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H C Patel

Publications and source records attributed to H C Patel.

At least 19 recordsLinked to original sources
PubMed2006

Radiation-induced brain tumours in nevoid basal cell carcinoma syndrome: implications for treatment and surveillance.

INTRODUCTION: We report two cases of radiation-induced intracranial tumours after treatment for medulloblastoma presenting in children with nevoid basal cell carcinoma syndrome. DISCUSSION: These cases illustrate the need for judicious use of post-operative radiotherapy as secondary tumors are commonly reported. This is particularly important as the initial tumour in this cohort is of the 'less aggressive' desmoplastic subtype.

Adolescent↗
PubMed2006

Neurodegenerative actions of interleukin-1 in the rat brain are mediated through increases in seizure activity.

The cytokine interleukin-1 (IL-1) is an established and important mediator of diverse forms of neuronal injury in experimental animals. However, its mechanisms of action remain largely unknown. We have reported previously that IL-1 markedly enhances excitotoxic injury induced in the rat by striatal administration of the excitotoxin alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), leading to widespread neuronal loss throughout the ipsilateral cortex. Here we tested the hypothesis that IL-1 causes this injury through induction and/or enhancement of seizure activity in the rat. Consistently with this hypothesis, intrastriatal injection of AMPA or AMPA with IL-1 in the rat brain increased c-Fos expression in regions similar to those in which c-Fos has been reported previously in response to seizures. A significant increase in cortical neuronal activity (number of c-Fos positive cells) was observed in response to AMPA with IL-1 compared with AMPA (8 hr after injection). Increased seizure duration [3,522 +/- 660 sec (SEM) vs. 1,415 +/- 301 sec; P < 0.001] and cell death volume (140 +/- 20 mm3 vs. 52 +/- 6 mm3; P < 0.001) were seen in response to coinfusion of AMPA with IL-1 vs. AMPA alone. In addition, the anticonvulsant diazepam (intraperitoneal) significantly reduced cell death (P < 0.001) and seizure duration (P < 0.001) induced by AMPA with IL-1, and a significant correlation was found between seizure duration and cell death volume. These findings support our hypothesis that IL-1 enhances excitotoxic injury by enhancement of seizures, which may be of relevance to IL-1 actions in other forms of neuronal injury, including cerebral ischemia.

Analysis of Variance↗
PubMed2006

Otitis media in adults with chlamydial conjunctivitis.

The aim of this study was to assess the prevalence of otological symptoms in patients with chlamydial conjunctivitis. We report four cases of chlamydial conjunctivitis, in association with otitis media, that were investigated by an otologist.

Adult↗
PubMed2003

Interleukin-1 in the brain: mechanisms of action in acute neurodegeneration.

Interleukin-1 (IL-1) exerts a number of diverse actions in the brain, and it is currently well accepted that it contributes to experimentally induced neurodegeneration. Much of this is based on studies using the IL-1 receptor antagonist, which inhibits cell death caused by ischemia, brain injury, or excitotoxins. Our aim is to determine how and where in the brain IL-1 acts to produce these effects. Most of the neurodegenerative effects of IL-1 are thought to be through IL-1 beta. However, we have data implicating IL-1 alpha in excitotoxic cell death. Furthermore mice lacking both IL-1 alpha and IL-1 beta show dramatically reduced ischemic cell death, whereas deletion of IL-1 alpha or IL-1 beta alone fails to modify damage. It has also been demonstrated that IL-1 exacerbates ischemic injury in mice in the absence of the type I IL-1 receptor, suggesting the existence of novel IL-1 receptors in the brain. IL-1 also dramatically exacerbates neuronal loss in response to intrastriatal administration of the excitotoxin AMPA in the rat brain, an effect accompanied by marked increases in cytokine expression in the frontoparietal cortex, which precedes subsequent cell death in this region. Intrastriatal AMPA also results in limbic seizures that are exacerbated by IL-1, and we hypothesize, therefore, that IL-1 exacerbates cell death through increased seizure activity. Therefore, IL-1 appears to induce acute neurodegeneration through a number of mechanisms.

