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Biomedical subjects

J D Lundgren

Publications and source records attributed to J D Lundgren.

At least 145 records · Page 8Linked to original sources
PubMed1991

Hydrocortisone inhibits rat basophilic leukemia cell mediator release induced by neutrophil-derived histamine releasing activity as well as by anti-IgE.

We determined the ability of hydrocortisone to inhibit rat basophilic leukemia cell mediator release induced by anti-IgE and by neutrophil-derived histamine-releasing activity (HRA-N). Serotonin release induced by HRA-N and anti-IgE was inhibited by 78 +/- 5 and 70 +/- 4%, respectively (IC50 7.5 x 10(-7)M) by hydrocortisone (10(-5)M). HRA-N does not cause arachidonic acid metabolism, however, anti-IgE induced the generation of PGD2 and leukotriene (LT)C4, and the generation of both mediators was inhibited by 10(-5)M hydrocortisone (IC50 = 4.8 x 10(-7)M, and 3.6 x 10(-9)M, respectively). Inhibition required at least 5 to 6 h of hydrocortisone exposure and was maximal after 22 h. The observed effects of hydrocortisone could be reproduced by human recombinant lipocortin-I (5 x 10(-7)M). Hydrocortisone, 10(-5)M, was a less potent inhibitor of calcium ionophore A23187-mediated serotonin release and PGD2 and LTC4 generation (inhibition of 20 +/- 2, 17 +/- 10, and 37 +/- 10%, respectively). Inasmuch as A23187-induced stimulation is not dependent on receptor coupling, the enhanced ability of hydrocortisone to inhibit IgE- and HRA-N-mediated events as compared with A23187 suggests that one possible site of action of hydrocortisone may be interruption of receptor-effector signals. In the presence of arachidonic acid, hydrocortisone-treated cells released as much LTB4 and PGD2 as control cells, however, serotonin release and LTC4 generation were inhibited 50 and 55%, respectively. Thus, these data suggest that hydrocortisone has three possible sites of action: 1) inhibition of phospholipase A2 activity, 2) inhibition of glutathione-s-transferase, and 3) inhibition of serotonin release by a third mechanism, possibly by interrupting the coupling of receptor and effector systems.

Animals↗
PubMed1991

Nosocomial outbreak of cryptosporidiosis in AIDS patients.

OBJECTIVE: To describe a nosocomial outbreak of cryptosporidiosis during four months after June 1989. SETTING: A department of infectious diseases in Copenhagen, seeing about half the patients with AIDS in Denmark. SUBJECTS: 73 HIV antibody negative subjects and 60 antibody positive subjects admitted as inpatients during the transmission period of the outbreak (20 June-14 August), of whom 18 (17 with AIDS, one with AIDS related complex), developed cryptosporidiosis. Two further HIV negative subjects (one departmental secretary, one visiting relative) developed cryptosporidiosis. MAIN OUTCOME MEASURES: Cryptosporidia in stool samples, clinical symptoms, CD4 cell count, HIV antigen concentration, chemotherapeutic treatment. RESULTS: The source of the outbreak was identified as ice from an ice machine in the ward, contaminated by an incontinent, psychotic patient with cryptosporidiosis picking out ice for cold drinks. The mean incubation time was at least 13 days-that is, twice that in HIV-negative patients. Of the 18 patients with AIDS who developed cryptosporidiosis, five recovered, two were symptomless carriers, three died of unrelated causes, and eight died after prolonged diarrhoea. Among the 57 exposed HIV antibody positive inpatients (excluding two patients and the index case with cryptosporidiosis diagnosed elsewhere), significantly more of those who developed symptomatic cryptosporidiosis received oral sulphonamides than those who did not (91%, 10/11 v 48%, 21/44, p less than 0.05). CONCLUSIONS: The clinical and epidemiological findings indicate that infection was the consequence of very small inocula. Increased sensitivity to cryptosporidiosis may be an unrecognised side effect of oral sulphonamide treatment in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Severe Rhodococcus equi pneumonia: case report and literature review.

