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Biomedical subjects

M Sensi

Publications and source records attributed to M Sensi.

At least 91 records · Page 5Linked to original sources
PubMed1983

Labelling of lymphocytes with indium 111 oxine: effect on cell surface phenotype and antibody-dependent cellular cytotoxicity.

Indium 111 oxine is currently used to label peripheral lymphocytes in order to study the kinetics of these cells in vivo. Since the quantity of radioisotope for labelling is still a matter of controversy, we have investigated in vitro the effect of increasing the concentration of indium 111 oxine on the lymphocyte surface phenotype and the antibody-dependent cellular cytotoxicity (ADCC) using lymphocytes from normal subjects. The cell surface phenotype, as evaluated by 2 monoclonal antibodies, was not affected whereas ADCC, at any of the doses used, was significantly reduced compared to the baseline value. The implications of these results for the use of indium 111 oxine for the in vivo studies are discussed.

Adult↗
PubMed1983

Monoclonal antibodies defined abnormalities of T-lymphocytes in type I (insulin-dependent) diabetes.

Peripheral T-lymphocytes subsets have been investigated in 36 patients with type I (insulin-dependent) diabetes of varying duration, 18 patients with type II (non-insulin-dependent) diabetes, and in 23 healthy subjects, using six different monoclonal antibodies. At the time of diagnosis of type I diabetes, there was evidence of an increase in cytotoxic T-lymphocytes, a decrease in suppressor T-lymphocytes, but a normal proportion of helper/inducer T-lymphocytes. In six of seven newly diagnosed cases studied, there was evidence of an increased number of activated T cells. An increase in activated T-cells was also found in 5 of 10 genetically susceptible islet cell antibody positive unaffected siblings in type I diabetic probands. In type I diabetes of long standing, the total T-cell population was decreased, largely due to a marked decrease in helper/inducer T-lymphocytes. Type II diabetic patients showed no abnormalities in T-lymphocyte subsets, making it unlikely that hyperglycemia was responsible for the changes observed. These results suggest that an imbalance of T-lymphocyte regulation is an important feature of type I diabetes and lend support for an immunologic role in its early pathogenesis.

Adolescent↗
PubMed1982

Histology of the islets of Langerhans following administration of human lymphocytes into athymic mice.

Lymphocytes from seven newly diagnosed insulin-dependent (Type 1) diabetics, five islet cell antibody positive unaffected children and five normal subjects were injected i.p. into athymic nude mice. A further six mice were injected with medium and six control mice received no injection. Blood was taken from the tail vein before injection for glucose determination. After 10 days blood was again obtained from the tail vein; the pancreas was removed under deep ether anaesthesia and the mice sacrificed by exsanguination. Routine histological sections of the pancreas were prepared. There was no difference between groups in respect of the initial blood glucose. However, final blood glucose levels were raised in all mice that had received an injection including medium only, the rise being statistically significant both after injection of lymphocytes from normal subjects (P less than 0.05) and from newly diagnosed diabetics (P less than 0.001). Histology did not reveal any evidence of 'insulitis' or islet cell damage although enlarged, hyperplastic islets could be found in each group of treated mice. We conclude that passive transfer of diabetes was not achieved in this animal model. Elevation of blood glucose levels and islet hyperplasia may simply reflect a non-specific 'stress' reaction.

Animals↗
PubMed1981

Increased killer cell activity in insulin dependent (type 1) diabetes mellitus.

Antibody dependent cell mediated cytotoxicity in relation to the levels of circulating killer cells was investigated in 16 newly diagnosed classical insulin dependent (Type 1) diabetics, 11 islet cell antibody positive non diabetic children with at least one HLA haplotype in common with their diabetic sibling, and in 15 normal controls. Antibody dependent cell mediated cytotoxicity was evaluated using, as target, 51Cr labelled human 0+ erythrocytes sensitised with an anti-CD antiserum. Killer cells were measured by the low affinity E-rosetting cell technique. Increased killer cell levels (greater than normal mean + 2SD) were accompanied by a significant enhancement in antibody dependent cell mediated cytotoxicity both in newly diagnosed diabetics (p less than 0.05) and in unaffected siblings (p less than 0.01). These preliminary results indicate that raised antibody dependent cell mediated cytotoxicity is a feature of insulin dependent diabetes at diagnosis and suggest that active B cell damage might be occurring some time before the onset of clinical symptoms.

