Biomedical subjects

Z N Lu

Publications and source records attributed to Z N Lu.

16 recordsLinked to original sources

PubMed1998

Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality.

Keratinocyte growth factor (KGF) stimulates the proliferation and differentiation of epithelial cells including those of the gastrointestinal tract. Although chemotherapeutics and radiation exposure kill rapidly proliferating tumor cells, rapidly dividing normal cells of the host's gastrointestinal tract are also frequently damaged, leading to the clinical condition broadly termed "mucositis." In this report, recombinant human KGF used as a pretreatment in several mouse models of chemotherapy and/or radiation-induced gastrointestinal injury significantly improved mouse survival. Using multiple-dose 5-fluorouracil, methotrexate, and radiation in combination and total body radiation alone models, KGF increased survival by 55% or greater. In the models that used chemotherapy with or without radiation, KGF significantly ameliorated weight loss after injury and accelerated weight gain during recovery. The basis of these systemic benefits appears to be due in part to the trophic effects of the growth factor on the intestinal epithelium because KGF pretreatment caused an increase in measures of mucosal thickness (villus height and crypt depth) that persisted during the course of 5-fluorouracil chemotherapy. Treatment with KGF also afforded a 3.5-fold improvement in crypt survival in the small intestine, suggesting that KGF also has a direct effect on the crypt stem cells. These data indicate that KGF may be therapeutically useful to lessen the intestinal side effects of current cancer therapy regimens.

Animals↗

PubMed1998

Ovarian steroids and serotonin neural function.

The serotonin neural system originates from ten nuclei in the mid- and hindbrain regions. The cells of the rostral nuclei project to almost every area of the forebrain, including the hypothalamus, limbic regions, basal ganglia, thalamic nuclei, and cortex. The caudal nuclei project to the spinal cord and interact with numerous autonomic and sensory systems. This article reviews much of the available literature from basic research and relevant clinical research that indicates that ovarian steroid hormones, estrogens and progestins, affect the function of the serotonin neural system. Experimental results in nonhuman primates from this laboratory are contrasted with studies in rodents and humans. The sites of action of ovarian hormones on the serotonin neural system include effects within serotonin neurons as well as effects on serotonin afferent neurons and serotonin target neurons. Therefore, information on estrogen and progestin receptor-containing neurons was synthesized with information on serotonin afferent and efferent circuits. The ability of estrogens and progestins to alter the function of the serotonin neural system at various levels provides a cellular mechanism whereby ovarian hormones can impact mood, cognition, pain, and numerous other autonomic functions.

Animals↗

PubMed1993

Somatosensory evoked potentials in patients with cerebral hemorrhage and infarct. Correlation with CT, clinical data and their prognostic significance on limb function.

Somatosensory evoked potentials (SEP) arising from median nerve stimulation were recorded in 102 patients with unilateral cerebral hemorrhage or infarct located in basal ganglion, internal capsule, thalamus or cerebral lobe. Of them 42 cases were followed up and reexamined with SEPs. Three types of SEPs were observed: 1) absence of all SEPs components, 39 cases; 2) slight to moderate abnormalities of SEPs, 37 cases; 3) symmetric and normal SEPs, 26 cases. The total abnormal rate of SEPs was 76.5%. There were no definite correlations between abnormal SEPs and lesion location, size and lesion nature. The diagnosis of cerebral vascular disease might be obtained more directly and precisely by CT scan than by SEPs. However, SEPs may serve as an objective neurophysiologic means in assessing the neurological function of the affected limb, in which their abnormalities and severity are of great value to evaluate the probability and the degree of sensorimotor functional rehabilitation of the limb. When SEPs are absent, the recovery of the limb functions may be very poor no matter whether it is hemorrhage or infarct regardless of its lesion size and location.

Adult↗

PubMed1991

Production of a factor, or factors, suppressing IL-2 production and T cell proliferation by Sertoli cell-enriched preparations. A potential role for islet transplantation in an immunologically privileged site.

