Biomedical subjects
Publications and source records attributed to A Chakraborty.
A 7-year-old child had unusual manifestation of cryptococcosis; liver and lymph node involvement predominated. There was evidence of cryptococcal hepatitis, extrahepatic biliary obstruction, and subsequent cirrhosis of the liver. Despite widespread dissemination, underlying immune disturbance was not evident. The patient was treated with two courses of amphotericin and 5-flucytosine.
Cell lines of cutaneous origin, namely melanocytes and keratinocytes, were previously demonstrated to exhibit functional melanocyte-stimulating hormone (MSH) receptors that are up-regulated by ultraviolet (UV) radiation and by MSH itself. In this study, it is demonstrated that UVB irradiation, exposure to MSH, or exposure to N6,O2-dibutyryl cyclic adenosine monophosphate stimulates production of mRNAs for both alpha MSH receptors and proopiomelanocortin in cultured mouse Cloudman S91 melanoma cells, and that UVB stimulates production and release of MSH and adrenocorticotropin peptides in both melanoma cells and transformed PAM 212 mouse keratinocytes. The results add support to the hypothesis that the effects of UVB on cutaneous melanogenesis are mediated through a series of coordinated events in which MSH receptors and proopiomelanocortin-derived peptides play a central role.
AIMS AND BACKGROUND: Natural killer (NK) cell activity is known to be depressed in neoplastic diseases, and ageing influences the cytotoxicity of NK cells. However, very little information is available on the responsiveness of NK cells of cancer patients to the stimulating effects of interleukin-2 (IL-2) as a function of age. METHODS: We assessed in vitro IL-2 induced modulation of NK activity in peripheral blood lymphocytes (PBL) from 7 young (30-50 years) and 9 elderly (55-78 years) male patients with carcinoma of the oral cavity. In these patients generation of lyphokine activated killer (LAK) activity was also studied. NK and LAK activity of PBL were measured in 14 age and sex matched healthy volunteers as who served as controls. Cytotoxicity of the NK and LAK cells was assayed against NK sensitive K562 and NK resistant Daudi cells in 4-h 51 Cr-release assays. RESULTS: NK activity in the cancer patients was significantly lower than that in healthy volunteers. In both groups the younger subjects had higher NK activity than the elderly ones. NK cells of both young and elderly healthy controls responded similarly to 24-hour in vitro exposure to human recombinant IL-2 (rIL-2, 100 u/ml) with highly increased cytotoxicity. Though there was significant enhancement of NK activity with rIL-2 in both young and elderly cancer patients, the rIL-2 induced NK cytotoxicity in the elderly patients was much lower than the basal level of NK activity of the age matched controls. Interestingly, LAK activity, generated by 3-7 days of in vitro exposure of PBL to rIL-2 was comparable in the cancer patients and healthy volunteers. CONCLUSION: The data suggest serious impairment of NK function in elderly patients with oral carcinoma. Generation of LAK activity with exogenous IL-2 could be an important modality of treatment in these patients.
An eIF-2 associated 67-kDa protein (p67) protects eIF-2 alpha-subunit from eIF-2 kinase(s) catalyzed phosphorylation and promotes protein synthesis in the presence of active eIF-2 kinase(s). p67 is a glycoprotein and contains multiple O-linked GlcNAc moieties. We have now studied the roles of hemin, p67, and the glycosyl residues on p67 in the regulation of eIF-2 alpha-subunit phosphorylation in reticulocyte lysates. The results are as follows: (i) Both hemin and p67 inhibited HRI (heme-regulated protein synthesis inhibitor) and dsI (double-stranded RNA activated protein synthesis inhibitor) catalyzed phosphorylation of eIF-2 alpha-subunit in vitro. However, only hemin, and not p67, inhibited casein kinase catalyzed phosphorylation of eIF-2 beta-subunit. (ii) Only p67, and not hemin, inhibited eIF-2 alpha-subunit phosphorylation by eIF-2 kinase(s) in reticulocyte lysate. Significant eIF-2 alpha-subunit phosphorylation was observed even in the presence of hemin when p67 in the reticulocyte lysate was removed by treatment with p67 antibodies. (iii) Reticulocyte lysate contains a p67-deglycosylase in latent form, and hemin prevents activation of this deglycosylase. In the absence of hemin, this p67-deglycosylase is activated. Once activated in the absence of hemin, the activated deglycosylase deglycosylates p67, even in the presence of hemin. This inactivates p67 and allows eIF-2 kinase to phosphorylate eIF-2 alpha-subunit and inhibit protein synthesis. Protein synthesis in reticulocyte lysate is thus regulated by two novel cascades of covalent modifications: protein deglycosylation leading to protein phosphorylation.
