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Biomedical subjects

D Reddy

Publications and source records attributed to D Reddy.

At least 19 recordsLinked to original sources
PubMed2004

In vitro biological activity and essential oil composition of four indigenous South African Helichrysum species.

Helichrysum species are used widely to treat various medical conditions. In this study, the anti-microbial, anti-oxidant (DPPH assay) and anti-inflammatory activity (5-lipoxygenase assay) of Helichrysum dasyanthum, Helichrysum felinum, Helichrysum excisum and Helichrysum petiolare were investigated. The essential oil compositions of these species were determined. The acetone and methanol extracts as well as the essential oils exhibited activity against Gram-positive bacteria, while both the methanol and acetone extracts of all four species were active in the anti-oxidant assay. The essential oils, on the other hand, displayed activity in the 5-lipoxygenase assay, which was used as an indication of anti-inflammatory activity. Two extracts exhibited promising activity in the anti-microbial assay, the acetone extract of Helichrysum dasyanthum with a MIC value of 15.63 microg/ml and the methanol extract of Helichrysum excisum with a MIC value of 62.5 microg/ml. The acetone extract of Helichrysum dasyanthum was the most active free radical scavenger in the DPPH assay (IC(50) of 9.53 microg/ml) while values for the anti-inflammatory activity of the essential oils ranged between 25 and 32 microg/ml. The essential oil compositions of three species (Helichrysum dasyanthum, Helichrysum excisum and Helichrysum petiolare) were dominated by the presence of monoterpenes such as alpha-pinene, 1,8-cineole and p-cymene. In the oil of Helichrysum felinum, monoterpenes were largely absent. Its profile consisted of a variety of sesquiterpenes in low concentrations with beta-caryophyllene dominating.

Helichrysum↗
PubMed2003

Role of chelate substituents and cis sigma-effect on the rate of ligand substitution at Pt(N-N-N) and Pt(N-N-C) centres.

Four complexes of the type [Pt(N-N-X)Cl](X = N or C) were tailor synthesized for mechanistic studies in methanol. The terdentate ligands included terpy, 4'-Ph-terpy, 4'-(2"-CF(3)-Ph)-terpy, and 4'-(2"'-CF(3)-Ph)-6-Ph-2,2'-bipy. The rate of substitution of the chloro ligand by thiourea, N,N'-dimethylthiourea, and N,N,N',N'-tetramethylthiourea was studied as a function of nucleophile concentration, temperature and pressure by using a stopped-flow technique. The observed pseudo-first-order rate constants for the substitution reactions obeyed the simple rate law k(obs) = k(2)[Nu]. Second-order kinetics and negative activation entropies and volumes support an associative substitution mechanism. At 298 K, the values of the second-order rate constant show a slight dependence on the nature of the moiety attached to the terpy ligand. Changing from a nitrogen sigma-donor to a carbon sigma-donor in the cis position, results in a deceleration of the substitution rate. The results suggest that the Pt-C bond in the cis position activates the metal centre in a different way than in the trans position.

Journal Article↗
PubMed2001

The Sambungmacan 3 Homo erectus calvaria: a comparative morphometric and morphological analysis.

The Sambungmacan (Sm) 3 calvaria, discovered on Java in 1977, was illegally removed from Indonesia in 1998 and appeared in New York City in early 1999 at the Maxilla & Mandible, Ltd. natural history shop. Here we undertake an analysis of its phylogenetic and systematic position using geometric morphometrics and comparative morphology. The coordinates of points in the sagittal plane from glabella to opisthion were resampled to yield "lines" of 50 semi-landmarks. Coordinates of glabella, bregma, lambda, inion, and opisthion were also collected and analyzed separately. Casts of Homo erectus fossils from Indonesia, China, and Kenya and of "archaic H. sapiens" from Kabwe and Petralona, as well as 10 modern human crania, were used as the primary comparative sample. The modern humans were well separated from the fossils in a graphical superimposition of Procrustes-aligned semi-landmarks as well as in principal component and canonical discriminant analyses. In all of these, Sm 3 falls intermediate between the fossil and modern groups. Morphological comparisons of Sm 3 with a selection of Homo erectus fossils revealed its greatest similarity to specimens from Ngandong and the Sm 1 calvaria. Compared to all other H. erectus, Sm 3 was distinctive in its more vertical supratoral plane, less anteriorly projecting glabella and less sharply angled occiput. In these features it was somewhat similar to modern humans. It is not yet possible to determine if this similarity implies an evolutionary relationship or (more likely) individual or local populational variation. Several features of Sm 3 (small size, gracile supraorbital torus and lack of angular torus, and position in principal component analysis) suggest that it was a female. The use of geometric morphometrics provides a means to statistically test the shapes of such fossils in a manner not easily duplicated by other methods. The intermediate position of Sm 3 between fossil and modern samples in several different subanalyses exemplifies the value of this approach.

