Cephalometrics and oral myofunctional impairment.

It is essential that the practitioner determine the factors that are etiologically operative in oral myofunctional therapy in order to establish effective methods of intervention. Of these methods, cephalometrics and facial analysis are especially valuable in revealing and differentiating open bite syndrome. They are discussed here along with procedures for their use.

Severe combined immunodeficiencies, primary T-cell defects and DiGeorge syndrome in humans: characterization by monoclonal antibodies and natural killer cell activity.

Peripheral blood mononuclear cells from three patients with severe combined immunodeficiency (SCID), three with SCID whether B cell positive or with pure T-cell defect, and two with DiGeorge syndrome were analyzed with a panel of monoclonal antibodies against immature and mature T-cell subsets. Natural killer (NK) cells were enumerated by the use of the HNK-1 monoclonal antibody. NK activity against the K562 and MOLT 4 cell lines was also investigated. According to the monoclonal antibodies profile and the NK activity, patients could be divided into three groups. Patients with classical SCID had no detectable circulating T cells as well as NK cells and activity, probably due to an early block in stem cell differentiation. Patients affected by SCID with B cells or pure T cell defect showed a decrease in lymphocytes with mature phenotypes but prothymocytes or immature thymocytes circulated in peripheral blood. Children with DiGeorge syndrome had a decrease in mature thymocytes and, in this study, NK cells were normal. These data help to clarify both the preeminent immunologic features of SCID and related syndromes and the character of NK cells.

In vitro effect of ketoconazole on human neutrophil chemotaxis and Candida albicans killing.

Ketoconazole, an antifungal agent, was investigated to discover its possible enhancing role on polymorphonuclear chemotactic and Candida killing functions in vitro. Polymorphonuclear leukocytes from 10 healthy subjects and two different strains of Candida albicans were used. At concentrations of 1 microgram/ml Ketoconazole showed no distinct synergistic effect on either of the above-mentioned polymorphonuclear cellular functions, but, on the other hand it operated directly on Candida cells. In addition, this drug did not demonstrate any chemotactic activity on granulocytes. These data could suggest that host cellular defence and Ketoconazole exert parallel rather than synergistic activity.

In vitro and in vivo effect of sisomicin and gentamycin on polymorphonuclear chemotaxis and phagocytosis.

Ten patients with acute bacterial infections were studied to demonstrate the influence of two aminoglycosides, sisomicin and gentamycin on polymorphonuclear (PMN) chemotactic and phagocytic functions. Five of these subjects were treated with gentamycin and five with sisomicin both at a dosage of 2.5 mg kg-1 day-1. The assays were performed before and after 5 days of therapy. Before beginning treatment, the in vitro action of the aminoglycoside antibiotics (20 micrograms ml-1) was also tested. Granulocytes from 8 healthy people were used as controls. After therapy, no significant difference in basic values was found in either the gentamycin treated or in the sisomicin treated group. Similar results were obtained in incubation tests on both patients and healthy subjects. In conclusion, we conclude that the use of these mentioned aminoglycoside antibiotics, at the therapeutical doses employed, does not interfere with the PMN functions.

Serum and salivary IgA levels in normal subjects: comparison between tonsillectomized and non-tonsillectomized subjects.

Serum IgA and secretory IgA (SIgA) were determined in 1,000 apparently healthy subjects; 274 were tonsillectomized. Four groups were identified in this study: (1) 0.3% of subjects had no serum IgA and SIgA; (2) 1.6% of subjects showed partial serum and SIgA deficiency; (3) 27.4% of individuals were tonsillectomized and had partial serum IgA deficiency but normal SIgA, and (4) 71.4% were normal, both with respect to serum IgA and SIgA. There results stress the relatively high incidence of IgA deficiency in the normal population and confirm the role of the tonsils in maintaining serum IgA levels.

Circulating immune complexes detected by C1q solid phase assay in leprosy.

Sixty-three sera of patients with leprosy were tested for the presence of circulating immune complexes (CIC) by C1q solid phase assay (C1qSPA). The mean values in CIC levels in leprosy patients were very high in comparison to native and European controls. No difference was found in the tuberculoid and lepromatous forms, but there was a good correlation between the presence of CIC and autoantibodies.

Thymopentin treatment of selective IgA deficiency.

