A Comparitive Study of Anticardiolipin Antibodies among Systemic Lupus Erythematosus Patients from Western and Eastern India.

INTRODUCTION: Anti-phospholipid antibodies (APA) like anticardiolipin antibodies (ACA) are important cause of venous and arterial thrombosis and other occlusive vascular diseases. Prevalence of these antibodies in SLE patients at the time of diagnosis is not known in Indian SLE patients. This study was conducted to evaluate the prevalence of ACA in SLE patients from Eastern and Western India and to correlate them with disease activity. MATERIAL AND METHODS: Seventy SLE patients from Assam Medical College, Dibrugarh, Assam and 85 SLE patients from Rheumatology Department, KEM Hospital, Mumbai were studied. SLE disease activity was evaluated by SLE Disease Activity Index (SLEDAI) score at the time of evaluation. All patients studied were in an active stage of disease. RESULTS: Demographic data showed significant variations in the clinical manifestations of SLE between two regions. Renal manifestations were higher (42.9%) among SLE patients from Eastern region as compared with 37.6% patients from Western region. These patients were categorized as Lupus Nephritis (LN) and patients that did not show any renal manifestations were categories as non-LN. ACA to IgG and IgM subclasses were tested by ELISA. IgGACA positivity was 20%, 12.9% and IgM-ACA positivity was 18.6%, 12.9% where asIgG + IgM ACA positivity as found in 12.9%, 3.5% patients respectively among SLE patients from Eastern and Western India. CONCLUSIONS: ACA positivity was higher among LN patients from Eastern India whereas the same was higher among non-LN patients from Western India. Hence detection of ACA alongwith associated clinical manifestations were helpful to evaluate their possible association with disease severity in SLE patients. A long term follow up of patients having ACA antibodies without thrombotic event is needed to detect their possible thrombotic event in future along with their clinical presentation from these two different geographic regions from India.

Pulmonary manifestations in systemic lupus erythematosus (SLE) with special reference to HR CT.

AIMS AND OBJECTIVES: 1. To evaluate whether CT helps in the early diagnosis of pulmonary manifestations in SLE. 2. To study the pulmonary involvement and determine the incidence and type of pulmonary involvement. MATERIALS AND METHODS: Thirty eight patients fulfilling ACR classification criteria for SLE were studied. Chest X-ray, pulmonary function tests (PFT), HRCT scan thorax were done. Investigations were done to detect other organ involvement. Patients with known interstitial lung disease (occupational hazard) or pregnant females were excluded. RESULTS: Clinical signs and symptoms referable to pulmonary involvement were present in 9 patients (23.68%). HRCT thorax detected abnormalities in 21 patients (55.26%); pulmonary function abnormalities were present in 11 patients (28.95%) and plain X-ray chest abnormalities were present in 7 patients (18.42%). Out of 38 patients pulmonary involvement was present in 22 (57.89%) cases and HRCT thorax findings were present in 21 (95.45%) of them. CONCLUSION: Pulmonary involvement is present in a significant number of SLE patients, who are often asymptomatic, with normal chest X-ray or normal PFT. HRCT scan thorax could diagnose the pulmonary involvement in asymptomatic patients with normal chest X-ray and uncertain PFT.

Elephantiasis Nostras Verrucosa: a rare thyroid dermopathy in Graves' disease.

Elephantiasis Nostras Verrucosa (ENV) is a rare form of pretibial myxedema, which is nearly always associated with Graves' disease. A case is presented here of Graves' disease who had elephantiasis variety of pre-tibial myxedema (PTM).

Symmetric peripheral gangrene and falciparum malaria.

Sudden onset symmetric peripheral gangrene (SPG) is a relatively uncommon clinical entity manifested by distal ischemic damage at two or more sites in the absence of large vessel obstruction. Here we report a case of complicated falciparum malaria with rapid onset SPG involving all the toes.

Characterization of cancer cell lines established from two human metastatic breast cancers.

