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H Wulff

Publications and source records attributed to H Wulff.

At least 37 records · Page 2Linked to original sources

A mathematical model of erythropoiesis in mice and rats. Part 2: Stimulated erythropoiesis.

A mathematical model of erythropoietic cell production and its regulation process has been proposed in a preceding paper. It is primarily based on the assumption that the number of cell divisions taking place in the CFU-E and erythropoietic precursor stages is regulated depending on the oxygen supply of the tissue. Quantitative dose-response relationships for in vivo erythropoiesis are suggested. Here, we demonstrate that this model adequately reproduces data obtained in situations of stimulated erythropoiesis in mice and rats. In detail, this implies a quantitative description of the following processes: (1) Changes in tissue oxygen tension (Pto2) following removal of red cells (bleeding, haemolytic anaemia) or increase in plasma volume (dilution anaemia) or decrease in atmospheric oxygen pressure (hypoxia). (2) Pto2 dependent erythropoietin (EPO) production. (3) Dose-response of EPO on erythropoietic amplification (up to two to four additional mitoses). (4) The changes of the marrow transit time. Model simulations are compared with experimental data for changes of erythropoiesis during hypoxia, EPO-injection, and different forms of anaemia. A satisfactory agreement suggests that the model adequately describes and correlates different direct and indirect ways to stimulate erythropoiesis. It quantifies the role and relative contribution of the haematocrit, haemoglobin concentration, atmospheric oxygen pressure, tissue oxygen pressure, and plasma volume as triggers in erythropoietic stimulation under various conditions. Furthermore, the model may allow to optimize the scheme of EPO-administration and to find the maximum increase of erythropoiesis for a given amount of erythropoietin.

Anemia↗

A mathematical model of erythropoiesis in mice and rats. Part 3: Suppressed erythropoiesis.

A mathematical model of erythropoietic cell production and its regulation process has been proposed in a preceding paper. It is primarily based on the assumption that the number of cell divisions taking place in the CFU-E and erythropoietic precursor stages can be regulated depending on the oxygen supply to the tissue. Here we provide evidence that this model adequately describes situations of suppressed erythropoiesis. In detail this implies a quantitative description of the following processes: (1) changes in tissue oxygen tension (Pto2) due to increase in red cell numbers (red cell transfusion, posthypoxia), decrease in plasma volume (dehydration) or increase in atmospheric oxygen pressure (hyperoxia), (2) Pto2 dependent reduction of erythropoietin (EPO) production, (3) dose-response of reduced EPO-levels on erythropoietic amplification (omission of three to five mitoses). Model simulations are compared to experimental data obtained from red cell transfusion, posthypoxia, hyperoxia and dehydration. A satisfactory agreement suggests that the model adequately describes and correlates different ways to suppress erythropoiesis. It quantifies the role and relative contribution of the haematocrit, haemoglobin concentration, atmospheric oxygen pressure, tissue oxygen pressure and plasma volume as triggers in erythropoietic suppression under various conditions. In conjunction with the preceding two papers it could be shown that one unique set of model parameters is sufficient to describe erythropoiesis in steady state, stimulation and suppression. Limitations of the model are discussed and experiments for a more detailed investigation of the feedback mechanisms are proposed.

Animals↗

Diagnosis of enterovirus 70 infection by demonstration of IgM antibodies.

Since outbreaks of severe acute hemorrhagic conjunctivitis occur worldwide [Hierholzer and Hatch, 1985] and the majority of the epidemics are caused by enterovirus 70 (EV-70), we developed an EV-70 IgM ELISA to simplify the diagnosis of these outbreaks. The test is based on the capture antibody technique and the use of monoclonal antibodies to EV-70. We detected EV-70 IgM antibodies in 55% of 76 convalescent-phase sera from an outbreak of acute hemorrhagic conjunctivitis in a Brazilian community. Among the 71 acute- and convalescent-phase serum pairs from this outbreak, 49 (69%) demonstrated a 4-fold or greater rise in neutralizing antibody-titer. The titer of IgM antibody began to drop by the fifth week after onset of illness. EV-70 IgM antibodies were not detected in 53 serum pairs with a 4-fold or greater rise in antibodies to other picornaviruses. The EV-70 ELISA proved to simple and relatively rapid to perform, appeared to be specific, and should be sensitive enough to diagnose outbreaks of EV-70 when multiple serum specimens can be tested.

Adolescent↗

Detection of antibodies and antigens of human parvovirus B19 by enzyme-linked immunosorbent assay.

Acute-phase serum from a patient with aplastic crisis provided sufficient human parvovirus B19 to make a monoclonal antibody against B19 and to develop antigen and immunoglobulin M (IgM) and IgG antibody detection enzyme-linked immunosorbent assays (ELISAs). The indirect capture antibody method was used for all three assays. Antigen was detected in 8 of 29 sera drawn within 2 days of onset of illness from patients with aplastic crisis. These sera had high titers of virus by electron microscopy and DNA hybridization and had no detectable B19 antibody. Antigen was not detected in serum specimens that had low titers of B19 DNA and had B19 antibody. With the IgM ELISA, we detected B19 IgM in over 85% of clinical cases of aplastic crisis and fifth disease and less than 2% of controls. The prevalence of B19 IgG antibodies increased with age. Approximately 2% of children less than 5 years of age and 49% of adults greater than 20 years of age had B19 IgG antibodies. The B19 antibody ELISAs are sensitive and specific tests to detect B19 infections.