Animals↗
PubMed2001

Outcome following heart transplantation in Maori and Polynesian patients: a comparison with European New Zealanders.

AIM: To compare demographic, clinical and outcome data of Maori and Polynesian with New Zealand European heart transplant patients. METHODS: A retrospective analysis was made of data from the 104 patients who underwent heart transplantation at Green Lane Hospital over a period of twelve years, of whom 79 were European, 23 Maori/Polynesian, and two Asian. Clinical characteristics, blood group, HLA matching and outcomes of recipients were compared. RESULTS: There was no significant difference in age and gender between the two groups. Maori and Polynesian patients were heavier, had a greater body mass index and were more likely to have rheumatic heart disease than their European counterparts. Maori/Polynesian patients were predominantly blood group A, whilst European patients were mainly group O. The waiting time for a donor heart was similar in both groups. There was no significant difference in number of rejection episodes and survival. CONCLUSIONS: Green Lane Hospital has the largest international experience of heart transplantation in Maori and Polynesian patients. Although there are some differences in clinical profile, outcome in terms of rejection episodes and survival is similar in the two groups.

Adolescent↗
PubMed2001

A comparison of the short and long forms of the Multiple Affect Adjective Check List-Revised (MAACL-R).

Brief, reliable, and valid assessment instruments are very important for clinical psychology research and practice. The possible equivalency of a short form and the long form of the Multiple Affect Adjective Check List-Revised (MAACL-R; Zuckerman & Lubin,1985) was studied by correlating both forms of the MAACL-R with the State Trait Personality Inventory (Spielberger,1995); the Affect Balance Scale (Bradburn,1969); and the Sensation Seeking Scale (Zuckerman,1978). Reliability and validity of the two forms were equivalent.

Adolescent↗
PubMed2000

Improved production of adenovirus vectors expressing apoptotic transgenes.

Adenovirus vectors expressing gene products that can induce apoptosis have potential utility in gene therapy applications ranging from the treatment of proliferative diseases to transplantation. However, adenovirus vectors carrying proapoptotic gene products are difficult to produce, as the apoptotic environment is not conducive to adenovirus gene expression and replication. Production of AdFasL/G, an adenovirus vector that expresses high levels of Fas ligand, was severely reduced in the 293 packaging cell line. Increased yields of AdFasL/G were achieved by inclusion of peptide-based caspase inhibitors in the growth medium. However, use of these inhibitors for large-scale production would be difficult and expensive. A screen for gene products that increase the yield of AdFasL/G in 293 cells revealed that the poxvirus serpin CrmA and the adenovirus 14.7K product were able to increase virus yields significantly. Apoptosis induced by AdFasL/G was attenuated in 293CrmA cell lines and virus titers were increased dramatically. However, serial passage of AdFasL/G on 293CrmA cells resulted in the generation of replication-competent adenovirus. To resolve this problem, the CrmA gene was introduced into AE25 cells, an E1-complementing cell line that has limited sequence identity with the vectors. AdFasL/G titers were increased 100-fold on AE25CrmA cells relative to the AE25 cells and RCA contamination was not detectable. In addition, adenovirus vectors that express FADD, caspase 8, and Fas/APO1 were produced efficiently in AE25CrmA and 293CrmA.

