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Biomedical subjects

P Nathan

Publications and source records attributed to P Nathan.

17 recordsLinked to original sources
PubMed1979

Rat thymic dihydrotestosterone receptor: preparation, location and physiochemical properties.

Castration in the male rat has been shown to produce enlargement of the thymus gland while treatment with dihydrotestosterone (DHT) results in a decrease in thymic size in these animals. To determine if these changes might be receptor mediated, thymus tissue from castrate male rats was removed and homogenized in buffer and centrifuged to produce cytosol. By Scatchard plot analysis, it was shown that a specific DHT receptor was present at a concentration of 0.24 +/- 0.02 pmoles/g tissue and it possessed a KA of 2.51 +/- 0.45 x 10(9)M-1. This thymic DHT receptor sedimented on 5--20% sucrose gradients in the 8s region. By competition analysis it was found that testosterone only partially competed (25%) for this receptor, with virtually no binding noted for estradiol, progesterone, and cortisol. The receptor was found to be localized in the reticuloepithelial matrix of the thymus and was not present in the thymic lymphocyte fraction.

Animals↗
PubMed1979

A micromethod for prospectively testing lymphocyte-mediated cytotoxicity (LMC) using fresh or frozen cells labelled with a fluorescent dye.

A direct, specific and rapid method has been developed to prospectively evaluate lymphocyte mediated cytotoxicity (LMC) for kidney transplant recipients. Donor lymphocytes, labeled with fluorescein diacetate, were incubated in a microtest plate for 2 h with recipients' effector cells. The percentage of fluorescent cells in each well was estimated relative to controls using an inverted phase fluorescence microscope. Lymphocytes obtained from seven of 12 recipients post-transplantation exhibited positive reactions, fluorescence of labeled donor cells was reduced to 30-65% of that observed in controls, and these reactive patients required nephrectomies. The responses of the remaining five patients were negative. Tests with their donor cells showed 80-95% control fluorescence, with favorable transplant results. Six of 21 recipients evaluated prospectively required nephrectomies within 34 days post-transplantation. Three of these subjects showed 15-65% control fluorescence, a positive LMC response; the other three yielded negative LMC responses but required nephrectomies possibly due to renal ischemia prior to transplantation. The remaining 15 patients demonstrated 85-90% control fluorescence with graft function continuing for 17 to 270 days. The results from direct LMC tests with a fluorescent label indicate that the system is of value in predicting early rejection of renal allotransplants.

Cytotoxicity Tests, Immunologic↗
PubMed1979

Immune adherence of platelets to sensitized leukocytes: a model of hyperacute rejection.

Specifically hypersensitized recipients of canine renal allotransplants demonstrate an accumulation of host platelets in the transplanted kidney within minutes following implantation. Transplant function is ra,idly lost. The present work describes an in vitro model of this hyperacute rejection mechanism. Renal donor leukocytes sensitized with host serum are incubated with donor platelets. Within a few minutes the platelets adhere to the sensitized leukocytes to form rosettes. Serum complement is required for platelet rosette formation. Platelets act as indicators in this reaction and they may be obtained from any dog. Donor platelets were used to avoid the transfer of specific antibody to the test mixture. The in vitro model supports the view that hyperacute rejection in the dog is a specific example of the immune adherence reaction in which platelets bind to antigen-antibody-complement complexes.

Animals↗
PubMed1978

Effect of exposure to lead on maturation of intestinal iron absorption of rats.

The influence of lead on iron absorption was investigated at various stages of development in rat pups exposed to lead first through mothers' milk and later in their solid diet. Hematocrit, hemoglobin, iron absorption, and tissue iron concentration were measured on d 14, 20, 23, 29, 35, 42, and 63 after birth. Both hematocrit and hemoglobin in the lead-exposed group were significantly below control levels at all periods earlier than d 42 and 63, respectively. Absorption of iron ([59Fe]-ferrous citrate in 10(-4)M FeSO4) from intestinal loops measured over 1/2 h remained at preweaning levels (10-12% of total activity added to the loop) for at least 1 wk after weaning in the lead-exposed rats, whereas in control animals iron absorption fell to adult levels (3-4%) at weaning. Spleen weight was significantly elevated in lead-exposed rats compared with control rats at all ages beyond d 14. However, spleen iron content (micrograms of Fe per gram of tissue) was not significantly elevated in the lead-exposed group before d 42. The results indicate that exposure to lead does not reduce iron absorption from the intestinal tract; thus alteration of intestinal iron absorption does not contribute to lead-induced anemia. Indeed, lead-exposed rats demonstrated increased iron uptake.

Aging↗
PubMed1977

The use of pooled sera for HLA cytotoxicity crossmatching.

A two-stage procedure is described for cytotoxicity tests in which three different sera from a prospective kidney recipient are pooled in each well of a standard microcytotoxicity test plate. The results are reproducible and as sensitive as those obtained with single sera tests. The technique permits a reduction in time required for a test and the number of wells that must be evaluated to screen a series of sera. It enables a laboratory to run all available sera on patients for cadaver kidney crossmatching and to eliminate hyperacute rejections. Serum pooling may also be used for screening of many sera against random cell panels.

Cytotoxicity Tests, Immunologic↗
PubMed1976

The effect of a collagen dressing on contaminated surgical wounds in rats.

