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Biomedical subjects

O J Stone

Publications and source records attributed to O J Stone.

At least 37 records · Page 2Linked to original sources
PubMed1989

A mechanism of peripheral spread or localization of inflammatory reactions--role of the localized ground substance adaptive phenomenon.

It is known that connective tissue-active peptides (CTAP) are released at sites of inflammation. Some of this material diffuses to immediately adjacent tissue and increases ground substance viscosity and fibroblast proliferation. This contributes to host protection against spread of infections and tumors. In a person with normal inflammatory reactivity, it should prevent spread of mediators and products of local inflammation. However, the host with an increased reactivity in sites of increased ground substance viscosity or who is highly reactive to dilution of tissue fluid would respond with more inflammation. A non-infectious, non-malignant process in a host with a highly reactive inflammatory or immune response could end up with peripheral spread. This could occur in any tissue but it occurs with great vigor in the skin. It could present as a peripheral extension of a local disease process, such as psoriasis, or the migration of cyclic lesions with clearing of the central area. There are over a dozen variants of peripherally spreading, ringed lesions described in the dermatologic literature. This includes erythema marginatum of rheumatic fever, erythema gyratum repens associated with cancer, and erythema annulare centrificum associated with allergic reactions to fungi. Many of the ringed dermatologic lesions have an immunologic component. They tend to be associated with inflammatory immune reactions at distant sites. Dermatologists have been gathering information on the ringed phenomenon at least since Hebra in 1854. The acute localized ground substance adaptive phenomenon is a broadly beneficial biologic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1988

Lupus erythematosus and rheumatoid arthritis--groups of defects in microdebridement (polygenetic defects exceeding the fault tolerance threshold--a consequence of natural defense mechanisms).

Lupus erythematosus (LE) and rheumatoid arthritis (RA) are groups of defects in microdebridement of tissue which includes removal of infectious agents and cellular debris. They are the phenotypic response to a number of polygenetic and/or induced defects. The recognized clinical patterns of these disorders are the responses to accumulated tissue debris and complications of secondary debridement mechanisms that cannot function properly due to basic defects in the debridement system. The series of events that occurs after infection or tissue damage is polygenetic and involve multiple pathways. Genetic polymorphism of this group of mechanisms increases survival against a wider variety of infections. An organism capable of bypassing or destroying a specific step in the host defense is still eliminated by the host in spite of the created defect (a fault tolerant system). However, a single mutant error of this same step creating the same defect will not disrupt the host to the point of clinical illness or death. The pathways are broad enough to bypass some mutant errors. It is the same fault tolerant system. Increased pressure on the system from infection or tissue damage or a combination of multiple genetic defects results in enough faults to exceed the threshold of fault tolerance and produce clinical patterns of disease. The large number of possible combinations of defects gives rise to marked disease variation among patients. The higher frequency of some defects or combination of defects ces subsets. Inbred strains of animals have less polymorphism and thus some strains have a greater susceptibility to infections, LE and RA. Many of the phenomena that occur in LE and RA are secondary to the basic defect of inadequate tissue debridement. Rheumatoid factor (RF) is generally a normal beneficial phenomenon of increasing particle size so that immune complexes can more readily be removed by the reticuloendothelial system. In the presence of defective microdebridement the system is overloaded and no longer effective. This results in circulating RF. There are clearly multiple basic genetic defects. For example, the known multiple genetic defects in complement in LE are relevant to the systems involved. They are important ligands for defense and debridement mechanisms. A null allele is not likely to be a secondary phenomenon. It might be in a fault tolerant site and contribute to disease in one host, and yet not contribute to disease in another host.(ABSTRACT TRUNCATED AT 400 WORDS)

Arthritis, Rheumatoid↗
PubMed1988

The role of the primitive sea in the natural selection of iodides as a regulating factor in inflammation.

Iodides have many non-endocrine biologic effects, including a role they play in the physiology of the inflammatory response. Iodides when given systemically or applied locally increase the movement of granulocytes into areas of inflammation. They improve the phagocytosis of bacteria by granulocytes and the ability of granulocytes to kill bacteria. They alter native protein to make it more susceptible to enzymes produced by granulocytes. They increase glandular secretions and make mast cells more labile. They concentrate around tumors and granulomas in man and animals. They also move into areas of tissue injury. When iodide is redistributing around sites of tumors or injuries there is decreased thyroid uptake and decreased renal excretion. The multiple effects of iodides have suggested that iodide may have a physiological role in inflammation. Iodides were once used widely in medicine, especially before a cure for syphilis. Understanding the many known effects of iodides requires crossing multiple fields. The purpose of this paper is to propose that the rising iodide content of the primitive sea played a role in the natural selection of a system which helped the organism recover from tissue injury or invasion. As primative life forms underwent mutations those with a defense system more responsive to environmental factors, such as iodide, had the best chance of survival. It was important for a defense system to move to any point of surface injury. The diverse biologic effects of iodides suggest a very primative role. This effect was so important that it was later internalized so that today iodides are concentrated in the host around sites of injury or tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Acute local inflammation causing generalized increased ground substance viscosity: guttate psoriasis, Reiter's syndrome, adjuvant disease, cancer regression.

