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Biomedical subjects

N Fox

Publications and source records attributed to N Fox.

At least 73 records · Page 4Linked to original sources
PubMed1983

Identification of human hepatoma-defined cell surface molecules.

BALB/c mouse splenocytes from mice immunized with cells of the human hepatoma line Hep G2 were fused with SP2/0-Ag 14 mouse myeloma cells. Two monoclonal antibodies recognizing antigenic determinants (Hag-1, Hag-2) of hepatoma cell surface molecules were investigated. Analysis of immunoprecipitates by sodium dodecyl sulfate (SDS) gel electrophoresis revealed that the Hag-1 antigenic determinant is born ona 115, kD MW glycoprotein, and that the second antibody immunoprecipitates a group of surface proteins with MW of 230 kD, 79 kD, 23 kD, and 20 kD from human hepatoma cells. These antigenic determinants are present on cell lines derived from other human tumors, thus neither of the antibodies is hepatoma-specific; cross-reactivity with human colorectal carcinoma and some mammary carcinoma cell lines is notable. Using indirect immunofluorescence on frozen sections Hag-1 was detected in one of three liver biopsies tested whereas Hag-2 was demonstrated in all three. Both antigens were detected in sections of human kidney with Hag-2 localized to the proximal tubules.

Animals↗
PubMed1983

Immunohistochemical localization of the mouse stage-specific embryonic antigen 1 in human tissues and tumors.

Normal human tissues and various human tumors were surveyed by immunohistochemical techniques for expression of the stage-specific embryonic antigen 1 (SSEA-1). The antibody reacted with many normal and neoplastic human tissues. In most instances, equivalent human and mouse tissues expressed SSEA-1; however, different tissue localization patterns were sometimes seen between these two species. Most SSEA-1-positive tumors originate from tissues that normally expressed this antigen; however, some breast and ovarian tumors are SSEA-1 positive, and these organs are SSEA-1 negative. SSEA-1-positive tumors were composed of both immunoreactive and nonreactive tumor cells. These data show that SSEA-1, initially defined as a mouse embryonic antigen, represents a heterogenetic antigen present in many normal human tissues. It is retained on many but not all neoplastic cells originating in these normal tissues and also appears on the surface of some tumor cells developing in SSEA-1-negative tissues.

Antigens, Neoplasm↗
PubMed1982

Motor asymmetries in preterm infants: effects of prematurity and illness.

Two types of motor asymmetry, postural asymmetry and lateral head turning, were assessed in 3 groups of preterm infants, one of which had experienced respiratory distress syndrome (RDS) in the postnatal period. Results reveal that maintenance of a right postural asymmetry is present as early as 34 weeks conceptional age and is not disrupted by postnatal illness. Lateral head turning after midline placement was evident as early as 36 weeks conceptional age but was disrupted by physiologic condition. Infants who had experienced RDS had poor muscle tonus and did not assume the head right position even at 39 weeks conceptional age. These data argue that lateral responding may be affected by illness and that studies of preterm populations must evaluate postnatal medical condition when assessing both the short- and long-term outcomes of lateral asymmetries.

Age Factors↗
PubMed1982

DNA dependence and inhibition by novobiocin and coumermycin of the nucleolar adenosine triphosphatase (ATPase) of human fibroblasts.

