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Biomedical subjects

S H Leech

Publications and source records attributed to S H Leech.

At least 19 recordsLinked to original sources
PubMed1992

Congenital 21-hydroxylase deficiency as a new deletion mutation. Detection in a proband during subsequent prenatal diagnosis by HLA typing and DNA analysis.

A child with 21-OH-def whose 9 weeks' pregnant mother was referred for prenatal diagnosis was found upon very careful histocompatibility testing to lack expression of any of his father's HLA antigens on his peripheral blood lymphocytes. The possibility of alternative paternity was considered to be extremely unlikely after additional genetic marker tests. The conclusion that the affected child's disease resulted from inheritance of a maternal CYP21B (21-OH) deletion and a de novo deletion in the paternal chromosome 6 segment that includes both the CYP21B (21-OH) and HLA genes was confirmed by subsequent DNA analysis using 21-OH, C4, DPB, and PCH6 probes. The presence of a heterozygous RFLP for DPB, the absence of a deletion for either CYP21B (21-OH) or C4 genes, and the presence of a paternal HLA antigen haplotype on the fetal cells additionally indicated that the fetus lacked the same deletion and could be predicted to be completely normal.

Adrenal Hyperplasia, Congenital↗
PubMed1991

The immune system in hereditary hemochromatosis: a quantitative and functional assessment of the cellular arm.

The objective of this investigation was to evaluate certain quantitative and functional characteristics of the effector cells of the cellular arm of the immune system in hereditary hemochromatosis (HH) with respect to treatment status. Two observations were consistent with the postulate that the elevated levels of storage iron has in vivo immunoregulatory properties: (1) the absolute number of CD8-positive T cells were significantly elevated in untreated HH patients (n = 7) and reduced in treated patients (n = 7), as compared with controls; and (2) the proliferative response of peripheral blood mononuclear cells from untreated HH patients to mitogens was suboptimal but the response of peripheral blood mononuclear cells (PBM) from treated HH patients was normal. Furthermore, immunoglobulin secretion by PBM from treated HH patients as compared to controls was altered. Finally, one T effector cell abnormality was unrelated to treatment status in that a subset of mature, non-activated T lymphocytes aberrantly formed thermostable erythrocyte-rosettes (TE-R), a lymphoid surface marker usually expressed on thymocytes or activated T cells. Taken together these data define certain immune alterations that are consistent with the interpretation that cellular immunity may be influenced by the high level of storage iron in HH patients.

Antibody Formation↗
PubMed1991

Sequential measurement of beta 2-microglobulin levels, p24 antigen levels, and antibody titers following transplantation of a human immunodeficiency virus-infected kidney allograft.

A renal allograft recipient developed symptoms suggestive of AIDS. Serological studies revealed that the donor was positive for human immunodeficiency virus (HIV). Retrospective testing of stored sequential serum samples showed that the recipient was negative for HIV pretransplant; anti-p24 and anti-p41 antibodies appeared 10 and 49 days posttransplant, respectively. The recipient's serum beta 2-microglobulin levels were elevated 14 days posttransplant, with normal renal function, 35 days before the detection of anti-p24 antibody. p24 Antigen was detected for the first time 21 days posttransplant. In addition to p24 antigen, elevated serum beta 2-microglobulins may be a useful marker for HIV infection prior to seroconversion.

Adult↗
PubMed1988

Allergic rhinitis relieved by aspirin and other nonsteroidal antinflammatory drugs.

Aspirin and other non-steroidal antiinflammatory drugs (NSAIDS) are known to cause urticaria and aggravate symptoms of bronchial asthma. This report describes a patient with allergic rhinitis whose symptoms were improved after ingestion of aspirin and the NSAIDS. The beneficial effect was confirmed by oral double-blind challenges.

Administration, Oral↗
PubMed1986

The immunoregulatory nature of iron. II. Lymphocyte surface marker expression.

Previously, we presented preliminary evidence that supported our hypothesis for the immunoregulatory nature of iron [7]. The objective of the present work was to test that hypothesis in greater detail. Our approach was to examine the effect that iron had on the expression of the surface markers on lymphocytes that had been activated by pokeweed mitogen (PWM). The two categories of lymphoid surface molecules were enumerated on those cells; first were those that identify T lymphocytes and second, those that appear on the membrane of T cells following activation. The results, as regards T cell-associated molecules, demonstrated that iron suppresses the expression of the molecules identified by the monoclonal antibodies OKT3 and OKT4. It suppressed expression of the T4 molecule in PWM-activated cells (30.6% +/- 4.5; n = 5) compared with untreated but activated cells (52.2% +/- 2.9; n = 5; P = 1.9 X 10(-3) resulting in a reduced helper:suppressor T cell ratio from 2.2 +/- 0.4 to 1.2 +/- 0.3. With regard to activation-associated lymphocyte markers, iron significantly enhanced expression of the receptor for transferrin as identified by the monoclonal antibody, OKT9. However, it failed to change significantly the expression of three other activation-associated markers, namely, Ia, T10, and the receptor that forms thermostable erythrocyte-rosettes (TE-R) with sheep red blood cells (SRC). We conclude from those results that iron has a differential immunoregulatory influence on the expression of certain lymphocyte surface molecules on actively dividing lymphocytes.

