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Biomedical subjects

Z Ali

Publications and source records attributed to Z Ali.

At least 73 records · Page 4Linked to original sources

Secondary hyperalgesia to mechanical but not heat stimuli following a capsaicin injection in hairy skin.

A psychophysical investigation was carried out to examine whether heat hyperalgesia exists within the secondary mechanical hyperalgesia zone surrounding a capsaicin injection site on hairy skin. A non-contact laser stimulator was used to deliver temperature controlled stimuli to sites within and outside the zone of mechanical hyperalgesia. Heat testing was carried out before and after the intradermal injection of 50 micrograms of capsaicin into the volar forearm. The zones of mechanical hyperalgesia to punctate and stroking stimuli and the region of flare were also mapped after the capsaicin injection. Heat pain thresholds inside the secondary mechanical hyperalgesic zone were not significantly different from thresholds outside the secondary mechanical hyperalgesia zone. In addition, pain ratings to an ascending series of heat stimuli delivered inside the zone of secondary hyperalgesia were not significantly different from pain ratings outside the zone of secondary hyperalgesia. Thus, there was no evidence for heat hyperalgesia within the zone of secondary hyperalgesia to punctate mechanical stimuli. Though the areas of punctate and stroking hyperalgesia were correlated, no correlation existed between the magnitude of capsaicin evoked pain and the areas mechanical hyperalgesia to punctuate and stroking stimuli or the area of flare. This suggests that independent mechanisms may mediate evoked pain, central sensitization that leads to mechanical hyperalgesia, and axon reflexive flare.

Analysis of Variance↗

The Drosophila engrailed and invected genes: partners in regulation, expression and function.

We isolated and characterized numerous engrailed and invected alleles. Among the deficiencies we isolated, a mutant lacking invected sequences was viable and phenotypically normal, a mutant lacking engrailed was an embryo lethal and had slight segmentation defects, and a mutant lacking both engrailed and invected was most severely affected. In seven engrailed alleles, mutations caused translation to terminate prematurely in the central or C-terminal portion of the coding sequence, resulting in embryonic lethality and segmentation defects. Both engrailed and invected expression declined prematurely in these mutant embryos. In wild-type embryos, engrailed and invected are juxtaposed and are expressed in essentially identical patterns. A breakpoint mutant that separates the engrailed and invected transcription units parceled different aspects of the expression pattern to engrailed or invected. We also found that both genes cause similar defects when expressed ectopically and that the protein products of both genes act to repress transcription in cultured cells. We propose that the varied phenotypes of the engrailed alleles can be explained by the differential effects these mutants have on the combination of engrailed and invected activities, that engrailed and invected share a regulatory region, and that they encode redundant functions.

Alleles↗

Cerebrospinal fluid adenosine deaminase activity for the diagnosis of tuberculous meningitis in children.

Adenosine deaminase (ADA) activity was measured in the cerebrospinal fluid (CSF) of 27 subjects suffering from tuberculous meningitis (TBM), 19 from bacterial meningitis, 10 from encephalitis, and 10 control subjects. The mean CSF ADA level was significantly raised (P < 0.001) in TBM patients as compared to other study groups. A cut-off CSF ADA level of > 5 IU/1 was considered for the diagnosis of TBM, and the test had sensitivity and specificity of 89 and 92 per cent, respectively. Overall, it was found to be a better test in comparison to any other single test for the diagnosis of TBM. Confirmed TBM patients had significantly higher CSF ADA activity when compared with clinical TBM (P < 0.01) and the levels did not differ significantly among different stages of disease. The ADA level in TBM cases had significant correlation with CSF cell count (P < 0.01), lymphocyte percentage (P < 0.02) and protein concentration (P < 0.02). Thus, the CSF ADA activity assay was found to be a simple, useful and rapid diagnostic test for the early recognition of TBM in children.

Adenosine Deaminase↗

Expression of exon 3-retaining and -deleted human growth hormone receptor messenger ribonucleic acid isoforms during development.