We have recently demonstrated by electron microscopic cytochemical methods that unfixed human fibroblasts exhibit intense MG2+ dependent adenosine triphosphatase (nATPase) activity in circumscribed areas of the cell nucleoli. The nATPase was specific for ATP and dATP and was inhibited by other ribonucleoside triphosphates. Its intranucleolar localization relative to nucleolar chromatin, and segregation into nucleolar zones after actinomycin treatment of the cells, suggested that the reaction took place in fibrillar centers. This ATPase has now been further characterized by electron microscopic cytochemistry. It was determined that short fixation permitted retention of most of the ATPase activity, and that the enzyme was active at high ionic strength (up to 400 mM KCl), but that the enzyme activity was very sensitive to elevated temperatures. DNA dependence of the enzyme was shown by inhibition of the reaction by DNase pretreatment in parallel with the removal of DNA from the cell, while pretreatment with RNase had no significant effect. The nATPase activity was also selectively inhibited by treatment of the cells with antagonists of the B subunit of DNA gyrase, novobiocin, and coumermycin, but not by nalidixic or oxolinic acids, which interfere with the A subunit of gyrase. Inhibitors of RNA synthesis, actinomycin D and aminonucleoside of puromycin, potentiate rather than inhibit nATPase reaction. The results suggest that nATPase functions to alter the degree of supercoiling or catenation of nucleolar organizer DNA, and is in reality a DNA topoisomerase that hydrolyzes ATP during its action.

Adenosine Triphosphatases↗
PubMed1982

Immunohistochemical localization of murine stage-specific embryonic antigens in human testicular germ cell tumors.

Monoclonal antibodies raised against and/or recognizing stage-specific antigens on preimplantation mouse embryos and stem cells of murine teratocarcinoma were used to localize these antigens immunohistochemically on human testicular germ cell tumors. SSEA-1, the antigen found on mouse embryonal carcinoma (EC) cells and embryonic cells from the 8-cell stage embryo onward, including the fetal primordial germ cells, was detected on yolk sac carcinoma components of human tumors, but not on EC cells. SSEA-3, the antigen found on follicular ova, fertilized eggs, early cleavage stage embryonic cells, and visceral endodermal cells of the mouse embryo, but not on mouse EC cells, was detected on human EC cells. Both antigens were found on the cell surface of fetal testicular germ cells but not in the seminiferous tubules of adult human testes. These data point out differences between human and murine EC cells suggesting that human EC cells correspond developmentally to a less mature embryonic cell than the murine EC cells. The possible histogenesis of human germ cell tumors from primordial and/or fetal germ cells is briefly discussed.

Animals↗
PubMed1981

Visualization of nucleolar substructure in cultured human fibroblasts by magnesium-activated adenosine triphosphatase reaction.

Discrete sites of adenosine triphosphatase (ATPase) activity were demonstrated within the nucleoli of unfixed cultured human fibroblasts (IMR90, VA13, and AG2804 cells) by an adaptation, for electron microscopic cyto-chemistry, of Wachstein and Meisel's lead nitrate method. The majority of nucleoli contained more than one ATPase-positive region, but the total ATPase-positive material appeared to occupy only a minor portion of the nucleolar volume. These regions were roughly spherical with an irregular contour, and at times appeared to be components of perinucleolar chromatin or to be located adjacent to nucleolar interstices. The distribution of these regions within the nucleolus and their segregation by actinomycin D suggested that the ATPase-positive regions correspond to the fibrillar centers, which represent nucleolar organizer regions. The cytochemically demonstrable nucleolar ATPase was strictly dependent on the presence of divalent cations. Optimal reactions was seen at 5 mM Mg2+, but near optimal activity was obtained with lower concentrations of Mg2+ in the presence of Ca2+. Calcium alone and Mn2+ alone produced suboptimal reaction. Studies with different nucleoside phosphates as reaction substrates showed that the enzyme is specific for adenosine derivatives, ATP and dATP being equally good substrates. Guanosine triphosphate, cytidine triphosphate, uridine triphosphate, and d-thymidine triphosphate were ineffective as substrates, as were nucleoside mono- and diphosphates and other phosphate esters tested. It is suggested that the cytochemical ATPase reaction visualized the regions of the nucleolus in which ribosomal DNA of intranucleolar chromatin is undergoing conformational alterations.

Adenosine Triphosphatases↗
PubMed1979

The growth of memory during infancy.

