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Biomedical subjects

S M Wolff

Publications and source records attributed to S M Wolff.

At least 55 records · Page 3Linked to original sources
PubMed1984

Induction of human interleukin-1 by a product of Staphylococcus aureus associated with toxic shock syndrome.

Certain strains of Staphylococcus aureus associated with toxic shock syndrome elaborate material that induces human blood monocytes to secrete interleukin-1 (IL-1). IL-1 was detected both by its ability to cause fever in rabbits using the leukocytic pyrogen (LP) assay and by its mitogenic activity towards thymocytes in the so-called lymphocyte-activating factor (LAF) assay. Anti-human IL-1 prevents the manifestation of both activities. Filtrates of control strains of S. aureus manifest neither activity. Thus, culture filtrates derived from toxic shock syndrome (TSS)-associated strains cause biphasic fever in rabbits when injected intravenously. The fever lasts several hours. Plasma taken at the peak of the fever and injected into a second set of rabbits produces a brief monophasic fever typical of LP. Further, human monocytes release LP when incubated with TSS filtrates in vitro. The monocyte products also stimulate the proliferation of mouse thymocytes in the presence of phytohemagglutinin in a manner characteristic of LAF. A bacterial filtrate is much less effective without an intermediate incubation with monocytes. The stimulation of monocyte IL-1 production is easily quantified, provides a simple method of assaying the TSS toxin, and since it involves human cells, is directly relevant to the human disease. The assay was used to monitor the purification of TSS toxin. Only 0.1 ng/ml of the purified material is required to induce monocyte IL-1 production. It is thus more potent than endotoxin. In contrast to endotoxin, its effect is not blocked by polymyxin B. We conclude that in TSS the sudden fever and probably other components of the acute phase response may be attributed to a massive release of IL-1.

Animals↗
PubMed1984

Cleavage of human interleukin 1: isolation of a peptide fragment from plasma of febrile humans and activated monocytes.

Interleukin 1 (IL 1) is a product(s) of mononuclear phagocytes, and has multiple biologic activities that mediate several host responses to infection and inflammation. Highly purified IL 1 activates lymphocytes, induces fever, increases hepatic acute phase protein synthesis, and increases muscle protein degradation. A 4.2 kd peptide has been purified from plasma of febrile humans which also induces muscle proteolysis in vitro (termed proteolysis-inducing factor, PIF). Because IL 1 purified from activated human monocytes induces muscle proteolysis in vitro, studies were performed to determine the relationship of human monocyte-derived IL 1 to plasma-derived PIF. Purified PIF was highly active in the IL 1 thymocyte assay. After gel filtration of plasma from febrile patients, fractions with PIF activity also induced thymocyte proliferation and fever in mice. Thus, it seems likely that the plasma peptide PIF has IL 1 properties and probably represents a small m.w. cleavage product of IL 1. Further studies confirmed this finding. Highly purified 15 kd IL 1, rechromatographed over different gel filtration media, consistently fragmented into a 4 kd peptide with both muscle proteolysis-inducing and lymphocyte-activating properties. The breakdown of the 15 kd IL 1 into biologically active smaller fragments increased with time, and could be accelerated by trypsinization. The monocyte-derived IL 1 fragments were partially destroyed by heat. Highly purified 125I-labeled 15 kd IL 1 also fragmented into subunits, and these radioactive subunits produced fever in mice and were active in the thymocyte assay. Fragmentation of 125I-labeled 15 kd IL 1 was reduced by agents that inhibit proteases. These results indicate that some of the biologic activities of human IL 1 are conserved in small m.w. fragments. These studies also provide evidence that IL 1 may circulate in humans as a 4.2 kd peptide, and that this cleavage product can function as an active mediator of IL 1 effects in the host.

Animals↗
PubMed1983

Amyloidosis and the serum amyloid A protein response to muramyl dipeptide analogs and different mycobacterial species.

Serum amyloid A protein (SAA) elevation accompanies induction of secondary amyloidosis in mice given Mycobacterium butyricum in Freund adjuvant. The synthesis of SAA by cultured hepatocytes is induced by a macrophage-derived mediator, which has been identified as interleukin 1. In these studies, SAA synthesis has been used as an index of macrophage activation to examine the in vivo response of mice to challenge with seven different mycobacteria and with synthetic analogs of the immunoadjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine [MDP(L-D)]. SAA synthesis was stimulated by administration (by the intraperitoneal route) of the mycobacteria dissolved in saline, with Mycobacterium vaccae being the most active and Mycobacterium leprae being the least stimulatory. MDP(L-D), which is the minimal structure (molecular weight, 492) able to substitute for mycobacteria in Freund adjuvant, stimulated SAA synthesis, whereas the MDP(D-D) isomer was inactive. The butyl ester of MDP, which induces no detectable pyrogenicity but retains adjuvanticity, required a 100-fold greater dosage than MDP(L-D) in stimulating SAA synthesis. Amyloidosis was detected histologically only when active SAA inducers MDP(L-D), M. vaccae, and M. butyricum, were administered in incomplete Freund adjuvant, with amyloid-enhancing factor. These studies demonstrated that SAA elevation was a sensitive in vivo marker of the capacity of antigens to stimulate macrophages to produce interleukin 1. A point of considerable relevance to the human use of MDP was the observation that repeated injections of the adjuvant MDP in saline did not induce secondary amyloidosis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years.

