Search PubMed⌕ Search

Biomedical subjects

M A Jacobson

Publications and source records attributed to M A Jacobson.

At least 109 records · Page 6Linked to original sources
PubMed1990

Acyclovir-resistant varicella zoster virus infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome (AIDS).

Four patients with human immunodeficiency virus (HIV) infection who received chronic oral acyclovir therapy for suppression of recurrent varicella zoster or herpes simplex virus infection developed persistent disseminated hyperkeratotic papules that failed to heal with intravenous or high-dose oral acyclovir therapy. Varicella zoster virus, resistant to acyclovir in vitro, was isolated from skin lesions of all four patients. Three patients were adults in whom the acquired immunodeficiency syndrome (AIDS) had been diagnosed 12 to 20 months before isolation of acyclovir-resistant varicella zoster virus. The fourth patient was a perinatally HIV-infected child who developed primary varicella infection at age 7 years when profoundly immunosuppressed (absolute CD4+ lymphocyte count less than 50 cells/microL). Mean antiviral susceptibilities (ED50 values) of the four clinical isolates compared with the ED50 values of the reference strain Oka were 85 compared with 3.3 mumol/L for acyclovir, 1.4 compared with 0.8 mumol/L for vidarabine, and 123 compared with 117 mumol/L for foscarnet. When assayed by [125I]-dC plaque autoradiography, 90% to 100% of the viral isolate populations had altered or no measurable thymidine kinase function. Acyclovir-resistant varicella zoster virus infection may complicate long-term oral acyclovir administration in patients with AIDS and may be associated with the appearance of atypical hyperkeratotic papules.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Determination of phosphonoformic acid in human plasma and urine by high-performance liquid chromatography with electrochemical detection.

Trisodium phosphonoformate (foscarnet) is used in the treatment of cytomegalovirus infections in immunocompromised patients, such as bone marrow and renal transplant recipients, as well as patients with the acquired immune deficiency syndrome. A simple high-performance liquid chromatographic assay is described using an electrochemical detector. The method is accurate, precise and reproducible. Hydrochlorothiazide is used as the internal standard. This assay allows measurement of foscarnet in biological fluids at concentrations as low as 33 microM. This method is being used for the analysis of samples in clinical trials and is important in the evaluation of the pharmacokinetic disposition of the drug.

Cathartics↗
PubMed1990

Heavy and light chain contributions to antigen binding in an anti-digoxin chain recombinant antibody produced by transfection of cloned anti-digoxin antibody genes.

We used immunoglobulin gene transfection to study the effect that substituting an homologous light (L) chain for a parental L chain has on antigen fine specificity and affinity. High-affinity monoclonal anti-digoxin antibodies 26-10 and 40-100 were selected for study because their L chains are 92% homologous (although the H chains differ), and their binding with digoxin and digoxin analogs show very different properties. In order to generate a recombinant transfectoma, the genes encoding the 26-10 H and L chains were cloned. After the sequenced clones had been shown to contain the V gene and the transcriptional control elements, the H and L chain V region genes were subcloned into different expression vectors. Both constructs were transfected into myeloma J558L, a lambda 1 chain producer, to verify that the genetic constructs expressed correctly. The recombined 26-10 antibody was identical to parental 26-10 antibody in fine specificity and affinity. The 26-10 L chain construct was then transfected into a cell line, CR-101, that expresses the 40-100 H chain and a lambda 1 chain. The transfectoma 1E6, secreting 40-100 H chain and 26-10 L chain, was selected. Appropriate gene expression in 1E6 was proven by polymerase chain reaction cloning and sequencing. The fine specificity properties of the 1E6 recombinant derive from both the 40-100 and 26-10 antibodies; however, the affinity of 1E6 is 130 times less than that of the parental antibodies. We conclude that, in 1E6, the H and L chains are codominant in their influence on antigen specificity and that homologous pairing of H and L chains is required for optimal affinity.

Amino Acid Sequence↗
PubMed1990

Red cell transfusion therapy for anemia in patients with AIDS and ARC: incidence, associated factors, and outcome.

The records of the San Francisco General Hospital (SFGH) Blood Bank were reviewed, and 263 likely AIDS and AIDS-related complex (ARC) patients were identified, who received 1545 units of packed red cells (PBRCs) between July 1, 1987, and June 30, 1988. A probability sample of 80 of these patients was selected randomly for detailed chart review. Of this sample, 78 (98%) were confirmed to have AIDS (86%) or ARC (14%). On the basis of the yearly census of the SFGH AIDS clinic, a transfusion incidence of 0.89 PRBC units per patient per year for patients with AIDS and 0.27 PRBC units per patient per year for those with ARC was estimated. Whereas 26 percent of the 177 transfusions studied in detail involved more than one associated (possibly causative) factor, antimicrobial drug therapy, zidovudine therapy, and disseminated Mycobacterium avium complex (MAC) infection were the sole associated factors in 20, 14, and 12 percent of the transfusions, respectively. To assess the role of MAC, the 263 transfused patients were compared with the 574 patients whose blood was submitted to the SFGH Mycobacteriology Laboratory during the same period. Patients whose blood yielded MAC had a relative risk of 5.2 for transfusion-requiring anemia. In 80 percent of cases, the patient returned home after transfusion. Most PRBC transfusions administered to AIDS or ARC patients were optimal therapy.

