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J Rao

Publications and source records attributed to J Rao.

At least 19 recordsLinked to original sources
PubMed2007

Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease.

OBJECTIVE: This multicenter, randomized, double-blind study was performed to compare the safety and efficacy of the once-daily dopamine agonist rotigotine, in a continuous-dosing transdermal-patch formulation, vs placebo in patients with early-stage Parkinson disease (PD). METHODS: Patients were randomized to receive placebo (n = 96) or rotigotine (n = 181), starting at 2 mg/24 h (10-cm(2) patch size; 4.5-mg total drug content), titrated weekly up to 6 mg/24 h (30-cm(2) patch size; 13.5-mg total drug content), and then maintained for 6 months. The primary efficacy measures were 1) the change in the Unified Parkinson's Disease Rating Scale (UPDRS) scores (parts II and III) from baseline to end of treatment and 2) responder rates (patients with > or =20% improvement). RESULTS: Patients receiving rotigotine had a mean absolute difference of 5.28 (+/-1.18) points lower in UPDRS subtotal scores compared with those receiving placebo (p < 0.0001). The mean change in part III motor scores was -3.50 (+/-7.26) (n = 177) and was the greatest contributor to UPDRS improvement. The rotigotine group had more responders (48 vs 19%; p < 0.0001). The most commonly reported adverse events were application site reactions (44% rotigotine vs 12% placebo), nausea (41 vs17%), somnolence (33 vs 20%), and dizziness (19 vs 13%), and most were mild or moderate in intensity. CONCLUSIONS: Transdermal rotigotine, when titrated to a dosage of 6 mg/24 h, was effective for the treatment of early-stage Parkinson disease in this trial. Adverse events were similar to those found with other transdermal systems and dopamine agonists.

Administration, Cutaneous↗
PubMed2006

Autocrine activation of PDGFRalpha promotes the progression of ovarian cancer.

Platelet-derived growth factor receptor (PDGFR)alpha expression was found in ovarian cancer cells and tumors by microarray hybridization. This led us to test whether ovarian cancers also produce ligands for this receptor, as this would demonstrate that such malignancies support their own growth and spread through autocrine activation. We assayed the expression of ligands for the PDGFR in ovarian tumors, cell lines and peritoneal fluid using RT-PCR, immunohistochemistry (IHC) and ELISA. We detected strong mRNA expression for the PDGFRalpha ligands in most ovarian tumors. Receptor and ligand expressions (PDGFRalpha and PDGF AB) were also detected by IHC in, respectively, 34 and 32 of 47 ovarian tumors. The stainings for PDGFRalpha and PDGF AB were strongly correlated (P-value=0.014), suggesting that an autocrine loop is functional in ovarian cancer. PDGF AA and BB were quantified in peritoneal fluid by ELISA. Both ligands are secreted at higher levels in ovarian cancer ascites specimens (n=54) than in fluid from nonmalignant disorders (n=8). PDGF was detected in media conditioned by ovarian cancer cells. Such conditioned media induced activation of the PDGFR, Akt and MAPK and stimulated cell proliferation. A neutralizing PDGF antibody blocked these effects. Specific PDGFR inhibition by siRNA or a neutralizing antibody to the receptor inhibited PDGF-stimulated receptor activation and cell proliferation, suggesting that receptor targeting has a role in ovarian cancer treatment.

Ascitic Fluid↗
PubMed2006

Biomechanical and histomorphometric analyses of monocortical screws at placement and 6 weeks postinsertion.

