Search PubMed⌕ Search

Biomedical subjects

M Malhotra

Publications and source records attributed to M Malhotra.

35 records · Page 2Linked to original sources
PubMed1997

Retinoic acid receptor-nuclear factor-interleukin 6 antagonism. A novel mechanism of retinoid-dependent inhibition of a keratinocyte hyperproliferative differentiation marker.

Retinoids inhibit the expression of migration inhibitory factor-related protein-8 (MRP-8), a marker of hyperproliferative or abnormal keratinocyte differentiation, in a retinoic acid receptor (RAR)-dependent manner in various cell culture systems. MRP-8 expression is also down-regulated in vivo in psoriatic lesions after topical application of an anti-psoriatic RARbeta/gamma-selective synthetic retinoid, tazarotene. We demonstrate that an MRP-8 promoter linked to a chloramphenicol acetyltransferase reporter (MRP8CAT) faithfully replicates the differentiation-specific regulation of the endogenous keratinocyte MRP-8 gene. Further, interferon gamma and serum-induced expression of MRP8CAT is inhibited by retinoid receptors in a ligand-dependent manner. We also show that NF-IL6 acts as a transcriptional enhancer of MRP-8, and that RARs inhibit MRP8CAT by inhibiting the enhancer action of nuclear factor-interleukin-6 (NF-IL6). The NF-IL6 antagonism function of RAR is a complex of the core of the DNA binding domain and the hydrophobic zipper region. This manuscript identifies NF-IL6 as another transcription factor, in addition to AP1, whose activity is inhibited by RAR in a ligand-dependent manner. The interdiction of NF-IL6-dependent signal transduction pathway by RARs may explain some of the therapeutic effects of retinoids in inflammatory and proliferative diseases.

Antigens, Differentiation↗
PubMed1997

Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin.

Retinoids exert their biologic effects through two families of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which belong to the superfamily of steroid/thyroid hormone nuclear receptors. By using a subtraction hybridization approach, we have identified a cDNA sequence TIG2 (Tazarotene-induced gene 2), whose expression is up-regulated by the treatment of skin raft cultures by an RAR beta/gamma-selective anti-psoriatic synthetic retinoid tazarotene [AGN 190168/ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl] nicotinate]. The retinoid-mediated up-regulation in the expression of TIG2 was confirmed by Northern blot analysis. Upon sequencing, TIG2 was found to be a cDNA whose complete sequence was not in the GenBank and EMBL data bases. The TIG2 cDNA is 830 bp long and encodes a putative protein product of 164 amino acids. TIG2 is neither expressed nor induced by tazarotene in primary keratinocyte and fibroblast cultures. Thus, TIG2 is expressed and induced by tazarotene only when keratinocytes and fibroblasts form a tissue-like 3-dimensional structure. We further demonstrate that RAR-specific retinoids increase TIG2 mRNA levels. In contrast, neither RXR-specific retinoids nor 1,25-dihydroxyvitamin D3 increased TIG2 levels. Finally, we demonstrate that TIG2 is expressed at high levels in nonlesional psoriatic skin but at lower levels in the psoriatic lesion and that its expression is up-regulated in psoriatic lesions after topical application of tazarotene.

Administration, Topical↗
PubMed1997

In vitro transcorneal permeation of ketorolac tromethamine from buffered and unbuffered aqueous ocular drops.

In vitro transcorneal permeation of ketorolac tromethamine from 0.5% w/v solutions containing equimolar (0.02 M) concentrations of citrate (pH 6.5), phosphate (pH 6.5 and 7), citrate-phosphate (pH 7) and borate (pH 7) buffers was studied using goat cornea. Cumulative % permeation was maximum with phosphate buffered drops of pH 6.5. The effect of pH and ionic strength on permeation of ketorolac tromethamine from buffered (phosphate) drops was next investigated. Cumulative % permeation of ketorolac tromethamine from buffered drops was pH dependent being maximum at pH 4.5. Adjustment of ionic strength of drops to 0.2 resulted in decreased permeation of drug. Permeation of ketorolac tromethamine from unbuffered drops of varying pH and ionic strength 0.2 was also pH dependent and was maximum at pH 4.5. Buffered drops of pH between 4.5-5.5, ionic strength 0.2, provided better permeation of drug compared to unbuffered drops of same pH and ionic strength. Above pH 6.5 unbuffered drops showed better permeation than buffered drops. Increase in molarity of phosphate buffer (pH 4.5) used in making drops, between 0 to 0.15 M increased permeation. Aqueous drops of ketorolac tromethamine formulated in 0.15 M phosphate buffer of pH 4.5 and ionic strength 0.2 showed maximum cumulative % permeation in vitro. Considering lacrimation induced drug loss in vivo, by buffer of high concentration, ketorolac tromethamine drops formulated in buffer of low molarity, pH 4.5 and ionic strength 0.2 appear suitable.

