Search PubMed⌕ Search

Biomedical subjects

S Varma

Publications and source records attributed to S Varma.

At least 127 records · Page 7Linked to original sources
PubMed1997

Histological and clinical evolution patterns of chronic myelocytic leukemia.

Trephine biopsies of 101 chronic myelocytic leukaemia (CML) patients were analysed to study the relationship between initial and subsequent histological features vis-a-vis clinical behaviour of the disease. The patients with blast crisis at presentation were excluded. At diagnosis 62 (61.4%) patients revealed granulocytic-megakaryocytic (gran-meg) proliferation whereas granulocytic (gran) proliferation was found in 39 (38.6%) patients. Gran pattern at diagnosis was associated with shorter survival and early evolution into blast crisis (36.8%) in 12 months, although the difference in the total incidence of blast crisis between the two histological groups was not statistically significant. Myelofibrosis was detected in more number of cases on follow up (89.1%) as compared to the initial biopsies (80.2%). However myelofibrosis did not correlate with initial cellular composition, overall survival or the phase of CML (P > 0.05). Transition from one histological type to another was observed in 15 out of 60 (25%) cases while remaining in the chronic phase.

Biopsy, Needle↗
PubMed1996

Sterol dependent LDL-receptor gene transcription in lymphocytes from normal and CML patients.

Sterol regulatory element (SRE) has been recognized to regulate various key genes coding for especially low density lipoprotein (LDL)-receptor, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and HMG-CoA synthase known to play a crucial role in the cholesterol feedback mechanism. The deranged cholesterol feedback mechanism has been widely recognised in initiation as well as progression of various types of cancers including chronic myeloid leukaemia (CML). Consequently, the present study was addressed to understand this phenomenon and revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects as well as its absence in lymphocytes from untreated CML patients. However, this factor appeared when the CML patients achieved complete haematological remission (CHR) through alpha-interferon therapy. Further, an inverse relationship was also observed between sterol modulated LDL-receptor gene transcription and the binding affinity of this 47 kDa factor to the SRE sequence. Based upon these results we propose that alpha-interferon through its receptor initiates phosphatidic acid dependent signalling which in turn regulates the affinity of 47 kDa sterol regulatory element binding factor as well as LDL-receptor gene transcription in lymphocytes from CML patients.

Bucladesine↗
PubMed1996

Co-expression of two FAB-specific chromosome changes, t(15;17) and t(8;21), in a case of acute promyelocytic leukemia.

We describe a case of acute promyelocytic leukemia ANLL-M3 with association of t(15;17) and t(8;21) and various chromosomal aberrations. Clinically, immunologically, and morphologically, our patient fits the diagnosis of typical ANLL-M3. The co-existence of two specific FAB chromosomal translocations in a single leukemic clone is rare. The rarity of this association enhances the significance of this report.

Adult↗
PubMed1996

Lymphocytes from CML patients lack a 47 kDa factor having affinity for a genomic sterol regulatory sequence.

Deranged cellular cholesterol homeostasis has been widely recognized in the initiation as well as progression of various types of cancers including chronic myeloid leukaemia (CML). Since the human genomic sterol regulatory element (SRE) has been shown to regulate various key genes involved in this phenomenon, the present study revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects, as well as its absence in lymphocytes from untreated CML patients. However, this factor appeared when these CML patients achieved complete haematological remission (CHR) through alpha-interferon therapy. Furthermore, an inverse relationship was also observed between the LDL receptor gene expression at the transcriptional level and the binding affinity of this 47 kDa protein factor to the SRE sequence. Based upon these results we propose that this factor may have a role in pathophysiology of chronic myeloid leukaemia.

Antineoplastic Agents↗
PubMed1996

Quantification of PML-RAR alpha transcripts in acute promyelocytic leukaemia: explanation for the lack of sensitivity of RT-PCR for the detection of minimal residual disease and induction of the leukaemia-specific mRNA by alpha interferon.