Maxillofacial screws are increasingly being used in orthodontics to provide anchorage for tooth movement. The objective of this study was to determine the biomechanical stability as well as the bone tissue response of screws at 6 weeks postinsertion in a canine model. Seven skeletally mature male dogs received 102 screws (2 x 6 mm or 2 x 8 mm) at predetermined sites. Twenty screws became loose or were lost during the 6-week undisturbed healing period. Forty-eight screws were randomized for mechanical testing and 34 for histology. Peak pullout strength was recorded and approximately 80-microm sections were examined for histomorphometric parameters. Statistical analyses were conducted by analysis of variance and Tukey-Kramer method. Mean +/- SE peak pullout strengths for the various sites ranged from 153.5 +/- 37.6 N to 389.3 +/- 32.5 N with no significant (P < .05) differences at immediate placement and 6 weeks postinsertion. Bone contact ranged from 79% to 95%. Histomorphometric analyses indicated higher bone formation rate in the mandible than in the maxilla and a gradient of decreasing turnover with increasing distance from the screw interface. These results provide the clinical orthodontist with an estimate of the holding power of these screws and an understanding of early biological healing response associated with self-drilling screws.

Adaptation, Physiological↗
PubMed2006

Regulation of cerebral glucose metabolism.

The brain uses glucose as a primary fuel for energy generation. Glucose gains entry into the brain by facilitated diffusion across the blood-brain barrier. Glucose transport may adapt during changes in cerebral glucose metabolism, neural activation and changes in plasma glucose levels. Within the brain, glucose is either oxidized to produce ATP or used to synthesize glycogen. To ensure the delivery of a continuous supply of glucose to maintain normal cellular function, the brain has developed a complex regulatory system to preserve its supply. Gluco-sensing neurons have been demonstrated in various regions of the brain and they appear to play an important role in not only detecting changes in brain glucose levels but also in initiating responses to maintain constant brain glucose levels. In this review, we will discuss the regulation of brain glucose metabolism (CMR(gluc)) and how it adapts to chronic changes in glycemia, like that seen in hyperglycemic patients with diabetes mellitus or patients with type 1 diabetes, recurrent hypoglycemia, and hypoglycemia unawareness. We will also consider the role of brain glycogen in providing fuel for energy under conditions of stress.

Blood-Brain Barrier↗
PubMed2004

Historical Article: Hirudo medicinalis: ancient origins of, and trends in the use of medicinal leeches throughout history.

Blood letting and the therapeutic use of Hirudo medicinalis date back to ancient Egypt and the beginning of civilisation. Their popularity has varied over the years, reaching such a peak in Europe between 1825 and 1850 that supplies were exhausted. Towards the end of the century they fell out of favour and, during this period, the leech, once used by the physicians of emperors and influential academic surgeons, became associated with lay therapists and quackery. Leeches have enjoyed a renaissance in reconstructive microsurgery during the last 15 years, having been used by maxillofacial [Br. J. Oral Maxillofac. Surg 41 (2003) 44] and other reconstructive surgeons to aid salvage of compromised microvascular free tissue transfers [Laryngoscope 108 (1998) 1129; Br. J. Plast. Surg. 34 (1984) 358], replanted digits [Int. J. Microsurg. 3 (1981) 265], ears [Ann. Plast. Surg. 43 (1999) 427], lips [Plast. Reconstr. Surg. 102 (1998) 358; J. Reconstr. Microsurg. 9 (1993) 327] and nasal tips [Br. J. Oral Maxillofac. Surg. 36 (1998) 462]. Peer-reviewed evidence suggests that the survival of compromised, venous-congested tissues is improved by early application of a leech [J. Reconstr. Microsurg. 12 (1996) 165; Arch. Otolaryngol. Head Neck Surg. 114 (1988) 1395; Br. J. Plast. Surg. 45 (1992) 235]. Leeches have also recently been used to treat a wide range of conditions, including periorbital haematomas [Br. J. Ophthalmol. 75 (1991) 755], severe macroglossia [Otolaryngol. Head Neck Surg. 125 (2001) 649; J. Laryngol. Otol. 109 (1995) 442] and purpura fulminans [Ann. Plast. Surg. 35 (1995) 300]. The first medicinal leech farm, Biopharm, was set up in Swansea in 1981 by Dr Roy Sawyer, and now supplies leeches to hospitals all over the world. In this paper, we summarise the history of treatment with Hirudo medicinalis from its origin to the present day, and take a brief look at the possible future of the annelid.

