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Biomedical subjects

A Goel

Publications and source records attributed to A Goel.

At least 145 records · Page 8Linked to original sources

Putative membrane components of signal transduction pathways for ambient pH regulation in Aspergillus and meiosis in saccharomyces are homologous.

The zinc finger regions of the Aspergillus nidulans PacC transcription factor, mediating regulation of gene expression by ambient pH, and the Saccharomyces cerevisiae Rim1p transcription factor, mediating control of meiosis and invasiveness, are homologous and both transcription factors undergo proteolytic processing of the C-terminus for conversion to the functional form. In both cases, functioning of a signal transduction pathway involving several gene products is a necessary prerequisite for processing. We now show that the Aspergillus PalI pH signal transduction component is homologous to the Saccharomyces Rim9p meiotic signal transduction component throughout a region containing four hydrophobic, putative membrane-spanning segments. This suggests that PalI might be a membrane sensor for ambient pH. Deletion of the palI gene established that the less extreme phenotype of palI mutations compared with mutations in the other five genes of the pH signalling pathway is a general feature of palI mutations.

Amino Acid Sequence↗

Spontaneous cerebrospinal fluid (CSF) rhinorrhoea in spongiform dysplasia of the cranium: an unusual presentation of neurofibromatosis.

A 20-year-old woman with neurofibromatosis presented with CSF rhinorrhoea. Spongiform dysplasia of the cranium was found. The dysplastic bone contained CSF. The exact site of the CSF fistula into the calvarium and into the paranasal sinuses could not be detected on investigation but nasal packing of the ethmoid and sphenoid sinuses controlled the rhinorrhoea. The unique features of this case are presented along with a brief review of the literature.

Adult↗

Multilayer reconstruction of the anterior cranial fossa floor.

A case is described where a reconstruction of a complex defect in the floor of anterior cranial fossa was successfully carried out using multiple layers of vascularised pedicle flaps. The 42-year-old male patient had previously undergone multiple surgical procedures for persistent cerebrospinal fluid (CSF) rhinorrhoea following a vehicular accident 16 years previously. The extensive vascular supply to the layers of the scalp, pericranium, temporalis muscle and its fascial coverings was exploited in fashioning the flaps.

Adult↗

Activation of H+-ATPase by hypotonicity: a novel regulatory mechanism for H+ secretion in IMCD cells.

The effect of hypotonicity on H+-ATPase activity was examined in cultured inner medullary collecting duct (mIMCD-3) cells. mIMCD-3 cells were grown to confluence, loaded with 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF), and assayed for H+-ATPase activity measured as the Na+- and K+-independent intracellular pH (pHi) recovery following an acid load. Exposure of mIMCD-3 cells to a hypotonic solution (150 mosmol/kgH2O) increased pHi recovery by approximately 350% (P < 0.0001). This effect was inhibited by diethylstilbestrol (an inhibitor of H+-ATPase) and was not dependent on external K+, indicating lack of involvement of H+-K+-ATPase. H+-ATPase activation was acute, independent of cell calcium, and was not secondary to Cl- channel activation. The magnitude of H+-ATPase upregulation was dependent on the osmolarity of the media, with maximum stimulation at 150 mosmol/kgH2O. H+-ATPase upregulation in hypotonicity was significantly blocked in the presence of staurosporine or calphostin C or in cells pretreated with phorbol 12-myristate 13-acetate (PMA), indicating involvement of protein kinase C. Hypotonicity inhibited the Na+/H+ exchanger activity in mIMCD-3 cells, indicating that its stimulatory effect is specific to H+-ATPase. In conclusion, a novel regulatory mechanism of H+-ATPase by hypotonicity is described. The increased H+-ATPase activity in hypotonicity may be responsible for increased HCO-3 reabsorption and maintained acid-base homeostasis in hyposmolar states.

Ammonium Chloride↗

Basilar invagination: a study based on 190 surgically treated patients.

OBJECT: The authors analyzed the cases of 190 patients with basilar invagination that was diagnosed on the basis of criteria laid down in 1939 by Chamberlain to assess the appropriate surgical procedure. METHODS: Depending on the association with Chiari malformation, the anomaly of basilar invagination was classified into two groups. Eighty-eight patients who had basilar invagination but no associated Chiari malformation were assigned to Group I; the remainder of the patients, who had both basilar invagination and Chiari malformation, were assigned to Group II. The principal pathological characteristic was observed to be direct brainstem compression due to odontoid process indentation in Group I and a reduction in posterior cranial fossa volume in Group II. CONCLUSIONS: Despite the anterior concavity of the brainstem in both groups, transoral surgery was the most suitable procedure for those patients in Group I and decompression of the foramen magnum was found to be appropriate for patients in Group II. After surgical decompression, a fixation procedure was found to be necessary in most Group I cases, but only in a small minority of Group II cases.

