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Biomedical subjects

N Lu

Publications and source records attributed to N Lu.

At least 55 records · Page 3Linked to original sources
PubMed1997

Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility.

Follicle stimulating hormone (FSH) is a member of the glycoprotein hormone family that includes luteinzing hormone (LH), thyroid stimulating hormone, and chorionic gonadotropin. These heterodimeric hormones share a common alpha subunit and differ in their hormone-specific beta subunit. The biological activity is conferred only by the heterodimers. FSH and LH are synthesized in the same cells of the pituitary, the gonadotrophs. FSH receptors are localized to Sertoli cells of the testes and granulosa cells of the ovary. Minimal data has been accumulated so far involving human mutations in the FSH beta, LH beta, or the gonadotropin receptor genes. There are no known mouse strains with mutations in the FSH beta gene. To generate animal models for human diseases involving the gonadotropin signal transduction pathway, we produced mice deficient in the FSH beta subunit and therefore in FSH using ES cell technology. FSH-deficient females are infertile due to a block in folliculogenesis prior to antral follicle formation. Although FSH was predicted to be necessary for spermatogenesis and Sertoli cell growth in males, FSH-deficient males are fertile despite having small testes. Our findings have important implications for male contraceptive development in humans.

Animals↗
PubMed1996

Growth differentiation factor-9 is required during early ovarian folliculogenesis.

Growth factors synthesized by ovarian somatic cells directly affect oocyte growth and function, but it is unclear whether oocyte-secreted factors play a reciprocal role in modulating somatic cell functions in vivo. During the functional analysis of members of the transforming growth factor-beta superfamily in mouse development, we have uncovered a new family member, growth differentiation factor-9 (GDF-9), which is required for ovarian folliculogenesis. GDF-9 messenger RNA is synthesized only in the oocyte from the primary one-layer follicle stage until after ovulation. Here we analyse ovaries from GDF-9-deficient female mice and demonstrate that primordial and primary one-layer follicles can be formed, but there is a block in follicular development beyond the primary one-layer follicle stage which leads to complete infertility. Oocyte growth and zona pellucida formation proceed normally, but other aspects of oocyte differentiation are compromised. Thus, GDF-9 is the first oocyte-derived growth factor required for somatic cell function in vivo.

Animals↗
PubMed1996

Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice.

Manganese superoxide dismutase (SOD2) converts superoxide to oxygen plus hydrogen peroxide and serves as the primary defense against mitochondrial superoxide. Impaired SOD2 activity in humans has been associated with several chronic diseases, including ovarian cancer and type I diabetes, and SOD2 overexpression appears to suppress malignancy in cultured cells. We have produced a line of SOD2 knockout mice (SOD2m1BCM/SOD2m1BCM) that survive up to 3 weeks of age and exhibit several novel pathologic phenotypes including severe anemia, degeneration of neurons in the basal ganglia and brainstem, and progressive motor disturbances characterized by weakness, rapid fatigue, and circling behavior. In addition, SOD2m1BCM/SOD2m1BCM mice older than 7 days exhibit extensive mitochondrial injury within degenerating neurons and cardiac myocytes. Approximately 10% of SOD2m1BCM/SOD2m1BCM mice exhibit markedly enlarged and dilated hearts. These observations indicate that SOD2 deficiency causes increased susceptibility to oxidative mitochondrial injury in central nervous system neurons, cardiac myocytes, and other metabolically active tissues after postnatal exposure to ambient oxygen concentrations. Our SOD2-deficient mice differ from a recently described model in which homozygotes die within the first 5 days of life with severe cardiomyopathy and do not exhibit motor disturbances, central nervous system injury, or ultrastructural evidence of mitochondrial injury.

Animals↗
PubMed1996

A paradigm for distinguishing the roles of mitogenesis and trophism in neuronal precursor proliferation.

