Test and teach. Number ninety one: Part 1. Subependymal giant cell astrocytoma.
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Adult↗
Biomedical subjects
M Singh
Publications and source records attributed to M Singh.
Purulent pericarditis: clinical profile and outcome following surgical drainage and intensive care in children in Chandigarh.
Purulent pericarditis, though rare in developed countries, is not uncommon in developing countries. However, the type of pericardial drainage required and the risk of subsequent constrictive pericarditis has not been clearly defined. Thirty children between the ages of 3 months and 12 years with a diagnosis of purulent pericarditis were studied retrospectively. Pericardial effusion was confirmed in all by echocardiography and the diagnosis of bacterial pericarditis was based on aspiration of purulent fluid with leucocytosis and high proteins. Purulent pericarditis was a part of the disseminated sepsis in 25 (83%) children. Fever was present in all, hepatomegaly in 28 and breathlessness in 25, whereas muffled heart sounds, raised JVP and pericardial rub were found in only 18, 16 and 7, respectively. The ECG was abnormal in only 16 children. Staphylococcus aureus was the causative organism in 24 (96%). Open surgical drainage was done in 26 children, 23 of whom underwent anterior pericardiectomy. Two children died of disseminated sepsis. None of the 21 who returned for follow-up for periods of between 4 and 24 months had any long-term sequelae.
Child↗
Immune responses to recombinant proteins of Mycobacterium leprae.
Identification of antigenic determinants of the polar immune response in leprosy may illuminate both protection and pathogenesis. Thirty subjects were studied (22 with polar disease and 8 healthy controls who were heavily exposed but disease-free) by assaying the proliferative, interferon (IFN)-gamma, and antibody responses to recombinant antigens of Mycobacterium leprae (10, 28, 36, and 65 kDa). The 10-kDa antigen elicited IFN-gamma production from all tuberculoid (TT) and borderline tuberculoid (BT) patients but little from controls, lepromatous (LL), or borderline lepromatous (BL) patients (P<.05). Production of 65-kDa-specific IFN-gamma was higher in TT/BT than in controls or LL/BL patients (P<.006). All subjects produced 65-kDa-specific antibody, but it was higher in LL/BL patients than in healthy controls, whose responses were higher than in TT/BT subjects (P=.035). The 36-kDa antibody responses were selectively increased in LL/BL subjects (P<.02). The intermediate phenotype of the controls suggests that M. leprae-specific production of IFN-gamma may contribute to pathology and to protection in leprosy.
Adult↗
Sequestration of T lymphocytes to body fluids in tuberculosis: reversal of anergy following chemotherapy.
The specificity of CD4 T lymphocytes was investigated in 6 patients affected by tuberculosis who had negative tuberculin purified protein derivative (PPD) skin tests at diagnosis. Polyclonal CD4 T cell lines from the peripheral blood failed to proliferate to PPD and to the 16- or 38-kDa proteins of Mycobacterium tuberculosis, while CD4 cell lines from the disease site responded to PPD and to the 16- and 38-kDa proteins and derived epitopes in vitro. Four months after chemotherapy, the patients became responsive to PPD. The proliferative response to PPD and to the 16- or 38-kDa proteins and their derived peptides decreased in CD4 T cell lines from the disease site and increased in lines from the peripheral blood. These results indicate that CD4 T cells recognizing a vast array of M. tuberculosis epitopes are compartmentalized at the site of disease in anergic patients but appear in peripheral blood after chemotherapy.
Antigens, Bacterial↗
Arene dioxides of substituted pyrenes: synthesis and X-ray structural studies.
The arene dioxides of five 1-substituted pyrenes have been synthesized using dimethyldioxirane. The diasteroisomeric distribution of the dioxides has been determined. X-ray crystallographic structures of the dioxides have also been obtained. These structures show that for the cis dioxides the molecular structures show a departure from planarity, the extent of which is dependent on the substituent.
Carcinogens↗
Mutational pattern of the nurse shark antigen receptor gene (NAR) is similar to that of mammalian Ig genes and to spontaneous mutations in evolution: the translesion synthesis model of somatic hypermutation.