Adolescent↗

Use of Gigli saw.

Explore the source record for details and available documents.

Craniotomy↗

Mitoxantrone, mitomycin-C, methotrexate combination chemotherapy with radiotherapy and/or surgery in stage III (T4B, NO-2, M0) breast cancer.

Results of primary surgery with or without locoregional radiotherapy (LRRT) are poor in stage III (T4b, NO-2, M0) breast cancer. Combination of mitoxantrone, mitomycin-c and methotrexate (MMM) has been reported to be as efficacious as doxorubicin based protocols with advantages of reduced nausea, vomiting, alopecia and cardiotoxicity. We tested MMM chemotherapy with LRRT and surgery in locally advanced breast cancer (LABC) with a view to assess response, survival, breast conservation, cost and toxicity. Fifty two previously untreated patients were given Mitoxantrone: 8 mg/m sq by infusion on days 1 and 21, Mitomycin-C: 8 mg/m sq by infusion on day 1 and Methotrexate: 35 mg/m sq i.v. on days 1 and 21. Cycles were repeated every 42 days. After 3 cycles LRRT was given if lump reduced to less than 2 cms. Otherwise patients were subjected to modified radical mastectomy (MRM) or radical mastectomy (RM). Following this 3 more cycles of chemotherapy were given. Patients with soft tissue, skin or heavy nodal involvement also received LRRT. Tamoxifen 20 mg daily was prescribed at the end of chemotherapy to postmenopausal patients. Complete/partial responses were seen in 5 and 26 patients, respectively after chemotherapy giving an overall response of 59.5%. Twenty four patients each had LRRT and MRM/RM. Responses could be significantly enhanced by LRRT/and or surgery. Nineteen out of 25 relapses were at distant sites. Breast conservation was achieved in 24/52 (46%) patients. Three year disease free and overall survival was 54% and 65%, respectively. There was 1 toxic death. Severe prolonged myelosuppresion was seen in those who also received LRRT. Mucositis, alopecia, nausea and vomiting were minor problems. Overall, combination was less expensive than doxorubicin based protocols.

Adult↗

Organophosphate poisoning: predicting the need for ventilatory support.

The present study evaluated 103 consecutive patients of organophosphate poisoning with special reference to the need for ventilatory support. Of 103 patients, 36(34.95%) required assisted ventilation. The need for ventilatory support was significantly more with greater time duration for institution of specific treatment, low level of sensorium at admission, pin-point pupils and generalized fasciculations, presence of convulsions, presence of respiratory insufficiency at admission, and higher initial atropine requirement for atropinization. The study also proposes a system of grading of severity, modified from the existing systems proposed.

Adolescent↗

Salivary gland tumors after childhood radiation treatment for benign conditions of the head and neck: dose-response relationships.

We have investigated the dose-response relationships for the incidence of salivary gland tumors in a cohort of 2945 individuals who were irradiated as children between 1939-1962. Most of the patients were treated to reduce the size of their tonsils and adenoids. The mean dose to the salivary glands (+/-SD) was 4.2 +/- 1.7 Gy. Eighty-nine patients developed 91 salivary gland neoplasms; 22 had single malignancies, 64 had single benign neoplasms, 2 developed two separate benign neoplasms, and 1 developed a single neoplasm but did not have surgery. The majority (81 of 89) of the patients developed neoplasms in the parotid glands. Mucoepidermoid carcinomas were the most common malignancy and mixed (pleomorphic) adenomas were the most common benign neoplasm. For all salivary gland tumors, the excess relative risk per gray (ERR/Gy) was 0.82; however, the 95% confidence interval was wide (0.04, upper bound indeterminate). The trend was determined principally by benign tumors, as there was no dose-response relationship for salivary gland cancer, although there were too few cases to draw definitive conclusions. Overall, our study provides support for an association between salivary gland tumors and radiation exposure. Although most salivary gland tumors are benign and are usually readily detected, they may cause morbidity, and people who have been irradiated in the area should be monitored for their occurrence.

Adenoids↗

Ala217 is important for the catalytic function and autoactivation of prostate-specific human kallikrein 2.