Cell lines are valuable resources for the study of the malignancy and potential therapy of human breast cancer. A major problem with adapting fresh breast tumor specimens to grow in vitro is contamination by fibroblasts. Previously, we have reported a technique to overcome this problem (Nayak, S. K; Dillman, R. O. Clin. Biotechnol. 3:237-242; 1991). We have recently established two new breast cancer cell lines, HH315 and HH375, that were derived from abdominal and supraclavicular lymph node metastases from two patients. They were characterized by (1) growth kinetics; (2) staining with monoclonal antibodies (MoAbs) to cytokeratin-19, epithelial membrane antigen (EMA), anticarcinoembryonic antigen (CEA), breast cancer antigen 1 (BRST-1), breast cancer antigen 2 (BRST-2), Her2/neu, and p53; (3) expression of domains of urinary plasminogen activator (uPA), neural cell adhesion molecule (NCAM), and haptoglobin (Hp) (Harvey et al., 1997); and (4) karyotypic analysis. Growth kinetic studies showed that doubling times for both lines ranged from 48 to 96 h. These two cell lines were found to have characteristics of the metastatic breast cancer cells. Both lines stained positive with MoAbs to cytokeratin-19 and EMA, thus confirming their epithelial origin. They also strongly reacted with the pan-breast carcinoma MoAbs BRST-1 and BRST-2, and carcinoembryonic CEA MoAb. Both cell lines overexpressed the oncogene proteins Her2/neu and p53. The tumor cells were negative for estrogen and progesterone receptors. HH315 cells were poorly differentiated, whereas the HH375 cells exhibited adenocarcinoma morphology. Both cell lines showed intense cell surface and some cytoplasmic staining for uPA, NCAM, and Hp domains, which is a characteristic of malignant neoplasms (Harvey et al., 1997). The HH375 cell line showed two cell types, of which 60% were hyperdiploids with 60-70 chromosomes and 5-10 marker chromosomes. The remaining cells were polyploid with more than 200 chromosomes. Cell line HH315 consisted of only a polyploid population. These cell lines may be useful in breast cancer research.

Association of germline p53 mutation with MLL segmental jumping translocation in treatment-related leukemia.

Segmental jumping translocations are chromosomal abnormalities in treatment-related leukemias characterized by multiple copies of the ABL and/or MLL oncogenes dispersed throughout the genome and extrachromosomally. Because gene amplification potential accompanies loss of wild-type p53, we examined the p53 gene in a case of treatment-related acute myeloid leukemia (t-AML) with MLL segmental jumping translocation. The child was diagnosed with ganglioneuroma and embryonal rhabdomyosarcoma (ERMS) at 2 years of age. Therapy for ERMS included alkylating agents, DNA topoisomerase I and DNA topoisomerase II inhibitors, and local radiation. t-AML was diagnosed at 4 years of age. The complex karyotype of the t-AML showed structural and numerical abnormalities. Fluorescence in situ hybridization analysis showed multiple copies of the MLL gene, consistent with segmental jumping translocation. A genomic region including CD3, MLL, and a segment of band 11q24 was unrearranged and amplified by Southern blot analysis. There was no family history of a cancer predisposing syndrome, but single-strand conformation polymorphism (SSCP) analysis detected identical band shifts in the leukemia, ganglioneuroma, ERMS, and normal tissues, consistent with a germline p53 mutation, and there was loss of heterozygosity in the ERMS and the t-AML. Sequencing showed a CGA-->TGA nonsense mutation at codon 306 in exon 8. The results of this analysis indicate that loss of wild-type p53 may be associated with genomic instability after DNA-damaging chemotherapy and radiation, manifest as a complex karyotype and gene amplification in some cases of t-AML.

Concurrent presence of inv(14)(q11q32) and t(4;11)(q21;q23) in pre-B acute lymphoblastic leukemia.

