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Biomedical subjects

Y D Zhao

Publications and source records attributed to Y D Zhao.

At least 19 recordsLinked to original sources

Neurosurgical trauma in People's Republic of China.

An epidemiological investigation for neurological disorders was conducted in the People's Republic of China in 1983 and 1985. The incidence of traumatic neurological injury was 55.4 patients per 100,000 population in the six big cities and 64.1 patients in the 21 rural areas. The mortality rates were 6.3 per 100,000 population (male:female = 1.7:1.0) in the six cities and 9.7 (m:f = 2.5:1) in the rural areas. In the cities, the causes of brain injury were vehicle accidents (31.7%), followed by assaults (23.8%), falls (21.8%), stumbles (15.4%), and others. Brain concussion was 68.4%, contusion was 26.0%, and intracranial hematoma was 5.6%. The incidence of spinal cord injury was 0.67 per 100,000 population in Beijing and 1.37 in Shanghai. Male versus female ratio was 7 to 1 and the peak incidence was found in ages from 20 to 30 years old. In the past decade, vehicle accidents increased along with the increasing number of cars and motor bicycles. As a result of a series of administrative measures, such as improvement of traffic control and safe-driving education, mean mortality decreased from 33.4 per 10,000 motor vehicles in 1990 to 22.0 in 1995. It has been estimated that approximately 50,000 to 60,000 people die from vehicle accidents per year. Among these cases, brain injury accounts for 39% to 57% and spinal cord injury about 10%. Since vehicle accidents are the most common cause for neurotraumatic death, an effort is needed to prevent and to decrease the incidence of these accidental traumatic injuries.

Brain Injuries↗

Abnormal aortic valve development in mice lacking endothelial nitric oxide synthase.

BACKGROUND: Endothelium-derived nitric oxide (NO) is produced by an oxidative reaction catalyzed by endothelial NO synthase (eNOS). NO plays a crucial role in controlling cell growth and apoptosis, as well as having well-characterized vasodilator and antithrombotic actions. More recently, endothelium-derived NO was shown to be involved in postdevelopmental vascular remodeling and angiogenesis, as well as in the formation of limb vasculature during embryogenesis. Therefore, we investigated the role of endothelium-derived NO during cardiovascular development using mice deficient in eNOS. METHODS AND RESULTS: We examined the hearts of 12 mature eNOS-deficient and 26 mature wild-type mice. Five of the mature eNOS-deficient mice had a bicuspid aortic valve; none of the 26 wild-type animals exhibited identifiable valvular or cardiac abnormalities. Immunohistochemical analysis revealed prominent eNOS expression localized to the endothelium lining the valve cusps of the aorta in mature wild-type mice; expression was localized to the myocardium and endothelial cell monolayer lining the valve leaflets in the developing embryo. CONCLUSIONS: These results show a strong association between eNOS deficiency and the presence of a bicuspid aortic valve; they provide the first molecular insight into one of the most common types of congenital cardiac abnormality.

Animals↗

Yi-Cheng Zhao: a founder of neurosurgery in China.

Yi-Cheng Zhao was trained in neurosurgery at the Montreal Neurological Institute by Wilder Penfield in 1938. This article presents Zhao's great contributions to the development of neurosurgery in China. He set up the first independent neurosurgical departments in Tianjin (1952) and in Beijing (1954). A basic research unit for neurosurgery, Beijing Neurosurgical Institute, was also established in 1960 under Zhao's insistent efforts. To raise the clinical level, he emphasized subspecialization of neurosurgery and divided the service into tumor, trauma, pediatrics, and miscellaneous groups. He was also enthusiastic about training neurosurgeons. More than 200 students have been trained by him, and most of them have set up centers in different cities in China. At present, the Beijing Neurosurgical Institute is the largest neurosurgical research unit. It plays an important role in the development of Chinese neurosurgery. Zhao devoted nearly 40 years to neurosurgery and died in 1974. The chinese Neurosurgical Association has honored Zhao as "a founder of neurosurgery in China."

