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Biomedical subjects

G Patel

Publications and source records attributed to G Patel.

At least 19 recordsLinked to original sources

Novel molecular basis of an Inab phenotype.

The Cromer blood group system consists of ten high-prevalence and three low-prevalence antigens carried on decay-accelerating factor (DAF). DAF is found in the cell membranes of RBCs, granulocytes, platelets, and lymphocytes and is widely represented in other body tissues. Sequence analyses of DNA were performed on a blood sample from a 91-year-old Japanese woman whose serum contained an alloantibody to a high-prevalence antigen in the Cromer blood group system (anti-IFC). A blood sample from her daughter was also studied. Sequence analysis revealed a substitution of 508C7>T in exon 4 of DAF in the proband. The proband's daughter was heterozygous for 508C/T. This study describes an Inab phenotype in which the 508C>T nonsense mutation is predicted to change arginine at amino acid residue 136 to a stop codon. This change is in SCR 3 of DAF. This study reports on the molecular basis of a new proband with the Inab phenotype who had no history of intestinal disorders.

Aged↗

Recurrent intravascular papillary endothelial hyperplasia developing from a pyogenic granuloma.

Intravascular papillary endothelial hyperplasia (IPEH) is a rare benign vascular tumour. Many histological features are similar to those of low-grade angiosarcoma, a common, but more serious condition. Clinical and histological differentiation is important to avoid overtreatment of this benign condition. We report on a 34-year-old woman who developed recurrent IPEH at the site of a previously excised pyogenic granuloma.

Adult↗

Distinct localization and function of (1,4,5)IP(3) receptor subtypes and the (1,3,4,5)IP(4) receptor GAP1(IP4BP) in highly purified human platelet membranes.

Platelet activation is associated with an increase of cytosolic Ca(++) levels. The (1,4,5)IP(3) receptors [(1,4,5)IP(3)R] are known to mediate Ca(++) release from intracellular stores of many cell types. Currently there are at least 3 distinct subtypes of (1,4, 5)IP(3)R-type I, type II, and type III-with suggestions of distinct roles in Ca(++) elevation. Specific receptors for (1,3,4,5)IP(4) belonging to the GAP1 family have also been described though their involvement with Ca(++) regulation is controversial. In this study we report that platelets contain all 3 subtypes of (1,4,5)IP(3)R but in different amounts. Type I and type II receptors are predominant. In studies using highly purified platelet plasma (PM) and intracellular membranes (IM) we report a distinct localization of these receptors. The PM fractions were found to contain the type III (1,4,5)IP(3)R and GAP1(IP4BP) in contrast to IM, which contained type I (1,4,5)IP(3)R. The type II receptor exhibited a dual distribution. In studies examining the labeling of surface proteins with biotin in intact platelets only the type III (1,4,5)IP(3)R was significantly labeled. Immunogold studies of ultracryosections of human platelets showed significantly more labeling of the PM with the type III receptor antibodies than with type I receptor antibodies. Ca(++) flux studies were carried out with the PM to demonstrate in vitro function of inositol phosphate receptors. Ca(++) release activities were present with both (1,4,5)IP(3) and (1, 3,4,5)IP(4) (EC(50) = 1.3 and 0.8 micromol/L, respectively). Discrimination of the Ca(++)-releasing activities was demonstrated with cyclic adenosine monophosphate (cAMP)-dependent protein kinase (cAMP-PK) specifically inhibiting (1,4,5)IP(3) but not (1,3,4, 5)IP(4)-induced Ca(++) flux. In experiments with both PM and intact platelets, the (1,4,5)IP(3)Rs but not GAP1(IP4BP) were found to be substrates of cAMP-PK and cGMP-PK. Thus the Ca(++) flux property of (1,3,4,5)IP(4) is insensitive to cAMP-PK. These studies suggest distinct roles for the (1,4,5)IP(3)R subtypes in Ca(++) movements, with the type III receptor and GAP1(IP4BP) associated with cation entry in human platelets and the type I receptor involved with Ca(++) release from intracellular stores.

Blood Platelets↗

Tinea faciei due to Microsporum canis abscess formation.

Superficial dermatophyte infections are common in children; however, complications are encountered rarely. We describe a child with tinea faciei caused by Microsporum canis, who subsequently developed an abscess. Complete resolution occurred after treatment with oral terbinafine.

Abscess↗

Polypoid clear cell acanthoma: case report.

Clear cell acanthoma of Degos is a rare benign tumour of epidermal origin with distinct histological features. Clinically, clear cell acanthoma is characterized by a 'stuck on' appearance of a nodule or dome-shaped plaque that usually occurs on the legs of middle-aged or elderly persons. We observed an unusual case of polypoid clear cell acanthoma on the right thigh of a 58-year-old male.