The inv(14)(q11q32) is a non-random chromosomal aberration which has been associated with a variety of T-cell malignancies. We have studied a case of inv(14)(q11q32) that is unique in several respects. First, the inversion, which is expressed at the mRNA level, occurred in the context of a pre-B acute lymphoblastic leukemia (ALL) as opposed to a T-cell malignancy. Second, cloning and sequencing of the inversion revealed that it resulted from a fusion between an immunoglobulin heavy chain variable (V) segment and a T-cell receptor delta diversity (D) segment. In addition, the patient had a second chromosomal abnormality at diagnosis, a t(4;11)(q21;q23) which disrupted the MLL gene. The fact that there were two distinct chromosomal abnormalities at diagnosis enabled us to address the question of leukemic clonal evolution during the course of this patient's disease. We present evidence suggesting that the t(4;11)(q21;q23) occurred first, with the inv(14)(q11q32) occurring as a second event.

Clinical evaluation of halofantrine in acute malaria.

Fifty patients suffering from acute malaria were treated with 'Halofantrine Hydrochloride'. They were observed for 4 weeks. Clinical, haematological and biochemical parameters were assessed for evaluation of halofantrine in acute malaria, with special reference to its effectiveness, tolerability and side effects.

Deletion of chromosome 22 without bcr rearrangement and without juxtaposition of c-abl in a case of acute myeloid leukemia.

We describe a patient with acute myeloid leukemia (AML) who had a deletion of chromosome 22 at q11 as a sole chromosomal abnormality, resulting in the karyotype 46,XY,del(22)(q11). Southern blot analysis showed no bcr rearrangement and fluorescence in situ hybridization indicated no juxtaposition of c-abl. This study indicates that molecular events other than bcr rearrangement and c-abl juxtaposition were involved in leukemogenesis in this patient. We hypothesize that a tumor suppressor candidate gene may be located on the long arm of chromosome 22; its loss may lead to malignant transformation.

Ramsay Hunt syndrome with aseptic meningitis.

A case of Ramsay Hunt Syndrome with characteristic vesicles on the lateral aspect of the left pinna, evidence of infranuclear palsy of the left 7th cranial nerve, associated with same sided loss of taste sensation in the presulcal area of the tongue and perceptive deafness without vestibular disturbances is reported here. The patient had evidence of aseptic meningitis.

Burkitt's lymphoma of the parapharyngeal space.

Burkitt's lymphoma is quite rare outside of Africa. It is even more uncommon for this nonendemic form of the disease to present in the head and neck region. To our knowledge, nonendemic Burkitt's lymphoma has not been previously reported arising from the parapharyngeal space. We review the case of a 10-year-old boy who presented with an asymptomatic mass at the angle of the mandible several weeks after blunt trauma to that area. We discuss the evaluation of this mass, including the results of computed tomography and magnetic resonance imaging, along with the findings of histopathologic and cytogenetic studies. We also discuss the differential diagnosis of parapharyngeal lesions, paying particular attention to the workup and management of Burkitt's lymphoma. Since Burkitt's lymphoma has the highest growth rate of any tumor in man, rapid diagnosis and immediate treatment are important and likely to improve outcome.

Constitutional extra chromosomal element in a family with Wilms' tumor.

We report the presence of an extra chromosomal element in a family with Wilms' tumor (WT). This family has three children, two of whom were affected. One son, the proband, had bilateral and one daughter had unilateral WT. The first child, the father, and the mother did not have WT. The son with bilateral WT had a ring chromosome (R) both in the lymphocytes as well as in the kidney tissue. The size of the ring varied considerably from cell to cell. The daughter with unilateral WT had an abnormal clone containing a small chromosomal ring (r) in phytohemagglutinin (PHA)-stimulated and Epstein-Barr virus (EBV)-transformed lymphocytes. The mother had a karyotype similar to that of the daughter with WT. We hypothesize that the proband's ring chromosome could be the amplified form of the r inherited from the mother. Chromosome 11 was cytogenetically normal in all the cells examined of the affected children and the unaffected mother. In situ hybridization with a centromere-specific DNA cocktail indicated dispersed centromeric DNA both in r and R.