Rhodococcus equi is an aerobic, gram-positive, non-motile pleomorphic bacillus infecting immunocompromised patients. Forty-nine cases of Rhodococcus equi infection have been reported, mainly in patients infected with the human immunodeficiency virus (HIV). A case in which Rhodococcus equi caused severe pulmonary infection, the most common presentation, is described. Clinically, patients have symptoms of pneumonia with hemoptysis as a prominent feature. X-ray will often show a cavitating upper-lobe infiltrate, resembling infection with mycobacteria. Rhodococcus equi is easily cultured from blood or sputum on standard media, but is frequently regarded as a contaminant. Mortality from Rhodococcus equi pneumonia is high (25%) and early surgical intervention has been recommended. Based on this review, the benefit of surgery seems dubious, whereas good results have been obtained using long-term antibiotic treatment with erythromycin plus rifampicin, or vancomycin in combination with either of these antibiotics.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Eosinophil cationic protein stimulates and major basic protein inhibits airway mucus secretion.

Possible roles of eosinophil (EO) products in modulating the release of mucus from airway explants were investigated. Cell- and membrane-free lysates from purified human EOs (1 to 20 x 10(5)) caused a dose-dependent release of respiratory glycoconjugates (RGC) from cultured feline tracheal explants. Crude extracts from isolated EO granules also stimulated RGC release, suggesting that a granular protein might be responsible. Three proteins derived from EO granules, EO-derived neurotoxin, EO cationic protein (ECP), and major basic protein (MBP) were separated by sequential sizing and affinity chromatography. ECP (0.025 to 25 micrograms/ml) caused a dose-dependent increase in RGC release from both feline and human airway explants and also stimulated the release of the serous cell-marker, lactoferrin, from human bronchial explants. EO-derived neurotoxin (0.025 to 50 micrograms/ml) failed to affect RGC release, whereas MBP (50 micrograms/ml) significantly inhibited RGC release from feline explants. Thus, ECP stimulates RGC and lactoferrin release from airway explants, whereas MBP inhibits RGC release.

Airway Obstruction↗
PubMed1991

HIV-associated lymphoma: histopathology and association with Epstein-Barr virus genome related to clinical, immunological and prognostic features.

All 51 cases of HIV-related malignant lymphoma in Denmark diagnosed from 1983 to 1989 were reviewed. There were 12 Burkitt-type lymphomas, 30 immunoblast-rich lymphomas and 9 other lymphomas. Patients with immunoblast-rich lymphomas had significantly lower CD4 cell counts (median 60 vs. 188 x 10(6)/l, P less than 0.05), and more often a history of previous AIDS-defining illnesses (50% vs. 0%, P less than 0.005), compared with patients with Burkitt-type lymphomas. Epstein-Barr virus (EBV) DNA was demonstrated in 14 of 19 immunoblast-rich tumours, and in 2 of 7 Burkitt-type lymphomas (P = 0.10). Compared with EBV DNA-negative tumours EBV DNA-positive tumours were associated with lower CD4 cell counts (median 39 vs. 188 x 10(6)/l, P = 0.01). It is concluded that two main types of HIV-related malignant lymphoma exist. One is associated with severe immunosuppression, is often of immunoblast-rich morphology, and may be linked to EBV, whereas the other may occur in the absence of immunosuppression, is often of Burkitt-type morphology, and is probably not linked to EBV. In addition to these two main types, other non-Hodgkin lymphomas and Hodgkin's disease do occur.

Adult↗
PubMed1991

Effect of protein kinase C activating agents on respiratory glycoconjugate release from feline airways.