It is known that at sites of acute inflammation there is increased ground substance formation and fibroblast proliferation. There is also increased serum glycoprotein following localized acute inflammation. The author proposes that a severe acute inflammatory response in a localized area of the body induces a generalized increase in ground substance viscosity (generalized ground substance adaptive phenomenon). This would increase host resistance to invasion and heighten the inflammatory response. There are multiple clinical and experimental facts which could be explained by this response. These include guttate psoriasis, pustular psoriasis, pustular bacterid of Andrew's, Reiter's syndrome, and others. This response would include some aspects of adjuvant disease. Increased generalized ground substance viscosity could also explain the beneficial effects of streptococcal cell fractions and streptococcal infections on tumor regression. A number of other clinical observations could be explained. Connective tissue-activating peptide released at the inflammation site could be having a systemic effect. It could be generally beneficial to have generalized increased ground substance viscosity when acute inflammation is occurring in a localized area. A few patients who already have a highly reactive inflammatory level could develop excess inflammation especially at sites of trauma, or preexisting inflammation.

Acute-Phase Reaction↗
PubMed1988

Non-immunologic enhancement and regression of self-healing squamous cell carcinoma (keratoacanthoma)--ground substance and inflammation.

Keratoacanthomas have many characteristics of squamous cell carcinoma and in the past were interpreted as squamous cell carcinomas. It is now known that these lesions spontaneously resolve if left untreated. In man the lesions occur on sunlight damaged areas or areas exposed to tar. Many of the experimental cancers of animals produced by topical carcinogens are keratoacanthomas. Ultraviolet light and tar are known to damage fibroblast and ground substance viscosity. It has recently been proposed that anything that decreases ground substance viscosity would encourage the spread of tumors, by weakening tissue resistance. The rapidly growing keratoacanthoma produces invasive pressure and moves into deeper, less damaged dermis. An inflammatory reaction occurs in the depth of the lesion and a very characteristic granulocytic response occurs. Granulocytes release connective tissue active peptides which stimulate fibroblast and ground substance formation. The fibroblast proliferation is followed by fibrosis and the shrinking and disappearance of the tumor. The characteristic pustule that spurts granulocytes into the depth of the tumor has been experimentally blocked by hyaluronidase and other substances that damage ground substance viscosity. Edema is essential to produce this inflammatory reaction. However, this inflammatory phenomenon occurs vigorously in keratoacanthoma. It is proposed that a keratoacanthoma is a tumor that does not produce hyaluronidase or other substances that decrease ground substance viscosity. It is a deviant cell that can only move through areas of decreased ground substance viscosity. When it reaches tissues of normal viscosity edema and an inflammatory reaction occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Autoantibodies--a mechanism of microdebridement.

Antibodies to foreign debris are generally beneficial because they speed inflammation and debridement of tissue. Intracellular components are debris if they reach extracellular space. If not rapidly debrided from extracellular space, intracellular components stimulate autoantibody production. If not debrided, cellular constituents like other foreign material can initiate a chronic tissue response. Antibodies will speed removal of debris if an effective microdebridement mechanism is present. This is their general biologic significance. If the patient has a defective microdebridement system as in lupus erythematosus or rheumatoid arthritis, the autoantibodies occur to large numbers of intracellular substances and accumulate and contribute to tissue damage. Tissue damage occurs and autoantibodies accumulate in lupus erythematosus and rheumatoid arthritis because of inadequate microdebridement. This should not detract from the fact that autoantibodies are a common secondary phenomenon which plays an important part in maintaining tissue microdebridement.

Aging↗
PubMed1987

A speculative on psoriasis as an evolutionary consequence.

I speculate that if the inflammatory reactivity of all humans were quantitated, the results would fall on a bell-shaped curve. Psoriasis or the psoriatic trait is the most reactive 3%. Any attempt by evolution to shift the general inflammatory response to lesser activity would result in consequences more significant than psoriasis. This speculation predicts that we might have to settle for quantitative rather than qualitative changes in inflammation in psoriasis.

Biological Evolution↗
PubMed1986

Cancer resistance, carcinogenesis and ground substance viscosity.

