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Biomedical subjects

R Malhotra

Publications and source records attributed to R Malhotra.

At least 127 records · Page 7Linked to original sources
PubMed1995

Binding of host collectins to the pathogenic yeast Cryptococcus neoformans: human surfactant protein D acts as an agglutinin for acapsular yeast cells.

Cryptococcus neoformans is an opportunistic pathogen in AIDS patients causing disseminated disease and lethal meningitis after inhalation of acapsular or sparsely encapsulated yeast cells. In this study we have investigated whether a recently described family of primitive opsonins, termed collectins, contribute to innate resistance against C. neoformans. The pulmonary surfactant proteins SP-A and SP-D as well as the serum collectins mannose-binding protein and CL-43 bound in a calcium-dependent manner to acapsular C. neoformans in vitro. Binding was concentration dependent and abolished by competition with defined mono- and oligosaccharides. In contrast, no binding of the collectins was observed with the encapsulated form of the yeast. Furthermore, binding of purified collectin SP-D, but not SP-A, mannose-binding protein, or CL-43, led to a concentration-dependent agglutination of acapsular C. neoformans. These data indicate that collectins recognize carbohydrate structures in the cell wall of an initial infectious form of C. neoformans and may play a role in early antifungal defenses in the lung.

Agglutinins↗
PubMed1995

Lectin-carbohydrate interactions in disease. T-cell recognition of IgA and IgD; mannose binding protein recognition of IgG0.

Two disease associated lectin-carbohydrate interactions have been studied. (1) A T-cell surface lectin which binds IgA1 and IgD is expressed on CD4+ and CD8+ T-lymphocytes in a number of diseases including systemic lupus erythematosus, rheumatoid arthritis (RA), Behcet's disease and IgA nephropathy. We have demonstrated that calcium independent binding to this receptor is mediated by the O-linked disaccharide Gal beta 3GalNAc which is associated with the hinge regions of both IgA1 and IgD. (2) In rheumatoid arthritis the proportion of IgG0 glycoform populations lacking terminal galactose increases. We have shown that terminal GlcNAc residues on oligosaccharides in the Fc region of IgG0 can bind to the C-type lectin, serum mannose binding protein, and thus activate the classical complement pathway. This provides a mechanism of activation of the complement system not available to the other classes of IgG glycoforms.

Carbohydrate Metabolism↗
PubMed1994

Binding of human collectins (SP-A and MBP) to influenza virus.

Collectins are a group of soluble proteins each of which has collagenous domains and non-collagenous globular domains, the latter containing the consensus residues found in C-type lectins. Members of the collectin family are the serum proteins mannan-binding protein (MBP), conglutinin, CL-43, and the lung-associated proteins surfactant protein A (SP-A) and surfactant protein D (SP-D). MBP and conglutinin have been shown previously to bind to influenza viruses and to inhibit the infectivity and haemagglutinating activity of influenza viruses. We report here that the lung protein SP-A, like MBP, can bind to influenza virus (strain A/X31) through its lectin domain and inhibit the virus-mediated agglutination of red cells. The binding of SP-A or MBP to influenza virus was saturable, concentration-dependent, and required the presence of Ca2+ ions. Ligand-blot analysis, using MBP as ligand, of the virus lysate indicated that MBP binds to a 68 kDa viral species. The 68 kDa species was isolated to homogeneity and was shown to be the viral neuraminidase. The purified 68 kDa species inhibited the binding of both MBP and SP-A to influenza virus.

Antibodies, Monoclonal↗
PubMed1994

Surfactant proteins A (SP-A) and D (SP-D): levels in human amniotic fluid and localization in the fetal membranes.

Surfactant proteins A (SP-A) and D (SP-D) are major proteins, in the lung, which are composed of collagenous and globular domains. They show an overall similarity to the serum complement protein Clq, which is involved in the initiation of antibody-dependent defence mechanisms. Both SP-A and SP-D were detected, immunochemically, in amniotic fluid as early as 26 weeks gestation and, as expected, SP-A levels rose sharply from 32 weeks towards term. By contrast, SP-D levels in the same samples rose only moderately. Immunochemistry of paraffin sections of fetal membranes, revealed the presence of both SP-A and SP-D in the amniotic epithelium and chorio-decidual layers. SP-A and SP-D are both lectins and therefore they may play a role in the antibody-independent recognition and clearance of pathogens in the amniotic fluid.

Amniotic Fluid↗
PubMed1994

Collectins: collagenous C-type lectins of the innate immune defense system.

