Surgical Outcome in IDEM Tumors in Short Term Follow Up

Background: To review the clinical and histological aspect of IDEM tumors with functional outcome after surgery of all radiologically diagnosed cases of IDEM. Methods: 12 cases of IDEM tumors, which had been surgically treated and studied in terms of clinical features as pain by VAS, functional score by Nuricks grading, in preoperative and postoperative period. The correlation of histopathology and tumor size in terms of clinical features and outcome was done. Results: Most common diagnosis was schwannoma (83.3%) and rest 2 patients were meningiomas(16.7%), distribution - 3(25%) dorsal, 5(41.6%) lumbar, 2(16.6%) cervical, 1(8%) cervico-dorsal and 1(8%) dorso-lumbar and average percentage of the intradural space occupied by tumor was 77.02%. Average age was 40 years. Meningioma was common in 55 to 60 yr age all female; schwannoma the mean age was 37 year. The most common symptoms were local pain, tingling and numbness, motor weakness which were observed in all the cases. All patients improved postoperatively. VAS score and Nurick grade inproved in all. Conclusion: Most common pathology was schwannoma then meningioma. All the tumors excised through the posterior approach. The postoperative recovery was good in all the cases regardless of any condition. Therefore, aggressive surgical excision is recommended even for cases with a long duration of symptoms or a severe neurologic deficit.

Implication of BRCA1 gene in breast cancer.

Breast cancer susceptibility gene (BRCA1) is known to be responsible for hereditary breast and ovarian cancer. This gene is highly penetrant conferring a risk for 0.92 by the age of 70. Germline mutation in this gene leads to susceptibility to breast and ovarian cancer, with a genotype phenotype correlation. Frequency of mutations of this gene in normal population of breast cancer is low suggesting that the effort of primary screening for BRCA1 gene should be restricted to only familial cases with a strong history of breast and ovarian cancer. Recent studies indicate that BRCA1 is a tumor suppressor gene responsible for both normal development and carcinogenesis of the breast. Normal function elucidated so far, reveal BRCA1 to be a multifunctional protein involved in DNA repair, cell cycle regulation and transcription. There is circumstantial evidence that gene interacts with p53, a protein involved in cell cycle control, DNA repair and apoptosis.

A simple technique for improving chromosome spreads from clumped metaphases.

A method has been described by which clumped metaphases either due to inadequate hypotonic KCl treatment or prolonged storage at 4 degrees C can be rescued. The cell pellet obtained from cell suspension following centrifugation was resuspended in freshly prepared Carnoy's fixative (1:3, acetic acid: methanol) at room temperature by vortexing. Twenty microliters of Triton X-100 at a concentration of 0.5% was added drop by drop while vortexing. Three changes with fixative containing 0.5% Triton X-100 were optimal for obtaining good metaphase spreads with complete removal of the cytoplasmic background. The advantage of this technique is that important patients' samples having clumped metaphases otherwise not useful for G-banding can be rescued and karyotyped by this method.

Detection of virus specific IgG subclasses in Japanese encephalitis patients.

During the Japanese encephalitis (JE) epidemic in 1988 at Gorakhpur, Uttar Pradesh, 34 cerebrospinal fluid (CSF) samples with 16 matching sera from 34 anti JEV IgM positive (confirmed JE) and 24 CSF samples with 4 matching sera from 24 anti JEV IgM negative (clinical encephalitis) patients were collected and tested for presence of JEV specific IgG by ELISA. Eighteen CSF samples and 8 matching sera from confirmed JE and 5 CSF samples and one matching serum from clinical encephalitis patients positive for JEV specific IgG were further assayed for subclass specificity using specific murine monoclonal antibodies. Almost all the samples exhibited IgG1 as the virus specific subclass. In addition to IgG1, one serum and one CSF sample each from two different confirmed JE patients showed the presence of virus specific IgG4 and IgG3 respectively. Half of the confirmed JE and clinical encephalitis patients exhibited intrathecal synthesis as evident from either elevated IgG index or CSF IgG/CSF albumin ratio. Most of the patients who recovered had predominantly virus specific IgG1 in CSF. It seems likely that IgG1 might have a protective role in clearance of virus from the central nervous system.

Circulating interferon-alpha in patients with Kyasanur forest disease.

Endogenous interferon (IFN) levels were monitored in acute (51) and convalescent phase (19) sera collected from patients suffering from Kyasanur forest disease (KFD). Levels of circulating IFN in the acute samples (GM 216.3 +/- 8.7) collected between 4 to 7 post onset day (POD) were significantly higher (P less than 0.001) than the convalescent samples (GM 13.19 +/- 1.6) collected between 30th to 90th POD. Interferonemia was concomitant with the viraemic phase. Neutralization studies indicated that the endogenous (circulating) IFN was antigenically similar to acid stable form of IFN-alpha.

Characterization of & induction of immune response to anti-idiotypic antibodies for JE virus.