Gongylonema infection in 11 captive wild herbivores out of 214 animals (5.14%) was recorded at post mortem examination. Species of animals affected were spotted deer (6.06%), sambar (7.14%), mouse deer (16.66%), nilgai (11.76%), serow (16.66%) and giraffe (20.0%). The affected areas showed fibrinous inflammation. On scanning electron microscopic study, destruction and disruption of the epithelium were noted, and cuticular bosses originating from the anterior tip of the parasite were observed.
Melanin synthesis of follicular melanocytes is strictly coupled to the growth stage of the hair cycle (anagen), ceases during follicle regression (catagen), and is absent throughout the resting stage (telogen). Having previously characterized the expression and activity of melanogenesis-related proteins during the telogen-anagen transition of the murine hair cycle (JID 96:172, 1991), we here report a biophysical and biochemical analysis of follicular melanogenesis during the anagen-catagen-telogen transformation of the C57 BL-6 mouse hair cycle. Tyrosinase activity and concentration as well as dopachrome tautomerase activity were compared with melanin synthesis, as measured by electron paramagnetic resonance spectroscopy (EPR). The visible changes in skin color and the histologically appreciable switch-off of melanin formation during the anagen-catagen transformation were accompanied by a steep decline in 1) the melanin-associated EPR signal of full-thickness mouse skin, 2) tyrosinase and dopachrome tautomerase activities, and 3) the skin concentration of 80-85-kD melanogenesis related protein and 66-68-kD tyrosinase protein. Telogen skin displayed a minimum of the EPR amplitude as well as of tyrosinase and dopachrome tautomerase activity detected. By EPR, only eumelanin was identified during all hair cycle stages. The gradual switch-off of melanogenesis during anagen VI started with an unexpectedly early decline of the EPR melanin signal, followed by dopachrome tautomerase activity and the concentration of 80-85-kD melanogenesis related protein. The initiation of catagen was characterized by a significant and rapid decrease in activity and concentration of tyrosinase, and was accompanied by a second drop in dopachrome tautomerase activity. Together, these biochemical and biophysical parameters of follicular melanogenesis serve as novel and differential markers for the imminent termination of anagen and the development of catagen. They also show that the switch-off of melanogenesis during the anagen-catagen-telogen transition is a stochastic process commencing already in mid anagen VI.
The protein and nucleic acid contents of liver, spleen, muscle, kidney, and brain were studied in experimental autoimmune thyroiditis. Protein and ribonucleic acid levels showed a positive increase in the case of liver, spleen, and muscle on days 56 and 98 after immunization and on day 147 they reached control levels. Spleen deoxyribonucleic acid showed a significant increase on day 56, whereas the other days showed no change. Kidney and brain tissue revealed no change.
Administration of vanadium as ammonium monovanadate (0.005 microgram/0.1 ml/mouse/day) was found to reduce the tumor cell proliferation in the host mice bearing Dalton's lymphoma. The high activity of gamma-glutamyl transpeptidase (GGT), a neoplastic marker, was seen in the host cells bearing lymphoma. Vanadium effectively prevented an increase in activity of gamma-glutamyl transpeptidase and maintained a sustained low activity of this enzyme. In addition, an improvement of the hematological aspects of the mice and almost fourfold elevation of erythropoietin (Epo) was obtained following vanadium treatment. This increase in Epo activity may play a vital role in regulating the growth of cellular neoplasia. The present study further confirms the antitumorigenic potential of vanadium in the control of tumor progression in lymphoma via modulating several factors involving erythropoiesis and may emerge as a new chemopreventive agent for the future.