Animals↗
PubMed1997

In vitro transcorneal permeation of ketorolac from oil based ocular drops and ophthalmic ointment.

Transcorneal permeation of ketorolac from oil based ocular drops and ophthalmic ointments was studied in vitro, using goat cornea. Cumulative (%) permeation of ketorolac through cornea, was found to be maximum with 0.2% (w/v) ketorolac drops in sesame oil followed by formulations in corn oil and soyabean oil. Ketorolac 1% (w/v) drops in castor oil increased the quantity permeated but cumulative (%) permeation was less. Permeation profiles of ketorolac were in consistence with the partition characteristic of drug between oil and aqueous phase. Formulations favouring corneal permeation of ketorolac increased corneal hydration. Addition of benzyl alcohol, a preservative, to oil drops reduced permeation of ketorolac and corneal hydration indicating possible protective effect of benzyl alcohol against corneal damage. Permeation studies on ointment formulations containing either ketorolac acid or ketorolac tromethamine salt indicated better permeation for formulation containing ketorolac tromethamine aqueous solution. Thus for better transcorneal permeation, ketorolac 0.2% (w/v) drops, formulated in sesame oil, containing 0.5% v/v benzyl alcohol and ophthalmic ointment containing 0.5% (w/w) ketorolac tromethamine in dissolved state appear suitable.

Animals↗
PubMed1996

Anomalous mobility of sulfitolysed proteins in SDS-PAGE. Analysis and applications.

Some cysteine-containing proteins upon sulfitolysis have been found to show anomalously retarded SDS-PAGE mobilities in non-reducing gels. These proteins include bovine serum albumin, ovalbumin, aldolase, ribonuclease and a recombinant fusion protein (XA) consisting of a portion of gamma-interferon linked to the A chain of human insulin. This mobility shift has been employed to determine the stability of the sulfonated products and to study the kinetics of the sulfitolysis reaction. Partially sulfonated products of intermediate shifts were observed at 0.01% beta-ME, while 0.05% beta-ME gave a shift characteristic of the completely reduced protein. The undiluted sulfitolysis reagent reacted with XA to give within 1 min a gel shift characteristic of the fully sulfitolysed protein. Its transition stages could be visualized at 15, 30 and 60 min when the reagent was diluted four-fold. In the presence of 8 M urea, the sulfitolysis of BSA was nearly complete at 30 min when the sulfitolysis reagent was used at a dilution of 1:5. However, under the same conditions BSA was predominantly unsulfitolysed in the absence of urea. In order to elucidate the mechanism of sulfonation shift, several derivatives of XA, e.g. performic acid oxidized, alkylated with (a) iodoacetamide and (b) iodoacetate, have been prepared. While the mobility of XASSO3- was sensitive to the presence of beta-ME, all other derivatives moved in a beta-ME-insensitive fashion. Furthermore, while the nonreducing mobilities of the acidic derivatives (-SSO3-, -SO3- and -SCH2CO2-) were anomalously retarded and identical, the mobility of the iodoacetamide derivative was intermediate between the retarded acidic derivatives above and XA below. These studies have suggested a role of the extended conformation of the A chain of insulin in causing a mobility shift of the acidic derivatives in this series. Similar results were observed in an analogous series of derivatives prepared from BSA. Non-denaturing gel filtration analyses of native vs. sulfitolysed samples of serum albumin, ovalbumin and ribonuclease have indicated that the sulfitolysed proteins elute earlier than their native counterparts and appear to be significantly larger than their true molecular weights. Circular dichroism analysis has indicated significant loss in helicity of sulfitolysed BSA. This suggests that the retarded mobility of sulfitolysed proteins seen on SDS-PAGE is likely to be due to an expansion in the hydrodynamic volumes of these proteins, a phenomenon triggered by cleavage of disulfide bonds and further accentuated by the introduction of strongly negatively charged sulfonates.