Antibodies, Monoclonal↗
PubMed1985

Comparison of peripheral blood lymphocyte C3 receptor capping properties in patients with chronic lymphocytic leukemia and lymphoma.

Bacteria-antibody complexes were used to study capping of receptors for the activated third component of complement on peripheral blood lymphocytes. The impairment of C3d receptor capping improves in patients with chronic lymphocytic leukemia responding to therapy, but this does not necessarily correspond to the fall in peripheral lymphocytosis. Following lymphapheresis, increased capping appears to be due to selective removal of noncapping cells, but the mechanisms of improvement remain unexplained following other therapeutic measures. Lymphoma capping at 37 degrees C was normal in untreated patients but impaired after treatment, suggesting that this is related to the therapy itself. A high proportion of lymphocytes had receptors in the capped configuration in the basal state before incubation. In non-Hodgkin's lymphoma this was unrelated to treatment status, but it occurred only in untreated patients with Hodgkin's lymphoma with no further increment in capping after incubation. These receptors may exist in the aggregated state without the addition of exogenous ligand.

Complement C3↗
PubMed1985

Genetic studies in multiple myeloma. II. Immunoglobulin allotype associations.

A weakly positive but statistically significant association between HLA-Cw5 and myeloma has been reported in black patients. The authors attempted to determine whether immunoglobulin allotypes of the Gm series demonstrate any such association. They were identified in the sera of 29 black patients and 160 healthy black control subjects by a standard hemagglutination-inhibition technique. The results indicate that the G3m(g5) allotype is significantly associated with myeloma. Furthermore, addition of that immunoglobulin allotype to a Gm phenotype that is negatively associated with myeloma gives a phenotype that is positively associated with the disease, both associations being statistically significant. It was concluded that G3m(g5) is a marker of inherited susceptibility to myeloma in black Americans. Furthermore, as G3m(g5) is present in almost 50% of normal control subjects, it was proposed that its expression in a much greater proportion of patients may be related to an underlying genetic rearrangement that is also associated with neoplastic transformation.

Adult↗
PubMed1985

Preparation for hapten help by glucan, muramyl dipeptide, and its L-ala-Glycerol-mycolate derivative.

Previously, we reported that one of the factors that determines whether or not an animal will be prepared for hapten help after priming is the type of adjuvant used. The present work was undertaken, therefore, to determine which of a diverse variety of adjuvants or biological response modifiers would be effective. They included Freund's complete (CFA) and incomplete (FICA) adjuvants, particulate glucan, muramyl dipeptide (MDP), and its L-ala-glycerol-mycolate derivative. Help by the azobenzenearsonate (ABA) hapten was measured as the augmentation of the anti-bovine gamma-globulin (BGG) plaque-forming cell (PFC) response to ABA-BGG of mice that had been hapten-primed with ABA conjugated to ovalbumin (OVA). The results showed that FICA was ineffective. MDP was effective but only if administered with FICA during hapten-priming. MDP-L-ala-glycerol-mycolate was effective without any adjuvant but only within a narrow dose range. Particulate glucan was as effective as CFA in preparing mice for hapten help. As the macrophage is the primary cellular target of those biological response modifiers that were effective, we conclude that it plays an important role in the cellular interaction involved in the mediation of hapten help.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Accidental administration of hepatitis B immune globulin to a patient positive for hepatitis B surface antigen.

Approximately 24 hours after receiving hepatitis B immune globulin (HBIG), a renal transplant surgeon developed localized urticaria at the site of injection followed by generalized urticaria and angioedema, which resolved after administration of corticosteroids but recurred ten days later. Blood drawn from the surgeon prior to his receiving the HBIG injection was positive for hepatitis B surface antigen (HBsAg). We believe that the adverse reaction may have been caused by HBsAg-HBIG immune complexes. This case illustrates the necessity for knowing the results of hepatitis serology before injection of HBIG is given in high risk individuals. It also re-emphasizes the value of periodic screening for hepatitis B in such persons and the need for hepatitis B vaccine.

Angioedema↗
PubMed1984

Thermostable erythrocyte rosette-forming lymphocytes in hereditary hemochromatosis. I. Identification in peripheral blood.

