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Biomedical subjects

L A Fernandez

Publications and source records attributed to L A Fernandez.

At least 73 records · Page 4Linked to original sources
PubMed1984

Normal T cell colony numbers in untreated patients with chronic lymphocytic leukaemia (CLL).

T cell colony formation in normal individuals and untreated patients with chronic lymphocytic leukaemia (CLL) was studied to determine if there is a deficiency in the number of T cells capable of forming colonies in this disease. In normal individuals, assays using enriched T cells did not reveal the total number of potential colony forming cells, preventing accurate assessment in patients with B cell CLL where enriched T cells are mandatory. Conditions were therefore optimized to obtain the maximal number of colonies, so that accurate comparisons could be made between the potential of normal individuals and patients with CLL. Addition of normal autologous non-T cells to enriched T cells enhanced colony numbers in normal individuals to those seen in the whole mononuclear population. However, addition of normal non-T cells to CLL T cells would have caused a mixed lymphocyte reaction (MLR), which influences T cell colony numbers. Therefore the MLR was bypassed by adding to the enriched T cells, supernatants having characteristics of Interleukin-1 or commercially obtained Interleukin-2. The supernatants with Interleukin-1 activity enhanced T cell colony numbers comparably in both normal individuals and patients with CLL. Interleukin-2 did not increase T cell colony numbers in normal individuals and the increase seen in patients with CLL were not significant. Thus the effect of the lymphokines on T cell colony numbers was comparable in both normal individuals and untreated patients with CLL. We therefore concluded that there are normal numbers of cells which have the potential to form T cell colonies in untreated patients with CLL.

B-Lymphocytes↗
PubMed1983

Immunoglobulin secretory function of B cells from untreated patients with chronic lymphocytic leukemia and hypogammaglobulinemia: role of T cells.

The mechanism of the hypogammaglobulinemia in patients with chronic lymphocytic leukemia (CLL) was studied by determining the generation of specific immunoglobulin-secreting cells in response to mitogen and antigen stimulation in culture. Normal peripheral blood B lymphocytes from 18 normal subjects cocultured with equal numbers of autologous T cells generated cells secreting 2,542 +/- 695 IgG, 2,153 +/- 615 IgA, and 2,918 +/- 945 IgM. Normal B lymphocytes cocultured with normal allogeneic T cells generated similar numbers. However, B lymphocytes from patients with chronic lymphocytic leukemia cocultured with T cells from the same patient generated only 0.5% as many cells secreting IgG and 11% and 23% as many secreting IgA and IgM, respectively. The reason for this markedly defective generation of immunoglobulin-secreting cells was investigated by evaluating T-helper, T-suppressor, and B-cell function using B cells from tonsil and T and B cells from peripheral blood of normal and leukemic individuals. T cells from patients with chronic lymphocytic leukemia provided somewhat greater help than did normal T cells to normal peripheral blood B cells and normal help to tonsil B cells, whether stimulated with mitogen or antigen. T cells from patients with chronic lymphocytic leukemia did not demonstrate increased suppressor function compared to normals with B cells from normal peripheral blood. The hypogammaglobulinemia in these patients therefore was associated with a markedly defective generation of immunoglobulin secreting cells, and as there was normal or increased T-cell helper activity without excessive suppressor activity, it seems likely that this was due to an intrinsic B-cell defect.

Adult↗
PubMed1982

Renin-angiotensin and development of collateral circulation after renal ischemia.

Aortic ligation between the origins of the renal arteries in the rat produces a left renal ischemia, renin-dependent hypertension, and a transitory hindlimb paralysis of less than 2 h. Removal of the left ischemic kidney at the time of aortic ligation curtails the rise of blood pressure, plasma renin activity is normal, and paralysis is still present 24 h after surgery. Administration of an angiotensin-converting enzyme inhibitor or saralasin also prevents recuperation from paralysis after aortic ligation. Independent manipulation of the mean arterial pressure or plasma renin activity by pretreatment with reserpine or deoxycorticosterone before surgery shows that the presence or absence of paralysis is dependent on the plasma renin activity and not on the high blood pressure. Blood flow measurements show that paralysis is due to a persistent impairment of blood supply to the hindlimb muscle and not to ischemia of the spinal cord. Infusion of angiotensin II to aortic-ligated, left-renoprival animals tends to restore blood flow to muscle. It is concluded that after renal ischemia the renin-angiotensin system, independent of its hypertensive effect, restores blood flow by stimulating the development of collateral circulation.

