithotripsy, 16 underwent surgery and 7 had their stones removed by endourological procedures. In the remaining 7 children, stones dissolved or were passed spontaneously during medical therapy. Nine children (10.6%) showed a primary metabolic defect leading to their stone formation, 10 (11.8%) had a predisposing anatomical anomaly and 15 (17.6%) presented with urinary tract infection. Of the remaining 51 patients (60%) with idiopathic disease, 6 showed hypercalciuria on investigation and 2 children may have formed their stones due to prolonged recumbency.

Adolescent↗

PubMed1995

Mammalian DNA ligase III: molecular cloning, chromosomal localization, and expression in spermatocytes undergoing meiotic recombination.

Three biochemically distinct DNA ligase activities have been identified in mammalian cell extracts. We have recently purified DNA ligase II and DNA ligase III to near homogeneity from bovine liver and testis tissue, respectively. Amino acid sequencing studies indicated that these enzymes are encoded by the same gene. In the present study, human and murine cDNA clones encoding DNA ligase III were isolated with probes based on the peptide sequences. The human DNA ligase III cDNA encodes a polypeptide of 862 amino acids, whose sequence is more closely related to those of the DNA ligases encoded by poxviruses than to replicative DNA ligases, such as human DNA ligase I. In vitro transcription and translation of the cDNA produced a catalytically active DNA ligase similar in size and substrate specificity to the purified bovine enzyme. The DNA ligase III gene was localized to human chromosome 17, which eliminated this gene as a candidate for the cancer-prone disease Bloom syndrome that is associated with DNA joining abnormalities. DNA ligase III is ubiquitously expressed at low levels, except in the testes, in which the steady-state levels of DNA ligase III mRNA are at least 10-fold higher than those detected in other tissues and cells. Since DNA ligase I mRNA is also present at high levels in the testes, we examined the expression of the DNA ligase genes during spermatogenesis. DNA ligase I mRNA expression correlated with the contribution of proliferating spermatogonia cells to the testes, in agreement with the previously defined role of this enzyme in DNA replication. In contrast, elevated levels of DNA ligase III mRNA were observed in primary spermatocytes undergoing recombination prior to the first meiotic division. Therefore, we suggest that DNA ligase III seals DNA strand breaks that arise during the process of meiotic recombination in germ cells and as a consequence of DNA damage in somatic cells.

Amino Acid Sequence↗

PubMed1994

Mammalian DNA ligase II is highly homologous with vaccinia DNA ligase. Identification of the DNA ligase II active site for enzyme-adenylate formation.

Mammalian cells contain three biochemically distinct DNA ligases. In this report we describe the purification of DNA ligase II to homogeneity from bovine liver nuclei. This enzyme interacts with ATP to form an enzyme-AMP complex, in which the AMP moiety is covalently linked to a lysine residue. An adenylylated peptide from DNA ligase II contains the sequence, Lys-Tyr-Asp-Gly-Glu-Arg, which is homologous to the active site motif conserved in ATP-dependent DNA ligases. The sequences adjacent to this motif in DNA ligase II are different from the comparable sequences in DNA ligase I, demonstrating that these enzymes are encoded by separate genes. The amino acid sequences of 15 DNA ligase II peptides exhibit striking homology (65% overall identity) with vaccinia DNA ligase. These peptides are also homologous (31% overall identity) with the catalytic domain of mammalian DNA ligase I, indicating that the genes encoding DNA ligases I and II probably evolved from a common ancestral gene. Since vaccinia DNA ligase is not required for DNA replication but influences the ability of the virus to survive DNA damage, the homology between this enzyme and DNA ligase II suggests that DNA ligase II may be involved in DNA repair.

Amino Acid Sequence↗

PubMed1994

Elevation of topoisomerase I messenger RNA, protein, and catalytic activity in human tumors: demonstration of tumor-type specificity and implications for cancer chemotherapy.

