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J Karl

Publications and source records attributed to J Karl.

6 recordsLinked to original sources

Three-dimensional structure of the developing mouse genital ridge.

We are interested in understanding how the field of cells which forms the gonad arises, and how the testis-determining gene, Sry, controls morphogenesis of a testis within this field of cells. To appreciate changes in the three-dimensional structure of the mouse genital ridge at this time in development, whole-mount genital ridges taken from male and female embryos over the developmental period when the initiation of testis cord morphogenesis takes place, were stained with an antibody against laminin. Samples were visualized using confocal microscopy. Anti-laminin illuminates the elaborate array of mesonephric duct and tubules which occupy the cranial two-thirds of the mesonephros at the earliest timepoint. This complex structure gradually regresses as testis cords form in male gonads. No structural organisation is recognized by this antibody in the female gonadal region during this period. Confocal sections in the Z-plane reveal continuous cellular connections between 3-6 mesonephric tubules and the gonadal primordium. These cellular bridges are present in male and female gonads, so they do not depend on the expression of Sry. We consider the possibility that these bridges constitute the pathways of the founder cells of the gonadal primordium.

Animals

Reduction of the estrogenic side effects of the mammary tumor-inhibiting drug [1,2-bis(2,6-dichloro-4-hydroxyphenyl)- ethylenediamine]dichloroplatinum(II) by variation of ring substituents.

[1,2-Bis(4-methoxy/4-hydroxyphenyl)ethylenediamine]dichloroplatinum-(II) complexes with Cl-, CH3-, or OCH3-substituents in the ortho-positions of the aromatic rings (meso-1-PtCl2, D,L-1-PtCl2, meso-2-PtCl2, D,L-2-PtCl2, meso-3-PtCl2, meso-4-PtCl2, meso-5-PtCl2) were tested on the MDA-MB 231 breast cancer cell line, the lymphocytic leukemia P388, and the estrogen receptor-positive and -negative MXT mammary carcinoma of the mouse (MXT,ER(+)-MC, MXT,ER(-)-MC). The comparison of the effects of methoxy-substituted complexes (meso-1-PtCl2, D,L-1-PtCl2, meso-3-PtCl2) with those of the respective hydroxy-substituted ones (meso-2-PtCl2, D,L-2-PtCl2, meso-4-PtCl2) shows that a reduction of estrogenic effects as well as a total loss of the mammary tumor-inhibiting activity takes place on methylation of the 4-OH group. The exchange of the 2,6-standing chlorine atoms by methyl groups in meso-2-PtCl2 led to the non-estrogenic, but on the MXT,ER(+)-MC highly effective derivative meso-4-PtCl2 which proved to be also cytotoxic on ER(-)-tumors such as MXT,ER(-)-MC, and the P388 leukemia.

Animals

Implementing a research-based protocol: an interactive approach.

Endotracheal suctioning (ETS) is a common procedure done in the critical care environment. There are many different practices related to ETS. With the proliferation of research studies about ETS, a change in practice is needed to incorporate these research findings. The authors present a creative teaching strategy that was used to implement a research-based ETS protocol.

Clinical Nursing Research

Ring-substituted [1,2-bis(4-hydroxyphenyl)ethylenediamine]dichloroplatinum (II) complexes: compounds with a selective effect on the hormone-dependent mammary carcinoma.

[1,2-Bis(4-hydroxyphenyl)ethylenediamine]dichloroplatinum (II) complexes with one substituent in the 2-position (CH3, CF3, F, Cl, Br, I: meso- and d,l-1-PtCl2, meso-(3-5)-PtCl2, meso-(7 and 8)-PtCl2) or two substituents in the 2,6-positions (CH3, Cl: meso-2-PtCl2, meso- and d,l-6-PtCl2) in both benzene rings were synthesized and tested for estrogenic and cytotoxic activities. Two complexes (meso-6-PtCl2 and meso-7-PtCl2) possess both effects. In comparative tests on estrogen receptor positive and negative mammary tumors in cell culture (MCF 7, ER+ and MDA-MB 231, ER-) and in animals (MXT, ER+ and MXT, ER-, mouse), meso-6-PtCl2 shows a selective effect on the estrogen receptor positive mammary carcinoma. A further increase of efficacy was achieved with the water-soluble (sulfato)platinum(II) derivative (meso-6-PtSO4). On the DMBA-induced hormone dependent mammary carcinoma of the SD rat, meso-6-PtSO4 is significantly more active than its ligand (meso-6) and cisplatin.

Animals

Effect of estrophilic platinum complex on the mouse uterus.

Resistance of hormone-dependent mammary carcinoma to cisplatin as a potent antitumor agent led to the synthesis of other estrophilic platinum complexes. In this investigation, the effects of a newly synthesized estrogen-receptor affine platinum complex on the mouse uterus were studied using light and electron-microscopy. The results have been compared with Tamoxifen, cisplatin and the estrophilic ligand. Both estrophilic ligand and estrophilic platinum complex produced strong estrogenic effects as well as features characteristic of the uterine epithelial cell in the luteal phase of the cycle, corresponding to a massive stimulation of the surface and glandular epithelial cells. The uteri showed large glandular lumina. An increase in the number of multivesicular and residual bodies, accompanied by a proliferation of eosinophilic granulocytes, was also seen. The appearance of inter- and intracellular lumina and the activation of smooth muscle cells represent further characteristic effects of the estrophilic ligand and estrophilic platinum complex. Anticipated increases in the incidence of cell death and/or deviant cyto-nuclear architecture in the uteri treated with cisplatin or platinum complex, were not observed.

Animals