Although the immunoregulatory role of iron has been demonstrated in vitro, evidence for a similar role in vivo is controversial. We have, therefore, studied certain functional and structural properties of lymphocytes in hereditary (idiopathic) hemochromatosis (HH), a disease characterized by iron overload. T- and B-lymphocyte percentages in peripheral blood, serum immunoglobulin levels, and proliferative responses of peripheral blood mononuclear cells (PBM) to lectins were comparable with those of controls. Furthermore, HH serum with elevated iron concentrations did not significantly alter proliferative responses of normal lymphocytes to mitogens. In contrast to those normal findings was the identification of a subset of T lymphocytes in HH that formed rosettes with sheep red blood cells (SRC) at 37 degrees C in abnormally high numbers. Those lymphocytes that formed thermostable erythrocyte rosettes (TE-R) were not immature thymocytes, activated T lymphocytes, or an artifact of passive attachment of anti-SRC antibodies to the HH lymphocyte surface. Their presence did not correlate with a concentration of iron in the serum, the length of treatment, or the presence of the HLA antigen, A3. We conclude that the cellular expression of HH may be detected not as an immunological abnormality, but rather as an abnormality in receptor expression.

Antibodies, Monoclonal↗
PubMed1984

Insulin receptor autoantibodies in sepsis.

This study was undertaken to investigate possible factors contributing to altered glucose homeostasis in a patient with a history of total pancreatectomy and intermittent sepsis. Blood was drawn when the patient had received no exogenous insulin for the previous 24 hours, had a serum insulin level of 0.3 microU/mL, and gave an inappropriately low glucose response to large amounts of infused glucose. The IgG fraction prepared from this serum stimulated glucose oxidation in vitro and inhibited binding of insulin labeled with I 125 to isolated rat adipocytes, thus fulfilling some of the criteria for autoantibodies to the insulin receptor. The results are compatible with the hypothesis that insulin-receptor autoantibodies may have developed as a result of perturbation of this patient's immune status promoted by intermittent septic episodes and that, preterminally, as these antibodies converted in vivo to their in vitro-type behavior, they may have been partially responsible for the severe disturbances of glucose homeostasis.

Adult↗
PubMed1984

Serum inhibitor in systemic lupus erythematosus associated with aplastic anemia.

Hematologic complications of systemic lupus erythematosus (SLE) usually involve peripheral destruction of blood elements. We report a case of SLE-associated aplastic anemia in which an IgG complement-dependent antibody, obtained from the patient's disease-phase serum but not remission-phase serum, suppressed growth of granulocyte-macrophage progenitor cells from bone marrow of normal donors in vitro. Therapy with plasmapheresis and immunosuppression resulted in lasting remission.

Adolescent↗
PubMed1983

Genetic studies in multiple myeloma. 1. Association with HLA-Cw5.

Human leukocyte antigens (HLA) were identified in 22 black Americans with multiple myeloma. No significant association was observed between antigens at either the A or the B locus. At the C locus, in contrast, HLA-Cw5 was more prevalent in the patient group, four of 22 having it, compared with the control group, in which two of 138 individuals possessed it. All four patients with HLA-Cw5 were males. Those results suggest that genetic factors, perhaps in conjunction with an environmental change, may be responsible for the recent increase in incidence in myeloma in black Americans, especially in males.

Adult↗
PubMed1983

The immunoregulatory nature of iron. I. Lymphocyte proliferation.

An increasing body of evidence suggests that iron may regulate certain immune functions in vitro. Its effects on proliferative responses of human peripheral blood mononuclear lymphocytes (PBM) to various mitogens was therefore investigated. The results showed that it enhanced such responses to pokeweed mitogen (PWM) but suppressed those to phytohemagglutinin (PHA) and to concanavalin A (Con A). Furthermore, the enhancement was mediated by T rather than B cells. In conclusion, those results provide further evidence for the hypothesis that iron has certain immunoregulatory properties in vitro.

Adult↗
PubMed1983

Thermostable erythrocyte rosettes in chronic renal failure and allograft rejection.

Rejection of an allograft usually is preceded by activation of T lymphocytes, in which state such cells may be identified by their ability to form thermostable rosettes with sheep erythrocytes (TE-R). The objective of the present work, therefore, was to determine whether or not enumeration of TE-R in the peripheral blood was of any value in the diagnosis of rejection. The results showed no significant differences between TE-R (mean +/- SEM) in normal subjects (9.9 +/- 1.3; n = 25), renal allograft recipients without rejections (13.5 +/- 1.7; n = 5) and in patients who suffered from acute tubular necrosis in the posttransplant period (12.4 +/- 2.5; n = 8). In contrast, recipients who had rejection episodes showed a marked rise in TE-R levels (43.0 +/- 4.0; n = 11) about two to seven days prior to the diagnosis of rejection by clinical and chemical criteria. Furthermore, TE-R remained high if the rejection episodes turned out to be irreversible after therapy (42.2 +/- 3.7) but fell if the episodes were reversible (19.9 +/- 3.2). TE-R values were elevated in patients with chronic renal failure on maintenance hemodialysis (45.7 +/- 4.9; n = 23). Neither acute dialytic runs or acute infections altered TE-R values. In conclusion, those results show that enumeration of TE-R may be helpful in the early diagnosis of allograft rejection, before clinical and chemical stigmata are apparent.

Erythrocytes↗