China↗

Neonatal polychlorinated biphenyl treatment increases adult testis size and sperm production in the rat.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants which decrease serum thyroxine (T4) concentrations. We have previously demonstrated that neonatal hypothyroidism in the rat increases Sertoli cell numbers, adult testis weight, and daily sperm production (DSP). The aim of this study was to determine if neonatal PCB treatment increases adult testis weight and DSP. Treated rats received either Aroclor 1242 or 1254 (0.4-3.2 mg/day), from birth to Day 25 by daily injection; some treated litters also received T4 replacement. Controls received vehicle alone. Tritiated thymidine autoradiography was used to assess Sertoli cell proliferation in 15-day control and Aroclor-treated rats. Serum T4 was measured at 25, 45, and 135 days of age, and serum testosterone, testis weight, DSP, and testicular histology were examined at 135 days. Both Aroclor 1242 and 1254 suppressed serum T4 concentrations; Aroclor 1254 was more potent and long lasting. Testis weight was increased 22 and 13% in rats that received the 1.6 and 3.2 mg/day Aroclor 1242 doses, respectively, while the 0.4 mg/day dose did not produce significant increases. Aroclor 1254 produced significant increases in testis weight of 13 and 23% at the 0.4 and 1.6 mg/day doses, respectively. The 1.6 mg/day Aroclor 1242 and the 0.4 and 1.6 mg/day Aroclor 1254 doses increased DSP by 27, 11, and 42%, respectively; other treatments did not produce significant increases. At 15 days of age, Sertoli cell proliferation was greater in treated rats than in controls. T4 replacement decreased or eliminated the increased testis weight and DSP seen in Aroclor-treated rats. The highest dose of Aroclor 1242 and both doses of Aroclor 1254 decreased adult body weight, while other treatments did not. These results indicate that neonatal PCB treatment increases adult testis weight and DSP in rats. PCBs produce this effect primarily by inducing hypothyroidism, which leads to increased Sertoli cell proliferation, testis weight, and DSP. Thus PCBs, despite inhibitory effects on adult reproductive organs, can paradoxically stimulate increases in adult testis weight and DSP when administered neonatally. These data emphasize the pleiotropic nature of PCB effects and the susceptibility of the developing reproductive system to environmental factors.

Animals↗

Postnatal changes in endothelin-1 binding in porcine pulmonary vessels and airways.

As the lung adapts to extrauterine life, the structure of the intrapulmonary arteries changes rapidly, in a similar manner in humans and pigs. The response to exogenous endothelin also changes in the perinatal porcine lung. Therefore we investigated the distribution and type of endothelin binding sites in the airways and vasculature of six to eight pig lungs in each of five age groups, from birth to adulthood. Using an in vitro autoradiographic technique, the distribution and density of 125I ET-1 binding was determined and characterized. At all ages, dense ET-1 binding was localized over the pulmonary and bronchial arteries and veins, bronchial smooth muscle, and the parenchymal region. Muscular pulmonary arteries and pulmonary veins had a higher density of binding than elastic arteries (P < 0.01). Between birth and adulthood, binding density decreased in extrapulmonary arteries (P < 0.05) and bronchial arteries (P < 0.01). The elastic intrapulmonary arteries showed a transient increase in binding density at 2 to 3 days of age (P < 0.05) and the muscular intra-pulmonary arteries showed one at 10 days of age (P < 0.05). The ETA antagonist BQ-123 and the ETB agonist sarafatoxin 6c were used to identify the receptor subtypes. Both subtypes were found on the medial smooth muscle cells at all ages. The majority of binding sites in the pulmonary arteries were ETA (75 to 92%). At 2 to 3 days of age only, ETB receptors were seen on the endothelium of the elastic pulmonary arteries, increasing the proportion of ETB receptors present. Thus we have demonstrated changes in endothelin receptors at a time when pulmonary vascular resistance falls. Their physiologic role remains to be elucidated.

Age Factors↗

Localization of endothelin-like immunoreactivity and endothelin binding sites in rabbit eyes.

