Hepatitis B infection and kidney-graft survival.
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Biomedical subjects
Publications and source records attributed to W T London.
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Into 14 juvenile cebus monkeys that lacked serum antibodies for RS virus 10(8) plaque-forming units (pfu) of wild-type respiratory syncytial (RS) virus were inoculated transtracheally. Roentgenographic evidence of pneumonia developed in 13 of 14 infected animals. Gross pathologic changes occurred in each of the 13 monkeys that were sacrificed. Patchy areas of red consolidation were seen in the lower lobes 24 hours after inoculation, and there was progression to gray consolidation seven days later. Each of the infected animals had histologic evidence of interstitial pneumonia. Changes were detected in the lung as early as 24 hours after inoculation; they consisted primarily of infiltration of the alveolar wall. By the fourth to sixth day after inoculation there was marked interstitial thickening, pulmonary consolidation, formation of multinucleated giant cells and development of eosinophilic cytoplasmic inclusion bodies within alveolar cells. RS viral antigens, detected by indirect immunofluorescence, were distributed throughout cells of the alveolar wall and the bronchiolar epithelium. The virus grew to highest titer in the lungs on the fourth to sixth day after inoculation; up to 10(8) pfu/gram of tissue were detected. The cebus monkey represents the first experimental host to develop extensive pulmonary lesions during infection with respiratory syncytial virus.
The development of microtiter solid-phase radioimmunoassays for the detection of Norwalk antigen and its antibody is described. The tests are simple to perform and are sensitive and specific. The test for antigen can be used on crude stool filtrates and suspensions. Both tests are at least as sensitive as immune electron microscopy and more sensitive than immune adherence assay.
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Five temperature-sensitive (ts) mutants of respiratory syncytial (RS) virus (ts-1, ts-1 NG-1, ts-1 NG-16, ts-2, and ts-7), previously evaluated forinfectivity and virulence in chimpanzees and owl monkeys, were also assayed for in vivo genetic stability. None of the five mutants tested was completely stable genetically. Thus, virus which had lost some or all of the ts property was recovered from each infected chimpanzee. Significantly, each ts-1 NG-1 isolate retained some degree of temperature sensitivity and hence was not true wild-type virus. Clonal analysis of viruses shed by ts-1, ts-1 NG-1, ts-1 NG-16, or ts-7 infected chimpanzees indicated that in most instances only a minority of the virus shed was altered genetically. Of five chimpanzees infected with the ts-2 mutant, three shed only ts virus, and the remaining two chimpanzees shed only ts+ virus. Such ts+ virus proved to be avirulent when evaluated in chimpanzees or owl monkeys, indicating that loss of the ts property did not restore virulence. Based upon these findings, the ts-2 mutant appears to be a suitable candidate for clinical trials in man.
Two strains of Ureaplasma urealyticum serotype V that had produced urethritis in human volunteers were, after a number of subcultures in artificial media, introduced intra-urethrally into three chimpanzees. One strain given to two chimpanzees rapidly multiplied 1000-fold whereas there was less evidence that organisms of another strain multiplied in a third animal. Over a 14-day period the ureaplasmas persisted in all animals, did not spread to the throat and did not produce an inflammatory response. After this time they were eliminated by tetracycline therapy.
A total of 28 cebus monkeys were inoculated intratracheally or intranasally with 10(6) 50% tissue culture infective doses of A/New Jersey/76 virus or 10(7) 50% tissue culture infective doses of A/Victoria/75 virus, and 8 additional monkeys received sterile allantoic fluid. Each of the animals became infected as evidenced by a serological response and/or shedding of the virus. Of the 10 animals inoculated intratracheally with A/Victoria/75 virus, 8 developed a systemic illness, and pulmonary infiltration was detected by X-ray in 7 of the 8. Administration of A/New Jersey/76 virus intratracheally to 10 monkeys produced a mild systemic illness in 2 animals and an upper respiratory tract illness in 6, but no illness developed in the remaining 2 monkeys; none of the animals developed X-ray evidence of lower respiratory tract disease. Intranasal administration of either virus failed to induce any illness or produced, at most, mild illness confined to the upper respiratory tract. These studies demonstrate that cebus monkeys are susceptible to respiratory tract infection with influenza A viruses and that the development of pulmonary disease is reflected in the appearance of easily recognizable radiological changes.
