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Biomedical subjects

Z Ali

Publications and source records attributed to Z Ali.

At least 55 records · Page 3Linked to original sources
PubMed1999

Application of the quartz crystal microbalance to the monitoring of Staphylococcus epidermidis antigen-antibody agglutination.

The change in solution properties due to the agglutination of an antigen with its specific antibody has previously been used as a marker of infection. This method has been modified to allow the binding activity between species to be followed using the frequency response of a quartz crystal microbalance (QCM). The Bayston agglutination plate assay for Staphylococcus epidermidis has been modified to allow the electrode of a QCM to act as a direct sensor for the change in solution properties as agglutination occurs. Antibody and antigen were introduced to the crystal surface and the agglutination process was followed as a change in crystal resonant frequency. Serum, known to be infected with the organism, gave a titre of 3.9x10(-2)% v/v (-118 Hz, +/-12 SD, N = 9) matching that given by triplicate plate assay. Uninfected serum gave no frequency changes at this concentration, yielding a titre of 2.5x10(-2)% v/v again matching the plate titre (N = 3). Infected serum gave responses 40 times faster then those of the uninfected serum. The piezoelectric quartz crystal method gave a positive or negative diagnosis in <15 min compared with the 24 h required for the plate assay.

Agglutination Tests↗
PubMed1999

Uninjured C-fiber nociceptors develop spontaneous activity and alpha-adrenergic sensitivity following L6 spinal nerve ligation in monkey.

We investigated whether uninjured cutaneous C-fiber nociceptors in primates develop abnormal responses after partial denervation of the skin. Partial denervation was induced by tightly ligating spinal nerve L6 that innervates the dorsum of the foot. Using an in vitro skin-nerve preparation, we recorded from uninjured single afferent nerve fibers in the superficial peroneal nerve. Recordings were made from 32 C-fiber nociceptors 2-3 wk after ligation and from 29 C-fiber nociceptors in control animals. Phenylephrine, a selective alpha1-adrenergic agonist, and UK14304 (UK), a selective alpha2-adrenergic agonist, were applied to the receptive field for 5 min in increasing concentrations from 0.1 to 100 microM. Nociceptors from in vitro control experiments were not significantly different from nociceptors recorded by us previously in in vivo experiments. In comparison to in vitro control animals, the afferents found in lesioned animals had 1) a significantly higher incidence of spontaneous activity, 2) a significantly higher incidence of response to phenylephrine, and 3) a higher incidence of response to UK. In lesioned animals, the peak response to phenylephrine was significantly greater than to UK, and the mechanical threshold of phenylephrine-sensitive afferents was significantly lower than for phenylephrine-insensitive afferents. Staining with protein gene product 9.5 revealed an approximately 55% reduction in the number of unmyelinated terminals in the epidermis of the lesioned limb compared with the contralateral limb. Thus uninjured cutaneous C-fiber nociceptors that innervate skin partially denervated by ligation of a spinal nerve acquire two abnormal properties: spontaneous activity and alpha-adrenergic sensitivity. These abnormalities in nociceptor function may contribute to neuropathic pain.

Adrenergic alpha-Agonists↗
PubMed1999

An analysis of common isodisomic regions in five mUPD 16 probands.

Intrauterine growth retardation (IUGR) with or without additional abnormalities is recognised as a common feature of maternal uniparental disomy for chromosome 16 (mUPD 16) and is usually associated with confined placental mosaicism (CPM). Although it is likely that the CPM largely contributes to the IUGR, postnatal growth retardation and other common abnormalities may also be attributed to the mUPD. Five cases with mUPD 16 and CPM were analysed for common regions of isodisomy using polymorphic markers distributed along the length of the chromosome. In each case the aberration was consistent with a maternal meiosis I error. Complete isodisomy was not detected in any of the patients although two patients were found to be mixed with both iso- and heterodisomy. Interestingly, the patient with the greater region of isodisomy was the most severely affected. The fact that there were no common regions of isodisomy in any of the patients supports the hypothesis that imprinted genes, rather than recessive mutations, may play a role in the shared phenotypes.

