Search PubMed⌕ Search

Biomedical subjects

J C Li

Publications and source records attributed to J C Li.

At least 91 records · Page 5Linked to original sources
PubMed1985

Deficient repair of DNA lesions in Alzheimer's disease fibroblasts.

DNA strand breaks, resulting from treatment with N-methyl-N'-nitro-N-nitrosoguanidine, were repaired more slowly in four strains of familial Alzheimer's disease fibroblasts than in five strains of fibroblasts from age-matched normals. These results were not due to differences between the two cell types in in vitro ages, in the initial DNA damage or in drug-induced cell lysis. Bleomycin-induced DNA double-strand breaks were repaired equally efficiently by both types of cells. Alzheimer's disease cells may have a DNA repair defect, which may be involved in the pathogenesis of this disease.

Aged↗
PubMed1984

Accumulation of DNA strand breaks and methotrexate cytotoxicity.

There was a progressive formation of strand breaks in mature DNA of Ehrlich ascites tumor cells that were treated with methotrexate. Cells were labeled with [14C]thymidine before incubation with methotrexate, and DNA strand breaks were measured by alkaline and by neutral filter elution methods. DNA single-strand breaks accumulated in a linear fashion as a function of time during the first 10 hr of incubation with 2 microM methotrexate. Thereafter, the accumulation of DNA strand breaks deviated from linearity because of progressive cell death. The extent of DNA strand breakage in cells that had been incubated with methotrexate for 24 hr was as high as in cells that had been irradiated with 300 rads. DNA strand breaks persisted in cells that were incubated, after exposure to methotrexate, in medium containing thymidine, hypoxanthine, and nonessential amino acids, indicating that these strand breaks were poorly repaired. Cell death commenced after 10 hr of incubation with methotrexate and continued during the following 3-4 days. These findings suggest that cell death was due to a lethal accumulation of DNA strand breaks. The formation of DNA strand breaks is probably due to inefficient DNA repair, resulting from the inhibition of syntheses of thymidylate and of purine nucleotides. The accumulation of DNA strand breaks was minimal in growth-arrested cells, which are resistant to methotrexate toxicity.

Animals↗
PubMedDate not supplied

Influences of light-dark shifting on the immune system, tumor growth and life span of rats, mice and fruit flies as well as on the counteraction of melatonin.

Animal models were designed to study the changes in immune function, oncogenicity and life span of rats, mice and fruit flies following light-dark (LD) shift manipulations. Alternating the photoperiod of LD 14:10 and DL 10:14 every 3 days in rats disrupted the circadian immune rhythm pattern, decreased the blood leukocyte concentration by 48% and lowered the percentage of lymphocytes in the blood from 71% (control) to 49.2%. In mice, the phagocytosis of neutrophils was only reduced by 7%, but the level of serum hemolysin dropped significantly in the photoperiod-shifted group as compared with animals kept under a constant photoperiod of LD 12:12 or LD 14:10. In Ehrlich-carcinoma- or sarcoma-180-injected mice, a reduction of survival duration, acceleration of tumor growth and depression of the immune system were recorded in the LD-shifted animals. In addition, the life span of fruit flies was shortened by 9.6% by photoperiodic shifting. Melatonin treatment evidently counteracted the deleterious influences of photoperiodic shifting in the above animals. It is suggested that repeated inversion of the LD cycle results in a chronobiological abnormality that, in turn, induces dysfunctions. Reentrainment by exogenous melatonin may inhibit the harmful influences of photoperiodic shifting.

Animals↗
PubMedDate not supplied

Effects of melatonin on hypothalamic gamma-aminobutyric acid, aspartic acid, glutamic acid, beta-endorphin and serotonin levels in male mice.

Effects of melatonin on hypothalamic neurotransmitters in male mice were studied. Exogenous melatonin administered intraperitoneally significantly increased (p < 0.05) hypothalamic concentrations of aspartic acid and gamma-aminobutyric acid by over 29 and 50% respectively. Conversely, hypothalamic beta-endorphin concentration was significantly decreased (p < 0.05) 30 min after melatonin administration with doses between 5- and 100 micrograms/kg. Similarly, melatonin, at a concentration of 100 micrograms/kg, decreased (p < 0.05) the serotonin level in mouse hypothalamus by 46%. Melatonin, however, did not affect the concentration of hypothalamic glutamic acid over a dose range of 0.5-300 micrograms melatonin/kg. Our findings suggested that actions of pineal melatonin in animals such as inhibition on serum corticosterone levels might be mediated by the potentiation of activities of hypothalamic neurons containing gamma-aminobutyric acid and aspartic acid or by the inhibition of the beta-endorphin and serotonin hypothalamic neurons. The neurons containing glutamic acid in the hypothalamus were, however, not influenced by melatonin. Our results are in line with the suggestion that melatonin actions on adrenal corticosterone release or other endocrine secretions may be mediated by way of its actions on hypothalamic neurotransmitter activities.

Animals↗
PubMedDate not supplied

Urinary urea nitrogen: too insensitive for calculating nitrogen balance studies in surgical clinical nutrition.