Animals↗
PubMed1982

A study of t cell populations in alcoholic cirrhosis and chronic alcoholism.

It has been suggested that the various immunological abnormalities found in patients with cirrhosis might have contributed to the development of liver disease. T cells and their subpopulations were enumerated in patients with alcoholic cirrhosis, in patients with severe alcoholism but no detectable liver disease, and in 2 control groups (non-drinkers and social drinkers) in an attempt to determine which changes, if any, are related to and a result of cirrhosis, and which are related to alcoholism and therefore contributing factors in the pathogenesis of cirrhosis. Patients with alcoholic cirrhosis were found to have a decreased percentage of T cells, but the normal %s of B cells and monocytes when compared with controls. There were no differences between the 4 groups in the %s of T cells composed by the subset that rosette with ox red cells coated with IgM anti-ox erythrocyte antibody (T mu cells). However, the %s of T cells composed by the subset that rosette with ox red cells coated with IgG anti-ox erythrocyte antibody (T gamma cells) were found to be significantly decreased in patients with chronic alcoholism when compared with controls, and in patients with alcoholic liver disease when compared with chronic alcoholics. Many factors contribute to the development of cirrhosis: low numbers of T gamma cells may be an indication of individual susceptibility to progressive liver disease in patients with chronic alcoholism.

Adolescent↗
PubMed1981

Increased T-cell reactivity to leukemic B cells in chronic lymphocytic leukemia with change of stable disease to its progressive form.

Some patients with chronic lymphocytic leukemia (CLL) have a relatively stable clinical course without treatment, but many of these eventually develop progressive disease. We have followed 68 patients over 5 1/2 years by employing conventional surface markers and lymphocyte reactivity, including that of separate enriched T cells to their own leukemic B cells, to phytohemagglutinin (PHA), and to normal allogeneic B cells; we have observed an unusual response in each of the seven patients who developed progressive disease over this period of time. During the stable phase of the disease the T cells from 27 leukemic subjects did not respond to their own leukemic B cells in culture. In the seven patients who developed progressive disease, a significant reactivity of their enriched T cells to their own leukemic B cells occurred. There was no consistent change in T-cell reactivity to PHA or to allogeneic B cells, suggesting a change in the leukemic B-cell populations that was not detected morphologically. The change in reactivity of T cells to leukemic B cells occurred prior to evidence of clinical or laboratory deterioration in one of the seven cases; there was increasing lymphocytosis and lymphadenopathy in six and two instances, respectively; and anemia and thrombocytopenia in the three and one cases, respectively.

Aged↗
PubMed1981

Liposome accumulation in ischaemic intestine following experimental mesenteric occlusion.

Partial intestinal ischaemia was produced by ligation of selected primary laterals of the mesenteric artery in the rat. Both positively and negatively charged liposomes (multiply labelled with [99mTc]diethylenetriamine pentaacetic acid, [3H]methoxy-inulin, and [4-14C]-cholesterol), administered 24 h following ligation, were accumulated in ischemic (necrotic) intestine.

Animals↗
PubMed1981

The suppressive effects of monocytes in the autologous mixed lymphocyte reaction.

