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Biomedical subjects

S J Friedman

Publications and source records attributed to S J Friedman.

At least 73 records · Page 4Linked to original sources

Monoclonal gammopathy and mycosis fungoides. Report of four cases and review of the literature.

Of four patients with mycosis fungoides and monoclonal gammopathy, one died of multiple myeloma that developed 4 years after the mycosis fungoides. The other three had monoclonal gammopathy of undetermined significance. This association does not appear to occur with a high frequency in patients with mycosis fungoides than in the general population. However, it demonstrates that B cell proliferation can occur in patients with primary cutaneous T cell disease.

Aged↗

Non-exponential growth by mammalian cells in culture.

The concept of exponential growth by mammalian cells in culture is based upon the apparent linearity of semilogarithmic data plots. This method of graphical analysis is known to be an unreliable test of the exponential hypothesis. We have re-examined the question of growth exponentiality using the more sensitive method of Smith plots, in which specific growth rate is plotted against either time or density on transformed graphical coordinates which linearize the mathematical expression of the growth hypothesis being tested. With exponential growth, data points fall on a horizontal straight line when specific growth rate is plotted against time or density. Using both our own and literature data, we have performed Smith plot analyses on the growth of 125 different mammalian and avian cell lines. Of these, only eleven exhibited an exponential phase. The remaining cell lines all had non-exponential growth patterns. The most common of these consisted of an initial period of growth acceleration followed by a later phase of deceleratory growth. A smaller number of lines exhibited deceleratory kinetics at all times after plating. We conclude that mammalian cell growth in culture is predominantly non-exponential, and that the apparent exponentiality of semilogarithmic data plots is usually a methodological artifact.

Animals↗

Effect of D-glucosamine on human natural killer activity in vitro.

D-Glucosamine has been shown in animal studies to have selective tumoricidal activity. In human cancer patients, preliminary data indicate that natural killer (NK) activity is increased secondary to D-glucosamine infusion. The present study examined the effect of D-glucosamine on several in vitro indices of human immune responsiveness including NK cell activity and T and B cell mitogenesis. NK activity in normal human peripheral blood mononuclear cells was significantly elevated in the presence of 10(-4) and 5 X 10(-4) M D-glucosamine. The increment in NK activity was mediated by nonadherent effector cells and was not due to an increased susceptibility of target cells. Analysis by single-cell assay indicated that the number of effector/target conjugates was not increased but that there was increased lytic activity of the NK cells. Previous studies from our laboratory indicated that several drugs which perturb thymidine (TdR) metabolism were effective in enhancing the in vitro NK activity. As D-glucosamine has been observed to alter cellular pyrimidine nucleotide pools and TdR metabolism in tumor cells, the effect of exogenous TdR was assessed on D-glucosamine-stimulated NK activity. Exogenous TdR inhibited D-glucosamine-induced augmentation of NK activity in a dose-dependent manner and completely abrogated the drug response at 10(-7) M. Similar experiments indicated that TdR did not affect the interferon-induced augmentation of NK activity in concentrations up to 10(-4) M. Although human NK activity was enhanced by D-glucosamine in vitro, there was no change induced in T or B lymphocyte mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗

Management of leg ulcers with hydrocolloid occlusive dressing.

Twenty-two patients with 31 leg ulcers of various causes received local wound management consisting of the application of an adhesive hydrocolloid (HC) occlusive dressing (DuoDerm). Group 1 comprised 15 patients (11 outpatients) with 19 ulcers. Approximately two thirds (12/19) of the ulcers healed when treated solely with the HC dressing; mean treatment time was 57 days. Group 2 comprised seven hospitalized patients with at least two leg ulcers of similar size and distribution. The 20 ulcers in the seven patients were treated with either mild topical antimicrobial wet dressings (Sweitzer's 1:32 solution) or HC dressings, with each patient serving as his own "control." All 20 ulcers healed; the average time to healing was 44 days with HC dressing and 42 days with wet dressing management. Most of the patients reported convenience in management and substantial relief of pain with the use of HC dressings.

Adult↗

Histoplasmosis presenting as erythema multiforme and polyarthritis.

Erythema multiforme and polyarthritis occurred in association with serologic evidence of primary histoplasmosis. Although such occurrences have been noted in epidemics, recognition of this triad outside of the epidemic setting has been described only once before.

Acute Disease↗

Gynecologic carcinoma associated with dermatomyositis-polymyositis.

Dermatomyositis-polymyositis was associated with gynecologic carcinoma in ten patients treated at the Mayo Clinic between 1952 and 1982. Only two patients did not manifest the typical skin changes of acute dermatomyositis. In all ten cases, the onset of dermatomyositis-polymyositis preceded evidence of carcinoma. The intervals between initial symptoms of dermatomyositis-polymyositis and subsequent diagnosis of carcinoma ranged from three months to six years. Usually, the carcinoma became evident within two years. The carcinomas were ovarian in five cases, cervical in three, endometrial in one, and vaginal in one. Ages of the ten patients ranged from 40 to 66 years (mean, 53 years). In most cases, symptoms of dermatomyositis-polymyositis regressed markedly after diagnosis and treatment of the underlying carcinoma. In selected patients for whom more detailed follow-up information was available, the manifestations of dermatomyositis-polymyositis progressed and regressed in synchrony with tumor spread and effective treatment, respectively.

Adenocarcinoma↗

Extracutaneous sporotrichosis.

