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Biomedical subjects

S Wadhwa

Publications and source records attributed to S Wadhwa.

At least 19 recordsLinked to original sources

Accelerated osteoarthritis in the temporomandibular joint of biglycan/fibromodulin double-deficient mice.

OBJECTIVE: To investigate whether the absence of biglycan and fibromodulin, two proteoglycans expressed in cartilage, bone and tendon, resulted in accelerated osteoarthritis in the temporomandibular joint (TMJ). METHODS: Histological sections of TMJ from 3-, 6-, 9- and 18-month-old wild-type (WT) and biglycan/fibromodulin double-deficient (DKO) mice were compared. Immuno-stainings for biglycan, fibromodulin and proliferating cell nuclear antigen (PCNA) were performed. RESULTS: Biglycan and fibromodulin were highly expressed in the disc and articular cartilage of the TMJ. At 3 months of age, both WT and DKO presented early signs of cartilage degeneration visible as small acellular areas under the articular surfaces and superficial waving. From 6 months of age, DKOs developed accelerated osteoarthritis compared to WT. At 6 months, small vertical clefts in the condylar cartilage and partial disruption of the disk were visible in the DKO. In addition, chondrocytes had lost their regular columnar organization to form clusters. At 9 months, these differences were even more pronounced. At 18 months, extended cartilage erosion was visible in DKOs when by comparison the thickness of the articular cartilage in WT controls was basically intact. PCNA staining was stronger in 3-month-old WT TMJ fibrocartilage than in 3-month-old DKO TMJ fibrocartilage suggesting that chondrocyte proliferation might be impaired in DKOs. CONCLUSION: The biglycan/fibromodulin double knock-out mouse constitutes a useful animal model to decipher the pathobiology of osteoarthritis in the TMJ.

Animals↗

Histopathological changes in the eyes in systemic lupus erythematosus: an electron microscope and immunohistochemical study.

This paper reports the histopathological findings in the eyes of a 26-year-old female patient diagnosed with systemic lupus erythematosus (SLE) with peripheral neuropathy. The patient had no significant ocular problems. She died of pneumonia after two years of suffering. The eyeballs were procured at autopsy and the retina, choroid and optic nerve processed for light and electron microscopy, and immunohistochemistry for immunoglobulin G (IgG), glial fibrillary acidic protein (GFAP), calbindin and parvalbumin. Histologically, there was haemorrhaging in the retinal nerve fibre layer. Ultrastructurally, the axons of this layer were swollen, and contained an unusual accumulation of microtubules and smooth endoplasmic reticulum. There were degenerative changes in the pericytes and smooth muscle cells of blood vessels. The capillary lumen was partially obliterated, and contained IgG, which was also detected throughout the choroid and wall of choroidal arterioles. The latter and Bruch's membrane showed fibrin deposits. The optic nerve showed infiltrated mononuclear cells near the degenerated axons, these axons lacked immunoreactivity to calbindin and parvalbumin. Compared to the control, the connective tissue sheaths of the central retinal vessels possessed a vast number of proliferated fibroblast cells, and trichrome staining showed transmural vessel scarring. Dense GFAP immunoreactivity was observed surrounding the vessel wall. These pathological changes are due to impaired blood circulation caused by haemorrhaging and vasculitis, and vessel occlusion by fibrin. The nature of the changes observed tends to indicate that a regular, thorough ophthalmic examination should be conducted even in the absence of significant ocular symptoms in SLE.

Adult↗

A recombinant luteinising-hormone-releasing-hormone immunogen bioeffective in causing prostatic atrophy.

Previous studies with a semi-synthetic vaccine indicated the utility of immunization against luteinising-hormone-releasing-hormone (LHRH) in prostate cancers. To overcome the limitations of the previous vaccine, which caused carrier induced suppression of antibody response on repeated immunizations and was costly to synthesize, two recombinant vaccines were designed, in which diptheria or tetanus toxoid used as carriers were replaced by 4-5 T non B peptides. The paper reports the immunogenecity, efficacy and safety of these multimer vaccines in rats, a homologous experimental animal. All animals generated anti-LHRH antibodies, which caused the decline of testosterone to castration levels at and above 0.15 OD units of antibody titres. The prostate was significantly atrophied in all animals immunized with these vaccines.

