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Biomedical subjects

R Mehrotra

Publications and source records attributed to R Mehrotra.

At least 37 records · Page 2Linked to original sources

Isolation and physical characterization of the MUC7 (MG2) mucin from saliva: evidence for self-association.

Saliva contains two major families of mucins (MG1 and MG2); the polypeptide of the smaller of these glycoproteins (MG2) has been assigned as the product of the MUC7 gene. In this study we have devised a rapid two-step procedure that recovers this glycoprotein essentially free of other components and in sufficient quantity to enable physical and self-interaction studies. Raw saliva was solubilized in 4 M guanidinium chloride and thereafter subjected to Sepharose CL-4B chromatography. The MG2-rich fraction was recovered free from the larger MG1 glycoproteins and also smaller proteins/glycoproteins (molecular mass less than 100 kDa). MG2 glycoproteins were finally purified by anion-exchange chromatography on Mono Q. The purity of the preparation was assessed by SDS/PAGE after radiolabelling of the molecules with [14C]acetic anhydride. Peptide mapping, N-terminal sequencing and amino acid analysis verified the polypeptide of the mucins as the MUC7 gene product. The isolated molecules were examined by electron microscopy and appeared as short flexible worm-like structures 30-120 nm in length. The distribution was heterogeneous, containing a major component with number-average and weight-average lengths of 52 and 55 nm respectively and a minor component with number-average and weight-average lengths of 94 and 98 nm respectively. We propose that the two differently sized populations represent monomeric and dimeric species of the mucins. Gel chromatography performed in 0.2 M NaCl indicated the presence of monomers, dimers and tetramers; an average molecular mass for the preparation was 192 kDa. However, in 4 M guanidinium chloride the molecular mass was 158 kDa and a similar molecular mass (155 kDa) was determined for the mucin preparation after reduction. These results suggest that the mucins might self-associate via a protein-mediated interaction. On the basis of the results a model is proposed for the self-association of the MUC7 mucin, which might be important for its biological function.

Acetic Anhydrides↗

Surgical experience with intracardiac myxomas: long-term follow-up.

BACKGROUND: Myxomas are the most common benign intracardiac tumors. This report summarizes our 20-year experience with these tumors. METHODS: Sixty-six patients (25 male) with a median age of 39 years (range, 6 to 70 years) underwent surgical excision of primary or recurrent intracardiac myxomas during the years 1976 to 1996. Symptom duration ranged from 2 to 8 months. There were 55 left atrial myxomas, 10 right atrial myxomas, and 1 biatrial myxoma. Three of the patients were in one family. The surgical approach comprised complete wide excision. RESULTS: There were two early deaths. Late follow-up is 89% (57/64) complete. There was one late death, which was not due to a cardiac cause. Echocardiography at a mean follow-up of 66.9 months (range, 7 to 241 months) showed no recurrence of sporadic myxomas. However, 2 of the 3 patients with familial myxomas had recurrence. CONCLUSIONS: Surgical excision of atrial myxoma gives excellent short-term and long-term results leading to eventual cure of nonfamilial myxomas. However, familial myxomas retain a strong tendency to recur even 20 years after excision.

Adolescent↗

A, B & H isoantigens in cervical lesions.

Expression of A, B and H isoantigens in cervical mucosa was demonstrated by specific red cell adherence test in 92 cervical lesions (40 chronic cervicitis, 12 dysplasia and 40 carcinoma cervix). Eighty percent cases of chronic cervicitis showed a moderate reaction. On the contrary, in carcinoma cervix, 75% cases were found to be SRCA negative. In dysplasia, the intensity of red blood cell adherence was found to be directly related to the degree of cellular differentiation. Study of A, B and H isoantigens might help in deciding the prognosis of dysplasia and/or early detection of malignancy.

ABO Blood-Group System↗

Interleukin 13 is secreted by human head and neck tumours and does not modulate their growth in vitro.

Expression of interleukin-13 (IL-13) has been examined in head and neck cancer cell lines. This interleukin was expressed by all human head and neck carcinoma cells studied, though in varying degrees. The effect of exogenous IL-13 on growth of squamous cell carcinomas of the head and neck cell lines was also studied. It was found that this cytokine did not modulate the proliferation of four cell lines studied. These results demonstrate that human squamous cell carcinoma of the head and neck secrete IL-13.

Carcinoma, Squamous Cell↗

"EXPATH" an expert system for pathology for the diagnosis of jaundice.

Computers are increasingly playing an important role in the field of medicine. A computer aided expert system has been developed for the differential diagnosis of jaundice. In this article the major features and application of this modular software are discussed.

Diagnosis, Computer-Assisted↗

Microfilariae identified in FNA of a thyroid nodule.

A patient presented with hyperthyroidism and a thyroid swelling, clinically thought to be malignant. Fine-needle aspiration of the thyroid nodule revealed microfilariae of Wuchereria bancrofti. After therapy the thyroid swelling subsided and the patient became euthyroid. The possible etiologic role of microfilariae in the genesis of the thyroid tumor and hyperthyroidism is discussed.