The pattern of somatic mutations of shark and frog Ig is distinct from somatic hypermutation of Ig in mammals in that there is a bias to mutate GC base pairs and a low frequency of mutations. Previous analysis of the new antigen receptor gene in nurse sharks (NAR), however, revealed no bias to mutate GC base pairs and the frequency of mutation was comparable to that of mammalian IgG. Here, we analyzed 1023 mutations in NAR and found no targeting of the mechanism to any particular nucleotide but did obtain strong evidence for a transition bias and for strand polarity. As seen for all species studied to date, the serine codon AGC/T in NAR was a mutational hotspot. The NAR mutational pattern is most similar to that of mammalian IgG and furthermore both are strikingly akin to mutations acquired during the neutral evolution of nuclear pseudogenes, suggesting that a similar mechanism is at work for both processes. In yeast, most spontaneous mutations are introduced by the translesion synthesis DNA polymerase zeta (REV3) and in various DNA repair-deficient backgrounds transitions were more often REV3-dependent than were transversions. Therefore, we propose a model of somatic hypermutation where DNA polymerase zeta is recruited to the Ig locus. An excess of DNA glycosylases in germinal center reactions may further enhance the mutation frequency by a REV3-dependent mutagenic process known as imbalanced base excision repair.
Amino Acid Sequence↗
Antibodies against human heat-shock protein (hsp) 60 and mycobacterial hsp65 differ in their antigen specificity and complement-activating ability.
Although complement activation appears to have an important role both in the early and late phases of atherosclerosis, the exact mechanism of the initiation of this activation is still unknown. Since injuries of the endothelial cells are known to result in increased stress-protein expression we tested the complement-activating ability of recombinant human 60 kDa heat-shock protein (hsp60). Human hsp60 was found to activate the complement system in normal human serum in a dose-dependent manner. Activation took place through the classical pathway. The lack of complement activation in agammaglobulinemic serum indicates that the classical pathway is triggered by anti-hsp60 antibodies. Hsp60 activated complement in the sera of 74 patients with coronary heart disease as well, and a strong positive correlation (r = 0.459, P < 0.0001) was found between the extent of complement activation and the level of anti-hsp60 IgG antibodies but there was no correlation to the level of anti-hsp65 IgG antibodies. Further distinction between anti-hsp60 and anti-hsp65 antibodies was obtained from competitive ELISA experiments: binding of anti-hsp60 antibodies to hsp60-coated plates was inhibited only by recombinant hsp60 and vice versa. Our present findings indicate that anti-hsp60 and anti-hsp65 antibodies are distinct, showing only partial cross-reactivity. Since complement activation plays an important role in the development of atherosclerosis and the levels of complement-activating anti-hsp60 antibodies are elevated in atherosclerosis-related diseases, our present findings may have important pathological implications.
Adult↗
Role of angiotensin in cardioprotective effect of ischemic preconditioning.
This study was designed to investigate the role of angiotensin (Ang II) in the cardioprotective effect of ischemic preconditioning. Isolated perfused rat heart was subjected to global ischemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically by using triphenyl tetrazolium chloride (TTC) staining. Four episodes of ischemic/Ang II preconditioning markedly reduced LDH and CK release in the coronary effluent and decreased myocardial infarct size. The cardioprotective effect of Ang II preconditioning was abolished by CV 11974, AT1-receptor antagonist, whereas no such effect was noted with CV 11974 in ischemic preconditioning. PD 123319, AT2-receptor antagonist, produced no marked effect on Ang II preconditioning and ischemic preconditioning induced reduction in myocardial injury. On the basis of these results, it may be concluded that activation of AT1 receptors may be involved in angiotensin-induced pharmacologic preconditioning. But it may not be involved in the cardioprotective effect of ischemic preconditioning in isolated rat heart.
Angiotensin II↗
SPET brain perfusion imaging in mild traumatic brain injury without loss of consciousness and normal computed tomography.
