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Biomedical subjects

J Albert

Publications and source records attributed to J Albert.

At least 199 records · Page 11Linked to original sources
PubMed1988

Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates.

According to their capacity to replicate in vitro, human immunodeficiency virus (HIV) isolates can be divided into two major groups, rapid/high and slow/low. Rapid/high viruses can easily be transmitted to a variety of cell lines of T-lymphoid (CEM, H9, and Jurkat) and monocytoid (U937) origin. In contrast, slow/low viruses replicate transiently, if at all, in these cell lines. Except for a few isolates, the great majority of slow/low viruses replicate in peripheral blood mononuclear cells and Jurkat-tatIII cells constitutively expressing the tatIII gene of HIV-1. The viruses able to replicate efficiently cause syncytium formation and are regularly isolated from immunodeficient patients. Poorly replicating HIV isolates, often obtained from individuals with no or mild disease, show syncytium formation and single-cell killing simultaneously or, with some isolates, cell killing only.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Group specific component and susceptibility to HIV infection and progression to AIDS.

The distribution of phenotypes of the group specific component (Gc) was examined in 85 AIDS patients and in 40 couples, each consisting of one HIV seropositive patient and one seronegative sexual partner. Phenotype and allele frequencies in these groups did not differ significantly from those in a Swedish control population. Our observations did not indicate any involvement of the Gc system in susceptibility to HIV infection or progression to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Advantages of total androgen blockade in the treatment of advanced prostate cancer.

Total androgen blockade has been proposed as a better therapeutic technique than castration alone for the management of metastatic prostate cancer. This is based on the theory that links adrenal androgens to tumor growth. We have carefully examined the role of adrenal androgens in prostate cancer. Work done in our laboratory, as well as the work of many others, has demonstrated the following in regard to the role of adrenal androgens in prostate cancer: (1) The adrenal cortex secretes significant amounts of adrenal androgens into the blood. (2) Adrenal androgens are converted into dihydrotestosterone (DHT), as indicated by studies of labeled DHT recovered from prostates resected one-half hour after infusion of 3H-androstenedione or 3H-dehydroepiandrosterone sulfate into patients. We have also shown that biopsies of prostates from patients who were previously castrated may contain significant amounts of DHT, which could only be derived from adrenal androgens. (3) We have quantified DHT derived from adrenal androgens by measuring prostate DHT concentrations in castrates and in patients treated with combined gonadal and adrenal blockade. The mean difference between these two groups, 0.32 ng/g of DHT lower with combined blockade, is statistically significant and represents DHT derived from adrenal androgens. (4) We have also demonstrated that the small amounts of DHT derived from adrenal androgens may be biologically significant in stimulating prostatic epithelial cell protein synthesis in humans; others have reported similar findings in animals. (5) A review of patients in relapse after castration, who are treated with adrenal androgen blockade, indicates that approximately one out of three patients will show an objective remission based on National Prostate Cancer Project (NPCP) criteria. Despite data supporting the importance of adrenal androgens in prostate cancer, clinical trials using combined adrenal and gonadal blockade in prostate cancer have shown only modest benefit over castration. The largest and best study to date is the Southwest Oncology Group (SWOG) study, which did show a near-significant (P less than 0.065) difference between patients treated for 20 months with a luteinizing hormone-releasing hormone (LH-RH) plus flutamide compared with LH-RH alone. The difference in median time to progression was approximately 2 months between the groups. However, when one considers the fact that two out of three patients are probably not responding to the total androgen blockade, the 2 month difference may actually represent 6 or more months in a subset of one-third of patients receiving that therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗
PubMed1987

Antibody response in primary human immunodeficiency virus infection.

The antibody response in 20 homosexual men with symptomatic primary HIV infection was studied with ten different antibody assays (enzyme-linked immunosorbent assays, indirect immunofluorescence assays, radioimmunoprecipitation [RIPA], and western blot). HIV antibodies were detectable by all the assays within 2 months after onset of illness. RIPA and western blot were more sensitive than the other assays--all serum samples obtained at 2 weeks and after were reactive. In all cases, the first serum sample reactive by RIPA precipitated gp160 whereas, by western blot, antibodies to p24 were first recognised. This study shows the necessity of including gp160 and p24 in any assay to detect early antibody response in primary HIV infection. 5 patients were studied by virus isolation. During the 2 first weeks after onset of symptoms, HIV was demonstrated in cell-free plasma in all cases and, in 4 cases, also in peripheral blood mononuclear cells. Samples obtained later contained demonstrable infectious virus in only 1 of 4 cases. Thus a phase of viraemia precedes the antibody response in symptomatic primary HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Site-directed ELISA with synthetic peptides representing the HIV transmembrane glycoprotein.