Prostate-specific human kallikrein, hK2, is a serine protease found in prostate tissues that has 78% amino acid sequence identity with prostate-specific antigen (PSA). We have previously reported the affinity purification of hK2 heterologously expressed in a hamster cell line and demonstrated an arginine-restricted substrate specificity. Here, we describe the cloning, expression, purification, and enzymatic activity of a mutant form of hK2 containing an alanine to valine substitution at residue 217 ([Val217]hK2). This mutant form was secreted into the serum-free spent media of recombinant cells as the stable proenzyme form ([Val217]phK2). Mild trypsin treatment was used to convert [Val217]phK2 to the active form, which had reduced catalytic function compared to the wild-type hK2. Kinetic studies using the chromogenic substrate D-H-Pro-Phe-Arg-4-nitroanilide showed that [Val217]hK2 has significantly decreased substrate binding, with a K(m) of 4200 microM compared to 11 microM for wild-type hK2. The k(cat) for [Val217]hK2 was more than 100-fold lower than for hK2. hK2, but not [Val217]hK2, was able to activate [Val217]phK2. [Val217]hK2 also showed altered specificity on a synthetic peptide substrate compared to wild-type hK2, which exhibited partial hydrolysis at a PSA chymotrypsin-like cleavage site as well as the trypsin-like site cleaved by hK2. These results indicate that Ala217 is a key residue affecting the catalytic properties of hK2.

Alanine↗

Increased nitric oxide production accompanied by the up-regulation of inducible nitric oxide synthase in vascular endothelium from patients with systemic lupus erythematosus.

OBJECTIVE: To investigate whether systemic lupus erythematosus (SLE) is accompanied by increased serum nitrite levels, whether active compared with inactive disease is associated with greater nitric oxide (NO) production, and whether endothelial cells or keratinocytes serve as cellular sources of NO by virtue of their increased expression of either constitutive nitric oxide synthase (cNOS) or inducible NOS (iNOS). METHODS: Fifty-one serum samples (46 from patients with SLE) were analyzed for NO production by measuring nitrite levels in a calorimetric assay. Skin biopsy samples from 21 SLE patients and 11 healthy volunteers were evaluated immunohistochemically, using monoclonal antibodies, for endothelial cell and keratinocyte cNOS and iNOS expression. RESULTS: Serum nitrite levels were significantly elevated in the 46 patients with SLE (mean +/- SEM 37 +/- 6 microM/liter) compared with controls (15 +/- 7 microM/liter; P < 0.01), and were elevated in patients with active SLE compared with those with inactive disease (46 +/- 7 microM/liter versus 30 +/- 7 microM/liter; P < 0.01). Serum nitrite levels correlated with disease activity (r = 0.47, P = 0.04) and with levels of antibodies to double-stranded DNA (r = 0.35, P = 0.02). Endothelial cell expression of iNOS in SLE patients (mean +/- SEM score 1.5 +/- 0.2) was significantly greater compared with controls (0.6 +/- 0.2; P < 0.01), and higher in patients with active disease compared with those with inactive SLE (1.7 +/- 0.2 versus 1.2 +/- 0.2; P < 0.01). Keratinocyte expression of iNOS was also significantly elevated in SLE patients (0.9 +/- 0.1) compared with controls (0.4 +/- 0.1; P < 0.001). With regard to expression of cNOS, there were no differences between patients with active SLE, those with inactive SLE, and normal controls in either the vascular endothelium or the keratinocytes. CONCLUSION: NO production is increased in patients with SLE, and 2 potential sources of excessive NO are activated endothelial cells and keratinocytes via up-regulated iNOS.

Adult↗

Recognition of the parasite infected cell surface determinants by homologous antiserum raised against infected cell membranes.

Identification of neo-antigenic determinant(s) on parasite infected cell surface is important to control intracellular infections. Such determinant(s) on the surface of intact Plasmodium berghei infected erythrocytes have not been conclusively demonstrated. To generate polyclonal antiserum selectively recognizing the parasite infected cell surface determinant(s), in natural state, we have examined the efficacy of the homologous immunizations, in BALB/c mice, with the membrane rich preparation of: i) erythrocytes in vivo infected with Plasmodium berghei and, ii) macrophages in vitro infected with Leishmania donovani. Anti-infected erythrocyte membrane antiserum specifically recognized, albeit at low level, the infected cell surface as determined by flow cytometry and immunoelectron microscopy. Immunoprecipitation of radiolabeled antigens revealed at least three parasite proteins of > 205 kDa, 160 kDa and 100 kDa specifically present on infected erythrocyte surface. Normal uninfected erythrocytes did not react with the antiserum. Anti-L. donovani-infected macrophage membrane antiserum also recognized only infected macrophage surface and not the normal macrophages. Thus, the approach may find wide application in delineating disease specific determinant(s) on the infected cell surface, particularly to those where animal models are available.