Isolated islet allografts survive indefinitely in the abdominal testis of nonimmunosuppressed diabetic rats. The predominant feature of these testes is that the presence of Sertoli cells, but not Leydig cells, is required for extended survival of the islet allografts. Sertoli cells cultures were therefore established in vitro and we examined the effects of the conditioned media on Con A--stimulated spleen lymphocyte proliferation. These studies revealed that a product(s) secreted by Sertoli cells inhibits Con A-stimulated lymphocyte proliferation in a dose-dependent manner. The synthesis of this product is both temperature-dependent, occurring predominantly at 37 degrees C, and hormone-dependent, requiring the presence of follicle stimulating hormone, in the culture medium. We further examined the mechanism of inhibition of lymphocyte proliferation and showed that Sertoli cell-enriched media inhibit the production of IL-2 in a dose-dependent manner. Furthermore, the finding that the addition of exogenous IL-2 is not able to reverse this inhibition indicates that the Sertoli cell-enriched media inhibit both IL-2 production and IL-2 responsiveness of T lymphocytes.

Animals↗

PubMed1991

Islet allografts in the cryptorchid testes of spontaneously diabetic BB/Wor dp rats: response to glucose, glipizide, and arginine.

The aim of this study was to examine insulin and glucagon secretory patterns in successfully transplanted spontaneously diabetic BB/Wor dp rats. Diabetic, BB/Wor dp rats received abdominal, intratesticular islet grafts of MHC-compatible BB/Wor dr donor rats without immunosuppression. After a period of 74 +/- 15 days of normoglycemia, they were given the following challenges: 1) glucose, by mouth, 2) a single oral dose of glipizide, with glucose, and 3) arginine, by iv infusion. The pertinent results included the mean fasting plasma glucose levels of control, Sprague-Dawley (C), of transplanted BB/Wor dp (T), and nontransplanted, insulin treated, diabetic BB/Wor dp (D), and they were, respectively, 97 +/- 4 mg/dl, 110 +/- 3 mg/dl, and 350 +/- 40 mg/dl. Fasting plasma insulin levels in C and T rats were 21.9 +/- 3 microU/ml, and 20.4 +/- 2 microU/ml, respectively. Fasting plasma glucagon levels in C, T, and D, were 37.8 +/- 5.7 pg/ml, 43.4 +/- 4.6 pg/ml, and 47.4 +/- 4.9 pg/ml, respectively. During oral glucose tolerance test, the pattern of insulin secretion in the C and T rats was identical with a peak attained at 15 min. Glucose caused a 70% suppression of plasma glucagon levels in C rats (P less than 0.01); T rats suppressed 14%, but this was not statistically significant; D rats failed to suppress. Glipizide plus glucose caused an improved glucose tolerance in T rats without significantly affecting insulin levels. In the same rats, glipizide resulted in a significant suppression of glucagon compared with levels in the presence of glucose alone. Arginine caused a minimal release of insulin in T rats and a major glucagon secretory response in D rats. Pancreatic glucagon content was significantly (P less than 0.03) lower in C and T, compared with D rats. Furthermore, the transplanted testes of T contained substantial amounts of glucagon. In summary, these data suggest that grafted testes in spontaneously diabetic BB/Wor dp rats contain both beta and alpha-cells and that these cells have the capacity to respond to specific secretagogues independently.

Animals↗

PubMed1990

Prevention of CTL and NK cell-mediated cytotoxicity by microencapsulation.

Graft rejection represents one of the major barriers preventing successful pancreatic islet transplantation. Microencapsulation of isolated islets has been proposed as a potential method of overcoming this problem. We present here for the first time evidence that the biocompatible semi-permeable capsule membrane prevents cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell-mediated cytotoxicity. The ability of the microcapsule to immunoisolate pancreatic and tumor cell (EL-4 and YAC-1) targets from these two mechanisms of the immune rejection response was assessed using a 51chromium-release assay. Significant cell lysis occurred when target cells were incubated with free effector cells, or with NK effector cells co-encapsulated with NK-sensitive target cells (via the release of NK cytotoxic factors (NKCF)). This effect was not observed with encapsulated effector cells alone. These results clearly demonstrate the efficacy of the microcapsule in protecting target cells against both specific cytotoxicity by CTL's, and nonspecific killing by NK cells. They also provide a method for the in vitro evaluation of the immunoprotective properties of the various new capsular materials, in terms of the effector limb or destructive phase of the allograft rejection response.

Animals↗

PubMed1990