Abnormal regulation of airway glycoprotein secretion may underlie many respiratory diseases. Experimental activation of the protein kinase C (PKC) family of cytosolic enzymes has been shown to induce a secretory response in many tissues. To estimate the effect of PKC activation on airway secretion, alteration in the amount of radiolabeled respiratory glycoconjugate (RGC) released into culture media was determined following feline airway explant exposure to PKC activating agents. Exposure to two known activators of PKC, phorbol 12-myristate 13-acetate (PMA) and mezerein (MEZ), resulted in profound increases in respiratory glycoconjugate release over a seven day experimental period. The response evolved over several hours and was dose dependent. Maximal RGC release, 90% above control, occurred 2 days after exposure to either PMA or MEZ. Pharmacological inhibition of the PKC effect using two PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and sphingosine, resulted in dose-dependent antagonism of the maximal PMA (10(-7) M)-stimulated RGC release, suggesting altered PKC activity was responsible for augmenting RGC release. Since altered arachidonic acid metabolism has been implicated in mediating some PKC effects, eicosanoids were assayed in airway explant supernatants following PMA exposure. Enhanced release of both cyclooxygenase and lipoxygenase pathway products was detected by radioimmunoassay. Cotreatment of explants with PMA and an inhibitor of oxidative arachidonic acid metabolism, nordihydroguaiaretic acid, blocked RGC release. These data demonstrate prolonged augmentation of respiratory glycoconjugate release from airway explants following exposure to PKC-activating agents.

Animals↗
PubMed1991

Substance P and neurokinin A in human nasal mucosa.

The tachykinins substance P (SP) and neurokinin A (NKA) were studied in human inferior turbinate nasal mucosa by radioimmunoassay, immunohistochemistry, and autoradiography and for their effect upon mucus release in an in vitro culture system in order to infer their potential functions in the upper respiratory tract. Similar amounts of SP (1.03 +/- 0.12 pmol/g wet weight; mean +/- SEM; n = 26) and NKA (0.76 +/- 0.23; n = 7) were found. NKA and SP immunoreactive nerve fibers were found in the walls of arterioles, venules, and sinusoids and as individual fibers in gland acini, near the basement membrane, and in the epithelium. [125I]SP bound to arterioles, venules, and glands. [125I]NKA bound only to arterioles. In short-term explant culture of fragments of human nasal mucosa, both 1 microM SP and 1 microM NKA stimulated release of [3H]glucosamine-labeled respiratory glycoconjugates. These results indicate that SP and NKA have similar distributions in nociceptive sensory nerves in human nasal mucosa. The distribution of [125I]SP binding sites is consistent with a role for SP as a vasodilator and mucous secretagogue. The presence of [125I] NKA binding sites on vessels suggests a primary role for NKA in regulating vasomotor tone.

Amino Acid Sequence↗
PubMed1991

Prevalence of HIV infection in seronegative high-risk individuals examined by virus isolation and PCR.

HIV seronegative individuals with high-risk behavior were tested for HIV infection by sensitive virus isolation techniques using T4 lymphocytes and monocyte/macrophages, and by detection of proviral DNA using PCR with three different sets of nested primers. No evidence of HIV infection was found among the 31 seronegative high-risk subjects, either by virus isolation of by PCR (97.5% confidence limits, 0-11). Our results indicate that ongoing HIV infection in seronegative persons at high risk of infection is a rare event.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Heterosexual HIV infection in Denmark. Observations from an infectious disease department].

Since January 1985, 77 women have been found to be HIV-positive in the Department for Infectious Diseases, Hvidovre Hospital. Thirty-four out of these 77 women had histories of intravenous drug abuse, 11 had probably been infected with HIV by transfusion while 32 had probably been infected heterosexually. Out of the heterosexually infected women, a total of 9 were found to be living in a regular partnership with a HIV positive partner and eight of these couples were suitable for investigation. Seven of the eight women were probably infected by their regular male partner, four of whom belonged to known risk groups. Six of the eight men were HIV tested on account of HIV related symptoms while all of the women were tested because their regular partners were found to be HIV positive. The diagnosis of AIDS was established in ten out of 16 persons. Six of the men and three of the women were found to have AIDS less than one year after the first positive HIV test while the diagnosis was established in one man 22 months after the HIV test. The six men with HIV related symptoms had sought medical help on an average eight weeks before a HIV test was carried out and the diagnosis of AIDS was established in five immediately after referral to the special department. It is emphasized that every Danish doctor should be aware of the symptoms of HIV and these should be borne in mind even in the case of patients who do not belong to the known risk groups.