Eighty-five patients with Wegener's granulomatosis were studied for 21 years at the National Institutes of Health. Patients were treated with a protocol consisting of cyclophosphamide, 2 mg/kg body weight d, together with prednisone, 1 mg/kg body weight d, followed by conversion of the prednisone to an alternate-day regimen. Complete remissions were achieved in 79 of 85 patients (93%). The mean duration of remission for living patients was 48.2 (+/- 3.6) months. Twenty-three patients are off all therapy for a mean duration of 35.3 (+/- 6.3) months without therapy. This study provides a prospective experience with Wegener's granulomatosis and shows that long-term remissions can be induced and maintained in an extremely high number of patients by the combination of daily cyclophosphamide and alternate-day prednisone therapy.

Adolescent↗
PubMed1983

[Demonstration of a bacterial structure in two human mediators: a sleep facilitating factor and a monokine].

A monoclonal anti-MDP antibody was found to bind to "Slow Wave Sleep" factor. This result confirms that this factor is a muramyl peptide and furthermore shows that it contains a structure characteristic of the synthetic adjuvant and of the bacterial cell wall, i.e. an acetylated muramic acid bound to L-alanine. This antibody was also shown to specifically inhibit a biological activity of a purified human monokine which induces fever. Because of these results and other recent observations we propose that a bacterial structure is present in certain mammalian mediators.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Strabismus after retinal detachment surgery.

In conclusion, we can summarize our experience as follows: Exoplants oriented radially and wherever placed can be productive of important degrees of astigmatism and diplopia. In our experience, they are often associated with torsional diplopia; Surgery under the rectus muscles may be responsible for adhesions and limitations of excursion of the globe; Anteriorly placed exoplants, especially those placed under the rectus muscles and particularly temporally or below, are apt to erode the overlying muscle sheath and tendon; a muscle so eroded may sometimes be found reattached to the globe just posterior to the exoplant; Repeated surgical intervention, perhaps in association with careless or inaccurate closure of the periocular tissues, Tenon's fascia and conjunctiva, may be important factors in the production of strabismus; Factors which have not been responsible for strabismus as far as we can tell are encircling elements without exoplants and intraoperative detachment and reattachment of the extraocular muscles. I know of no instance where these alone have been productive of an important postoperative strabismus.

Adult↗
PubMed1982

Production of fever and its effects on the host.

Leukocytic pyrogen (LP) is a polypeptide that is released from phagocytic leukocytes and mediates fever, by direct action on the thermoregulatory centers in the hypothalamus. During the mediation a complex series of biochemical events occurs in the hypothalamus, including increases in prostaglandin synthesis. The production of LP by phagocytic leukocytes (predominantly monocyte/macrophage) requires synthesis of protein and new messenger-RNA. Recently, it has been discovered that LP has other direct effects on the host. Amongst these effects are: increases in acute phase reactants, including serum amyloid A protein (SAA); release of specific granule contents from neutrophils in vitro; a similarity (if not identity) to human lymphocyte activating factor (LAF) which is a monokine. Thus, LP may have a much broader role to play in the inflammatory response than just mediating fever.

Animals↗
PubMed1982

Lymphomatoid Granulomatosis. Prospective clinical and therapeutic experience over 10 years.

Fifteen patients with lymphomatoid granulomatosis were studied prospectively over a 10-year period. Thirteen of the patients received the therapeutic protocol of cyclophosphamide (2 mg per kilogram of body weight per day) and prednisone (1 mg per kilogram on alternate days). Previous reports had indicated that mortality from lymphomatoid granulomatosis was as high as 90 per cent. Of the 13 patients who received the cyclophosphamide and prednisone protocol, seven had complete remissions lasting for 5.2 +/- 0.6 years (mean +/- S.E.M.) Six of the seven with disease in remission have received no therapy for 28.3 +/- 5.7 months. Malignant lymphomas developed in seven of the eight who died, and only two of the eight had therapy for an adequate period. Since virtually all patients who did not have complete remission went on to have malignant lymphoma, early recognition and prompt treatment during the lymphomatoid-granulomatosis phase of disease may not only lead to complete remissions but also percent the development of a lymphoid neoplasm.

Adolescent↗
PubMed1982

Studies on the active site of human leukocytic pyrogen.

