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Biomedical subjects

P Ghosh

Publications and source records attributed to P Ghosh.

At least 199 records · Page 11Linked to original sources
PubMed1994

Trans-ethmoidal optic nerve decompression.

Blunt head injury frequently results in visual impairment, the optimal treatment of which is still debated. Over a 5-year-period (1987-1991) 111 patients with indirect optic nerve injury resulting from closed head trauma have been treated. In each case loss of vision was the only neurological deficit. In group A, 66 patients were initially treated with large doses of prednisolone (80 mg/day) for 3 weeks. Twenty-seven patients improved on steroids alone. In the remaining 39 patients in whom either unsatisfactory or no improvement occurred a transethmoidal optic nerve decompression was performed. Twenty-two patients in the latter group improved, thus yielding an overall improvement rate of 74.2% in group A. Group B (control), in which 45 patients were treated with prednisolone only (80 mg/day for 3 weeks), had an overall improvement rate of 51% (23 patients). The study reveals that while nearly half of such patients can improve on steroids alone, optic nerve decompression significantly improves recovery rates in patients where conservative treatment is unsatisfactory (P < 0.05). Total loss of vision not responding to steroids, absence of waveform on visual evoked response, and presence of an optic canal fracture indicate a poor prognosis.

Adult↗
PubMed1994

Intraluminal duodenal diverticulum causing recurrent pancreatitis: treatment by endoscopic incision.

Intraluminal duodenal diverticulum is a recognised but rare cause of acute pancreatitis. This patient had three attacks of pancreatitis, each requiring a stay in hospital, within a four month period. The apex of the diverticulum was incised endoscopically, whereupon peas and food debris gushed from the incision site. The patient has had no further symptoms in the 12 months since the endoscopic procedure.

Acute Disease↗
PubMed1994

Studies on functioning of reconstituted gap junctional channels.

We examine the functioning of isolated rat liver gap junction protein after reconstituting into unilamellar liposomes with the help of fluorescence-efflux assay. Monitoring of the dequenching of a fluorescence marker 5, (6) CF due to its efflux from proteoliposomes into extra-liposomal space via its passage through reconstituted gap junctional channels has been performed. The efflux of dye from intra-liposomal to extra-liposomal compartment (both final release or Feq and initial rate or IR) was found dependent on gap junction concentrations. The opening and closing of reconstituted gap junctional channels were found influenced by pH and osmolarity of the extra-liposomal solution.

Animals↗
PubMed1994

The effects of intraarticular hyaluronan on cartilage and subchondral bone changes in an ovine model of early osteoarthritis.

OBJECTIVE: Intraarticular (ia) hyaluronan (HA) is reported to provide symptomatic relief in osteoarthritis (OA); however, there is limited information on the effects that this treatment may have on joint articular cartilage or subchondral bone. Our objective was to address this issue using an ovine model of early OA. METHODS: Unilateral medial meniscectomy was performed in 10 adult merino sheep, and 5 unoperated animals were used as controls (UOC). Sixteen weeks postmeniscectomy, joints of 5 operated animals were injected with 2 ml of HA (Artz, 10 mg/ml, M(r) = 0.9 x 10(6) Da) ia while the remaining 5 operated animals received 2 ml of sterile saline ia. This protocol was continued for a further 4 weeks. All animals were sacrificed 5 weeks after the last injection; however 3 weeks before sacrifice they were given tetracycline (20 mg/kg intravenously) weekly. Bone slabs, including articular cartilage, were cut from the medial tibial plateaux and femoral condyles, processed for histology, histomorphometry and fluorescence microscopy to assess articular cartilage and subchondral bone pathology. RESULTS: Meniscectomy and saline treatment increased osteoid volume and surfaces as well as increased the extent of tetracycline labelling of the subchondral bone relative to UOC. The articular cartilage also exhibited a significantly higher modified Mankin's score than UOC. In the HA injected group the aforementioned articular cartilage and subchondral bone changes were modified such that the observed variables were indistinguishable from UOC. CONCLUSION: Using this animal model intraarticular HA appeared to limit the development of articular cartilage and subchondral bone changes characteristic of early OA.