Two partially overlapping 19 and 22 amino acids long peptides representing a highly immunogenic site of the transmembranous glycoprotein (gp41) of human immunodeficiency virus (HIV) were used as antigen in ELISA tests. The results of antibody determination with this assay were compared with those of three or more conventional ELISAs and Western blot (WB) tests and radioimmunoprecipitation assay. Twenty-six sera from patients with AIDS or LAS and from asymptomatic carriers of HIV infection all showed a pronounced reaction in the peptide ELISA as well as positive results with other tests. In contrast, 27 sera from laboratory workers and blood donors were negative by all tests. A group of 39 blood donor sera, which had shown false positive or ambiguous results in the ELISAs and sometimes in WB tests employed for confirmation, also were negative in all cases with the peptide ELISA. Consecutive samples collected from individuals with primary HIV infection were also analyzed. In 6 out of 9 cases, the peptide ELISA revealed an antibody response within one month after onset of clinical symptoms and sensitivity for antibody detection equaled that of other ELISA tests. Eight sera from five West African persons infected with HIV-related viruses did not react in the peptide ELISA, reflecting differences in properties of the envelope components. The peptide ELISA used in this study appears to represent a simple technique employing chemically synthesized antigen for accurate and sensitive estimation of antibodies to the HIV group of nontransforming human retroviruses.

AIDS-Related Complex↗
PubMed1987

Isolation of human immunodeficiency virus (HIV) from plasma during primary HIV infection.

Human immunodeficiency virus (HIV) has been isolated from plasma in 6 of 7 patients showing clinical symptoms of a primary HIV infection. Parallel cultures from peripheral blood mononuclear cells (PBMC) yielded virus in 5 patients. In one case, virus could only be isolated from the cerebrospinal fluid but not from peripheral blood. Detectable viremia was transient and preceded the appearance of HIV specific antibodies. After cessation of acute symptoms, the frequency of HIV isolations was similar to that of asymptomatic carriers (23 and 26%, respectively). The role of the immune response in terminating detectable viremia remains to be established.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Effects of castration compared with total androgen blockade on tissue dihydrotestosterone (DHT) concentration in benign prostatic hyperplasia (BPH).

We compared the effect of a variety of drug regimens to lower prostate DHT concentration. Patients with BPH were treated for one week prior to surgery with either tamoxifen, flutamide, megestrol acetate, megestrol acetate plus tamoxifen and megestrol acetate plus DES or ketoconazole. DHT concentration in the surgically resected tissue was compared with tissues obtained from untreated patients. We also obtained prostate tissue at the time of relapse in patients with prostate cancer who had been treated with orchiectomy with or without estrogen therapy. Megestrol acetate plus the mini-dose of DES (0.1 mg) and megestrol acetate plus ketoconazole both decreased DHT concentrations in prostate tissue to levels (0.79 ng/g) significantly below those noted with orchiectomy (1.16 ng/g). The difference between the DHT concentration in the two groups (orchiectomy vs. total androgen blockade) represents the contribution of adrenal androgens to prostate tissue DHT. This small amount of DHT (approximately 0.4 ng/g) may be biologically important in stimulating prostate epithelial cell growth.

Androgen Antagonists↗
PubMed1987

Radioimmunoprecipitation and Western blotting with sera of human immunodeficiency virus infected patients: a comparative study.

The sensitivity and specificity of radioimmunoprecipitation assay (RIPA) and Western blot (WB) test were compared by use of a collection of 183 sera, representing different categories of individuals, noninfected or infected with the human immunodeficiency virus (HIV). The sera were subdivided on the basis of their reactivity in at least two anti-HIV enzyme-linked immunosorbent assays (ELISA); 53 sera were negative and 61 sera were positive in both tests, whereas 69 sera showed ambiguous reactions. The reaction patterns in RIPA could be divided into 6 different groups. The same grouping could to some extent be applied to the results of WB test. RIPA provided the most efficient means for identification of the large viral envelope glycoproteins, gp120/160, whereas gp41 was detected more effectively by WB. Internal virus components reacted to a varying extent with specific antibodies in the two tests. The reaction with pol products was more pronounced with the WB tests in which extracellular material was used as antigen. In a few WB tests, however, the reaction with internal components did not reflect a prior HIV infection. No such ambiguity was observed with RIPA, reflecting the advantage of a test that uses a minimally denaturated antigen and provides appropriate conditions for identification of the large viral glycoproteins. The practical choice of confirmatory tests to be used in diagnostic laboratories requires evaluation of both the sensitivity and specificity of the tests but also their economy and convenience.