Immunohistochemistry and in vitro autoradiographic techniques were used to investigate the localization of endothelin (ET)-like immunoreactivity and [125I]ET-1 binding sites in sections of ocular tissues of normal rabbits. ET-like immunoreactivity was localized to the corneal endothelium and the pre-epithelial layer of the cornea, which was specifically inhibited by addition of exogenous ET-1. Immunoreactivity for ET was also observed in the retinal ganglion layer and periocular fat tissues. These, however, were not inhibited in the presence of ET-1. Autoradiography showed binding sites for ET-1 in the iris and ciliary body. Emulsion-dipped slides of sections of rabbit eyes incubated with [125I]ET-1 showed specific labeling for binding sites over structures that were identified from serial sections stained with hematoxylineosin. These were the anterior stroma of the iris root, the walls of capillaries, the circular arteries, and the veins of the ciliary body and extraocular muscles. No binding sites were found in the cornea or conjunctiva. The difference in regional distributions of ET storage and binding sites in rabbit ocular tissue suggests that the peptide may have specific physiologic functions.

Animals↗

Localization and characterization of endothelin-1 binding sites in the transplanted human lung.

The localization and characterization of endothelin-1 (ET-1) binding in sections of transplanted and control human lung tissues was investigated by in vitro autoradiography. Binding of [25I]ET-1 was saturable and specific, and demonstrated a single class of binding sites. Scatchard analysis of the data revealed a Kd of 0.52 +/- 0.15 nM and a Bmax of 61.17 +/- 4.5 amol/mm2 to normal lung parenchyma, and a Kd of 0.48 +/- 0.29 nM and a Bmax of 123.9 +/- 18.5 amol/mm2 to normal bronchial smooth muscle. In transplanted human lung, the binding characterizations were similar to those of normal lung. Scatchard analysis indicated high-affinity sites having a Kd of 0.8 +/- 0.19 nM and a Bmax of 153.6 +/- 9.2 amol/mm2 to lung parenchyma and a Kd of 0.59 +/- 0.21 nM and a Bmax of 141.77 +/- 14.6 amol/mm2 to bronchial smooth muscle. Binding in transplanted and control tissues was similar and was inhibited by co-incubation with an excess of unlabeled ETs (ET-1 > ET-2 > ET-3) but not by other unlabeled peptides. Binding was mainly localized to lung parenchyma, small blood vessels [muscular pulmonary artery (100-500 mm) and bronchial blood vessels], pulmonary veins, and bronchial smooth muscle. The specific binding in small blood vessels was lower in transplanted lung than in control lung. Less specific binding was found in elastic pulmonary vessels than in small blood vessels in both transplanted and control lungs. No binding was found in the cellular perivascular infiltrates of the transplanted lung. These results suggest that ET-1 acts intrinsically and that high-affinity receptors for it exist in transplanted lung both in the parenchyma and bronchial smooth muscle.

Adolescent↗

Localization and characterization of endothelin-1 receptor binding in the blood vessels of human pulmonary tumors.

We have demonstrated endothelin-1 (ET-1) binding sites in the blood vessels of human pulmonary tumors by in vitro autoradiography. The blood vessels of the tumors were confirmed by immunostaining with von Willebrand factor. Specific [125I]ET-1 binding was identified in the blood vessels of all sizes in both tumor and stromal tissues. Nonspecific binding was observed in squamous cell carcinomas and in carcinoids. The ET-1 binding in blood vessels was specific, saturable, and time-dependent. The binding reached equilibrium at 120 min. Scatchard analysis of [125I]ET-1 binding to sections of blood vessels of squamous cell carcinoma indicated binding to a single class of binding sites, with a dissociation constant (Kd) of 0.16 nM and a maximal density of binding sites (Bmax) of 126 amol/mm2. The binding was competitively inhibited by ET-1 >> VIC > ET-2 > sarafotoxin (SRb) > ET-3 but not by other unrelated peptides. Our results provide evidence that ET-1 binding is localized in the blood vessels of pulmonary tumors and in stromal tissues surrounding the tumor nest. ET may play a role in the angiogenesis of tumor growth.

Autoradiography↗

Triiodothyronine inhibits proliferation and stimulates differentiation of cultured neonatal Sertoli cells: possible mechanism for increased adult testis weight and sperm production induced by neonatal goitrogen treatment.