Animals↗

Abnormal musculoaponeurotic tunnel in the arm: possible entrapment of the median nerve and brachial artery with high origin of nerve to pronator teres within the tunnel.

Median nerve and brachial artery in the arm are not usually overlapped by any structure. Connective tissue bands and muscular slips draping or enclosing this neurovascular bundle have been reported, however, which may produce clinical symptoms of nerve compression and vascular changes. We report an unusual musculoaponeurotic band that originates as the ligament of Struthers but terminates as the brachiofascialis muscle of Wood and in the process may have entrapped both the median nerve and brachial artery. The nerve to pronator teres originates from the median nerve within this tunnel. On histological examination the nerve was flattened and showed some perineurial thickening. In view of the flexor function of brachialis muscle, this anomalous musculoaponeurotic band may be considered a clinically important entity in the causation of idiopathic neurovasculopathy in the hand.

Brachial Artery↗

Comparison of new clinical and scintigraphic algorithms for the diagnosis of pulmonary embolism.

Since the publication of the modified Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria for the diagnosis of pulmonary embolism (PE), new clinical and scintigraphic diagnostic algorithms (the McMaster clinical criteria, the PisaPED simplified scintigraphic grading and the Miettinen logistic regression analysis) have been reported although the results have not been reproduced in other sites. Ventilation-perfusion lung scintigraphy was performed in 238 consecutive patients with a provisional diagnosis of PE. Scans were reported as normal/very low, low, intermediate or high probability for PE using standardized criteria. Each patient received a clinical grading of probability of PE as low, moderate or high using the McMaster clinical criteria. Using the PisaPED criteria (an alternate simplified scintigraphic grading system using the perfusion scan alone) each scan was also graded as normal/near normal, abnormal but not PE, or abnormal and PE. Using the logistic regression algorithm of Miettinen each scan received a numerical probability of PE. Frequencies for differing levels of probability of PE varied widely between the various algorithms. Cross tabulations revealed correlation of the standardized criteria with the Miettinen grading but not with the McMaster or the PisaPED gradings. We were unable to reproduce similar results using the McMaster clinical grading or the PisaPED simplified scintigraphic grading although the Miettinen logistic regression formula gave comparable results. New algorithms are not automatically transferable to new environments.

Adolescent↗

Effect of prenatal auditory enrichment on developmental expression of synaptophysin and syntaxin 1 in chick brainstem auditory nuclei.

Neural activity plays an important role in shaping the developing brain. We have determined the consequence of increased auditory stimulation on the developmental profile of synaptic proteins, synaptophysin and syntaxin 1, in the chick brainstem auditory nuclei, nucleus magnocellularis and nucleus laminaris, by immunohistochemistry and western blotting techniques. The chick embryos were provided with patterned sounds of species-specific calls or musical notes of a sitar, a stringed instrument, in a graded manner from embryonic day 10 (E10) through hatching, for 15 min every hour. During normal synaptogenesis of nucleus magnocellularis and nucleus laminaris, synaptophysin immunoreactivity increased significantly from E8 to E20, in parallel with synapse formation, and reduced at hatching. The embryos receiving species-specific sound stimuli exhibited a similar pattern with higher levels of immunoreactivity, though the difference between the study groups was not statistically significant. The music stimulated embryos showed an earlier peak at E16, followed by a gradual decline until hatching. In all three groups studied, syntaxin immunoreactivity showed a surge at E12, followed by a decline at E16 and subsequent stabilization. The stimulated groups continually expressed higher amounts of syntaxin immunoreactivity. The results suggest that prenatal sound stimulation enhances the normal pattern of synaptic protein expression in these auditory nuclei.

Acoustic Stimulation↗

Differential expression of syntaxin-1 and synaptophysin in the developing and adult human retina.

