The S100 protein family: History, function, and expression

Publisher Summary This chapter reviews the evidence for cell-mediated immune reactions against tumors in animals and man, particularly, the reactions that can lead to destruction of neoplastic cells cultivated in vitro. Various mechanisms by which tumor cells can escape from immunological destruction have been discussed, most notably one involving blocking factors, present in the serum. Findings analogous to those obtained when studying tumor immunity (coexistence of cell-mediated reactivity and blocking serum activity) have been summarized from three other areas (pregnancy, allografting, and chimeras). The studies reviewed in the chapter have given a relatively large amount of evidence for various cell-mediated and humoral immunological reactions against growing tumors, and at least some of the reactions observed in vitro appear to be able to influence tumor growth in vivo .

Lymphocyte-Mediated Cytotoxicity And Blocking Serum Activity To Tumor Antigens

The modern era of neuroendocrinology was ushered in just over a decade ago with the isolation and characterization, from ovine1 and porcine2 hypothalamic tissue, of a tripeptide (pyroglutamyl-histi...

Thyrotropin-releasing hormone

Of 300 patients who were hospitalized for acute cervical injuries, 216 lived, fifty-one died within four months of injury, and thirty-three were lost to follow-up. The important findings in a retrospective review were that laminectomy resulted in a high mortality rate and loss of motor function and that steroids did not improve neural recovery in quadriplegics and their use was associated with gastrointestinal hemorrhage. Closed or open reduction followed by posterior fusion for subluxations or dislocations, and anterior decompression and fusion for vertebral compression fractures, offered the best chance for recovery of neural function and restoration of stability. Massive epidural hemorrhage was found only in patients with ankylosing spondylitis.

Acute fractures and dislocations of the cervical spine. An analysis of three hundred hospitalized patients and review of the literature.

✓ Spinal cord injury in children often occurs without evidence of fracture or dislocation. The mechanisms of neural damage in this syndrome of spinal cord injury without radiographic abnormality (SCIWORA) include flexion, hyperextension, longitudinal distraction, and ischemia. Inherent elasticity of the vertebral column in infants and young children, among other age-related anatomical peculiarities, render the pediatric spine exceedingly vulnerable to deforming forces. The neurological lesions encountered in this syndrome include a high incidence of complete and severe partial cord lesions. Children younger than 8 years old sustain more serious neurological damage and suffer a larger number of upper cervical cord lesions than children aged over 8 years. Of the children with SCIWORA, 52% have delayed onset of paralysis up to 4 days after injury, and most of these children recall transient paresthesia, numbness, or subjective paralysis. Management includes tomography and flexion-extension films to rule out ...

Spinal cord injury without radiographic abnormalities in children

We describe the trajectory of the human sex ratio from conception to birth by analyzing data from (i) 3- to 6-d-old embryos, (ii) induced abortions, (iii) chorionic villus sampling, (iv) amniocentesis, and (v) fetal deaths and live births. Our dataset is the most comprehensive and largest ever assembled to estimate the sex ratio at conception and the sex ratio trajectory and is the first, to our knowledge, to include all of these types of data. Our estimate of the sex ratio at conception is 0.5 (proportion male), which contradicts the common claim that the sex ratio at conception is male-biased. The sex ratio among abnormal embryos is male-biased, and the sex ratio among normal embryos is female-biased. These biases are associated with the abnormal/normal state of the sex chromosomes and of chromosomes 15 and 17. The sex ratio may decrease in the first week or so after conception (due to excess male mortality); it then increases for at least 10–15 wk (due to excess female mortality), levels off after ∼20 wk, and declines slowly from 28 to 35 wk (due to excess male mortality). Total female mortality during pregnancy exceeds total male mortality. The unbiased sex ratio at conception, the increase in the sex ratio during the first trimester, and total mortality during pregnancy being greater for females are fundamental insights into early human development.

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The human sex ratio from conception to birth

Letter: Prenatal diagnosis.

—The concentration of a protein specific to brain, the S-100 protein, was measured in various regions of the human foetal brain at gestational ages ranging from 10 weeks until term. The relative increase in concentrations of the S-100 protein during development of the human foetal brain proceeded in a caudal-rostral fashion. This observation is emphasized by the delayed appearance of the S-100 protein in the frontal cerebral cortex until the 30th week of gestation.

Appearance of a brain specific antigen (th S-100 protein) during human foetal development.

Suckling elevated serum prolactin but had no effect on circulating thyrotropin, tri-iodothyronine and thyroxine in seven post-partum women. Injections of 6 and 300 μg of thyrotropin-releasing hormone raised serum concentrations of both prolactin and thyrotropin, but not of tri-iodothyronine and thyroxine. One or 2 μg of thyrotropin-releasing hormone had no effect on either prolactin or thyrotropin, although in three subjects, 6 μg caused similar relative increases in both serum prolactin and thyrotropin. Lactotrophs and thyrotrophs in the post-partum pituitary gland appear to be similarly responsive to exogenous thyrotropin-releasing hormone, and the failure to observe thyrotropin release with suckling is not due to blockade of the response of thyrotrophs by high levels of circulating thyroid hormones. The selective increase in serum prolactin induced by suckling, therefore, is not caused solely by release of endogenous thyrotropin-releasing hormone. (N Engl J Med 290:1162–1165, 1974)

Thyrotropin-releasing hormone is not the sole physiologic mediator of prolactin release during suckling.

ALTHOUGH the infant possesses histocompatibility antigens which differ significantly from those of the mother, the foetal allograft manages to survive the period of gestation without being rejected. To explain this apparent paradox of transplantation immunology, Medawar in 1953 advanced several hypotheses1. These included (1) that the uterus may be an immunologically privileged site; (2) that the foetal antigens are weakly expressed; (3) that there may be an anatomical barrier separating the maternal and foetal circulations, and (4) that pregnancy may be accompanied by some reduction in the immunological capacity of the mother. We have attempted to evaluate one aspect of this problem using an in vitro correlate of cellular hypersensitivity to study the immunological response of the mother's lymphocytes to those of her infant. This technique, the macrophage migration inhibition assay2, measures the elaboration of a soluble material, migration inhibitory factor (MIF), from sensitized lymphocytes after stimulation by specific antigen3,4. Previous work with mice has shown that when peritoneal exudate cells from two genetically different strains were mixed together for 24 h their migration was not inhibited, that is, no MIF was generated, unless one strain had been previously sensitized to the other5. In these conditions, the assay appeared to be measuring a cellular immune response indicating prior sensitization. This is in contrast to the response observed in the standard mixed lymphocyte reaction which measures at 5 days the incorporation of 3H-thymidine into lymphocyte DNA. The latter response records an event of primary sensitization between lymphocytes of individuals with different histocompatibility antigens.

James E. Zuckerman

Papers

The human sex ratio from conception to birth

Letter: Prenatal diagnosis.

Appearance of a brain specific antigen (th S-100 protein) during human foetal development.

Thyrotropin-releasing hormone is not the sole physiologic mediator of prolactin release during suckling.

Effect of Multiparity on Human Maternal Hypersensitivity to Foetal Antigen