AIDS-Related Complex↗
PubMed1990

Failure of adjunctive cytomegalovirus intravenous immune globulin to improve efficacy of ganciclovir in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis: a phase 1 study.

Six men with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis, treated with combined ganciclovir induction therapy and hyperimmune globulin (CMV-IGIV) for 10 days followed by CMV-IGIV alone, had a median time to retinitis progression shorter (7 days) than had eight historical controls given ganciclovir maintenance therapy (54 days; P = 0.06) and similar to that in eight controls given ganciclovir for 10 days only (19 days; P = 0.97). CMV-IGIV, which also failed to inhibit CMV replication in blood and urine, did not appear to add markedly to the efficacy of ganciclovir in acquired immunodeficiency syndrome-associated CMV retinitis.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Campylobacter-like organisms are uncommon pathogens in patients infected with the human immunodeficiency virus.

Over a 25-month period, we prospectively evaluated 36 patients with symptomatic human immunodeficiency virus disease (including 27 with unexplained chronic diarrhea) by flexible sigmoidoscopy for the presence of Campylobacter-like organisms. No Campylobacter-like organisms were isolated. Campylobacter-like organisms appear to be an uncommon cause of idiopathic chronic diarrhea in symptomatic human immunodeficiency virus disease.

Campylobacter↗
PubMed1989

Expression and secretion of biologically active echistatin in Saccharomyces cerevisiae.

A synthetic gene coding for a platelet aggregation inhibitor, echistatin (ECS), was inserted into a Saccharomyces cerevisiae expression vector utilizing the alpha-mating factor pre-pro leader sequence and galactose-inducible promoter, GAL10. Cleavage of the pre-pro leader sequence in vivo results in the secretion of a properly processed recombinant ECS with the native N-terminal glutamic acid residue. Recombinant ECS was recovered from yeast supernatants and purified by reverse phase high performance liquid chromatography. Recombinant ECS expressed and purified from yeast was identical to native ECS in its ability to inhibit platelet aggregation.

Amino Acid Sequence↗
PubMed1989

Foscarnet therapy for severe acyclovir-resistant herpes simplex virus type-2 infections in patients with the acquired immunodeficiency syndrome (AIDS). An uncontrolled trial.

STUDY OBJECTIVE: To determine whether trisodium phosphonoformate (foscarnet) is efficacious in treating severe mucocutaneous disease due to acyclovir-resistant herpes simplex virus type-2 (HSV-2) infection in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Open-labeled drug administration to patients with AIDS and severe ulcerative disease due to acyclovir-resistant HSV-2 infection. SETTING: Medical floors of acute care hospital. PATIENTS: Four patients with AIDS who developed progressive ulcerative mucocutaneous lesions of the genitals, perineum, perianal region, or finger due to acyclovir-resistant, thymidine-kinase (TK)-negative strains of HSV-2. INTERVENTION: Foscarnet, 60 mg/kg body weight intravenously every 8 hours (with reduced dosage for renal impairment), for 12 to 50 days. MEASUREMENT AND MAIN RESULTS: All patients receiving foscarnet had dramatic improvement in their clinical findings with marked clearing of mucocutaneous lesions and eradication of HSV from mucosal surfaces. CONCLUSION: Foscarnet may be an effective treatment for severe mucocutaneous disease due to acyclovir-resistant, TK-negative strains of HSV-2.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Mycobacterium kansasii diffuse pulmonary infection in a patient with acquired immune deficiency syndrome. Successful therapy with an antituberculous regimen.

Mycobacterium kansasii is a rare cause of disseminated mycobacterial infection in patients with the acquired immune deficiency syndrome (AIDS). It occurs as the index AIDS diagnosis in only 0.2% of AIDS cases. Previously reported cases of AIDS-associated M. kansasii infection have manifested as diffuse interstitial pneumonitis and diffuse small bowel inflammation and have been refractory to antimycobacterial therapy. The authors now report success in treating a hypoxemic patient with AIDS-associated M. kansasii diffuse granulomatous interstitial pneumonitis that was diagnosed by open lung biopsy. The patient has no evidence of mycobacterial disease after 12 months of therapy with isoniazid, rifampin, and ethambutol.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Serum beta 2-microglobulin decreases in patients with AIDS or ARC treated with azidothymidine.

Abnormally elevated serum beta 2-microglobulin has been associated with progression of human immunodeficiency virus (HIV) disease and could reflect in vivo HIV activity. We prospectively studied the effect of azidothymidine therapy on serum beta 2-microglobulin concentration in 41 patients with AIDS or AIDS-related complex. Median beta 2-microglobulin concentration decreased from 4.02 mg/L before therapy to 3.73 mg/L at week 24 of therapy (P = .016). Individual changes in beta 2-microglobulin during azidothymidine therapy correlated with changes in serum HIV p24 antigen (Spearman, r = .42, P = .007). Also, in a randomized placebo-controlled study, median beta 2-microglobulin concentration decreased after 16 w of therapy in 5 azidothymidine-treated patients compared with levels in 7 placebo-treated controls (P = .05). Serum beta 2-microglobulin appears to be a sensitive marker for in vivo antiretroviral drug activity and may be a better marker than serum p24 antigen for early intervention trials involving antiretroviral agents.

AIDS-Related Complex↗