Adenoviridae↗
PubMed2000

Variants of trophic factors and expression of cardiac hypertrophy in patients with hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HCM) exhibit variable expression of left ventricular hypertrophy (LVH), a major determinant of mortality and morbidity, which is partly due to the diversity of causal mutations, genetic background (modifier genes), and probably environmental factors. We determined association of functional variants of tumor necrosis factor (TNF)- alpha, interleukin-6 (IL6), insulin-like growth factor-2 (IGF2), transforming growth factor- beta 1 (TGFB1), and aldosterone synthase (CYP11B2) genes, all previously implicated in cardiac hypertrophy, with the severity of LVH in patients with HCM. Two-dimensional echocardiography was performed and demographic variables were recorded in 142 genetically independent patients. Indices of LVH including interventricular septal thickness (IVST), left ventricular mass index (LVMI), and LVH score were measured/calculated. TNF-alpha-308G/A, IL6-174G/C, IGF2 820G/A, TGFB1-509C/T, and CYP11B2-344T/C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were identified by the presence of specific electrophoretic patterns and their distributions were according to the Hardy-Weinberg equilibrium. Demographic variables were not significantly different among the genotypes. Subjects with the AA genotype of TNF-alpha (n=8) were approximately 13 years younger at the time of clinical diagnosis. Despite a younger age, they had a greater mean LVMI than those with the GG (n=94) or GA (n=33) genotypes (191.8+/-59.5 v 139.1+/-47.3 v 132.1+/-34.3, respectively, P=0.004). TNF-alpha-308G/A genotypes accounted for 6.0% of variability of LVMI (P=0.002). Mean IVST, LVEDD, and LVH score were not significantly different. Variants of IL6, IGF2, TGFB1, and CYP11B2 were not associated with indices of LVH. The uncommon allele of TNF-alpha-308G/A polymorphism, known to produce more TNF- alpha, was associated with greater LVMI and clinical diagnosis at a younger age in patients with HCM. Functional variants of other trophic factors, previously implicated in cardiac hypertrophy, were not associated with the indices of LVH. These results suggest that TNF-alpha is a modifier gene for HCM.

Adult↗
PubMed2000

Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity.

Herbal medicines are gaining widespread popularity. Much of the public believes that botanical herbs are both harmless and useful for the treatment of a variety of symptoms. This belief stands in contrast with the fact that many herbal therapies have been shown to be toxic. In the present case report, cascara sagrada (CS) has been associated with the development of cholestatic hepatitis, complicated by portal hypertension. CS is a mixture of ingredients, among which is anthracene glycoside--an herbal agent that previously has been associated with chronic hepatitis. The liver injury in the case herein reported is believed to be related to either anthracene glycoside or one of the other constituents of CS.

Biopsy↗
PubMed1998

Modulation of platinum-induced toxicities and therapeutic index: mechanistic insights and first- and second-generation protecting agents.

Platinum-type drugs have proven to be valuable in the treatment of a variety of solid tumors, beginning with the commercial approval of cisplatin 18 years ago. There are several clinically important toxicities commonly associated with the administration of these drugs. Despite the extensive use of cisplatin and carboplatin, the fundamental chemical transformations and mechanisms that underlie their antitumor and toxic effects have not been fully characterized. Several first-generation protective thiols have been clinically studied in an attempt to reduce the toxicity of platinum-type drugs; while some of these agents appear to protect against certain toxicities, nearly all platinum-protecting drugs have their own intrinsic toxicities, which can be additive to the toxicity of platinum-type drugs. Tumor protection by platinum-protecting drugs is an additional untoward effect that is associated with certain types of agents and must be addressed with care. Recent advances in theoretical and laboratory methods and the use of supercomputers have extended our understanding of the possible major mechanisms underlying platinum drug antitumor activity and toxicity; we present strong evidence that there are two classes of chemical species of platinum drug. One class appears to predominantly account for the antitumor activity, and the other class of chemical species produces many of the toxic effects of platinum drugs. We have discovered a new nontoxic, second-generation platinum-protecting agent, known as BNP7787, which appears to selectively inactivate and eliminate toxic platinum species. BNP7787 has recently entered phase I clinical testing in cancer patients.