The response of isolated T cells to autologous non-T mononuclear cells is called the autologous mixed lymphocyte reaction (AMLR). The responding T cells show immunological memory and specificity. This reaction was present in all thirty normal individuals tested. Since the AMLR in the absence of evidence of in vivo excessive lymphoproliferation must somehow be controlled, we have studied the interactions of enriched T cells, B cells and monocytes in culture as possible means of regulation of this reaction. Increased rate of [3H] thymidine incorporation by T lymphocytes were observed when they were cultured with mitomycin-treated autologous non-T cells. This was increased when the stimulating cells were enriched for B lymphocytes and was significantly decreased when the stimulating cells were enriched for monocytes. Addition of monocyte-enriched cells to B-enriched cells in a 1:1 ratio, significantly suppressed the AMLR (P- less than 0.01). Equivalent numbers of monocytes did not suppress T-cell responses to phytohaemagglutinin (PHA). Monocyte-enriched cells were separated from stimulating B-enriched cells by nucleopore (0.6 mu) or dialysis tubing (0.12 mu) in Marbrook chambers. Soluble products released from monocyte-enriched cells also suppressed the AMLR. The significance of the AMLR in vivo is uncertain but it may be important in immunoregulation, monocytes playing an important role.

Adult↗
PubMed1980

Proliferative responses of peripheral blood lymphocytes to polyclonal activation: a comparison of young and elderly individuals.

Associated with human aging is a decline in immune activity, of both the cell-mediated and humoral types. In vivo, autoantibodies increase with aging and antibody responses to flagellin are decreased in the elderly as compared to the young. These abnormalities may be due to defects in helper or suppressor T cells, or innate defects in B cells. In vitro, the proliferative response of B cells to pokeweed mitogen (PWM) is dependent upon T cells. We studied the proliferative response of peripheral blood mononuclear cells (MNC) to polyclonal activation with PWM in young and elderly normal individuals and found that the number of IgA- and IgM-bearing B cells produced was increased in elderly subjects. This difference was statistically significant for IgA-bearing cells when MNC were placed with 5 and 15 microliter of PWM for 5 days and with 15 microliter of PWM for 6 days. Statistically significant increases in IgM-bearing cells were seen when MNC were plased with 5 microliter of PWM for 5 days and 5 and 10 microliter of PWM for 7 days. The differences in numbers of IgG-bearing cells were less consistent. Significant increases were seen when MNC were cultured with 10 microliter of PWM for 5 days and 5 microliter of PWM for 6 days. Our results suggest that in elderly normal individuals numbers of immunoglobulin-bearing cells are increased after polyclonal activation of MNC. This increase in immunoglobulin-bearing B cells associated with reports of in vivo humoral abnormalities suggests that there is loss of regulation of T cells on B cells in normal elderly individuals.

Adult↗
PubMed1980

Decreased autologous mixed lymphocyte reaction with aging.

The responses of T cells to autologous non-T mononuclear cells is called the autologous mixed lymphocyte reaction (AMLR). It seems to be an immunological response, as there is evidence of both immunologic specificity and memory. The AMLR is absent in systemic lupus erythematosis and chronic lymphocytic leukemia, and our data in normal human show that AMLR decreases with aging. Reactive T cells in the AMLR are subsequently cytotoxic to autologous B cells. We propose that the AMLR may be a protective phenomenon particularly against aberrant or neoplastic clones of B cells; and its decrease in the elderly may play an important permissive role for the development of either increased autoantibodies and/or B cell neoplasias.

Adult↗
PubMed1980

Characterization of null cells in chronic lymphocytic leukaemia with B-cell allo- and hetero-antisera.

Chronic lymphocytic leukaemia peripheral blood mononuclear cells (CLL-PBMN) were separated into B, T and Null-enriched lymphocyte sub-populations using sequential mouse and sheep red blood cell rosetting depletions on Hypaque-Ficoll gradients. The procedure produced viable cell populations with mean percentage purities of 90, 87 and 75 for B, T and non-rosetting (Null-enriched) sub-populations, respectively. More than 80% of PBMN cells were generally accounted for by mouse and sheep rosetting. The purified lymphocyte sub-populations were examined with a panel of B-cell specific alloantisera obtained from kidney transplant recipients and a rabbit antiserum to B cell antigen isolated from a human B-lymphoblastoid line. The results illustrated that the antigens detected by these sera also have potential as a marker for characterizing the CLL population. Where conventional markers were weak or absent, B cell antigens were readily detected in both fluorescent and cytotoxic tests. The majority of the non-rosetting cells (less than 90%) in CLL followed similar patterns of reactivity to the purified B cells, suggesting they are a subset of B cells. A small residual population (0--5% of PBMN) did not react with the antisera, the significance of which is unknown.