Leukocytic pyrogen, a polypeptide produced by phagocytic mononuclear cells, is thought to be the endogenous mediator of fever. In addition to its effects on thermoregulation, leukocytic pyrogen has been shown to induce synthesis of acute-phase proteins, increase lymphocyte blastogenesis to mitogens, and cause release of neutrophil-specific granule contents. Despite its important role in biologic responses, little is known concerning the structure-function relationship of the molecule. In the present studies several protein-modifying conditions were used in order to examine specific amino acid participation at the active site. Because the state of purity of leukocytic pyrogen may be critical during certain reaction conditions, highly purified preparations were used. Experiments suggest that the active site requires the gamma-carboxyl group of glutamic acid and that blocking arginine reduces both the pyrogenic and neutrophil releasing properties of the molecule. Other studies demonstrate that the pyrogenicity of human leukocytic pyrogen is not due to serine esterase or carboxypeptidase B activity and that the 15,000-dalton molecule may be a glycoprotein. These experiments provide further evidence that the lymphocyte-activating and neutrophil-granule-releasing properties of human leukocytic pyrogen require the same active site which produces fever.

Arginine↗
PubMed1982

Molecular basis of fever in humans.

This review presents several areas of research on the pathogenesis of fever in humans and updates new information concerning the role of fever in host defense mechanisms. Fever is mediated by a polypeptide of phagocytic cell origin called leukocytic pyrogen. Several agents and disease processes are associated with the synthesis and release of leukocytic pyrogen. Although the original studies on leukocytic pyrogen suggested that the neutrophil was the primary source, recent experiments indicate the mononuclear phagocyte to be the major producer of leukocytic pyrogen. The mechanism by which human monocytes are stimulated to produce leukocytic pyrogen is discussed, including the effects of corticosteroids, estrogens and antipyretics on the synthesis of leukocytic pyrogen in vitro. The ability of leukocytic pyrogen to alter the hypothalamic thermoregulatory center by increasing arachidonic acid metabolite levels is the most likely mechanism by which leukocytic pyrogen initiates fever. Antipyretics prevent the synthesis of certain cyclooxygenase metabolites, which accounts for their ability to reduce fever. Studies on the chemical and physical properties of human leukocytic pyrogen are reviewed and form the basis for current experiments on the similarities between leukocytic pyrogen and lymphocyte activating factor. These studies suggest that leukocytic pyrogen, in addition to producing fever, also stimulates non-hypothalamic cells involved in aspects of the acute-phase response. In this regard, leukocytic pyrogen may be an important mechanism for host defenses. Hyperthermia may also be beneficial to the host but is distinct from fever; the role of leukocytic pyrogen as well as hyperthermia as a defense mechanism is discussed.

Adjuvants, Immunologic↗
PubMed1982

Ear disease in patients with Wegener's granulomatosis.

From a group of 60 patients with histologically-proven Wegener's granulomatosis managed at the National Institute of Allergy and Infectious Disease, approximately 45% were found to have disease that involved the ears. The majority of these patients had either recurrent or persistent serous otitis, resulting from eustachian tube dysfunction as a consequence of nasopharyngeal inflammations. Other pathologies included suppurative otitis, cholesteatoma, facial nerve paralyses, temporal bone granulomata, and sensory hearing losses. The presentation and management of these changes and their relationships to underlying disease are described in selected case reports, and a general philosophy of patient management is presented.

Adult↗
PubMed1981

Properties of reference Escherichia coli endotoxin and its phthalylated derivative in humans.

The properties of a reference bacterial endotoxin prepared from Escherichia coli and its phthalylated derivative were studied in normal human volunteers infected intravenously with the compounds. The minimal pyrogenic dose of the reference endotoxin is about 0.1-0.5 ng/kg. The increase in white blood cell count, absolute granulocyte count, absolute immature granulocyte count, and concentrations of serum amyloid A, cortisol, and growth hormone was directly related to the concentration of reference endotoxin administered. Phthalylated reference endotoxin up to 1,000 ng/kg (at least 500 ng of the patent compound/kg) was administered to normal human volunteers without significant changes in temperature, white blood cell count, absolute granulocyte count, and concentrations of serum amyloid A, cortisol, and growth hormone. Thus, this study defines biologic properties of the new reference bacterial endotoxin in humans and demonstrates effective detoxification by phthalylation of the present compound.

Adult↗
PubMed1981

Production of leukocytic pyrogen from phagocytes of neonates.

To study the lack of fever during the human newborn period, cord blood leukocytes obtained at birth were stimulated to produce leukocytic pyrogen (LP) in vitro. Phagocytic leukocytes from infants who were born by Caesarean section and whose mothers had not experienced natural onset of labor produced no LP or significantly less LP than leukocytes from adults or from infants born after natural onset of labor. There was a significant difference between total white blood cell count in cord blood of infants whose phagocytic cells produced LP and those whose cells did not. This observation could not be accounted for by anesthetic agents, phagocytosis of staphylococci, or number of leukocytes producing LP; thus, they suggest an intrinsic defect in the ability to produce LP before birth. Of interest is that a nondialyzable substance(s) present in crude preparations of human chorionic gonadotropin markedly suppressed LP production from adult human monocytes, but purified human chorionic gonadotropin had no effect.

Blood Proteins↗