Mechanism of regulation of eIF-2 alpha-subunit phosphorylation by dsI and p67 was studied. The results are as follows: (1) At low dsI concentration, p67 protected equimolar concentration of eIF-2. (2) At high dsI concentration, dsI efficiently phosphorylated eIF-2 alpha-subunit even when equimolar concentrations of both p67 and eIF-2 were present. Significantly increased p67 concentration was necessary to protect eIF-2 alpha-subunit at high dsI concentration. (3) dsI was also phosphorylated as it phosphorylated eIF-2 alpha-subunit. p67 inhibited both eIF-2 alpha-subunit and dsI phosphorylation similarly. (4) Although the [32P]-labelled dsI formed during the reaction could be effectively chased upon subsequent addition of excess unlabelled eIF-2 and ATP, the [32P] labelled eIF-2 formed under identical conditions, retained most of the radioactivity. (5) dsI coimmunoprecipitated with three subunit eIF-2 and p67 inhibited this coimmunoprecipitation reaction. It has been proposed: Three subunit eIF-2 and free p67 are in equilibrium with eIF-2 bound to p67 and, eIF-2.p67 complex is resistant to dsI phosphorylation. Activated dsI is already phosphorylated. At high concentration, dsI(P) can bind to free three subunit eIF-2 and form eIF-2.dsI(P) complex. dsI(P) in this complex then transfers its phosphoryl residue to eIF-2 and forms eIF-2 alpha(P) in an irreversible reaction. In a subsequent reaction, unphosphorylated dsI is autophosphorylated using [gamma 32P]-ATP and the cycle continues. Inhibition of eIF-2 alpha-subunit phosphorylation by p67 blocks this phosphorylation cycle and consequent dsI phosphorylation.
The survey carried out on 201 infants of Calcutta aged 6-12 months to find out the localised disturbances associated with the eruption of the primary teeth, as judged through a questionnaire revealed that the most common disturbance was the inflammation of gums followed by flushing of cheeks, ulcers in mouth, cheek rash and eruption cyst.
Neuro-2a neuroblastoma cells, when differentiated via a cAMP-dependent pathway by treatment with anti-GM3 monoclonal antibody, accumulated a high level of pp60c-src protein and pp60c-src kinase activity just before the onset of neurite formation. The specific kinase activity of the accumulated c-src protein was found to be comparable to that of normal cerebellar neurons, but was about 6- to 8-fold higher than that of normal astrocytes. These results, and migrations of peptide fragments in the SDS-polyacrylamide gels after V8 proteolysis, strongly indicate the accumulation of the neuron-specific isoform of the c-src protein (pp60c-srcN) in the GM3 antibody-treated Neuro-2a cells. Similar high levels of pp60c-src protein and pp60c-src kinase activity were observed in the Neuro-2a cells differentiated via a cAMP-dependent pathway by treatment with dibutyryl cAMP, but not in the same cell line when differentiated via a cAMP-independent pathway with 5-bromo-2'-deoxyuridine. These results demonstrate that the accumulation of high levels of the neuron-specific isoform of the pp60c-src protein (pp60c-srcN) in the Neuro-2a neuroblastoma cells depends on the specific signal transduction pathway involved during the differentiation of these cells.