Animals↗

Hypokalemic metabolic alkalosis with hypomagnesuric hypermagnesemia and severe hypocalciuria: a new syndrome?

Bartter's and Gitelman's syndromes are characterized by hypokalemia, urinary potassium wasting, elevated plasma renin activity and aldosterone levels, normotension, and prostaglandinuria. They differ in that hypomagnesemia and hypocalciuria are universal in Gitelman's syndrome; 20% of cases of Bartter's syndrome have hypomagnesemia and hypercalciuria. We present a 44-year-old white man referred for hypokalemia. Clinical evaluation was unremarkable. He had hypokalemia (P(K), 2.8 to 3.0 mEq/L), hypochloremic metabolic alkalosis, mild azotemia (serum creatinine, 1.4 to 1.8 mg/dL; creatinine clearance, 59 mL/min), normocalcemia, marked persistent hypocalciuria (FE(Ca), 0.08% to 0.09%), and normal intact parathyroid hormone levels (51 pg/mL) and glucosuria. He had persistent hypermagnesemia (P(Mg), 2.1 to 2.8 mEq/L) with relative hypomagnesuria (FE(Mg), 3.2% to 5.2%) given the level of renal impairment and hypermagnesemia. Supine plasma renin activity and aldosterone levels were high (11 ng/mL/hr and 43 ng/dL, respectively). An excessive dietary intake of magnesium, including medications, was excluded. Studies were performed after withdrawing all medications for 8 days. A maximum water diuresis was established (an oral load of 20 mL/kg; stable Uosm, 120 mOsm/kg), and free water and solute clearances were studied at baseline and after sequential intravenous injections of 125 mg chlorothiazide and 40 mg furosemide. The patient had moderate renal impairment (technetium diethylene triamine pentacetic acid [DTPA] clearance, 35.4 mL/min/1.73 m2) and, in contradistinction to Bartter's and Gitelman's syndromes, sodium and water handling in the thick ascending limb of the loop of Henle and the distal tubule (fractional distal solute reabsorption) was normal, but there was evidence of a defect in the proximal tubule reabsorption (glucosuria, supranormal C(H2O) and high distal delivery). Hypomagnesuria and hypocalciuria appeared to be secondary to an increase in their absorption in the loop of Henle (increased excretion following furosemide). In conclusion, this combination of metabolic abnormalities has never been described. We postulate a proximal tubular defect in the absorption of NaCl leading to hypocalciuria, hypomagnesuria, and potassium wasting. Whether the tubular defect is primary or secondary to a renal parenchymal disease is, however, unclear.

Acute Disease↗

Aortic valve replacement with a homovital valve.

"Homovital" allografts (viable homografts) are a good substitute for native aortic valves. A case of aortic valve replacement with a homovital aortic allograft is reported along with the results of immunologic investigations. Postoperatively, there was no clinical or echocardiographic evidence of valve dysfunction, and immunologic tests did not show evidence of graft versus host reaction.

Aortic Valve↗

Diagnosis of human sarcocystis infection from biopsies of the skeletal muscle.

Sarcocystis is an uncommon parasitic infection. We report four cases that presented with lumps, pain in the limbs or a discharging sinus of unknown etiology. Microscopic examination of the excised tissue in all cases showed characteristic cysts of the sarcocystis parasite. A discussion of the identification and recognition of this uncommon infection from muscle biopsies is given.

Adolescent↗

Evaluation of healing and external tunnel histology of silver-coated peritoneal catheters in rats.

A previous study showed that silver-coating peritoneal catheters tended to decrease the incidence of early exit-site infections in rats. This study was designed to further evaluate the healing, biocompatability, and external tunnel morphology of standard and silver-coated catheters. Catheters were coated with silver by an ion beam-assisted process. Fourteen male Sprague-Dawley rats underwent implantation of either a standard or silver-coated double-cuff peritoneal catheter. Weekly observation and photographs documented exit-site characteristics. Erythema, exudate, loose fit, and poor hair growth were evidence of an inflamed exit. Overt infection was indicated by the presence of three or more of the following: erythema, purulent exudate, exuberant granulation tissue, loose fit, and poor hair growth. Animals were sacrificed at six weeks, and catheters were removed and processed for histology of the external tunnel. Multiple measurements were taken using a Filar eyepiece, and data were expressed as a mean of several readings. Inflammation, vascularity, and fibrosis were judged semiquantitatively. At the end of six weeks, six of the seven exits of the silver catheters showed excellent healing, while one exit site had signs of excessive inflammation. Four of the exit sites of the standard catheters healed well, two were inflamed, and one was overtly infected. The sinus tract of the standard and silver catheters had similar characteristics: keratinized and nonkeratinized epithelium lined the external part of the sinus tract and merged into granulation tissue. A fibrous sheath was noted in some sinus tracts between the granulation tissue and the cuff. The cuff evoked a foreign body reaction, with fibrosis, multiple giant cells, and vascularization. Poorly healing or infected sinus tracts had highly vascular granulation tissue with overlying exudate. The cuff of these catheters had marked inflammation and scanty giant cells, although collagen bundle thickness was similar to the well-healing catheters. In conclusion, silver-coating potentially enhances healing of the exit sites of peritoneal catheters. Additionally, the similarity of the tunnel histomorphology of standard and silver catheters confirms the favorable biocompatibility of silver.

