Search PubMed⌕ Search

Biomedical subjects

A K Bhalla

Publications and source records attributed to A K Bhalla.

At least 73 records · Page 4Linked to original sources

1 alpha,25-dihydroxyvitamin D3 induces maturation of the human monocyte cell line U937, and, in association with a factor from human T lymphocytes, augments production of the monokine, mononuclear cell factor.

The monocyte factor, interleukin 1, or other factors homologous with interleukin 1, modulates functions of a variety of cells, including T and B lymphocytes, synovial cells, and chondrocytes. We have reported that a human monocyte cell line, U937, produces interleukin 1 when incubated with a soluble factor from lectin-stimulated T lymphocytes. We have also shown that U937 cells have a specific cytosolic receptor for 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25[OH]2D3). We now report that 1 alpha,25(OH)2D3(10(-11)-10(-10) M) induces maturational changes in the U937 cells similar to those produced by conditioned medium from lectin-stimulated T lymphocytes (increase in Fc receptors and OKM1 binding and decrease in proliferation), but does not induce monokine production as measured by mononuclear cell factor activity. 1 alpha,25(OH)2D3 is 200-300-fold more effective than 25-hydroxyvitamin D3, which is consistent with the known biological potency of these vitamin D3 metabolites. 1 alpha,25(OH)2D3 and the lymphokine together markedly augment maturational effects and, in addition, augment monokine production. The specificity of the interaction is further demonstrated by the lack of augmentation of monokine production with 1 beta,25-dihydroxyvitamin D3 in the presence of lymphokine. These interactions of a classical hormone and the hormonelike product(s) of the immune system with U937 cells serve as a model for human monocyte/macrophage differentiation and suggest a role for these interactions in some aspects of inflammation.

Antigens, Surface↗

1,25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation.

The proliferative response of murine spleen and thymus cells to antigen but not to lectin was inhibited by the active metabolite of vitamin D3, 1,25-(OH)2D3. To directly examine the effect of 1,25-(OH)2D3 on T cell activation in the absence of other complicating interactions, we utilized a panel of cloned Ia-restricted T cell hybridomas that secrete IL 2 on activation by cloned Ia-bearing stimulator cells (TA3) or when stimulated by mitogen. Physiologic concentrations of 1,25-(OH)2D3 (0.01 to 0.1 nm) inhibited the antigen-induced secretion of IL 2 by several of these T cell hybridomas. This inhibition was dependent on the concentration of the free hormone and could be overcome by increasing the number of Ia-bearing stimulator cells used. Pretreatment of the T hybridoma but not the TA3 stimulator cell with 1,25-(OH)2D3 resulted in inhibition of activation. These results are consistent with the finding that specific 1,25-(OH)2D3 receptors are present on the T cell hybridomas but are lacking in TA3 cells. 1,25-(OH)2D3 failed, however, to inhibit the activation of the T cell hybridomas by lectin or by an anti-Thy-1 antibody. These findings suggest that 1,25-(OH)2D3 may be interfering with early events of antigen-induced T cell activation, perhaps by hindering T cell recognition of the relevant antigen on stimulator cell surfaces. This system should prove useful in studying the molecular mechanisms by which 1,25-(OH)2D3 acts to inhibit T cell activation and subsequent IL 2 production.

Animals↗

Specific high-affinity receptors for 1,25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation.

Human peripheral blood monocytes have high affinity binding sites for 1,25-(OH)2D3 (Kd 0.14 nM, sedimentation coefficient 3.7S). Resting human peripheral blood T lymphocytes, however, do not have a demonstrable 1,25-(OH)2D3 receptor. After activation with phytohemagglutinin the T cells exhibit the receptor within 24 h, and this expression is blocked by cycloheximide. The receptor in activated T lymphocytes has a sedimentation coefficient of 3.7S and a high affinity (Kd 0.10 nM) for the ligand.

Calcitriol↗

The synthesis and secretion of cartilage procollagen.

