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Biomedical subjects

F J Weaker

Publications and source records attributed to F J Weaker.

11 recordsLinked to original sources
PubMed1992

Expression of a human chimeric transferrin gene in senescent transgenic mice reflects the decrease of transferrin levels in aging humans.

Transgenic mice provide a means to study human gene expression in vivo throughout the aging process. A DNA sequence containing 668 bp of the 5' regulatory region of the human transferrin gene was fused to the bacterial reporter gene chloramphenicol acetyl transferase (TF-CAT) and introduced into the mouse genome. Expression of the human chimeric transferrin gene was similar to the tissue patterns of mouse and human transferrin. In aging transgenic mice, expression of the human chimeric transferrin gene was found to diminish 40% in livers between 18 and 26 months of age. Transferrin levels and serum iron levels in aging humans also diminish, as observed from measurements of total iron binding capacity and percent iron saturation in sera from 701 individuals ranging from 0 to 99 years of age. In contrast, in transgenic mice and nontransgenic mice, the mouse endogenous plasma transferrin and endogenous Tf mRNA increase significantly during aging. Neither the decrease of human TF-CAT nor the increase of mouse transferrin during aging appears to be part of a typical inflammatory reaction. Although the 5' regions of the human transferrin and mouse transferrin genes are homologous, sequence diversities exist which could account for the different responses to inflammation and aging observed.

Adolescent↗
PubMed1990

Human transferrin. Expression and iron modulation of chimeric genes in transgenic mice.

Transferrin (TF) is a plasma protein that transports and is regulated by iron. The aim of this study was to characterize human TF gene sequences that respond in vivo to cellular signals affecting expression in various tissues and to iron administration. Chimeric genes were constructed containing 152, 622, and 1152 base pairs (bp) of the human TF5'-flanking region with the coding region of a reporter gene, CAT (chloramphenicol acetyltransferase), and introduced into the germ line of mice. Transgenes containing TF 5'-flanking sequences to -152 bp were expressed poorly in all tissues examined. In contrast, transgenes containing TF sequences to -622 or -1152 bp were expressed at high levels in brain and liver, greater than or equal to 1000-fold higher than tissues such as heart and testes. Liver and brain are major sites of endogenous TF mRNA synthesis, but liver mRNA levels are 10-fold higher than brain. A significant diminution of CAT enzymatic activity in liver accompanied iron administration in both TF(0.67) and TF(1.2)CAT transgenic mice, mimicking the decrease of transferrin in humans following iron overload. Levels of endogenous plasma transferrin also decreased in iron-treated transgenic mice. Transgenic mouse lines carrying human TF chimeric genes will be useful models for analyzing the regulation of human transferrin by iron and for determining the molecular basis of transferrin regulation throughout mammalian development into the aging process.

Animals↗
PubMed1990

Tissue specific expression of mouse transferrin during development and aging.

Transferrin (TF) is a major plasma protein that binds ferric iron and transports it to all target tissues of the body. This study is the first step to identify the tissue specific expression of the transferrin gene in mice during development, into maturity and throughout the aging process. The transferrin gene expresses mainly in mouse liver, the cerebral hemispheres and cerebellum. In mouse, transferrin is expressed in peritoneal macrophages and in mouse macrophage cell line MO59. At 19 days of gestation, transferrin mRNA is detected in the fetal lung, heart, stomach and kidney. TF mRNA levels increase in liver throughout gestation with maximum expression occurring at 19 days. Transferrin mRNA was detected in placentas of pregnant mice, with levels progressively increasing throughout the term of pregnancy. The levels of liver TF mRNA in mouse vary in a cyclic manner during the development increasing with the aging processes. Because of the dynamic nature of tissue requirements for transferrin during homeostasis the TF gene serves as a promising system for analyzing tissue-specific regulation in vivo during development and aging. Results from this study designate periods in the life-span of the mouse where regulatory mechanisms interacting with the TF gene appear to dynamically alter its expression.

Aging↗
PubMed1989

Proto-oncogene analyses in brain tumors.

The present study determined which oncogenes (N-myc, c-myc, v-sis, or v-fos) were amplified and which messenger ribonucleic acids (mRNA's) accumulated in 10 primary human brain tumors of neuroectodermal origin. The tumors included four glioblastomas multiforme, one mixed glioma (astrocytoma grade I and ependymoma), one astrocytoma grade II, one cystic cerebellar astrocytoma, one ependymoma, one ganglioglioma, and one medulloblastoma. The relative amounts of polyadenylated (poly(A)+) RNA's homologous to these genes and their copy number were determined using the RNA and deoxyribonucleic acid blot hybridization techniques. The N-myc and v-sis probes hybridized strongly to the poly(A)+ RNA from the same recurrent glioblastoma with gene amplifications (N-myc 80 copies; v-sis three to four copies). The c-myc probe hybridized strongly to the recurrent medulloblastoma without gene amplification. The amplification or abundant accumulation of mRNA's homologous to their oncogenes may be involved in tumorigenesis or the aggressiveness of these malignant brain tumors of neuroectodermal origin and may be good molecular indicators of an extremely malignant state in these tumors.

Adolescent↗
PubMed1979

Staining calcified tissues in plastic embedding medium.

Two procedures for staining sections of calcified teeth and/or bone embedded in plastic without dissolving the embedding medium were developed to study early bone regeneration in proximity to carbon implants in monkey alveolar bone and tissue degeneration in pathological human bone. These procedures allow differential staining of delicate bone tissues and prevent breakage of sections because the supporting plastic does not have to be removed.

Animals↗
PubMed1978

A modified processing and sectioning technique for hard tissues.