B-Lymphocytes↗
PubMed1980

Restricted genetic heterogeneity in families of patients with acute lymphocytic leukemia.

HLA antigens of the A and B loci were determined on the lymphocytes of 30 patients with acute lymphocytic leukemia (A.L.L.), as well as all of their mothers and 26 of the fathers. Seven of the 26 parents shared a common haplotype. This incidence of 269 per 1,000 contrasts with an expected incidence of 90.7 per 1,000, calculated from haplotype frequencies in a North American population (X2=7.61, P smaller.than 0.01) and a frequency of one in 27 in parents of patients with renal failure in the local population (X2=3.91, P smaller than 0.05). There was no statistical difference between the latter group and the North American controls (X2=0.39, P greater than 0.10). This suggests that the genetic background of a large proportion of patients with A.L.L. has restricted heterogeneity, presumably leading to the increased expression of leukemia associated recessive genes.

Female↗
PubMed1980

Lithium and T cell colonies.

In humans, therapeutic doses of lithium causes granulocytosis and lymphopenia. In vitro increased numbers of colony forming units (CFU-GM) are observed. The effect of lithium on lymphocyte colonies is unknown. We grew T cell colonies from normal individuals and patients who were on lithium only and found that T cell colony numbers were decreased in patients who were taking lithium. Recent evidence suggests that there is a PRECURSOR common to the granulocytic and lymphocytic cell lines. Since lithium causes increased granulocytic colonies and seems to decrease lymphocyte colonies we propose that lithium may have an effect on the precursor cell resulting in preferentially shifting maturation from the lymphocytic to the granulocytic series.

Hematopoietic Stem Cells↗
PubMed1980

Generation of suppressor cells by concanavalin A: a new perspective.

Significantly lower mitogenic responses of fresh cells co-cultured with Con A-stimulated cells were found when compared with the responses of fresh cells co-cultured with preincubated control cells. We do not agree with the interpretation that this effect represents the generation of suppressor cells by Con A, since the responses of fresh cells cultured alone were also significantly less than when co-cultured with control cells and the same as when co-cultured with the Con A-stimulated cells. Treatment with mitomycin C was sufficient to prevent the preincubated cells from contributing to the mitogenic response of the fresh cells. The increased responses of fresh cells when co-cultured with preincubated cells seems analagous to the increased mitogenic responses of cells aged in vitro by preincubation without mitogen. This effect seems to be transferable to fresh cells in the absence of cell division. Although preincubation in the presence of Con A abrogates this effect, we do not interpret this as the generation of suppressor cells.

Cell Division↗
PubMed1980

Cardiomyopathy produced in rats with acute renal hypertension.

Acute renal hypertension was produced in Sprague-Dawley female rats by the AL between the origins of the renal arteries. These were compared with an LN group. A sham group in which the ligature was placed but not tied was also prepared. MAP was recorded, and the animals were sacrificed at 1, 2, or 4 days after surgery. The hearts were examined histologically, and the lesions, consisting of focal or confluent necrosis of myocardial fibers with mononuclear cellular infiltrate, were scored. In the AL group the intensity of the lesions increased with time. The score on day 1 was 0.92 +/- 0.09; on day 2, 1.37 +/- 0.08; and on day 4, 1.75 +/- 0.01. Values at comparable intervals in the LN group were 0.14 +/- 0.04, 0.27 +/- 0.12, and 0.09 +/- 0.07, respectively (p less than 0.001). No coronary lesions were found. Arterial pressures were significantly elevated in the AL group but not in the LN or sham groups. Ventricular water and potassium were unchanged with the exception of a significant decrease of [K+] in the AL group 2 days after ligation. It is concluded that rats with acute renal hypertension develop cardiac necrosis, with a secondary fall in myocardial [K+]. The possibility that this is due to endogenous renin-angiotensin will require further study.

Animals↗