Biomedical subjects
Publications and source records attributed to M S Bajaj.
Human cysticercosis and tuberculosis are endemic diseases in developing countries. Both these diseases have certain common factors of origin. We would like to present the co-existence of these infections in a 20-year-old female. She was a known case of pulmonary and ocular tuberculosis and she acquired cysticercosis of the eye and brain.
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Fungal infections of the skin and deeper tissues of the periorbital region are quite rare. We report a case of a localized, deep periorbital necrotizing Fusarium infection in an otherwise healthy, elderly lady. Since the clinical features and histopathological findings of Fusarium infection are by no means characteristic, the definitive diagnosis was achieved with the help of microbiological examination of cultured organisms. A combined medical and surgical therapy led to adequate control of infection. To conclude, localized, deep periorbital necrotizing soft tissue infection by Fusarium in an immunocompetent lady is not reported in literature. One should have a high index of suspicion for emerging fungal pathogens in the differential diagnosis of necrotizing orbital or adnexal conditions, even in an immunocompetent patient. The histologic findings of septate, branching hyphae and vascular invasion cannot distinguish Fusarium species from various other moulds such as Aspergillus species; microbiologic studies are essential for confirming the diagnosis.
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Tissue factor pathway inhibitor (TFPI) is the primary physiologic inhibitor of tissue factor-induced clotting. The TFPI gene contains three GATA motifs in the region flanking its transcription initiation sites. GATA motifs present in promoters of other genes bind GATA-2 transcription factor and thereby regulate their transcriptional expression. Both TFPI and GATA-2 transcription factor are synthesized by a variety of normal as well as malignant cells including hepatocellular carcinoma HepG2 and bladder carcinoma ECV304. Here, we studied whether the three GATA motifs flanking the transcription initiation sites regulate TFPI gene expression in HepG2 and ECV304 cells by binding to the GATA-2 transcription factor. Synthetic oligonucleotides containing GATA sequences from the TFPI regulatory region formed DNA-protein complexes with HepG2 and ECV304 nuclear extracts in an electrophoretic mobility shift assay. Using a 740-bp fragment (-496/+244) from TFPI regulatory region, the effect of base substitutions at each of the three GATA motifs was studied in a luciferase reporter gene system. TFPI promoter activity in HepG2 cells was increased 3-fold with mutation in one of the three GATA motifs and in ECV304 cells was essentially unchanged with mutations in all three GATA motifs. Thus, GATA motifs appear to serve a tissue-specific regulatory role in TFPI gene expression in malignant cells.
PURPOSE: To study the demographic factors, clinical diagnosis, results of investigation, modalities of treatment and their outcome in ocular and extraocular cysticercosis. METHOD: A total of 20 patients were recruited for the study. Ultrasonography and computed tomography were done for all the patients. Serial ultrasound was obtained in patients receiving medical treatment. Therapy was individualized according to the location of the cyst. RESULTS: The commonest clinical presentation was proptosis (9 of 20) with restriction of ocular movements, followed by subconjunctival cyst, subretinal cyst, papilloedema, atypical optic neuritis, lid nodule and intraretinal cyst. Ultrasonography was comparable with computed tomographic scan for detection of scolex. Two of the twenty patients had associated cysts in the brain parenchyma. Medical or surgical therapy as indicated, had a satisfactory outcome. CONCLUSION: Cysticerci can lodge themselves in any part of the ocular and extra ocular tissue. Associated brain parenchyma involvement is quite rare. The clinical presentation, treatment and outcome mainly depends on the location of the cyst.
Human tissue factor pathway inhibitor (TFPI) is a modular protein comprised of three Kunitz type domains flanked by peptide segments that are less structured. The sequential order of the elements are: an N-terminal acidic region followed by the first Kunitz domain (K1), a linker region, a second Kunitz domain (K2), a second linker region, the third Kunitz domain (K3), and the C-terminal basic region. The K1 domain inhibits factor VIIa complexed to tissue factor (TF) while the K2 domain inhibits factor Xa. No direct protease inhibiting functions have been demonstrated for the K3 domain. Importantly, the Xa-TFPI complex is a much more potent inhibitor of the VIIa-TF than TFPI by itself. Furthermore, the C-terminal basic region of TFPI is required for rapid physiologic inhibition of coagulation and is needed for the inhibition of smooth muscle cell proliferation. Although a number of additional targets for attachment have been reported, the C-terminal basic region appears to play an important role in binding of TFPI to cell surfaces. A primary site of TFPI synthesis is endothelium and the endothelium-bound TFPI contributes to the antithrombotic potential of the vascular endothelium. Further, increased levels of plasma TFPI under septic conditions may represent endothelial dysfunction. We have proposed that the extravascular cells that synthesize TF also synthesize TFPI providing dual components necessary for the regulation of clotting in their microenvironment. Like the TF synthesis in these cells is augmented by serum, so is the case with the TFPI gene expression. TFPI gene knock out mice reveal embryonic lethality suggesting a possible role of this protein in early development. Since TF-induced coagulation is thought to play a significant role in many disease states, including disseminated intravascular clotting, sepsis, acute lung injury and cancer, recombinant TFPI may be a beneficial therapeutic agent in these disease states to attenuate pathologic clotting. The purpose of this review is to outline recent developments in the field related to the structural specificity and biology of TFPI.