Acute Disease↗
PubMed1999

Quantitative component analysis of mixtures for risk assessment: application to eye irritation.

A methodology called quantitative component analysis of mixtures (QCAM) was used to analyze an existing set of product formulation data to determine if the irritating ingredients in the mixtures could be identified. Eye irritation scores, based on a rat model, for 18 mixtures having a composite total of 37 components, were analyzed by QCAM. QCAM relates a net toxicity measure of a mixture to the toxicities of the individual components of the mixture through linear, quadratic, and pairwise cross-component concentration-dependent interactions. A correlation model is established using a particular genetic algorithm employing either multidimensional linear regression or partial least-squares regression fitting. Cornea eye irritation and average eye irritation are well-explained in terms of a linear model of, at most, three components over the set of mixtures. Moreover, extensive cornea and average eye irritations are due to only one of these three components of the mixtures. Also, one of the three significant components was predicted to decrease the extent of eye irritation, and subsequently identified as an "anti-irritant" in contact lens solutions. A reasonable linear correlation model could also be developed for conjunctiva irritation, but no significant iris irritation model could be constructed. The addition of quadratic and/or cross-component concentration terms to a linear correlation model did not statistically improve the overall resultant model. The QCAM models permit estimation of the intrinsic (self) toxicity of each of the components of a mixture, and may aid in the reduction, and ultimate elimination, of the need for animal eye irritation studies.

Algorithms↗
PubMed1999

Traumatic subarachnoid haemorrhage.

The presence of subarachnoid blood following head injury is a significant risk factor for poor outcome. Treatment aims to prevent and treat secondary hypoxia, hypotension, intracranial haematoma, epilepsy and infection. There is good evidence for the benefit of nimodipine in aneurysmal subarachnoid haemorrhage. Its role in preventing cerebral ischaemia following trauma is currently under investigation.

Calcium Channel Blockers↗
PubMed1997

Molecular modeling of polymers 16. Gaseous diffusion in polymers: a quantitative structure-property relationship (QSPR) analysis.

PURPOSE: The purpose of this study was to identify the key physicochemical molecular properties of polymeric materials responsible for gaseous diffusion in the polymers. METHODS: Quantitative structure-property relationships, QSPRs were constructed using a genetic algorithm on a training set of 16 polymers for which CO2, N2, O2 diffusion constants were measured. Nine physicochemical properties of each of the polymers were used in the trial basis set for QSPR model construction. The linear cross-correlation matrices were constructed and investigated for colinearity among the members of the training sets. Common water diffusion measures for a limited training set of six polymers was used to construct a "semi-QSPR" model. RESULTS: The bulk modulus of the polymer was overwhelmingly found to be the dominant physicochemical polymer property that governs CO2, N2 and O2 diffusion. Some secondary physicochemical properties controlling diffusion, including conformational entropy, were also identified as correlation descriptors. Very significant QSPR diffusion models were constructed for all three gases. Cohesive energy was identified as the main correlation physicochemical property with aqueous diffusion measures. CONCLUSIONS: The dominant role of polymer bulk modulus on gaseous diffusion makes it difficult to develop criteria for selective transport of gases through polymers. Moreover, high bulk moduli are predicted to be necessary for effective gas barrier materials. This property requirement may limit the processing and packaging features of the material. Aqueous diffusion in polymers may occur by a different mechanism than gaseous diffusion since bulk modulus does not correlate with aqueous diffusion, but rather cohesive energy of the polymer.

Carbon Dioxide↗
PubMed1997

Murine monoclonal IgG antibodies: differences in their IgG isotypes can affect the antibody effector activity when using human cells.