The RT-PCR technique for the identification of the PML-RAR alpha fusion mRNA is widely used for the detection of minimal residual in acute promyelocytic leukaemia (APL). A positive result after remission induction is highly predictive of early relapse, but the vast majority of patients have no detectable disease by this technique after chemotherapy consolidation, despite the fact that many later relapse. We report a quantitative PCR technique for the PML-RAR alpha cDNA which was used to show that less than 1000 PML-RAR alpha molecules are obtained from 1 microgram of diagnostic bone marrow RNA derived from approximately 1 million APL blasts. The lack of sensitivity of currently employed RT-PCR methods may therefore be explained by their poor yield of PML-RAR alpha cDNA. Minor modifications to the reverse transcription procedure improved this yield 3 fold. Furthermore, expression of the leukaemia-specific transcript increased by approximately one order of magnitude after incubation of the patient's cells for 24 h in vitro with 100 iu/ml alpha interferon.

DNA, Neoplasm↗
PubMed1996

Delayed diagnosis of psychological erectile dysfunction because of the presence of macroprolactinemia.

Idiopathic hyperprolactinemia can be found in men with either normal or low serum testosterone (T) levels. The explanation for the differing effects on T of similar PRL levels has not been found. Macroprolactinemia, as a clinical entity, has been reported mostly in women. These macromolecules are biologically less active and/or are transported less easily across the capillary bed than the 22-kDa molecules. Therefore, women with elevated PRL levels retain normal menses and fertility. We studied six men, aged 28-53 yr (mean, 45 yr), in whom hyperprolactinemia was initially considered to be the cause of their erectile dysfunction. PRL levels ranged from 25-92 ng/mL (normal, 2-15 ng/mL), but T and gonadotropin levels were normal, suggesting that PRL was not disrupting gonadotropin and gonadal steroid function. The results of magnetic resonance imaging studies of the pituitary gland were normal. Separation by Sephadex G-100 column chromatography showed a predominance (85-90%) of big (60 kDa) and big big ( > 150 kDa) PRL, in contrast to the predominance of 22-kDa PRL in normal subjects. Nocturnal tumescence testing was normal, supporting the diagnosis of psychogenic impotence in these subjects, and potency returned after counseling. Hence, the biologically inactive macroprolactinemia did not cause any organic derangement in erectile function. It further obscured and delayed the appropriate diagnosis and treatment of these individuals.

Adult↗
PubMed1996

Growth hormone synthesized and secreted by human thymocytes acts via insulin-like growth factor I as an autocrine and paracrine growth factor.

There is increasing evidence that GH can influence immune function and that it is secreted by lymphocytes. In the present study we investigated the endogenous synthesis and secretion of GH and insulin-like growth factor I (IGF-I) from human thymocytes and evaluated the autocrine/paracrine effects of GH and IGF-I on T cell and thymic epithelial cell proliferation. First, the presence of thymic GH and IGF-I was detected by RIA of thymocyte extracts. Next, using a hormonal enzyme-linked immunoplaque assay, we found that thymocytes secreted GH and IGF-I. Further, we documented the endogenous synthesis of GH by human thymocytes using [35S]methionine labeling followed by immunoprecipitation, gel electrophoresis, and autoradiography. We then evaluated the physiological role of endogenously generated GH and IGF-I. Using an affinity-purified-GH polyclonal antibody, we observed a marked inhibition (P < 0.04) of phytohemagglutinin-stimulated thymocyte proliferation, suggesting an autocrine/paracrine role for the secreted GH. Further, we observed significant (P < 0.001) increases in thymocyte proliferation in cultures stimulated with varying doses of GH and IGF-I. Also, conditioned medium of human thymocytes (1 x 10(5) cells) stimulated with GH for 48 h contained a significant (P < 0.001) amount of IGF-I. Thymocyte proliferation stimulated by GH was significantly (P < 0.01) inhibited by monoclonal as well as polyclonal human IGF-I antisera. Finally, we studied the paracrine effect of thymocyte-secreted GH on human primary thymic epithelial cell (TEC) cultures. A significant (P < 0.05) increase in [3H]thymidine uptake in TEC cultures after GH addition was observed, which was abolished by GH antiserum. Polyclonal and monoclonal IGF-I antisera significantly (P < 0.05) inhibited GH-stimulated TEC proliferation. In summary, human thymocytes synthesize and secrete GH and IGF-I. Further, GH functions as an autocrine/paracrine growth factor in the human thymus via locally synthesized IGF-I.

