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Biomedical subjects

R Snyderman

Publications and source records attributed to R Snyderman.

At least 181 records · Page 10Linked to original sources
PubMed1979

Neisseria meningitidis and Neisseria gonorrhoeae bacteremia associated with C6, C7, or C8 deficiency.

We summarize data from 24 previously described or newly diagnosed cases of homozygous deficiency of the sixth, seventh, or eighth components of complement. Thirteen of 24 patients had at least one episode, and usually two or more episodes of Neisseria meningitidis or Neisseria gonorrhoeae bacteremia, or both. Deficiency of C6, C7, or C8 is a meaningful risk factor for repeated neisserial bacteremia; conversely, hemolytic complement studies are indicated in patients who develop recurrent neisserial infections. When a person with C6, C7, or C8 deficiency is identified, family members should also be studied.

Adolescent↗
PubMed1979

Hereditary C2 deficiency associated with cutaneous lupus erythematosus: clinical, laboratory, and genetic studies.

Selective congenital deficiency in the second component of complement has been described in association with lupus erythematosus (LE) and other connective tissue disorders. We identified a 59-year-old woman with a 13-year history of cutaneous LE and no detectable serum C2. The patient's photosensitivity, large polycyclic erosive cutaneous lesions, lack of renal disease, paucity of serological findings, and high incidence of bacterial infection is consistent with previously described patients with this association. Uniquely, the patient demonstrated secondary infection with Staphylococcus aureus and Trichophyton rubrum in the skin lesions themselves. Immunologic studies disclosed depression in both humoral and cellular immunity. Moderation in her clinical disease and immunologic measurements has been observed after treatment with levamisole hydrochloride. Immunogenetic studies of the patient's four-generation kindred was consistent with an autosomal recessive inheritance of C2 deficiency genetically linked to HLA, segregating with the B18 allele. Mixed lymphocyte culture determinations reinforce evidence for linkage between the HLA-D locus and the trait for C2 deficiency.

Complement C2↗
PubMed1978

Resistance of neoplasms to immunological destruction: role of a macrophage chemotaxis inhibitor.

Several tissue culture lines of 6C3HED, a murine lymphoma, were more susceptible to immunologic destruction in vivo than the highly virulent 6C3HED line maintained by serial intramuscular transplantation. The attenuated tissue culture cells were rejected by normal syngeneic recipients, but thymectomized mice were unable to reject attenuated cells. In such mice, the growth rate of attenuated cells was equivalent to the growth rate of virulent cells in normal syngeneic mice. The increased susceptibility of attenuated cells to destruction by syngeneic hosts was shown to correlate with decreased production by the tumor cells of a macrophage chemotaxis inhibitor, and not with altered antigen density. In addition, when inhibitor isolated from virulent cells was administered to mice challenged with attenuated cells, the latter cells became virulent in vivo. When attenuated and virulent cells were administered simultaneously in the same host, the attenuated cells were able to develop into progressively growing tumors. The data suggest that the successful growth of neoplastic cells in normal may require tumor cells to produce factors which subvert the ability of the host to mobilize macrophages rapidly at the tumor site.

Animals↗
PubMed1978

Requirement of S-adenosyl-L-methionine-mediated methylation for human monocyte chemotaxis.

The chemotactic response of motile bacteria requires the methylation of specific proteins by S-adenosyl-L-methionine. To determine whether methylation is required for the chemotaxis of human leukocytes, we studied the effects of inhibition of S-adenosyl-L-methionine-mediated methylation on monocyte chemotactic responsiveness. Methylation was inhibited in monocytes by treating the cells with substances that produced elevations in intracellular S-adenosyl-L-homocysteine, a competitive inhibitor of S-adenosyl-L-methionine methylation. Treatment of isolated monocytes with the adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine, plus exogenous adenosine and L-homocysteine thiolactone increased intracellular S-adenosyl-L-homocysteine levels by as much as 1500-fold. Concomitant with increases in S-adenosyl-L-homocysteine were a decrease in monocyte protein carboxy-O-methylation as well as a marked inhibition of monocyte chemotactic responsiveness. Conditions that almost completely inhibited methylation and chemotaxis did not depress monocyte phagocytosis, indicating that this latter function either is independent of S-adenosyl-L-methionine-mediated methylation or is extremely resistant to inhibition of such reactions by S-adenosyl-L-homocysteine. These studies indicate that S-adenosyl-L-methionine-mediated methylation is required for the chemotaxis of eukaryotic cells and that the chemotactic and phagocytic functions of human monocytes have different requirements for methylation.

