Biomedical subjects

V Malhotra

Publications and source records attributed to V Malhotra.

At least 37 records · Page 2Linked to original sources

PubMed2001

Recruitment of protein kinase D to the trans-Golgi network via the first cysteine-rich domain.

Protein kinase D (PKD) is a cytosolic protein, which upon binding to the trans-Golgi network (TGN) regulates the fission of transport carriers specifically destined to the cell surface. We have found that the first cysteine-rich domain (C1a), but not the second cysteine-rich domain (C1b), is sufficient for the binding of PKD to the TGN. Proline 155 in C1a is necessary for the recruitment of intact PKD to the TGN. Whereas C1a is sufficient to target a reporter protein to the TGN, mutation of serines 744/748 to alanines in the activation loop of intact PKD inhibits its localization to the TGN. Moreover, anti-phospho-PKD antibody, which recognizes only the activated form of PKD, recognizes the TGN-bound PKD. Thus, activation of intact PKD is important for binding to the TGN.

Amino Acid Substitution↗

PubMed2001

Polo-like kinase is required for the fragmentation of pericentriolar Golgi stacks during mitosis.

The pericentriolar stacks of Golgi cisternae undergo extensive reorganization during mitosis in mammalian cells. GM130 and GRASP65 (Golgi reassembly stacking protein of 65 kDa) are Golgi-associated proteins that are targets of mitotic kinases, and they have also been implicated in the reorganization of the Golgi structure during cell division. Previous studies have reported that mitogen-activated protein kinase kinase-1 (MEK1) and Cdc2 protein kinases are involved in these dynamic changes in the Golgi structure. More recently, the mitotic polo-like kinase (Plk) has been shown to interact with and phosphorylate GRASP65. Here, we provide evidence that Plk is involved in the mitosis-specific fragmentation of the Golgi apparatus. The addition of kinase-defective Plk or immunodepletion of Plk disrupts the fragmentation process. Furthermore, Golgi fragmentation is inhibited by the addition of either full-length or truncated GRASP65. These findings suggest that phosphorylation of GRASP65 by Plk may be a critical event in the reorganization of the Golgi structure during mitosis.

Animals↗

PubMed2001

Protein kinase D regulates the fission of cell surface destined transport carriers from the trans-Golgi network.

When a kinase inactive form of Protein Kinase D (PKD-K618N) was expressed in HeLa cells, it localized to the trans-Golgi network (TGN) and caused extensive tubulation. Cargo that was destined for the plasma membrane was found in PKD-K618N-containing tubes but the tubes did not detach from the TGN. As a result, the transfer of cargo from TGN to the plasma membrane was inhibited. We have also demonstrated the formation and subsequent detachment of cargo-containing tubes from the TGN in cells stably expressing low levels of PKD-K618N. Our results suggest that PKD regulates the fission from the TGN of transport carriers that are en route to the cell surface.

Biological Transport↗

PubMed2001

Proboscis lateralis of nose.

A rare case of congenital malformation of the nose that was successfully corrected surgically is reported.

Child, Preschool↗

PubMed2001

Brush cytology: an adjunct to diagnostic upper GI endoscopy.

Endoscopic brush cytology (EBC) was performed in antral and duodenal brushings of children subjected to upper GI endoscopy for the detection of H. pylori (Hp) and trophozoites of Giardia lamblia (Glt) in addition to routine endoscopic grasp biopsy (EGB). It was hospital based prospective study. EBC was performed in children subjected to upper GI endoscopy with a sheathed cytology brush. Mucosal brushings were collected from antrum, body of the stomach and second or third part of duodenum by gently rubbing the surface of the brush with the mucosal wall in all the directions, brush withdrawn and brushings performed on a glass slide. The smears were placed in 95% ethyl alcohol and later examined for Glt and Hp using Giemsa and Hematoxylin & Eosin stain. EGB was taken from antrum, body of the stomach and duodenum from sites other than those used for brushings. One hundred and seventy children between 1-13 years (median age = 5 years) were subjected to upper GI endoscopy for malabsorption (n = 94), recurrent abdominal pain (n = 49), failure to thrive (n = 16) and recurrent vomiting/regurgitation (n = 11) and EBC was performed in addition to routine EGB. Thirty five children (20.4%) were colonized by Hp, 14 (8.2%) were detected to have Glt and in 6 cases (3.5%) both Hp as well as Glt were detected. Out of 41 cases colonized by Hp, 24 cases (58.5%) were detected by EGB and 27 cases (65.8%) were detected by EBC. Out of 20 children in whom Glt were detected from their duodenum, the detection was by EBG in 12 cases (60%) and by EBC in as many as 19 cases (95%). Comparison of EGB and EBC suggested that detection rates with EBC were higher than EGB. Detection by EBC was significantly higher for Glt than Hp. There were no complications attributed to EBC and procedure time for endoscopy was not significantly prolonged. On the contrary, detection of Hp and particularly Glt in higher proportion of cases with the help of EBC was helpful in their appropriate management. Our results suggest that EBC is a safe and useful tool to enhance the value of diagnostic endoscopic procedure when used in combination with routine EGB.

