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Biomedical subjects

J D Stinnett

Publications and source records attributed to J D Stinnett.

14 recordsLinked to original sources

A comparison of immunologic profiles and their influence on bacteremia in surgical patients with a high risk of infection.

Prospective sequential studies of the antibacterial function of neutrophils, lymphocyte responsiveness, opsonic capacity of serum and serum levels of C3(B), properdin, factor B, IgG, and albumin were made in 32 patients with severe burn injury (greater than or equal to 45%), 21 patients with severe multisystem traumatic injury, 20 high-risk, infected patients, and 22 renal transplant patients. Fifty-five episodes of bacteremia occurred in 37 of the 95 patients. Abnormal neutrophil function was clearly associated as a predisposing factor to these episodes, whereas there was no association between bacteremia and low serum levels of C3, IgG, factor B, or properdin. C3, factor B, and IgG usually rose following bacteremia as acute phase proteins, but there was evidence of a consumptive opsoninopathy in 11% of episodes. Defective opsonization was associated with a high risk of bacteremia only when there was a coexisting abnormality of neutrophil function (88% of such patients became bacteremic). None of 27 nonburned patients tested with delayed hypersensitivity antigens responded normally, and there was regularly depression of lymphocyte responsiveness to phytohemagglutinin-A and concanavalin-A in a whole blood assay related to serum immunosuppressive factors, but poor responsiveness was not associated with bacteremia.

Adolescent

Fresh-frozen plasma vs. plasma protein derivative as adjunctive therapy for patients with massive burns.

Twenty patients with burn injuries involving 45% or more total body surface area were randomly allocated to receive either fresh-frozen plasma (plasma), 200 ml/m2/d (11 patients), or an approximately equal amount of plasma protein derivative (Plasmanate) (nine patients) during the first 45 days postburn. To study the potential effects of these two adjunctive therapies on host resistance to infection, measurements were made twice weekly of the antibacterial funciton of neutrophils, the opsonic index (ability to opsonize alternative pathway dependent E. coli 075), C3(B), IgG, properdin, factor B, total protein, and albumin. The average size of burn in the plasma group was 61.5% total and 42% 3 degrees compared with 61% total and 46% 3 degrees in the Plasmanate group. Ten and 18 episodes of bacteremia occurred in the plasma and Plasmanate groups, respectively. Analysis of the results indicates only slightly better support of host resistance when plasma is administered, but this is counterbalanced by the increased risk of viral hepatitis.

Adolescent

A sequential, prospective analysis of immunologic abnormalities and infection following severe thermal injury.

A sequential, prospective analysis of humoral and cellular immune function was performed on 20 burn patients with injuries involving >/=45% total body surface area. Infected patients had significantly worse neutrophil bactericidal activity against Staphylococcus aureus 502A than did noninfected patients. Chemotaxis of neutrophils correlated poorly with infection although chemotaxis was frequently abnormal. The opsonic index of serum was depressed early after the burn but returned to nearly normal values by the fourth to the fourteenth postburn day. There was no difference between infected and noninfected patients. Serum levels of IgG, properdin and C3, while initially low, remained within the normal range after the ninth postburn day in both groups. Factor B levels rose rapidly during the first three weeks after injury to more than double normal levels in many patients. Suggestive evidence for consumption of opsonic protein occurred with five of 19 episodes of bacteremia. The responsiveness of isolated lymphocytes to PHA was normal. However, patients' sera were shown to significantly inhibit the responsiveness of normal lymphocytes to PHA. Analysis of immunologic profiles for individual patients indicates that abnormalities of neutrophil function are the most important acquired defect predisposing patients to the development of bacteremia following major thermal injury; abnormalities of opsonic action play a secondary but important role.

Bacterial Infections

Whole blood vs. packed red cells for resuscitation of hemorrhagic shock: an examination of host defense parameters in dogs.

Whole blood vs. packed red cells for resuscitation of acute blood loss in dogs was compared with respect to a number of variables of host defense. Dogs subjected to a controlled blood loss equal to 8% of their body weight exhibited significant depressions in serum protein, C3, IgG, and total opsonic activity when resuscitated with packed red cells in saline. No such depression in serum components or activity was observed in identically bled dogs resuscitated with whole blood. There were no differences in the rate of clearance of intravenously injected bacteria indicating an intact reticuloendothelial system (RES) function in both groups. These experiments suggest that whole blood may be preferable to packed cells for resuscitation of acute hemorrhagic shock when the effect on resistance of infection is considered.

Animals

Growth patterns and metastatic behavior of human tumors growing in athymic mice.