The current studies were aimed at investigating why certain murine anti-CD3 isotypes (e.g. IgG2b) were poor activators of human T cells despite binding to the same epitope as the IgG2a anti-CD3. Most experiments were conducted with a human T cell line (HuT-78) and U937 a human histiocytic cell line with Fc gamma RI and Fc gamma RII. HuT-78 cells lack Fc gamma R. Anti-CD3-TCR of IgG2a isotypes and some antibodies of the IgG1 isotype, but not IgG2b, activated HuT-78 to secrete IL-2 only in the presence of U937. Epitope binding differences could not entirely explain these observations as OKT3E(IgG2a) but not its switch variant (IgG2b) activated HuT-78 in the presence of U937. Of interest, OKT3D(IgG1) in its intact form, but not its F(ab')2, activated HuT-78 to secrete IL-2 in the absence of U937 suggesting therefore that OKT3D activates T cells in the absence of macrophages and provided its Fc domain is intact. All three anti-CD3 with IgG2b isotypes (but none with the IgG2a isotypes) activated HuT-78 to secrete IL-2 only when these antibodies were immobilized onto plastic (in the absence of U937). Of considerable importance, anti-CD3 activation of human T cells with the IgG2b isotype was efficient in the presence of murine macrophages. These observations would suggest that murine anti-CD3 with IgG2b and certain antibodies of IgG1 isotypes, have inherent human T cell activating potential provided the Fc domain is in some manner activated, as for example, by binding to plastic or to Fc gamma R on murine macrophages. Macrophage cytokines are not essential. Therefore, ineffectual anti-CD3-mediated human T cell activation when using murine mAb with the IgG2b isotypes can best be explained on lack of Fc domain activation by human macrophages. This may indeed be the case as IgG2b and certain antibodies of IgG1 isotype, failed to bind to Fc gamma R on macrophages at 37 degrees C. These studies would indicate that murine mAb with the IgG2b isotype may be potentially useful for human use, especially in situations where receptor blockade (without cell activation) is of prime importance.

Animals↗
PubMed1995

Interpretation of Chlamydia trachomatis antibody response in chlamydial oculogenital infection.

OBJECTIVE: To study: (a) the chlamydial antibody response (to the D-K serovars) using the micro-immunofluorescence (micro-IF) test in the following groups: (I) chlamydial genital infection only, (II) chlamydial ocular infection only, (III) combined chlamydial ocular and genital infection (oculo-genital infection), (IV) chlamydial ocular infection with chlamydia-negative non-gonococcal urethritis, (V) adenovirus conjunctivitis (control group 1), (VI) male partners of group I-IV with no chlamydial oculogenital infection or non-gonococcal urethritis (control group 2) (b) the cross reactivity of antibodies in patients' sera between the three chlamydial species and within the serovars of C trachomatis in those with culture-positive chlamydial oculo-genital infection. SETTING: oculogenital (diagnostic) clinic at Moorfields Eye Hospital, London, UK. SUBJECTS: 209 consecutive patients attending the clinic with Chlamydia trachomatis oculogenital infection and 86 patients with adenovirus conjunctivitis (control group 1) and 55 male partners with no evidence of chlamydial oculogenital infection or non-gonococcal urethritis (control group 2). RESULTS: Of all the patients with proven chlamydial oculogenital infection, 10.5% (22/209) and 94% (197/209) had IgM and IgG antibodies respectively. The geometric mean IgG antibody titres (GMT) were 1:98, 1:123, 1:245 and 1:101 in groups I to IV respectively. The IgG GMT values seen in control groups 1 and 2 were 1:45 and 1:36 respectively. Only 2/86(2%) patients in group V (control group 1) had IgG chlamydial antibodies of 1:32 and 1:64, whilst only 1/55(1.8%) and 4/55(7.3%) of patients in group VI(control group 2) had chlamydial IgG antibody titres of > or = 1:256 and > or = 1:128 respectively. A four-fold rise or fall in IgG antibody titre occurred in 56%(107/192) of patient groups I-IV over 2-6 weeks. Low titre cross-reactive antibody responses against different chlamydial species and serovars were commonly seen; 71%(148/209) of all patients showed cross-reactivity with Chlamydia pneumoniae or psittaci species or both, whilst 92% (193/209) of patients showed some level of cross reactivity to other pooled serovars of C trachomatis (A-C and L 1-3). CONCLUSIONS: Serological diagnosis of chlamydial infection as evidenced by a positive IgM antibody response, high IgG titre (> or = 1:256) or > or = 4-fold rise or fall in IgG antibody titre was seen in 78%(163/209) of patients with culture-positive chlamydial oculogenital infection. Chlamydial IgG antibody titres of > or = 1:256 had a sensitivity of 42.6%, specificity of 98.2%, positive predictive value of 98.8% and a negative predictive value of 31% for chlamydial infection at any site, when considering groups I-IV and control group 2. In this study of 216 patients with conjunctivitis, a positive IgG antibody response (titre > or = 1:16) had a sensitivity of 98.5%, specificity of 97.7%, positive predictive value of 98.5% and a negative predictive value of 97.7%, for chlamydial conjunctivitis. Patients with dual chlamydial infection of conjunctiva and genital tract had a higher IgG GMT titre than those with ocular or genital infection alone: infection at a second site may produce an anamnestic response. Although the micro-IF test is a useful adjunct for the diagnosis of chlamydial infection, cross-reactivity between different chlamydial species and serovars is common. Chlamydial seroepidemiological studies should be interpreted with caution, as studies may attribute a serological response to a particular species or serovar in a setting where two or more are prevalent.