Animals↗

PubMed2001

Investigation of the biological mode of action of clerocidin using whole cell assays.

Clerocidin, a diterpenoid natural product, has been shown in vitro to inhibit DNA religation following cleavage by topoisomerase II. Herein, we characterize the efficacy and specificity of clerocidin in HeLa cells. Our results suggest that clerocidin recognizes topoisomerase II as its main intracellular target and binds to this enzyme prior to formation of the 'cleavable complex' with DNA. These pharmacological features attest to the promising chemotherapeutic potential of this natural product.

Anti-Bacterial Agents↗

PubMed2001

Profile of hepatocellular carcinoma in India: an insight into the possible etiologic associations.

BACKGROUND: Several etiologic factors including hepatitis viruses, alcohol and aflatoxin have been implicated in the pathogenesis of hepatocellular carcinoma (HCC). There is, however, limited information from the Indian subcontinent. METHODS: Seventy-four consecutive cases of HCC were studied. A detailed history, tests for hepatitis B virus (HBV; HBsAg, HBeAg, anti-HBe, IgG anti-HBc, anti-HBs and HBV-DNA), hepatitis C virus (HCV; anti-HCV and HCV-RNA) infection, liver histopathology and HBV-DNA integration by using Southern blot hybridization were studied. A p53 gene mutation was also studied by using PCR and single-strand conformation polymorphism. RESULTS: Hepatocellular carcinoma patients were predominantly males (mean age 49.5 +/- 14.0 years). Portal hypertension and cirrhosis were seen in 56 (76%) patients, more often (P < 0.05) in viral marker positive cases. Forty-five percent of patients had features of hepatic decompensation at presentation. Evidence of HBV infection was present in 53 (71%) patients. Twenty-six (49%) of these patients had either HBeAg + ve, HBV-DNA + ve (n = 12), or HBsAg - ve, HBV-DNA + ve (n = 14) forms of HBV infection. Hepatitis B virus DNA integration in the liver tissue was seen in 10 of 17 (59%) patients. Infection with HCV alone was detected in three (4%) and dual HBV and HCV infection in six (8%) patients. A majority (78.5%) of the chronic alcoholics had associated viral infection. The etiology of HCC remained undetermined in 15 (20%) patients. The p53 gene mutations were detected only in three of 21 (14%) liver tissues. Aflatoxin toxicity, oral contraceptive use or metabolic disorder were not seen. CONCLUSIONS: In India: (i) HBV infection is the predominant factor for the development of HCC, often related to mutant forms of HBV; (ii) a majority of the HCC patients have overt cirrhosis of the liver; and (iii) HCV and alcohol per se are uncommonly associated.

Aflatoxin B1↗

PubMed2001

Autoimmune hepatitis in the Indian subcontinent: 7 years experience.