Adolescent↗
PubMed1979

Evidence for raised K-cell levels in type-I diabetes.

The proportion of blood mononuclear cells forming low-affinity rosettes with sheep erythrocytes (K cells) was abnormally high in 13 (57%) of 23 children with classical type-1 diabetes at diagnosis but normal in children who had had diabetes for more than a year. A raised proportion of K cells was also found in 5 out of 10 unaffected siblings with islet-cell antibodies and at least one HLA haplotype in common with the diabetic proband; and in 10 (45%) of 22 subjects with type-1 diabetes and co-existent autoimmune thyroid disease irrespective of the duration of diabetes or the presence of islet-cell antibodies. These findings may be new evidence for lymphocyte-mediated beta-cell destruction and support the idea of immunogenetic heterogeneity within type-1 diabetes.

Adolescent↗
PubMed1978

Elevation of rat erythrocyte nucleotide levels following acute renal failure induced by glycerol or mercuric chloride.

Biochemical changes in the blood following induction of renal failure by glycerol or mercuric chloride have been studied in 16 rats. Plasma creatinine, urea and Pi levels indicated that renal impairment followed the same time course in both renal failure models, with the severest effects on day 3 and returning to normal by day 7. Erythrocyte ATP and guanine triphosphate (GTP) levels were significantly elevated above contorl values on day 1 and remained elevated in both models. ATP/ADP and GTP/GDP ratios also increased in both models. In renal failure the increased purine 'salvage' in the erythrocyte may be attributed to accumulation of purine metabolites in the serum associated with increased P-ribose-PP levels due to elevated cellular Pi. Nucleotide changes in both these models are analogous to those found in chronic renal failure in man.

Acute Kidney Injury↗
PubMedDate not supplied

Antibody-dependent and natural killer cytotoxicity in type 1 diabetes.

The antibody-dependent cell-mediated cytotoxicity and the spontaneous cell-mediated cytotoxicity against Chang liver cells in relation to the levels of circulating K-cells (low affinity E-rosetting cells) were investigated in 23 newly diagnosed insulin-dependent (Type 1) diabetics, and in 17 unaffected islet cell antibody-positive subjects. Antibody-dependent cell-mediated cytotoxicity was significantly increased in those newly diagnosed diabetics with K-cells levels greater than 2 SD above the mean of normal controls (p less than 0.02). A similar but not significant trend was also found in islet cell antibody-positive subjects with raised K-cells. Spontaneous cell-mediated cytotoxicity was not different in any of the groups. These results lend further support to the concept that antibody-dependent lymphocyte cytotoxicity is enhanced in type 1 diabetes at diagnosis.

Adolescent↗
PubMedDate not supplied

The importance of measuring Fc+ (killer) cells in insulin-dependent (type 1) diabetes.

The measurement of Fc+ (killer or K) cells in insulin dependent (Type 1) diabetes may be of considerable value in monitoring activity of immune disturbance. K cells were investigated in Type 1 diabetics, their relatives and normal controls employing two methods based upon different principles. A close positive linear correlation was observed between the two methods in all subjects. Type 1 diabetic patients showed an increased level of K-cells with both techniques. In addition there was a good correlation between raised levels of K-cells and the occurrence of organ specific autoantibodies.

Adolescent↗
PubMedDate not supplied

Inhibition of killer cell cytotoxicity induced by carbimazole in vitro.

The in vitro effect mediated by carbimazole (CBZ), a classical anti-thyroid agent on the antibody dependent cellular cytotoxicity (ADCC), low affinity E-rosetting cells (E-RFC) and high affinity E-RFC was investigated using lymphocytes from 11 normal subjects. CBZ at the doses of 250 and 500 mumol/l significantly reduced ADCC in all subjects studied. Low affinity E-RFC--mainly cells possessing receptors for the Fc portion of IgG and expressing cytotoxic properties in the ADCC system--were also significantly reduced following incubation with the same CBZ doses. These results suggest that CBZ, in addition to the known inhibitory effect on thyroid hormone synthesis, may be useful by depressing lymphocyte cytotoxicity in the treatment of autoimmune thyroid disease.

Antibody-Dependent Cell Cytotoxicity↗
PubMedDate not supplied

Formation and ways of detecting advanced glycation end-products in isolated human glomerular basement membrane and human serum albumin nonenzymatically glycated in vitro.

