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Biomedical subjects

M Angeles

Publications and source records attributed to M Angeles.

9 recordsLinked to original sources

The neorule: a new instrument to measure linear growth in preterm infants.

OBJECTIVES: To compare measurements of crown-heel length (CHL) made with the neorule with CHL measurements made with a stadiometer in term infants. To examine safety and reproducibility of CHL measurements in infants < 32 weeks gestational age (GA) using the neorule. METHODS: Three measurements of CHL were made by three teams during the first 2 days of life in healthy term infants. One team used the stadiometer and two the neorule. Two different teams made three measurements of CHL on four occasions at two week intervals in infants less than 32 weeks GA. Infants were continuously monitored, and any adverse event was recorded. RESULTS: Fifty term infants were studied, median (range) birth weight 3440 (2020-5010) g. The mean (SD, 95% confidence interval) difference between values obtained with the stadiometer and neorule was 0.08 (6.22, -1.69 to +1.85) mm and between the two neorule teams was 0.8 (4.48, -0.47 to +2.08) mm. Twenty preterm infants were studied, GA median (range) 29 (25(+0)-31(+6)) weeks, median (range) CHL 397 (339-475) mm. There were no adverse events. The difference (SD, 95%CI) between teams in the mean CHL measurement was 0.18 (4.79, -1.02 to +1.38) mm, with interobserver limit of agreement -9.2 to +9.6 mm and coefficient of variation 1.2%. There were no significant differences between measurements made by single observers; the F ratio was 0.449 (df = 61, p = 0.6). CONCLUSION: The neorule is a safe and accurate way to measure CHL in newborn infants.

Analysis of Variance↗

Point mutation in kit receptor tyrosine kinase reveals essential roles for kit signaling in spermatogenesis and oogenesis without affecting other kit responses.

The Kit receptor tyrosine kinase functions in hemato- poiesis, melanogenesis and gametogenesis. Kit receptor-mediated cellular responses include proliferation, survival, adhesion, secretion and differentiation. In mast cells, Kit-mediated recruitment and activation of phosphatidylinositol 3'-kinase (PI 3-kinase) produces phosphatidylinositol 3'-phosphates, plays a critical role in mediating cell adhesion and secretion and has contributory roles in mediating cell survival and proliferation. To investigate the consequences in vivo of blocking Kit-mediated PI 3-kinase activation we have mutated the binding site for the p85 subunit of PI 3-kinase in the Kit gene, using a knock-in strategy. Mutant mice have no pigment deficiency or impairment of steady-state hematopoiesis. However, gametogenesis is affected in several ways and tissue mast cell numbers are affected differentially. While primordial germ cells during embryonic development are not affected, Kit(Y719F)/Kit(Y719F) males are sterile due to a block at the premeiotic stages in spermatogenesis. Furthermore, adult males develop Leydig cell hyperplasia. The Leydig cell hyperplasia implies a role for Kit in Leydig cell differentiation and/or steroidogenesis. In mutant females follicle development is impaired at the cuboidal stages resulting in reduced fertility. Also, adult mutant females develop ovarian cysts and ovarian tubular hyperplasia. Therefore, a block in Kit receptor-mediated PI 3-kinase signaling may be compensated for in hematopoiesis, melanogenesis and primordial germ cell development, but is critical in spermatogenesis and oogenesis.

Animals↗

A mouse homolog of the Saccharomyces cerevisiae meiotic recombination DNA transesterase Spo11p.