A eukaryotic initiation factor 2 (eIF-2) associated 67-kDa polypeptide (p67) protects the eIF-2 alpha-subunit from eIF-2 kinase(s) catalyzed phosphorylation, and this promotes protein synthesis in the presence of active eIF-2 kinase(s), [Datta, B., et al. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 3324-3328]. This report presents the results of studies related to characteristics of p67 action and the mechanism of p67:eIF-2 interaction: (1) p67 antibodies inhibited protein synthesis in hemin-supplemented rabbit reticulocyte lysates, and such inhibition was reversed by preincubation of the antibodies, specifically with p67. (2) p67 inhibited HRI- and dsI-catalyzed phosphorylations of the eIF-2 alpha-subunit and histones, but it did not inhibit casein kinase catalyzed phosphorylation of the eIF-2 beta-subunit. (3) p67 bound specifically to the eIF-2 gamma-subunit. p67 co-immunoprecipitated with the eIF-2 subunits when a p67/eIF-2 mixture was treated with p67 or eIF-2 subunit antibodies and protein A agarose. However, when eIF-2 was preincubated specifically with the eIF-2 gamma-subunit antibodies, subsequent co-immunoprecipitation of p67 with the eIF-2 subunits was completely inhibited. Similarly, preincubation of p67 and p67 antibodies prevented subsequent p67 binding to eIF-2. Preincubation of eIF-2, with either eIF-2 alpha- or beta-subunit antibodies, had no effect on p67 co-immunoprecipitation with the eIF-2 subunits. (4) p67:eIF-2 interaction is necessary for p67 activity to protect the eIF-2 alpha-subunit from eIF-2 kinase(s) catalyzed phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)
Receptors for melanotropin (MSH) were found to be expressed by immortalized primary human epidermal keratinocytes (RHEK-1). Using 125I-beta MSH as a probe, the MSH receptors from mouse melanoma cells and human keratinocytes were found to be remarkably similar. In each cell line, there were high and low affinity receptors, with the high affinity classes showing positive cooperativity. Competition of 125I-beta MSH for binding with non-radioactive MSH revealed similar profiles. Cross-linking studies, followed by gel electrophoresis and autoradiography, showed almost identical gel migration patterns. Both cell types expressed internal as well as plasma membrane binding sites. MSH receptors on both cell types were up-regulated by ultraviolet light and by MSH itself. Although the function of MSH receptors expressed by the immortalized keratinocytes is unknown, the results are consistent with recent reports that proliferation of epidermal keratinocytes is stimulated by MSH and that proopiomelanocortin genes are expressed in the epidermis. These results support a model in which keratinocytes and melanocytes, interacting in an "epidermal-melanin unit," each respond to UV light signals with increased MSH receptor activity.
Hydroquinone administration in Bufo melanostictus causes an induction of indole amine 2,3-dioxygenase in skin and liver while simultaneously inhibiting tyrosinase in these organs. The result is discussed with the reports of higher urinary excretion of abnormal indole metabolites including derivatives of anthranilic acid in vitiliginous subjects (Roychoudhury and Chakraborty, Clinica. Chim. Acta 22, 298, 1968; Kurbanov and Berezov, Vopr. Med. Khim. 22, 683, 1976).
The pattern of human retinoblastoma (RB1) gene protein expression was directly examined in normal and malignant human colorectal tissues and in seven colorectal carcinoma cell lines by immunohistochemistry using the mouse monoclonal antibody (RB-MAb-1) directed against the retinoblastoma protein (RB). This is the first demonstration of RB immunostaining in adult human colonic epithelium and colorectal carcinomas. Specificity using RB-MAb-1 was confirmed by western blot analysis, which showed bands of 110-116 kDa corresponding to the sizes of unphosphorylated and phosphorylated RB. RB staining of normal adult colonic epithelium was confined to the nucleus and was most intense in the transitional zone of the crypt, whereas lumenal cells (fully differentiated) were RB negative. Primary colorectal carcinomas and all the colon cancer cell lines stained positively for nuclear RB, but the expression was heterogeneous with varying fractions of RB negative cells present. Because we and others have previously shown that loss or inactivation of the RB1 gene is infrequent in colorectal carcinomas, reduced RB expression in such cells is probably due to a cellular regulatory mechanism. For example, RB negative cells may be those in early-G1 phase (known to have reduced RB levels) or growth-arrested cells that have differentiated. The ability to directly detect RB in primary colorectal carcinomas will permit assessment of whether heterogeneous expression of the RB1 gene product has prognostic significance for survival of patients with this cancer.
Explore the source record for details and available documents.
Seventy-nine cases of one specific type of depressive reaction in children who had mild fever during or just prior to the episode of depression were studied during a period of 16 years between 1968 and 1984. Comparison of the observed group with the control groups established the specificity of the episode depression with only one type of fever which was most probably of viral origin.
Alterations in large gut associated lymphatic tissues (LGALT) were studied histologically during 20-methylcholanthrene (MCA) induced colorectal carcinogenesis. Precancerous changes in LGALT included hyperplasia, hyperchromasia of lymphocytes and enlargement of lymphoid follicles. In addition, follicular invasion in muscular layer and cellular disorganization of diffuse lymphatic tissues were observed in neoplasia. Since, LGALT showed remarkable changes during carcinogenesis, this aspect may be considered during assessment of preneoplastic lesions, along with other histologic features of early neoplasia.