Animals↗
PubMed1996

Negative regulation of two hyperproliferative keratinocyte differentiation markers by a retinoic acid receptor-specific retinoid: insight into the mechanism of retinoid action in psoriasis.

Retinoids down-regulate the expression of metalloproteinases, cytokines, and other genes involved in cell proliferation and inflammation. Tazarotene (AGN 190168), a retinoic acid receptor (RAR)-specific retinoid, is effective in the treatment of psoriasis, a hyperproliferative and inflammatory skin disease. Because negative regulation of genes appears to be important in the antiproliferative and antiinflammatory action of retinoids, we studied the down-regulation of genes in skin raft cultures by this antipsoriatic retinoid. By subtraction hybridization, we found that migration inhibitory factor-related protein (MRP-8) and skin-derived anti-leukoproteinase (SKALP) are down-regulated by AGN 190168. MRP-8 and SKALP are overexpressed in psoriatic lesions as compared to the normal epidermis, and they are markers of hyperproliferative keratinocyte differentiation. We also show that MRP-8 expression is retinoid inhibitable in cultured keratinocytes induced to differentiate with 10% serum or IFN-gamma, and that MRP-8 is inhibited by RAR but not by retinoid X receptor-specific retinoids in a dose-dependent manner. Finally, MRP-8, SKALP, and the previously characterized differentiation marker, transglutaminase I, are all down-regulated in vivo in psoriatic lesions after treatment with AGN 190168 in comparison to placebo. Taken together, these data suggest that these markers may be down-regulated by tazarotene in psoriasis through direct action on keratinocyte gene expression rather than by an overall tazarotene effect on lesional therapeutic status.

Antigens, Differentiation↗
PubMed1991

Interodontoblastic collagen (von Korff fibers) and circumpulpal dentin formation: an ultrathin serial section study in the cat.

The collagenous fibers of von Korff pass from the dentin matrix between the odontoblasts into the dental pulp. Although collagen fibrils are known to be present between odontoblasts, the existence of von Korff fibers has remained controversial. This may be because their continuity between the dentin matrix and the pulp has not been demonstrated ultrastructurally. In this study we have examined the odontoblast layer in the middle to apical regions of perfusion-fixed permanent canine teeth of cats by using transmission electron microscopy. Ultrathin sections of demineralized specimens revealed frequent bundles of collagen fibrils 1) entering the odontoblast layer from the predentin, 2) present between odontoblast cell bodies, and 3) passing from between the odontoblasts into the pulp. The question of continuity of these bundles from the predentin, across the odontoblast layer into the pulp was examined in ultrathin serial sections. Unbroken continuity of a collagen bundle from the predentin between the odontoblasts into the pulp was established in a reconstruction of one series of 22 serial sections and was very strongly suggested by a number of other series in which the numbers of available sections restricted their full visibility. This investigation has shown, therefore, that classical von Korff fibers are present and that these fibers are present in fully erupted teeth with closed apices, i.e., at a time when secondary circumpulpal dentinogenesis is in progress. The findings call for a reexamination of the question of von Korff fibers during mantle dentinogenesis and primary circumpulpal dentinogenesis. Resolution of their existence at the earlier stages of dentinogenesis should be possible by using the ultrathin serial-sectioning technique.

Animals↗
PubMed1991

High levels of polysaccharides in Aplysia hepatopancreas and penis: differential effects of nutrition and development.

1. Carbohydrate levels in tissues of Aplysia californica were measured. In animals maintained in the laboratory without feeding for 1-2 weeks, the penis contained the highest concentration of glycogen. 2. Blood glucose ranged between 2.5 and 4.8 mg/dl and averaged 3.2 +/- 0.2 mg/dl. 3. Fed animals had significantly greater tissue glycogen levels than starved animals. The penis exhibited the smallest per cent increase in glycogen concentration in response to feeding. 4. In contrast, the hepatopancreas exhibited a large increase, attaining glycogen concentrations near that of the penis. 5. Most of the increase in total tissue glycogen in fed animals occurred in the hepatopancreas. 6. Starved and fed animals did not differ significantly in blood glucose concentration, thus indicating that blood glucose is regulated and excess glucose is stored. 7. The hepatopancreas is the major mobile glucose store. 8. The high concentrations of glycogen found in the penis were not affected by mating activity. 9. However, penis glycogen concentration increased greatly with reproductive maturation of Aplysia; in contrast, hepatopancreas glycogen concentration was relatively unaffected by development. 10. A structural role by carbohydrates in the penis is suggested.