Egypt↗
PubMed2004

Tomorrow's skeleton staff: mesenchymal stem cells and the repair of bone and cartilage.

Stem cells are regenerating medicine. Advances in stem cell biology, and bone marrow-derived mesenchymal stem cells in particular, are demonstrating that many clinical options once thought to be science fiction may be attainable as fact. The extra- and intra-cellular signalling used by stem cells as they differentiate into lineages appropriate to their destination are becoming understood. Thus, the growth stimuli afforded by LIF, FGF-2 and HGF, as well as the complementary roles of Wnt and Dickkopf-1 in stem cell proliferation are evident. The ability to direct multi-lineage mesenchymal stem sell (MSC) potential towards an osteogenic phenotype by stimulation with Menin and Shh are important, as are the modulatory roles of Notch-1 and PPARgamma. Control of chondrocytic differentiation is effected by interplay of Brachyury, BMP-4 and TGFbeta3. Smads 1, 4 and 5 also play a role in these phenotypic expressions. The ability to culture MSC has led to their use in tissue repair, both as precursor and differentiated cell substitutes, and with successful animal models of bone and cartilage repair using MSC, their clinical use is accelerating. However, MSC also suppress some T-cell functions in transplanted hosts, and could facilitate tumour growth, so a cautious approach is needed.

Animals↗
PubMed2003

Identification of three genomic haplotypes 5' to the human CD1D gene and their distribution in four ethnic groups.

CD1d presents lipid antigen to a conserved population of natural killer (NK) T cells, which participate in host immune defense, tumor cell rejection and suppression of autoimmunity. The levels of human CD1d expression vary significantly between individuals. To understand such variation, we sequenced the region up to 1.7 kb 5' upstream of the translation start site and partially through exon 2 in 44 white Americans. We also studied two tagged single nucleotide polymorphisms (SNP) in 112 white Americans, 60 African-Americans, 88 Europeans, and 84 Chinese people from the region. Six SNP present in the region (-836C-->T, -773C-->T, -764C-->G, -713A-->T, -365A-->G and +363A-->G) were found to be in a complete linkage disequilibrium and comprised three haplotypes. Haplotype 1 had -836C, -773C, -764C, -713A, -365A and +363A. Haplotype 2 had -836C, -773T, -764C, -713A, -365A and +363A. Haplotype 3 had -836T, -773C, -764G, -713T, -365G and +363G. -773C-->T and -764C-->G can serve as the tagged SNP to differentiate the three haplotypes. The frequency of haplotype 1 was significantly higher in African Americans than in the other three ethnic groups, whereas the frequency of haplotype 3 was significantly higher in the Chinese people than those in the other three groups. The finding of the three haplotypes provides a genetic marker for CD1d and facilitates the study of the functional role of the genetic variations in human CD1d expression and regulation.

Antigens, CD1↗
PubMed2002

Audit of primary care angina management in Sandwell, England.