Recent investigations have suggested that human GH (hGH) and its receptor may have specific functions during human fetal life. To improve our understanding of the mechanisms of hGH action during gestation, we characterized the ontogenic appearance of hGH receptor messenger ribonucleic acid (mRNA) in multiple human fetal and postnatal tissues. Using RT-PCR assays, followed by Southern hybridization to confirm the specificity of the amplified fragments, we scanned the entire coding region of the hGH receptor mRNA. Transcription of the hGH receptor gene was observed in all fetal tissues studied (liver, kidney, skin, muscle, lung, adrenal, spleen, intestine, central nervous system, pancreas, and placental villi) from the earliest stage that could be examined [7-14.8 weeks fetal age (FA)]. Furthermore, we identified only 2 isoforms of the hGH receptor mRNA-coding region: exon 3 can be retained or deleted. Surprisingly, we found individual-specific, not tissue-specific, expression patterns of these two transcripts when we examined multiple tissues (n = 2-6) from 15 individuals (11.5-33 weeks FA); this individual-specific pattern of expression is maintained in cultured dermal fibroblasts for at least 12 generations (n = 2; 16 and 20 weeks FA). In addition, a cross-sectional study of 78 individuals (9 weeks FA to 43 yr postnatal age) showed that the exon 3-deleted transcript is predominantly expressed in tissues from fetuses of 9-20 weeks FA (P < 0.002). Finally, we showed that the absence of exon 3 from the mRNA is not due to genomic deletion of exon 3 by amplifying exon 3 from genomic DNA of 3 fetuses (13.3-19 weeks FA) expressing only the exon 3-deleted mRNA transcript. We conclude that 1) transcription of the hGH receptor gene occurs in multiple tissues as early as the first trimester of human fetal life; 2) the exon 3-retaining and -deleted transcripts are the only two isoforms of the hGH receptor mRNA-coding region during gestation; and 3) the pattern of expression of these transcripts is individual specific and may be developmentally regulated.

Base Sequence↗

Neonatal meningitis: a 3-year retrospective study at the Mount Hope Women's Hospital, Trinidad, West Indies.

The objective of this 3-year (1988-1990) retrospective study was to report the experience with neonatal meningitis at the Neonatal Intensive Care Unit, Mount Hope Women's Hospital, Trinidad, West Indies. Neonates were included in the study if organisms were cultured from the cerebrospinal fluid (CSF) and/or if there was a pleocytosis (> or = 100/mm3) in the CSF. There were 49 neonates with meningitis out of a total of 17,048 live born (LB) infants during the 3-year period to give an overall incidence of 2.87/1000 LB. This was five times higher than the incidence reported in the literature. There were an additional five who were outborns to give a total of 54 cases. There were 34 males (63 per cent) with a mean birth weight of 2389 g. Antenatal risk factors included preterm delivery (50 per cent), prolonged rupture of the amniotic membranes (37 per cent). Associated maternal conditions included hypertension and antepartum haemorrhage (9 per cent). In contrast to other reported studies, there was early onset of the condition (mean age at presentation was 4 days) and the commonest organism found was Group B streptococcus while the least common were the Gram-negative organisms. Also different in the present study was the high percentage (56 per cent) of meningitis associated with Group B septicaemia, the low mortality rate (13) and the low rate of neurological sequelae (40 per cent).

Female↗

Creating a Drosophila wing de novo, the role of engrailed, and the compartment border hypothesis.

Anterior/posterior compartment borders bisect every Drosophila imaginal disc, and the engrailed gene is essential for their function. We analyzed the role of the engrailed and invected genes in wing discs by eliminating or increasing their activity. Removing engrailed/invected from posterior wing cells created two new compartments: an anterior compartment consisting of mutant cells and a posterior compartment that grew from neighboring cells. In some cases, these compartments formed a complete new wing. Increasing engrailed activity also affected patterning. These findings demonstrate that engrailed both directs the posterior compartment pathway and creates the compartment border. These findings also establish the compartment border as the pre-eminent organizational feature of disc growth and patterning.

Animals↗

Cerebrospinal fluid adenosine deaminase activity and C-reactive protein in tuberculous and partially treated bacterial meningitis.