BACKGROUND: Autoimmune hepatitis (AIH) is presumed to be rare in India. The present prospective study was carried out to determine the prevalence, clinical, biochemical and histological profile of patients with AIH in India. METHODS: Consecutive patients with chronic liver disease suspected to be AIH, were screened for antinuclear antibodies (ANA), antismooth muscle antibodies (ASMA), antimitochondrial antibody (AMA), and anti-liver kidney microsomal antibodies (anti-LKM-1). Serum protein electrophoresis and liver biopsy were done. Autoimmune hepatitis was diagnosed according to the International Autoimmune Hepatitis Group criteria. RESULTS: Fifty of 1358 (3.43%) patients with chronic liver disease were diagnosed as autoimmune liver disease; 39 with AIH, two with overlap syndrome, five with primary sclerosing cholangitis, and four with primary biliary cirrhosis. Twenty-nine patients were categorized as definite AIH and 10 as probable AIH. Autoimmune hepatitis was common in females (males : females 1:3), with a mean age of 31 +/- 17 years. Patients often presented with fatigue, jaundice and anorexia. Skin lesions (58%), joint symptoms (30%), and menstrual abnormalities (26%) were not uncommon. Mildly elevated alkaline phosphatase and hyper gamma globulinemia were seen in 78 and 91% patients, respectively. Eighty percent of patients were type I AIH, while 20% of cases remained unclassified. Histopathological changes included piecemeal necrosis (100%), plasma cell infiltration (91%), rosette formation (82%), and cirrhosis (76%). Overall mortality was 25% during a mean follow up of 15.7 +/- 17.0 months. CONCLUSIONS: Our results clearly demonstrate that: (i) AIH is not uncommon in India; and (ii) while the profile and spectrum of AIH resembles that seen in the West, Indian patients present late, often in a cirrhotic state.

Adolescent↗

PubMed2001

The ablation of atrial fibrillation with the loop catheter design: what we have learned from the animal model.

Ablation of chronic atrial fibrillation (AF) with the use of transcutaneous catheter ablation is yet to become a clinical tool. This article summarizes the development of the technology and the technique for the ablation of AF that was tested on the rapidly paced AF dog model. The current ablation technology using the standard ablation technique used in humans is not suitable for the creation of transmural contiguous linear lesions, and such technology is subjecting the patient to the prolonged procedures with considerable risk of complication. The use of the loop catheter design or other designs of ablation technology, which is specifically targeted for the creation of linear lesions, should be developed if the catheter approach for the ablation of AF is to succeed. This article describes the data available for the loop catheter design that is currently undergoing human feasibility studies.

Animals↗

PubMed2001

Dysembryoplastic neuroepithelial tumors: report of 10 cases from a center where epilepsy surgery is not done.

Dysembryoplastic neuroepithelial tumor (DNT) is a recently recognized tumor entity with distinctive clinicopathological features and an excellent long-term prognosis. We report 10 cases of DNT out of neurosurgical specimens sent for histopathological examination since 1994. Epilepsy surgery is not done at our center, and all the cases were sent with a clinical diagnosis of glioma. On histopathological examination, all the 10 cases contained the specific glioneuronal element. In 6 cases, glial nodules were noted in addition. This study therefore reports 4 cases of simple DNT and 6 cases of complex DNT. There was no nuclear atypia or mitosis in any of the cases. Proliferative index by PCNA varied from negative to <1%. It is very important to recognize this entity, as surgery cures the patient, and radiotherapy or chemotherapy is not required.

Adolescent↗

PubMed2001

Benign signet ring cell change with multilayering in the gallbladder mucosa--a case report.

We describe a case of benign signet ring cell change in the gallbladder mucosa. On histopathological examination of H&E-stained sections, the gallbladder epithelium showed multilayering. The epithelial cells were large, columnar to polygonal with a small round basal or eccentric nucleus and vacuolated cytoplasm, giving them a signet ring appearance. There was no nuclear atypia, hyperchromatism or mitotic activity. The cells showed uniform positivity with mucicarmine, PAS and Alcian blue stains. The cytoplasmic vacuolations were negative for fat stains (Oil red O and Sudan IV). On immunohistochemistry, the cells showed positivity with antibodies for pancytokeratin (PCK) and epithelial membrane antigen (EMA). A diagnosis of benign signet ring cell change with multilayering in the gall bladder mucosa was made. Thoroughly reviewing the literature, we found only one case of benign signet ring cell aggregates in the gallbladder mucosa documented earlier. The lesion is hereby reported because of the unique histomorphology and the diagnostic dilemma which can occur as a malignant change in situ has to be excluded.

Adult↗

PubMed2001

Radiation-induced and chemotherapy-induced pulmonary injury.