The formation of advanced glycation end-products (AGE) was investigated in samples of isolated human glomerular basement membrane (hGBM) and human serum albumin (hSA) which had been nonenzymatically glycated in vitro. In order to measure AGE, two methods which differ in principle--the standard spectrofluorescence technique and the spectrophotometric diazonium salt reaction--have been used and compared. Samples of finely homogenized hGBM and hSA were incubated for 10 days in buffer containing 500 mmol/L (9 x 10(3) mg%) and 100 mmol/L (1.8 X 10(3) mg%) D-glucose respectively. At the end of the incubation period, the ambient glucose was removed and the samples were incubated for a further 10 days in glucose-free buffer. During this time, loosely bound sugar was released into the buffer; at the end of the incubation, the emission fluorescence at 440 nm (following continuous excitation at 370 nm) and the absorbance at 492 nm of the glycated hGBM and hSA samples were measured and found to be significantly increased by comparison with native samples (1-way ANOVA: p less than 0.05 with both techniques). Comparison of the two techniques used for AGE detection showed a positive linear correlation (Pearson's correlation coefficient r = 0.714; n = 8; p = 0.02). The released glucose probably originates from reversal of the Schiff base (the first and reversible step of the nonenzymatic glycation reaction), whereas fluorescence and photometric findings prove the presence of stable AGE on both hGBM and hSA. It is concluded that AGE can indeed be formed and detected by two different methods in hGBM (and hSA) subjected to nonenzymatic glycation in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Basement Membrane↗
PubMedDate not supplied

The functional basis for nephrographic patterns in acute tubular necrosis.

There is considerable evidence that the principal functional abnormality in patients with acute reversible renal failure (ARF, or "acute tubular necrosis") is reduced cortical perfusion with diminished glomerular filtration. However, in such patients, high-dose intravenous urograms most commonly show an immediate obvious nephrogram. Since nephrographic density is believed to depend on the filtration of contrast medium into the tubular lumen, it is difficult to reconcile the early development of the nephrogram if glomerular filtration is reduced. Extensive experiments with both mercuric chloride and glycerol rat models of ARF have confirmed rapid intraluminal accumulation of contrast medium, albeit in reduced amounts. Studies using the normally filtered compound sodium nitroprusside and its precipitation as "prussian blue" suggest rapid transtubular diffusion from peritubular capillaries in kidneys with ARF. This, it is suggested, is also the mechanism for the rapid intraluminal ingress of contrast media and explains the early appearance of nephrogram. The less common intravenous urogram finding in ARF of a slowly developing and increasingly dense nephrogram may then represent cases with only slight tubular necrosis with predominant reduction in glomerular filtration.

Acute Kidney Injury↗
PubMedDate not supplied

Two autologous melanoma-specific and MHC-restricted human T cell clones with identical intra-tumour reactivity do not share the same TCR V alpha and V beta gene families.

Among tumour infiltrating lymphocytes (TIL) of a melanoma patient, A CD8+, WT31+ CTL clone (8B3) had been previously isolated which exhibited specific and MHC-restricted lytic activity against the autologous tumour. To molecularly characterize T cell receptor (TCR) alpha and beta transcripts of clone 8B3, sequence analysis of several cDNA isolates was carried out. Such analysis indicated that the functional alpha and beta chain of 8B3 are composed of V alpha 2.1/J alpha/C alpha and V beta 8.2/D beta/J beta 1.2/C beta 1 gene segments. Eleven additional melanoma-reactive T cell clones from the same patient (one MHC-restricted and 10 MHC-unrestricted) were analysed for usage of the 8B3 V alpha 2 and V beta 8 gene segments by Northern blot hybridization. Neither the V alpha 2 nor the V beta 8 segments were used by 8D9, the second MHC-restricted melanoma-specific TIL clone that displayed intra-tumour reactivity identical to that of 8B3 recognizing only 4 out of 25 melanoma clones isolated from the same metastases. No V beta 8 expression was found among the MHC-unrestricted T cell clones and all but two (found in duplicate as 4C4 and 4A6) were also negative for V alpha 2 expression. Southern blot analysis revealed different TCR beta chain rearrangements in most MHC-unrestricted T cell clones providing evidence of their independent derivation. Taken together these findings show that TCR of clone 8B3 is unique in composition and not shared by MHC-unrestricted melanoma-reactive T cell clones. The different set of V alpha and V beta families used by clone 8D9 further indicates that the TCR usage in the specific and MHC-restricted response to melanoma can be polyclonal.

Amino Acid Sequence↗