Animals↗
PubMed1994

Developmental regulation of the hypothalamic metabotropic glutamate receptor mGluR1.

The expression of the metabotropic glutamate receptor mGluR1 was studied with Northern and Western blot analysis, with immunocytochemistry, and with Ca2+ digital imaging in the developing rat hypothalamus. mGluR1 is coupled to a G protein and activation by glutamate and related agonists leads to intracellular phosphotidylinositol hydrolysis and Ca2+ mobilization. mGluR1 RNA could be detected in embryonic hypothalamus, and by the day of birth and prior to the primary period of synaptogenesis, both mGluR1 RNA and protein were strongly expressed. In parallel experiments with digital imaging of cultured hypothalamic cells, some embryonic day 18 hypothalamic neurons and many astrocytes after 3 d in vitro showed Ca2+ responses to quisqualate and t-ACPD, and to glutamate in the absence of extracellular Ca2+. A greater number of embryonic neurons responded to NMDA than to agonists of the metabotropic receptor. With increased development time in culture, the number of neurons that responded to metabotropic glutamate receptor agonists increased. In the adult hypothalamus, mGluR1-immunoreactive neurons were widespread, and particularly dense in the dorsomedial, lateral, and anterior hypothalamus/preoptic areas, and in the mammillary body. Strongly immunoreactive cells were interspersed among neurons with no immunoreactivity. In developing neurons a diffuse immunostaining appeared along dendrites and somata. With time, beginning in the first week after birth, strongly stained puncta appeared, possibly associated with synaptic specializations. These puncta were numerous on dendrites of some adult neurons, and were the most strongly stained regions of neurons. Neurons developing in vitro at low neuron densities showed a development of mGluR1 immunoreactivity similar to that of neurons in vivo, but with a delayed progression of immunostaining. We found no obvious staining of axons or of astrocytes. A strong expression of mGluR1 protein was found in the hypothalamus during the first 2 postnatal weeks; this expression was partially reduced in adults. In contrast, cerebellum showed no reduction in mGluR1 protein in adults. Together these data suggest a complex regulation of mGluR1 during development, with sufficient expression of functional receptors in the developing hypothalamus to modulate morphogenesis and synaptogenesis, and later to play a role in transduction of glutamate signals in the adult. Different regions of the brain showed dramatic differences in the way each expresses mGluR1 during development.

Aging↗
PubMed1993

Secretory leucocyte proteinase inhibitor is produced by human articular cartilage chondrocytes and intervertebral disc fibrochondrocytes.

The objective of this study was to examine the expression of the secretory leucocyte proteinase inhibitor (SLPI) gene by human articular cartilage chondrocytes and intervertebral disc fibrochondrocytes. RNA was extracted from human articular cartilage chondrocytes, synovial fibroblasts and fibrochondrocytes of the annulus fibrosus. Expression was analysed by Northern blotting and hybridisation to a SLPI RNA probe. SLPI was isolated from chondrocyte culture supernatant by gel-permeation and cation-exchange chromatography and examined by a solid-phase enzyme-linked immunofiltration assay for SLPI and by SDS/PAGE using Western blotting with polyclonal IgG samples against bronchial mucus leucocyte proteinase inhibitor and SLPI. This identified biochemically and immunologically the major serine proteinase inhibitory protein synthesised by chondrocytes as SLPI. Secretory leucocyte proteinase inhibitor mRNA was detected in RNA preparations from articular cartilage chondrocytes and annulus fibrosus fibrochondrocytes. The results presented here allowed us to deduce that human articular cartilage chondrocytes and intervertebral disc fibrochondrocytes synthesized SLPI whereas human synovial fibroblasts did not.

Adult↗
PubMed1993

The interleukin 2 CD28-responsive complex contains at least three members of the NF kappa B family: c-Rel, p50, and p65.