The mesothelial lining of the pleura and malignant mesothelioma promote fibrin deposition in pleural injury or neoplasia via expression of tissue factor (TF). It was hypothesized that these cells might also regulate intrapleural coagulation by elaborating TF pathway inhibitor (TFPI). TFPI activity and antigen in pleural fluids were assayed from patients with congestive heart failure (CHF), pneumonia, empyema, metastatic pleural cancer and malignant mesothelioma. The authors also assessed expression of TF and TFPI messenger ribonucleic acid (mRNA) as well as TFPI activity and antigen by human pleural mesothelial cells, malignant mesothelioma cells (MS-1 cell line) and human lung fibroblasts. Immunohistochemical analyses of normal, fibrotic, and neoplastic pleura were performed to determine whether TFPI antigen was expressed in vivo. The study revealed that TFPI was present in transudates from patients with CHF and exudative pleural effusions from patients with pneumonia, empyema or pleural carcinoma. TFPI mRNA, activity and antigen were expressed by pleural mesothelial cells, MS-1 cells and lung fibroblasts. Cytokines and serum stimulated a significant early increase in TF mRNA levels with minimal enhancement of TFPI mRNA, activity and antigen levels. TFPI antigen was found in normal, fibrotic and neoplastic pleural tissues. The current observations indicate that tissue factor pathway inhibitor is locally expressed in pleural disease, but that it does not prevent the development of a prothrombotic environment favouring local fibrin deposition in pleural inflammation or cancer.
Remote flaps may be used for lid reconstruction when tissue loss is extensive and there is insufficient tissue in the adjoining areas. Median forehead flaps are usually used for upper lid, medial canthal or nasal repairs. We describe a complicated reconstruction of the lid and correction of a deformity which resulted from the injudicious use of a glabellar flap for lower lid repair. Improper use of a median forehead flap may interfere with the functioning of the lid, leading to corneal exposure and poor cosmesis. Lower lid defects are better repaired by advancement flaps or techniques like Tenzel's semicircular flap, reverse Cutler Beard, Hughes procedure or Mustarde's repair.
Ophthalmoscopically guided intraocular fine-needle aspiration biopsy (FNAB) under general anesthesia was performed in three suspected cases of retinoblastoma (Rb). The first case presented with uveitis and the second with unusual radiological features. The third case had classical clinical features of bilateral Rb but the parents refused enucleation. After a cytologic diagnosis of retinoblastoma, two cases were subjected to enucleation and a histologic confirmation was obtained. The present article discusses the technique of guided intraocular FNAB and its limitations as well as utility in the preoperative diagnosis of retinoblastoma (Rb). The authors are of the opinion that FNAB should be considered a viable diagnostic option in selected cases of leucocoria when conventional investigative modalities prove inconclusive or for tissue diagnosis when a patient of suspected Rb refuses enucleation.
