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Biomedical subjects

J Folkman

Publications and source records attributed to J Folkman.

At least 253 records · Page 14Linked to original sources
PubMed1979

Oxygen content determined by acrylamide polymerization: screening of anticancer agents, generation of oxyhemoglobin dissociation curves, and potential applications.

Many investigators have endeavored to accurately measure oxygen content produced or consumed from substrates or tissues. Most of the techniques currently available are time consuming or exceedingly complex. Many require expensive apparatus and demand the skills of a highly trained technician. We have deveoloped a rapid and sensitive method of measuring oxygen content or consumption. This method is based upon the time for polymerization of acrylamide gels. The time of acrylamide polymerization is directly proportional to the oxygen content of the test medium. We have used this method to generate oxyhemoglobin dissociation curves which closely resemble those published by Severinghaus and Duvelleroy, as well as those we determined by the conventional Van Slyke analysis. We have also used this method to measure the oxygen consumption of tumor cells and to evaluate the effects of Actinomycin, cyclohexamide and cytosine arabinoside on Walker 256 ascites tumor. The results correlate with the known in vivo effects of these drugs on this tumor cell line. Therefore, because of its sensitivity and adaptability this method may be useful in a variety of clinical and biological situations.

Acrylamides↗
PubMed1979

Angiogenesis capacity as a diagnostic marker for human eye tumors.

Solid tumors have the capacity to continuously stimulate the proliferation of new capillaries. Aliquots (0.1 cc) of aqueous humor were aspirated from the anterior chamber of the eye of 38 patients undergoing elective ophthalmologic surgery. The material was lyophilized and then inplanted on the chorioallantoic membrane (CAM) of 10-day-old chick embryos for bioassay. The angiogenesis capacity of each sample was graded as negative or positive. Nine of 10 patients with histologically proven retinoblastoma had positive vascular responses. Seven of 11 patients with choroidal malignant melanoma had a positive response to their aqueous humor on the CAM. Aqueous samples from eyes with an iris and ciliary body malignant melanoma and a metastatic breast carcinoma to the iris had a positive angiogenic response. By contrast, only one of 15 patients undergoing operation for cataracts, glaucoma, or other nonmalignant ocular disease showed an angiogenesis response. The one patient who a positive assay later developed lymphocytic leukemia. These studies show that certain intraocular tumors display angiogenesis capacity before clinically evident neovascular changes of floating tumor cells are seen. Patients without tumors showed no angiogenesis response.

Angiogenesis Inducing Agents↗
PubMed1978

Role of cell shape in growth control.

Tissue culture plastic adhesivity was precisely varied by applying different concentrations of poly(2-hydroxyethyl methacrylate). The extent of cell spreading was thus accurately controlled so that cells cultured on these substrata could be held at any one of a graded series of quantitated cell shapes. Cell shape was found to be tightly coupled to DNA synthesis and growth in nontransformed cells. These findings suggest a mechanism that is important in growth control of mammalian cells, and provide a more fundamental interpretation of such phenomena as density dependent inhibition of cell growth and anchorage dependence.

Cell Adhesion↗
PubMed1978

Controlled drug release from polymers.

Unlike conventional routes of drug administration, controlled-release systems that use implanted, inserted, or surface-applied noninflammatory polymeric vehicles can deliver a steady quantity of drug to a target area over long periods of time. This is now true for drugs of both high and low molecular weight. Some of the devices are described, and existing as well as potential clinical applications are discussed.

Animals↗
PubMed1977

Glycogen storage disease: new approaches to therapy.

Detailed studies of the effect of 32 days of intravenous alimentation on the metabolic, hormonal and clinical status of a 4-year-old boy with Type I glycogenosis revealed that the biochemical abnormalities and growth failure in this disorder are a consequence of glucose lack after brief periods of fasting which results from the inborn enzyme deficiency. Long-term (1.5-5.7 years) observations of the therapeutic effects of portacaval shunt without and with continuous overnight intragastic glucose by gastrostomy in two brothers, and of continuous overnight intragastric glucose alone in five other patients with this disorder, on metabolic status and physical growth and development suggest that adequate glucose can be provided by the intragastric route without hepatic portal circulatory by-pass. The introduction of this therapy in the first year of life should prevent the serious risk to life and long-term failure in growth and development previously observed in patients with Types I and III glycogenosis.

Child↗
PubMed1977

Experimental retinal neovascularization induced by intravitreal tumors.

Adult rabbit retinal vessels underwent neovascularization in response to tumor implantation within the vitreous body. The neovascular response was presumably elicited by the tumor angiogenesis factor (TAF). The response of adult retinal vessels to an angiogenic stimulus raises the possibility that a similar substance may cause retinal neovascularization in humans, and that in normal conditions the vitreous may be able to suppress angiogenic activity.

Angiogenesis Inducing Agents↗
PubMed1977

Inhibition of neovascularization by an extract derived from vitreous.