Acquired Immunodeficiency Syndrome↗
PubMed1987

A new human retrovirus isolate of West African origin (SBL-6669) and its relationship to HTLV-IV, LAV-II, and HTLV-IIIB.

A new human retrovirus of West African origin (SBL-6669) has been isolated from a patient with immunological and clinical signs of immunodeficiency. Using radioimmunoprecipitation assays (RIPA) and Western blot (WB) tests with human sera, the new virus isolate has been compared with HTLV-IV, LAV-II, and the HTLV-IIIB prototype strain of the human immunodeficiency virus (HIV). The West African isolates appeared to be members of the same virus group since their glycoproteins were antigenically indistinguishable. West African sera showed no detectable cross reaction with HTLV-IIIB glycoproteins. The external glycoprotein in the different virus strains only showed minor variations in size. The size of the transmembranous protein was not unambiguously defined. In the West African virus isolates a 30-35 kD protein was seen similar to the protein previously described possibly to represent this component. However, in SBL-6669 a distinct 41 kD protein was also identified. There were interstrain variations in the size of several viral proteins among the West African virus isolates. Only minor differences were seen between SBL-6669 and LAV-II. The variations were most pronounced in two core proteins corresponding to the 19 kD and 24 kD proteins of HTLV-IIIB. In addition, West African human retroviruses appear to differ in pathogenicity. LAV-II and SBL-6669 are associated with immunodeficiency, whereas HTLV-IV was isolated from healthy individuals. Since further spread of these viruses to other parts of the world is imminent, it is necessary to consider their antigenic and immunogenic properties in serodiagnosis of HIV infections and in planning for immunoprophylactic interventions.

Antigens, Viral↗
PubMed1987

Relationship between human prostatic epithelial cell protein synthesis and tissue dihydrotestosterone level.

To evaluate the role of small amounts of prostatic tissue dihydrotestosterone (DHT) as a stimulus to epithelial cell protein synthesis, we studied tissue from 27 patients given various androgen-blocking drugs for 1 week before transurethral resection of the prostate (TURP) and measured epithelial protein synthesis and DHT levels in the tissue specimens. Test drugs before TURP included megestrol acetate 160 mg per day, with and without Tamoxifen 40 mg per day, or ketoconazole 1200 mg per day. The tissue was processed immediately and epithelial cells separated by digestion of tissue with 0.5% collagenase. After separation, epithelial cells were labelled with either 3H-leucine or L-35S-methionine. The DHT level was measured in whole prostatic tissue. Megestrol acetate alone and with tamoxifen significantly decreased both the incorporation of 3H-leucine into protein and the tissue concentration of DHT; megestrol acetate plus ketoconazole significantly decreased L-35S-methionine incorporation into protein and the DHT level. When the data correlating DHT with protein synthesis using both labelling techniques were combined, the curves were parallel and a strong correlation was noted between DHT and protein synthesis over a wide range of values (P less than 0.001). These results suggest that in hormone-dependent prostatic cancer even small amounts of prostatic DHT such as may occur from adrenal androgens following castration may significantly stimulate protein synthesis of the tumour epithelial cells.

Aged↗
PubMed1986

Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection.

T-lymphotropic viruses were isolated from 31 patients with different clinical manifestations of human immunodeficiency virus (HIV) infection. Lymphocyte cultures from patients with the acquired immunodeficiency syndrome (AIDS) or pre-AIDS yielded virus rapidly, as indicated by high levels of reverse transcriptase (RT) activity in culture fluids. These viruses were able to establish a persistent infection in several T4-antigen-positive tumour cell-lines. In contrast, lymphocyte cultures from patients with mild or no symptoms yielded virus more slowly and the RT activity was low. Co-cultivation of slow/low-yielding lymphocytes with T4-positive tumour cell-lines showed no or only transient virus production. In 14 out of 23 cases virus could be detected by their fatal cytopathic effects on tumour cells. The relation between severity of illness and in-vitro replication potential of the viruses suggests that in the course of an infection selection may occur for HIV variants that replicate efficiently in T4 cells.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Effects of androgen blockade with ketoconazole and megestrol acetate on human prostatic protein patterns.