Adenosine Deaminase Inhibitors↗
PubMed1978

Familial deficiency of the seventh component of complement associated with recurrent bacteremic infections due to Neisseria.

The serum of a 29-year old woman with a recent episode of disseminated gonococcal infection and a history of meningococcal meningitis and arthritis as a child was found to lack serum hemolytic complement activity. The seventh component of complement (C7) was not detected by functional or immunochemical assays, whereas other components were normal by hemolytic and immunochemical assessment. Her fresh serum lacked complement-mediated bactericidal activity against Neisseria gonorrhoeae, but the addition of fresh normal serum or purified C7 restored bactericidal activity as well as hemolytic activity. The absence of functional C7 activity could not be accounted for on the basis of an inhibitor. Opsonization and generation of chemotactic activity functioned normally. Complete absence of C7 was also found in one sibling who had the clinical syndrome of meningococcal meningitis and arthritis as a child and in this sibling's clinically well eight-year-old son. HLA histocompatibility typing of the family members did not demonstrate evidence for genetic linkage of C7 deficiency with the major histocompatibility loci. This report represents the first cases of C7 deficiency associated with infectious complications and suggests that bactericidal activity may be important in host defense against bacteremic neisseria infections.

Adult↗
PubMed1978

Abnormal monocyte chemotaxis in patients with breast cancer: evidence for a tumor-mediated effect.

The chemotactic responsiveness of peripheral blood monocytes was measured in 194 individuals: 37 patients with breast cancer, 17 patients with a history of breast cancer but clinically free of disease after surgery, 42 patients with benign breast masses, and 98 normal controls. Monocyte chemotactic responsiveness (MCR) in vitro was not significantly different from normal [mean = 72.8 migrating monocytes/oil immersion field, +/- 9.3 (1 SD)] in 2 groups of patients: a) those with benign breast masses (mean = 72.6 +/- 15.1; P greater than 0.3) and b) those previously having breast cancer resected and remaining clinically free of disease (mean = 69.0 +/- 12.5; P greater than 0.4). However, MCR was significantly depressed in the group of patients with active breast cancer (mean = 57.2 +/- 20.7; P less than 0.0025). Resection of malignant breast masses resulted in a significant change in MCR (P less than 0.0025), whereas resection of benign lesions did not (P greater than 0.4). MCR was abnormal in all clinical stages of breast cancer, including breast cancer without evidence of metastasis to regional lymph nodes. These data supported the hypothesis that neoplasms adversely affect monocyte function and may thereby hinder immunologically mediated destruction of malignant cells.

Adenocarcinoma↗
PubMed1978

Abortive and productive infections of human mononuclear phagocytes by type I herpes simplex virus.

The ability of Type I herpes simplex (HSV) to replicate in normal human monouclear phagocytes was investigated. Mononuclear leukocytes were obtained from the peripheral blood of patients by Ficoll-Hypaque gradient centrifugation, and the monocytes were isolated by allowing the cells to adhere to tissue culture dishes. The monocytes (10(5.0) cells) were infected (10(7.0) PFU HSV) either immediately after isolation or were cultured in vitro for varying numbers of days and were then infected. Inoculation of freshly isolated monocytes resulted primarily in an abortive infection. HSV antigens were produced by the cells, as determined by a indirect fluorescent antibody technique, and empty herpes capsid structures were detected by electron microscopy of the inoculated monocytes; however, no increase in virus titer was noted in the cultures. Inoculation of viable cells that had been maintained for 7 days in culture resulted in a productive infection. An increase in titer was noted 24 hours after inoculation, and normal virus maturation was documented by ultrastructural study of the infected cells. The experiments show that the interaction of HSV with human mononuclear phagocytes is complex, and the data suggest that whether or not the cell replicates infectious virus may depend on the functional activity of the cell.