Blotting, Southern↗
PubMed1999

An analysis of the distribution of hetero- and isodisomic regions of chromosome 7 in five mUPD7 Silver-Russell syndrome probands.

Silver-Russell syndrome (SRS) shares common features of intrauterine growth retardation (IUGR) and a number of dysmorphic features including lateral asymmetry in about 50% of subjects. Its genetic aetiology is complex and most probably heterogeneous. Approximately 7% of patients with SRS have been found to have maternal uniparental disomy of chromosome 7 (mUPD7). Genomic DNA samples from five SRS patients with mUPD7 have been analysed for common regions of isodisomy using 40 polymorphic markers distributed along the length of chromosome 7. No regions of common isodisomy were found among the five patients. It is most likely that imprinted gene(s) rather than recessive mutations cause the common phenotype. Heterodisomy of markers around the centromere indicated that the underlying cause of the mUPD7 is a maternal meiosis I non-disjunction error in these five subjects.

Abnormalities, Multiple↗
PubMed1998

Anti-phospholamban and protein kinase A alter the Ca2+ sensitivity and maximum velocity of Ca2+ uptake by the cardiac sarcoplasmic reticulum.

The activity of the SERCA2a Ca2+ pump in the sarcoplasmic reticulum (SR) of cardiac muscle is inhibited by phospholamban. When phospholamban is phosphorylated by cyclic-AMP-dependent protein kinase (PKA) this inhibition is relieved. It is generally agreed that this results in an increase in the Ca2+ sensitivity of the SR Ca2+ pump; however, some investigators have also reported an increase in the maximum velocity of the pump. We have used a sensitive fluorescence method to measure net Ca2+ uptake by native cardiac SR vesicles and compared the effects of a constitutively active subunit of PKA (cPKA) with those of a monoclonal antibody (A1) that binds to phospholamban and is thought to mimic the effect of phosphorylation. Both the Ca2+ sensitivity and the maximum velocity of uptake were increased by cPKA and by A1. The effects of cPKA and A1 on uptake velocity were only slightly additive. No changes in uptake were detected with denatured cPKA or denatured A1. These results indicate that the functional effect of phospholamban phosphorylation is to increase both the Ca2+ sensitivity and the maximum velocity of net Ca2+ uptake into the SR.

Animals↗
PubMed1998

Expression of the insulin-like growth factors and their receptors in term placentas: a comparison between normal and IUGR births.

Intrauterine growth retardation (IUGR) is defined as growth retarded to be below the tenth centile. The insulin-like growth factors and their receptors are implicated in pre- and postnatal growth and development, and it is believed that alteration in their activity may contribute to IUGR. In this study nine normal and nine intrauterine growth retarded births were followed and term placentas examined for expression of the insulin-like growth factors and their receptors. It was found that the expression of insulin-like growth factor 1 (IGF1), insulin-like growth factor 2 (IGF2), and the insulin, IGF1 and IGF2 receptor transcripts (IGF1R and IGF2R, respectively) was present in all term placentas examined. Expression of insulin was not detected. Quantitative polymerase chain reaction (PCR) was used to compare transcription levels in term placentas from normal with IUGR births. There was no significant difference in the levels of transcripts for IGF1, insulin receptor, or IGF2R between normal and IUGR term placentas. However, the IUGR term placentas had significantly higher levels of IGF2 and IGF1R expression compared with the normal term placentas. The increase in the transcription of IGF2 and IGF1R in IUGR term placentas may represent a counter regulatory mechanism in response to the growth retardation.

Adult↗
PubMed1998

Ruthenium red reduces the Ca2+ sensitivity of Ca2+ uptake into cardiac sarcoplasmic reticulum.

