Unusual enhancement on gadolinium-enhanced MRI in a case of primary cerebellar lymphoma.
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Biomedical subjects
Publications and source records attributed to S Gupta.
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Recent evidence suggests that high rates of schizophrenia in first- and second-generation immigrants could be due to exposure to environmental factors such as viral infections in the host country. These findings are discussed alongside parallel data relating to other diseases such as multiple sclerosis and diabetes mellitus. It is argued that in each case the interaction between the environmental agent and constitutional factors related to the immune system need to be considered.
Myelin basic protein (MBP)-specific T-cell lines from patients with multiple sclerosis (MS) and healthy controls were analyzed for the expression of CD45 isoforms and adhesion molecules. In the multiple sclerosis group, 22 of 24 MBP-specific T-cell lines were CD4+. Two distinct patterns were observed with regard to CD45 isoform expression. Pattern I showed dual expression of CD45 isoforms (CD4+CD45RA+CD45RO+CD29+) and Pattern II included cells with a single CD45 isoform (CD4+CD45RA-CD45RO+CD29+). All 10 cell lines from healthy controls were CD4+ and displayed Pattern II (CD4+CD45RA-CD45RO+CD29+). The dual expression of CD45 isoform in T-cell lines from MS was stable, did not represent a transition stage from CD45RA to CD45RO, and was cell-cycle independent. All cell lines from MS and controls expressed increased levels of LFA-1 (CD11a), LFA-2 (CD2), LFA-3 (CD58), ICAM-1 (CD54), and VLA-4 (CDw49d). These data show the presence of unique MBP-specific T cells (CD4+CD45RA+CD45RO+CD29+) that might play a role in the pathogenesis of MS.
P-glycoprotein, a 170-kd glycoprotein encoded by the MDR 1 gene, is a member of a highly conserved superfamily of ATP-binding cassette (ABC) transport proteins. It shares extensive homology with numerous bacterial and eukaryotic ABC transport proteins. P-glycoprotein acts as an energy-dependent efflux pump that appears to transport structurally diverse agents ranging from ions to peptides. P-glycoprotein (P-gP) has been implicated as playing a role in multidrug (MDR) resistance in cancer, chloroquine-resistant Plasmodium falciparum infection, and possibly human immunodeficiency virus-1 (HIV-1) resistance to nucleoside compounds. A number of normal tissues in humans and rodents have been shown to express high levels of P-gp. The expression and function of P-gp in cells of the immune system have been explored in the past 2 years. This review presents a state of the art regarding the expression, regulation, and function of Pgp in cells of the immune system. In addition, its alteration in aging and HIV-1 infection is reviewed. A possible physiologic role of P-gp in cytokine secretion, antigen processing/presentation, and effector functions is also discussed.
Nineteen patients with recurrent high grade gliomas were treated in a phase I/II trial with aggressive debulking of the tumor, mitogen activated IL-2 stimulated peripheral blood lymphocytes (MAK cells), and rIL-2. Phytohemagglutin (PHA) was introduced into the tumor site in 16 patients prior to implanting MAK cells and IL-2 in an attempt to trigger more effective lysis of the tumor in vivo. In vitro both TNF bioactivity and cytolytic activity of long term cultured MAK (LMAK) cells were dramatically enhanced by adding PHA to the cultures of these activated PBL. Three of eleven patients (27%) had a decrease in size of the enhancing lesion on CT and/or MRI. Seven (37%) patients clinically improved. Median survival after therapy was 30 weeks. PHA was shown to be safe in vivo and more effective than IL-2 triggering enhanced effector function in vitro.
Optic nerve (ON) damage especially from papilloedema can be prevented with timely detection. The detailed ocular and radiographic status of 33 unoperated craniosynostosis (CS) was documented prospectively; the ON was also assessed by flash VER and A-scan echography for ON thickness. Fluorescein angiography (FA) was done for all suspected and early papilloedemas. ON involvement diagnosed in 10/33 showed highly significant correlations with multiple suture synostoses (p = 0.004) and exorbitism (p < 0.001). VER latency was increased in all 5 ON atrophies; and also in 1/5 papilloedemas without atrophic changes, urgent surgery in which reversed VER changes, and vision later improved from 6/60 to 6/9. FA was valuable for confirming the clinical diagnosis of the earliest papilloedemas; the FA also returned to normal with immediate therapy along with reversal of the clinical picture. ON echography especially helped in monitoring regression of disc oedema. Ours seems the first report especially in CS where a critical follow-up of all above parameters in 21 operated/33 could objectively establish the role of each investigation in conjunction with careful clinical monitoring especially of the ON head. Such comprehensive evaluation should help reduce the blindness often seen in such children.
A case of painful bilateral hip effusions resolving spontaneously in the diuretic phase of steroid responsive nephrotic syndrome in a 6-year-old girl is reported.
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Retrospective evaluation of MR images of nine intraspinal dermoid (n = 4) and epidermoid (n = 5) tumours was undertaken. T1-weighted images were available in all the patients while proton density (PD) and T2-weighted images were available in seven patients. Except for one lesion (only T1-weighted images were available in this case), all the lesions were clearly delineated on MR images. Most (5 out of 7) were better appreciated on T1- and PD-weighted images than on T2-weighted images. On T1-weighted images, the epidermoids were either iso- to mildly hypointense to the cord (n = 3), isointense to CSF (n = 1) or markedly hyperintense (n = 1). On the PD images, the epidermoids were either isointense to cord (n = 3) or markedly hyperintense (n = 1). All the lesions were iso- to hyperintense to CSF on T2-weighted images. Of the four dermoids three showed a mixed intensity pattern on all sequences; the dominant component gave short T1 and short T2 values, consistent with fat. The fourth lesion showed homogenous material with a signal intensity intermediate between that of CSF and cord on T1-weighted images. Dermal sinus tracts were present in four of the nine patients; three patients had an intraspinal component. This study shows that although MR imaging is excellent for their detection, it cannot differentiate the two tumour types.