Animals↗

Vascularized pedicled laminoplasty.

BACKGROUND: Various advantages of a laminoplasty over the conventional laminectomy have been listed in the recent literature. An alternative method of vascularized pedicled laminoplasty is described in this report. METHODS: A linear cut is made in the laminae in their lateral aspects and two or more laminae are elevated as a flap and pedicled on supraspinous, interspinous, and interlaminar ligaments. The procedure was performed in 10 cases where surgery was performed for spinal intradural pathology. The ages of these patients ranged from 21 to 60 years. RESULTS: In an average observation period of 8 months, no demonstrable resorption of the laminar flap was observed in any case. None of the patients complained of any additional discomfort, pain, or deformity that could be related to the laminoplasty. CONCLUSIONS: Laminoplasty using laminae with a vascularized pedicle as described may be better tolerated by the patient; the segment seems to be more resistant to infection and radiotherapy. It is a simple, safe, and stable alternative to the procedures of laminoplasty previously described. No sophisticated instrumentation, prosthetic material, or technically complex maneuvers are required to harvest and reposition the laminar flap.

Adult↗

Versatility of Inoue balloon catheter.

Inoue rubber nylon single balloon catheter is being used worldwide for performing balloon mitral valvuloplasty (BMV). The popularity of Inoue balloon is attributed to its self-positioning configuration, size-adjustability, rapid inflation-deflation sequence and the ease of performance. We report its use in performing various non-mitral interventions. Its utility in treating patients with mitral stenosis and combined mitral and tricuspid stenosis is well established. Seventeen patients with valvular pulmonic stenosis (age 32+/-16 years; 11 males and 6 females) achieved significant reduction of peak systolic gradient (PSG) from 125+/-28 to 32+/-16 mmHg (P<0.005). Four patients with inferior vena-cava obstruction (age 20-48 years; 3 males and 1 female) derived symptomatic benefit following successful dilatation. Inoue balloon was used to create percutaneous pericardial window in four cases (age 43-68 years; 2 males and 2 females) of recurrent pericardial collection secondary to carcinoma lung/breast, thus alleviating the symptoms of tamponade. One patient each with coarctation of aorta (32 years, male), discrete subaortic membrane (16 years, female), and critical valvular aortic stenosis (13 years, male) derived immediate hemodynamic improvement with Inoue balloon dilatation. No major complications were encountered. We conclude that Inoue balloon can be used to successfully manage various stenotic lesions.

Adolescent↗

Plant cell biodegradation of a xenobiotic nitrate ester, nitroglycerin.

The ability of plants to metabolize the xenobiotic nitrate ester, glycerol trinitrate (GTN, nitroglycerin), was examined using cultured plant cells and plant cell extracts. Intact cells rapidly degrade GTN with the initial formation of glycerol dinitrate (GDN) and the later formation of glycerol mononitrate (GMN). A material balance analysis of these intermediates indicates little, if any, formation of reduced, conjugated or cell-bound carbonaceous metabolites. Cell extracts were shown to be capable of degrading GTN with the simultaneous formation of GDN in stoichiometric amounts. The intermediates observed, and the timing of their appearance, are consistent with a sequential denitration pathway that has been reported for the microbial degradation of nitrate esters. The degradative activities of plant cells are only tenfold less than those reported for bacterial GTN degradation. These results suggests that plants may serve a direct degradative function for the phytoremediation of sites contaminated by organic nitrate esters.

Biodegradation, Environmental↗

Fatal tumoural haemorrhage following decompressive craniectomy: a report of three cases.

Three cases of large and deep seated anaplastic cerebral glioma were treated by bone and dural decompression. The patients worsened suddenly within 12 h of surgery and later died. Postmortem examination revealed a large intratumoural clot in each case. The effects of decompression and the probable causes of fatal bleeding are analysed in this report.

Adolescent↗

A shunting procedure employing cannulation of the lumbar theca through the meningocele sac.

An alternative thecoperitoneal shunting procedure is described to counter the problem of cerebrospinal fluid (CSF) fistula following surgery for meningocele and related conditions. The lumbar end of the shunt traverses the meningocele sac. The procedure was effectively employed to deal with postoperative CSF fistula in two cases operated on earlier for lipomeningomyelocele.

Catheterization↗