Topoisomerase I has been identified as an intracellular target of camptothecin, a plant alkaloid with anticancer activity. Various lines of evidence suggest that the sensitivity of cells to this drug is directly related to the topoisomerase I content. In humans, the levels of topoisomerase I have been shown to be elevated in colorectal tumors, compared to normal colon mucosa. The aim of our study was to determine whether (a) topoisomerase I levels are elevated in other solid tumors, (b) the elevated enzyme is catalytically active in these tumors, and (c) the increase in topoisomerase I levels in colorectal tumors is a result of increased transcription or translation. Topoisomerase I levels were quantitated in crude extracts from colorectal, prostate, and kidney tumors and their matched normal counterparts by Western blotting and by direct determination of catalytic activity, and mRNA levels were determined by Northern blotting. By Western blotting, colorectal tumors showed 5-35-fold increases in topoisomerase I levels, compared to their normal colon mucosa. In the case of prostate tumors, the increase was 2-10-fold, compared with benign hyperplastic prostate tissue from the same patients. However, no difference was observed in topoisomerase I levels in kidney tumors, compared to their normal counterparts. The catalytic activity of topoisomerase I was determined by a quantitative 32P-transfer assay in crude homogenates, without isolating nuclei. Colorectal and prostate tumors exhibited 11-40- and 4-26-fold increases, respectively, in catalytic activity. However, kidney tumors did not show any alteration in catalytic activity, compared to their normal matched samples. Thus, for all three tumor types there was a good correlation between enzyme levels and catalytic activity. Finally, colorectal tumors were analyzed for steady state mRNA levels. A 2-33-fold increase in mRNA levels was found in colorectal tumors, compared to normal colon mucosa. These results suggest that alterations in topoisomerase I expression in humans are tumor type specific and that the increase in topoisomerase I levels results from either increased transcription of the topoisomerase I gene or increased mRNA stability.

Amino Acid Sequence↗

PubMed1994

Primary extracorporeal shockwave lithotripsy in management of large bladder calculi.

Large bladder calculi are often outside the range of treatment with conventional endoscopic lithotrites because of either anatomic factors or the mechanical limits of available instruments. Alternative methods of cystolithotripsy: ultrasonic, electrohydraulic, or laser, can prove time-consuming or even hazardous, so that open surgery is often the most expeditious option. We report our experience using Dornier HM3 extracorporeal shockwave lithotripsy (SWL) for initial bladder stone reduction preparatory to transurethral litholapaxy and definitive treatment of any underlying obstructive pathology. Primary cystolitholapaxy was judged impractical in these 24 patients (21 adults and 3 children) presenting 31 large bladder stones (mean size 35.6 mm). In all patients, primary transpelvic SWL was followed immediately by endoscopic evacuation of stone debris or cystolitholapaxy. In addition, 10 of the 24 patients (42%) underwent a definitive endoscopic operation for treatment of an underlying obstructive lesion at either the same or a follow-on session. Morbidity was minimal, and the mean hospital stay after the initial SWL treatment was 3.5 days. In our experience, Dornier SWL has proved invaluable in enabling cystolitholapaxy of very large bladder calculi that would otherwise require protracted and difficult endoscopic manipulation or open surgery.

Adolescent↗

PubMed1994

Multisite point-of-care potassium testing for patient-focused care.

In the past two decades, a dominant paradigm has been the main laboratory, which is often located far from the patient and characterized by slow response times. The invention of whole blood biosensors and the innovation of point-of-care testing have initiated a paradigm shift in diagnostic medicine that supports the trend toward patient-focused care. The objective of this study was to compare point-of-care potassium testing performed with a handheld potassium analyzer (STAT K, PDx Technologies Inc, Westlake Village, Calif) in the cardiac and intensive care units with potassium measurements obtained similarly in the main laboratory. Two critical care nurses performed point-of-care testing for critically ill patients. In a series of 56 specimens, the mean +/- SD potassium levels were 3.91 +/- 0.53 and 3.94 +/- 0.57 mmol/L when testing was performed at the bedside and in the main laboratory, respectively. The mean paired difference, -0.03 mmol/L, between point-of-care and main laboratory results was not statistically or clinically significant. Point-of-care potassium testing is accurate and precise, as well as clinically efficient for use in patient-focused care settings.