Collectins are humoral lectins found in mammals and birds. They are oligomers whose subunits comprise three polypeptide chains each containing a collagenous section and a C-terminal lectin domain. They are related structurally and functionally to the first component of the classical complement pathway, C1q, and seem to serve important roles in innate immunity through opsonization and complement activation. The lectin domains bind carbohydrates on microorganisms, while the collagenous regions are ligands for the collectin receptor on phagocytes and also mediate C1q-independent activation of the classical complement pathway.

Animals↗
PubMed1994

Free flap valvular transplantation for refractory venous ulceration.

PURPOSE: Nonoperative therapeutic approaches to chronic venous ulceration, although effective, often require prolonged dressing care and immobilization with leg elevation. Results of skin grafting, perforator ligation, and valve interpositions and reconstructions improve results of ulcer healing but have not uniformly prevented ulcer recurrence. Our hypothesis is that reconstruction of chronic venous ulcers by excision of the diseased tissue bed and replacement with a free flap containing multiple competent microvenous valves and a normal tissue microcirculation will result in long-term cure of these debilitated patients. METHODS: Six patients with chronic venous insufficiency and recurrent ulceration (class 3) underwent excision of ulcers and surrounding liposclerotic tissue beds and reconstruction with fasciocutaneous free flaps (two bilateral). Preoperative and postoperative photoplethysmography was used to assess venous refilling times. Duplex scanning was performed to assess deep venous reflux. RESULTS: There were no flap failures. Photoplethysmographic venous refilling times measured on flaps demonstrated significant immediate and long-term increases from preoperative values (all results +3 by Society of Vascular Surgery outcome grading). Long-term maintenance of tissue integrity is shown by absence of recurrent ulceration and no evidence of recurrent tissue lipodermatosclerosis in all flaps at follow-up (8 months to 7.5 years; mean 24 months). No recurrent lipodermatosclerosis was seen on flap biopsy at 2 and 7 years. Separate cadaveric injection studies, including scanning electron microscopy, revealed numerous microvenous valves directed toward the draining pedicle in the flaps used for reconstruction. CONCLUSIONS: This is the first comprehensive report providing combined laboratory and clinical evaluation, anatomic rationale, and long-term outcome of surgical rehabilitation of patients with chronic venous ulceration who have undergone microsurgical flap reconstruction.

Adult↗
PubMed1994

Mixed cryoglobulinemia in chronic hepatitis C infection. A clinicopathologic analysis of 10 cases and review of recent literature.

We present 10 cases of mixed cryoglobulinemia in patients infected with hepatitis C, including pertinent clinical, serologic, and pathological data. The findings attributable to MC appear to be similar in patients who are HCV-infected as in those with unknown HCV status. The prevalence of MC in HCV-infected patients appears to be lower in our region (13%) than in southern Europe (50-90%) although some of this difference is due to our requirement that patients included in our study have a cryocrit of at least 5%. In our patients, cryoglobulins were shown to be deposited in skin and kidney, but not in liver. The mechanisms by which HCV and MC are related remain uncertain. Although we and others have evidence for enrichment of HCV RNA in the cryoprecipitates of some patients, this was not always the case, and it is not yet clear that this finding is of fundamental pathogenic importance. Finally, it appears that some patients with HCV and MC may have a beneficial clinical response of vasculitic symptoms to therapy with alpha-interferon, as well as to glucocorticoids or other immunosuppressants. In our group, no predictors were apparent to distinguish responders from nonresponders before treatment. Similarly, the duration of response remains to be determined.

Adult↗
PubMed1994

Localization of neurofibromin to keratinocytes and melanocytes in developing rat and human skin.

Pigmentation defects are common in the inherited disease type 1 neurofibromatosis (NF1), predicting a role for the NF1 gene product, neurofibromin, in the skin. We used immunohistochemistry to determine the distribution of neurofibromin in normal developing and adult rat skin, normal neonatal and adult human skin, and skin from patients affected with NF1. The distribution of NF1 mRNA in the epidermis was also analyzed by in situ hybridization. NF1 mRNA and neurofibromin are highly enriched in the keratinocytes in the stratum spinosum of the epidermis in the embryonic, but not adult, rat and in both neonatal and adult humans. Immunoelectron microscopic analysis confirmed that neurofibromin is associated with the keratinocyte plasma membrane, particularly adjacent to desmosomes. Neurofibromin is also detectable in human melanocytes. Analysis of skin from NF1 patients showed normal neurofibromin expression in nine of ten hyperpigmented cafe-au-lait macules and in adjacent unaffected skin. We conclude that 1) neurofibromin expression in the perinatal rat closely parallels expression in the human; 2) reduction in detectable neurofibromin cannot be used to distinguish NF1 and normal human skin; and 3) neurofibromin might function in keratinocytes, as well as melanocytes.