We present SPET brain perfusion findings in 32 patients who suffered mild traumatic brain injury without loss of consciousness and normal computed tomography. None of the patients had previous traumatic brain injury, CVA, HIV, psychiatric disorders or a history of alcohol or drug abuse. Their ages ranged from 11 to 61 years (mean = 42). The study was performed in 20 patients (62%) within 3 months of the date of injury and in 12 (38%) patients more than 3 months post-injury. Nineteen patients (60%) were involved in a motor vehicle accident, 10 patients (31%) sustained a fall and three patients (9%) received a blow to the head. The most common complaints were headaches in 26 patients (81%), memory deficits in 15 (47%), dizziness in 13 (41%) and sleep disorders in eight (25%). The studies were acquired approximately 2 h after an intravenous injection of 740 MBq (20.0 mCi) of 99Tcm-HMPAO. All images were acquired on a triple-headed gamma camera. The data were displayed on a 10-grade colour scale, with 2-pixel thickness (7.4 mm), and were reviewed blind to the patient's history of symptoms. The cerebellum was used as the reference site (100% maximum value). Any decrease in cerebral perfusion in the cortex or basal ganglia less than 70%, or less than 50% in the medial temporal lobe, compared to the cerebellar reference was considered abnormal. The results show that 13 (41%) had normal studies and 19 (59%) were abnormal (13 studies performed within 3 months of the date of injury and six studies performed more than 3 months post-injury). Analysis of the abnormal studies revealed that 17 showed 48 focal lesions and two showed diffuse supratentorial hypoperfusion (one from each of the early and delayed imaging groups). The 12 abnormal studies performed early had 37 focal lesions and averaged 3.1 lesions per patient, whereas there was a reduction to--an average of 2.2 lesions per patient in the five studies (total 11 lesions) performed more than 3 months post-injury. In the 17 abnormal studies with focal lesions, the following regions were involved in descending frequency: frontal lobes 58%, basal ganglia and thalami 47%, temporal lobes 26% and parietal lobes 16%. We conclude that: (1) SPET brain perfusion imaging is valuable and sensitive for the evaluation of cerebral perfusion changes following mild traumatic brain injury; (2) these changes can occur without loss of consciousness; (3) SPET brain perfusion imaging is more sensitive than computed tomography in detecting brain lesions; and (4) the changes may explain a neurological component of the patient's symptoms in the absence of morphological abnormalities using other imaging modalities.
Adolescent↗
A recombinant measles virus expressing biologically active human interleukin-12.
Suppression of cell-mediated immunity (CMI) is well-documented during and after measles. This immunosuppression is suggested to result from decreased production of interleukin-12 (IL-12), a key interleukin for CMI. In an attempt to clearly discern the role of IL-12 in measles-induced immunosuppression, a measles virus (MV) that expresses biologically active human IL-12 was generated. This was achieved by inserting the coding sequences of the two subunits (p35 and p40) of human IL-12 separated by an internal ribosome entry site in an additional transcription unit between the H and the L genes of MV. Although the IL-12-expressing MV grew slightly slower than the normal MV, it stably maintained the inserted sequences (3.2 kb) and uniformly expressed the foreign genes after 10 passages in cell culture. These findings suggest that MV is a well-suited vector for delivery of proteins of immunogenic and therapeutic importance.
Animals↗
Protective efficacy and immunogenicity of Vi-porin conjugate against Salmonella typhi.
A conjugate vaccine against Salmonella typhi was prepared by covalently binding capsular polysaccharide (Vi) with porin, both isolated from S. typhi. First, Vi and porins were extracted. The Vi was purified from S. typhi Ty2. The purified Vi conformed to the requirements of the World Health Organization. Porins were purified from S. typhi 0901. The Vi was bound to the porins by a heterobifunctional cross-linking reagent, N-succinimidyl-3-(2-pyridyl dithio)-propionate (SPDP). After preparing the Vi-porin conjugate, its protective ability and immunogenicity were studied in mice following systemic immunization. The results showed that the conjugate is 6.5-fold more protective than Vi alone against S. typhi. The mice immunized with conjugate elicited higher anti-Vi antibody (IgG) levels (P < 0.01) than the mice immunized with Vi alone. Anti-porin antibodies were also induced by the conjugate. To study the mucosal immune responses, secretory IgA (sIgA) in the intestinal fluid was measured. Conjugate-immunized mice showed the induction of sIgA as compared to Vi alone. The results showed that when Vi is bound to porins, both isolated from same organism, the resultant conjugate induced both systemic and mucosal immune responses and provided better protection against S. typhi than Vi alone.
Animals↗
In vivo nickel allergic contact dermatitis: human model for topical therapeutics.