Synaptophysin and syntaxin-1 are membrane proteins that associate with synaptic vesicles and presynaptic active zones at nerve endings, respectively. The former is known to be a good marker of synaptogenesis; this aspect, however, is not clear with syntaxin-1. In this study, the expression of both proteins was examined in the developing human retina and compared with their distribution in postnatal to adult retinas, by immunohistochemistry. In the inner plexiform layer, both were expressed simultaneously at 11-12 weeks of gestation, when synaptogenesis reportedly begins in the central retina. In the outer plexiform layer, however, the immunoreactivities were prominent by 16 weeks of gestation. Their expression in both plexiform layers followed a centre-to-periphery gradient. The immunoreactivities for both proteins were found in the immature photoreceptor, amacrine and ganglion cells; however, synaptophysin was differentially localized in bipolar cells and their axons, and syntaxin was present in some horizontal cells. In postnatal-to-adult retinas, synaptophysin immunoreactivity was prominent in photo-receptor terminals lying in the outer plexiform layer; on the contrary, syntaxin-1 was present in a thin immunoreactive band in this layer. In the inner plexiform layer, however, both were homogeneously distributed. Our study suggests that (i) syntaxin-1 appears in parallel with synapse formation; (ii) synaptogenesis in the human retina might follow a centre-to-periphery gradient; (iii) syntaxin-1 is likely to be absent from ribbon synapses of the outer plexiform layer, but may occur at presynaptic terminals of photoreceptor and horizontal cells, as is apparent from its localization in these cells, which is hitherto unreported for any vertebrate retina.

Adult↗

Thoracoabdominal intestinal duplication with absent inferior vena cava.

We report a rare case of thoracoabdominal intestinal duplication with absent inferior vena cava (IVC). The patient was initially explored with a mistaken diagnosis of diaphragmatic hernia on the basis of a chest radiograph and barium meal. However, a subsequent computed tomography scan revealed a mediastinal mass with an air-fluid level, a hugely dilated azygos vein, and an absent IVC. Thoracoabdominal exploration was required to excise the duplication cyst arising from the jejunum. We believe that this is the first report of this association.

Azygos Vein↗

Luminescent ruthenium(II) bipyridyl-phosphonic acid complexes: pH dependent photophysical behavior and quenching with divalent metal ions.

The synthesis, redox behavior, and photophysical properties of a series of Ru(II) bipyridyl complexes having diimine ligands with phosphonate and phosphonic acid substituents are presented. The phosphonate-containing ligands examined include diethyl 4-(2,2'-bipyrid-4-yl)benzylphosphonate (bpbzp), diethyl 4-(2,2'-bipyrid-4-yl)-phenylphosphonate (bppp), and 4,4'-(diethyl phosphonato)-2,2'-bipyridine (bpdp), and the [(bpy)2Ru(L)](PF6)2 complexes of both the diethyl phosphonate and the phosphonic acid were prepared. The Ru(III/II) potentials are more positive for the phosphonate complexes than for the phosphonic acids, and the first reduction is localized on the phosphonate-containing ligand for the bppp and bpdp complexes. The first reduction of the phosphonic acid complexes is at more negative potentials and cannot be distinguished from bpy reduction. For the bppp and bpdp complexes luminescence arises from a Ru(d pi)-->bpy-phosphonate (pi*) MLCT state; the phosphonic acid complexes luminescence at higher energies from a MLCT state not clearly isolated on one ligand. Iron(III) and copper(II) complex with and very efficiently quench the luminescence of all the phosphonic acid complexes in nonaqueous solvents. The quenching mechanism is discussed on the basis of luminescence decay and picosecond transient absorption measurements.

Journal Article↗

Neurotrophin receptors (Trk A, Trk B, and Trk C) in the developing and adult human retina.

In this study, the ontogeny and distribution patterns of three neurotrophin receptors (Trk A, Trk B, and Trk C) were examined in the human retinas. Immunohistochemistry was performed on sections of retina and optic nerve from fetuses (11-24 weeks of gestation, wg), one infant (4-month-old) and two adult (35- and 65-years-old) subjects. At 11 wg, Trk A was expressed in the nerve fiber and inner plexiform layers, while Trk B and Trk C were expressed in many neuroblastic cells. By 16-17 wg, the photoreceptors showed immunoreactivity for all three receptors. The ganglion cell layer and amacrine cells were conspicuously immunoreactive for Trk A and Trk C, but labeled diffusely for Trk B. The horizontal cells were labeled for Trk A and Trk B. The pattern was same in the retinas at midgestation (20-21 wg). Shortly after this period, there was an apparent decrease in receptor immunoreactivity in the fetal retinas. In the infant retina, Trk A immunoreactivity was absent from horizontal cells. The photoreceptors were immunopositive for Trk B and Trk C, in infant and adult retinas. In the adults, few cells of the ganglion cell layer and inner nuclear layer were clearly labeled for Trk A and Trk C, and diffusely for Trk B. The glial cells of the retina and optic nerve immunoreacted for Trk A only, right from fetal 16 wg. The early expression of Trk B and Trk C on neuroblastic cells suggests that both play a role in cell proliferation. The developmental distribution pattern of Trk A, on the other hand, provides evidence for its involvement in differentiation of the inner plexiform layer, horizontal cells and neuroglia. The results strongly suggest that photoreceptor development is mediated by Trk receptors. The novel localization of Trk B and Trk C on adult photoreceptors points to a possible therapeutic potential for BDNF and NT-3, respectively, in photoreceptor diseases.

