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Biomedical subjects

M Cottler-Fox

Publications and source records attributed to M Cottler-Fox.

At least 73 records · Page 4Linked to original sources

Pulmonary fibrosis after bone marrow transplantation responsive to treatment with prednisone and cyclosporine.

Interstitial pneumonitis and biopsy-proven pulmonary fibrosis developed in a 35-year-old man with acute myeloblastic leukemia 4 months after conditioning with total body irradiation, etoposide and cyclophosphamide and allogeneic marrow transplantation from an HLA-identical sister. The patient had no evidence of graft-versus-host disease. Under treatment with cyclosporine and prednisone the patient became asymptomatic and radiographic changes of the chest normalized. Following discontinuation of immunosuppressive treatment the patient again became dyspneic, and chest radiographs showed bilateral diffuse interstitial infiltrates. Concurrently there was a rise in serum transaminases. Treatment with prednisone again resulted in resolution of all symptoms and normalization of radiographic and hepatic function abnormalities. This case indicates that late onset interstitial pneumonitis may respond to immunosuppressive therapy. Conceivably, such pulmonary disease may represent the first or only manifestation of chronic graft-versus-host disease.

Adult↗

Escalating doses of etoposide with cyclophosphamide and fractionated total body irradiation or busulfan as conditioning for bone marrow transplantation.

In a phase I study 28 patients with lymphohematopoietic malignancies were treated with escalating doses of etoposide combined with cyclophosphamide 120 mg/kg and either fractionated total body irradiation (TBI) 1320 cGy in 11 fractions (n = 17) or busulfan 16 mg/kg (n = 11). Twenty transplants were allogeneic, seven autologous and one syngeneic. The maximally tolerated dose of etoposide in combination with TBI and cyclophosphamide was 60 mg/kg; at etoposide doses of 65 mg/kg three patients developed life-threatening or fatal mucosal toxicity. In combination with busulfan, the maximally tolerated dose of etoposide was 30 mg/kg. At an etoposide dose of 40 mg/kg two patients developed life-threatening or fatal toxicity (one mucosal, one hepatic). Mucositis requiring narcotic analgesics, hepatotoxicity, hematologic toxicity and interstitial pneumonitis were otherwise similar in TBI and busulfan-treated patients. Skin toxicity was observed significantly more often in the busulfan group. Five deaths occurred before day +30, two in the TBI group and three in the busulfan group. Eleven patients are surviving, ten in continuous complete remission, at a median of 9 (range 3-23) months following transplantation. Etoposide in combination with TBI and cyclophosphamide or busulfan and cyclophosphamide is associated with significant but acceptable toxicities. The maximally tolerated dose of etoposide is higher when combined with TBI than with busulfan. Promising response rates in this high risk group of hematologic malignancies warrant further evaluation of these etoposide containing conditioning regimens.

Adolescent↗

Ultraviolet B light inactivates bone marrow T lymphocytes but spares hematopoietic precursor cells.

Bone marrow cells from ten normal donors were exposed to ultraviolet (UV)C or UVB light for total exposures of 0.1 to 100 mJ/cm2, and assayed for granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and phytohemagglutinin (PHA)-stimulated proliferative responses. After exposure to UVC CFU-GM, BFU-E and PHA responses showed a UV dose-dependent sharp decrease to levels less than 1% of controls with 0.5, 2.0, and 10 mJ/cm2, respectively. With UVB, PHA responses were most sensitive, declining to less than 1% at 5 mJ/cm2. BFU-E decreased to less than 1% of control with 15 mJ/cm2 UVB. CFU-GM, at UVB doses of 0.1 to 2.0 mJ/cm2, increased to 125% to 130% of control and decreased to less than 1% only at exposures greater than 20 mJ/cm2. Thus, these studies show that UVB, but not UVC light, can be used to inactivate bone marrow T lymphocytes selectively while sparing hematopoietic precursor cells. The data suggest that UVB irradiation can be used for T-lymphocyte purging for allogeneic marrow transplantation.

Bone Marrow↗

Acute esophageal stricture after bone marrow transplantation.

Gastrointestinal complications following bone marrow transplantation are common and may result from the conditioning regimen, immunosuppression, graft-versus-host disease, or a combination of these factors. These effects may be acute (mucositis, enteritis, esophagitis) or delayed (xerostomia, stricture formation) in onset. We describe here a case of esophageal stricture developing within 1 month of allogeneic bone marrow transplantation.

Adult↗

Fixation and occurrence of dark and light cells in taste buds of fungiform papillae.

The fine structure of taste buds of the fungiform papillae of the Old World monkey Cynomolgus (Macaca fascicularis) was found to vary with the primary fixative solution used. Standard primary fixative solutions of glutaraldehyde as well as fixatives containing both formaldehyde and glutaraldehyde gave non-reproducible and usually poor results. Osmium tetroxide in distilled water gave reproducible fixation of acceptable quality. Further, when fixed in osmium tetroxide in distilled water, taste buds of the fungiform papillae did not show the dark and light cells well known from other studies. It is therefore suggested that the terms dark and light cells not be used as synonyms for receptor or support cells, since the appearance of taste bud cells is affected by fixation.

Animals↗

Cytotoxic effects of cobalt-chromium alloys on fibroblasts derived from human gingiva.