Transient neonatal hypothyroidism in the rat causes prolonged Sertoli cell proliferation, delayed Sertoli cell maturation, and increased adult Sertoli cell number, testis weight, and sperm production. Conversely, neonatal hyperthyroidism decreases Sertoli cell proliferation and ultimate testis size. This suggests that thyroid hormones might normally directly inhibit Sertoli cell proliferation while promoting maturation. However, these Sertoli cell effects could be due to secondary hormonal or metabolic effects of hypo- or hyperthyroidism. In this study, we directly tested thyroid hormone effects on Sertoli cell proliferation and differentiation in vitro. Sertoli cells from 5-day-old rat testes were grown in serum-free medium alone (controls) or with additional triiodothyronine (T3; 1-200 nM) and/or FSH (1 microgram/ml). After 4 days, cultures were used to obtain RNA for Northern hybridization or for thymidine autoradiography. Labeling index (LI) for control cultures and cultures receiving 100 nM T3 alone was 5.2 +/- 0.5% and 5.0 +/- 0.4%, respectively. The LI of FSH-treated cultures increased to 8.4 +/- 0.8% (p < 0.01 vs. control). Cultures treated with FSH and 1, 10, 100, or 200 nM T3 had LIs of 8.0 +/- 0.9%, 6.1 +/- 0.4%, 5.3 +/- 0.6%, and 4.8 +/- 0.6%, respectively; the last three values were less than for cells receiving FSH alone (p < 0.01) or FSH + 1 nM T3 (p < 0.05). Northern hybridization indicated that mRNA levels for clusterin and inhibin-beta B, Sertoli cell secretory proteins whose production normally increases during postnatal differentiation in vivo, were significantly increased by T3 or FSH alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Localization and characterization of binding sites for endothelin in Harder's gland in rabbits.

The characterization and localization of binding sites for endothelin-1 (ET-1) labeled with iodine 125I were investigated in homogenized tissues and sections of Harder's glands of normal rabbits. The membrane of Harder's glands was harvested and incubated with 125I-ET-1 (0.25-1 nmol/L) in 20 +/- 4 mg of protein per 0.25 mL at 37 degrees C for 90 min in the presence of protease inhibitors. Specific labeling was assessed by coincubating unlabeled ET-1, ET-2, ET-3 and other unrelated cytokines. The tissue labeled with 125I-ET-1 was collected by filtration and counted in a gamma counter. For an in vitro autoradiography study, 15 microns cryostat sections were incubated with 125I-ET-1 (0.1 nmol/L). They were fixed, dipped in liquid emulsion and kept for 6 days before development. Membrane counting showed that the binding of 125I-ET-1 to Harder's gland was saturable. Scatchard data analysis revealed one class of binding with a dissociation constant (Kd) of 0.33 nmol/L and a maximal density of binding (Bmax) of 794 attomole/mg of protein. The binding was inhibited most by ET-1, followed by ET-2 and then ET-3 but not by unrelated peptides. Emulsion-dipped slides with sections showed specific high-density labeling mainly over structures identified from serial sections stained by hematoxylin-eosin as the walls of capillaries, arterioles, arteries, and veins of the glands. Less dense binding was found in both white and pink lobes of the gland. No binding was found in fat and connective tissues. The distribution of endothelin action sites in the glandular blood vessels and Harder's gland suggests that the peptide may have a role in the regulation of blood circulation and glandular secretion in the normal rabbit.

Animals↗

Autoradiographic localization of endothelin-1 binding sites in porcine skin.

Autoradiographic techniques and 125I-labeled endothelin-1 were used to study the distribution of endothelin-1 binding sites in porcine skin. Specific endothelin-1 binding sites were localized to blood vessels (capillaries, deep cutaneous vascular plexus, arteries, and arterioles), the deep dermal and connective tissue sheath of hair follicles, sebaceous and sweat glands, and arrector pili muscle. Specific binding was inhibited by endothelin-2 and endothelin-3 as well as endothelin-1. Non-specific binding was found in the epidermis and the medulla of hair follicles. No binding was found in connective tissue or fat. These vascular binding sites may represent endothelin receptors, in keeping with the known cutaneous vasoconstrictor actions of the peptide. If all binding sites are receptors, the results suggest that endothelin could also regulate the function of sweat glands and may have trophic effects in the skin.

Animals↗