Adult↗

Anticoagulant versus amidolytic activity of tissue factor pathway inhibitor in coronary artery disease.

In view of raised levels of endothelial markers in coronary artery disease (CAD), the aim of the present study was to investigate the status of tissue factor pathway inhibitor (TFPI), another endothelium-associated glycoprotein and coagulation protease inhibitor, in CAD. The intravascular pool of TFPI is heterogeneous with respect to assay-dependent activity. While the standard amidolytic assay works well with both full-length and truncated (lipoprotein-associated) TFPI, the anticoagulant assay works better with the former. The anticoagulant activity of TFPI can be estimated using dilute tissue factor (TF) to trigger clotting of plasma. In the present study, recombinant TF diluted 2,000-fold was used to initiate coagulation. A dose-dependent shortening of clotting time of normal plasma pools with polyclonal antibody against the C-terminal but not the N-terminal peptide of TFPI demonstrated the importance of the C-terminal region, and hence that of full-length TFPI, in conferring its anticoagulant activity, corroborating current opinion. As a further confirmation, the C-terminal peptide itself prolonged dilute TF clotting time of normal pooled plasma in a concentration-dependent manner. The amidolytic and anticoagulant activities of TFPI were determined in 20 patients with clinically and angiographically assessed CAD and in 68 asymptomatic controls. The mean +/- SD ages of patients and controls were 54.9 +/- 10.3 and 48.8 +/- 11.6 years, respectively, the difference being statistically significant (P = 0.04). The mean TFPI activity measured by amidolytic assay was comparable for patients and controls (1.2 +/- 0.3 and 1.3 +/- 0.5 U/ml, respectively). However, the dilute TF clotting time was 115 +/- 26 s in patients, against 99 +/- 10 s in controls (P < 0.0001, irrespective of age adjustment). Since none of the patients had received heparin or had coagulation factor deficiency that may interfere with the assay, prolongation of clotting time may be attributed to the presence of TFPI, particularly the full-length form. To verify this inference, 33 extra aliquots left over from 88 samples (62.5%), 21 from controls and 12 from patients, were incubated with 1:10 diluted antibody against the C-terminal peptide of TFPI prior to dilute TF assay. The mean clotting time of both patients and controls decreased, and the between-group difference leveled (90 +/- 10 versus 88 +/- 20 s for controls and patients, respectively; P = 0.841). The mean drop in clotting time was 9% for the controls and 24% for the patients. This illustrates the specificity of dilute TF assay for full-length TFPI and supports the conclusion that relative to lipoprotein-associated TFPI, the proportion of the full-length form was possibly greater in patients with CAD. Contribution of lipoprotein-associated TFPI to the overall anticoagulant activity by its activated factor X-dependent inhibition of activated factor VII-TF complex seems less important considering the similar between-group mean amidolytic activities.

Anticoagulants↗

Is routine removal of intramedullary nails justified.

This study investigates the outcome of 100 cases of lower limb intramedullary nail removal. 12 femoral and 25 tibial nails were removed for pain and 4 tibial nails for infection. For 22 tibial nails and 38 femoral nails there was no recorded indication. There where 3 operative complications, 2 abandoned procedures and 1 tibial fracture (nail extraction without prior removal of the distal locking screw). In 9 out of 16 cases anterior knee pain improved after tibial nail removal. 4 patients, previously asymptomatic, developed anterior knee pain following tibial nail removal. 40 patients who were discharged without crutches returned in pain and had to be given crutches to alleviate leg pain. 62 patients took a mean of 11 days sick leave. We conclude that all complications were avoidable. Intramedullary nail removal is safe. Patients with anterior knee pain should be told that their pain may persist and that knee pain may even arise. Most patients will require crutches and an average of 2 weeks away from work.

Adult↗

Oxygen isotope ratios of juice water in Australian oranges and concentrates.

Australian orange juices from major growing regions have been surveyed over a 5 year period with a view to establishing a database of (18)O/(16)O isotope ratios against which retail samples can be tested for authenticity. The (18)O/(16)O ratios were found to follow a consistent pattern that had both a cyclic seasonal and a regional influence. Oxygen delta values ranged from a summer maximum of >+15 per thousand for oranges from inland regions to a winter minimum of approximately +1 per thousand for oranges grown in coastal areas. However, over a shorter time period, the range of values was markedly less than this. Concentrated orange juices, pulpwashes, and peel extracts, as well as other citrus types, were also tested. The effect of some industry practices that have an effect on (18)O/(16)O ratios was also investigated.

Beverages↗

A cyclic peptide analogue of the loop III region of platelet-derived growth factor-BB is a synthetic antigen for the native protein.