Adolescent↗

[Mathematical models in hematology].

The use of mathematical models in haematology is shown by some examples concerning stem cell kinetics, erythropoiesis and thrombopoiesis. At first, model assumptions are formulated which include the biological knowledge and some regulatory hypotheses. Then, the reaction of the model on stimulation and suppression is calculated. Finally, by comparison with experimental or clinical data one can evaluate how far the model assumptions are sufficient to understand the measurements. Thus one can exclude wrong hypotheses and identify the important regulatory influences.

Blood Platelets↗

[Prospective studies on pregnancy following induced and spontaneous abortion of primigravidae and assessment of fertility. IV. report].

Prospects for imminent and spontaneous abortion were studied in three groups of probands. These included secundigravidae following induced abortion, secundigravidae after spontaneous abortion, and primigravidae. --Chronological distribution of abortion was determined for two periods of time, up to the 16th week of pregnancy and between the 17th and 27th weeks of pregnancy. Reference is made to correlations between abortion and cervical insufficiency. Poor prognosis in a group with a record of spontaneous abortions was compared with accumulation of functional bleeding in the same group. --An account is given also of the incidence of defective infants in all three groups, in the context of prematurity.

Abortion, Induced↗

Kawasaki syndrome: description of two outbreaks in the United States.

Investigation of two outbreaks of Kawasaki syndrome (KS) in the United States in 1979 and in 1980 revealed no evidence of person-to-person transmission or of a common-source exposure among patients. Questionnaire data showed that KS was more likely to occur in children of middle and upper socioeconomic status than in those of lower status (P less than 0.05 and P less than 0.001 for the respective outbreaks) and that patients with KS had a higher incidence of an antecedent, primarily respiratory illness than did controls matched for age, sex, and race (83% of patients in the first outbreak vs. 30% of one control group, P less than 0.01, and vs. 36% of another control group, P less than 0.02; and 56% of patients in the second outbreak vs. 32% of their controls, P less than 0.02). However, laboratory studies did not identify an etiologic agent for either KS or for the antecedent illness that may be a risk factor for KS.

Adolescent↗

Immunoglobulin M and G responses measured by immunofluorescence in patients with Lassa or Marburg virus infections.

Immunoglobulin M antibodies can be measured by indirect immunofluorescence in sera of patients suffering from Lassa fever or Marburg virus disease 4-7 days after onset of illness. Titres reach a peak 1-2 weeks later. These antibodies disappear, or titres decrease considerably, 1-2 months after onset of illness. Antiviral IgG antibodies can be detected at the same time as, or a little later than, IgM antibodies, but they persist much longer. None of the three patients discussed in this paper who died of Lassa fever developed IgG antibodies and only one developed IgM antibodies.

Animals↗

Epidemiologic investigation of Marburg virus disease, Southern Africa, 1975.

During the first 10 days of February 1975, an Australian hitchhiker contracted Marburg virus disease while traveling through Rhodesia and died; the infection was subsequently passed to two other persons, who recovered. Investigators retraced the hitchhiker's steps in March and again in June 1975 in an effort to uncover the natural reservoir of the virus and determine how it was transmitted. Serum samples were collected from humans and animals wherever the patient had come in close contact with animals or insects. Arthropods of various types were collected in June 1975 and again in February 1976 for virus isolation attempts; at no time did the patient come in direct contact with nonhuman primates of any kind, or any other animals. Indirect contact with bats, monkeys, and birds through aerosols was possible, though at some distance. Direct contact with arthropods occurred throughout the trip; on several occasions it was notably severe. We believe that during this outbreak the first Marburg virus infection occurred by vector-borne transmission from an arthropod yet to be identified, and that patients 2 and 3 acquired the disease by exposure to the oropharyngeal secretions of patients 1 and 2, respectively. Studies are underway to identify the species of arthropod involved in this transmission.

Adult↗

Early detection of antigen and estimation of virus yield in specimens from patients with Marburg virus disease.

Autopsy specimens from patients with Marburg disease having at least 10(4.5) TCID(50) of virus per gram of tissue were found to contain sufficient fluorescent antigen-positive cells to make a specific diagnosis possible in less than 3 h. Liver, heart, spleen, and kidney tissues were found to contain significant amounts of virus. Tissue suspensions, as well as blood or serum samples, inoculated into Vero cell cultures produced virus-specific immunofluorescence within 2-5 days. At least one specimen of all virus-positive persons yielded Marburg virus-specific antigen on day 2 or 3 after inoculation. Furthermore, tissues with at least 10(5.5) TCID(50) of virus/g had Marburg antigen of sufficient titre to be used in complement fixation tests.

Animals↗

Lassa fever: response to an imported case.