Animal Nutritional Physiological Phenomena↗
PubMed1990

An investigation of lymphatic vessels in the feline dental pulp.

The existence of lymphatic vessels in the dental pulp has been a matter of continuing controversy. We have now used light microscopy to examine semithin transverse sections of perfusion-fixed incisors and canines in cats. Lymphatics were found in all the teeth studied. In most teeth they were present in the coronal, middle, and apical regions of the pulp; but in a few they were lacking coronally and in the middle. Within individual teeth, lymphatics were found in the subodontoblastic zone or more centrally in the pulp; but none were found in the odontoblast layer or in the pulp horns. Vessels located by light microscopy were subsequently examined by transmission electron microscopy. Their ultrastructural features were typical of lymphatics and included irregular, attenuated endothelium with adjacent cells joined in different ways. Occasional gaps connected the extracellular spaces with their lumens, and abluminal endothelial projections appeared to form open end bulbs. There was very little basement membrane, but anchoring filaments were found near the abluminal surface of the endothelium and near collagen fibrils. The total cross-sectional area of lymphatic vessels was measured in semithin sections and, with pulp area, increased from the coronal region to the middle. However, both areas decreased from the middle to the apical region suggesting either that lymph flows faster as it reaches the foramens of the apical delta or that some vessels leave the tooth through lateral root canals. Using the methods of light and transmission electron microscopy, therefore, we have shown that pulp lymphatic vessels exist. Questions remain, however, about their distribution within teeth, variations between teeth, and routes of exit from teeth.

Animals↗
PubMed1990

Respiratory disorders in females of Delhi.

A retrospective study was carried out on 1532 female patients attending chest clinic, over a period of 13 years. The incidence of smoking was found to be 6.6%, maximum incidence (17%) being in those above 60 years of age. High incidence (66%) of exposure to kitchen smoke was observed in women above 40 years of age. Chronic bronchitis was found to be the commonest illness followed by bronchial asthma, pulmonary tuberculosis and bronchiectasis. Bronchial asthma and pulmonary tuberculosis were common in younger age groups, while above the age of 40 years 42% patients had chronic bronchitis and 27% had bronchiectasis. Incidence of smoking and exposure to kitchen smoke was also high in this subset. This shows that they may be important contributory factors for chronic obstructive pulmonary disease in females. Evidence of chronic cor pulmonale was found in 130 (8.5%) patients. Maximum incidence (28%) was seen in the age group of above 60 years. Chronic bronchitis with or without emphysema turned out to be the commonest cause of cor pulmonale, followed by bronchiectasis, pulmonary tuberculosis and bronchial asthma.

Female↗
PubMed1990

Pulmonary complications of septicaemia in women.

Twenty-five female patients of septicaemia aged 15-50 years comprised this study. Twenty-three patients (92%) were in the reproductive age group (15-35 years). Sixteen patients (64%) had some relation to parity, suggesting an increased risk of septicaemia in women with puerperal sepsis. The commonest primary source of infection was the female genital tract (48%). Gram-negative septicaemia was the commonest. The pleuropulmonary complications observed were pneumonia (10 cases), lung abscess (7 cases), empyema (3 cases), septic pulmonary embolisation (4 cases) and adult respiratory distress syndrome (4 cases). Seven cases of the total 25 died. Adult respiratory distress syndrome with septicaemia was the commonest cause of mortality in these patients.

Adolescent↗
PubMed1978

A genetic survey in the Bhil tribe of Madhya Pradesh, Central India.

Examination of blood groups, plasma proteins and red cell enzyme types (23 loci), in a sample of 145 Bhils, a tribal group of Madhya Pradesh, Central India, demonstrates their genetic uniqueness. They differ in a number of systems from the nearby nontribal groups both of Hindus and Muslims. The results suggest that the Bhil frequencies include vestiges of the ancestral genepool of a more widespread aboriginal population whose influence is detectable in the gene frequencies of some other populations in India.

Adenosine Deaminase↗