The in vitro toxicity of 15 different cobalt-chromium alloys used in removable partial dentures and dental implants was studied. The composition of the alloys was determined by X-ray spectrometry. Alloys were tested on human oral fibroblasts in low density, semiconfluent or confluent cultures. The cultures were observed in a phase contrast microscope over a period of 3 wk. The alloys could be divided into three groups depending upon the degree of cell injury evoked. Group I alloys caused no cell injury. Group II alloys caused slight to moderate cell injury seen first after 3-7 days of exposure. Group III alloys caused severe cell injury with signs of cell damage detected after 12 h and total cell death after 3-14 days. The alloys' composition varied considerably with regard to cobalt, chromium and nickel as well as other components. Nevertheless, group II and III alloys had a higher nickel content than group I alloys in general.

Cells, Cultured↗

Transformation-associated increase of adhesion, cellular fibronectin, and stress fiber development in a liver epithelial cell line.

Cytoskeletal and adhesion characteristics of DL-ethionine (CAS: 67-21-0)-transformed rat liver epithelial cells (ETC) were compared with those of nontumorigenic, untreated cells of the same cell line both at the same passage level as ETC and at an early low passage level. ETC and high-passage-level cells (HPC) showed increased cell spreading and prominent actin stress fibers compared to low-passage-level cells (LPC). The number of adhesion plaques per unit cell area was higher for ETC than for LPC. At confluence, fibronectin expression was high for ETC, moderate for HPC, and low for LPC. The observed increases in cell spreading and in actin and fibronectin expression appeared to be associated with transformation of this cell line rather than being specific responses to ethionine treatment. This conclusion is suggested by the fact that HPC, which display preneoplastic markers, are similar in many respects to ETC.

Actins↗

Fine structure of taste buds in the human fungiform papilla.

The fine structure of taste buds on fungiform papillae from man was examined with particular reference to different cell types and to cell-nerve contacts. Most of the elongated cells of the taste bud extended from the basal lamina to the apical pore, terminating in irregular microvilli. The cells contained clear apical vesicles, mitochondria, filament bundles and Golgi cisternae. Unmyelinated nerve fibers, containing mitochondria as well as both dense-cored and clear synaptic-type vesicles, were scattered throughout the whole taste bud but were most numerous at the base. The nerve fibers were either in simple appositional contact or in mesaxonal contact with the taste bud cell. Typical synapses with the postsynaptic densities in the taste bud cell were sometimes seen. In addition, single taste bud cells were observed to have more than one type of contact with nerve fibers. As in the Old World monkey Cynomolgus it was not possible to distinguish different cell types described earlier in other species.

Adult↗

Taste buds of the fungiform papillae in Cynomolgus monkey.

A study of the number of taste buds borne on 145 fungiform papillae from 20 Cynomolgus monkeys showed that, in contrast to the situation in man, most papillae are bud-bearing. The fine structure of taste buds on fungiform papillae of these monkeys was also examined. The cells contained clear apical vesicles, mitochondria, filament bundles and stacks of Golgi cisternae. Nerve fibres containing mitochondria, as well as clear and dense-cored vesicles, were scattered throughout the whole bud, but were more numerous near the base. It was, however, not possible to distinguish different cell types in these taste buds as a function of cell shape, electron density of the ground cytoplasm, presence of different organelles or relation to nerve processes.

Animals↗

Adhesion of metastatic and non-metastatic carcinoma cells to glass surfaces.

Adhesion in vitro is described in cells from a tumor pair originating from a single methylcholanthrene-induced mouse carcinoma. One member of this tumor pair shows a high incidence of metastases while the other does not metastasize. Cells from the non-metastasizing carcinoma were found to form close and focal contacts with a glass substrate consecutively, as do normal mouse kidney epithelial cells. Cells from the metastasizing carcinoma, however, had only limited areas of close contact and generally failed to form focal contacts. It is suggested that this alteration in cell-substrate adhesion contributes to the release and mobility of metastatic cells.

Animals↗

Effects of dental root posts on human gingival fibroblasts in vitro.

Dental root posts of gold-plated brass and German silver caused injury of human gingival fibroblasts in vitro. Posts made of stainless steel, titanium and gold alloys showed no discernible effects of cell morphology of apparent metabolic activity during the two-week period of observation.

Cells, Cultured↗

A simple and inexpensive culture device for cell growth, quantitative microscopy and autoradiography.

An inexpensive culture chamber suitable for subsequent preparations for cytochemical or radiographic work is demonstrated. The chamber consists of two glass microscope slides suitably prepared for cell growth and a gasket of silicone rubber. The slides and gasket are sealed and held together with two ordinary spring letter clips or clothes-pins. Cells may be inoculated by piercing the gasket with a hypodermic needle, or by removing the top slide and adding cells directly. Long-term cultivation with medium replacement is easy and efficient and addition of isotopes or other materials may be done aseptically.

Autoradiography↗

Analysis of oncornavirus RNA subunits by electron microscopy.

Subunits of oncornavirus (avian myeloblastosis virus) RNA were isolated from purified 60--70S viral RNA by heat dissociation. Molecules sedimenting at 35 S, assumed to be the major component of the viral genome, were visualized in the electron microscope and their lengths were statistically analyzed. The results indicate a rather heterogeneous population of molecules with five distinct, reproducible size groups, an observation that excludes the assumption of random degradation of the genome. In addition, molecules of 28 and 18S RNA, always present in oncornavirus RNA preparations, were examined with the same methods. Some of these molecules possess secondary-structure regions similar to those characteristic for ribosomal RNA.

Avian Leukosis Virus↗