Techniques to determine efficacy of topical agents on allergic contact dermatitis (ACD) may benefit from refinement. The aim of this study was to develop an in vivo human model system for the bioengineering and visual quantification of the effect of topical agents on nickel ACD, and to correlate ACD parameters. 14 nickel patch-test-positive subjects were included in a placebo-controlled, double-blind study after a pre-screening procedure with a standard diagnostic patch test with nickel sulfate in 54 healthy human volunteers. 5% nickel sulfate in petrolatum in a Finn Chamber was applied on forearm skin for 48 h to create a standardized dermatitis. Thereafter, the dermatitis was treated with a model topical agent and a placebo control while recording endpoint parameters daily for 10 days. Resolution was quantified with 4 parameters: visual scoring (VS), transepidermal water loss (TEWL) (Tewameter), skin blood flow volume (BFV) (laser Doppler flowmeter), and skin color (a* value) (Colorimeter). The model agent reduced cutaneous allergic reactions, especially on day 8 to 10, in comparison with the placebo control. A highly significant linear relationship exists among all parameters, except between a* and BFV. This model may provide robust biometrics for determining the efficacy of topical therapeutics on experimentally induced ACD.
Administration, Cutaneous↗
Double blind clinical trial of a remineralizing dentifrice in the prevention of caries in a radiation therapy population.
OBJECTIVES: The purpose of this study is to determine the efficacy and safety of a specially formulated remineralizing toothpaste in controlling caries in a group of high risk, head and neck radiation patients. DESIGN: The study compares the performance of the remineralizing toothpaste with a leading conventional fluoride dentifrice using double-blind randomization. TEST PRODUCTS: The products compared both contain equivalent quantities of fluoride (1150 ppm). The remineralizing toothpaste also delivers soluble calcium and phosphate ions, the essential components of teeth. SUBJECTS: On completion, 50 subjects who received > 50 Gy of radiation to the head and neck. MEASUREMENTS: Examinations include coronal and root caries using the Pitts Diagnostic Criteria, salivary flow rate, plaque and gingival indices and microbiological counts over one year. RESULTS: At this point subjects are enrolled in the study at various phases. However, the current average for the net increment per month per subject is -0.12 (+/- 1.30) for coronal caries and 0.06 (+/- 0.73) for root caries in subjects using the remineralizing toothpaste and 0.53 (+/- 1.62) for coronal caries and 0.45 (+/- 0.98) for root caries in subjects using the conventional fluoride dentifrice. Non-parametric analysis of rank scores for net root surface increments/month was statistically significant (p = 0.02), suggesting lower net root surface increment/month for the remineralizing toothpaste relative to the conventional toothpaste. No significant differences were noted on coronal surfaces. CONCLUSIONS: The results to date indicate that the remineralizing toothpaste is significantly superior to the conventional fluoride dentifrice in preventing root caries in high risk patients.
Adult↗
Differential T-cell recognition of native and recombinant Mycobacterium tuberculosis GroES.
Mycobacterium tuberculosis GroES was purified from culture filtrate, and its identity was confirmed by immunoblot analysis and N-terminal sequencing. Comparing the immunological recognition of native and recombinant GroES, we found that whereas native GroES elicited a strong proliferative response and release of gamma interferon-gamma by peripheral blood mononuclear cells from healthy tuberculin reactors, the recombinant protein failed to do so. The same difference in immunological recognition was observed in a mouse model of TB infection. Both the native and recombinant preparations were recognized by mice immunized with the recombinant protein. Biochemical characterization including sodium dodecyl sulfate-polyacrylamide gel electrophoresis, two-dimensional electrophoresis, and mass spectrometry analysis of both proteins demonstrated no differences between the native and recombinant forms of GroES except for the eight additional N-terminal amino acids derived from the fusion partner in recombinant GroES. The recombinant fusion protein, still tagged with the maltose binding protein, was recognized by T cells isolated from TB-infected mice if mixed with culture filtrate before affinity purification on an amylose column. The maltose binding protein treated in the same manner as a control preparation was not recognized. Based on the data presented, we suggest that the association of biologically active molecules from culture filtrate with the chaperone GroES may be responsible for the observed T-cell recognition of the native preparation.
Animals↗
A recombinant measles virus expressing hepatitis B virus surface antigen induces humoral immune responses in genetically modified mice.