Blotting, Western↗
PubMed1996

Alteration of peripheral blood lymphocyte subsets in essential hypertension.

OBJECTIVE: To assess lymphocytic subpopulation by labelled monoclonal antibody technique in a small group of patients with untreated essential hypertension (EH) and to detect any alteration with control of blood pressure. DESIGN: Prospective study with phenotypic estimation of lymphocytes at presentation and a minimum of two weeks after the control of blood pressure. SETTING: Referral, tertiary care hospital. PATIENTS: Group 1, normotensive controls (n = 10); group 2, mild to moderate essential hypertension (n = 10); group 3, severe (accelerated/malignant) hypertension (n = 10). All the secondary causes of hypertension were ruled out by a thorough history, physical examination and appropriate radiological and biochemical investigations. TESTS: Venous blood samples, taken at entry and a minimum of two weeks after control of blood pressure, were analyzed by alkaline phosphatase antialkaline phosphatase (APAAP) antibody technique for CD4, CD3, CD8 and CD22. Peripheral lymphocytes were separated and cocultured with phytohemagglutinin (PHA) for 72 h and assayed for CD25 by the APAAP technique. MAIN RESULTS: In untreated patients with EH (groups 2 and 3), there was a significant down regulation of CD3, and CD4 lymphocytes whereas the proportion of mature CD22 cells increased. In group 3 there was a significant down regulation of CD25 with PHA stimulation. A negative correlation was observed between CD25 and diastolic pressure upon pooling the results of groups 2 and 3. No significant alteration in these parameters was observed following control of blood pressure with drugs for up to two weeks. CONCLUSION: In this small group of patients with untreated EH, a significant alteration in the lymphocytic repertoire was observed. Whether this will be found in large groups of hypertensives remains to be seen.

Adult↗
PubMed1996

Role of immunophenotyping in characterisation of blast crisis of chronic myeloid leukemia--a study of 25 cases.

The blast cell populations of 25 patients of chronic myeloid leukemia in blast crisis (CML-BC) were studied for morphological, cytochemical and immunophenotypic features. The patients were divided into 6 broad groups based upon the pattern of surface marker positivity-myeloblastic, mixed myeloblastic, megakaryoblastic, mixed lineage, lymphoid and undifferentiated blast crisis. Myeloperoxidase (MPO), Sudan Black B (SBB) and Chloroacetate esterase (CAE) stains showed 100% specificity for the myelomonocytic lineage but the sensitivity was low. Periodic acid Schiff (PAS) stain was neither specific nor sensitive for the lymphoid lineage. Immunophenotyping as compared to morphologic and cytochemical assessment, was seen to be most useful for assigning a lineage to leukemic cells in CML-BC.

Adult↗
PubMed1995

Aplastic anaemia versus hypocellular myelodysplastic syndrome.

It is important to differentiate non-dyplastic aplastic anaemia from hypocellular myelodysplastic syndrome (MDS). Four patients presenting with hypocellular bone marrow and different evolution patterns are being described. Certain morphological features and variable hypocellularity were found to be useful indices for this purpose.

Adolescent↗
PubMed1995

Paraproteins and plasma cell dyscrasias.

Serum protein electrophoresis done on 1100 patients with various diseases in one year demonstrated M-band in 31 patients. Most (87%) had the classical features of plasma cell dyscrasia (PCD), however a few had unusual presentations which are highlighted. A 22-year-old male operated for a massive tumour of the scapula clinically diagnosed as chondrosarcoma revealed plasmacytoma with amyloid on histology. Another case of kala-azar presented with features akin to that of PCD and one case had dual malignancies. Such a high incidence of PCDs with varied picture in a short time is not usually seen in other parts of this country; a fact which may be due to lack of awareness.

Adult↗