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Ketan Patel

Publications and source records attributed to Ketan Patel.

At least 19 recordsLinked to original sources
PubMed2007

Selective protein kinase C inhibition attenuates pulmonary artery cytokine expression without affecting hypoxic pulmonary vasoconstriction.

Hypoxic pulmonary vasoconstriction may be an adaptive response to shunt blood to well-oxygenated areas of the lung, but hypoxia-induced inflammatory cytokine production leads to acute lung injury. We have previously shown that protein kinase C (PKC) mediates both hypoxic pulmonary vasoconstriction and inflammatory cytokine expression from the pulmonary artery; however, the effect of specific PKC isoform inhibition is currently unknown. We hypothesized that inhibition of classical PKC (cPKC) isoforms would attenuate hypoxic pulmonary vasoconstriction and downregulate hypoxia-induced pulmonary artery cytokine expression. To study this, isometric force displacement was measured in isolated rat pulmonary artery rings (n = 6 per group) during hypoxia (95% N2/5% CO2) in the presence of the nonspecific PKC inhibitor bisindolylmaleimide (1 micromol/L), the cPKC inhibitor Gö 6976 (1 - 10 micromol/L), or vehicle (dimethyl sulfoxide, 0.001%). After 60 min of hypoxia, pulmonary artery rings were analyzed for tumor necrosis factor (TNF) alpha and interleukin (IL) 1beta messenger RNA via reverse transcriptase-polymerase chain reaction. Nonspecific PKC inhibition (bisindolylmaleimide) significantly attenuated hypoxic pulmonary vasoconstriction (44.59 +/- 10.52% vs. 87.06 +/- 10.91% vehicle; P < 0.001) and downregulated hypoxia-induced expression of pulmonary artery TNF-alpha. Specific cPKC inhibition (Gö 6976) attenuated pulmonary artery TNF-alpha expression but had no effect on hypoxic pulmonary vasoconstriction. These data are indicative of the following: (1) nonspecific PKC inhibition attenuates both hypoxic pulmonary vasoconstriction and pulmonary artery TNF-alpha expression, (2) cPKC inhibition downregulates hypoxia-induced pulmonary artery TNF-alpha expression but has no effect on hypoxic pulmonary vasoconstriction, and (3) hypoxic pulmonary vasoconstriction and hypoxia-induced pulmonary artery cytokine expression are independent processes.

Animals↗
PubMed2006

Regulation of scapula development.

The scapula is a component of the shoulder girdle. Its structure has changed greatly during evolution. For example, in humans it is a large quite flat triangular bone whereas in chicks it is a long blade like structure. In this review we describe the mechanisms that control the formation of the scapula. To assimilate our understanding regarding the development of the scapula blade we start by addressing the issue concerning the origin of the scapula. Experiments using somite extirpation, chick-quail cell marking system and genetic cell labelling techniques in a variety of species have suggested that the scapula had its origin in the somites. For example we have shown in the chick that the scapula blade originates from the somite, while the cranial part, which articulates with the upper limb, is derived from the somatopleure of the forelimb field. In the second and third part of the review we discuss the compartmental origin of this bone and the signalling molecules that control the scapula development. It is very interesting that the scapula blade originates from the dorsal compartment, dermomyotome, which has been previously been associated as a source of muscle and dermis, but not of cartilage. Thus, the development of the scapula blade can be considered a case of dermomyotomal chondrogenesis. Our results show that the dermomyotomal chondrogenesis differ from the sclerotomal chondrogenesis. Firstly, the scapula precursors are located in the hypaxial domain of the dermomyotome, from which the hypaxial muscles are derived. The fate of the scapula precursors, like the hypaxial muscle, is controlled by ectoderm-derived signals and BMPs from the lateral plate mesoderm. Ectoderm ablation and inhibition of BMP activity interfers the scapula-specific Pax1 expression and scapula blade formation. However, only somite cells in the cervicothoracic transition region appear to be committed to form scapula. This indicates that the intrinsic segment specific information determines the scapula forming competence of the somite cells. Taken together, we conclude that the scapula forming cells located within the hypaxial somitic domain require BMP signals derived from the somatopleure and as yet unidentified signals from ectoderm for activation of their coded intrinsic segment specific chondrogenic programme. In the last part we discuss the new data that provides evidence that neural crest contributes for the development of the scapula.