Adult↗
PubMed1994

Collectins, collectin receptors and the lectin pathway of complement activation.

The collectins are a group of soluble multimeric lectins, which contain collagenous segments, and resemble the complement protein C1q in aspects of their structures and functions. This group of proteins, which includes MBP, SP-A, SP-D, conglutinin and CL-43, are known to act as opsonins in various circumstances, and are likely to have roles in innate immunity. The focus of current research is to pursue the hypothesis that the collectins recognize and bind to non-host carbohydrate structures on microorganisms and particles, and participate in the processing or elimination of such material, either by direct interaction with phagocytic cell receptors, or by indirect routes such as complement activation .

Animals↗
PubMed1994

Autoimmune-like activity of sperm specific LDH: a pathophysiological and electron microscopic study of atrophied testis and epididymis.

Hyper-immunization of male mice with human LDH-C4 evoked autoimmune reactions illustrated by the loss of LDH activity, associated histopathological changes in testes and epididymis and induction of sterility in mice. This was substantiated by the altered morphology of sperm mitochondria and plasma membrane, and by reduced number of cytoplasmic droplets as observed by electron microscopy. However, the presence of lymphoblasts and other lymphoid cells in testes indicated that the testicular damage is accentuated by activated T lymphocytes. It is concluded that immunization with human LDH-C4 produces lesions in mouse testis and epididymis, which are similar to experimentally induced autoimmune orchitis.

Animals↗
PubMed1994

Mannan-binding protein levels in human amniotic fluid during gestation and its interaction with collectin receptor from amnion cells.

Collectins are a group of soluble proteins, each of which has collagenous and non-collagenous globular domains, and may be complement associated and/or have lectin activity. The complement protein C1q is structurally and functionally related to the collectins. Members of the collectin family are mannan-binding protein (MBP), lung surfactant protein A, CL-43, conglutinin and lung surfactant protein D. All except the last of these proteins have been shown to interact with a single, widely distributed receptor, named collectin receptor (also called C1q receptor). It has been proposed that collectins play an important role as opsonins in innate immunity. MBP is a serum protein and has been shown to activate the classical complement pathway. MBP has also been shown to opsonize bacteria and enhance clearance of bacteria by phagocytosis. In this article we demonstrate the presence of MBP in amniotic fluid and the localization of collectin receptor on the surface of amniotic epithelium. MBP levels in amniotic fluid were found to increase sharply from about 32 weeks of gestation. Collectin receptor was purified from a cell line, FL, derived from amniotic epithelium and was shown to interact with MBP. These results suggest that MBP may play a role in the antibody-independent recognition and clearance of pathogens in the amniotic cavity, towards term.

Amino Acid Sequence↗
PubMed1994

Regulation of fertility in female mice after immunization with human sperm specific LDH: role in conception and contraception.

Effects on fertility of female mice after hyper-immunization with human lactate dehydrogenase-C4 have been studied at (50 + 25 x 4) and (50 + 50 x 4) micrograms doses of protein for two consecutive cycles of pregnancy. Results of heterologous immunization are described in relation to the role of LDH-C4 in conception and contraception. (i) Low dose of Immunization produced higher antibody (Ab) titer as tested before mating followed by higher infertility (70%) than by a higher dose of immunogen (46%), taking pregnancy as the end point. (ii) However, the results were reversed after second mating. For example, low dose of immunogen produced insignificant infertility, whereas high dose of immunogen gave 80% infertility. Similar order was shown by humoral Ab titer before mating i.e., high infertility was associated with high Ab titer and viceversa. (iii) It shows that the LDH-C4 induced infertility is reversible as is evidenced by low dose of immunization. (iv) In contrary to infertile dams, immunized fertile dams delivered a significantly higher litter size as compared to non-immunized control dams. It is concluded that immunity due to LDH-C4 is beneficial for embryo survival suggesting an immuno-suppressive nature of LDH-C4. Nonetheless, infertility ensues when immune-suppression is overcome by its own immune-activation.

Animals↗
PubMed1994

Posttraumatic cutaneous meningioma of the face.

We present the CT and MR features of a posttraumatic cutaneous meningioma of the face. We postulate that the patient's trauma and associated skull fracture resulted in a trapping of extracranial meningeal tissue, which many years later gave rise to a secondary facial meningioma.

Aged↗