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Biomedical subjects

M Lieber

Publications and source records attributed to M Lieber.

At least 37 records · Page 2Linked to original sources
PubMed1995

Treatment with finasteride following radical prostatectomy for prostate cancer.

OBJECTIVES: The objective of this study was to evaluate the effect of finasteride (10 mg/d) or placebo on serum prostate-specific antigen (PSA) and recurrence rates in men with detectable PSA levels after radical prostatectomy. METHODS: A total of 120 men, 48 to 89 years old, previously treated with radical prostatectomy for prostate cancer within the past 10 years, with serum PSA levels between 0.6 and 10.0 ng/mL, with no evidence of skeletal metastasis on bone scan, and with no previous androgen deprivation therapy, were treated with 10 mg finasteride or placebo in a double-blind fashion for 12 months. After the first year, all patients were treated with finasteride for an additional 12 months. Primary endpoints were serum PSA levels and recurrence rates defined as positive bone scan or positive biopsy. RESULTS: Patients treated with finasteride had a delayed increase in serum PSA compared with placebo of approximately 9 months in the first year and 14 months by the end of the second year. Patients with baseline PSA levels less then 1.0 ng/mL had no significant increase in serum PSA during the 2 years of treatment. Fewer recurrences were observed in the finasteride group, but these differences were not statistically significant. Finasteride was well tolerated, and side effects were balanced between treatment groups. CONCLUSIONS: The results of this study indicate that treatment with finasteride delays but does not prevent the rise in serum PSA observed in untreated patients with detectable PSA levels after radical prostatectomy. The reduction in local and distant recurrences in the finasteride group suggests that the effect on PSA reflects a direct effect on tumor growth without affecting the initial response to subsequent hormonal therapy. These data require confirmation by studies that are longer and larger, focused on demonstrating significant differences in progression rates and survival before the use of finasteride can be considered as an option for men with detectable PSA levels after radical prostatectomy.

Aged↗
PubMed1994

Clinical utility of cellular DNA measurements in prostate carcinoma. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

At a WHO consensus conference on Early Diagnosis and Prognostic Parameters in Localized Prostate Cancer, a working group discussed the clinical utility of DNA measurements in stages T2 and T3 prostate carcinoma. Incidentally discovered prostate cancer of stage T1 was excluded. The members of the working group, representing various clinical and laboratory disciplines, discussed technical considerations of DNA measurements by flow and image analysis, pretreatment prediction of prognosis, and posttreatment clinical relevance. The group agreed to subdivide tumors into diploid, tetraploid and non-tetraploid aneuploid, expressing various degrees of aggressiveness and gave guidance for the definition of limits of these groups. The panel agreed that knowledge on DNA ploidy prior to treatment is of value in treatment decisions, particularly when surveillance is a treatment option. Aneuploid tumors can be expected to respond very poorly to either irradiation or endocrine therapy, and the presence of aneuploid tumor, either on pretreatment biopsies or in radical prostatectomy specimens, is an ominous sign. The identification of a group of patients with a uniformly poor prognosis should encourage medical oncologists and basic scientists to develop adequate treatment options for this particular group. The panel expressed a strong opinion that DNA ploidy should be uniformly studied in clinical trials, particularly in patients with localized prostate cancer.

Biopsy↗
PubMed1991

Incidence and outcome of surgery for benign prostatic hyperplasia among residents of Rochester, Minnesota: 1980-87. A population-based study.

The incidence and outcome of surgery for benign prostatic hyperplasia (BPH) was studied in Rochester, Minnesota, during the period 1980-1987. Three hundred thirty Rochester men without a diagnosis of prostate or bladder cancer underwent prostatectomy for BPH for the first time. Mean and median ages were both seventy (range: 46-95). The incidence of initial prostatectomy for BPH among men forty-five years of age and older age-adjusted to the 1980 U.S. white male population was 642 cases per 100,000 persons per year (py). Among the 330 men undergoing initial prostatectomy for BPH, 14 (4.2%) had serious intraoperative complications, 32 (9.7%) were rehospitalized for urologic complications within thirty days of surgery, and 13 (3.9%) had other serious complications within thirty days after surgery, including 1 death (surgical mortality 0.3%). Forty-five patients (14%) required blood transfusions within thirty days of surgery. The likelihood of reoperation within six years of the initial surgery was 15.1 percent (95% CI 9.7, 20.6). Short- and long-term postoperative mortality was not statistically significantly different than expected based on age- and sex-specific mortality statistics for Rochester, Minnesota.