Ruthenium red inhibits mitochondrial Ca2+ uptake and is widely used as an inhibitor of ryanodine-sensitive Ca2+ channels that function to release Ca2+ from the sarcoplasmic reticulum (SR) of muscle cells. It also has effects on other Ca2+ channels and ion transporters. To study the effects of ruthenium red on Ca2+ transport into the SR of cardiac muscle cells, fluorescence measurements of Ca2+ uptake into cardiac SR vesicles were made. Ruthenium red significantly decreased the Ca2+ sensitivity of SR uptake in a dose-dependent manner at concentrations ranging from 5 microM to 20 microM. There were no significant effects of ruthenium red on the maximum velocity or the Hill coefficient of SR Ca2+ uptake.

Animals↗
PubMed1998

Infants in Trinidad excrete more 5-L-oxoproline (L-pyroglutamic acid) in urine than infants in England: an environmental not ethnic difference.

The demand for glycine to satisfy normal growth during early life is considerable and most has to be made endogenously. The extent to which adequate glycine is available can be assessed by measuring the urinary excretion of 5-L-oxoproline. The excretion of 5-L-oxoproline at 6 weeks of age for infants in Trinidad of African, Indian or mixed parentage (398 mumol/mmol creatinine) was significantly greater than for infants born in England of Caucasian parentage (194 mumol/mmol creatinine). There was no relationship between 5-L-oxoproline excretion and either sex or pattern of feeding. There were significant inverse relationships between 5-L-oxoproline/creatinine and birth weight, and head circumference either at birth or 6 weeks of age, suggesting that limited availability of glycine is associated with poorer growth before and after birth. For a group of infants born in England of Indian parentage, excretion of 5-L-oxoproline (155 mumol/mmol creatinine) was not different to infants of Caucasian parentage, but significantly less than infants born in Trinidad. The demonstration that 5-L-oxoproline/creatinine was similar in infants born in England, regardless of parentage, shows that the differences between England and Trinidad are related to environment and are unlikely to be accounted for by genetic differences or ethnicity.

Africa↗
PubMed1998

Adenosine deaminase activity in protein-energy malnutrition.

Cell-mediated immunity (CMI) was evaluated in 69 children with protein-energy malnutrition (PEM) and 20 healthy controls. Significantly decreased responses to purified protein derivative (PPD) (p < 0.02) and absolute lymphocyte count (ALC) (p < 0.01) and increased serum adenosine deaminase (ADA) activity (p < 0.001) were observed in PEM cases compared with the controls. The mean values of ALC and ADA activity in PEM patients were 85.9% and 158.7% of the normal mean, respectively. A significant negative correlation was observed between the two parameters (r=- 0.2765, p < 0.01). The CMI tests were abnormal in all three grades of PEM, except for the response to PPD in grade I, when compared with the controls. No significant differences were found between infected and uninfected PEM cases. Thus, impaired CMI was observed not only in grades II and III but also in grade I PEM patients and the concomitant infection did not affect its status. However, ADA activity demonstrated a more pronounced change than the other tests.

Adenosine Deaminase↗
PubMed1997

Structure of active chromatin: isolation and characterization of transcriptionally active chromatin from rat liver.

Rat liver nuclei were isolated in low-ionic-strength buffer in the absence of bi- and multi-valent cations. Digestion of these nuclei by endogenous nuclease, micrococcal nuclease and DNase I revealed that a minor chromatin fraction was preferentially digested into poly- and oligo-nucleosomes. Southern blot hybridization with various active gene probes confirmed that these chromatin fragments represent coding and 5' upstream regions of transcriptionally active chromatin. Active chromatin fragments were released selectively into the medium, with inactive chromatin remaining inside the nuclei, under the above ionic conditions. The inclusion of bivalent cations during the digestion of nuclei reversed the solubility behaviour of active chromatin. Rearrangement and exchange of histone H1 between chromatin fragments was prevented by using low-salt conditions in all steps in the absence of bivalent cations. All histones, including H1, were present in stoichiometric amounts in this active chromatin fraction. Active nucleosomes showed a lower electrophoretic mobility than bulk nucleosomes in an acrylamide/agarose composite gel in the absence of Mg2+, but were selectively bound to the gel in the presence of this ion.