The Saccharomyces cerevisiae Spo11 protein is thought to catalyze formation of the DNA double-strand breaks that initiate meiotic recombination. We have cloned cDNA and genomic DNA for a mouse gene encoding a protein with significant sequence similarity to conserved domains found in proteins of the Spo11p family. This putative mouse Spo11 gene maps to the distal region of chromosome 2 (homologous to human chromosome 20q13.2-q13.3) and comprises at least 12 exons, spanning approximately 15-18 kb. Strong expression of the Spo11 message is seen in juvenile and adult testis by RNA in situ hybridization, RT-PCR, and Northern blot, with much weaker expression in thymus and brain. In situ hybridization detects expression in oocytes of embryonic ovary, but not of adult ovary. RT-PCR and in situ hybridization analyses of a time course of juvenile testis development indicate that Spo11 expression begins in early meiotic Prophase I, prior to the pachytene stage, with increasing accumulation of mRNA through the pachytene stage. Taken together, these results strongly suggest that this gene encodes the functional homolog of yeast Spo11p, which in turn suggests that the mechanism of meiotic recombination initiation is conserved between yeast and mammals.

Amino Acid Sequence↗

mRNAs for activin receptors II and IIB are expressed in mouse oocytes and in the epiblast of pregastrula and gastrula stage mouse embryos.

Activin is a potent inducer of mesoderm in frog embryos. We showed previously that in the mouse, activin beta A is expressed in the uterine decidua near the embryo before and during the first appearance of mesoderm (E4.5-E6.5). Here, using Northern blotting and in situ hybridization, we show that mouse oocytes, E6.5 and E7.5 embryos, and E6.5 and E7.5 decidua contain mRNAs for both activin receptors type II and IIB. The expression of activin receptor type IIB is particularly strong in embryonic ectoderm apparent at E5.5 and continuing through E8.5. These results support the hypothesis that activin derived from the decidua promotes development of mesoderm in the period E5.5-E6.5.

Activin Receptors↗

The expression pattern of the c-kit ligand in gonads of mice supports a role for the c-kit receptor in oocyte growth and in proliferation of spermatogonia.

The tyrosine kinase receptor c-kit and its ligand KL are required for postnatal development of germ cells, in addition to their role in primordial germ cells. To clarify their function, a detailed examination of the pattern of expression of KL in postnatal gonads was undertaken. In ovaries, the expression of KL as seen by RNA blot analysis and by RNase protection assays is relatively high at birth (P0), low from P5 to P8, and high from P12 onward. KL expression is relatively high in testes of all ages. The forms of KL RNA present in the testes suggest that from P5 onward the membrane-bound form of KL predominates, while in the ovary significant amounts of both forms are present. As observed by in situ hybridization and immunohistochemistry, in the newborn ovary KL is highly expressed in central cords whose cells contribute to the formation of central growing follicles. Expression is low in follicle cells of small growing follicles and increases to high levels in three-layered follicles during late oocyte growth. Large amounts of the ligand are found within growing oocytes. After oocyte growth ceases, expression continues only in the outer layers of multilayered follicles. In the testis, from P0 through P9, KL expression is distinct in Sertoli cells, but not in germ cells. Thereafter, the intensity of KL expression declines as the number of spermatogenic cells increases within the tubules. KL in Sertoli cells appears to be concentrated basally at the stage of the cycle of the seminiferous epithelium when it is known to interact with differentiating type A spermatogonia. These data are consistent with a role for KL in oocyte growth and in facilitating proliferation and/or differentiation of type A spermatogonia.

Aging↗

Hemangiosarcoma of the breast followed by term pregnancy.

AIMS AND BACKGROUND: Primary angiosarcoma of the breast is an unusual neoplasm which is generally associated with a dismal prognosis. Given the poor prognosis and the predominance in the third and fourth decades of life when fertility tends to decrease, reports of term pregnancies after treatment of this disease are rare. METHODS AND STUDY DESIGN: We report a case of angiosarcoma of the breast in a 17-year-old patient with a recurrent breast nodule treated by local surgery only. After three years of follow-up without evidence of disease recurrence she became pregnant. RESULTS: A girl weighing 2,430 g was delivered at 38 weeks and two days. The patient has been free of disease for five years now. CONCLUSIONS: Our experience of the present case shows the lack of full information about this tumor. Pregnancy does not seem to interfere negatively with the course of the disease.

Adolescent↗