This audit aimed to assess the identification and treatment of coronary risk factors, lifestyle advice given and use of drug therapy, among patients with angina in Sandwell. It was designed to help general practices evaluate their angina management, and highlight areas where practice could be improved. Criteria were based on Sandwell's published angina audit and local clinical guidelines. Each participating practice was asked to identify all patients with angina, from which a 10% sample was randomly selected. The notes of each selected patient were examined for evidence showing whether agreed standards of care had been achieved. Fifteen practices took part, and contributed data on a total of 358 patients. Of patients without contraindications, 66.5% were taking aspirin, 62.1% were prescribed short-acting nitrates and 58.4% were prescribed beta-blockers. Non-white patients were significantly less likely to receive short-acting nitrates (p < 0.001) and women were significantly less likely to receive beta-blockers (p < 0.01). A total of 83.5% of patients had received smoking cessation advice, 75.1% had weight advice, 75.1% were advised about alcohol use and 64.5% about exercise. Overall, 77.4% had a blood pressure check within the previous twelve months, 40.5% had their cholesterol measured and 33.5% had their blood glucose measured. Non-white patients were significantly less likely to receive smoking cessation, weight, exercise and alcohol advice and were less likely to have their blood pressure checked (all p < 0.0001). Patients aged 65 and over were significantly less likely to receive a cholesterol check (p < 0.0001). None of the auditable standards were actually met. This study shows that there is considerable scope to improve the management of angina patients, with particular regard to aspirin. We recommend that practices develop systems to ensure that the appropriate treatment, advice and checks are given to all patients with angina, paying particular attention to those from ethnic minority backgrounds.

Angina Pectoris↗
PubMed2001

The chaperone protein 14-3-3eta interacts with the nicotinic acetylcholine receptor alpha 4 subunit. Evidence for a dynamic role in subunit stabilization.

By using the large cytoplasmic domain of the nicotinic acetylcholine receptor (AChR) alpha4 subunit as a bait in the yeast two-hybrid system, we isolated the first cytosolic protein, 14-3-3eta, known to interact directly with neuronal AChRs. 14-3-3eta is a member of a family of proteins that function as regulatory or chaperone/ scaffolding/adaptor proteins. 14-3-3eta interacted with the recombinant alpha4 subunit alone in tsA 201 cells following activation of cAMP-dependent protein kinase by forskolin. The interaction of 14-3-3eta with recombinant alpha4 subunits was abolished when serine 441 of the alpha4 subunit was mutated to alanine (alpha4(S441A)). The surface levels of recombinant wild-type alpha4beta2 AChRs were approximately 2-fold higher than those of mutant alpha4(S441A)beta2 AChRs. The interaction significantly increased the steady state levels of the alpha4 subunit and alpha4beta2 AChRs but not that of the mutant alpha4(S441A) subunit or mutant alpha4(S441A)beta2 AChRs. The EC50 values for activation by acetylcholine were not significantly different for alpha4beta2 AChRs and alpha4(S441A)beta2 AChRs coexpressed with 14-3-3eta in oocytes following treatment with forskolin. 14-3-3 coimmunopurified with native alpha4 AChRs from brain. These results support a role for 14-3-3 in dynamically regulating the expression levels of alpha4beta2 AChRs through its interaction with the alpha4 subunit.

14-3-3 Proteins↗
PubMed2001

Injury to the ligamentum teres. Mechanism, findings, and results of treatment.

In this article we discuss the role of the ligamentum teres in relation to the hip joint. The anatomy of the ligamentum teres is used to help with an understanding of the mechanism of the ligament's actions. This action and the modes of injury to the ligament are explored. We describe a simple classification system for injuries to the ligamentum teres, such that Group I are complete tears to the ligament; Group II are partial tears; and Group III are degenerative tears. As more experience is gained with the diagnosis and treatment of injuries to this integral structure, the clearer will be our understanding of the role of the ligamentum teres in the hip joint.

Arthroscopy↗
PubMed2001

Outer dense fiber proteins are dominant postobstruction autoantigens in adult Lewis rats.

Obstruction of the male reproductive tract commonly results in generation of antisperm autoantibodies. However, only a few of the sperm autoantigens recognized by these antibodies have been characterized. To identify postobstruction rat sperm autoantigens, sperm proteins were separated by two-dimensional(2-D) gel electrophoresis. Spots corresponding to proteins that were stained by at least 50% of postvasectomy rat sera on 2-D Western blots were removed from polyacrylamide gels and microsequenced by tandem mass spectrometry. From a total of 21 spots, 12 contained peptides that matched solely to either of two outer dense fiber proteins, odf1 or odf2. Six additional spots contained peptides comprising odf1 or odf2 and were accompanied by peptides representing other proteins. Only three spots lacked outer dense fiber peptides but did contain sequences of other known proteins. The results indicate that the outer dense fiber proteins odf1 and odf2 are dominant postobstruction autoantigens because they were detected in the majority of the immunoreactive protein spots examined. Possible explanations for this observation include the abundance of outer dense fiber proteins in spermatozoa, slow solubility, which may provide a sustained supply of antigen, and testis-specific expression during spermiogenesis.