Adenosine deaminase (ADA) activity measurement and C-reactive protein (C-RP) detection were done in CSF of 27 tuberculous meningitis (TBM) and 8 patients of partially treated bacterial meningitis, apart from routine biochemical tests. Both the groups had comparable CSF cell count, protein and sugar concentrations. The mean CSF ADA activity was significantly raised in TBM as compared to partially treated bacterial meningitis patients (p < 0.05). A cut-off ADA level < or = 5 IU/L and C-RP positively were used for differentiation of partially treated bacterial from TBM cases. Based on this, the sensitivity and specificity of ADA and C-RP were 62.5%, 88.9% and 75%, 100%, respectively. Since both the tests are simple and take lesser time to perform, they can be used as rapid diagnostic tests to remove diagnostic dilemma between the two diseases.

Adenosine Deaminase↗

Properties of oligonucleosomes from active genes of rat liver.

Active chromatin fraction from rat liver nuclei has been isolated under the lower ionic strength conditions, to prevent salt induced rearrangement and exchange of linker histone H1. Salt induced higher order folding in these oligonucleosomes was determined by sedimentation, viscosity, aggregation and circular dichroism studies. Sedimentation studies indicate that upon raising the ionic strength from 25 mM to 65 mM (mainly NaCl), active oligonucleosomes show intrafragmental interaction and formation of soluble oligomers. These oligomers disaggregate into unfolded monomers at 90 mM ionic strength. In contrast, oligonucleosomes from inactive genes show gradual increase in intrafragmental higher order folding without any interfragmental interaction on raising salt concentration. A much higher decrease in viscosity of active oligonucleosomes in comparison to bulk oligonucleosomes also support the above conclusion. However, on raising salt concentration above 100 mM NaCl, both the chromatin fractions are capable of forming insoluble aggregates. Decrease in the molar ellipticities of bulk oligonucleosomes at 273 and 282 nm is observed on raising ionic strength from 25 mM to 65 mM. A different pattern of this decrease is observed in case of active oligonucleosomes, indicating adaptation of a different type of salt induced secondary structure of DNA in these oligonucleosomes. Melting profile of DNA from active and bulk chromatin suggests that the base composition of both the chromatin fractions is same.

Animals↗

The actions of 5-HT1 agonists and antagonists on nociceptive processing in the rat spinal cord: results from behavioural and electrophysiological studies.

We have developed a technique which allows drugs to be microinjected intrathecally intrathecally in anaesthetised rats whilst single unit recordings are made from dorsal horn neurones. Using this technique together with recordings of tail flick latency (TFL) elicited from lightly anaesthetised rats we have found that the specific 5-HT1a agonist 8-OH DPAT (15, 150, 300 nmol) increases nociceptive responses recorded from single dorsal horn neurones and decreases TFL. The non-specific 5-HT1b agonist TFMPP (300 nmol) and the general 5-HT1 agonist 5-CT (0.3, 3.0, 30 nmol) both decreased nociceptive responses and has inconsistent effects on TFL. Intrathecally applied 5-HT (130, 260 nmol) generally reduced nociceptive neuronal responses and increased TFL. In a minority of experiments, however, 5-HT increased nociceptive responses and it is suggested that this effect is associated with activation of 5-HT1a receptors. Activity at 5-HT1b receptors has the effect of suppressing or reducing responsiveness. The increased responsiveness of dorsal horn neurones to noxious stimulation associated with activity at 5-HT1a receptors may be associated either with increases in receptive field size, promotion of spinal nocifensive reflexes or the facilitation of the rostral transmission to specific brainstem sites.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Human maternal uniparental disomy for chromosome 16 and fetal development.

Two severely growth-retarded fetuses found to have maternal uniparental disomy (UPD) for chromosome 16 and trisomy 16 placental mosaicism both had an unfavourable outcome. Antenatally, the first case was complicated by an unexplained raised maternal serum alpha-fetoprotein concentration, preterm premature rupture of the membranes, and growth retardation detectable at 21 weeks' gestation, whilst the other had an unexplained raised maternal serum human chorionic gonadotrophin level, a two-vessel cord on ultrasound, and cessation of growth at 25 weeks. At post-mortem, both babies had an imperforate anus. Fetal maternal UPD may explain the poor outcome that occurs in some cases of confined placental mosaicism for chromosome 16 and is also associated with specific fetal abnormalities.