Amifostine↗
PubMed1997

Transfection and overexpression of the calcium binding protein calbindin-D28k results in a stimulatory effect on insulin synthesis in a rat beta cell line (RIN 1046-38).

Calbindin-D28k, a calcium binding protein that is thought to act as a facilitator of calcium diffusion in intestine and kidney, is known to be regulated by vitamin D in these tissues. Calbindin-D28k is also present in pancreatic beta cells, but its function in these cells is not known. To determine a role for calbindin-D28k in the beta cell, rat calbindin-D28k was overexpressed in the pancreatic beta cell line RIN 1046-38 by transfection of calbindin in expression vector, and changes in insulin mRNA were examined. Five transfected RIN cell clones were found to overexpress calbindin 6- to 35-fold as determined by radioimmunoassay. Northern blot analysis revealed increases in abundance in calbindin mRNA (>20-fold for most clones). Overexpressed calbindin was functional because it was capable of buffering calcium in response to a rapid calcium influx induced by 1 and 5 microM calcium ionophore. In cells transfected with calbindin, there was a marked increase in the expression of insulin mRNA (>20-fold for most clones compared with vector transfected cells). Besides an increase in insulin mRNA, calbindin overexpression was also associated with an increase in insulin content and release (a 5.8-fold increase in insulin release was noted for clone C10, and a 54-fold increase was noted for clone C2). To begin to address the mechanism whereby overexpression of calbindin results in increased insulin gene expression, calbindin-overexpressing clones were transiently transfected with plasmids incorporating various regions of the rat insulin I (rInsI) promoter linked to the chloramphenicol acetyltransferase coding sequence. Transient transfection with reporter plasmids bearing the regulatory sequences of the rInsI promoter (-345/+1) or five copies of the Far-FLAT minienhancer (-247/-198) from the rInsI promoter suggests that increased insulin mRNA in calbindin transfected cells is due, at least in part, to enhanced insulin gene transcription. These studies provide the first direct evidence (to our knowledge) for a role for calbindin in beta cell function.

Animals↗
PubMed1997

Central opiate mu-receptor-mediated suppression of tissue protein synthesis.

We determined the dose-dependent effects of central mu-opioid receptor stimulation on rates of tissue protein synthesis. Chronically catheterized conscious rats received an intracerebroventricular injection of [D-Ala2, N-Me-Phe4,Gly5-ol]enkephalin (DAGO, 0.5, 2, or 8 nmol/rat) or water (5 microliters) 45 min before determination of protein synthesis by the flooding dose technique. DAGO produced a significant decrease in tissue protein synthesis in liver (57%), spleen (54%), gut mucosa (36%), gut serosa (23%), kidney (48%), gastrocnemius (33%), and plantaris muscle (27%), but it did not alter rates of protein synthesis in the brain, heart, and soleus muscle. DAGO produced an acute dose-dependent respiratory depression 30 min after intracerebroventricular injection; this depression resulted in acidosis, hypoxia, and hypercapnia (pH 7.19 +/- 0.04, arterial partial O2, pressure 44.2 +/- 3.4 Torr, arterial O2 saturation 65.3 +/- 5.5%, and PCO2 66.3 +/- 4.4 Torr). Intracerebroventricular DAGO increased circulating levels of catecholamines, corticosterone, and growth hormone but did not alter those of insulin and insulin-like growth factor I. Significant positive correlations between protein synthesis and pH were observed in the tissues studied (i.e., liver protein synthesis vs. pH, P < 0.0001, r = 0.902; gastrocnemius protein synthesis vs. pH, P < 0.0001, r = 0.830). Our results indicate that mu-receptor stimulation inhibits tissue protein synthesis, and this effect appears to be secondary to respiratory depression and the resulting acidosis and/or hypoxia. Furthermore, our findings suggest differential sensitivity in tissue response to alterations in pH, hypoxia, and stress hormone elevation.