Thymic hormones have been shown to modulate immunoglobulin production in a number of experiments and it is generally agreed that this action is mediated by modulation of helper and/or suppressor T cell activities. The possibility of upregulating the immunoglobulins is of particular relevance in patients with hypogammaglobulinemias and this paper reports on the results of thymopentin treatment in 9 patients with selective IgA deficiency. Two out of 4 patients responded positively in an open-label trial; in one the serum IgA values remained stable up to 8 weeks after discontinuation of treatment whereas there was a rapid fall in the other. Both responders had consistently normal T4/T8 ratios during the treatment, whereas the nonresponders revealed high ratios with large fluctuations of the T4/T8 ratio. In a subsequent (still ongoing) double-blind trial in 5 patients (3 thymopentin, 2 placebo) no significant change of serum or secretory IgA levels has been observed. Taken together, the data suggest that the tested dose regimen of thymopentin (i.e. daily i.m. injections of 1 mg/kg for 2 weeks, then same dose 3 time weekly for 10 weeks) may only work in a subset of patients with selective IgA deficiency. In the present study we did not attempt to distinguish to which of the three known subgroups the 9 patients belonged, nor did we try alternative dose regimens of thymopentin.

Usefulness of monoclonal antibodies in the diagnosis and monitoring of patients with primary immunodeficiencies: combined experience in three clinical immunology centers.

Circulating levels of T-cell subsets and NK cells were determined in 78 patients with primary immunodeficiencies, 35 children with recurrent respiratory infections, and healthy age-matched controls. Normal T cell and natural killer (NK) cell values were observed in individuals with immunoglobulin A (IgA) deficiency and X-linked agammaglobulinemia, while reduced OKT4/OKT8 cell ratios and low levels of 5/9+ T helper cells were found in approximately 60% of patients with common variable immunodeficiency. Infants with severe combined immunodeficiency (SCID) and lymphopenia had virtually no cells expressing T-cell or NK-cell surface antigens, but had normal numbers of monocytes and other types of blood cells. Infants with DiGeorge syndrome, other primary T-cell defects, or SCID with B cells had few or no circulating cells of mature T helper-suppressor phenotypes, but had normal numbers of NK cells (HNK-1+) and NK function. These results support the idea of a common stem cell precursor for T, B, and NK cells, each of which follows a separate pathway of differentiation. Profound alterations were observed in the distribution and function of T-cell subsets in ataxia-telangiectasia patients who were previously shown to have thymic dysplasia. A significant reduction in the frequencies of OKT3+ and OKT4+ cells was observed in children with frequent respiratory infections during infancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Thymopoietin pentapeptide treatment of primary immunodeficiencies.

26 patients with primary immunodeficiencies (3 infants with severe combined immunodeficiency [SCID] 3 with DiGeorge syndrome, 6 with T-cell defect or SCID with B cells, 4 with common variable hypogammaglobulinaemia and associated T-cell defect, 5 with ataxia-telangiectasia, and 5 with hyper-IgE syndrome) were treated with thymopoietin pentapeptide (TP-5) at a dose of 0 . 5 mg/kg daily for 2 weeks and then 3 times a week at 0 . 5 mg/kg for 10 weeks, 3 patients with DiGeorge syndrome and 3 with primary T-cell defect demonstrated pronounced clinical and immunological improvement during treatment. None of the patients with SCID and 3 of 6 patients with SCID with B cells or primary T-cell defect showed any clinical or immunological changes during therapy. In 5 patients with ataxia-telangiectasia clinical manifestations and immunological tests were unchanged by TP-5. Abnormality of T cells in cases of hyper-IgE syndrome was not corrected by TP-5 treatment.

Immunological and virological investigation in patients with lymphoadenopathy syndrome and in a population at risk for acquired immunodeficiency syndrome (AIDS), with particular focus on the detection of antibodies to human T-lymphotropic retroviruses (HTLV III).

Thirteen patients affected with unexplained lymphoadenopathy, fever, weight loss, and diarrhea (lymphoadenopathy syndrome; LAS) were evaluated for the possible appearance of acquired immunodeficiency syndrome (AIDS) and for immunological and virological characterization. The patients belonged to categories of individuals at risk for AIDS and were homosexual and/or drug abusers or hemophiliacs. Lymph node biopsy showed the histological picture of a follicular hyperplasia. The study of cell-mediated immunity (CMI), humoral immune response, and natural killer (NK) activity demonstrated a significant decrease in T cells with the helper/inducer phenotype (OKT4+ cells) and a relatively increased number of lymphocytes with the suppressor/cytotoxic phenotype (OKT8+ cells). NK activity was significantly lower than in normal controls. The in vitro response to polyclonal activators (phytohemagglutinin; PHA) and the cutaneous responsiveness to recall skin tests were impaired, whereas immunoglobulin production was increased, mainly in the IgG fraction. Virological studies showed high serum antibody titers to cytomegalovirus (CMV) but a lack of specific CMI as assayed by the leukocyte migration inhibition test (LMIT). CMV was also isolated from the urine specimen of one patient. The antibody pattern to Epstein-Barr virus (EBV) showed the uncommon contemporary presence of both Epstein-Barr nuclear antigen (EBNA) and early antigen (EA) antibodies. Antibodies to human T-lymphotropic retroviruses (HTLV III) were positive in 10 patients and the virus was isolated in 3 of them. In some patients the presence of serum antibodies to HTLV III was not associated with an impairment of the immune function. A group of individuals at risk for AIDS without LAS was also evaluated for the presence of HTLV III antibodies; the percentage of positive sera was 11.4.(ABSTRACT TRUNCATED AT 250 WORDS)

Defective interferon-gamma production in ataxia-telangiectasia.