Animals↗
PubMed1997

Structure of active chromatin: covalent modifications of histones in active and inactive genes of control and hypothyroid rat liver.

Covalent modifications of histones in active and bulk chromatin fractions were studied in liver tissue from control and hypothyroid rats. The levels of acetylation and ubiquitination of histones were similar in the active and bulk chromatin fractions, and were not influenced by hypothyroidism. Histone H2A only was phosphorylated in control active and bulk chromatin fractions. The extent of this phosphorylation did not differ between the two fractions, but hypothyroidism greatly suppressed it. Indicating an association with tissue growth. ADP-ribosylation of histones was found to be mainly associated with transcriptional inactivation of the chromatin, while histone methylation was correlated with growth inhibition of the tissue, as observed with hypothyroidism. The validity of these conclusions will, however, depend upon the similarity of the turnover rates of these covalent modifications between active and inactive chromatin and between control and hypothyroid states.

Acetylation↗
PubMed1997

Structure of active chromatin: higher-order folding of transcriptionally active chromatin in control and hypothyroid rat liver.

Investigation have been carried out into the salt-induced higher-order folding in the transcriptionally active chromatin region of rat liver nuclei by nuclease digestion, sedimentation and CD. The sensitivity of active chromatin in nuclei to micrococcal nuclease was suppressed by raising the ionic strength from 25 to 90 mM, indicating the occurrence of salt-induced condensation. The rate of sedimentation of fractionated inactive chromatin fragments of both moderate (approximately 3.5 kbp) and large (approximately 8.8 kbp) size increased maximally to the same extent, while that of active chromatin fragments was dependent on their size. The rate of sedimentation of moderately sized active chromatin fragments (approximately 5.5 kbp) showed a maximal 15% increase at 90 mM ionic strength. In contrast, a large increase (at least 60%) in the sedimentation rate of large active chromatin fragments (approximately 21 kbp) was observed at 65 mM ionic strength. A reasonable degree of higher-order folding was observed in large active chromatin fragment even at 25 mM ionic strength. On considering the percentage increase in sedimentation rate as a measure of the higher-order folding of chromatin, a different type of higher-order folding was observed in active chromatin fragments. Although the percentage increase in sedimentation decreased from 40 to 24% with an increase in the size of active chromatin from approximately 3 to approximately 9 kbp, a further increase in size up to 16 kbp brought the percentage increase back to 40%. CD studies agreed with the conclusions drawn from sedimentation studies. Active chromatin from hypothyroid rats showed similar folding behaviour, but the order of folding was slightly lower than for control active chromatin, at all sizes.

Animals↗
PubMed1997

The incidence of uniparental disomy associated with intrauterine growth retardation in a cohort of thirty-five severely affected babies.

OBJECTIVE: Our purpose was to screen for uniparental disomy 35 babies with idiopathic intrauterine growth retardation < 5th percentile. STUDY DESIGN: The placenta and the baby's blood were conventionally karyotyped. Deoxyribonucleic acid from the parents, the baby's blood, and the placenta were then screened for uniparental disomy for 12 candidate chromosomes with use of chromosome-specific polymorphic deoxyribonucleic acid markers. RESULTS: Two cases of maternal uniparental disomy for chromosome 16 were found associated with confined placental mosaicism for chromosome 16. No other uniparental disomy was found for any of the 12 chromosomes tested. Four structural chromosome abnormalities were also found in this cohort through standard karyotyping. CONCLUSION: Uniparental disomy for the chromosomes tested does not explain the etiology of the majority of cases of intrauterine growth retardation < 5th percentile. Maternal uniparental disomy for chromosome 16 accounts for 5% of this cohort. Structural chromosomal abnormalities are also much higher than expected at 11%.