Urinary urea nitrogen (UUN) has been used as an estimate of total urinary nitrogen (TUN) when calculating nitrogen output for nitrogen balance (NB) studies. UUN is assumed to constitute 80 to 90% of the total nitrogen output; when estimating TUN from UUN, UUN values are multiplied by 1.25 to correct for non-urea nitrogen components. In order to evaluate the validity of estimating total urinary nitrogen output from measured UUN in a clinical setting, 491 UUN:TUN paired studies were performed on 24-hour urine collections in general surgical/trauma patients who had measured TUN outputs ranging from 0.04 to 54.0 g/d. Assessment of 315 NB studies was done to compare NB values of those calculated by using UUN as an estimate of TUN with those calculated from measured TUN. Patients in both studies were subdivided into four stress categories, using TUN/day as the index: less than 5 g, 5-10 g, 10-15 g, and greater than 15 g. On average, 80 to 90% of TUN is represented by the UUN. However, in our patient population the variability ranged from 12 to 112%. If these UUN values are used as estimates for TUN in calculating NB, variations of up to 12 g/d would result. Application of the correction factor of 1.25 is not consistent in correcting for nonurea nitrogen components in this clinical setting. The use of actual rather than estimated TUN may be a more accurate and appropriate method than UUN when calculating NB.

Adolescent↗
PubMedDate not supplied

Regulation of Sertoli cell myotubularin (rMTM) expression by germ cells in vitro.

Recent studies have shown that rat myotubularin (rMTM), the homolog of human myotubularin, which is a putative protein tyrosine phosphatase (PTP), is expressed by Sertoli cells in the rat testis. In addition, a significant increase in its steady-state mRNA level was detected in Sertoli cells at the time of inter-Sertoli tight junction (TJ) assembly in vitro. Since the interplay of protein kinases and phosphatases that determines the intracellular phosphoprotein content can, in turn, regulate the assembly and maintenance of TJ and anchoring junctions (AJ) in vitro, as demonstrated in different cell types, such as Madin-Darby canine kidney (MDCK) cells, endothelial cells, and Sertoli cells, rMTM may be an important molecule in regulating the assembly and maintenance of inter-Sertoli TJs during spermatogenesis. We thus sought to characterize its regulation. During testicular maturation, it was shown that the rMTM steady-state mRNA level increased drastically with aging. The expression of rMTM increased by as much as 2-4-fold in the rat testis at 45-60 days of age versus 20 days of age, coinciding with the onset of spermiation. This result seemingly suggests that rMTM may participate in the release of spermatids by disassembling the Sertoli-spermatid AJs, since PTP inhibitor was shown to perturb the inter-Sertoli TJ permeability barrier in vitro. Unexpectedly, when Sertoli cells were isolated from 20-, 45-, and 90-day-old rats and the steady-state rMTM level was quantified, it was shown that there is a drastic reduction in rMTM expression in adult Sertoli cells. Studies that used Sertoli-germ cell cocultures and Sertoli cells incubated with increasing germ cell-derived proteins have shown that the high level of testicular rMTM expression in the testis might be maintained by germ cells. Although work remains to be done to delineate the role of rMTM in the testis, these results illustrate that germ cells play a very active role in regulation testicular function by altering the phosphoprotein content.

Animals↗
PubMedDate not supplied

The inter-Sertoli tight junction permeability barrier is regulated by the interplay of protein phosphatases and kinases: an in vitro study.

The timely opening and closing of inter-Sertoli cell tight junctions in the rat testis are essential cellular events in the completion of spermatogenesis. They permit the passage of preleptotene and leptotene spermatocytes to cross the blood-testis barrier from the basal compartment to the adluminal compartment of the seminiferous epithelium so that these cells can continue their further development into spermatids. However, the mechanism by which these events is regulated remains a mystery in male reproductive physiology. As part of our long-term goal of understanding the biology of this event and its regulation, transepithelial electrical resistance (TER) across the Sertoli cell epithelia when inter-Sertoli tight junctions were being assembled in vitro was quantified to assess the effects of different inhibitors of phosphatases and kinases on the inter-Sertoli tight junction permeability barrier. It was shown that inhibitors of protein tyrosine phosphatases (PTPi) and inhibitors of protein Ser/Thr phosphatases (PPi) could perturb the assembly and maintenance of the inter-Sertoli tight junction permeability barrier. Moreover, the inhibitory effects of PTPi were abolished by pretreating Sertoli cells with protein tyrosine kinase inhibitor (PTKi), which illustrates the specificity of the PTPi treatment. A cyclic adenosine monophosphate-dependent protein kinase A (PKA) activator and inhibitors of calcium-diacylglycerol-dependent protein kinase C (PKC) can also perturb the inter-Sertoli tight junction permeability barrier, which suggests that opening and closing of the inter-Sertoli tight junctions during spermatogenesis is likely regulated, at least in part, by the PKA/PKC pathways. Needless to say, these results illustrate that the interplay of protein kinases and phosphatases, which regulate the intracellular phosphoprotein content of Sertoli cells possibly via PKA and PKC signal transduction pathways, plays a crucial role in modulating the assembly and maintenance of inter-Sertoli tight junctions in the testis.

Animals↗