Adult↗

Immunological approach for the identification of isozymes of CAM-stimulated phosphatase.

Monoclonal antibodies are frequently used to identify protein isoforms. The present study documents certain artifacts in such applications and suggests methods for their testing. Two alpha subunit specific anti-calcineurin antibodies, VJ6 and VD3, reacted strongly with a brain isozyme, BPI, but not with the phosphatases from liver and spleen. Controlled proteolysis of BPI indicated that epitopes of both antibodies are localized to aminoterminal region, thus is suggesting that the lack of antibody reactivity could result from proteolytic artifacts. The occurrence of proteolysis during sample preparation can be monitored by including small quantity of BPI in the tissue extraction buffer. Rapid isolation procedure has been used to obtain liver and spleen isozymes reacting with VD3 but not VJ6 antibody.

Animals↗

Adenosine deaminase activity in typhoid fever.

Serum adenosine deaminase (ADA) activity was determined in 41 patients of typhoid fever and 15 normal controls. The mean ADA activity was significantly raised in typhoid fever patients as compared to controls (p < 0.001). The peak enzymatic activity was observed in the first week of illness. Complicated patients had lower mean ADA activity at diagnosis as compared to uncomplicated group and they showed a rise in enzyme level during defervescence, repeated in a few cases. A significant correlation between serum ADA activity and lymphocyte percentage was found (r = 0.4245, p < 0.001). It is concluded that ADA activity in typhoid fever patients not only indicates immunity but also has a prognostic value.

Adenosine Deaminase↗

Brain proline-directed protein kinase phosphorylates tau on sites that are abnormally phosphorylated in tau associated with Alzheimer's paired helical filaments.

Brain proline-directed protein kinase (BPDK), which contains a catalytic subunit homologous to and displaying site-specific phosphorylation similar to p34cdc2 kinase (Lew, J., Winkfein, R. J., Paudel, H. K., and Wang, J. H. (1992) J. Biol. Chem. 267, 25922-25926), has been examined for possible involvement in tau phosphorylation. Immunoblot analyses using peptide antibodies specific for BPDK have revealed the presence of the kinase in bovine brain microtubules purified extensively by repeated polymerization and depolymerization cycles. When the microtubule proteins are separated into the tubulin and microtubule-associated protein fractions, BPDK is found exclusively in the latter fraction. BPDK phosphorylates both tau and MAP2, the former protein being phosphorylated to a stoichiometry of 3.8 mol of phosphate/mol of tau. Analysis of the phosphopeptides isolated from the tryptic digest of the phosphorylated bovine tau has revealed seven phosphorylation sites. Based on the sequence alignment between bovine and human tau proteins, these sites correspond to Ser-195, Ser-202, Thr-205, Thr-231, Ser-235, Ser-396, and Ser-404 of human tau. Mass spectrometric analysis of the tau protein isolated from Alzheimer's paired helical filaments (PHFs) has determined three abnormal phosphorylation sites and two phosphopeptides containing a total of five abnormal phosphates (Hasegawa, M., Morishima-Kawashima, M., Takio, K., Suzuki, M., Titani, K., and Ihara, Y. (1992) J. Biol. Chem. 267, 17047-17054). Two of the sites in tau phosphorylated by BPDK, Thr-231 and Ser-235, are among the abnormal phosphorylation sites, and the other sites phosphorylated by BPDK are within phosphopeptides from PHF-tau. These results suggest that BPDK may be one of the kinases responsible for the abnormal phosphorylation-associated PHF-tau.

Alzheimer Disease↗

Isozyme-specific monoclonal antibodies of CaM-stimulated phosphatase: identification of an enzyme domain involved in metal ion activation.