Adolescent↗
PubMed1990

Platelet activating factor and tracheobronchial respiratory glycoconjugate release in feline and human explants: involvement of the lipoxygenase pathway.

It has been suggested that platelet activating factor (PAF) may participate in many aspects of bronchial asthma, including stimulation of mucus secretion. Feline tracheal and human bronchial explant production of respiratory glycoconjugates (RGC) in response to platelet activating factor (PAF) was investigated, in order to differentiate the actions of this putative mediator on mucus secretion. PAF caused a dose-dependent increase in RGC release in concentrations ranging from 100-0.5 microM during a 1-2 hours incubation with either feline or human explants, and the effect was inhibited by the PAF receptor antagonists Ro 19-3704. Several lines of evidence suggest that PAF enhances RGC release indirectly through stimulation of the production of lipoxygenase metabolites of arachidonic acid. 1) Incubation of 10 microM PAF together with arachidonic acid (100 micrograms/ml) enhances PAF's stimulatory effect on RGC release in cats. 2) The cyclooxygenase inhibitor ibuprofen (65 and 420 microM) either failed to effect or slightly enhanced PAF induced RGC release in both species. 3) The combined cyclooxygenase and lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) as well as the putatively specific 5-lipoxygenase inhibitor L-651,392 (both at 50 microM) inhibited the response to PAF in both species. 4) The putative LTD4 receptor antagonists (L-660,711, 100 microM) slightly reduced the PAF secretory response in human bronchi. We conclude that PAF causes specific receptor mediated RGC release. This response is indirectly mediated through the generation of lipoxygenase metabolite formation including 5-lipoxygenase pathway metabolites.

Animals↗
PubMed1990

Improved detection of Pneumocystis carinii by an immunofluorescence technique using monoclonal antibodies.

To assess whether a recently developed indirect immunofluorescent stain using monoclonal antibodies was more sensitive in detecting Pneumocystis carinii than the combination of Giemsa and methenamine silver nitrate stains which has routinely been used in the laboratory, 88 lavage fluid specimens and 34 induced sputum specimens were examined. All specimens were stained by five techniques: immunofluorescence using a combination of three monoclonal antibodies (from the National Institutes of Health, USA), immunofluorescence using a single monoclonal antibody (from Dakopatts), Giemsa, methenamine silver nitrate and toluidine blue O. Immunofluorescence using the monoclonal antibodies from the NIH was significantly more sensitive than any other single staining method and than the combination of Giemsa and methenamine silver nitrate staining. The study also showed that the cytospin centrifuge was very suitable for the preparation of slides with lavage fluid and processed induced sputum. Finally, the sensitivity of examination of induced sputum to detect Pneumocystis carinii was found to be 50% when compared with bronchoalveolar lavage fluid. However, this sensitivity may increase through practice.

Antibodies, Monoclonal↗
PubMed1990

CD4 lymphocyte counts and serum p24 antigen of no diagnostic value in monitoring HIV-infected patients with pulmonary symptoms.

The diagnostic value of the CD4 cell counts and the HIV p24 antigen were evaluated in a consecutive series of 105 HIV-infected patients experiencing 128 episodes of pulmonary symptoms which required bronchoscopy. One-third of patients with opportunistic infection (OI) had CD4 counts greater than 0.200 x 10(9)/l, and 60% of patients without OI had CD4 counts less than 0.200 x 10(9)/l; 47 and 42% of patients with and without OI, respectively, had detectable p24 antigen in serum. Only 36% of the patients with OI presented the combination of CD4 cells less than 0.200 x 10(9)/l and p24 in serum. In conclusion, the CD4 cell counts and the presence of p24 antigen in serum had a very limited predictive value for the presence of OI in HIV-infected patients with pulmonary symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Opportunistic infections and malignancies in 231 Danish AIDS patients.