Tumor host resistance and promotion are multiple complex simultaneous phenomena. This paper relates only to the effect of ground substance viscosity on tumor host interaction. Tar, anthralin, ultraviolet light, x-ray and arsenic have been widely used to treat inflammatory skin disorders such as psoriasis. They are also well known carcinogens. It is proposed that both the anti-inflammatory effect and part of the carcinogenic effect could occur by decreasing ground substance viscosity and suppressing fibroblasts. Streptococcal infections, chloroquine and pyridoxine deficiency increase inflammatory skin disorders and are known to be beneficial to tumor resistance. It is proposed that both effects could occur because of their effect of increasing ground substance viscosity and, at least with streptococcal infections, by stimulating fibroblasts. Within certain limits, vitamin C has a stimulant effect on fibroblast and ground substance viscosity. Beta carotene is active in stimulating wound healing. Localized edema of the dermal papillae precedes granulocytic inflammation in disorders like psoriasis. Anything that decreases ground substance viscosity will prevent dilution of tissue fluids by decreasing localized edema and thus decrease formation of some mediators of inflammation. Anything that increases ground substance and its viscosity will promote local dilution of tissue fluid. Increasing dilution of tissue fluids promotes the formation of some mediators of inflammation. Tumors commonly secrete hyaluronidase. It is proposed that substances that decrease ground substance viscosity (hyaluronidase-like activity) encourage tumors and substances that increase ground substance viscosity (anti-hyaluronidase-like effect) increase resistance to tumors.

Carcinogens↗
PubMed1986

Inflammation spurts: the role of ground substance viscosity.

A cyclical phenomenon of spurting polymorphonuclear leukocytes occurs in a number of skin diseases. The phenomenon is easy to observe because the polymorphonuclear leukocytes move into the epidermis and away from the vascular area. It is proposed that repeated spurting of polymorphonuclear leukocytes may be a broad biologic phenomenon. Edema appears essential to initiate the phenomenon by diluting the tissue fluids. The chemicals released by inflammation decrease ground substance viscosity and therefore interfere with dilution of tissue fluids. This stops the mediation of inflammation. The polymorphonuclear leukocytes also release connective tissue activating peptides which lead to increased glycosaminoglycans production and stimulate fibroblast to proliferate. The tissue activating peptides thus restore the viscosity of the ground substance and the cycle can be repeated. What we interpret as chronic inflammation could be the result of this repeated spurting phenomenon.

Humans↗
PubMed1986

Hyperinflammatory proliferative (blastomycosis-like) pyodermas: review, mechanisms, and therapy.

Some sites of chronic localized infection have a vigorous granulocytic inflammatory response and develop marked tissue proliferation. This is most common in patients with poor nutrition, halogen ingestion or foreign bodies. The granulocytes release connective tissue-activating peptides which cause fibroblast proliferation and ground substance formation. The dermal papillae enlarge and support a larger germinative cell volume, producing pseudoepitheliomatous hyperplasia. Hypertrophic granulation tissue or "proud flesh" appears to be a similar phenomenon without the epithelial component. In a milder physiologic range this phenomenon probably accounts for the term "laudable pus."

Blastomycosis↗
PubMed1985

Clubbing and koilonychia.

Although some cases of spoon nails and clubbing are manifestations of internal disease, a significant number are completely idiopathic and of no consequence to the patient. Many patients have been forced to pay high insurance premiums or have been denied employment because of insignificant nail changes. When a patient has spoon nails or clubbing, a thorough but reasonable search for a primary etiology should be made. It should be recalled that when the complete syndrome of hypertrophic osteoarthropathy is present and joint pain is prominent, the possibility of a bronchogenic carcinoma is great. If a cause of spooning or clubbing is found, it should be treated. However, when the physician becomes satisfied that no associated disorder exists, he should reassure the patient. In the author's experience koilonychia is most commonly due to psoriasis, fungus, or trauma. It is hypothesized that the curvature changes in spoon and clubbed nails are the result of angulation of the nail matrix secondary to connective tissue changes. The structural hypothesis presented here is largely based on observations of congenital and traumatic deformities. These cases have allowed visualization of the angle of the nail matrix. Both spoon nails and clubbing are such definite reaction patterns that there must be some common mechanism for each deformity. Structural rules that should apply to the nail have been used. It is easy to think of multiple internal disorders producing the same connective tissue changes that alter the angle of the nail matrix. It is difficult to think of another mechanism by which internal disease could alter the bonds in hard keratin.

Cardiovascular Diseases↗
PubMed1985

Bandage-induced nail disorders.

It can be helpful at times to bandage around fingernails but constant bandaging can produce excess maceration. Chronic paronychia can be induced by the excess wetness. Other disorders that occur because of maceration are reviewed.

Bandages↗