Publisher Summary The classification of cell death can be based on morphological or biochemical criteria or on the circumstances of its occurrence. Currently, irreversible structural alteration provides the only unequivocal evidence of death; biochemical indicators of cell death that are universally applicable have to be precisely defined and studies of cell function or of reproductive capacity do not necessarily differentiate between death and dormant states from which recovery may be possible. It has also proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances. One of these patterns is the swelling proceeding to rupture of plasma and organelle membranes and dissolution of organized structure—termed “coagulative necrosis.” It results from injury by agents, such as toxins and ischemia, affects cells in groups rather than singly, and evokes exudative inflammation when it develops in vivo. The other morphological pattern is characterized by condensation of the cell with maintenance of organelle integrity and the formation of surface protuberances that separate as membrane-bounded globules; in tissues, these are phagocytosed and digested by resident cells, there being no associated inflammation.

Cell death : the significance of apoptosis

Publisher Summary This chapter explores that the changes that take place in the protein molecules during denaturation constitute one of the most interesting and complex classes of reactions that can be found either in nature or in the laboratory These reactions are important because of the information they can provide about the more intimate details of protein structure and function They are also significant because they challenge the chemist with a difficult area for the application of chemical principles The chapter reviews that the denaturation is a process in which the spatial arrangement of the polypeptide chains within the molecule is changed from that typical of the native protein to a more disordered arrangement The chapter also discusses the classification of protein structures: primary, secondary, and tertiary structures The primary structure is that expressed by the structural chemical formula and depends entirely on the chemical valence bonds that the classical organic chemist would write down for the protein molecule The secondary structure is the configuration of the polypeptide chain that results from the satisfaction of the hydrogen bonding potential between the peptide N-H and C=O groups The tertiary structure is the pattern according to which the secondary structures are packed together within the native protein molecule The term “denaturation” as used in this chapter is indented to include changes in both the secondary and tertiary structures

Some factors in the interpretation of protein denaturation.

The rat estrogen receptor (ER) exists as two subtypes, ER alpha and ER beta, which differ in the C-terminal ligand binding domain and in the N-terminal transactivation domain. In this study we investigated the messenger RNA expression of both ER subtypes in rat tissues by RT-PCR and compared the ligand binding specificity of the ER subtypes. Saturation ligand binding analysis of in vitro synthesized human ER alpha and rat ER beta protein revealed a single binding component for 16 alpha-iodo-17 beta-estradiol with high affinity [dissociation constant (Kd) = 0.1 nM for ER alpha protein and 0.4 nM for ER beta protein]. Most estrogenic substances or estrogenic antagonists compete with 16 alpha-[125I]iodo-17 beta-estradiol for binding to both ER subtypes in a very similar preference and degree; that is, diethylstilbestrol > hexestrol > dienestrol > 4-OH-tamoxifen > 17 beta-estradiol > coumestrol, ICI-164384 > estrone, 17 alpha-estradiol > nafoxidine, moxestrol > clomifene > estriol, 4-OH-estradiol > tamoxifen, 2-OH-estradiol, 5-androstene-3 beta, 17 beta-diol, genistein for the ER alpha protein and dienestrol > 4-OH-tamoxifen > diethylstilbestrol > hexestrol > coumestrol, ICI-164384 > 17 beta-estradiol > estrone, genistein > estriol > nafoxidine, 5-androstene-3 beta, 17 beta-diol > 17 alpha-estradiol, clomifene, 2-OH-estradiol > 4-OH-estradiol, tamoxifen, moxestrol for the ER beta protein. The rat tissue distribution and/or the relative level of ER alpha and ER beta expression seems to be quite different, i.e. moderate to high expression in uterus, testis, pituitary, ovary, kidney, epididymis, and adrenal for ER alpha and prostate, ovary, lung, bladder, brain, uterus, and testis for ER beta. The described differences between the ER subtypes in relative ligand binding affinity and tissue distribution could contribute to the selective action of ER agonists and antagonists in different tissues.

Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta

Protein extracts derived from bone can initiate the process that begins with cartilage formation and ends in de novo bone formation. The critical components of this extract, termed bone morphogenetic protein (BMP), that direct cartilage and bone formation as well as the constitutive elements supplied by the animal during this process have long remained unclear. Amino acid sequence has been derived from a highly purified preparation of BMP from bovine bone. Now, human complementary DNA clones corresponding to three polypeptides present in this BMP preparation have been isolated, and expression of the recombinant human proteins have been obtained. Each of the three (BMP-1, BMP-2A, and BMP-3) appears to be independently capable of inducing the formation of cartilage in vivo. Two of the encoded proteins (BMP-2A and BMP-3) are new members of the TGF-beta supergene family, while the third, BMP-1, appears to be a novel regulatory molecule.

https://science.sciencemag.org/content/sci/242/4885/1528.full.pdf

Novel regulators of bone formation: molecular clones and activities.

