The whn transcription factor encoded by the nude locus contains an evolutionarily conserved and functionally indispensable activation domain.

Mutations in the whn gene are associated with the phenotype of congenital athymia and hairlessness in mouse and rat. The whn gene encodes a presumptive transcription factor with a DNA binding domain of the forkhead/ winged-helix class. Two previously described null alleles encode truncated whn proteins lacking the characteristic DNA binding domain. In the rat rnu allele described here, a nonsense mutation in exon 8 of the whn gene was identified. The truncated whnrnu protein contains the DNA binding domain but lacks the 175 C-terminal amino acids of the wild-type protein. To facilitate the identification of functionally important regions in this region, a whn homolog from the pufferfish Fugu rubripes was isolated. Comparison of derived protein sequences with the mouse whn gene revealed the presence of a conserved acidic protein domain in the C terminus, in addition to the highly conserved DNA binding domain. Using fusions with a heterologous DNA binding domain, a strong transcriptional activation domain was localized to the C-terminal cluster of acidic amino acids. As the whnrnu mutant protein lacks this domain, our results indicate that a transactivation function is essential for the activity of the whn transcription factor.

Prolactin increases CD4/CD8 cell ratio in thymus-grafted congenitally athymic nude mice.

One distinctive effect on T-cell development was analyzed by selectively increasing serum prolactin (PRL) concentration in thymus-grafted congenitally athymic nude mice and by neutralizing PRL in suspension cultures of thymus from 1-day-old neonatal mice. Flow cytometric analysis of single-positive CD4+ and CD8+ cells derived from inguinal lymph nodes revealed a CD4/CD8 cell ratio of 2.2 +/- 0.18 (mean +/- SEM) in thymus-grafted nude mice that is similar to the ratio for immune-competent BALB/c mice (2.0 +/- 0.06). Addition of the pituitary to thymus-grafted nude mice significantly elevated serum PRL (P < 0.005) and increased the CD4/CD8 cell ratio (2.8 +/- 0.12; P < 0.005), demonstrating preferential stimulation of CD4+ cell development. T cells in nude mice receiving sham (submandibular salivary gland) or pituitary grafts alone were below detectable levels. Suspension cultures of neonatal thymus treated with anti-mouse PRL antiserum resulted in 20% and 30% decreases in double-positive CD4+8+ thymocytes and thymocyte viability, respectively. A 10-fold increase in double-negative CD4-8- thymocytes expressing the interleukin 2 receptor alpha chain, CD25, was also observed concurrently. Our findings illustrate an important way in which PRL may participate in two interrelated mechanisms: the regulation of peripheral single-positive cells and the maintenance of thymocyte viability during the double-positive stage of intrathymic differentiation.

Delivery of herpesvirus and adenovirus to nude rat intracerebral tumors after osmotic blood-brain barrier disruption.

The delivery of viral vectors to the brain for treatment of intracerebral tumors is most commonly accomplished by stereotaxic inoculation directly into the tumor. However, the small volume of distribution by inoculation may limit the efficacy of viral therapy of large or disseminated tumors. We have investigated mechanisms to increase vector delivery to intracerebral xenografts of human LX-1 small-cell lung carcinoma tumors in the nude rat. The distribution of Escherichia coli lacZ transgene expression from primary viral infection was assessed after delivery of recombinant virus by intratumor inoculation or intracarotid infusion with or without osmotic disruption of the blood-brain barrier (BBB). These studies used replication-compromised herpes simplex virus type 1 (HSV; vector RH105) and replication-defective adenovirus (AdRSVlacZ), which represent two of the most commonly proposed viral vectors for tumor therapy. Transvascular delivery of both viruses to intracerebral tumor was demonstrated when administered intraarterially (i.a.) after osmotic BBB disruption (n = 9 for adenovirus; n = 7 for HSV), while no virus infection was apparent after i.a. administration without BBB modification (n = 8 for adenovirus; n = 4 for HSV). The thymidine kinase-negative HSV vector infected clumps of tumor cells as a result of its ability to replicate selectively in dividing cells. Osmotic BBB disruption in combination with i.a. administration of viral vectors may offer a method of global delivery to treat disseminated brain tumors.

Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts

Tagging of RNases, such as the ribotoxin α-sarcin, with the variable domains of antibodies directed to surface antigens that are selectively expressed on tumor cells endows cellular specificity to their cytotoxic action. A recombinant single-chain immunotoxin based on the ribotoxin α-sarcin (IMTXA33αS), produced in the generally regarded as safe (GRAS) yeast Pichia pastoris, has been recently described as a promising candidate for the treatment of colorectal cancer cells expressing the glycoprotein A33 (GPA33) antigen, due to its high specific and effective cytotoxic effect on in vitro assays against targeted cells. Here we report the in vivo antitumor effectiveness of this immunotoxin on nude mice bearing GPA33-positive human colon cancer xenografts. Two sets of independent assays were performed, including three experimental groups: control (PBS) and treatment with two different doses of immunotoxin (50 or 100 μg/ injection) (n = 8). Intraperitoneal administration of IMTXA33αS resulted in significant dose-dependent tumor growth inhibition. In addition, the remaining tumors excised from immunotoxin-treated mice showed absence of the GPA33 antigen and a clear inhibition of angiogenesis and proliferative capacity. No signs of immunotoxin-induced pathological changes were observed from specimens tissues.Overall these results show efficient and selective cytotoxic action on tumor xenografts, combined with the lack of severe side effects, suggesting that IMTXA33αS is a potential therapeutic agent against colorectal cancer.

The presence of a woman : images of La Malinche in el Lienzo de Tlaxcala

La Malinche’s serene face and beautifully dressed figure dominates the first half of the lost sixteenth century manuscript El Lienzo de Tlaxcala, which exists today in the form of a copy made after the original. In this paper I propose an expanded study of these twenty-one representations of La Malinche as they offer insight into the Tlaxcalan’s reverence, respect, and spiritual belief in La Malinche. The Tlaxcalan leaders recognized her influence on both the Spanish and indigenous leaders during the conquest and cleverly designed a painted narrative to reinforce their connection with La Malinche to enhance their position with the Spanish. Through a multi layered study that consists of a detailed account of her biography in contrast to gender roles in Pre-Hispanic America, as well as formal and iconographic analysis of rarely examined images from the Lienzo de Tlaxcala that link La Malinche to the Virgin Mary, and a review of the ethnographic research on religious beliefs among contemporary Tlaxcalans, I will demonstrate that the mutable history of this woman made her the ideal supernatural protagonist for the people of Tlaxcala.

Overexploitation, malnutrition and stigma in a woman's illness: chlorosis in contemporary Spanish medicine (1877-1936)

The work was financed by the Project: 'Antecedentes históricos de la nutrición comunitaria en España: los primeros intentos de institucionalización, 1923-1947' (HUM2005-04961-C03-01).

“I'm not the woman I was”: Women´s perceptions on the effects of fibromyalgia on private life

In this qualitative study we explored how gender shapes the women´s experiences of living with Fibromyalgia and how it affects their private lives. Through thematic analysis of data from 13 in-depth interviews in Spain, we identified 7 themes which reflect that these women feel remorse and frustration for not being able to continue to fulfil the gender expectation of caring for others and for the home. This research contributes to a better understanding into what suffering from fibromyalgia implies for women and provides insights into how family and providers can support women with fibromyalgia in order to achieve a beneficial lifestyle.

The woman who toils: being the experiences of two gentlewomen as factory girls

by Mrs. John Van Vorst and Marie Van Vorst.

The college, the market, and the court, or, Woman's relation to education, labor, and law

by Caroline H. Dall.

Letters of a business woman to her daughter, and, Letters of a business girl to her mother

by Zora Putnam Wilkins.

A new day for the colored woman worker: a study of colored women in industry in New York City

Joint Committee to Study the Employment of Colored Women in New York City and Brooklyn.

Photograph of an older woman, ca. 1880-1890

Cabinet card featuring a portrait of an unidentified older woman. "Weiss RW 1314 Bushwick Ave., Brooklyn N.Y." The back of the card has a printed inscription with the photographer, R. Weiss's business information.