The in vitro production of interferon-alpha and -gamma (IFN) by peripheral blood mononuclear cells from four patients with ataxia-telangiectasia was compared to that of healthy controls. Normal values of IFN-alpha were obtained in all cases. However, patients with ataxia-telangiectasia showed a great reduction or absence of IFN-gamma production after induction with either staphylococcal enterotoxin B or galactose oxidase. This defect was accompanied by the absence of secretion of another lymphokine, namely, interleukin 2 (IL-2), in one case. Lymphoproliferative response to phytohemagglutinin (PHA) was severely depressed in all patients. Near normal values of T lymphocytes were found, but the ratio of OKT4+/OKT8+ subsets was reduced in most patients, due to a decrease of OKT4+ lymphocytes. Deficiency of IFN-gamma may contribute to the abnormalities of immune functions and immunoregulation observed in ataxia-telangiectasia, and it may represent an additional cause of the high incidence of viral infections and neoplasia in this disease.

Interferon production in primary immunodeficiencies.

Alpha- and gamma-interferon (IFN) production by peripheral blood mononuclear cells (PBMC) from 18 patients affected by primary immunodeficiency syndromes was examined and compared with that of 20 normal donors. Patients included 8 with common variable immunodeficiency (CVI), 2 with congenital agammaglobulinemia, 4 with ataxia-telangiectasia, 2 with hyper-IgE syndrome, 1 with chronic EBV infection, 1 with combined immunodeficiency, and 1 with immunodeficiency with hyper-IgM. No spontaneous IFN production was observed in either patients and controls. Newcastle disease virus-induced alpha-IFN production was found to be normal in all patients. Gamma-IFN was induced by both galactose oxidase and staphylococcal enterotoxin (B). Gamma-interferon production was low or undetectable in patients with ataxia-telangiectasia, in immunodeficiency with hyper-IgM, and in hyper-IgE syndrome. No major defect of gamma-IFN was found in other types of immunodeficiency, despite the presence of occasional low producers (1 of 8 CVI patients and 1 case of congenital agammaglobulinemia). No correlation was found between IFN production and natural killer activity in individual patients. The analysis of lymphocyte subsets by monoclonal antibodies revealed gross imbalances of helper/inducer and suppressor/cytotoxic subpopulations, but no overall correlation could be established with gamma-IFN production. The observation of major defects in gamma-IFN yield only in diseases with depression of T cell-mediated immunity might contribute to a better understanding of the pathogenetical mechanisms in these diseases. Moreover, future studies should monitor these in vitro functions and their modifications by in vitro or in vivo manipulations.

Chronic granulomatous disease in two sisters.

Two sisters with chronic granulomatous disease (CGD) have been studied. The diagnosis was suggested by the histopathological findings from the spleen and lymph nodes of the proband and confirmed by the low values obtained in the following tests performed on polymorphonuclear leukocytes (PMN): chemiluminescence, nitroblue tetrazolium (NBT) reduction, killing of Staphylococcus aureus, and O2- production. NADPH oxidase activity was not detected in the homogenates of the patients' PMN but cytochrome b was normally present. In addition, PMN depolarization induced by phorbol-myristate acetate was absent, thus suggesting a defect of the activation mechanism of the respiratory enzyme. The normal depolarization induced by ouabain indicated that the membrane polarity regulated by the Na/K pump in the patients' cells was not affected. The low, but not completely absent, respiratory activity of the patients' PMN could suggest an X-linked mode of inheritance with incomplete Lyonization. From a clinical point of view, one sister had mild symptoms whereas the other was almost symptomless, thus confirming once more the heterogeneity of CGD syndrome.

[In vitro effects of lysozyme on some specific and non-specific functions of the immune system]. / Gli effetti in vitro del lisozima su alcune funzioni specifiche e non specifiche del sistema immunitario.

In this paper the in vitro effects of lysozyme on several immunological function was investigated. Henn-egg-white lysozyme (at concentrations ranging between 1 and 10 micrograms/ml) has shown an inhibitory action on mitogen-induced lymphoblastigenesis and autologus mixed lymphocyte reaction. On the other hand, NK activity against K 562 cell line resulted to be increased in the presence of lysozyme. In addition lysozyme has shown to behave as chemokinetic factor increasing PMN random locomotion and inhibiting PMN response only towards complement derived chemotaxins, whereas there was no effect against other chemotactic factors. Then, in addition to its enzymatic activity, a role of lysozyme as modulator of the inflammatory response may be proposed.