Adenosine Triphosphate↗
PubMed1996

Detection of bony metastases of androgen-independent prostate cancer by PET-FDG.

Fourteen F-18 fluorodeoxyglucose (FDG) studies were carried out in 13 patients known to have bony metastases from carcinoma of the prostate. One patient was newly diagnosed. The remaining patients had various types of therapy and were considered hormonally resistant. The average age was 67. All patients had extensive bony metastases shown on the conventional Tc99m-MDP bone scans. Only about 18% of bony lesions apparent on the conventional bone scans showed corresponding increase of FDG uptake. Anatomical correlation was performed by using co-registered images of SPECT and PET in the same area. The positive FDG uptake was not related to the duration of illness, level of PSA, previous therapy, and magnitude of disease involvement. It appears that only a small percentage of bony metastases is associated with increased glycolysis. It is possible that other metabolic processes are more important than glycolysis for providing prostate cancer with a source of energy and nutrients.

Aged↗
PubMed1996

Attitudes towards parental presence at induction of anaesthesia.

OBJECTIVE: To determine the attitudes of South African anaesthetists with regard to allowing parents to be present during the induction of anaesthesia in children, and to determine the source and extent of resistance to this controversial practice. DESIGN: Questionnaire survey consisting of three parts and based on a previous study. SETTING: Southern Africa. PARTICIPANTS: All practising anaesthetists, specialist and non-specialist, on the mailing list of a major pharmaceutical company. RESULTS: Responses were obtained from 222 anaesthetists from 80 different localities in southern Africa. The majority of the respondents were specialist anaesthetists in private practice with between 5 and 15 years' experience. Of the respondents 55% agreed that it was acceptable to allow parents to be present at induction and that this did not compromise the child's safety; 117 claimed that there was resistance to the practice, perceiving the matron and nursing staff as the major source of resistance, both currently and in the past. Lack of facilities and loss of operating theatre sterility were cited as the main reasons for resistance. CONCLUSION: Although the practice is still controversial, the majority of anaesthetists who responded to the survey would be happy to allow parents to accompany children at induction. It should be catered for and encouraged according to certain guidelines.

Anesthesia↗
PubMed1994

Parathyroid hormone-related protein as a prohormone: posttranslational processing and receptor interactions.

Since the elucidation of the structures of the three human PRHrP isoforms in 1987, information has rapidly accured which indicates that the role of PTHrP in normal physiology will prove to be crucial as well as exceedingly complex. The importance of the role of PTHrP in normal physiology is underscored by its broad tissue expression, by its intense evolutionary conservation, by its extremely early expression after fertilization of the ovum, and by the lethal consequences of PTHrP gene disruption. The complexity of the role of PTHrP in normal physiology increases almost monthly. This complexity is reflected in the broad tissue distribution of the peptide, its complex transcriptional regulation and mRNA instability motifs, and its multiple transcripts and isoforms. It is now clear that additional complexity exists at the level of posttranslational processing. Expression of the PTHrP gene leads to the tissue-specific processing and secretion of an increasingly complex family of derivative peptides, each with its own repertoire of cognate receptors, signal transduction pathways, and physiological consequences. Further elucidation of the posttranslational processing pathways and mechanisms can be anticipated in the coming years, coupled with a corresponding elucidation of multiple PTHrP receptors, their specific signal transduction pathways, and their unique physiological roles. The role of PTHrP in causing HHM is now clearly established. Work in the coming decade will focus on the normal physiological roles played by PTHrP.

Amino Acid Sequence↗
PubMed1994

Identification of a novel microtubule-binding domain in microtubule-associated protein 1A (MAP1A).

Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short sequences with repeated amino acids motifs. A microtubule-binding domain has hitherto not been defined for the adult brain microtubule-associated protein 1A (MAP1A). We have searched for a microtubule-binding domain by expressing different protein regions of MAP1A in cultured cell lines using cDNA constructs. One construct included an area with homology to the microtubule-binding domain of MAP1B (Noble et al. (1989) J. Cell Biol. 109, 437-448), but this did not bind to microtubules in transfected cells. Further investigation of other areas of MAP1A revealed a protein domain, capable of autonomously binding to microtubules, which bears no homology to any previously described microtubule-binding sequence. This MAP1A domain is rich in charged amino acids, as are other mammalian microtubule-binding domains, but unlike them has no identifiable sequence repeats. Whereas all previously described mammalian microtubule-binding domains are basic, this novel microtubule-binding domain of MAP1A is acidic. The expression of this polypeptide in cultured cell lines led to a rearrangement of the microtubules in a pattern distinct from that produced by MAP2 or tau, and increased their resistance to treatment with the microtubule depolymerising agent nocodazole. When the MAP1A microtubule-binding domain was co-expressed in cultured cell lines together with MAP2c, the MAP1A microtubule-binding domain was able to bind to the MAP2c-induced microtubule bundles. These results suggest that different microtubule-binding sequences have a common ability to stabilise microtubules but differ in their influence on microtubule arrangement in the cell. This may be significant in neurons, where microtubule-associated proteins with different microtubule-binding sequences are expressed in different cell compartments and at different times during development.

Amino Acid Sequence↗
PubMed1993

Attenuation of microtubule-associated protein 1B expression by antisense oligodeoxynucleotides inhibits initiation of neurite outgrowth.

Microtubule-associated protein 1B, formerly also known as microtubule-associated protein 5, is the first structural microtubule accessory protein to appear in outgrowing axons. In PC12 pheochromocytoma cells microtubule-associated protein 1B levels increase several-fold after the addition of nerve growth factor and this increase is correlated with the initiation of process formation. To determine whether microtubule-associated protein 1B is essential for neurite outgrowth, we used antisense oligodeoxynucleotides to inhibit its expression in nerve growth factor-treated PC12 cells in the rat. The application of several different antisense oligodeoxynucleotides to the microtubule-associated protein 1B mRNA sequence inhibited both microtubule-associated protein 1B expression and neurite extension. Specificity was shown by the lack of effect of control sense oligonucleotides and by the lack of effect of the microtubule-associated protein 1B antisense oligodeoxynucleotides on the expression of either tubulin or microtubule-associated protein 3, another microtubule-associated protein whose synthesis is stimulated by nerve growth factor treatment of PC12 cells. After removal of the antisense oligodeoxynucleotides, microtubule-associated protein 1B expression recovered to normal levels and the cells grew normal neurites with the timing and morphological characteristics of normal nerve growth factor-induced outgrowth, indicating that the blockade was not because of non-specific toxic effects. These results indicate that microtubule-associated protein 1B is an essential component of the molecular mechanism underlying the formation of neuronal processes.

Animals↗
PubMed1993

The low molecular weight form of microtubule-associated protein 2 is transported into both axons and dendrites.

In the developing brain microtubule-associated protein MAP2 occurs as both a high molecular weight form, MAP2b, which is present only in dendrites, and a low molecular weight form, MAP2c, which is also present in axons. Because the MAP2c amino acid sequence is entirely contained within that of MAP2b it is not possible to raise a MAP2c-specific antibody, so that it has been impossible to determine whether MAP2c is present in dendrites along with MAP2b. To answer this question we have generated a MAP2c cDNA clone tagged with a 10 amino acid epitope from human c-myc. This additional sequence does not alter either the binding of MAP2c to microtubules or its effects on microtubules in non-neuronal cells. When expressed in cultured primary neurons by transfection, the myc tag allowed the distribution of MAP2c to be determined independently of endogenous MAP2 protein by immunostaining with an anti-myc antibody. This showed that MAP2c is present in all processes, indicating that it can enter all kinds of processes and is stable in their cytoplasm. The results further suggest that the selective association of high molecular weight MAP2 with dendrites depends on a mechanism that prevents either its entrance or survival in the axonal compartment.

Amino Acid Sequence↗