Optimal activation of T cells requires at least two signals. One signal can be delivered by the antigen-specific T-cell receptor, and the second signal is provided by the costimulatory molecule(s) delivered by the antigen-presenting cell. CD28 is a T-cell surface molecule and stimulation through this protein plays an important role in delivering the second activation signal. In this report, we show that in human peripheral blood T cells, CD28-mediated signal transduction involves the rel family proteins--c-Rel, p50, and p65. Treatment of peripheral blood T cells with phorbol 12-myristate 13-acetate (PMA) and anti-CD28 monoclonal antibody (mAb) results in augmentation of nuclear c-Rel, p50, and p65, and this augmentation can occur in the presence of the immunosuppressant cyclosporin A. It is also shown in this report that, in response to PMA/anti-CD28 mAb or anti-CD3/anti-CD28 mAb, c-Rel, p50, and p65 are associated with CD28-responsive element present in the promoter of the human interleukin 2 gene. The functional significance of c-Rel involvement in the CD28-responsive complex is demonstrated by transient transfection analysis, where cotransfection of c-Rel augments the level of expression of a chloramphenicol acetyltransferase reporter gene linked to the CD28-responsive element.

Antigens, CD↗
PubMed1993

Cloning, expression, and sequence of an allosteric mutant ADPglucose pyrophosphorylase from Escherichia coli B.

Escherichia coli B mutant strain SG14 accumulates glycogen at 28% of the rate observed for the parent strain. This is due to the presence of an ADPglucose pyrophosphorylase with altered allosteric properties including lower apparent affinities for substrates, the activator, fructose-1,6-bisphosphate, and the inhibitor, AMP. The mutant enzyme also is completely insensitive to activation by NADPH. To clone this mutant, an SG14 library was constructed by insertion of the chromosomal DNA into the PstI site of pBR322. Screening of the library via colony hybridization with a wild-type gene (glgC) probe resulted in the successful isolation of a recombinant plasmid, designated pPJ2, which contained the mutant glgC gene. The enzyme expressed from pPJ2 was partially purified and found to be very similar in kinetic and allosteric properties to the enzyme isolated from the SG14 strain. The mutant glgC gene, a HincII fragment from pPJ2, was then subcloned into pUC118/119 for dideoxy sequencing of both strands. One amino acid change was found in a region that is highly conserved in all known sequences: a single point mutation at the deduced amino acid residue 44 resulted in a change of alanine to threonine. The properties of this mutant are discussed in comparison to other known allosteric mutants.

Adenosine Monophosphate↗
PubMed1993

Nuclear magnetic resonance (NMR) imaging of iron oxide-labeled neural transplants.

Nuclear magnetic resonance (NMR) imaging in vivo of adult rat brains was used to observe the fate of iron oxide-labeled intracerebral neural grafts. The host animals received grafts of fetal (E17-E18) rat tissue prepared as cell suspensions and labeled by incubation with reconstituted Sendai viral envelopes containing iron oxide particles. Control studies were performed in animals following surgical trauma alone or transplantation of unlabeled cell suspensions. In vivo NMR imaging (either two-dimensional Fourier transform or three-dimensional Fourier transform) was performed once on each animal between 5 and 60 days postsurgery. The NMR images of the host brains containing the labeled cells showed sufficient anatomical detail for the identification of the major brain structures. The graft sites were seen in the T2-weighted NMR images as dark regions (low-intensity signal) in the cortex. Histochemical staining for ferric iron (prussian blue stain) demonstrated the presence of numerous prussian blue-positive cells in tissue sections corresponding to the dark regions in the NMR images. Surviving prussian blue-positive cells with neuron-like morphology were relatively more numerous 10 days after transplantation than at 1-2 months postgrafting. The NMR images and immunohistochemical and histochemical staining of hosts containing labeled cells suggest cell migration of astrocytes and macrophages up to 2 mm away from the graft sites. The migrating cells were primarily along fiber tracts in the host white matter. Prussian blue deposits were also present within the brains of the control animals, but the NMR images from the same animals did not contain distinct dark regions like those in the images of brains which had received labeled cell transplants. These results demonstrate that NMR imaging can be used to study cell survival and migration following neural grafting procedures.

Animals↗
PubMed1993

Animal models of early osteoarthritis: their use for the evaluation of potential chondroprotective agents.

Medial meniscectomy was undertaken in adult merino sheep and after 16 weeks exercise each group was administered five weekly intra-articular injections of saline, pentosan polysulphate (PPS), hyaluronic acid (HA) or a combination of PPS + HA. Gait analysis and x-rays were undertaken before and after drug treatment. At sacrifice (26 weeks), joints were examined for gross pathological and histochemical changes. Only the PPS-treated group showed an improvement in gait, with low radiological and histology scores. The HA-treated group showed similar but less significant changes to these parameters.