The growth characteristics and metastatic behavior of human tumors growing in athymic nude mice were studied. Human tumor cell lines HEp-2 (carcinoma or larynx) and SW480 (colon carcinoma) were transplanted into athymic nude mice of BALB/c origin. Tumor cells (1 x 10(6) and 2 x 10(7)) were given either s.c. or i.p. Following s.c. injection tumors developed rapidly to become easily palpable with 2 weeks forming a s.c. tumor focus surrounded by a thick fibrous capsule. Animals with s.c. transplants were little affected by the growing tumor. At the time they were sacrificed at Day 34 (HEp-2) and 62 (SW480), a large part of the tumor was necrotic. Capsular infiltration and invasion of lymphatic vessels and perineural and perivascular lymphatic spaces were observed. Metastases to regional lymph nodes were seen in animals kept alive for up to 6 months. Following i.p. transplantation, tumors spread widely in the peritoneal cavity, invaded intraabdominal organs, and metastasized to mediastinal lymph nodes and lungs. Fifteen of 26 animals (60%) developed metastases. Necrosis of the i.p. growing tumors was minimal. All animals in this group died as a result of tumor growth.

Animals

The effects of malnutrition on variables of host defense in the guinea pig.

Studies were conducted in young guinea pigs to determine the effects of malnutrition on selected variables of host resistance. Malnutrition was produced differently in two experiments. In the first the quantity of a standard, normal diet was reduced progressively so that test groups were fed 25% less each week over a 4 week period. Control groups were fed ad libitum. In the subsequent experiment, animals were fed defined guinea pig diets containing 5%, 30%, and 60% casein, respectively, which were similar in caloric content, vitamins, and minerals. Measurements of phagocytic bactericidal activity, serum opsonization, serum IgG and C3 levels, and mitogenic response of lymphocytes were made at weekly intervals. Results obtained from both experiments were comparable. There was a significant decline in phagocyte function by the third week in malnourished animals while the numbers of phagocytes per milliliter of peritoneal washings were similar to controls at all time periods. A depression of serum opsonization was observed when animals became moribund even though serum IgG levels remained unchanged. Serum C3 levels in malnourished animals were significantly lower than controls. Mitogenic response of lymphocytes to phytohemagglutinin was 85% lower in the 5% casein group after the third week. These results indicated that a marasmus-like condition and protein malnutrition depress critical functions of resistance.

Animals

Chemoattractant properties of Corynebacterium parvum and pyran copolymer for human monocytes and neutrophils.

Both pyran copolymer and the Burroughs-Wellcome vaccine of Corynebacterium parvum were able to elicit a migratory response by human neutrophils or monocytes when incubated with serum. However, in the absence of serum, neither agent elicited such a response. The generation of the chemotactic factor by pyran was dependent on heat-labile components in the serum, while suggested involvement of the complement sequence. Conversely, the migratory response of C. parvum in heated serum was equivalent to that in normal serum. No specificity for either monocytes or neutrophils was observed.

Chemotaxis, Leukocyte

Identification of a macrophage-specific cell surface antigen.

A mouse-specific macrophage antigen (MSMA) was identified in NP-40 extracts of 125I-radiolabeled mouse preitoneal macrophages by using a rabbit anti-mouse macrophage serum (AMS) and SDS-polyacrylamide gel electrophoresis. The antigen was shown to have a m.w. of 83,000 daltons and was present on both normal and "activated" peritoneal macrophages. MSMA was also present on syngeneic adherent spleen cells, allogeneic peritoneal macrophages, a mouse macrophage cell line (P388D1), and exhibited some cross-reactivity with peritoneal macrophages from closely related species (rats and hamsters). MSMA was not present on nonadherent peritoneal exudate cells, spleen cells, erythrocytes, thymocytes, or bone marrow cells. Extensive absorptions of AMS with thymocytes and erytrocytes from mice were necessary to remove other antibodies that reacted with other mouse membrane antigens. An antiserum directed against a specific membrane antigen has great potential in elucidating structure-function relationships with regard to a number of macrophage activities.

Animals

A model system for studying protein-lipopolysaccharide synthesis, assembly, and insertion in the outer membrane of Pseudomonas aeruginosa.

Ethylenediaminetetraacetate (EDTA) has been previously shown to cause the release of a complex of protein and lipoplysaccharide (PrLPS) from the outer membrane of Pseudomonas aeruginosa. In this present work, cells of P. aeruginosa were incubated in a solution of EDTA, phosphate buffer, and hypertonic sucrose to prepare osmoplasts (osmotically sensitive cells). Osmoplasts were able to undergo self-repair of the outer-membrane damage resulting from EDTA treatment and to regain osmotic stability when incubated in growth medium/hypertonic sucrose for 2 h in the absence of exogenous PrLPS and in the absence of cell division. This repair process was inhibited by either chloramphenicol or KCN. Examination of freeze-etched preparations demonstrated that 40% of the PrLPS units in the outer membrane were removed by EDTA; after 2 h in growth medium/hypertonic sucrose, cells were able to repair this damage by synthesizing and inserting new PrLPS units into the outer membrane. Osmoplasts could also be restored to osmotic stability by suspension in osmoplast supernatant fluid containing PrLPS and Mg2+. This latter restoration process, which was not inhibited by chloramphenicol or KCN, was purely physical while the self-repair restoration process was metabolic. These data are consistent with the concept that the outer membrane proteins, especially the PrLPS units play a role in stabilizing the cell envelope and in maintaining the osmotic stability of P. aeruginosa.

Bacterial Proteins