Eight middle class infants were administered a series of tasks over a nine month period from 5 to 14 months of age. Major procedures included object permanence, vacillation, memory for locations and pictures, and reaction to unfamiliar adults and to separation. The results suggested that during the last half of the first year there is a major enhancement in the ability to retrieve a representation of a past event, to compare that representation with present experience, and to tolerate both longer delays between an original and transformed event and greater interference during those delays. It was suggested that many of the diverse phenomena that appear during the last half of the first year are mediated, in part, by an amplification of memorial capacity.

Attention↗
PubMed1977

Attachment of kibbutz infants to mother and metapelet.

122 children, born and reared on Israel kibbutzim, were observed in a cross-sectional study of infant attachment behaviors. Their reaction to either mother or metapelet (caretaker) separation and reunion was recorded over a 13-sequence experimental paradigm. Results indicated that children protested equally to either mother or metapelet separation when left with a stranger. Reunion behaviors seemed to be sensitive to the different attachment relationships the infant had with each caretaker, while separation behaviors were not. The quality of the infant-mother interactions as it is related to the infant's ordinal position had a significant effect on infant attachment behavior in the experimental situation. Firstborn (only) children were more anxious than later-borns during the session. Speculation as to the origin of these significant ordinal differences is discussed.

Female↗
PubMed1976

Absorption and disposition of econazole nitrate after application to the skins and vaginas of rabbits.

1. The absorption and tissue distribution of radioactivity has been studied in rabbits after application of a cream containing 10 mg of the 3H-labelled 1-(2,4-dichloro-beta-[(p-chlorobenzyl)oxy]phenethyl) imidazole nitrate (econazole nitrate, Pevaryl) to the normal or abraded skins of rabbits. 2. Approximately one-third of the dose was absorbed through the occluded normal skins of rabbits during 8 days, mainly during 7 to 24 h. In the same time interval, slightly more of the dose was absorbed through the occluded abraded skins of rabbits at slightly greater rates. Co-formulation of triamcinolone acetonide in the cream reduced and delayed the peak rates of absorption through normal and abraded skin, but the extent of absorption during 8 days was similar in the presence or absence of triamcinolone acetonide. 3. After application to normal skin or abraded skin, the peak of mean concentrations in the plasma of 220 ng/ml (range 132-276 ng/ml) or 307 ng/ml (range 270-321 ng/ml), respectively, occurred at 24 h. Tissue distribution of radioactivity was similar after application to normal or abraded skin, and concentrations were highest in the liver, kidneys and gastrointestinal tract (which are the organs of biotransformation and excretion) and also in the adrenals and to a lesser extent in the uterus, ovaries and untreated skin. 4. After application of a cream containing 5 mg of 3H-econazole nitrate to the vaginas of rabbits, approximately one-third of the dose was absorbed during 8-24 h, and rates of excretion were higher through the more permeable vaginal membrane. 5. After vaginal doses of 5 mg, a peak concentration of 209 ng/ml occurred at 6 h in the plasma. Tissue concentrations of radioactivity after vaginal doses were highest in liver, kidneys, gastrointestinal tract, adrenals and ovaries, and the tissue distribution was similar to that observed after cutaneous doses.

Administration, Oral↗
PubMedDate not supplied

Protein folding, nucleation phenomena and delayed neurodegeneration in Alzheimer's disease.

This hypothesis attempts to explain how Alzheimer's disease can be both sporadic and autosomal dominant with catastrophic neurodegeneration occurring after decades of normal function. The production of A beta peptide, the subunit of amyloid plaques, from the ubiquitous amyloid precursor protein is discussed. Conformational changes are argued to be crucial to the formation of these amyloid plaques and to their neurotoxicity. Parallels are drawn with prion disease where similarly a normal cellular protein becomes pathogenic once a conformational change is induced. Post-mitotic neurons in the brain are susceptible to this destructive process which is initiated by nucleation phenomena and is then self propagating. An understanding of the conformational changes involved in plaque formation may open new therapeutic avenues in Alzheimer's disease.

Aged↗