1. Isolation of free and membrane-bound ribosomes from embryonic chick sternal-cartilage cells labelled for 4min with [14C]proline and their subsequent analysis for hydroxy[14C]proline indicated that cartilage procollagen biosynthesis occurs on bound ribosomes. 2. Nascent procollagen polypeptides on bound ribosomes isolated from cells labelled with [14C]lysine were found to contain hydroxy[14C]lysine indicating that hydroxylation of lysine commences while the growing chains are still attached to the ribosomes. 3. Analysis of bound ribosomes labelled with either [14C]proline or [14C]lysine on sucrose density gradients indicated that cartilage procollagen is synthesized on large polyribosomes in the range 250-400S. 4. Microsomal preparations isolated from cells pulse-labelled for 4 min with [14C]proline were used to determine the direction of release of nascent procollagen polypeptides. Puromycin induced the vectorial release of nascent procollagen polypeptides into the microsomal vesicles suggesting that the first step in the secretion of procollagen polypeptides is their transfer from the ribosomes through the membrane of the endoplasmic reticulum into the cisternal space. 5. The procollagen polypeptides secreted by cartilage cells were shown to be linked by inter-chain disulphide bonds. 6. Examination of the state of aggregation of pro-alpha chains in subcellular fractions isolated from cartilage cells labelled with [14C]proline for various periods of time have provided data on the timing and location of inter-chain disulphide-bond formation. This process commences in the rough endoplasmic reticulum after the release of completed pro-alpha chains from membrane-bound ribosomes. Pro-alpha chains isolated from fractions of smooth endoplasmic reticulum were virtually all present as disulphide-bonded aggregates, suggesting that either disulphide bonding is completed in this cellular compartment, or that procollagen needs to be in a disulphide-bonded form to be transferred to this region of the endoplasmic reticulum. 7. Comparison of these results with previously published data on disulphide bonding in tendon cells suggest that the rate of inter-chain disulphide-bond formation is significantly slower in cartilage cells.

Animals↗

Retro-peritoneal cystic lymphangioma in association with fetal hydantoin syndrome.

Antiepileptic drugs are known to be teratogenic. Use of phenytoin during pregnancy can cause various congenital malformations leading to 'fetal hydantoin syndrome'. One such case reported is unique in the sense that it occurred with retroperitoneal cystic lymphangioma, itself a rare condition. Such an association is not described elsewhere.

Abnormalities, Drug-Induced↗

Osteoporosis in early ankylosing spondylitis: a primary pathological event?

Patients with severe ankylosing spondylitis of long duration often have spinal osteoporosis secondary to ankylosis and immobility. Bone mineral density of defined regions of the lumbar spine, femoral neck, and carpus was measured in 25 men who met accepted diagnostic criteria for ankylosing spondylitis but had early disease, with normal mobility and no, or very minor, radiological evidence of lumbar spine involvement. Compared with age-matched male controls, patients with ankylosing spondylitis had a significantly lower hydroxyapatite density in the lumbar spine (mean [SD] 0.82 g/cm2 [0.12] vs 0.91 g/cm2 [0.11]) and in the femoral neck (0.83 g/cm2 [0.11] vs 0.92 g/cm2 [0.11]). There was no significant difference in carpal bone mineralisation density. The pattern of bone loss in these patients indicates early loss of trabecular bone in ankylosing spondylitis, possibly from a systemic cause, but biochemical indices of calcium turnover were similar in patients and controls.

Adolescent↗

A longitudinal study of growth in length and weight of Punjabi infants in Chandigarh, India.

One hundred and fifty-four Punjabi infants (86 male, 68 female) were followed longitudinally and their lengths and weights measured each month during the first year of life. Monthly distance and velocity means for their weight and crown-heel length with the respective standard deviations are presented. The general pattern of growth is characterized by a period of rapid initial increase followed by a period of slower increment during the second half of infancy. Length velocity decreased from birth onwards, but weight velocity shows a peak at around 1.5 months, followed by a decline.

Aging↗

Assessment of malnutrition in alcoholic and non alcoholic cirrhotics.

OBJECTIVE: To study the nutritional status in patients with chronic liver disease using anthropometric techniques. METHODS: A total of 60 cirrhotic patients (30 Alcoholic (AC), 30 Non-alcoholic (NAC) and 30 control (CO) subjects were studied. Nutritional status was assessed using anthropometric measurements such as stature, body weight, body mass index, (BMI), skinfold thickness measurements and mid upper arm muscle circumference. Serum protein, serum albumin and globulin were measured. RESULTS: The skinfold thicknesses were significantly lower in NAC group of patients. In contrast the AC group of patients showed significantly lower mid upper arm muscle circumference values. Both groups of cirrhotic patients showed significantly lower total serum protein and serum albumin levels. CONCLUSION: Body fat is relatively more affected in NAC group of patients and muscle mass is more affected in AC group of patients.

Adult↗