Antigens, Viral↗
PubMed1978

Monocyte chemotactic mechanisms in patients with hypernephroma.

Peripheral blood monocyte chemotaxis was evaluated in 15 patients with hypernephroma, 10 of whom were evaluated preoperatively and postoperatively. Five patients had a significantly reduced response preoperatively that returned to normal levels after radical nephrectomy. Animal experiments confirm the presence of a low-molecular weight (6,000--10,000 daltons) inhibitor, which is heat labile and functions at the macrophage level. Preliminary experiments indicate inhibitors of macrophage chemotaxis can be extracted from renal cell carcinomas. The importance of these inhibitors in modulating immune surveillance is discussed.

Adenocarcinoma↗
PubMed1977

Generalized microsporum audoninii infection and depressed cellular immunity associated with a missing plasma factor required for lymphocyte blastogenesis.

Described herein is a 15 year old girl with a generalized, possibly systemic Microsporum audouinni infectin associated with anergy and defective lymphocyte transformation as a consequence of a deficiency of an uncharacterized plasma factor. Intravenous administration of plasma, obtained from normal donors, has produced consistent although incomplete clinical improvement. Defective lymphocyte transformation to M. audiouinii antigen cultured in autologous plasma became normal after infusions of normal plasma were instituted. Systemic administrations of griseofulvin, clotrimazole and miconazole produced transient and incomplete clinical improvement. Clearing of the cutaneous infection and stabillization of the neurologic status was finally achieved with plasma infusions combined with parenterally administered amphotericin B.

Adolescent↗
PubMed1977

Abnormalities of leukotaxis in atopic dermatitis.

Leukocyte chemotaxis studies were performed in 14 patients with atopic dermatitis. Monocyte chemotactic responsiveness (MCR), polymorphonuclear leukocyte (PMN) chemotactic responsiveness (PCR), and patient serum inhibition of normal monocyte chemotaxis were evaluated. The most common defect noted was depressed MCR. This was found in 8 of the 14 patients and was associated with a chemotactic inhibitor in the serum of 5 of 6 of the 8 with depressed MCR whose sera were so tested. Depressed PCR was found in 3 of 10 patients studied. Ten of the 14 patients had depressed chemotaxis of at least one cell type. Depressed chemotaxis was not related to the presence of infection, to the serum IgE level, or to the severity of the eczema, and it could not be produced in vitro by incubating normal cells with histamine or IgE myeloma. These studies demonstrate a high frequency of leukocyte chemotactic abnormalities in patients with severe atopic dermatitis. Elucidation of the clinical significance of the leukotactic abnormalities observed and determination of whether they are basic or secondary to the disease process must await further study.

Adolescent↗
PubMed1977

Disorders of leukocyte chemotaxis.

The rapid accumulation of inflammatory cells at sites of microbial invasion or neoplastic transformation is a central event in immunologically-mediated host defense. The availability of methodology to accurately quantify leukocyte migration in vitro has allowed the disclosure of previously unrecognized clinical disorders, namely leukocyte dysmotility syndromes. Although this area of clinical investigation is in its infancy, one can identify several processes associated with abnormal leukocyte accumulation. Abnormalities of immune recognition, chemotactic factor production, cellular motility or inhibitors of chemotaxis have been identified in different human diseases. In the upcoming years, pharmacological intervention directed at correcting specific causes of leukocyte dysmotility may well enhance our ability to treat certain infectious, inflammatory, and neoplastic diseases.

Antibody Formation↗