The management of cancer has continued to advance with the development of new chemotherapeutic agents and improved techniques of radiation therapy. Although new therapeutic approaches have improved survival in cancer patients, each form of intervention has the potential to produce adverse effects on normal host tissues. Some of these toxicities may be accentuated with combined modality therapy. The use of chemotherapy and radiation therapy, alone or combined, can be associated with clinically significant pulmonary toxicity. The pulmonary toxic effects of chemotherapy can be divided into (1) early onset, resulting in interstitial lung injury, and (2) late onset, with pulmonary fibrosis as a sequela. These toxic effects are frequently dose related but may be enhanced by radiation therapy. Similar to chemotherapy, radiation can produce acute or chronic lung injury depending on dose rate, duration, preexisting lung disease, and concomitant steroid use. Acute radiation injury typically occurs 2 weeks to 3 months after treatment and is usually limited to the irradiated field. Mild injury often resolves without treatment, whereas more serious injury results in fibrosis 6 to 12 months after treatment. Histopathologic evaluation of acute lung injury is no different from drug-induced injury, and damage to vascular endothelial cells and alveolar lining cells is seen. This article reviews and provides an update on the clinically important chemotherapy and radiation-induced pulmonary injuries, the pathologic mechanisms, where known, and the treatment advances that have occurred in this field.

Antibiotics, Antineoplastic↗

PubMed2001

Periampullary gangliocytic paraganglioma.

A33-year-old man presented with features of obstructive jaundice. Enterohepatic retrograde cholangiopancreatography examination revealed a periampullary growth. After pancreatoduodenectomy, histologic examination of the growth revealed three elements: a spindle cell element, large ganglion cells, and smaller paraganglioma-like cells arranged in small nests and groups. A diagnosis of gangliocytic paraganglioma was given. Gangliocytic paraganglioma is a rare benign duodenal tumor, with uncertain histogenesis. It is possible to identify the three components that are essential for its diagnosis on routine hematoxylin and eosin sections without the use of immunohistochemical markers. Because this lesion may present clinically as a periampullary carcinoma, it is important to recognize and diagnose this rare, but benign, entity.

Adult↗

PubMed2001

Geldanamycin inhibits NF-kappaB activation and interleukin-8 gene expression in cultured human respiratory epithelium.

Geldanamycin is a benzoquinone ansamycin with multiple pharmacologic properties. Recent data demonstrated that geldanamycin conferred protection in an animal model of inflammation-associated acute lung injury. In the current study, we investigated the effects of geldanamycin on interleukin (IL)-8 gene expression and nuclear factor (NF)-kappaB activation. Geldanamycin inhibited tumor necrosis factor (TNF)-alpha-mediated IL-8 gene expression in A549 human respiratory epithelial cells as measured by enzyme-linked immunosorbent assay and Northern blot analyses. In cells transiently transfected with an IL-8 promoter-luciferase reporter plasmid, geldanamycin inhibited TNF-alpha-mediated luciferase activity. Geldanamycin inhibited TNF-alpha-mediated NF-kappaB activation as measured by electromobility shift assays and transient transfections with a NF-kappaB-dependent luciferase reporter plasmid. In contrast, geldanamycin did not affect TNF-alpha-mediated degradation of the NF-kappaB inhibitory protein IkappaBalpha and did not block nuclear translocation of the NF-kappaB p65 subunit as measured by Western blot analyses. Geldanamycin added directly to nuclear extracts of TNF-alpha-treated cells reduced the formation of the NF-kappaB/DNA complex. These results demonstrate that geldanamycin inhibits TNF-alpha-mediated IL-8 gene expression in A549 cells by inhibiting activation of the IL-8 promoter. The mechanism of inhibition involves inhibition of NF-kappaB activation, which is independent of IkappaBalpha degradation or p65 nuclear translocation. Geldanamycin appears to directly inhibit the ability of NF-kappaB to bind DNA. The observed in vitro effects could account, in part, for the anti-inflammatory properties of geldanamycin observed in vivo.

Benzoquinones↗

PubMed2001

Intramedullary cavernous haemangioma.

A 35 years old male presented with episodic weakness of left upper limb followed by gradually progressive neurological deterioration. MRI revealed an intra medullary cervical cord angiomatous lesion. Histopathology revealed it to be cavernous haemangioma. A complete surgical removal of the haemangioma was carried out.