Animals↗
PubMed2006

Skeletal muscle translocation in vertebrates.

It is now over 30 years since Bodo Christ first demonstrated that the musculature of the limb originated from the somites and overturned the then prevailing view that limb muscle develops from a local source. Subsequently, using electron microscopy and histological procedures, Bodo Christ identified that cells of the somites undergo an epithelial to mesenchymal transition which enabled them to move from their paraxial point of origin to distal locations. These studies defined this translocation as one of the major mechanisms allowing myogenic cells to translocate around the body. The other means used to translocate muscle involves the movement of cells as a sheet. The deployment of one of these two mechanisms has been postulated to be involved in the formation of all the hypaxial musculature of the vertebrate body. In this paper we describe the formation of muscles both in the head and in the body, which use a translocatory mechanism during their development. We highlight recent data showing that muscle translocation is a far more complex process than first thought but which in itself can be used as a valuable tool to address questions regarding tissue patterning and development.

Animals↗
PubMed2006

Expression and regulation of Nkd-1, an intracellular component of Wnt signalling pathway in the chick embryo.

The Wnt family of secreted signalling molecules control a wide range of developmental processes in all metazoans. The intracellular response to Wnt signalling depends on the choice of signalling cascade activated in the responding cell. Cells can activate either the canonical pathway that modulates gene expression to control cellular differentiation and proliferation, or the non-canonical pathway that controls cell polarity and movement. Recent work has identified the protein Naked Cuticle to act as an intracellular switch to promote the non-canonical pathway at the expense of the canonical pathway. We have cloned chick Naked Cuticle-1 (cNkd-1) and show that it is expressed in a dynamic manner during early embryogenesis. We show that it is expressed in the somites and in particular regions where cells are undergoing movement. Lastly, we show that the expression of cNkd-1 is regulated by Wnt expression originating from the neural tube. This study provides evidence that non-canonical Wnt signalling plays a part in somite development.

Amino Acid Sequence↗
PubMed2006

Pax3 and Pax7 expression and regulation in the avian embryo.

Satellite cells are essential for postnatal growth and repair of skeletal muscle. The paired-box transcription factors Pax3 and Pax7 are expressed in emerging muscle precursors. Recent studies have traced the origin of satellite cells to the embryonic dermomyotome, however, their developmental regulation throughout embryogenesis remains unclear. We show the overlying surface ectoderm and lateral plate are essential for Pax3 expression, and that the overlying surface ectoderm and neural tube are necessary for Pax7 expression within the dorsal somite. Furthermore we show that the notochord acts to down regulate the expression of both genes. Moreover, we identify diffusible factors within these tissues that act to maintain expression of Pax3 ( + ) and Pax7 (+) muscle precursors. We show that Wnt1, 3a, 4 and 6 proteins are able to up regulate and expand the expression of Pax3 and Pax7 within the dorsal somite. Finally, we show that Wnt6 can mimic the effect of the dorsal ectoderm to maintain Pax3 and Pax7 expression.

Animals↗
PubMed2006

Myostatin imposes reversible quiescence on embryonic muscle precursors.

We have previously shown that Myostatin, a member of the transforming growth factor beta (TFG-beta) family of signalling molecules, is expressed in developing muscle, and that treatment with recombinant Myostatin inhibited the expression of key myogenic transcription factors during chick embryogenesis. In this study, we followed the fate of muscle precursors after exposure to Myostatin. We report that in contrast to the down-regulation in expression of Pax-3, Myf-5, MyoD, and Myogenin, expression of Pax-7 was maintained. However, Myostatin completely inhibited cell division in the Pax-7-expressing cells. The inhibitory effect of Myostatin was reversible, as upon withdrawal myogenic cells re-initiated cell proliferation as well as expression of Pax-3 and MyoD. These results led us to investigate the temporal and spatial distribution of quiescent muscle precursors during development. To this end, we analysed distribution and mitotic behaviour of Pax-7-expressing cells during muscle development. Our studies revealed two populations of Pax-7-expressing cells, one that proliferated and incorporated BrdU, whilst the other did not. At early developmental stages, a high proportion of Pax-7-expressing cells proliferated, but there was a significant number of non-dividing Pax-7-expressing cells intermingled with differentiated muscle. Proliferating precursors became less frequent as development proceeded and at late fetal stages all Pax-7-expressing cells were mitotically quiescent. We suggest that Myostatin is an important signalling molecule responsible for imposing quiescence upon myogenic precursors during embryonic and foetal development.