Delivery of Health Care↗

PubMed1994

Synthesis and biological studies on some organo-tin and lead halo and mixed halo-pseudohalo anionic complexes.

Some new anionic complexes of organo-tin(IV) and lead (IV) isolated in combination of tetraorgano-ammonium phosphonium and stibonium cation(s). L[R4-nMXnY] and L2[R2MX2Y2], where R = C2H5, C4H9 or C6H5; M = Sn or Pb; X = Y = Cl = Br, I, N3, NCS; n = 1, 2 and L = R4M1 (M1 = N, P, Sb), whose structures were confirmed by correct elemental analyses, molar conductance values, van't Hoff factor and IR spectral studies, were synthesized and evaluated for anti-convulsant activity in vivo and antiviral and antibacterial activity in vitro. A few of them exhibited promising activity. In addition, the toxicity (ALD50) and effects on the central nervous system of these complexes have been studied in mice.

Animals↗

PubMed1993

Incidence of bacteremia and bacteriuria in patients with non-infection-related urinary stones undergoing extracorporeal shock wave lithotripsy.

In a prospective pilot study, 26 patients with non-infection-related renal or ureteric stones and sterile urine were examined for evidence of bacteriuria and bacteremia following extracorporeal shock wave lithotripsy (SWL). Blood samples were obtained for aerobic and anaerobic bacterial culture at the end of, and 1 hour after, the SWL procedure. Urine cultures were performed 24 hours before and after treatment. Bacteremia was recorded in 7.7% of the patients immediately after SWL but in no patient at 1 hour after treatment. None of the patients manifested significant bacteriuria or post-SWL fever. These findings support the contention that, provided the urine is sterile and a negative history of urosepsis is available, antibiotic prophylaxis is unnecessary in patients with non-infected renal stones submitted to SWL treatment.

Adolescent↗

PubMed1993

Narcolepsy.

Narcolepsy afflicts more than 200,000 Americans. In most cases the first symptom of the disease, excessive daytime sleepiness, develops during childhood or adolescence. This initial presentation is followed by cataplexy or other auxiliary symptoms several years later. Not infrequently, many years pass before the proper diagnosis of narcolepsy is made. Narcolepsy is a chronic lifelong disease without periods of remission. Excessive daytime sleepiness, inappropriate sleep attacks, and the pathognomonic symptom of cataplexy, are diagnostic of narcolepsy. Confirmation of the disease is made by a multiple sleep latency test. Although still not being used for diagnostic purposes, the association between narcolepsy and the human leukocyte group A (HLA) antigen DR2 is the strongest so far described for any disease. With the help of psychosocial support, therapeutic naps, and medications, the patient with narcolepsy may be able to lead a normal life. Methylphenidate and imipramine are the two most widely used drugs for the treatment of daytime somnolence and cataplexy, respectively.

Diagnosis, Differential↗

PubMed1991

Sequence effect on incision by (A)BC excinuclease of 4NQO adducts and UV photoproducts.