It has been shown previously that measles virus (MV) can be successfully used to express foreign proteins (M. Singh and M. A. Billeter, J. Gen. Virol. 80:101-106, 1998). To develop an inexpensive MV-based vaccine, we generated recombinant MVs that produce structural proteins of hepatitis B virus (HBV). A recombinant virus that expressed the HBV small surface antigen (HBsAg) was analyzed in terms of its replication characteristics, its genetic stability in cell culture, and its immunogenic potential in genetically modified mice. Although this virus showed a progression of replication slightly slower than that of the parental MV, it appeared to stably maintain the added genetic information; it uniformly expressed the appropriately glycosylated HBsAg after 10 serial passages. Genetically modified mice inoculated with this recombinant MV produced humoral immune responses against both HBsAg and MV proteins.
Animals↗
Safety and effectiveness of BCG vaccination in preterm babies.
AIM: To assess the cell mediated immune response to BCG vaccine in preterm babies. METHODS: Sixty two consecutive preterm babies born at < 35 weeks of gestation were randomly allocated into two groups. Babies in group A were vaccinated early at 34-35 weeks and group B were vaccinated late at 38-40 weeks of postconceptional age. The two groups were similar in terms of: gestational age (mean (SD) 33.1 (1. 1) and 33 (1.2) weeks, respectively); birthweight 1583 (204) and 1546 (218) g; neonatal problems; socioeconomic status; and postnatal weight gain. The cell mediated immune response to BCG was assessed using the Mantoux test and the lymphocyte migration inhibition test (LMIT) 6-8 weeks after BCG vaccination. Induration of >5 mm after the Mantoux test was taken as a positive response. RESULTS: There was no significant difference in the tuberculin conversion rates (80% and 80.7%, respectively), positive LMIT (86.6% and 90.3%, respectively), or BCG scar (90.0% and 87.1%, respectively) among the two groups. CONCLUSIONS: Prematurity seems to be an unlikely cause for poor vaccine uptake. Preterm babies can be effectively vaccinated with BCG at 34-35 weeks of postconceptional age, the normal time of discharge in a developing country.
BCG Vaccine↗
Inhibition of arteriosclerosis by T-cell depletion in normocholesterolemic rabbits immunized with heat shock protein 65.
Previous studies in our laboratory have shown that arteriosclerotic changes can be induced in normocholesterolemic rabbits by immunization with mycobacterial heat shock protein (hsp) 65. To further investigate the immunologic mechanisms underlying such vascular lesions, 39 male New Zealand White rabbits were treated by triple immunization with fortified Freund's complete adjuvant containing 5 mg/mL Mycobacterium tuberculosis as a source of hsp65 and simultaneous immunosuppressive therapy twice per week with either anti-CD3 monoclonal antibody (1 mg/kg) and prednisolone (1 mg/kg) or prednisolone (1 mg/kg) alone. Sixteen weeks after the first immunization the animals were killed, and as expected, severe arteriosclerotic lesions in the intima of the aortic arch were found in 9 of 10 immunized rabbits. However, only 1 of 10 rabbits immunized and immunosuppressed with the combined anti-CD3 monoclonal antibody and prednisolone treatment showed a single moderate lesion in the aorta, whereas 5 of 9 rabbits immunized and immunosuppressed by prednisolone treatment alone showed lesions, albeit mild. In conclusion, the early inflammatory stages of arteriosclerotic lesions induced by immunization with hsp65 can be inhibited by immunosuppressive therapy with anti-CD3 monoclonal antibody.
Animals↗
Clinical, echocardiographic, and angiographic profile of patients with double-chambered right ventricle: experience with 48 cases.
Forty-eight patients with double-chambered right ventricle (DCRV) were prospectively studied over a 3-year period. Clinical, echocardiographic, hemodynamic, and angiographic studies were done in all. Three patients were studied postoperatively also. Fifteen patients underwent surgery confirming the diagnosis. Echocardiography detected anomalous muscle bundles (AMBs) in 39/41 patients in whom this study was carried out. Angiographically AMBs were best demonstrated in anteroposterior views in a systolic frame. Common associated anomalies found with DCRV were ventricular septal defects (69%), pulmonary valve stenosis (38%), and double-outlet right ventricle (10%).
Adolescent↗