Animals↗
PubMed2006

Identification of blottin: a novel gastric trefoil factor family-2 binding protein.

The trefoil factor family (TFF) peptides are important in gastro-intestinal mucosal protection and repair. Their mechanism of action remains unclear and receptors are sought. We aimed to identify and characterise proteins binding to TFF2. A fusion protein of mouse TFF2 with alkaline phosphatase was generated and used to probe 2-D protein blots of mouse stomach. The resulting spots were analysed by MS. The protein identified was characterised by bioinformatics, rapid amplification of cDNA ends, in situ hybridisation (ISH) and immunohistochemistry (IHC). Functional assays were performed in gastrointestinal cell lines. A single major murine protein was identified and named blottin. It was previously unknown as a translated product. Blottin is also present in rat and human; the latter gene is also known as GDDR. The predicted full-length proteins are 184 amino acids long (20 kDa), reducing to 164 amino acids (18 kDa) after signal peptide cleavage. ISH of gastrointestinal tissues shows abundant blottin mRNA in gastric surface and foveolar epithelium. IHC shows cytoplasmic staining for blottin protein, and by immunoelectron microscopy in mucus granules and Golgi stacks. Previous work showed that blottin is down-regulated in gastric cancers. Blottin contains a BRICHOS domain, and has 56% similarity with gastrokine-1. Cultured HT-29 cells express blottin and show increased DNA synthesis with antiblottin antibody; however, this effect is reversed by the immunising peptide. We have identified and characterised a TFF2-binding protein produced by gastric epithelium. Blottin may play a role in gastrointestinal mucosal protection and modulate gut epithelial cell proliferation.

Alkaline Phosphatase↗
PubMed2005

Ectodermal Wnt-6 promotes Myf5-dependent avian limb myogenesis.

Limb muscles of vertebrates are derived from precursor cells that migrate from the lateral edge of the dermomyotome into the limb bud. Although several signaling molecules have been reported to be involved in the process of limb myogenesis, none of their activities has led to a consolidate idea about the limb myogenic pathway. Particularly, the role of ectodermal signals in limb myogenesis is still obscure. Here, we investigated the role of the ectoderm and ectodermal Wnt-6 during limb muscle development. We found that ectopic expression of Wnt-6 in the limb bud specifically extends the expression domains of Pax3, Paraxis, Myf5, Myogenin, Desmin and Myosin heavy chain (MyHC) but inhibits MyoD expression. Ectoderm removal results in a loss of expression of all of these myogenic markers. We show that Wnt-6 can compensate the absence of the ectoderm by rescuing the expression of Pax3, Paraxis, Myf5, Myogenin, Desmin and MyHC but not MyoD. These results show that, in chick, at least two signals from the limb ectoderm are necessary for muscle development. One of the signals is Wnt-6, which plays a unique role in promoting limb myogenesis via Pax3/Paraxis-Myf5, whereas the other putative signaling pathway involving MyoD expression is negatively regulated by Wnt-6 signaling.

Animals↗
PubMed2005

Wnts and the neural crest.

The neural crest is a multipotent tissue that originates between the neural epithelium and non-neural ectoderm, which can develop into numerous cell types, including neurons, glia, pigment cells, smooth muscle, cartilage and bone. Work in a variety of animal models has shown that a number of signalling factors are necessary for the induction, delamination and differentiation of neural crest cells. However one family of proteins, the Wnts, shows an overriding influence on this tissue. Here we review recent studies that pinpoint specific roles that Wnts play in the development of the neural crest.

Animals↗
PubMed2005

Activin A inhibits formation of skeletal muscle during chick development.