Amino Acid Sequence↗
PubMed2001

Successful use of eptifibatide as an adjunct to coronary stenting in a patient with abciximab-associated acute profound thrombocytopenia.

A 72-year-old male who was given abciximab for unstable angina developed acute profound thrombocytopenia with a platelet count nadir of 6,000/mm3. He was treated with steroids and platelet transfusion. Four days later, he underwent coronary angioplasty after pretreatment with eptifibatide without development of thrombocytopenia. This suggests that the development of thrombocytopenia with abciximab is not necessarily a contraindication to subsequent use of glycoprotein (GP) IIb/IIIa receptor antagonists. Eptifibatide may be an appropriate consideration in high-risk patients who would benefit from a GP IIb/IIIa receptor antagonist, in spite of acute profound thrombocytopenia due to abciximab therapy.

Abciximab↗
PubMed2001

Effect of whole-body (18)F-FDG PET imaging on clinical staging and management of patients with malignant lymphoma.

UNLABELLED: Correct staging is important in selecting the appropriate treatment for lymphoma patients. PET imaging with (18)F-FDG is useful for staging of lymphoma as well as for monitoring of therapy. However, to our knowledge, the clinical impact of PET on staging and management of lymphoma patients has not been reported. METHODS: Standardized questionnaires were mailed to referring physicians asking them whether and how the results of PET imaging had influenced clinical staging and management of the disease in their patients. Management changes, when present, were classified as intermodality (e.g., medical to surgical, surgical to radiation, medical to no treatment) or intramodality (e.g., altered medical, surgical, or radiotherapy approach). RESULTS: The referring physicians returned 52 of 108 questionnaires (48.1%). Physicians indicated that PET led to a change in the clinical stage in 44% of patients: 21% were upstaged and 23% were downstaged. Findings of the PET examination resulted in intermodality changes in management in 42% of patients, in intramodality changes in 10%, and in a combination of the management changes in 10%. Other, not further specified, treatment changes were reported in 6% of patients. PET did not result in any management changes in only 32% of patients. CONCLUSION: This survey-based study of referring physicians indicates that FDG PET has a major impact on the management of lymphoma patients, contributing to changes in clinical stage in 44% and changes in treatment in >60% of cases.

Adolescent↗
PubMed2001

Impact of whole-body 18F-FDG PET on staging and managing patients with breast cancer: the referring physician's perspective.

UNLABELLED: FDG PET has emerged as an important clinical imaging modality for diagnosing and staging cancer. However, the impact of FDG PET on staging and managing patients with breast cancer from the referring physician's point of view is unknown. METHODS: The referring physicians of 160 breast cancer patients received standardized questionnaires inquiring if and how PET findings altered their patient's stage and their clinical management decisions. Management changes were classified as intermodality if the change was from one modality to another (e.g., medical to surgical, surgical to radiation, medical to no treatment, and vice versa) or as intramodality if the change was within the same modality (e.g., altered medical or radiotherapy approach). RESULTS: Fifty of the 160 surveys were completed (31% response rate). PET changed the clinical stage in 36% of patients (28% upstaged, 8% downstaged) and resulted in intermodality changes in 28% of patients and intramodality changes in 30% of patients. CONCLUSION: The results of this prospective survey show that FDG PET has a major impact on the management of breast cancer patients, influencing both clinical stage and management in more than 30% of patients.

