SIV and FIV vaccine studies at UC Davis: 1991 update.
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Biomedical subjects
Publications and source records attributed to M Gardner.
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Most patients who require emergency airway control receive drugs to induce rapidly sufficient anesthesia for direct laryngoscopy and endotracheal intubation, but there are no protocols that outline the use of specific drugs in general use. Drugs should safely and rapidly produce (1) unconsciousness; (2) paralysis; and (3) blunt intracranial pressure (ICP) responses to airway procedures. Consequences to be considered include increased ICP, hemorrhagic shock, and a full stomach. To refine the use of drugs used for airway procedures in pediatric trauma patients, the authors reviewed all cases of emergency endotracheal intubation over a recent 12-month period (1) to see whether medications used met the goals of producing unconsciousness and paralysis and blunting ICP responses were met safely; and (2) to identify potential drug-related complications. From July 1, 1990, to June 30, 1991, 60 of 791 children (7.6%) required endotracheal intubation at the scene of injury, at the referring hospital, or in our emergency department (15; 25%). Ten patients died (16.7%). Three fourths were younger than 9 years of age. All except one suffered blunt injuries. Nearly all (95%) suffered head injuries, isolated in 39 of 57 (68.4%) and combined with injuries in other regions in 18 (31.6%). Fifteen patients were in apnea (25%); seven were both apneic and pulseless. Three fourths (45 of 60) had diminished levels of consciousness; one fourth (15 of 60) were awake. Immediate endotracheal intubation proceeded appropriately without drugs in all seven patients in cardiopulmonary arrest. Only eight of the remaining 53 patients (15.1%) received an optimal medication regimen. Many patients with head injury were inadequately protected against increases in ICP. Thiopental, an effective anesthetic agent that effectively lowers intracranial pressure, was not used in 25 of 35 stable patients with isolated head injury (71.4%). Intravenous lidocaine was not used in 38 of 50 head-injured patients in whom it would have been an appropriate adjunct to control increases in ICP (76%). Eight patients received paralyzing agents alone, without sedatives or narcotics. Medications were thought inadequate to relieve the pain and discomfort of laryngoscopy and endotracheal intubation in 32 of the 53 patients who should have received them (60.4%). No paralyzing agents were used in 36 of the 53 instances where it would have been appropriate (67.9%). In two of 11 instances (18.3%) where succinylcholine was administered, no prior nondepolarizing agent was used. Complications of a full stomach at the time of emergency endotracheal intubation became evident in 10 patients (16.7%) who vomited during procedures to control the airway. Two patients (3.3%) aspirated.(ABSTRACT TRUNCATED AT 400 WORDS)
Rhesus macaques were immunized with live vaccinia virus recombinants expressing the envelope glycoproteins (gp70 and gp22) of simian type D retrovirus (SRV), serotype 1 or 3. All of the animals immunized with either the SRV-1 env or the SRV-3 env vaccinia virus recombinant developed neutralizing antibodies against the homologous SRV. In addition, both groups developed cross-reactive antibodies and were protected against an intravenous live-virus challenge with SRV-1. The four control animals immunized with a vaccinia virus recombinant expressing the G protein of respiratory syncytial virus were not protected against the same SRV-1 challenge. Although SRV-1 and SRV-3 immune sera showed cross-neutralization, they failed to neutralize a separate, more distantly related serotype, SRV-2, in an in vitro assay. These findings are consistent with the known degree of serologic and genetic relatedness of these three SRV strains.
Subacute intraperitoneal administration of the lipid portion of the unripe ackee arillus, referred to as "ackee oil", resulted in marked neutropenia (p less than 0.001) and increase in platelets (p less than 0.01) without anaemia, in rats. Blood urea, sodium and aspartate aminotransferase levels were significantly decreased but glucose and bilirubin levels were similar to those of controls. The lungs showed areas of petechial haemorrhages and a dose-related perivascular and peribronchial mononuclear cell infiltration. The pulmonary toxicity may be interpreted as a hypersensitive reaction to ackee oil. Further research is in progress on the neutropenic effects of ackee oil.