Bovine brain and lung extracts each contain three forms of CaM-stimulated phosphatase, designated BPI, BPII, and BPIII, and LPI, LPII, and LPIII, respectively. The different forms show uniform immunoreactivity toward one alpha subunit-specific monoclonal antibody, VD3, but differential reactivity toward another antibody, VJ6. Using the procedure of limited clostripain digestion, the binding sites for mAb VD3 and mAb VJ6 have been localized to the carboxylterminal region of about 40 amino acid residues and to the carboxylterminal one-third of the alpha subunit, respectively. The result has substantiated our previous suggestion that the isolated multiple forms of the brain and lung phosphatases represent isozymes rather than in vitro proteolysis artifacts. The effects of the two monoclonal antibodies on p-nitrophenylphosphatase activities of the bovine brain phosphatase isozymes have been examined. BPI and BPIII, the two VJ6 reactive brain isozymes, can be inhibited by VJ6 antibody in a metal ion and CaM-dependent manner; none of the isozymes are inhibited by mAb VD3. The inhibition of BPI by mAb VJ6 is most pronounced when the assay is carried out in the presence of CaM and Ni2+, whereas little or no effect is seen if Mg2+ plus Ca2+ are used as metal ion activators. Thus, VJ6 appears to identify an alpha-subunit domain important for the Ni(2+)-induced activation of CaM-stimulated phosphatase.

Animals↗

Effect of pH adjustment of bupivacaine on onset and duration of epidural anaesthesia.

The effect of pH adjustment of bupivacaine on onset and duration of sensory and motor block was studied in 45 patients undergoing lower abdominal and lower limb surgery. The study was done in 3 groups with the mean pH adjustment of 5.85, 7.14 and 7.21. Each patient was given 30 ml of 0.4% pH adjusted bupivacaine solution in epidural space. Onset of sensory block and duration were noticed by pin-prick method while motor block was observed by asking the patient to raise the thigh. It was observed that increase in pH of bupivacaine solution quickens the onset of sensory and motor block and increases the overall duration of neural blockade.

Adolescent↗

Cutaneous thermal thresholds in patients with painful burning feet.

Small nerve fibre sensory function was assessed by psychophysical estimates of cutaneous thermal thresholds in 30 patients who presented with the symptoms of painful burning feet. Thresholds were abnormal in 12 and normal in 18 patients although symptoms in the two groups were very similar. Various hypotheses for the mechanism of pain in small fibre neuropathy have been proposed previously and these are discussed, but the cause of symptoms in patients with normal thresholds, is unknown. The possibility exists that these patients have a neuropathic disorder which affects only those unmyelinated fibres involved with pain.

Adult↗

Replacement of histone H1 by H5 in vivo does not change the nucleosome repeat length of chromatin but increases its stability.

In vivo competition between histones H1 and H5 for chromatin has been studied in rat sarcoma XC10 cells transfected with a glucocorticoid responsive MMTV-H5 gene. Activation of H5 expression results in accumulation of H5 in the nuclei where it partially replaces H1. H5 displaces H1 from its primary binding sites presumably during chromatin replication and also binds with high affinity to secondary chromatin sites normally not occupied by H1. Replacement of H1 by H5 to levels similar to those of mature chicken erythrocytes does not alter the nucleosome repeat length of chromatin. This indicates that H5 is not solely responsible for the increase in nucleosome spacing of maturing erythroid cells. Exchange of H1 by H5 in vivo or in vitro results in a higher compaction/stability of chromatin.

Animals↗

Resurgence of congenital syphilis in Trinidad.

Twenty-eight cases of congenital syphilis (CS) were diagnosed shortly after birth at the Mount Hope Women's Hospital, Trinidad, during the period January 1985 to December 1988. The average annual incidence of CS was 115 per 100,000 live births, and the absolute number of cases and annual incidence doubled in the latter 2 years of the study. Diagnostic criteria used were a positive VDRL test in the 23 liveborn infants (100 per cent), signs suggestive of CS and confirmatory post-mortem findings. All mothers attended antenatal clinic at least once and 18 (64 per cent) were 25 years or younger. Only 17 (68 per cent) of the 25 gravidae with a positive VDRL test received treatment. Of 11 untreated gravidae, two did not have a VDRL test done, one had a negative VDRL test, three delivered before test results became known, one went into labour before going for treatment, and four (two of whom were substance abusers) did not comply with instructions to obtain treatment. There were five stillbirths and five neonatal deaths. There was no perinatal mortality when treatment was given earlier than 5 weeks before delivery, but mortality increased steeply if treatment was delayed or not given at all during pregnancy. Factors which contributed to this rise in the incidence of CS were an increased incidence of syphilis in females and failure to treat infected pregnant women.

Adolescent↗