In this study we investigated the effect of recombinant activin A on the differentiation of limb muscle precursors of chick embryos. We show that treatment with activin resulted in a downregulation of Pax-3 and MyoD expression within 6 h after treatment, whereas expression of Myf-5 and Pax-7 was largely unaffected. The effect on gene expression was transient because 1 day after activin exposure the development of the premuscle masses had proceeded, and Pax-3 and MyoD expression was reexpressed at normal levels. Unlike other transforming growth factors-beta, activin did not induce programmed cell death in limb mesenchyme, thus myogenic cells were not permanently lost. In high-density cultures of embryonic chick limb mesenchyme (micromass cultures), activin repressed the generation of Pax-7-expressing muscle precursors. Furthermore, in the presence of activin, fewer muscle precursors differentiated, and the population of differentiating cells failed to fuse and form myotubes. Our data suggest that activin reversibly inhibited expression of two transcription factors, Pax-3 and MyoD, and thus transiently inhibited proliferation and differentiation of limb muscle precursors. However, myogenic cells were not lost as they continued to express Pax-7 and Myf-5, and this may have allowed precursors to commence development after the activin effect faded. We suggest that activin acts in conjunction with a closely related signalling molecule, myostatin, to prevent excessive growth of skeletal muscle.

Activins↗
PubMed2005

The function of Myostatin and strategies of Myostatin blockade-new hope for therapies aimed at promoting growth of skeletal muscle.

Genetic deletion of Myostatin, a member of the Transforming Growth Factor-beta family of signalling molecules, resulted in excessive growth of skeletal muscle. It demonstrated the remarkable intrinsic growth potential of skeletal muscle and led to the proposal that growth stimulation could amend diseased muscle without having to correct the primary cause of the disease. Furthermore, the presence of Myostatin in skeletal muscle in a number of muscle diseases and disease models suggested that it aggravated the primary pathology. Inhibition of Myostatin activity in mdx mouse, the animal model for Duchenne muscular dystrophy, resulted in increased force production and better tissue architecture which implicated Myostatin as a target for new therapeutic strategies. In this review we will discuss the phenotypes of animal models in which Myostatin function is altered. We will highlight the particularities of the Myostatin signalling pathway and describe molecular strategies that have been developed to inhibit the function of Myostatin on muscle. Finally, we will summarise the role of Myostatin in diseased muscle and discuss blockade of Myostatin as a potential therapy for muscular dystrophies.

Animals↗
PubMed2005

Arthrotome: a specific joint forming compartment in the avian somite.

Somitocoele cells previously have been shown to form the proximal part of the ribs, the intervertebral discs, and the intervertebral joints (synovial joints). To determine whether the somitocoele cells are necessary for the development of axial skeleton joints, we microsurgically ablated the somitocoele cells in epithelial somites of 2-day-old chick embryos. The operated embryos were analyzed after whole-mount skeletal preparations and in sections. Removal of the somitocoele cells led to two major outcomes: (1) Intervertebral joints failed to develop and resulted in the fusion of the superior articular process and the inferior articular process; (2) Adjacent vertebral bodies fused and lacked the intervertebral disc. These results demonstrate that somitocoele cells specifically give rise to intervertebral joints and discs. Furthermore, these results suggest that neighboring sclerotome cells cannot adapt to form vertebral joints in the absence of the somitocoele compartment. Thus, we provide for the first time experimental evidence for the existence of a joint forming compartment in the somites, which we term the "arthrotome."

Animals↗
PubMed2005

A newly described ictal pattern: the initial ictal slow shift.

This report deals with a newly described ictal pattern, called the initial ictal slow shift (IS)2. This pattern may be seen in subdural records as the first sign of an ictal event, occurring before the later typical rhythms of a seizure state appear. A positive shift, very similar in appearance from one seizure to another, usually lasted for 1-2 sec, followed by a negativity for 7-9 sec that included the typical rhythmical discharges. At times, a negative shift occurred first, seen up to 15 mV very high in amplitude, for a few seconds before the typical ictal rhythms were seen. Scalp records may also demonstrate slow shifts, and examples are shown of the typical 3/sec bilateral spike and wave (S+W) complexes of absence seizures. A slow shift occasionally appeared 1 sec before the onset of these complexes, but more often a few seconds after the onset. Finally, after the end of the S+W complexes, a positive shift, for as long as 5-6 sec may occur, up to 600 microV in amplitude. These shifts could relate to data showing that patients are not really back to a normal responsiveness for at least 5 sec after the end of the S+W complexes (see Discussion).