In maintaining the rat, the collagen dressings, Aviderm Amine and Aviderm, are as effective as skin in low bacterial levels in contaminated surgical wounds. In the scald-burn wound in the rat the effect of skin dressing is confirmed. Also, 48 h after collagen dressing in the wound the bacterial contamination was the same as that seen under autograft dressings. We have elsewhere suggested that skin and some other dressings modify the local host defense by their effect on the accumulated white blood cells. We believe that collagen, as well as some synthetics, can alter the local environment permitting the destruction of invading bacteria by the accumulated white blood cells.

Animals↗
PubMed1976

Proteolytic enzyme activity in the granulation tissue of the human burn wound.

A procedure for adsorbing enzymes from the human burn wound onto solid sheets of substrate is described. Using this technique, low levels of enzyme activity with chymotrypsin-like specificity can be demonstrated in the wound approximately 2 weeks after injury. This activity disappears at about 5 weeks after the burn. The enzyme activity corresponds with the clinical experience for the time course of natural loss of the burn eschar. A trypsin-like enzyme of very low level activity is present in the wound. No collagenase was detected in the human burn wound. Preliminary evidence shows an additional leucine-specific enzyme in the human burn wound. A more detailed analysis of enzymes in the human burn wound should permit the development of a useful artificial debriding agent. Presently these preparations must be used with caution.

Adolescent↗
PubMed1976

Burn wounds: selection and preservation of skin, natural products, blood, and blood products for burn therapy.

Skin allografts and xenografts are routinely used as dressings to control infection, pain and fluid loss from the burn wound. The procedure for preparing and storing grafts will be reviewed and suggested indications for use will be considered. A method for preparing porcine xenograft will be discussed in some detail. Skin banking by low temperature preservation including conditions and processing necessary for obtaining viable grafts will be discussed. The use of tissue typing matching procedures for obtaining prolonged survival will be considered. Possible harmful effects of grafts will be reviewed. The use of blood and blood products for resuscitation of burn patients is of primary importance in burn patients. The literature will be reviewed concerning a variety of blood and blood products including a consideration of washed cells, single donoplasma, serum albumin and purified blood components for treatment of burned patients. The use and indications for hyper-immune serum and gammu-globulin will be considered. Coagulopathy syndromes, burn wound sepsis, and support of immunologically deficient patients will be discussed on the basis of current literature.

Adolescent↗
PubMed1976

A new biomaterial for the control of infection in the burn wound.

A synthetic dressing has been developed that isolates the burn wound to protect patients from microbial contamination. This dressing is unique as it is formed from a 2-component system directly on the wound, leaving no voids for microbial proliferation. The synthetic cover, HYDRON Burn Dressing, adheres to the entire wound surface so that additional dressings are not required. It is sufficiently flexible to permit patient mobility. The components used to form the dressing are an ultra-pure, high molecular weight form of HYDRON, a hydrophilic polymer, poly (2-hydroxyethyl methacrylate) and Polethylene Glycol-400. The dressing is intended to be applied directly to the wound immediately post-burn, prior to sloughing or removal of the eschar, a period in the burn therapy regimen for which satisfactory alternative dressings are not readily available. Decreased frequency of dressing changes compared to conventional procedure provides an additional benefit with a corresponding reduction in pain to the patient. Gross examination of the wounds under the dressing has shown that the healing process proceeds similarly to that of wounds under conventional treatment. There is no evidence of fluid accumulation or maceration or desiccation of the eschar. In our series of 32 patients the barrier dressing formed on the wound has offered a new, effective procedure for treatment of the burn wound.

Acrylic Resins↗
PubMed1975

In situ production of a synthetic barrier dressing for burn wounds in rats.

We describe the in situ production of a burn wound dressing applied to eschar that completely isolates burned tissue from contamination with Pseudomonas aeruginosa. Anesthetized, adult rats were subjected to a scald burn over 10% of their body surfaces. One-half hour later a test dressing presumed to be a barrier to bacterial contamination of the wound was applied to the burned surface. Tannic acid, vaseline, ethyl linoleate, collodion, and polyhydroxethylmethacrylate (PHEMA) were evaluated. Each agent was applied directly to the burned surface. A solid film of the PHEMA was produced on the eschar by addition of solvent and a powdered form of the polymer. The surface of each synthetic dressing was contaminated 30 min after application by the addition of 10(8) P. aeruginosa. Also, a control set of rats was burned and their eschars were directly contaminated without application of the test dressing. Seven days later the contaminated muscle under the burned area in 10 control rats had P. aeruginosa counts of 10(7) to 10(8) per g of muscle (wet weight). Of the materials tested, only PHEMA consistently acted as an effective barrier dressing, reducing bacteria in the muscle to undetectable levels in 11 of 14 tests. It was also possible to treat contaminated eschar through this synthetic dressing by topical application of antibiotics to the barrier surface. The results suggest a novel clinical approach in which a barrier dressing could be used to isolate a burn eschar from environmental and subject contamination until the wound site is ready for grafting.

Acrylic Resins↗
PubMedDate not supplied

The correlation of kidney transplant survival with lymphocyte mediated cytotoxicity on B cell targets.

A LMC micromethod using specific B lymphocyte target cells labeled with a fluorescent dye has been developed to select matched donors and recipients for kidney allotransplantation. The fluorescence of the B lymphocyte target cells was 85% or less of control levels in 9 of 28 patients. In 8 of these 9 hosts graft loss occurred. Nineteen sets of target cells showed 90-95% of control fluorescence. Only 5 of these recipients lost their transplants (p less than 0.01). The fluorescent LMC test correlates with successful renal transplant outcome when the target cells are purified B cells.

Antigen-Antibody Reactions↗