Distribution and relation of radiation induced chromosomal aberrations in human lymphocytes as seen in the first and second cell cycles.

Different types of chromosomal damage in the G(o) phase of human lymphocytes have been studied in the first (M1) and second cell lymphocytes (M2). Large populations of cells containing one dicentric chromosome and one acentric (DIC+) were observed in the second cycle. This indicates that these dicentric and acentric fragments have a normal distribution in M2 or, arose through loss of one acentric fragment (AC) from cells containing one dicentric and two acentric fragments (DIC++) in M1. Similarly, a large number of metaphases in M2 have unpaired differentiated ACs. Our data indicates that aberrant metaphases containing single AC or a DIC+ may undergo normal cell division and that these cells may not represent cells in the first cycle only, as was suggested by earlier workers. For radiation experiments to G(o), a desirable time to harvest human lymphocyte cultures appears to be 72 hours and screening of M1 and M2 cells by sister chromatid differentiation.

Abnormally banded region in a poorly differentiated sarcoma is not correlated with amplification of c-MYC or c-MOS protooncogenes.

A poorly differentiated sarcoma in a 32-year-old female revealed a large, abnormally banded region in one chromosome #8 in all metaphases. The modal karyotype was 46,XX, -8, +mar. Southern blot hybridization was performed with probes for two protooncogenes located in chromosome 8q (c-MYC and c-MOS). No amplification or rearrangement was observed to account for the cytogenetic abnormality.

Comparison of radiation-induced chromosomal damage between normal individuals and patients with familial polyposis coli.

Cultured leukocytes of peripheral blood obtained from normal, healthy individuals and from patients with familial polyposis coli (FP) were exposed to 0 rads or 300 rads of 137Cs gamma radiation at G0 to compare damage in these two groups. Only cells in the first mitotic division were considered. The average chromosomal damage in the FP patients was not significantly higher than that in the normal group. The induced chromosomal damage at G0 was normally distributed in both the control and the patient groups as well as when they were combined.

The human int-1 gene is located at chromosome region 12q12-12q13 and is not rearranged in myxoid liposarcoma with t(12;16) (q13;p11).

The mouse cellular oncogene int-1 is often transcriptionally activated as a consequence of nearby proviral insertions in mouse mammary tumors. A highly conserved sequence has been found in the human genome, called int-1 gene, the role of which in human tumors is not known. By somatic hybrids, the human int-1 gene has been assigned to the segment 12q14-12pter. Using a genomic DNA clone containing the fourth exon of the human int-1 gene we have mapped the human int-1 gene to 12q12-12q13. To determine whether this gene, which is located close to the 12q13 breakpoint associated with myxoid liposarcoma, is rearranged in these tumors, we have performed Southern blot analysis of DNA from myxoid liposarcomas carrying the translocation t(12;16) (q13;p11). In the two tumors investigated, the translocation does not disrupt the int-1 gene.

Cytogenetic findings in a primary adrenocortical carcinoma.

Cytogenetic analysis of a primary adrenocortical carcinoma revealed clonal rearrangements of several autosomes and sex chromosomes. In all metaphases the following marker chromosomes were present: 4p+,t(3;12)(p14;p13),14q+, t(15;20)(p11;q11), t(5;18) (p13.3;p11.2), psu dic(18)t(18.3)(p11.39;p12), and psu dic(20)t(20;9)(q11.2;p11). The results are discussed in relation to the cytogenetic findings in other solid tumors, especially of the kidney.

Gardner syndrome in a man with an interstitial deletion of 5q.

Chromosome analysis of blood cells from a 42-year-old white male with mental retardation, colon carcinoma, horseshoe kidney, absence of left lobe of the liver, agenesis of the gallbladder, and possible Gardner syndrome revealed a constitutional marker chromosome due to del(5)(q13q15) or del(5)(q15q22). A polymorphic chromosome #22 with enlarged satellites was inherited from the father, who is phenotypically normal, and was probably unrelated to the congenital malformations. This is the first report of a Gardner syndrome patient with an interstitial deletion of 5q.