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Biomedical subjects

D H Walker

Publications and source records attributed to D H Walker.

At least 163 records · Page 9Linked to original sources

Familial cases of boutonneuse fever.

Pairs of cases of Boutonneuse Fever (BF) occurred in three families. The illness appeared almost simultaneously in both members of each family, but was generally more serious in one as judged by clinical and laboratory parameters. The possibility of a "bed rickettsiosis", that is reactivation of rickettsiae by the blood meal obtained from the first individual by the same tick which fed upon the second individual, could be excluded in two of the three pairs of cases. In only one of the case pairs were the individuals sharing the same bed. The differences in severity of symptoms may be related to the different immunological pattern observed in these patients. Previous rickettsial infection may have provided partial immune protection, as is repeatedly reported in the literature. In one couple, the more seriously ill patient had antibodies of the IgM class, suggesting that this was his first exposure to Rickettsia conorii. The less severely ill patient had antibodies of the IgG class only, presumably as the result of re-exposure after previous asymptomatic infection with spotted-fever-group rickettsia.

Adult↗

Phosphatidylinositol kinase is activated in membranes derived from cells treated with epidermal growth factor.

The ability of epidermal growth factor (EGF) to stimulate phosphatidylinositol (PtdIns) kinase activity in A431 cells was examined. The incorporation of 32P from [gamma-32P]ATP into PtdIns by A431 membranes was increased in membranes prepared from cells that had been pretreated with EGF. Demonstration of a stimulation of the PtdIns kinase activity by EGF required the use of subconfluent cultures and was dependent on the inclusion of protease inhibitors in the buffers used to prepare the membranes. Stimulation of the PtdIns kinase activity was rapid. The activation peaked 2 min after the addition of EGF and declined slowly thereafter. Half-maximal stimulation of the PtdIns kinase occurred at 7 nM EGF. Kinetic analyses of the reaction indicated that treatment of the cells with EGF resulted in a decrease in the Km for PtdIns with no change in the Vmax. The kinetic parameters for the utilization of ATP were unchanged in the EGF-treated membranes compared to the control membranes. Pretreatment of the cells with the phorbol ester phorbol 12-myristate 13-acetate blocked the ability of EGF to stimulate PtdIns kinase activity. These findings demonstrate that a PtdIns kinase activity in A431 cells is regulated by EGF and provide a good system for examining the mechanism by which EGF stimulates the activity of this intracellular enzyme.

1-Phosphatidylinositol 4-Kinase↗

The pathology of fatal Mediterranean spotted fever.

A 77-year-old woman from rural Spain had a febrile summertime disease develop with rash, eschar, and pulmonary, abdominal, and neurologic signs and symptoms. Mediterranean spotted fever (MSF) was diagnosed late in the course, and antirickettsial treatment was given only during the last 30 hours of life. Clinical manifestations of severe disseminated vascular injury included thrombocytopenia, hypoalbuminemia, edema of the lungs and legs, and severe prerenal azotemia. The diagnosis was documented by specific serology. Necropsy revealed vascular injury with perivascular lymphohistiocytic infiltrates suggestive of rickettsiosis in the central nervous system, lung, heart, kidneys, esophagus, stomach, colon, pancreas, spleen, and thyroid. Gastric hemorrhage and acute pneumonia contributed to the patient's death on day 18 of illness. Antimicrobial treatment and host defenses apparently reduced rickettsiae to an undetectable quantity. MSF has increased in incidence in the Mediterranean basin and has been reported in travelers returning to the United States.

Aged↗

Analysis of T-cell-dependent and -independent antigens of Rickettsia conorii with monoclonal antibodies.

