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

Conclusion 1. Four protein fractions were observed in 4 normal and one pathological semen specimens subjected to electrophoretic analysis. 2. The electrophoretic mobilities of these protein fractions after dialysis are identical with those of the albumin, alpha, beta, and gamma globulins of normal serum. 3. Average values for these components as percentages of the total nondialyzable semen protein are: beta globulin, 39.6; alpha globulin, 21.3; albumin, 19.9; and gamma globulin, 19.1. 4. The protein composition of the one pathological semen studied did not differ from the 4 normal semens.

http://ebm.sagepub.com/content/50/2/351.full.pdf

Electrophoretic Analysis of Human Semen.

THE PRESENT INVESTIGATION WAS CONDUCTED to determine, a) the normal values for urinary acid phosphatase in men, women and children; h) the site of origin of urinary phosphatase; and c) the influence of altered physiological states on urinary phosphatase excretion. That the urine of humans contains an enzyme capable of splitting organic phosphates has been demonstrated by Demuth (1) and others (2, 3, 4). These authors agree that optimal phosphate splitting in urine occurs in an acid medium close to a pH of 5. Kutscher (4) found an alkaline phosphatase present at plasma level in the urine. Considerable controversy exists, however, as to the site of formation of urinary phosphatase, its levels of excretion and sex differences in excretion levels. WaldschmidtLeitz and Nonnenbruch (2) found a phosphatase present in urine with an optimum pH range of 5 to 6 and in concentrations much stronger than in serum. They believed

The acid phosphatase activity of human urine, an index of prostatic secretion11

In adult mammals and birds there is a great quantitative difference in the reticulo-endothelial system content of the bone marrow of central bones as compared with distal outlying bones. Experimental procedures reported in the accompanying communication effecting development and increase of hemopoiesis in inactive yellow marrow also effect a reticulo-endothelial cell increase.

/pdf/an-increase-in-reticulo-endothelial-cells-in-outlying-bone-qwr9utmw8c.pdf

An increase in reticulo-endothelial cells in outlying bone marrow consequent upon a local increase in temperature

A set of intraveous injections of 7,8,12-trimethylbenz[a]anthracene consistently elicited leukemia in more than 75% of young adult Long-Evans female rats. There was a profound reduction in the incidence of leukemia in companion groups of rats fed small amounts (1--10 mg) of Sudan III or Sudan IV prior to each injection of the carcinogenic hydrocarbon. Repeated feedings of 1 mg of Sudan III induced cumulative increases in the concentration of menadione reductase (EC 1.6.99.2) in liver, whereas protein concentration was unchanged. A single feeding of 1 mg of Sudan III prevented fatal toxicity in all members of large groups of rats injected with massive doses of 7,12-dimethylbenz[a]anthracene, but 50% of the survivors developed leukemia; unprotected rats succumbed in 1--3 days. Sudan III was not carcinogenic under the experimental conditions.

Azo dyes prevent hydrocarbon-induced leukemia in the rat

1. Factors contributing to the variability in growth rate of a transplantable tumor have been analyzed.

2. The Walker tumor was selected because it presents a malignant growth, to which there is 96 per cent susceptibility in either sex of albino rats of the Sprague-Dawley strain. Regressions are extremely rare, and the growth rate is reliable, reproducible, and rapid.

3. The most important factor contributing to variations in growth rate is the site of implantation. Subcutaneous implants show a large variability in size, depending upon whether the tumor becomes vascularized from muscle or skin. Uniform symmetrical growths may be obtained by resorting to bilateral intramuscular implantation into the flexor muscles of the thighs.

4. The growth rate of the tumor is not significantly affected by relatively large changes in the size of the inoculum.

5. In weaned rats, the size and sex of the animal do not influence the growth of the tumor but the carcass weight is greatly affected by the growth phase of the host animal.

Charles Huggins

Papers

Electrophoretic Analysis of Human Semen.

The acid phosphatase activity of human urine, an index of prostatic secretion11

An increase in reticulo-endothelial cells in outlying bone marrow consequent upon a local increase in temperature

Azo dyes prevent hydrocarbon-induced leukemia in the rat

Studies on the Walker Tumor I. Standardization of the Growth of a Transplantable Tumor