During nervous system development, the generation of neuronal populations is subject to regulation by extracellular growth factors. Traditional views suggest that growth factors promote proliferation by increasing the fraction of precursors that enter the mitotic cycle and subsequently divide (that is, enhance mitosis). However, recent evidence indicates that dividing precursors may undergo cell death. Consequently, a given molecule may also increase neuroblast proliferation by promoting survival of dividing precursors. In the present work, we developed a new approach to distinguish these two distinct effects of growth factors on dividing neuroblasts. By using a brief 6 h culture paradigm of embryonic day 15.5 sympathetic neuroblasts, we minimized cell death, thereby excluding the survival-promoting (trophic) activity of growth factors. In the absence of trophism, measured increases in [3H]thymidine incorporation reflected growth factor mitogenic activity only. Using a well-characterized sympathetic model, we found that insulin, EGF and vasoactive intestinal peptide (VIP) increased [3H]thymidine incorporation 30%, 20% and 46% respectively, consistent with their previously reported mitogenic activity. In contrast, neurotrophin-3 (NT3) and nerve growth factor (NGF), which serve as trophic signals for the neuroblasts, did not elicit any change in [3H]thymidine incorporation, indicating that the neurotrophins are not mitogenic for sympathetic precursors. This approach may be useful in distinguishing mitogenic and trophic regulation of proliferation in other brain precursor populations.

Animals↗
PubMed1995

Multiple defects and perinatal death in mice deficient in follistatin.

Follistatin, an activin-binding protein and activin antagonist in vitro, can bind to heparan sulphate proteoglycans and may function in vivo to present activins to their receptors. In the mouse, follistatin messenger RNA is first detected in the deciduum (on embryonic day 5.5), and later in the developing hindbrain, somites, vibrissae, teeth, epidermis and muscle. In Xenopus laevis, overexpression of follistatin leads to induction of neural tissue. Here we use loss-of-function mutant mice to investigate the function of follistatin in mammals. We find that follistatin-deficient mice are retarded in their growth, have decreased mass of the diaphragm and intercostal muscles, shiny taut skin, skeletal defects of the hard palate and the thirteenth pair of ribs, their whisker and tooth development is abnormal, they fail to breathe, and die within hours of birth. These defects are more widespread than those seen in activin-deficient mutant mice, indicating that follistatin may modulate the actions of several members of the transforming growth factor-beta family.

Animals↗
PubMed1995

Effects of gypenosides on mouse splenic lymphocyte transformation and DNA polymerase II activity in vitro.

AIM: To study the effects of gypenosides (Gyp) on lymphocyte transformation and DNA polymerase II activity. METHODS: Lymphocyte transformation response was induced by concanavalin A and lipopolysaccharides respectively. The activity of DNA polymerase II and DNA synthesis were assayed with TTP and [3H]TdR incorporation respectively in mixed lymphocyte culture test. RESULTS: Gyp 2.5-20 mg L-1 enhanced splenic T- and B- cell transformation, increased the DNA synthesis and potentiated the activity of DNA polymerase II. However, Gyp > 40 mg L-1 showed contrary effects. CONCLUSION: Gyp regulated lymphocyte transformation and DNA synthesis by regulating DNA polymerase II activity.

Animals↗
PubMed1992

[Primary neuroendocrine carcinoma of the skin (Merkel cell tumor)].

Primary neuroendocrine carcinoma of the skin (Merkel cell tumor), a rare malignancy originating from the skin, has only been established in the recent years. It has a main predilection on the skin in the head and neck region with an obvious tendency of local recurrence and early metastasis. Histopathologically, it resembles the neuroendocrine carcinoma from other sites of the body in morphology, immunohistochemistry and ultrastructure. Diagnosis of this tumor is quite difficult. Based upon two of our cases as verified by electron microscopy and/or immunohistochemistry, the clinical and pathological features of this tumor are described and the literature reviewed.

Adult↗
PubMed1992

[Contrast sensitivity in the fellow eye of unilateral age-related macular degeneration].

The VCTS 6000 Contrast Sensitivity Test System was used in testing the fellow eyes of 20 cases of unilateral age-related macular degeneration (ARMD), with age-matched normal controls. Among the patients, 25% of the fellow eyes showed minor contrast sensitivity reduction at medium and high spatial frequencies. This test may be useful in the diagnosis of subclinical ARMD.

Age Factors↗
PubMed1992

[Contrast sensitivity study in the fellow eyes of patients with central serous chorioretinopathy].

In clinical practice, it has been shown that the contrast sensitivity (CS) test is one of the most sensitive visual functional tests. In our experiment, we used a U.S.-made VCTS 60000 CS test plate to test the fellow eyes (20) of 20 cases with unilateral central serous chorioretinopathy (CSC), along with age-matched normal controls. From the control group, we obtained a group of bell-shaped normal CS curves which showed some degree of decrease with age. 40% of the fellow eyes of the patient group showed a slight CS decrease at mid-high spatial frequencies, though other visual functional tests show no abnormality. These fellow eyes may be at risk for CSC. Our experiment, for the first time, showed the possibility of using the CS test as a diagnostic test for subclinical CSC.

Adult↗