We studied the effects of megestrol acetate (MA) and ketoconazole (KC) on protein synthesis of epithelial and stromal cells of human prostate. Patients with benign prostatic hypertrophy (BPH) were treated with MA (160 mg/day) plus KC (1,200 mg/day) for 7 days. Prostate tissues obtained from transurethral resection (TURP) were separated into epithelial and stromal cells with 0.5% collagenase. The separated cells were incubated with L-35S-methionine in methionine-free MEM at 37 degrees C for 3 hr. The protein synthesis in both epithelial and stromal cells was significantly inhibited in the group treated with MA and KC when compared to a control group (p less than 0.05). The proteins incorporated with L-35S-methionine were analyzed by SDS-PAGE and autoradiography. The molecular weights of the epithelial and stromal proteins inhibited ranged between 35-55K.

Androgen Antagonists↗
PubMed1986

Effect of antiandrogen and/or antiestrogen blockade on human prostate epithelial and stromal cell protein synthesis.

To evaluate the role of small amounts of DHT in prostate tissue as a stimulus to epithelial cell growth (protein synthesis) we studied tissue from patients given various androgen-blocking drugs prior to transurethral resection of the prostate (TURP) and measured epithelial protein synthesis and DHT in the tissue specimens. We also studied the effects on stromal cell protein synthesis of an antiestrogen, tamoxifen. Test drugs prior to TURP included Megace 160 mg per day, Megace 160 mg per day plus Tamoxifen 40 mg per day, Megace 160 mg a day plus ketoconazole 1200 mg per day and tamoxifen 40 mg/day. The tissue was processed immediately and epithelial and stromal cells separated by digestion of tissue with 0.5% collagenase. After separation, epithelial cells were labeled with either [3H]leucine or L-[35S]methionine. Stromal cells were labelled with [3H]proline. DHT was measured in whole prostate tissue. Megace alone and Megace plus tamoxifen significantly decreased both [3H]leucine incorporation into protein and tissue concentration of DHT; Megace plus ketoconazole significantly decreased L-[35S]methionine incorporation into protein and DHT. Tamoxifen significantly decreased stromal protein synthesis. When the data correlating DHT with epithelial protein synthesis using both labeling techniques were combined, the curves were parallel and a strong correlation was noted between DHT and protein synthesis over a wide range of values (P less than 0.001). These results suggest that in hormone-dependent prostate cancer even small amounts of prostate DHT such as may occur from adrenal androgens following castration may significantly stimulate growth of the tumor epithelial cells. Since tamoxifen decreased stromal protein synthesis, estrogen is likely a significant growth stimulus to the increased stromal mass characteristic of benign prostatic hypertrophy.

Dihydrotestosterone↗
PubMed1986

Flow cytometric sorting of human epidermal pure basal cell suspensions using a specific antikeratin monoclonal antibody.

A method is described for flow cytometric sorting of epidermal basal cells, based on the cellular keratin content. KL1, a monoclonal antikeratin antibody specific for the 56.5 kD polypeptide present in suprabasal cells was used to distinguish suprabasal from basal cells. After the action of Triton X-100, epidermal cells were stained in suspensions with KL1 antibody, and KL1-positive cells were separated by flow cytometry from KL1-negative cells (basal cells). This makes it possible to sort and analyze pure fractions of human epidermal basal cells since no less than 99% of the KL1 sorted cells were bearing bullous pemphigoid antigen. Therefore, the use of specific antibodies to cytoplasmic antigens can be of help in sorting pure fractions of cells of a particular tissue for further studies.

Antibodies, Monoclonal↗
PubMed1986

A GABA-activated chloride-conductance not blocked by picrotoxin on spiny lobster neuromuscular preparations.

Conductance increases to gamma-aminobutyric acid (GABA) were recorded in the gm6b and opener muscle of the spiny lobsters, Panulirus interruptus and P. argus. GABA-evoked responses were insensitive to picrotoxin at concentrations as high as 5 X 10(-5) M. Some blockade by picrotoxin was observed at higher concentrations. In normal physiological saline, the reversal potential of the Panulirus GABA-induced response was near the resting potential. The reversal potential was unaffected by reductions in sodium and calcium. Reduction of chloride by 50% resulted in a greater than 10 mV shift in the reversal potential of the GABA-induced response. Muscimol was able to mimic the action of GABA while baclofen was without effect. Bicuculline was a weak blocker. Avermectin B1a irreversibly increased the chloride permeability of the gm6b membrane. This conductance increase was blocked by picrotoxin over a range of concentrations similar to those required for blockade of the GABA-induced response. GABA-induced responses of the gm6b muscle of Homarus americanus were blocked almost completely by picrotoxin 10(-6) M. Sensitivity to picrotoxin is not invariably associated with GABA-activated chloride-mediated conductance increases. It is suggested that alteration in the binding-site for picrotoxin on the GABA-activated chloride-ion channel does not change other functional characteristics of the GABA-induced response.

Action Potentials↗