Data from 338 blood samples of 31 patas monkeys is presented to show the normal hematolgoic development from birth to one year of age, and is compared to 120 samples from normal adults. Marked changes in hematocrit, hemoglobin, red cell numbers, and leukocyte distribution which occurred during the first month were followed by a slow progression to adult values. Body weight data is also presented which shows a linear growth rate during the first year of life.
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Serological comparison of the prototype and an epizootic (Corbell) strain of simian hemorrhagic fever virus revealed that the two viruses were serologically similar. The prototype strain differs from the Corbell strain in that the latter cannot be cultivated in vitro. Serological comparison of the prototype virus grown in tissue culture and its homologous antibody and the prototype and Corbell viruses recovered from rhesus monkey serum and their homologous antibodies showed differences and suggest that a complex relationship exists which has not yet been defined.
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Bedbugs of the species Cimex hemipterus (F) were collected on four separate occasions from the bedding in the huts of village dwellers in Senegal, West Africa. Hepatitis-B surface antigen (HBSAg) was detected in unengorged nymph and adult bedbugs in each of the first three collections. 3 of 28 such specimens were HBSAg(+) in the first collection and 3 of 17 specimens were positive in the second collection. In the third, 6 of 9 were HBSAg(+) when the bed occupant was known to be HBSAg(+). 2 of these 6 positive insects did not contain human serum proteins. Bedbugs in the fourth collection were captured and kept alive without a blood meal for 30 days. 3 of 89 of these samples were HBSAg(+). These are the highest field infection-rates of hepatitis-B virus reported in any insect species. The bedbug must be considered a potential vector of hepatitis-B virus.
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We studied the relation of host response to hepatitis B infection before transplantation with survival of kidney grafts in 79 patients receiving 87 transplants. Antibody to hepatitis B surface antigen (anti-HBs) signaled early graft rejection (median survival congruent to two months), whereas hepatitis B surface antigen (HBsAg) signaled delayed rejection (greater than 22 months). Patients with neither HBsAg nor anti-HBs had graft survival times (median congruent to 16 months) similar to the HBsAg carriers but significantly longer than the anti-HBs-positive patients (p less than 0.01). Similar results were observed when patients who received HLA-identical kidneys or had anti-HLA antibodies before transplantation were excluded. The highest probability of graft rejection was in patients with anti-HBs who received kidneys from male donors. The probability that such grafts would survive for four months was less than 20 per cent. HLA-nonidentical kidneys transplanted into patients with anti-HBs have a poor prognosis, whereas such grafts in HBsAg carriers have as good a prognosis as grafts in uninfected recipients.
The functional capacity of neutrophils of twenty children who are chronic carriers of hepatitis-B surface antigen (HBsAg) was investigated by histochemical and quantitative nitroblue tetrazolium tests (N.B.T.), an assay of bactericidal capacity against Encherichia coli, and an immunofluorescence test for HBsAg in neutrophils, The histochemical N.B.T. test showed that there was a higher proportion of stimulated neutrophils in chronic HBsAg carriers than in controls, but HBsAg particles were not detected in these cells. Bactericidal activity was significantly reduced in chronic carriers. If the defects in neutrophil function in the HBsAg carrier children preceded their hepatitis-B infections they could have influenced the development of the carrier state. Newborn infants infected with hepatitis-B virus are likely to become chronic carriers and neutrophil functions in uninfected newborn infants are similar to those seen in these carriers of HBsAg.
The distribution of T, B and null lymphocytes was studied in the peripheral blood (PB) of 34 children with acute lymphocytic leukemia (ALL), at diagnosis and during the course of their disease. All patients received the same chemotherapy. At diagnosis, the proportion and absolute numbers of T lymphocytes fell into 2 groups, a "low" group (medians 8%, 318/mm3) and a "normal" group (medians 60%, 1405/mm3). Patients with a low proportion of T cells tended to have a high proportion and absolute number of null cells (correl. coeff. r = 0.94). This group has had high white blood cell counts (median = 29,600/mm3) and a high proportion of blasts (84%). During remission, the proportion of T cells returned toward normal (40-75%) in both groups. Four patients in the low T group relapsed; T cells again fell to low levels and returned to normal in response to new therapy. Three interpretations of these observations are suggested: 1) Active leukemia may cause normal lymphocytes (T cells and to a lesser degree B cells) to lose their surface markers; 2) Acute leukemia may inhibit maturation of normal lymphoid cells, and thus T or B markers are not sufficiently developed to be detectable; and 3) Cells without surface markers (null cells) may be a part of the malignant population, even though they are not morphologic blasts. Further studies are necessary to test these hypotheses.