We analysed cumulative disease frequencies in the first 231 adult Danish AIDS patients with life tables. There was a certain hierarchical pattern in the occurrence of complicating diseases. Herpes zoster, Kaposi's sarcoma and Pneumocystis carinii pneumonia were early manifestations, whereas diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion of patients who developed particular diseases changed with calendar time. Most striking was a three to fourfold decrease in diseases caused by cytomegalovirus. In conclusion, the study showed that disease frequencies in patients with AIDS may vary with the patients risk behaviour and duration of AIDS, and that the frequencies of particular diseases may change with calendar time.

Acquired Immunodeficiency Syndrome↗
PubMed1990

T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HIV seroconverters.

Seven consecutive patients who presented with a severe acute mononucleosis-like illness associated with HIV seroconversion were evaluated by T-cell subset enumerations and measurements of lymphocyte transformation responses to mitogens and antigen during both their primary illness and a 1-year follow-up period. We observed a characteristic pattern of response to primary HIV infection; initial lymphopenia was followed by CD8 lymphocytosis and inversion of the CD4:CD8 ratio. During follow-up, the CD8 count gradually returned to normal, whereas the CD4:CD8 ratio remained inverted because of a relatively low number of CD4 lymphocytes. Primary infection was followed by prolonged and severe cellular hyporesponsiveness to both mitogens and antigen. At the last follow-up, responses to pokeweed mitogen were still severely impaired, with a median 19% (range 7-50%) of that observed in healthy controls. We conclude that severe primary HIV infection may be followed by sustained lymphocyte hyporesponsiveness, a sustained low percentage of CD4 lymphocytes and sustained inversion of the CD4:CD8 ratio.

Adult↗
PubMed1990

Trends in survival of Danish AIDS patients from 1981 to 1989.

Length of survival was analysed in relation to year of diagnosis, AIDS-indicative disease, age, risk behaviour, zidovudine therapy, and CD4 cell count and serum immunoglobulin (Ig) levels at the time of diagnosis in a group of 231 consecutive adult Danish AIDS patients reported before 1 January 1988. The cumulative survival rate was 53% (95% confidence interval 47-59%) at 1 year, 29% (22-36%) at 2 years and 18% (10-26%) at 3 years. Length of survival increased significantly (P less than 0.001) over time for patients who were initially diagnosed with Pneumocystis carinii pneumonia (PCP), 17% (3-31%) at 2 years prior to 1986, 32% (16-49%) in 1986 and 52% (34-69%) in 1987, whereas survival remained stable for patients with other AIDS-indicative diseases. Survival was similar for patients who were diagnosed with Kaposi's sarcoma alone and PCP alone. Independent predictors of a shortened survival were a CD4 cell count less than 200 x 10(6)/l, a serum IgA level greater than 4 g/l, and an initial diagnosis with opportunistic infections other than PCP. In addition, the multivariate analysis suggested an improved survival in recent years for patients diagnosed with PCP, independent of other factors examined. We conclude that length of survival in AIDS patients is highly variable. Determinants of progression include CD4 cell count, serum IgA level, and presenting disease. Survival has increased markedly for patients with PCP and median survival now exceeds 24 months.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Identification of Pneumocystis carinii chromosomes and mapping of five genes.

Pulsed field gel electrophoresis was used to identify the chromosome-size DNA of Pneumocystis carinii, a major pathogen of immunocompromised patients. Thirteen chromosomes of rodent Pneumocystis carinii, ranging in size from 300 to 700 kilobases (kb), were identified. The minimum genome size for P. carinii, estimated on the basis of the sizes of chromosomes, is 7,000 kb. Genetic heterogeneity among different P. carinii isolates was documented by demonstration of chromosomal size variability. By hybridization studies, the genes for topoisomerase I, dihydrofolate reductase, rRNA, actin, and thymidylate synthase were mapped to single chromosomes of approximately 650, 590, 550, 460, and 350 kb, respectively. Hybridization studies further confirmed the genetic heterogeneity of P. carinii.

Actins↗