Four monoclonal antibodies from euthymic mice and two monoclonal antibodies from athymic mice were directed against antigens of Rickettsia conorii, as shown by both indirect immunofluorescence and an enzyme immunoassay. There was extensive cross-reactivity with other spotted fever group rickettsiae. Euthymic monoclonal antibodies 3-2 and 9-2 (immunoglobulin G2a [IgG2a]) and 27-10 (IgG1) distinctly outlined the acetone-fixed rickettsial surface, as determined by indirect immunofluorescence; only monoclonal antibody 3-2 reacted with the intact rickettsial surface, as determined by colloidal gold-protein A negative-stain electron microscopy. Athymic monoclonal antibodies 32-2 and 35-3 (IgM) and euthymic monoclonal antibody 31-15 (IgG3) all demonstrated an irregular, extrarickettsial morphology, as determined by immunofluorescence, and ultrastructural cell wall blebs that were readily shed from the rickettsial surface. Monoclonal antibody 3-2, the only antibody to confer protection in lethally challenged mice, reacted with a high-molecular-weight protein in Western immunoblots. Monoclonal antibodies 31-15, 32-2, and 35-3 reacted with a "ladder" of proteinase K-resistant, lipopolysaccharidelike antigens. None of the monoclonal antibodies stabilized the ultrastructural rickettsial slime layer, but both athymic and euthymic polyclonal antibodies to R. conorii did. This is, to the best of our knowledge, the first report of the production of monoclonal antibodies to R. conorii and their use for antigenic analysis.

Animals↗

Gamma interferon as a crucial host defense against Rickettsia conorii in vivo.

Gamma interferon (IFN-gamma) plays an important role as a host defense in rickettsial infection. Swiss Webster mice, which are resistant to Rickettsia conorii (Malish 7 strain) infection, were treated with a monoclonal antibody against mouse IFN-gamma. When the antibody-treated mice were inoculated with 12 50% tissue culture infective doses of R. conorii, the mortality was 47% and the morbidity was 100%. None of the control mice, which received the same dose of R. conorii, died or became ill. The enumeration of rickettsiae in organs by direct immunofluorescence in paraffin sections demonstrated higher quantities of rickettsiae in the spleen had liver of IFN-gamma-depleted mice as compared with those of the infected controls. The kinetic analysis of IFN-gamma levels in sera showed depletion in the treated mice. These results indicate that IFN-gamma plays an important role as a host defense in the early stage of rickettsial infection. Survival of some mice despite continued treatment with antibody to IFN-gamma suggests that other immune mechanisms may also be important.

Animals↗

Isolation of a spotted fever group rickettsia from a patient and related ecologic investigations in Xinjiang Uygur Autonomous Region of China.

Investigation of patients, healthy persons, and ticks in Jinghe County, Xinjiang Uygur Autonomous Region, People's Republic of China, for evidence of spotted fever group (SFG) rickettsiosis demonstrated strong evidence for a high prevalence of pathogenic SFG rickettsiae. Antibodies to SFG rickettsiae were detected in 62.5% of healthy subjects tested by enzyme-linked immunosorbent assay and 20% tested by complement fixation test. Two febrile patients were documented as having acute spotted fever rickettsiosis by complement fixation seroconversion. One, and 11-year-old Kazakh boy with eschar and regional lymphadenopathy, had an SFG rickettsia (An strain) isolated from his blood. A hemolymph test revealed that 20% of ticks contained rickettsiae. Two strains of SFG rickettsiae were isolated from male and female Dermacentor nuttalli ticks. The human SFG rickettsial isolate is the first to be obtained in the People's Republic of China.

Animals↗

Rickettsial and serologic evidence for prevalent spotted fever rickettsiosis in inner Mongolia.

A field study in northeastern Inner Mongolia, People's Republic of China, in June of 1985 demonstrated a spotted fever group rickettsiosis. Two strains of spotted fever group rickettsiae were isolated. One strain was obtained from the blood of a patient with an eschar, regional lymphadenopathy, and history of a recent tick bite. The other strain originated from ova of ticks, Dermacentor nuttalli. These represent the second isolate of a spotted fever group rickettsia from a human and the first isolate from tick ova in the People's Republic of China. Antibodies to these rickettsiae were demonstrated by indirect immunofluorescence in the sera of 4% of healthy children and 34% of healthy human adults, in 58% of sheep, and in 76% of cattle in the same location. Hemolymph test revealed rickettsiae in 6 of 36 D. nuttalli examined.