An extract of the vitreous body, inhibited the growth of new blood vessels induced by tumors in the rabbit cornea. This extract was delivered by an inert, continuously releasing polymer. The average vessel growth rate in the region surrounding the polymer was 32% less in corneas containing the inhibitory substance than in control corneas.

Animals↗
PubMed1977

Avascular and vascular phases of tumour growth in the chick embryo.

The chick embryo was used to study the relationship between the onset of tumour neovascularization and tumour growth. Walker 256 carcinosarcoma was implanted on the chrioallantoic membrane (CAM) of about 600 embryos aged 5-16 days. Tumour diameter and changes in the CAM vasculature in response to the implants were recorded daily. Representative tumours were examined by light microscopy of Epon-embedded tissue and autoradiography after injection of [3H]-thymidine. Tumours remained avascular for 72 h, after which they were penetrated by new blood vessels and began a phase of rapid growth. The rate of growth during this vascular phase was greatest for implants on 5- and 6-day-old embryos and decreased the later the day of implantation. The time of onset of tumour angiogenesis appears to be independent of the immunological state of the chick embryo, although the rate of growth after vascularization may be modified by the onset of immunity. This study suggests that the avascular and vascular phases of tumour growth are separable, and that the avascular tumour population lives under the growth constraints which limit the size of a tumour spheroid growing in soft agar or aqueous humour.

Animals↗
PubMed1977

Erythromelalgia.

Erythromelalgia is an extraordinary disease which remains elusive in its pathophysiology and management. Victims suffer intense burning and redness of the hands and feet. In what appears to be the antithesis of Raynaud's disease, the pain is relieved by emersion in cold. A child with erythromelalgia is described whose symptoms began at age 3 years. Pharmacological management trials and thermography are incorporated in the report.

Child, Preschool↗
PubMed1976

Mast cells and tumor angiogenesis.

Tumor angiogenesis factor (TAF) elicits a strong vasoproliferative response when implanted upon the chorioallantoic membrane (CAM) of the chick embryo. This response is first observed stereomicroscopically 2-3 days after implantation. A 40-fold increase in mast cell density is observed within the vicinity of this implant by 24 h. Mast cells that have been isolated from retired breeder Sprague-Dawley rats fail to evoke a vascular reaction when implanted on the CAM. An intermediate role for the mast cell in tumor angiogenesis is suggested.

Angiogenesis Inducing Agents↗
PubMed1976

Vascular injury in transplanted tissues. Fine structural changes in tumor, adult, and embryonic blood vessels.

Adult, embryonic and tumor tissues from the rat were grafted to the chorioallantoic membrane (CAM) of the chick embryo. Fine structural changes in the microvasculature of the transplants were compared, with emphasis on the condition of endothelial cells. Endothelial cells in tumor grafts appeared irreversibly injured 2 h after grafting and most had degenerated by 8 h. In normal adult tissues, endothelial cells disintegrated more slowly, but lipid accumulation and blebbing leading to occlusion of vascular lumina, were prominent by 1 day. Cells were swollen and vacuolated 2 days after grafting and most were disrupted by 3 days. Embryonic endothelial cells were only mildly damaged and vessel lumina were patent for up to 3 days. Vessels were then reperfused with chick blood. It is concluded that the microvasculature in tumor tissue is extremely susceptible to ischemic damage and that this phenomenon may be involved in the central necrosis which develops in many animal tumors after they grow beyond a small size. Furthermore, only blood vessels and endothelium in embryonic tissues were sufficiently resistant to ischemic changes so that the graft microvasculature could be reperfused.

Animals↗
PubMed1976

Isolations of a cartilage factor that inhibits tumor neovascularization.

A cartilage fraction isolated by guanidine extraction and purified by affinity chromatography inhibits tumor-induced vascular proliferation and consequently restricts tumor growth. This fraction contains several different proteins; the major one has a molecular weight of about 16,000. The fraction strongly inhibits protease activity.

Carcinoma↗
PubMed1976

Lymphoid depletion in ileal loops: mechanism and clinical implications.

Recent long-term follow-up studies of children undergoing ileal loop urinary diversion have shown a number of complications arising in these patients: recurrent urinary tract infections, deteriorating renal function, and late midloop stricture. We suggest that all three may be related to the same underlying problem, namely, a severe depletion of lymphoid elements in the intestine. In both clinical and animal studies urine exposure to intestinal segments resulted in a marked depletion of lymphoid elements from the Peyer's patches and from beneath the intestinal villi in the intestine. In addition there was an associated hypertrophy of the lymph nodes in the ileal loop mesentery. When the intestine was no longer exposed to urine, there was a prompt regeneration and reappearance of the lymphoid elements. The lymphocytes seemed to "home in" on the submucosal areas and reform Peyer's patches once the urine was removed. The hyperplastic lymph nodes in the ileal loop mesentery regressed when urine exposure was removed. Conventional treatment of ileal loop infections focuses on the upper urinary tracts. Mid-loop stenoses are treated by resection and creation of a new ileal loop conduit. Local therapy in the form of antibiotics and/or steroid enemas may relieve some late midloop obstruction and prevent further damage to renal parenchyma.

Animals↗