Anti-idiotypic antibodies (anti-Ids, Ab2s) were prepared by immunizing rabbits with two murine monoclonal antibodies (Ab1) having specificities for two independent haemagglutinin (HA) epitopes on JE virus [viz., Hs-1, monoclonal antibody (MAb) specific for Japanese encephalitis virus (JEV) and Hx-1, MAb common to flaviviruses]. Anti-Hs-1 (S-Ab2) and Anti-Hx-1 (X-Ab2) reacted specifically with the immunizing Ab1. In addition, they could react with other MAbs whose reactivity was similar to their immunizing homologous Ab1. The paratope inhibition assay indicated that both anti-idiotypes recognized paratope related idiotopes on their respective Ab1 and could therefore be designated as Ab2 beta. Experimental animals (Swiss mice, Balb/c mice and guineapigs) immunized with S-Ab2 or X-Ab2 produced anti-JE virus antibodies (Ab3) which could be detected by enzyme linked immunosorbent assay, immunofluorescence, haemagglutination inhibition and neutralization tests. The anti-idiotypes were also found to stimulate a cellular immune response in vitro as assessed by 3H thymidine incorporation by lymphocytes from JE vaccinated individuals and experimentally immunized Balb/c mice. The findings of the present study suggest that both the anti-Id antibodies are homobodies which may act as surrogate antigens to manipulate the immune response against JEV.

Protective effect of 6-MFA, a fungal interferon inducer against Japanese encephalitis virus in bonnet macaques.

6-MFA, an extract from the fungus Aspergillus ochraceus was administered to 8 bonnet macaques. An equal number of monkeys matched for age, sex and weight received placebo and served as controls. Twenty hours after the administration of the 6-MFA/placebo the monkeys were challenged with an Indian strain of Japanese encephalitis virus by the intranasal route. Signs and symptoms of the disease such as fever, tremors, loss of appetite, dehydration, flaccid paraplegia or quadriplegia were pronounced in all the control monkeys, while in the 6-MFA treated group only two developed symptoms. Virus could be isolated from only one of the 6-MFA treated monkeys on day 6, and from four control monkeys; one each from CSF, spinal cord, blood and from both nasal swab and blood of the fourth monkey. The appearance of HI and N antibodies in 6-MFA treated group was either delayed or completely suppressed. The results indicate that 6-MFA is a potential antiviral agent which can be used to reduce the morbidity and mortality in bonnet macaques (Macaca radiata) experimentally infected with Japanese encephalitis virus.

Selection of a neutralization-escape variant strain of Japanese encephalitis virus using monoclonal antibody.

An Indian strain of Japanese encephalitis virus (JEV), 733913, a human isolate from Bankura, West Bengal in 1973, with all the functional epitopes designated by a panel of murine monoclonal antibodies (MAbs), was treated with one of the JEV specific HI reactive MAb(Hs-I). This led to selection of a neutralization-escape variant which showed loss of reaction to three different MAbs belonging to the same domain (Hs) and assumed similar characteristics to another JEV strain (755468) also isolated from Bankura in 1975 from mosquitoes. It is possible that selection of such variant might occur in presence of pre-existing JE antibody (Hs-I type) in pigs which are amplifying hosts of JEV. Subsequent dissemination of such variant virus could occur through mosquitoes.

Epitope analysis of strains of Japanese encephalitis virus by monoclonal antibodies.

Twenty one strains of Japanese encephalitis (JE) virus, including 16 from India, were compared antigenically on the basis of their reactivity in immunofluorescence (IF), haemagglutination inhibition (HI), ELISA with captured antigen (ECA), and neutralization (N) tests with JE monoclonal antibodies (MAbs). These MAbs represented three domains of distinct epitopes on the envelope protein, designated as Hs-1 to 4 (JE specific in HI), Hx-1 to 5 (flavivirus cross reactive in HI) and NHs-1 to 2 (non-HI JE virus specific). Fifteen of the 21 strains studied were placed in group I. These reacted with MAbs representing the three domains in all the tests indicating presence of the three types of epitopes with full functional activity. The remaining six strains were placed in group II and showed loss in HI reactivity with Hs MAbs but not with Hx MAbs. All the group II strains also reacted in IF and ECA with NHs-1. Hs epitopes in three strains, G9473 (Tamil Nadu), 641686 (Tamil Nadu) and 822199 (Karnataka), appeared to have mutated partially, indicating loss in HI reactivity with Hs MAbs only, while there was retention of other reactivities, viz., IF, ECA and to some extent N test with G9473 and 641686. The remaining three strains, 691004 (Sri Lankan), 755468 (West Bengal) and Yoken (Japan) of group II showed almost complete loss of Hs-1 and Hs-2 epitopes as there was absence of reactivity in IF, ECA and N test in addition to HI. However, Hs-3 MAb showed reactivity in IF with these strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Interferon producing capacity (IPCA) of peripheral mononuclear cell in oral cancer patients.

Interferon producing capacity (IPCA) of peripheral blood mononuclear cells is ability of these cells to produce IFN with suitable IFN inducer. In Vitro IPCA of cryopreserved mononuclear cells (MNC) from peripheral blood of 46 oral cancer patients was studied and was compared to that of healthy, age matched donors. New castle disease virus (NDV) and staphylococcal enterotoxin A (SEA) were used as inducers for evaluating Type alpha IPCA (AIPCA) and Type gamma IPCA (GIPCA) respectively. Age of healthy donors did not influence the AIPCA or GIPCA. Oral cancer patients demonstrated significant low AIPCA (P less than 0.05) (Range Healthy donors 3.5 to 4.6 log 10Iu/ml Oral Cancer 2.0 to 4.6 log 10Iu/ml GIPCA was found to be further depressed (P less than 0.005) (Range Healthy donors 2.87 to 3.6 Log 10 U/ml, Oral cancer 1.7 to 3.6 log 10 U/ml. The depression in IPCA was found to be more pronounced in advanced stage of disease.