Adolescent↗

Isolation on "VERO" cells of a spotted fever group rickettsia "Mortilli strain" from Rhipicephalus sanguineus.

The isolation of a Spotted Fever Group (SFG) Rickettsia "Mortilli strain" from brown dog ticks Rhipicephalus sanguineus removed from dogs associated with a confirmed case of Boutonneuse Fever (BF) in a site of a Western Sicily is reported. The need is stressed for isolation and adaption on cell cultures of SFG rickettsial strains for analysis of antigenic structure employing modern methodology.

Animals↗

Epidemiology of boutonneuse fever in western Sicily. Distribution and prevalence of spotted fever group rickettsial infection in dog ticks (Rhipicephalus sanguineus).

The distribution and prevalence of spotted fever group rickettsial infection in the ixodid dog tick Rhipicephalus sanguineus were found to occur at a rate of 19.7% with variation related to geographic and sociooccupational factors. A higher rate of infection was demonstrated in ticks removed from dogs associated with documented cases of boutonneuse fever. The results fit into available clinical and seroepidemiologic data on Rickettsia conorii infection in western Sicily.

Animals↗

Humoral immune response to Rocky Mountain spotted fever in experimentally infected guinea pigs: immunoprecipitation of lactoperoxidase 125I-labeled proteins and detection of soluble antigens of Rickettsia rickettsii.

Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever, purified from infected L-929 cells by density gradient banding were extrinsically radioiodinated with lactoperoxidase. Immunodominant 125I-labeled antigens were identified by radioimmunoprecipitation of detergent-solubilized antigens with protein A-Sepharose and anti-R. rickettsii sera collected 0, 3, 7, 11, 32, and 163 days after infection of guinea pigs. The average fever greater than or equal to 40 degrees C was detected by days 3 and 4 after infection with 6 X 10(7) and 6 X 10(6) PFU, respectively. By microagglutination and complement fixation assays, anti-R. rickettsii antibodies were detected as early as day 3 after infection, with titers increasing markedly between days 7 and 163. Convalescent sera, collected on day 163, from infected guinea pigs were used to identify seven 125I-labeled antigens with apparent molecular sizes of 186,000 (I), 145,000 (II), 49,000 (III), 32,000 (IV), 27,500 (V), 17,500 (VI), and 16,500 (VII) daltons. Differences in antibody reactivity and specificity against the seven antigens were demonstrated with serially obtained sera. Sera from a guinea pig infected with 6 X 10(7) PFU exhibited antibody-antigen interactions with all seven 125I-labeled antigens by day 7, whereas the same antibody activity required 32 days for an animal infected with 6 X 10(6) PFU. Prominent antibody activities toward proteins II and IV were demonstrated both early and late after infection. The fluids obtained from infected L-929 cells contained three soluble antigens which were detected with the 11-, 32-, and 163-day sera by an immunodiffusion assay. The soluble and 125I-labeled antigens of R. rickettsii identified in this study may be important candidates for vaccines against Rocky Mountain spotted fever.

Animals↗

Rocky mountain spotted fever: hepatic lesions in childhood cases.

We studied 16 fatal childhood cases of Rocky Mountain spotted fever (RMSF). Hepatic histologic lesions with statistically significant differences from age- and sex-matched controls were portal triaditis consisting of polymorphonuclear leukocytes and large mononuclear cells, portal vasculitis, sinusoidal leukocytosis, erythrophagocytosis by Kupffer cells, and gross hepatic weight. Hepatocellular necrosis, cholestasis, and congestion were not more frequent in RMSF than in controls. Using immunofluorescence microscopy, we were able to demonstrate rickettsial organisms in portal blood vessels and sinusoidal lining cells of 7 cases.

Adolescent↗