Antibodies, Bacterial↗
PubMed1994

Cloning and sequencing of ATP sulfurylase from Penicillium chrysogenum. Identification of a likely allosteric domain.

Fungal (Penicillium chrysogenum) and yeast (Saccharomyces cerevisiae) ATP sulfurylases were shown to have very similar kinetic and chemical properties except that the fungal enzyme (a) contains a highly reactive Cys residue (SH-1) whose modification results in sigmoidal velocity curves (Renosto, F., Martin, R. L., and Segel, I. H. (1987) J. Biol. Chem. 262, 16279-16288) and (b) is allosterically inhibited by 3'-phosphoadenosine 5'-phosphosulfate (PAPS), while the yeast enzyme displays neither of these properties. The fungal enzyme subunit (64.3 kDa, 572 amino acids) is also larger than the yeast enzyme subunit (59.3 kDa, 521 amino acids). To correlate the unique allosteric properties of the fungal enzyme with specific structural features, we cloned and sequenced the ATP sulfurylase gene (aps) from P. chrysogenum. The yeast and fungal enzymes are homologous over the first 400 amino acids and contain two regions high in basic residues which are conserved in sulfurylases from Arabidopsis and the Riftia pachyptila (hydrothermal vent tube worm) chemolithotrophic symbiont. These regions may participate in forming the binding sites for MgATP2- and SO4(2-). The fungal enzyme has no sites for MgATP2- and SO4(2-). The fungal enzyme has no significant sequence homology to the yeast enzyme in the C-terminal 172 amino acids. This C-terminal region contains SH-1 (Cys-508) and has homology to MET14 (S. cerevisiae), CYSC (E. coli), and NODQ (Rhizobium meliloti), i.e. adenosine 5'-phosphosulfate (APS) kinase. The cumulative results suggest that (a) the allosteric PAPS binding site of P. chrysogenum ATP sulfurylase is located in the C-terminal domain of the protein and (b) that this domain may have evolved from APS kinase. In spite of the homology, this C-terminal region does not account for the APS kinase activity of P. chrysogenum. Fungal ATP sulfurylase has no significant homology to (or regulatory properties in common with) CYSD or CYSN, proteins reported to comprise E. coli ATP sulfurylase (Leyh, T., Vogt, T. F., and Suo, Y. (1992) J. Biol. Chem. 267, 10405-10410).

Allosteric Site↗
PubMed1994

A novel role for MHC class II antigens: evidence implicating a protective effect on tumour cells against cytotoxicity by NK and LAK cells.