Aged↗
PubMed1991

Benign prostatic hyperplasia: a population-based study.

To evaluate the incidence and outcome of initial surgery for benign prostatic hyperplasia (BPH) and to clarify the natural occurrence and progression of such urologic diseases, two studies have been conducted in a free-living population in Rochester, MN. The first followed 330 men who had not been diagnosed with prostate or bladder cancer at the time of prostatectomy. All surgery subjects were area residents and between 46 and 95 years of age (mean age 70 years). Among the operated subjects, 14 (4.2%) had serious intraoperative complications, 32 (9.7%) were rehospitalized for urologic complications within 30 days after surgery, and 13 (3.9%) experienced other serious complications in that same time period. Blood transfusions within 30 days of surgery were necessary in 45 patients (14%). The risk of reoperation within 6 years of the initial surgery was calculated at 15.1% (95% CI: 9.7, 20.6). On the basis of age- and sex-specific mortality statistics for Rochester, short- and long-term postoperative mortality was not statistically significantly different from that expected. Results of the second study are not yet available. This population-based evaluation of the natural history of urologic disease is expected to clarify the relative utility of various treatment options and provide a useful perspective on the management of BPH.

Aged↗
PubMed1990

Mutagenesis as viewed from another perspective.

Mutation has generally been considered a random process, not directed. Thus, a mechanism allowing for adaptively responsive mutagenesis has conceptually been precluded. However, an adaptively directed mutagenesis in response to environmental stress can be based upon genetic mutator systems. Such systems, known for years, have been seen as exceptional and not considered in terms of an adaptively responsive mutagenesis. Environmental stress which invokes this type of mutagenesis can thus be regarded as mutagenic itself, and our concept of what is mutagenic must therefore be broadened. Relevant matters are also discussed.

Adaptation, Physiological↗
PubMed1989

New developments on the generation of mutations in Escherichia coli lysogens.

Through the lytic process, P1 is a bacteriophage or virion capable at very low frequency of carrying out generalized transduction between strains of Escherichia coli. When P1 is not involved in lytic functions, it exists as a prophage in the form of circular DNA molecule, persisting in an extra-chromosomal or plasmid state, and not integrating into the host chromosome. E. coli carrying such plasmids have been referred to as lysogens. Earlier research dealt with P1 plasmids carrying drug-resistant factors. Up to the present study, P1 plasmids of any type were not known to have any mutagenic effect on the E. coli chromosome (genome), nor was it known that generalized transduction can be associated with mutagenicity. From P1 plasmids carrying a chloramphenicol resistance-factor, mutant plasmids of a particular type were isolated in the present study. P1 plasmids of this type carried a mutant factor which greatly impaired the capacity of phage derived from such plasmids, upon the completion of the lytic cycle, to lysogenize recA E. coli through phage promoted recombination. The plasmid of this mutant type is referred to as P1CMrec, and lysogens carrying such are referred to as P1CMrec lysogens. This paper describes the history of these P1CMrec lysogens and the genetic mutability within the E. coli chromosome of such P1CMrec lysogens, and the relationship of such genetic mutability (instability) to the incorporation of virion-DNA, following the absorption of P1 phage by these lysogens. As illustrated in the paper, a mutagenic effect was generated within the E. coli chromosome of P1CMrec lysogens by means of the P1CMrec plasmid. Furthermore, this mutagenic effect was found to be greatly, non-locally, and uniformly enhanced as a consequence of P1 virion incorporation by, or likely generalized transduction of, such lysogens. More specifically, the plasmid of this mutant type (P1CMrec) is responsible for the creation of a wide range of genetic mutabilities (instabilities) of differing degree within the E. coli genome (not carrying recA), some mutabilities being very high upon extended incubation. The P1CMrec plasmid was also involved in the creation of new mutant genes within the E. coli genome (not carrying recA), some mutabilities being very high upon extended incubation. The P1CMrec plasmid was also involved in the creation of new mutant genes within the E. coli chromosome, some of which manifested high mutability.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteriophages↗
PubMed1984

DNA sequence of the 5' flanking region of the human interleukin 2 gene: homologies with adult T-cell leukemia virus.