Animals↗
PubMed1993

The metabolic response of articular cartilage to abnormal mechanical loading induced by medial or lateral meniscectomy.

The effects of medial versus lateral meniscectomy on articular cartilage (AC) of adult sheep was investigated. In vitro incorporation of 35S into proteoglycans (PGs) and their release into media was used to assess cartilage metabolism. Lateral meniscectomy produced higher loss of PGs from AC and lower 35S-PG biosynthesis than for AC from medial meniscectomized joints. These findings were consistent with the proposed role of the lateral meniscus in joint mechanics.

Animals↗
PubMed1993

A carboxy-terminal fragment of colicin Ia forms ion channels.

A carboxy-terminal, 18 kD fragment of colicin Ia, a bacterial toxin, forms ion channels in artificial phospholipid bilayers. This fragment, which comprises a quarter of the intact 70 kD molecule, is resistant to extensive protease digestion and probably constitutes a structural domain of the protein. The ion channels formed by the 18 kD fragment are functionally heterogeneous, having conductances that range from 15 to 30 pS at positive voltages and from 70 to 250 pS at negative voltages, and open lifetimes that range from at least 25 msec to 5 sec. In contrast, ion channels formed by whole colicin Ia open only at negative voltages, at which their conductances range from 6 to 30 pS, and their open lifetimes range from 1 sec to 3 min. Additionally, the open state of the 18 kD fragment channel is characterized by noisy fluctuations in current, while the open state of the whole molecule ion channel is often marked by numerous, stable subconductance states. Since the properties of the fragment channel differ substantially from those of the whole molecule channel, we suggest that portions of the molecule outside of the 18 kD fragment are involved in forming the whole molecule ion channel.

Colicins↗
PubMed1993

Pentosan polysulphate and glycosaminoglycan polysulphate stimulate the synthesis of hyaluronan in vivo.

Pentosan polysulphate (PPS) and glycosaminoglycan polysulphate (GAGPS) were examined for their ability to alter hyaluronan synthesis in vivo. The inflamed rat subcutaneous air pouch model was used for the study. PPS or GAGPS injected into the air pouch at a dose of 2.5 mg/kg daily for 7 days resulted in higher molecular weight hyaluronan in the pouch fluid compared with control non-drug-treated pouch fluid. The quantity of the hyaluronan was increased by PPS, but not by GAGPS. We concluded that both drugs could be beneficial in the treatment of inflammatory arthritides in which a decrease in normal synovial hyaluronan concentration and molecular weight occurs.

Animals↗
PubMed1993

Pharmacokinetics of tiaprofenic acid in normal rabbits and rabbits subjected to joint immobilisation.

In a previous study, tiaprofenic acid (TA) was administered daily over a 30-day period at 5 and 10 mg/kg of body weight subcutaneously (s.c.) to animals with arthritis induced by immobilisation. The 10 mg/kg dose exacerbated the loss of proteoglycan from joint cartilage but the 5 mg/kg dose showed protective effects on articular cartilage. These results led us to investigate the concentration of TA achieved in synovial fluid of both the immobilised and non-immobilised rabbit joints after single s.c. doses of 5 or 10 mg/kg. The half-lives of elimination of TA from the synovial fluids of the immobilised joints were 1.27 and 1.07 h after the 5 and 10 mg doses, respectively, and 0.66 and 0.39 h in the non-immobilised contralateral joints. Clearances from synovial fluid to plasma were found to be 0.41 and 0.55 ml/h/kg from the immobilised joints after the 5 and 10 mg doses, respectively, and 0.11 and 0.25 ml/h/kg from the non-immobilised contralateral joints. The peak concentration of TA achieved in synovial fluid of immobilised knee joints after a single s.c. injection of 10 mg/kg was approximately two times greater than the concentrations achieved after administration of 5 mg/kg by the same route and two to six times greater than the levels achieved after oral administration of TA at 600 mg/day in humans.

Animals↗