There are several lines of evidence clearly demonstrating that major histocompatibility complex (MHC) class I antigens are important in protecting haemopoietic tumour cells from natural killer (NK)-mediated cell lysis. In the present studies we examined the role of MHC class II antigens in affording such protection to haemopoietic tumour cell lines. NK and lymphokine-activated killer (LAK) lysis were performed on two human B lymphoma cell lines and their mutants lacking HLA class II expression, i.e. DR, DP and DQ. Raji and T5-1 were compared to their mutants RM3 and 6.1.6, respectively. Significantly more lysis was observed with the mutants compared to the parent cell line. Effectors used included (1) peripheral blood NK effectors, (2) a human NK cell line (NK 3.3), and (3) peripheral blood LAK effectors. The increased lysis with the mutants could not be explained on the basis of (1) increased conjugate formation, (2) increased cell fragility or (3) ineffectual expression of HLA class I and other non-HLA antigens. These findings suggest that HLA class II molecules may have a novel role. They may be relevant not only in antigen presentation but may also protect tumour cells (and possibly normal activated lymphoid cells) against lysis mediated by NK and LAK cells.

Antigens, Neoplasm↗
PubMed1993

ATP sulfurylase from higher plants: kinetic and structural characterization of the chloroplast and cytosol enzymes from spinach leaf.

Two forms of ATP sulfurylase were purified from spinach leaf. The major (chloroplast) form accounts for 85 to 90% of the total leaf activity (0.03 +/- 0.01 adenosine-5'-phosphosulfate (APS) synthesis units x gram fresh weight-1). Both enzyme forms appear to be tetramers composed of 49- to 50-kDa subunits with the minor (cytosolic) form being slightly larger than the chloroplast form. The specific activities (units x milligram protein-1) of the chloroplast form at pH 8.0, 30 degrees C, were as follows: APS synthesis, 16; molybdolysis, 229; ATP synthesis, 267; selenolysis, 4.1; fluorophosphate activation, 11. Kinetic constants for the physiological reaction were as follows: KmA = 0.046 mM, K(ia) = 0.85 mM, KmB = 0.25 mM, KmQ = 0.37 microM, K(iq) = 64-85 nM, and KmP = 10 microM, where A = MgATP, B = SO4(2-), P = total PPi at 5 mM Mg2+, and Q = APS. The kinetic constants for molybdolysis were similar to those of the APS synthesis reaction. The kinetic constants of the minor (cytosol) form were similar to those of the major form with two exceptions: (a) The molybdolysis activity was 120 units x milligram protein-1, yielding a Vmax (ATP synthesis)/Vmax (molybdolysis) ratio close to 2 (compared to about unity for the chloroplast form) and (b) KmA was greater (0.24 and 0.15 mM for APS synthesis and molybdolysis, respectively). Initial velocity measurements (made over an extended range of MgATP and SO4(2-) concentrations), product inhibition studies (by initial velocity methods and by reaction progress curve analyses), dead end inhibition studies (with monovalent and divalent oxyanions), and kcat/Km comparisons (for SO4(2-) and MoO4(2-) support a random AB-ordered PQ kinetic mechanism in which MgATP and SO4(2-) bind in a highly synergistic manner. Equilibrium binding studies indicated the presence of one APS site per subunit. HPLC elution profiles of chymotryptic and tryptic peptides were essentially the same for both enzyme forms. The N-terminal sequence of residues 5-20 of the cytosol enzyme was identical to residues 1-16 of the chloroplast enzyme.

Adenosine Phosphosulfate↗
PubMed1991

Conformational analysis and aqueous hydration studies of model peptides for the adhesive protein of the mussel, Mytilus edulis L.