Nucleotide excision repair in Escherichia coli is initiated by (A)BC excinuclease, an enzyme which incises DNA on both sides of bulky adducts and removes the damaged nucleotide as a 12-13 base long oligomer. The incision pattern of the enzyme was examined using DNA modified by 4-nitroquinoline 1-oxide (4NQO) and UV light. Similar to the cleavage pattern of UV photoproducts and other bulky adducts, the enzyme incises the 8th phosphodiester bond 5' and 5th phosphodiester bond 3' to the 4NQO-modifed base, primarily guanine. The extent of DNA damage by these agents was determined using techniques which quantitatively cleave the DNA or stop at the site of the adduct. By comparison of the intensity of gel bands created by (A)BC excinuclease and the specific cleavage at the damaged site, the efficiency of (A)BC excinuclease incision at 13 different 4NQO-induced adducts and 13 different photoproducts was determined by densitometric scanning. In general, incisions made at 4NQO-induced adducts are proportional to the extent of damage, though the efficiency of cutting throughout the sequence tested varies from 25 to 75%. Incisions made at pyrimidine dimers are less efficient than at 4NQO-adducts, ranging from 13 to 65% incision relative to modification, though most are around 50%. The two (6-4) photoproducts within the region tested are incised more efficiently than any pyrimidine dimer.

4-Nitroquinoline-1-oxide↗

PubMed1991

Polyurethane internal ureteral stents in treatment of stone patients: morbidity related to indwelling times.

The morbidity and complications associated with use of internal polyurethane ureteral stents in a series of 290 stone patients treated endourologically or with extracorporeal shock wave lithotripsy were retrospectively reviewed. Of the 299 stents retrieved 141 were also tested for patency to relate the rate of luminal blockage with stent caliber, indwelling time and clinical evidence of obstruction in the stented tract. Stent indwelling times ranged from a few days to 18 months: 11.3% were indwelling longer than 6 months and 1.9% were lost to followup. Incrustation occurred in 9.2% of the stents retrieved before 6 weeks, 47.5% indwelling 6 to 12 weeks and 76.3% thereafter. In 19 cases over-all (6.4%) an auxiliary procedure was required to decrease incrusted stone burden and enable stent retrieval. Other complications included stent migration (3.7%), infection (6.7%) and breakage (0.3%). Despite a 30% rate of luminal blockage in stents retrieved after indwelling times up to 3 months, the incidence of clinical obstruction in stented tracts up to 3 months was 4%, confirming other reports that significant urine flow occurs around rather than through hollow, vented stents. Our findings underline the importance of restricting the use of stents to stone patients who will be reliable at followup. Morbidity was minimal if stent indwelling times did not exceed 6 weeks.

Catheters, Indwelling↗

PubMed1990

Role of carrier ligand in platinum resistance in L1210 cells.

We have examined the effect of carrier ligands on platinum accumulation, incorporation of platinum into DNA, cytotoxicity of Pt-DNA adducts, and repair of Pt-DNA adducts in three L1210 cell lines: L1210/0, which is sensitive to most types of platinum compounds; L1210/DDP, which is resistant to platinum compounds with the ethylenediamine (en) carrier ligand but sensitive to those with the diaminocyclohexane (dach) ligand; and L1210/DACH, which is resistant to dach-Pt compounds but sensitive to en-Pt compounds. There was a selective decrease in accumulation of dach-Pt in the L1210/DACH line and of en-Pt in the L1210/DDP line. Intracellular dach-Pt was incorporated into DNA to a lesser extent than en-Pt in both resistant cell lines. Cytotoxicity of en-Pt adducts was less than that of dach-Pt adducts in the L1210/DDP line, while the reverse was true in the L1210/DACH line. Increased repair was seen in both resistant cell lines; a carrier ligand effect was seen only in the L1210/DDP line, which showed a greater initial rate of repair for en-Pt than dach-Pt adducts. These data suggest that carrier ligand effects seen in resistant cell lines may be due, in part, to differences in accumulation of platinum, repair of Pt-DNA adducts, and tolerance of Pt-DNA adducts.

Animals↗

PubMed1990

Effect of the diaminocyclohexane carrier ligand on platinum adduct formation, repair, and lethality.