Adult↗

Developmental expression of calretinin immunoreactivity in the human retina and a comparison with two other EF-hand calcium binding proteins.

This paper reports the localization pattern of calretinin, a calcium-binding protein, in the human retina during development, as studied by immunohistochemistry. A comparison is made of the cellular distribution of calretinin with two other calcium-binding proteins, calbindin and parvalbumin, recently reported by us in the human retina, and by parallel labeling with both antisera in the same tissues. At 11-12 weeks of gestation, calretinin immunoreactivity was expressed in many prospective ganglion cells of the central inner neuroblastic zone. At 16-17 weeks of gestation, the immunoreactivity was localized in the ganglion cell layer, inner plexiform layer, and in most differentiated amacrine, horizontal and cone cells located in the central (1-2 mm temporal from optic disc) to midperipheral parts of the retina. By midgestation (20-21 weeks), calretinin immunoreactivity was strongly developed in the cone photoreceptors. Parallel labeling with calbindin and parvalbumin antisera revealed that the calretinin-positive horizontal cells were somewhat smaller and less frequent and less intense than the calbindin- and parvalbumin-positive counterparts, at 16-21 weeks of gestation. No horizontal cells were calretinin immunopositive in the postnatal (four-month-old infant) and adult retinas examined. Also, at both stages, a few bipolar and cone cells were weakly immunoreactive. These observations suggest a critical role for calretinin in the development and maturation of a select class of horizontal cells. The widespread expression of immunoreactivity in the early ganglion cells indicates that calretinin may be involved in their differentiation. The weak immunoreactivity pattern noted in the adult photoreceptor and bipolar cells, and an apparent lack of immunoreactivity in the mature horizontal cells, tends to indicate that, unlike calbindin and parvalbumin, calretinin plays little role in the transport and physiological buffering of Ca2+ in these neurons of the human retina. It appears, however, that calretinin is predominantly involved in both processes in amacrine cells.

Calbindin 2↗

Quantitative study of plasticity in the auditory nuclei of chick under conditions of prenatal sound attenuation and overstimulation with species specific and music sound stimuli.

Morphological effects of prenatal sound attenuation and sound overstimulation by species specific and music sounds on the brainstem auditory nuclei of chick have been evaluated quantitatively. Changes in length, volume, neuron number, size of neuronal nuclei and glial numbers of second and third order auditory nuclei, n. magnocellularis (NM) and n. laminaris (NL), were determined from thionine-stained serial sections of control and experimental groups on posthatch day 1 using stereological methods. Significant increase in volume of both auditory nuclei attributable to increase in length of nucleus, number and size of neurons, number of glia as well as neuropil was observed in response to both species specific and music overstimulation given during the critical period of development. The enhanced development of auditory nuclei in response to enriched environment prenatally indicates a positive effect of activity on neurons which may have clinical implications in addition to providing explanation for preference to auditory cues in the postnatal life. Reduction in neuron number with a small increase in proportion of cell nuclei of large size as well as an increase in glial numbers was seen in both NM and NL of the prenatally sound attenuated chicks. The increase in size of some neuronal nuclei may probably be evidence of enhanced synthesis of proteins involved in cell death or an attempt at recovery. The dissociated response of neurons and glia under sound attenuated and auditory stimulated conditions suggests that they are independently regulated by activity-dependent signals with glia also being under influence of other signals for a role in removal of dead cell debris.

Acoustic Stimulation↗