We previously reported the sequence of the gene for human interleukin 2 (IL-2) which included about 220 b.p. of the 5' flanking region. In this report we have extended the 5' sequence to 1263 b.p. before the start site of transcription and have compared the entire sequence of the IL-2 gene and its 5' flanking region with that of Adult T-cell leukemia virus (ATLV). Four regions of limited homology were noted. Three areas of homology to the viral long terminal repeat (LTR) were seen in the 5' sequence flanking IL-2. A fourth region of homology to the viral LTR was located within the second intron of the IL-2 gene. While the significance of these homologies is not known, it is possible that they are involved in regulating the expression of ATLV and IL-2, both of which are generally restricted to T cells.

Adult↗
PubMed1984

Lifespan changes in the index of cephalization.

This study compares the lifespan changes in respect to several brain-body weight parameters between several rat strains and human population groups. In the rat, following an initial potential decline, these parameters remain essentially constant throughout the lifespan. In the human, following a similar postnatal decline, there is a further progressive decline after about age 50. However, this decline with age disappears when correction is made for percent body fat. Thus, while both brain and body weight decline with age in humans, they do not decline proportionately. In both species brain and body weights are greater in males than in females, but when the data are translated into the several brain-body parameters females generally show higher indices than males, and this correlates with their superior longevity. These findings are discussed in respect to the role of the brain in aging.

Adolescent↗
PubMed1982

Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue.

The cytotoxic peptide from honeybee venom, melittin, and a synthetic peptide analogue of it lyse human erythrocytes in a biphasic process. The kinetics of the lysis in 0.30 M sucrose, 0.01 M sodium phosphate, pH 7.30 at 4 degrees C were investigated. Our results show that melittin rapidly binds to the outer surface of the erythrocyte membrane, and the surface-bound monomers produce transient openings through which approximately 40 hemoglobin molecules can escape. Concomitantly, the melittin loses its ability to effect the process, presumably by translocation through the bilayer. The half-life for this process is 1.2 min. In a much slower process, dimers of this internalized melittin again produce transient membrane openings in a steady state. On a molar basis, the synthetic peptide analogue produces a fast process comparable to that caused by melittin, but is more efficient in the slow phase. Escape of hemoglobin and of carbonic anhydrase through the openings is diffusion controlled. These results suggest that the functional units necessary for the activity of melittin-like cytotoxic peptides are a 20 amino acid amphiphilic alpha-helix with a hydrophobic:hydrophilic ratio greater than 1 and a short segment with a high concentration of positive charges.

Animals↗
PubMed1977

Latent adenocarcinoma in renal cysts.

A case is presented in which repeat examination of a benign cyst disclosed a latent adenocarcinoma near the cyst wall. Since statistically there is a greater incidence of tumor associated with cyst and since there is a 90% accuracy rate in the diagnosis of cystic lesions it appears that reinvestigation seems justified in some cases, especially if there is a change in or new development of symptoms.

Adenocarcinoma↗
PubMed1976

A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells.

The A549 tumor-cell line, initiated from a human alveolar cell carcinoma, has been continuously propagated in vitro for more than 3 years (more than 1,000 cell generations). These cells have a human karyotype and appear to have been derived from a single parent cell. All A549 cells examined by electron microscopy at both early and late passage levels contain multilamellar cytoplasmic inclusion bodies typical of those found in type II alveolar epithelial cells of the lung. At early and late passage levels, the cells synthesize lecithin with a high percentage of disaturated fatty acids utilizing the cytidine diphosphocholine pathway; such a pattern of phospholipid synthesis is expected for cells believed to be responsible for pulmonary surfactant synthesis. The A549 cell line should permit in vitro analysis of human surfactant synthesis and secretion and possibly provide a source of human surfactant for therapeutic intervention in pulmonary disease states characterized by surfactant deficiency.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1975

Establishment of a continuous tumor-cell line (panc-1) from a human carcinoma of the exocrine pancreas.

An epithelioid cell line, started from a human pancreatic carcinoma of ductal cell origin, has been maintained in culture for over 2 years and has been subcultured more than 40 times. The PANC-1 cell line has a doubling time of 52 h and G6PD activity of the slow mobility of B type. Chromosome studies show a modal number of 63 with three distinct marker chromosomes and a small ring chromosome. The malignant nature of the PANC-1 cell line was verified by: (1) the ready growth of PANC-1 cells in soft agar and on top of a fibroblast monolayer; and (2) the formation of a progressively growing anaplastic carcinoma after injection of a nude-athymic mouse with PANC-1 cells.

Carcinoma↗