Platinum compounds with the diaminocyclohexane (dach) carrier ligand are of particular interest because cell lines that have developed resistance to platinum compounds in general often retain sensitivity to dach-platinum compounds, suggesting that the dach carrier ligand affects the formation, repair, or lethality of platinum-DNA adducts. The effect of the dach ligand on platinum adduct formation was assessed by using the (HaeIII-HindIII)146 fragment of pBR322 treated to give equal amounts of dach- or ethylene-diamine-platinum adducts. The sites of adduct formation were mapped by digestion with Escherichia coli ABC excinuclease. There were no significant effects of the dach carrier ligand on the types or sites of platinum adduct formation. The effect of the dach ligand on platinum adduct repair was determined by using synthetic oligomers designed to have single, specific platinum adducts (G monoadduct; GG, AG, or GNG diadduct) with either the dach or ethylenediamine (en) carrier ligand. These adducts differed significantly in their ability to serve as substrates for ABC excinuclease with GNG greater than or equal to G greater than AG greater than GG. The dach carrier ligand had little effect on the recognition of AG and GG adducts by ABC excinuclease, but significantly improved the ability of ABC excinuclease to excise G monoadducts and GNG diadducts. These data suggest that if the carrier ligand has any effect on the repair of platinum adducts, it is more likely to exert that effect on the repair of platinum monoadducts or GNG diadducts rather than on the more abundant AG or GG diadducts. [14C]Thiourea incorporation was used to quantitate the rate of monoadduct to diadduct conversion.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1990

Critique of the Dornier HM3 lithotripter as a clinical algesimeter.

The power and nociceptive intensity of shock waves generated by the Dornier HM3 extracorporeal shock wave lithotripter (ESWL) are voltage dependent and suited to algesimetry in a controllable voltage range of 8-30 kV. Fidelity of the HM3 as an algesimeter was tested by: (1) In vitro measurements of shock pressure at voltages between 14 and 30 kV were recorded by a force transducer at the point of clinical focus. (2) Unanaesthetized volunteer (n = 5) assessment and VAS pain scores of shocks in the range of 10-24 kV, yielding highly significant correlations between blinded randomized shock voltage (r = 0.88), and VAS scores (r = 0.84). (3) Voltage-tolerance curves generated from 33 ASA class 1 or 2 patients undergoing ESWL treatment under epidural analgesia with 0.125% bupivacaine, fortified with a bolus epidural dose of 100 micrograms fentanyl if pain arose during treatment. Voltage tolerance was increased by 50% after an epidural bolus of 100 micrograms fentanyl (P less than 0.001). The respiratory consequences of epidural fentanyl were assessed by changes of respiratory rate and rhythm recorded from capnographic tracings of expired carbon dioxide. This study indicates that the Dornier HM3 system provides a valuable opportunity to conduct precise, quantitative measurements of induced deep truncal pain, as well as the effectiveness and respiratory cost of analgesic interventions directly applicable to the safe management of acute pain.

Analgesia, Epidural↗

PubMed1990

Synapse formation on quail trochlear neurons transplanted in duck embryos before naturally occurring motor neuron death.

About half of the trochlear motor neurons in duck and quail embryos die during normal development. In a previous study the role of target muscle in controlling the number of surviving motor neurons was investigated by reducing the number of neurons innervating the muscle. This was accomplished by removing the midbrain of the duck embryo and grafting in its place the midbrain of the quail embryo before motor neuron death begins. It was observed that the number of surviving trochlear motor neurons in the quail-duck chimera embryos was not significantly different from that of the normal quail. The present investigation was undertaken to determine whether trochlear motor neurons in the chimera embryos received afferent synapses. Brains of duck, quail and chimera embryos on days 16 and 20 were processed for electron microscopical observations. Synapses formed on motor neurons of the chimera embryos. Surprisingly, synapses on motor neurons of quail differed from those of duck, both qualitatively and quantitatively. Synapses on the motor neurons of the chimera embryos developed in a fashion similar to that for the duck motor neurons. Our failure to rescue trochlear motor neurons in the chimera embryos suggests that the developing motor neurons may respond to a larger target muscle only if they received a normal complement of afferent synaptic input.

Animals↗