OBJECTIVE: To determine if the plasma levels of three endothelial-specific proteins, von Willebrand factor (vWF), tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) may be useful in predicting the development of acute respiratory distress syndrome (ARDS). DESIGN: Blood samples were obtained from normal healthy volunteers and on the first day from patients at risk for ARDS and those with ARDS. Daily sequential measurements of vWF and TFPI were performed in two patients. SETTING: Normal subjects were employees at Saint Louis University Hospital, St. Louis, Missouri. Patients at risk and those with ARDS were patients admitted to the medical and surgical floors and the intensive care units at St. Louis University Hospital. PATIENTS AND PARTICIPANTS: Plasma levels of vWF, TFPI and TM were measured in 27 normals, and on day 1 in 15 patients at risk for ARDS and 18 patients with ARDS from different etiologic factors. MEASUREMENTS AND RESULTS: Plasma levels of vWF were significantly elevated in the at-risk (p < 0.01) and ARDS group (p < 0.001) as compared to normals but did not differ significantly between the two groups (p > 0.05). Plasma levels of TFPI were not significantly different between the normal and the at-risk group (p > 0.05); however, they were significantly elevated in ARDS as compared with at-risk and normal groups (p < 0.001). Levels of TM were significantly increased in the at-risk group as compared to normals (p < 0.01) but were not significantly different from the ARDS group (p > 0.05). Eight patients at risk progressed to develop ARDS. A vWF level of > 300% in patients at risk was 62% sensitive and 71% specific for predicting the development of ARDS with a positive predictive value of only 34%. TFPI levels were normal in 7 of the 8 patients who developed ARDS. A TM level of > 100 ng/ml in patients at risk was 50% sensitive and 57% specific with a positive predictive value of merely 8% for development of ARDS. There was no significant difference in the mean plasma levels of the three proteins on day 1 in patients at risk who developed ARDS as compared with those who did not develop ARDS. There was also no difference in mean plasma levels of the three proteins in patients with ARDS from sepsis as compared with ARDS from other etiologies. Plasma levels of vWF and TFPI correlated significantly. CONCLUSION: Plasma levels of vWF, TFPI and TM did not appear to serve as useful markers for predicting ARDS in patients at risk.
Under normal physiologic conditions, tissue factor pathway inhibitor (TFPI) is synthesized primarily by the microvascular endothelium. Using Northern blotting, we studied its transcriptional expression in different organs and compared it with the expression of two other endothelial specific proteins, namely thrombomodulin (TM) and von Willebrand factor (vWF). The order of mRNA expression for each protein was: TFPI-placenta>lung>liver>kidney>heart>skeletal muscle> or =pancreas>brain; TM-heart>pancreas>lung>skeletal muscle>kidney> or =liver>placenta>brain; and vWF-heart>skeletal muscle>pancreas>lung> or =kidney>placenta>brain>liver. Notably, heart expressed TM and vWF mRNA in large amounts and only small amounts of TFPI whereas lung expressed all three mRNAs in significant amounts. Placenta, on the contrary, expressed large amounts of TFPI but only small amounts of TM and vWF mRNAs. Brain by this technique was found to express undetectable amounts of TFPI and TM mRNAs but small amounts of vWF mRNA. The expression of TFPI mRNA in the brain was however detected by RT/PCR and the antigen was localized to the endothelium of microvessels as well as to the astrocytes and oligodendrocytes. Since ultimate expression of proteins is linked to the expression of their mRNAs, our data support a concept that vascular endothelium is made up of phenotypically diverse groups of cells and that endothelial cells of different vascular beds express specific sets of genes that enable them to carry out tissue-specific functions. Importantly, since astrocytes are known to express tissue factor, the TFPI expression by these cells may control coagulation in their microenvironment and their response to injury and inflammation.
Tissue factor pathway inhibitor (TFPI) plays an important role in regulating tissue factor (TF)-initiated blood coagulation. Since serum stimulation of fibroblasts, vascular smooth muscle cells and cardiac myocytes in culture increases the expression of TF mRNA and antigen (Ag) in these cells, we hypothesized that serum may also induce increased synthesis of TFPI in these cells to regulate the TF-induced extravascular clotting at an injury site. To test this concept, we used primary isolates of the following human cell types - fetal and adult lung fibroblasts, pulmonary and aortic smooth muscle cells, and cardiac myocytes. Serum-stimulation of these cells resulted in an increased expression of TF mRNA and Ag (8 to 10-fold). Upon serum stimulation, expression of TFPI mRNA and Ag was also increased in these cells. However, the increase in TFPI-Ag (6 to 8-fold) was significantly greater than the TFPI mRNA (2 to 3-fold). Notably, increased expression of TFPI persisted after the TF expression had declined. Further, increased synthesis of TFPI initially led to the saturation of heparin-releasable binding sites. TFPI-Ag was detected by Western blotting, 35S-metabolic labeling and activity assays on the conditioned media, heparin-released material from cells, and in cell lysates. TFPI-Ag was also detected by immunofluorescence staining of cells. Actinomycin D partially whereas cycloheximide completely prevented the serum-induced increased expression of TFPI synthesis by these cells, suggesting control primarily at the translational but some at the transcriptional level as well. The Mr of undegraded TFPI in all cases was approximately 45 kDa and was of full length. TFPI synthesized locally by fibroblasts, vascular smooth muscle cells and cardiac myocytes could play a significant role in regulating TF-initiated extravascular clotting especially since plasma TFPI that may be available at the injury site lacks a portion of the carboxyl segment and is a less efficient inhibitor.