Conformations of model peptides of the adhesive protein of the mussel, Mytilus edulis L were investigated using molecular mechanics. The protein structure was represented as the repeat of a 10-residue unit. This decamer, and di- and tri-decamers of it, were considered in the modeling. Incorporation of the unusual dopamine residue in the decamer repeat may be explained by its hydrogen bond forming ability via its 3-OH group to a proline carbonyl oxygen. This bond contributes to maintaining a double reverse beta-turn structure in the decamer. This conformation was found more stable than 3(1) and alpha helical conformations. Adjacent reverse beta-turn structures are connected by short segments (2 to 3 residues) having little conformational preference. Thus, the overall protein can possess a significant random nature, yet have a highly ordered embedded conformational component. Hydrophilic character is in line with the larger number of OH groups on the phenyl ring for residue 9 (the site of the Dopa residue). The dehydration free energy of the (3-OH)-Phe as compared to the Dopa derivative is less by 1.4 kcal per decamer unit. This amounts to more than 100 kcal energy gain in the dehydration process for the total protein.

Amino Acid Sequence↗
PubMed1990

Alpha,beta-dehydro residues in the design of peptide and protein structures.

The results of X-ray studies on 19 structures containing dehydro residues have been analysed. The observed average C alpha = C beta distance in the dehydro residues is 1.331 (2) A. The average values of the C alpha = C beta - C gamma bond angle in dehydro-Phe and dehydro-Leu are 131.2 (2) and 127.3 (1) degrees, respectively. The dehydro residue is essentially planar. A beta-turn of type II is formed if the dehydro residue is placed either at the (i + 1) or at the (i + 2) corner position of the beta-turn. If the dehydro residues occur consecutively in an amino-acid sequence, the backbone folds into an alternating right- and left-handed alpha-helix. The peptide bond is planar in all these structures. The beta-turn is stabilized by an intramolecular hydrogen bond between CO of the ith and NH of the (i + 3)th residue.

Amino Acid Sequence↗
PubMed1990

Synthesis, crystal structure, and molecular conformation of peptide N-Boc-L-Pro-dehydro-Phe-L-Gly-OH.

The peptide N-Boc-L-Pro-dehydro-Phe-L-Gly-OH was synthesized by the usual workup procedure and finally coupling the N-Boc-L-Pro-dehydro-Phe to glycine. The peptide crystallizes in monoclinic space group P2(1) with a = 8.951(4) A, b = 5.677(6) A, c = 21.192(11) A, beta = 96.97(4) degrees, V = 1069(1) A3, Z = 2, dm = 1.295(5) Mgm-3, and dc = 1.297(4) Mgm-3. The structure was determined by direct methods using SHELXS86. The structure was refined by the block-diagonal least-squares procedure to an R value of 0.074 for 1002 observed reflections. The C alpha 2-C beta 2 distance of 1.33(2) A is an appropriate double bond length. The angle C alpha 2-C beta 2-C gamma 2 is 133(1) degrees. The peptide backbone torsion angles are theta 1 = -167(1) degrees, omega 0 = 179(1) degrees, phi 1 = -48(1) degrees, psi 1 = 137(1) degrees, omega 1 = 175(1) degrees, phi 2 = 65(2) degrees, psi 2 = 15(2) degrees, omega 2 = -179(1) degrees, and phi 3 = -166(1) degrees. These values show that the Boc group has a trans-trans conformation while the peptide backbone adopts a beta-turn II conformation, which is stabilized by an intramolecular hydrogen bond of length of 3.05(1) A. The structures of dehydro-Phe containing peptides suggest that the dehydro-Phe promotes the beta-turn II conformation. The five-membered pyrrolidine ring of the Pro residue adopts an ideal C gamma-exo conformation with torsion angles chi 1(1) = -24(1) degrees, chi 2(1) = 34(1) degrees, chi 3(1) = -30(1) degrees, chi 4(1) = 15(1) degrees, and theta 0(1) = 6(1) degrees. The side-chain torsion angles in dehydro-Phe are chi 1(2) = -1(2) degrees, chi 2,1(2) = -176(1) degrees, and chi 2,2(2) = 8(2) degrees. The plane of C alpha 2-C beta 2-C gamma 2 is rotated with respect to the plane of the phenyl ring at 7(1) degrees, which indicates that the atoms of the side chain of dehydro-Phe are essentially coplanar. The molecules form a 2(1) screw axis related hydrogen-bonded rows along the b axis.

Amino Acid Sequence↗