Adult↗
PubMed2005

A dual fate of the hindlimb muscle mass: cloacal/perineal musculature develops from leg muscle cells.

The cloaca serves as a common opening to the urinary and digestive systems. In most mammals, the cloaca is present only during embryogenesis, after which it undergoes a series of septation events leading to the formation of the anal canal and parts of the urogenital tract. During embryogenesis it is surrounded by skeletal muscle. The origin and the mechanisms regulating the development of these muscles have never been determined. Here, we show that the cloacal muscles of the chick originate from somites 30-34, which overlap the domain that gives rise to leg muscles (somites 26-33). Using molecular and cell labelling protocols, we have determined the aetiology of cloacal muscles. Surprisingly, we found that chick cloacal myoblasts first migrate into the developing leg bud and then extend out of the ventral muscle mass towards the cloacal tubercle. The development of homologous cloacal/perineal muscles was also examined in the mouse. Concordant with the results in birds, we found that perineal muscles in mammals also develop from the ventral muscle mass of the hindlimb. We provide genetic evidence that the perineal muscles are migratory, like limb muscles, by showing that they are absent in metd/d mutants. Using experimental embryological procedures (in chick) and genetic models (in chick and mouse), we show that the development of the cloacal musculature is dependent on proximal leg field formation. Thus, we have discovered a novel developmental mechanism in vertebrates whereby muscle cells first migrate from axially located somites to the pelvic limb, then extend towards the midline and only then differentiate into the single cloacal/perineal muscles.

Animals↗
PubMed2004

Safety and antiretroviral effectiveness of concomitant use of rifampicin and efavirenz for antiretroviral-naive patients in India who are coinfected with tuberculosis and HIV-1.

OBJECTIVE: To study the safety and antiretroviral effectiveness of concomitant use of rifampicin and efavirenz for antiretroviral-naïve patients in India who are coinfected with tuberculosis (TB) and HIV-1. DESIGN AND METHODS: The study was an observational longitudinal cohort investigation. HIV-1-infected patients with CD4 cell counts of < or = 200/microL who attended the Infectious Disease Clinic of Sterling Hospital (Ahmedabad, India) from June 2001 to December 2002 were recruited for the study. Patients were divided in 2 groups: group A, patients with active TB (n = 126); and group B, patients without TB (n = 129). Group A patients were given efavirenz with 2 nucleoside reverse transcriptase inhibitors along with rifampicin-containing anti-TB treatment. Group B patients were treated for presenting opportunistic infections and started therapy with efavirenz plus 2 nucleoside reverse transcriptase inhibitors. The nucleoside reverse transcriptase inhibitors were either zidovudine and lamivudine (n = 30) or stavudine and lamivudine (n = 225). Patients self-funded their investigations and medications (antiretroviral, anti-TB, and other opportunistic infection-related agents). Indian generic medications were used. RESULTS: Efavirenz-based highly active antiretroviral therapy with rifampicin for HIV/TB-coinfected patients resulted in an immunologic response that was comparable with that of the group not receiving rifampicin. Median CD4 cell counts at baseline, 3 months, 6 months, and 9 months in group A were 84/microL (range, 5-200/microL), 225/microL (range, 26-528/microL), 251/microL (range, 65-775/microL), and 275/microL (range, 61-611/microL), respectively, and in group B, these values were 118/microL (range, 2-200/microL), 244/microL (range, 38-881/microL), 294/microL (range, 23-1322/microL), and 295/microL (range, 26-991/microL), respectively. The overall increase in CD4 cell count was greater in group A than in group B at 9 months (190 vs. 176/microL, respectively). Patients in both groups tolerated the therapy well; the adverse effects profile was comparable except that group A patients had a higher incidence of hepatitis than group B patients (13.49% vs. 0, respectively; P < 0.0001). CONCLUSION: Clinical and immunologic benefits are comparable for patients receiving efavirenz-based antiretroviral therapy with or without rifampicin.

Adult↗