SIV vaccines made of inactivated whole virus, modified live virus and native and recombinant envelope antigens have protected macaques against experimental infection with low doses of cell-free SIV given systemically. The few vaccinated monkeys that do become infected have tended to live longer than the infected controls. Protection against cell-associated virus has not as yet been tested. The recombinant envelope vaccines now on test have generally not been as effective as the whole virus vaccines. Post-infectious immunotherapy with SIV vaccines has been ineffective. The same whole virus and modified live virus vaccines that protect against systemic infection fail to protect against genital mucosal challenge with cell-free virus. Since sexual transmission is the major route of HIV spread on a global scale, a major effort is now required to develop vaccines in this animal model that induce genital mucosal as well as systemic immunity against infection with both cell-free and cell-associated SIV.
Patients with juvenile periodontitis frequently have elevated levels of serum immunoglobulin A (IgA) antibodies to antigens of Actinobacillus actinomycetemcomitans. IgA occurs in two subclasses, IgA1 and IgA2, and in monomeric and polymeric forms. Because IgA1 is susceptible to cleavage by IgA1 proteases produced by microorganisms found at mucosal sites and in the gingival crevice, we wished to determine the IgA subclass distribution of antibodies to antigens of A. actinomycetemcomitans. The molecular form was examined because it may indicate the origin of the IgA and because the form differs in acute and chronic infections. There is also evidence that monomeric and polymeric IgA have different biological functions. Serum was taken from patients with juvenile periodontitis before and at intervals during and after initiation of therapy. IgA subclass distribution was determined against a sonic extracts of A. actinomycetemcomitans ATCC 2952a (serotype b) by using monoclonal anti-subclass reagents in an enzyme-linked immunosorbent assay. To determine the molecular form of the antibodies, sera were separated by high-performance liquid chromatography on a size-exclusion column. Fractions were assayed for antibody activity by the enzyme-linked immunosorbent assay, and described above. The results of the subclass analysis of the sera indicated that while both IgA1 and IgA2 antibodies to A. actinomycetemcomitans sonic extract are often found before, during, and after treatment, IgA1 antibodies dominated the response. There was a predominance of monomeric IgA1 antibodies to A. actinomycetemcomitans sonic extracts in most samples before, during, and after treatment. The monomeric form is consistent with what is seen in other chronic infections. The predominance of IgA1 antibodies implies that any protective effects of the IgA response to A. actinomycetemcomitans could be compromised by microbial IgA1 proteases.
This study compared immediate recall of prescription information when the message content was presented in a highly organized format versus a less-organized approach. Two groups of pharmacy students viewed separate videotapes, which described information for a patient about three fictitious medications. Students were then asked to recall the medications' name, colour, purpose, dosage, duration, side-effects and quantity prescribed. Students who viewed the organized version correctly recalled more information in every category except drug colour. Both groups made more errors in recalling dosage than any other category. Thus, organizing information facilitates recall of medication information.
Abnormalities of neutrophil function have been highly correlated with severe, early onset periodontal diseases. Nonetheless, the identification of these patients and diagnosis of specific disease states, such as LJP or prepubertal periodontitis, are difficult and costly. In this report, the identification and quantification of neutrophil cell surface markers specific to LJP patients with neutrophil chemotaxis defects are described. GP110 and FMLP receptors were quantified by flow cytometry on neutrophils from LJP patients with neutrophil chemotaxis defects, LJP patients without chemotaxis defects, other patients with primary neutrophil chemotaxis defects, and controls. Results suggest that reduction of GP110 and FMLP receptor on neutrophils is specific for LJP patients who exhibit neutrophil chemotaxis abnormalities.
HIV-1BR was isolated from the autopsied brain tissue of a 57-year-old man who died of progressive dementing illness. This virus was shown to be HIV-1 by hybridization to HIV-specific DNA probes. The expression of viral proteins as tested by radioimmunoprecipitation assay revealed the presence of HIV-1-specific proteins. HIV-1BR replicated in cultures of CD4+ T-lymphoid cells and induced cytopathic effects in these cells. HIV-1BR also replicated in monocytoid cell lines. The genetic nature of this isolate was determined by molecular cloning and sequencing of the 3'-half of the genome. DNA sequence information established that HIV-1BR is a unique HIV-1 isolate. A stretch of approximately 30 bases in the nef gene of HIV-1BR was found duplicated when compared with the other sequenced HIV-1 genomes. The functional significance of this duplication remains to be determined.