We report the synthesis and characterization of a cyclic peptide analogue of the loop III region of platelet-derived growth factor (PDGF) B-chain sequence, cyclo(73Arg-Lys-Ile-Glu-Ile-Val-Arg-Lys-Lys81-Cys), incorporating a C-terminus cysteine residue for the conjugation to a carrier protein. The synthesis involved solid-phase chemistry, utilizing Fmoc-tBu chemistry and acid labile side-chain protecting groups, followed by 'head-to-tail' cyclization using the allyl-protected glutamic acid anchored on its side chain to the solid support with HATU/HOAt as the coupling agent. Conformational differences between the cyclic and its linear counterpart PDGF peptides were determined by circular dichroism measurements in aqueous media. High titre antisera were raised to both cyclic and linear peptide immunogens. Antisera raised to the cyclic peptide cross-reacted with PDGF-BB in both Western blot and ELISA, whereas antisera raised to the linear peptide had no reactivity with PDGF-BB. The cyclic peptide (conformational design analogue) produces an immunogen which is able to antigenically mimic the secondary structure of loop III of PDGF-BB and forms a basis from which further small molecular mimetics of PDGF may be designed for use as both immunogens and also potential agonists/antagonists of PDGF. Similarly constructed immunogens may also be useful in the design of vaccines which direct responses to loop regions in other target proteins.

Animals↗

Lyme disease associated with unilateral interstitial keratitis.

PURPOSE: To report a case of Lyme disease that presented with a single nummular unilateral interstitial keratitis. METHODS: Case report and review of the literature. RESULTS: A 57-year-old black man who had contact with freshly killed deer had a chief complaint of foreign-body sensation in his right eye (OD) that had been diagnosed and treated for herpes simplex stromal keratitis. The patient underwent a systemic workup for interstitial keratitis. All results including RPR and MHA-TP were negative except for Lyme antibody titer (enzyme-linked immunosorbent assay [ELISA]) 178 U/ml (normal, <159 U/ml). CONCLUSION: Interstitial keratitis from Lyme disease has been regarded as a bilateral disease in the literature. We present this infrequent ocular manifestation of Lyme disease as a rare single nummular unilateral presentation.

Anti-Bacterial Agents↗

Experimental pathogenicity of aeromonas spp. for the zebra mussel, dreissena polymorpha

Experiments were conducted to determine whether species of Aeromonas were pathogenic to the zebra mussel Dreissena polymorpha. A. jandaei, A. veronii, and A. media, identified with Biolog, were originally isolated from dead zebra mussels. When inoculated into living mussels, these bacteria resulted in the mortality of the bivalves. Two additional species, A. salmonicida salmonicida (ATCC 33678) and A. hydrophila (ATCC 7966), were also demonstrated to be pathogenic to the mussels. In addition to the pathogenicity, the data also suggest that the zebra mussels may be an important reservoir for these bacteria in freshwater environments.

Journal Article↗

Lasso procedure to revise overcorrection with radial keratotomy.

PURPOSE: To report three patients who underwent the lasso procedure to revise overcorrection with radial keratotomy. METHODS: Case report and review of the literature. RESULTS: Four eyes of three patients who had undergone radial keratotomy with resultant hyperopic overcorrection underwent a lasso procedure. Before the procedure, average cycloplegic refraction spherical equivalent was +3.656 +/- 1.352 diopters, and average manifest refraction spherical equivalent was +2.250 +/- 0.621 diopters. A 10.0 monofilament nylon suture was placed in a circumferencial manner through the corneal stroma and overlapping the old radial keratotomy incisions. At 1 month postoperatively, best-corrected visual acuity was 20/20 in all four eyes, with average cycloplegic refraction spherical equivalent +0.438 +/- 1.423 diopters and average manifest refraction spherical equivalent -0.156 +/- 1.147 diopters. Mean delta cycloplegic refraction spherical equivalent was 3.219 +/- 1.724. CONCLUSIONS: The lasso procedure provides an immediate solution for symptomatic overcorrected hyperopic eyes after radial keratotomy. Predictability and long-term stability necessitate further follow-up.

Adult↗

Do the magnocellular and parvocellular visual pathways contribute differentially to subitizing and counting?

We investigated the neurobiological basis of visual processes involved in object enumeration. Subitizing, the ability to rapidly and accurately enumerate four or fewer objects, is thought to depend on preattentive processing of visual stimuli, whereas counting of more numerous objects is thought to require serial shifts of attention. We attempted to distinguish between the hypothesis that the magnocellular (M) visual pathway is the preferential route for subitizing, and the alternative hypothesis that there is no selectivity for the M pathway or its counterpart, the parvocellular (P) visual pathway, in visual object enumeration. Green rectangles were presented on an equiluminant red background to impair M pathway processing. This slowed enumeration performance relative to a control condition in which object/background luminance differed, especially when the rectangles were relatively large and widely spaced and had constant retinal eccentricity. When low luminance contrast was used to impair processing along the P pathway, enumeration performance was slowed relative to a high-contrast control condition, especially when the rectangles were small and closely spaced. Overall, our manipulations affected enumeration performance without selectivity for subitizing or counting ranges and without altering the slope of the functions relating reaction time to numerosity. Thus, our results favor the hypothesis that visual enumeration does not depend preferentially on either the M or the P pathway.