The typical infection with Sporothrix schenckii is characterized by superficial cutaneous nodules occurring along the lines of lymphatic drainage of the limbs. Review of the medical records at the Mayo Clinic from 1937 to the present disclosed 58 patients with sporotrichosis. Eleven patients had evidence of extracutaneous infection. Eight of the patients were men whose ages ranged from 25 to 71 years; the ages of the three women were 54, 64, and 67. Seven patients had predominantly joint involvement, with the knee and wrist joints being most often infected. Other sites of infection included the mandible and ethmoid sinuses. Three patients had disseminated systemic infection, and one patient died within a year of the initial diagnosis. Nine patients had been in good health before the infection, although five patients were taking systemic corticosteroids before their infection was diagnosed. Therapies included supersaturated potassium iodide, amphotericin B, and 2-hydroxystilbamidine isethionate. Although most commonly seen as a cutaneous disease, sporotrichosis is a potentially disseminated infection with life-threatening consequences.

Adult↗

Favre-Racouchot syndrome associated with radiation therapy.

A 56-year-old woman developed Favre-Racouchot syndrome involving her face and scalp primarily at the sites of x-ray irradiation for therapy of an astrocytoma. The patient had not had comedones prior to radiotherapy and did not have a history of excessive sun exposure. The patient showed an excellent response to topical retinoic acid gel. To the best of our knowledge, this is the first case of Favre-Racouchot syndrome developing after radiation therapy to be reported in the literature; its pathogenesis is discussed in this paper.

Brain Neoplasms↗

Management of leg ulcers.

Although leg ulcers have many causes, the most common etiology is venous or arterial insufficiency. The prime objective in the evaluation of leg ulcers is to uncover the precipitating pathologic process, and the first goal of therapy is to correct or control this underlying condition. Simple laboratory tests and office procedures are adjuncts in diagnosis. Topical care of leg ulcers includes gentle debridement, use of wet dressings and, in selected cases, skin grafting.

Anti-Bacterial Agents↗

Deceleratory growth by a rat glial tumor line in culture.

Tumors in vivo usually exhibit deceleratory rather than exponential growth kinetics. Deceleration results from a negative feedback inhibition of growth the effectiveness of which increases progressively with tumor size. A major obstacle to understanding the fine mechanisms of deceleratory growth has been the lack of a tissue culture system proven to exhibit these kinetics. Rat C6 glioma cells in culture enter a prolonged phase of deceleratory growth about 72 hr after subculture. As with tumor growth in vivo, the kinetics of the C6 deceleratory phase can be described with high accuracy by Gompertz, logistic, inverse cube root, and power functions. The least-squares correlation coefficients for the linearized forms of the rate equations for these functions were typically in the range of 0.75 to 0.90. During the deceleratory phase, the equilibrium growth rate of C6 cells is a monotonically decreasing function of population density at all observable densities, whether sub- or supraconfluent. Any change in density produces a compensatory change of opposite direction in the growth rate. To account for these relationships, a density-equilibrium hypothesis of C6 growth regulation is presented. The fine mechanisms responsible for this regulation do not involve medium or substratum depletion, production of conditioned medium factors, or the extracellular matrix. The development of growth deceleration appears to correlate with the extent of contact interactions between cells and their neighbors, indicating that deceleratory growth regulation is probably mediated by contact interactions. However, these interactions are fundamentally different from those postulated by the traditional contact inhibition theory. Confluency is irrelevant to the contact modulation which produces C6 growth deceleration. Any degree of contact, even at very sparse subconfluent densities, appears capable of exerting some degree of growth inhibition.

Animals↗

Membrane-active drugs potentiate the killing of tumor cells by D-glucosamine.

D-Glucosamine is toxic to several malignant cell lines and in vivo tumors at concentrations that have little effect upon normal host tissues. Evidence is presented to support the hypothesis that cellular membranes may be the primary targets of glucosamine's tumoricidal activity. Treatment of rat C6 glioma cells with a cytotoxic concentration of glucosamine (20 mM) caused fragmentation of rough endoplasmic reticulum, proliferation of Golgi complexes, evagination of outer nuclear and mitochondrial membranes, and the accumulation of membranous vacuoles and lipid droplets in the cytoplasm. These changes were detected within the first 3 hr after treatment of cultures with glucosamine and became increasingly severe until cell lysis occurred between 24 and 48 hr of treatment. The cytotoxicity of glucosamine was potentiated by the local anesthetic lidocaine, and by other membrane-active drugs, at concentrations that were growth inhibitory but nonlytic. Most of these drugs possessed local anesthetic activity and inhibited glioma sterol synthesis. Within the same period of time required for ultrastructural changes in cellular membranes, glucosamine inhibited the incorporation of [2-(14)C]acetate into sterols and into an unidentified 400-dalton lipid that migrated close to sterols on thin-layer chromatograms. This inhibition was potentiated by lidocaine and increased over the same range of D-glucosamine concentrations that led to increased cell toxicity after a 48-hr treatment. These findings suggest that the effects of glucosamine upon cellular membranes may be central to its tumoricidal activity and that glucosamine, in combination with membrane-active drugs, may be useful in the treatment of certain types of tumors, particularly those of the central nervous system.

Anesthetics, Local↗

Cellular senescence and the analysis of generation time distributions.

Generation time analysis by time lapse cinematography is an important method for investigating cellular senescence in culture, but its interpretation is complicated by several types of bias and artifact, including small sample size, cut-off bias, changes in global growth rate, and phase of the population growth cycle. When these factors are considered, interpretation of the data base used by previous investigators changes considerably, and does not reveal any differences in growth behavior between middle and late passage WI-38 cells. Nor does it support the transition probability theory either of cell cycle transit or of culture senescence.

Cell Cycle↗