Thereisgrowinginterestinthepossiblehealththreatposedbyendocrine-disruptingchemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor , retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness. (Endocrine Reviews 30: 293–342, 2009)

/pdf/endocrine-disrupting-chemicals-an-endocrine-society-3fgbtp8gql.pdf

Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

Introduction "The whole problem in cases of resection of the liver has turned upon the question of the control of hemorrhage from the wound." 1 Oozing from the cut liver surface results in considerable blood loss and obscures the operative field, making identification and control of bleeding from major vessels difficult. Various techniques of mass hemostasis have been developed to cope with this problem; through-and-through mattress sutures, with or without compression plates, 1,2 cautery, 3 exteriorization and gradual removal of peripheral hepatic lesions. 4 Although success has been reported with these methods, they have the following disadvantages: (1) deliberate resection with definitive hemostasis and control of biliary leakage is not permitted; (2) devitalized tissue is left within the abdomen, and (3) the techniques are suitable only for small peripheral lesions. Preliminary isolation and ligation of vessels supplying and draining the right or left lobe before hepatic lobectomy has been described

Differential hypothermia in experimental hepatic surgery; application of this technique to a problem in clinical surgery.

Hormone-dependent stem-cell rat leukemia evoked by a series of feedings of 7,12-dimethylbenz(a)anthracene.

Proteolytic Enzymes and Acid Phosphatase in Theprostatic Fluid in Chronic Prostatitis12

A standard series of five intravenous injections of N-nitroso-N-methylurea (NMU) elicited selective patterns of neoplasms in male rats of the Sprague-Dawley strain; the neoplastic pattern was related to the age of the recipients. When the injections of NMU were started in weanling male rats, a specific triad of neoplasms developed that consisted of mammary carcinoma, primary myelocytic leukemia, and ear duct cancer. When the injections of NMU were started in males at age 100 days, a specific dyad of neoplastic growths was evoked that consisted of primary myelocytic leukemia and ear duct cancer, whereas mammary cancer and other neoplasms were not evident. Secondary myelocytic leukemia and myelocytic sarcoma were produced when blood from the foregoing rats with advanced primary myelocytic leukemia was injected in a subcutaneous site in newborn allogeneic rats. In a proportion of animals, primary and secondary myelocytic leukemia and myelocytic sarcoma underwent dramatic and continued regression after hypophysectomy.

https://www.jstor.org/stable/pdfplus/22732.pdf

Regression of myelocytic leukemia in rats after hypophysectomy.

Determination of the water and electrolyte concentrations of tumors of the testis in dogs, and of the normal tissue of origin, was the objective of this study. Testicular tumors had not been studied chemically previous to this work. Since testicular neoplasms are of diverse histological patterns these data were compared with similar analyses of testes from which the germinal epithelium had been eliminated by physiological means, namely, by artificial cryptorchism or by administration of estrogen. The electrolyte content of tumors has been extensively studied, but many of the older observations are unsatisfactory because of the methods of analysis used, particularly for sodium and potassium. All the articles describe a search for distinct electrolyte patterns that might characterize malignant disease but this paper will demonstrate that no such generalization is feasible in the case of the principal electrolytes, chloride, sodium, and potassium. The tissue analyses that have been reported by other workers are as follows: Electrolytes o[ tumors.--The older data have been presented in a critical review by Shear (25); a complete survey of that literature therefore is not within the scope of this paper. Water.--The water content has generally been found increased in cancers. In the Jensen rat sarcoma it was stated to vary from 824 gin. 1 in young tumors to 867 gin. in older ones (13), and to average 750 gin. (24). In the Twort mouse carcinoma the water content was 788 to 791 gm. (11), and in a paper on various human and animal cancers values of 660 to 880 gm. (20) were recorded. Minerals.--Two articles report that the mineral content of tumors is increased over the tissue of origin (22, 23). Potassium. Previous communications are in general agreement concerning an increased potassium content of tumors, which was referred to the high cell content. Beebe (2) was the first to report increased

Charles Huggins

Papers

Differential hypothermia in experimental hepatic surgery; application of this technique to a problem in clinical surgery.

Hormone-dependent stem-cell rat leukemia evoked by a series of feedings of 7,12-dimethylbenz(a)anthracene.

Proteolytic Enzymes and Acid Phosphatase in Theprostatic Fluid in Chronic Prostatitis12

Regression of myelocytic leukemia in rats after hypophysectomy.

Studies on Tumors of the Testis. I. Water and Electrolyte Content of Testicular Tumors and of Normal, Cryptorchid, and Estrogenized Testis