Adult↗

PubMed2001

Angio-access for haemodialysis--current perspective.

Vascular access for haemodialysis has seen many developments in recent times. Double lumen catheters introduced into wide bore veins have replaced the traditional Scribner shunt as temporary access thus reducing the complications and morbidity associated with it. Cuffed tunnelled internal jugular catheters and synthetic arteriovenous (AV) grafts usually made of polytetrafluoroethylene are the new additions to the vascular access armamentarium, but the AV fistula introduced in 1966 still remains the life-line for chronic haemodialysis patient. However, in elderly and diabetic patients, synthetic AV grafts are beneficial. The added advantage of synthetic grafts is short maturation time and multiple potential access sites. Access failure in 80% cases is due to venous stenosis and thrombotic episodes while infections or other complications are there in 20% cases. The complications of vascular access are not only a major cause of morbidity in haemodialysis patients but a major cost for the end stage renal disease programme. In western countries, access related morbidity accounts for almost 25% of all hospital stays for end stage renal disease patients and may contribute to as much as 50% of all hospitalisation cost. Access salvage includes prospective monitoring and treatment of outflow stenosis. The direct intra-access measure of blood flow by ultrasound dilution and duplex colour flow Doppler technique is the ideal method detecting venous outflow stenosis; however, conventional and digital subtraction angiography has an advantage, that total vasculature and blood flow may be visualised. The various treatment modalities for outflow stenosis include use of percutaneous transluminal angioplasty, stents and surgical correction. The lyses of secondary thrombosis can be done by surgical, medical and mechanical thrombolysis. The various methods being used to prevent graft stenosis include use of dipyridamole and radiation. The gene therapy holds promises for the future.

Catheters, Indwelling↗

PubMed2001

Pattern of cancer in Dayanand Medical College & Hospital, Ludhiana (a ten year retrospective study).

A ten year retrospective study was undertaken to ascertain the pattern and incidence of cancer in Ludhiana which is an industrial town with catchment area of Ludhiana consisting of Ludhiana distt., Sangrur, Jalandhar, Hoshiarpur, Faridkot, Ferozepur, Ropar, Kapurthala, some parts of Himachel Pradesh and Haryana. A total number of 56,565 biopsies were received for histopathological examinaiton in 10 years and 4,730 cases of cancer were diagnosed. The incidence of total malignant tumors was 8.36%. Females out numbered males in the incidence of cancer, with male to female ratio being 1:1.09. Most of the cancers were seen in the age group of 41-50 years. In females the two most common cancer sites were breast (21.07%) and cervix (19.4%) while in males hypopharynx--larynx (13.94%) and prostate (9.65%) were the most common sites of cancer.

Adult↗

PubMed2000

A specific activation of the mitogen-activated protein kinase kinase 1 (MEK1) is required for Golgi fragmentation during mitosis.

Incubation of permeabilized cells with mitotic extracts results in extensive fragmentation of the pericentriolarly organized stacks of cisternae. The fragmented Golgi membranes are subsequently dispersed from the pericentriolar region. We have shown previously that this process requires the cytosolic protein mitogen-activated protein kinase kinase 1 (MEK1). Extracellular signal-regulated kinase (ERK) 1 and ERK2, the known downstream targets of MEK1, are not required for this fragmentation (Acharya et al. 1998). We now provide evidence that MEK1 is specifically phosphorylated during mitosis. The mitotically phosphorylated MEK1, upon partial proteolysis with trypsin, generates a different peptide population compared with interphase MEK1. MEK1 cleaved with the lethal factor of the anthrax toxin can still be activated by its upstream mitotic kinases, and this form is fully active in the Golgi fragmentation process. We believe that the mitotic phosphorylation induces a change in the conformation of MEK1 and that this form of MEK1 recognizes Golgi membranes as a target compartment. Immunoelectron microscopy analysis reveals that treatment of permeabilized normal rat kidney (NRK) cells with mitotic extracts, treated with or without lethal factor, converts stacks of pericentriolar Golgi membranes into smaller fragments composed predominantly of tubuloreticular elements. These fragments are similar in distribution, morphology, and size to the fragments observed in the prometaphase/metaphase stage of the cell cycle in vivo.

Animals↗