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From June 1975 to December 1987, 231 patients underwent aortic valve replacement with a viable cryopreserved allograft aortic valve. Throughout this era, a uniform procurement and preservation was used to maintain leaflet fibroblast viability. The allograft valve was obtained from coroner's autopsies within 24 hours of death, and more recently from organ donors, incubated for 24 hours in low dose antibiotic solution followed immediately by cryopreservation (mean time interval 39 hours after donor death). Viability was ensured by monitoring glucose utilization of the aortic and pulmonary valves and by demonstrating fibroblast growth in tissue cultured from the pulmonary valve. A uniform protocol for valve preparation was used during the entire experience. Nine allograft aortic valves have been obtained by eight reoperations (two were for leaflet degeneration) and one autopsy. The time intervals from implantation to explantation were 2 months, 10 months, 20 months, 22 months, 2.2 years, 5 years, 8.3 years, 9.2 years, and 10.8 years. Histologic examination of the leaflet tissue disclosed a variable degree of cellularity, ranging from a highly cellular matrix (9.2 years) to minimal cellularity (20 months). Within the same valve (10 months), one leaflet was completely acellular with a moderate degree of cellularity in the other two leaflets. The competent valve recovered at autopsy (8.2 years) was essentially acellular. Fibroblasts could consistently be cultured from leaflets in which viable cells were seen histologically. Chromosomal analysis of cultured cells from a valve leaflet (9.2 years) that was implanted with a donor and recipient sex mismatch demonstrated persistence of donor cells.(ABSTRACT TRUNCATED AT 250 WORDS)
One hundred and twenty-four patients underwent aortic valve replacement with a nonviable 4 degrees C refrigerated aortic allograft valve. One hundred and eighty-four patients underwent aortic valve replacement with a viable cryopreserved aortic allograft valve in a later era. The longest follow-up was 16 years for the group with the nonviable valve and 11 years for the group with the viable valves. Within this time frame, reoperation was required in 23 patients with nonviable valves for leaflet perforation or rupture whereas no patients in the group with viable valves developed this complication (p less than 0.0001). The prevalence of endocarditis and thromboembolism was very low in both groups. Viability of leaflet tissue is associated with an important improvement in durability over nonviable allograft valves. Consequently, long-term follow-up results of allograft valves might be best expressed in terms of viability. The current evidence suggests that the viable cells are donor in origin. The viable cryopreserved aortic allograft valve offers significant advantages over current nonviable allograft valves, mechanical valves, and bioprostheses.
A dominant restriction allele, Akvr-1r, from California wild mice (Mus musculus domesticus) confers resistance to exogenous ecotropic murine leukemia virus (MuLV) infection. The presence of an ecotropic MuLV envelope-related glycoprotein in uninfected virus-resistant cells suggests that viral interference is a possible mechanism for this resistance. We molecularly cloned the ecotropic MuLV envelope-related sequence from the genomic DNA of a wild mouse homozygous for the Akvr-1r locus. The cloned provirus was defective and contained a C-terminal end of the pol gene, a complete envelope gene, and a 3' long terminal repeat. The presence of this provirus was directly correlated with Akvr-1r-mediated virus resistance in cell cultures and hybrid mice. The Akvr-1r provirus restriction map and partial DNA sequence were identical to those of the Fv-4r allele, an ecotropic MuLV resistance locus from Japanese feral mice (M. musculus molossinus), which was previously shown to be allelic with the Akvr-1r gene. The 3' host flanking sequences of Fv-4r and Akvr-1r also had identical restriction maps. These findings indicate that Akvr-1r and Fv-4r are the same gene. It was probably acquired by interbreeding of these feral species in recent times. Conservation of this locus might be favored by the useful function that it performs in protection against ecotropic MuLV infection endemic in both populations of wild mice.
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Hematologic abnormalities were defined in 31 rhesus monkeys (Macaca mulatta) with simian acquired immune deficiency syndrome (SAIDS). Animals manifested anemia (hypochromic/microcytic), severe neutropenia and progressive lymphopenia, monocytosis and occasional thrombocytopenia. Bone marrow studies showed erythroid hyperplasia with a marked left shift and adequate megakaryocytes. Two animals showed profound hypoplasia of all hematopoietic elements. Most animals were iron deficient, but the course of the anemia suggested additional factors. There was no evidence of immune hemolysis. The pathogenesis of these abnormalities is not clear and will require further study. This reproducible disease will allow studies to elucidate the mechanisms of viral-induced hematologic abnormalities.
The case of a patient who underwent left pneumonectomy at 23 years of age is described. When he was 54 years old, he required resection of the right upper and middle lobes. He survived and lived an active life for more than three years with the right lower lobe as his only lung tissue.
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