In February, 1976, a Peace Corps worker returned to the United States from Sierra Leone with an undiagnosed illness later recognized as Lassa fever. To assess the risk of transmission and to contain a potential outbreak, we identified 552 contacts as having had exposure to the patient before the start of strict isolation procedures, and maintained intensive surveillance on these contacts for 21 days. At the end of the surveillance period, no illness had developed in contacts. One month later, a serologic survey among 29 of the contacts judged to be at high risk gave no evidence of infection. In response to the importation of this communicable and highly fatal disease, procedures for the isolation of the patient, the identification, surveillance and management of contacts and the handling of laboratory specimens were developed and implemented. These procedures could be adapted to future introductions of highly contagious diseases.

Adult↗

Isolation of an arenavirus closely related to Lassa virus from Mastomys natalensis in south-east Africa.

Five unidentified virus strains were recovered from the multimammate mouse ,Mastomys natalensis, during the course of studies on arbovirus infections in Mozambique. These agents were found to be morphologically and immunologically related to Lassa virus. Four of 19 sera from Mastomys captured in the study area had antibodies to both Lassa virus and one of the unidentified strains. Although not definitive, the differences noted in results of complement fixation and indirect immunofluorescent tests suggest that these viruses from south-east Africa are not identical to West African Lassa virus.

Africa, Northern↗

Cytomegalovirus infection in a volunteer blood donor population.

Among 223 volunteer blood donors who were studied for evidence of cytomegalovirus (CMV) infection, 58 percent had complement-fixing antibody and 59 percent had indirect hemagglutinating antibody to CMV. No virus was isolated from any donor's washed leukocytes or leukocyte-rich plasma in fibroblast monolayer culture. In seven asymptomatic donors (3 percent), CMV was recovered from urine cultures obtained at the time of blood donation. However, at the time of reexamination, viruria was no longer present and serum antibody titers had not changed. In the three patients studied who received blood from three of the cytomegaloviruric donors, serological evidence of CMV infection developed (fourfold or greater indirect hemagglutinating antibody rise), and one recipient also developed cytomegaloviruria; no illnesses was associated with these infections. Further study is needed to establish that the detection of viruria in donors may identify potentially infective blood.

Antibodies, Viral↗

Lassa fever in Onitsha, East Central State, Nigeria in 1974.

Three cases of Lassa fever occurred in Onitsha, East Central State, Nigeria, in January and February 1974. The first case was a 19-year-old Nigerian; the other 2 cases were German missionary physicians at St Charles Borromeo Hospital, Onitsha, one of whom cared for the patient who was the first case. Thus, 2 of the 3 cases were hospital acquired. Investigations failed to discover a village outbreak or the source of virus for the first case. A serosurvey of 258 hospital staff members and contacts of the 3 cases showed no other persons with antibody to Lassa virus. The absence of Lassa virus antibody in a high-risk group indicates a low or nonexistent level of past Lassa virus activity in southeastern Nigeria.

Adult↗

Recent isolations of Lassa virus from Nigerian rodents.

Rodents were trapped in the Benue-Plateau and North-Eastern States of Nigeria where Lassa fever had been reported in previous years. Eight Lassa virus strains were isolated from tissues and blood of rodents identified in the field as being of 3 different species: Mastomys natalensis, Rattus rattus, and Mus minutoides. All the infected rodents were collected in village habitats. These isolations indicate the presence of Lassa virus in wild rodents in Nigeria during periods when no human infections were evident.Prior studies in Sierra Leone have indicated that a single rodent species, M. natalensis, may be the important reservoir host of Lassa virus. Since the present study indicates that other rodent species may be involved as well, the ecology of Lassa virus may be more complicated than was heretofore supposed. In view of the importance of determining the geographic and species range of rodent hosts of Lassa virus, and because of the problems inherent in rodent identification under austere field conditions, it is urgent that further studies be conducted in the same areas of Nigeria to confirm these findings.

Animals↗

Experimental Lassa virus infection in the squirrel monkey.

Experimental Lassa virus infection was investigated in a nonhuman primate in order to elucidate the target organs of the viral infection and the course of pathologic events. Four squirrel monkeys (Saimiri scirreus) were inoculated intramuscularly with Lassa virus and sacrificed for organ titrations and histopathology, one each day, on Days 7, 12, 14, and 28 after inoculation. The animals showed a variable clinical course, with an incubation period of 8 to 18 days. The virus was demonstrated to be virtually pantropic; however, lymph node, liver, and kidney were key early targets. After the onset of overt disease, patterns of lymphoreticulotropism, hepatotropism, nephrotropism, adrenotropism, and persistent viremia were evident. Complement-fixing antibody failed to develop after 28 days of infection. Histopathologic findings included germinal center necrosis in spleen and lymph node; myocarditis; acute arteritis; renal tubular necrosis and regeneration; hepatocytic regeneration; chronic inflammation of choroid plexus, ependyma, and meninges; and cerebral perivascular cuffing. There is a relationship between many of these lesions and certain features of other arenavirus infections. The model offers the opportunity to pursue investigations of experimental pathogenesis, transmissibility, and efficacy of immunotherapy.

Animals↗