Chromosome Aberrations↗
PubMed1997

Adenosine deaminase activity in nephrotic syndrome.

Cell-mediated immunity (CMI) was evaluated in 40 children with idiopathic nephrotic syndrome and 20 healthy controls. The significantly decreased response to purified protein derivative (PPD)(P < 0.001), absolute lymphocyte count (ALC) (P < 0.02), T-lymphocytes percentage (P < 0.001) and elevated serum adenosine daminase (ADA) activity (P < 0.001) were observed in patients with active nephrotic syndrome (ANS) in comparison to controls. The overall mean values of T-lymphocytes percentage and ADA activity in ANS patients were 73.7 and 213.7 per cent of normal mean, respectively. A significant negative correlation was observed between the two parameters (r = -0.5649, P < 0.001). In remission, the ALC and T-lymphocytes percentage showed significant increase in levels in comparison to their corresponding ANS values (P < 0.05 and P < 0.001, respectively), but the latter remained significantly lower when compared with controls (P < 0.001). The ADA activity did not differ significantly in comparison to corresponding ANS level. Thus, impaired CMI was observed both in active, as well as in remission stage of the disease and ADA activity demonstrated a more pronounced change than other parameters.

Adenosine Deaminase↗
PubMed1997

Immunoglobulins and circulating immune complexes in nephrotic syndrome.

Serum immunoglobulin (IgG, IgA and IgM) levels were measured in 40 children with idiopathic nephrotic syndrome and 20 healthy controls. Significantly decreased IgG (P < 0.001), normal IgA and increased IgM (P < 0.05), averaging 92 per cent, 99 per cent and 104 per cent of normal mean, respectively, were observed in active nephrotic syndrome (ANS). The mean immunoglobulin levels did not differ significantly among different subgroups of ANS cases. In remission, a significant increase in IgG (P < 0.01), a decrease in IgA (P < 0.05) and in IgM (P < 0.01) levels were found in comparison to their corresponding ANS values. Their concentrations were significantly abnormal also when compared with controls. The circulating immune complexes (CIC), detected by polyethylene glycol (PEG) per cent index, demonstrated that overall mean serum level was significantly higher (P < 0.01, 168 per cent of normal) in ANS patients. Among different subgroups, the mean level was significantly elevated (P < 0.001, 205 per cent of normal) only in relapsing nephrotic syndrome cases. Thus, the abnormal levels of immunoglobulins were found both in active as well as in remission stage of the disease, while elevated levels of CIC were seen only in patients with relapse.

Antigen-Antibody Complex↗
PubMed1996

The role of 5HT3 in nociceptive processing in the rat spinal cord: results from behavioural and electrophysiological studies.

Recent studies have suggested that activity at different 5HT receptor subtypes in the spinal cord either inhibits or facilitates nociceptive processing in the spinal cord. The present study has examined the role of 5HT3 receptors in nociceptive processing in the dorsal horn of the rat spinal cord. Using both behavioural and electrophysiological studies, 5HT3 ligands have been applied by a common route (i.e. intrathecal microinjection). In addition, only noxious heat has been used as a form of stimulation. Intrathecal injection of mCPBG (0.02-0.2 nmol) increased the responsiveness of dorsal horn neurones to noxious stimulation. In contrast, two 5HT3 antagonists (ICS 205-930 (0.015-0.15 nmol) and GR 380032F (ondansetron 34 nmol)) reduced nociceptive responses. Using doses which influenced nociceptive neuronal responses no significant change in TFL was recorded. These findings suggest that activation at 5HT3 receptor facilitates nociceptive responses of some dorsal horn neurones; these results are discussed in relation to earlier reports concerning alternative effects.

Animals↗