Animals↗

Asymptomatic visceral leishmaniasis in a child with acute lymphoblastic leukaemia.

Visceral leishmaniasis was detected incidentally in a patient with acute lymphoblastic leukaemia in remission, during maintenance therapy. Absence of fever, a normal haemogram, normal serum globulins, a negative serology and testicular involvement were the hallmarks of the case. Treatment with sodium stibogluconate (20 mg/kg for 55 days) failed. Subsequent therapy with pentamidine resulted in complete parasite clearance. Prolonged therapy with pentavalent antimony compounds or a higher dose of second line drugs such as pentamidine are recommended for complete clearance.

Antimony Sodium Gluconate↗

Spectrum of liver disease and duck hepatitis B virus infection in a large series of Chinese ducks with hepatocellular carcinoma.

The striking difference in the geographical distribution of liver cancer in ducks raised the question of whether duck hepatitis B virus (DHBV), like mammalian hepadnaviruses, could be an oncogenic agent. Hepatocellular carcinomas (HCCs) have been found only in domestic ducks in Qidong, China, where hepatitis B virus infection and aflatoxin B1 (AFB1) are both risk factors and where a high frequency of human HCCs has been reported. To date, the study of liver pathology occurring in Chinese ducks has been hampered by the small number of samples available. We describe here a series of 59 Chinese brown duck livers that were collected in Qidong more than 20 years ago and formalin fixed. Thirty-six HCCs, which ranged from well-differentiated trabecular to highly anaplastic type, were identified in relatively young ducks (average age, 3.3 years). Several unique features not previously reported, such as tumor giant cells, tumor necrosis, tumor thrombi in blood vessels, and inactive cirrhosis, were observed. Bile ductule proliferation, known to be a prominent feature of AFB1 exposure in ducks, was present in 86% of livers. Using polymerase chain reaction (PCR) and two primer pairs, located within conserved portions of the DHBV S and C genes, we demonstrated the presence of DHBV DNA in 23 of 34 HCCs analyzed (68%). The spectrum of liver pathology that we report in brown ducks from Qidong was never observed in Pekin ducks of the same age chronically infected with DHBV and followed under controlled conditions outside China, suggesting that causative factors other than virus infection may be involved in duck liver carcinogenesis observed in this area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Duck hepatitis B virus infection, aflatoxin B1 and liver cancer in domestic Chinese ducks.

The oncogenicity of Duck hepatitis B virus (DHBV) is unclear since hepatocellular carcinomas (HCCs) have been reported only in domestic ducks in Qidong, an area of China where hepatitis B virus (HBV) and aflatoxin B1 (AFB1) are risk factors for liver cancer in man. In order to better define the association between DHBV infection, AFB1 and HCC we analysed a series of 16 duck liver samples collected from local farms in Qidong. HCC was found in eight and cirrhosis in one of these samples. Furthermore bile duct proliferation, characteristic of AFB1 exposure in ducks and other animal species, was found in these ducks. Integration of DHBV DNA into cellular DNA was observed in only one out of four DHBV positive HCCs, indicating that viral integration is not prerequisite for tumour development. In four remaining HCCs the polymerase chain reaction (PCR) failed to show any DHBV DNA suggesting that liver tumours do occur in polymerase chain reaction (PCR) failed to show any DHBV DNA suggesting that liver tumours do occur in these ducks in the absence of DHBV infection. In addition, AFB1-DNA adducts were detected by hplc-immunoassay in one such DHBV-negative tumour. In summary we demonstrate that risk factors other than DHBV, including AFB1 exposure, may be important in duck liver carcinogenesis in Qidong.

Aflatoxin B1↗

Absence of p53 mutation at codon 249 in duck hepatocellular carcinomas from the high incidence area of Qidong (China).

Dietary aflatoxin and hepatitis B virus infection may play a role in generating the p53 tumor suppressor gene codon 249 hotspot mutation found in human hepatocellular carcinomas (HCCs) from Qidong (China) and southern Africa. No data are available on the HCC site-specific mutation of the p53 gene in hepadnavirus-infected animals exposed to AFB1. We have searched for the presence of p53 gene codon 249 mutations in both duck hepatitis B virus (DHBV) positive and negative HCCs of domestic ducks from Qidong, where the human p53 hotspot is so prevalent, as well as in duck HCCs experimentally induced by AFB1. Direct sequencing of DNA amplification products encompassing p53 codon 249 did not reveal any mutations in 11 HCCs from Qidong ducks, regardless of the status of DHBV infection. In addition no mutation was detected in four HCCs from AFB1-treated ducks. This contrasts with the human data; however, in humans, the mutation and the preferential binding of AFB1 to codon 249 occurs at the third nucleotide G, while in duck, the codon 249 lacks this G residue. The DNA sequence of adjacent codons is also different in the two species even though the amino acid sequence is identical. This may explain the low frequency of mutation we have observed. In addition, species differences in metabolism and DNA repair could influence the occurrence of codon 249 mutations.

Aflatoxin B1↗