Adult↗
PubMed2000

Functional interaction of human Cdc37 with the androgen receptor but not with the glucocorticoid receptor.

Cdc37 is a molecular chaperone closely associated with the folding of protein kinases. Results from studies using a yeast model system showed that it was also important for activation of the human androgen receptor (AR). Based on results from the yeast model system (Fliss, A. E., Fang, Y., Boschelli, F., and Caplan, A. J. (1997) Mol. Biol. Cell 8, 2501-2509), we initiated studies to address whether AR and Cdc37 interact with each other in animal cell systems. Our results show that Cdc37 binds to AR but not to glucocorticoid receptors (GR) synthesized in rabbit reticulocyte lysates. This binding occurs via the ligand-binding domain of the AR in a manner that is partially dependent on Hsp90 and the presence of hormone. Further studies using the yeast system showed that Cdc37 is not interchangeable with Hsp90, suggesting that it functions at a distinct step in the activation pathway. Expression of a dominant negative form of Cdc37 in animal cells down-regulates full-length AR but has very little effect on an AR truncation lacking the ligand-binding domain or full-length GR. These results reveal differences in the mechanisms by which AR and GR become active transcription factors and strengthen the notion that Cdc37 has a wider range of polypeptide clients than was realized previously.

Binding Sites↗
PubMed2000

Neural cell response to multiple novel sites on laminin-1.

The basement membrane protein laminin-1 is a potent stimulator of neurite outgrowth for a variety of neuronal cell types. Previous studies have identified neurite outgrowth activity in several distinct regions of the laminin-1 molecule. In this study, 545 overlapping 12- to 14-mer synthetic peptides, corresponding to most of the amino acid sequence of the alpha1, beta1, and gamma1 chains of laminin-1, were screened for cell attachment and neurite outgrowth activity using primary cultures of mouse cerebellar granule neurons and two neuronal cell lines. We identified 48 peptides derived from novel regions of the laminin-1 molecule that were positive for neural cell adhesion activity. Only the cerebellar cells were found to have true neurite outgrowth activity with certain of the peptides, whereas some peptides induced short spike-like process with the cell lines. Although 23 of these peptides were active on all 3 cell types screened, 25 others showed cell-type specificity in their activity. These studies show that (1) there are multiple and distinct sites on laminin-1 for cell adhesion and neurite-like outgrowth and (2) that there are neural cell-type-specific active domains. The multiple active sites found explains, in part, the potent activity of laminin-1 on neurite outgrowth.

Amino Acid Sequence↗
PubMed2000

Inhibition of p38 MAP kinase activity up-regulates multiple MAP kinase pathways and potentiates 1,25-dihydroxyvitamin D(3)-induced differentiation of human leukemia HL60 cells.

Differentiation therapy for neoplastic diseases has potential for supplementing existing treatment modalities but its implementation has been slow. One of the reasons is the lack of full understanding of the complexities of cellular pathways through which signals for differentiation lead to cell maturation. This was addressed in this study using HL60 cells, a well-established model of differentiation of neoplastic cells. SB 203580 and SB 202190, specific inhibitors of a signaling protein p38 MAP kinase, were found to markedly accelerate monocytic differentiation of HL60 cells induced by low concentrations of 1,25-dihydroxyvitamin D(3) (1,25D(3)). Surprisingly, inhibition of p38 activity resulted in sustained enhancement of p38 phosphorylation and of its in vitro activity in the absence of the inhibitor, indicating up-regulation of the upstream components of the p38 pathway. In addition, SB 203580 or SB 202190 treatment of HL60 cells resulted in a prolonged activation of the JNK and, to a lesser extent, the ERK pathways. The data are consistent with the hypothesis that in HL60 cells an interruption of a negative feedback loop from a p38 target activates a common regulator of multiple MAPK pathways. The possibility also exists that JNK and/or ERK pathways amplify a differentiation signal provided by 1,25D(3).

Calcitriol↗