A new procedure for embedding and sectioning hard tissues was developed to study bone regeneration in relation to carbon implants used in crown and bridge preparations of maxillas and mandibles of nonhuman primates. Tissues were fixed in 10 percent neutral buffered formalin, dehydrated in 95 percent and 100 percent ethyl alcohol, and embedded in a modified Spurr's low-viscosity embedding medium. Tissues were sectioned as thin as 50 to 100 micron with a Buehler Isomet Model 11-1180 low speed saw. Unstained sections, as well as tissue stained with hematoxylin and eosin and Gomori's trichrome, were examined with a light microscope. The sections were of high quality without distortion. This new procedure expedited experimental work because decalcification of tissues was not needed and implants did not fragment.

Animals↗
PubMed1977

Testicular involution following optic enucleation. An ultrastructural and cytochemical study.

The testes of adult male Syrian hamsters underwent involution within six weeks after optic enucleation. The diameter of the seminiferous tubules was 39% less than controls. Sertoli cells, spermatogonia, and primary spermatocytes were still present, but all steps of spermatids were completely absent from the involuted testes. Lipid droplets filled the Sertoli cell cytoplasm and often encroached upon the nucleus. Sertoli cells had sparse mitochondria and smooth endoplasmic reticulum, but Golgi cisternae were abundant. Typical Sertoli-Sertoli junctions attached contiguous Sertoli cells. With lanthanum tracers it was demonstrated that these junctions were impenetrable; therefore, the blood-testis barrier was deemed intact. Irregularly shaped protrusions often arose from the peritubular tissue and extended inward toward the seminiferous epithelium, often displacing the cytoplasm of the Sertoli cells and spermatogonia. The core of these protrusions consisted of irregular extensions of myoid cell cytoplasm surrounded by the myoid cells' basal lamina. External to the myoid cell basal lamina were bundles of collagen filaments with the basal lamina of the seminiferous epithelium forming the outermost layer of these protrusions. The apices of the Sertoli cells gave rise to numerous leaf-like processes that extended into and obliterated the lumen of the tubules. The Sertoli cell basal cytoplasm often contained phagocytized degenerating germ cells that appeared to give rise to the lipid droplets that filled the Sertoli cell cytoplasm. Acid phosphatase rich lysosome-like organelles were seen fusing with the degenerating germ cells and lipid droplets. The degenerating germ cells also were shown to contain acid phosphatase activity.

Acid Phosphatase↗
PubMed1977

Spermatogonia and the cycle of the seminiferous epithelium in the nine-banded armadillo.

The cycle of the seminiferous epithelium of the nine-banded armadillo can be divided into ten stages. As in most mammals, only one stage is observed per tubular cross-section. The process of spermiogenesis can be divided into thirteen steps according to the development of the acrosomal system and the flagellum. Four generations of spermatogonia are abserved in the germinal epithelium: 1) stem cells, 2)type "A", 3) intermediate, and 4) type "B" spermatogonia. The stem cell is characterized by a highly irregular nucleus and the presence of glycogen in its cytoplasm. The type "A" spermatogonium contains an oblong nucleus with one or two shallow infoldings of the nuclear membrane. The intermediate spermatogonium contins an ovoid nucleus characterized by one or two nuclei and heterochromatin scattered in the nuceoplasm. The nucleus of the type "B" spermatogonium is more spherically shaped with a centrally placed nucleolus and heterochromatin associated with the nuclear envelope.

Animals↗
PubMed1977

The fine structure of the interstitial tissue of the testis of the nine-banded armadillo.

The interstitial tissue of the testis of the nine-banded armadillo is composed of blood vessels, clusters of Leydig cells, the usual connective tissue elements, and a network of lymphatic sinusoids. The endothelial walls of the sinusoids are separated from the peritubular contractile cell layer surrounding the seminiferous tubules by a thin layer of collagen. The pertibular contractile cell is characterized by filaments and dense bodies within the cytoplasm, whereas the endothelial cells lack these structures. Within each cluster, several Leydig cells surround one or more blood vessels. Adjacent Leydig cells are jointed by 2- to 3-nm wide gap junctions and desmosome-like specializations. The Leydig cell is polygonal in shape with an ovoid nucleus. The cell is characterized by an abundance of smooth endoplasmic reticulum which appears as sheets of membranes, concentric whorls around vacuoles, and a random tubular network. Only a few short cisternae of rough endoplasmic reticulum are observed. Centrioles are closely associated with the Golgi apparatus. Rod-like mitochondria with tubular cristae are scattered throughout the cytoplasm. In addition, the cells contain vacuoles resulting from lipid extraction, filaments, microtubules, and glycogen. The surface of the cell exposed to the intercellular spaces exhibit numberous pinocytotic vesicles and cell processes which indicate active movement of material across the plasma membrane. In comparison to other mammalian species, the ultrastructural organization of the interstitium and the fine structure of Leydig cell of the armadillo resemble those of the guinea pig.

Animals↗
PubMed1977

Chromatin ultrastructure changes during spermatogenesis in armadillos.

The chromatin fibres of the male gamete nucleus of Dasypus novemcinctus contain fibrils. Measurements indicate that the chromatin fibre diameter and the number of fibrils within the fibre increase, whereas the diameter of the fibrils decreases during spermiogenesis. It is suggested that the fibrils represent a DNA-protein complex. It is further suggested that the increased fibre diameter, and the increased number of fibrils correlates with the formation of larger fibres during the condensation of the spermatid nucleus, whereas the decrease in fibril diameter is correlated with the replacement of histones with new low molecular weight acid-soluble proteins.

Animals↗