Humans↗

A cyclic peptide analogue of loop III of PDGF-BB causes apoptosis in human fibroblasts.

A cyclic peptide analogue of platelet-derived growth factor-BB (PDGF-BB), P1 [77IVRKK81-C-73RKIE76], has recently been shown to inhibit specifically [125I]PDGF-BB/receptor binding, and PDGF-BB-induced DNA synthesis in cells expressing PDGF receptors. Here we demonstrate that P1 induces apoptosis in exponentially growing human fibroblasts as confirmed by characteristic changes in cell and nuclear morphology, by TUNEL staining and by flow cytometry. Following incubation with P1 (100 microM), the percentage of cells exhibiting DNA fragmentation increased from 24% after 8 h to 76% after 28 h as exponentially growing cells progressed through the cell cycle. We conclude from these findings taken together that apoptosis accounts for the major proportion of P1-induced cell death. Omission of the Cys residue from P1 or replacement by Ser did not alter the potency of the peptide confirming that peptide dimerisation is not important for its activity. PDGF-BB, EGF, FGF, thrombin and foetal bovine serum were not able to rescue cells from the effects of P1. P1 is a useful tool for investigation of the balance of cellular proliferation/apoptosis in wound healing, atherosclerosis and restenosis, and constitutes a basis from which to design compounds with greater potency.

Animals↗

Identification of a cyclic peptide inhibitor of platelet-derived growth factor-BB receptor-binding and mitogen-induced DNA synthesis in human fibroblasts.

Peptides corresponding to residues from Loops I and III of platelet-derived growth factor-BB (PDGF-BB) were examined for their potential to act as PDGF antagonists. We have identified two peptides which directly stimulated DNA synthesis in human dermal fibroblasts and a cyclic peptide which inhibited PDGF-induced DNA synthesis. The inhibitory action of cyclic PDGF-BB(73-81), on DNA synthesis was shown to be restricted to cells which express PDGF receptors. Also cyclic PDGF-BB(73-81) specifically competed for 125I-labelled PDGF-BB but not for 125I-labelled EGF binding to their respective cellular receptors. The cyclic peptide therefore provides a minimum structure to investigate PDGF/receptor interactions and our findings confirm the importance of the loop configuration of PDGF-BB(73-81) in the native molecule. The cyclic peptide may constitute a basis for developing more potent inhibitors of PDGF action.

Amino Acid Sequence↗

4-Methyl-3-oxo-4-aza-5alpha-androst-1-ene-17beta-N-aryl-carboxamides: an approach to combined androgen blockade [5alpha-reductase inhibition with androgen receptor binding in vitro].

4-Aza-5alpha-androstan-3-one 17beta-(N-substituted carboxamides) are potent human type 2 5alpha-reductase (5aR) inhibitors with generally poor binding to the human androgen receptor (hAR). When the 17-amide N-substituent included an aromatic residue, potent dual inhibitors of both type 1 and 2 5aR are produced, but hAR binding remained poor. Tertiary-substituted-17-amides have reduced inhibition of both 5aR isozymes. The addition of an N4-methyl substitutent to the A-ring profoundly increased hAR affinity and the addition of unsaturation to the A-ring (delta1) modestly augmented hAR binding. The unsubstituted carbanilides in the delta1-N4-methyl series show some selectivity for type 1 5aR over the type 2 isozyme, whereas addition of aryl substituents, particularly at the 2-position, increased type 2 5aR binding to provide dual inhibitors with excellent hAR binding, e.g. N-(2-chlorophenyl)-3-oxo-4-methyl-4-aza-5alpha-androst-1-ene-17bet a-carboxamide (9c). Compounds of this type exhibit low nanomolar IC50s for both human 5aR isozymes as well as the human androgen receptor. Kinetic analysis confirms that the prototype 9c displays reversible, competitive inhibition of both human isozymes of 5aR with K(i) values of less than 10 nM. Furthermore, this compound binds to the androgen receptor with an IC50 equal to 8 nM. Compounds in this series are projected to be powerful antagonists of testosterone and dihydrotestosterone action in vivo, with potential utility in the treatment of prostatic carcinoma (PC).

5-alpha Reductase Inhibitors↗