Transplacental passage of fluorides was studied in 25 randomly selected neonates. Blood samples collected simultaneously from the mother and the umbilical cord showed that average fluoride concentration in the cord blood was 60% of that in mother's blood. When concentration in the mother's blood exceeded 0.4 ppm, the placenta acted as a selective barrier.
To understand the mechanism for the expulsion of Nippostrongylus brasiliensis from rats, age-dependent variations in the metabolism of reactive oxygen species in the parasite and the host intestines were examined. N. brasiliensis showed an age-dependent increase in its susceptibility to xanthine-xanthine oxidase and t-butyl hydroperoxide generated oxidants as well as to H2O2. Protection obtained with several scavengers suggested that the worms were damaged by the combined action of oxidants generated by the in vitro systems employed. The level of superoxide dismutase in the nematode and its release into the surroundings exhibited a marked depression with advancement of age. No such alteration was, however, recorded for catalase and glutathione peroxidase. An appreciable decrease in the level of reduced glutathione in older N. brasiliensis appears to render them prone to oxidant attack. The rat intestines, on the other hand, exhibited an appreciable depression in catalase and a reduced glutathione content with progress of the infection. Vitamin E levels were elevated. The release of O2-. and H2O2 by the intestines was also found to be greater during later stages of the infection. The combined effect of the changes observed in N. brasiliensis and in the rat intestines may be at least partly responsible for expulsion of the nematode from the rats after day 10.
Hepatocytes transplanted into the host liver engraft promptly, retain normal function, and survive indefinitely. Although intrasplenic transplantation is effective in delivering hepatocytes to the liver, to define potentially limiting complications, we studied its safety in normal, cirrhotic, and partial portal vein-ligated rats. In normal rats, portal pressures increased severalfold after hepatocyte transplantation but returned to normal within 3 weeks. In contrast, in portal hypertensive rats with partial portal vein ligation or cirrhosis, portal pressures were either unchanged or increased less after hepatocyte transplantation. However, more transplanted cells migrated to the lungs along with a rise in right atrial pressures in portal hypertensive rats. Further quantitative studies using 111Indium-labeled hepatocytes showed that intrasplenic retention of transplanted hepatocytes was similar in all animal groups. Intrahepatic cell translocation was comparable in normal and cirrhotic rats, whereas fewer cells migrated to the liver in partial portal vein-ligated rats. The most remarkable difference, however, was significantly greater intrapulmonary translocation of hepatocytes in portal hypertensive rats, which was presumably related to portosystemic shunting. These results indicate that because intrasplenic hepatocyte transplantation induces only temporary portal hypertension in normal subjects, potential strategies to augment liver repopulation could include repeated cell transplantation. This should be useful for optimizing the results of ex vivo gene therapy, or other hepatocyte-based therapies. However, the hepatic and portal hemodynamic status requires careful evaluation in portal hypertensive or cirrhotic subjects if serious complications are to be avoided.
Twenty-six patients with prostatic cancer were treated with courses of epirubicin at 3-week intervals, starting at an initial intravenous dose of 75 mg/m2. All patients had progressive disease after orchiectomy and/or antiandrogen therapy and had measurable soft tissue lesions. There were three partial responders (response rate: 12%; 95% confidence limits: 4-29%). Major toxicity was myelosuppression, and there were two drug-related deaths. Epirubicin in this dose and schedule cannot be recommended for treatment of prostatic cancer.
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A rare case of atlanto-axial block vertebra and fusion of anterior arch with the dens, with instability at the atlanto-occipital joint, is reported. The literature is briefly reviewed.
A series of 335 children with antenatally diagnosed hydronephrosis which persisted after the postnatal period was prospectively assessed. Idiopathic hydronephrosis (85 patients) and pelviureteric junction obstruction (73 patients) were the commonest conditions. All patients with idiopathic hydronephrosis were managed conservatively; 87% have had a complete resolution of hydronephrosis and 13% have remained unaltered. No patient managed conservatively has shown a deterioration in renal function.
Since 1980, the automatic implantable cardioverter defibrillator (ICD) has evolved as effective therapy for prevention of sudden cardiac death following documented sustained ventricular tachycardia or fibrillation. During a 5-year period, 412 ICD devices were implanted at the University of Michigan Hospitals with a wound complication rate of 4.1%. In this group, there were 13 infections, 3 erosions of the generator pocket, and 1 wound hematoma. Of the 16 patients with infection or erosion, 12 patients were treated with a rectus abdominis muscle flap closure and 4 with ICD generator removal. In 83% (n = 12) of the muscle flap patients, the wound healed uneventfully. Preoperative chest CT scanning was found to be helpful in identifying probable infection of the epicardial leads. In these cases, all hardware had to be removed to achieve resolution of the infection. We concluded that rectus abdominis muscle flaps were helpful in salvaging infected or exposed ICD generators in the absence of infected epicardial leads.