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Biomedical subjects

R S Yang

Publications and source records attributed to R S Yang.

At least 19 recordsLinked to original sources

The structural basis for the electrophoretic isoforms of normal and variant human platelet arylsulphatase A.

Human platelet arylsulphatase A (ASA) exhibits a multiple banding pattern when examined by PAGE. The isoform pattern (IVa) of the enzyme obtained from normal subjects differs from variants (IIIa, IIIb, IVb) which are primarily found in alcoholic patients. Alkaline phosphatase and endo-N-acetylglucosaminidase H treatments, as well as ion-exchange chromatography, demonstrate that the isoforms of ASA arise because of charge heterogeneity caused by phosphoglycan moieties. The isoform with the slowest mobility in PAGE lacks phosphate substituents. Based upon mannose-6-phosphate-receptor affinity chromatography it can be concluded that most, if not all, of the enzyme-linked phosphate is in the form of 6-O-phospho-D-mannosyl units. Lectin affinity chromatography and peptide-N-glycosidase F treatment followed by SDS/PAGE and Western-blot analysis indicate that normal platelet ASA contains two oligomannose and/or hybrid glycan moieties of which one, or both, possess a 6-O-L-fucosyl substituent on the asparagine-linked N-acetylglucosamine residue. Comparative analysis indicates that the variant IIIa and IIIb types of ASA differ from the IVa ASA with regard to the level of glycan phosphorylation and glycan structure, as well as the polypeptide structure.

Alcoholism

Strategy for studying health effects of pesticides/fertilizer mixtures in groundwater.

This paper is a "historical account" of the entire process leading to the final implementation of a toxicology research program on the health-effect studies of pesticide and fertilizer contaminants in groundwater conducted at the National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP). Starting with the perception of a potential problem area, the program evolved through several stages, including planning and information-gathering, deliberation on experimental designs, formulation of a draft protocol, peer-review and public comments on the protocol, finalization of the protocol, announcement of open bidding to the NTP master agreement laboratories (i.e., a group of laboratories that has been previously evaluated and approved to conduct NTP toxicology contract work), implementation of chemistry developmental work, selection of toxicology laboratories and awarding of contracts, final implementation of toxicology studies, and cultivation of special collaborative efforts among NIEHS in-house scientists as well as colleagues at the neighbouring laboratories in Research Triangle Park. To put things in perspective, the author's present approach, a coupling of physiologically based pharmacokinetics/pharmacodynamics and computer modeling with the toxicology of chemical mixtures at Colorado State University, is used to address the issues of toxicology and risk assessment of chemical mixtures with respect to rationale and reality.

Animals

Morphological and immunocytochemical characterization of osteoblast cultures from long bones of neonatal rats.

The present study reports a successful culture system of rat bone cells obtained from the bare long bone fragments of neonatal Wistar rats. The morphology, histochemical and immunocytochemical properties of the cultured cells were characterized by phase contrast microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), histochemical staining with alkaline phosphatase (ALP), and immunocytochemical staining with the anti-osteocalcin antibodies. Under phase contrast microscopy, the cultured rat bone cells changed their morphology from being slender with relatively-short cytoplasmic processes to becoming polygonal with longer processes, and subsequently flattened. These cultured bone cells formed bone nodules after 3 weeks. Under SEM, the cultured bone cell appeared polygonal with some microvilli. The TEM showed that their cytoplasm contained abundant endoplasmic reticulum and well-developed Golgi apparatus. Positive histochemical staining of ALP was also detected as a blue coloration and granular appearance in the cultured bone cells. Immunocytochemistry with the polyclonal and monoclonal anti-osteocalcin antibodies showed the localization of osteocalcin in both the cytoplasm and nucleus. All these data lead us to consider that the cultured bone cells in our system were probably osteoblasts from growing bone tissue in vitro. This provides a convenient test system for further studies on the regulation of the growth and metabolism of rat bone cells.

Alkaline Phosphatase

Bizarre parosteal osteochondromatous proliferation of the phalanx: report of a case.

The bizarre parosteal osteochondromatous proliferation of the hand and foot is a benign lesion which occasionally may mimic osteochondromas, chondrosarcomas or osteosarcomas clinically, radiologically and histopathologically. This rare benign entity should be recognized in order to avoid unwarranted destructive therapy. The authors report a case of this disease and discuss the differential diagnosis and the relevant features of this disease entity. A 27-year-old female patient suffered from a painful swelling at the proximal middle phalanx of the right middle finger for five months. The lesion was excised but the residual lesion developed a distinct parosteal growth by radiologic studies one-and-a-half years later. The patient underwent reexcision of the lesion twice. No recurrence was noted 11 months following the last excision. Histopathologically, the first specimen contained bizarre chondrocytes. The recurrent nodular tumors, submitted in the second and third operations, were composed of cancellous bone with fatty marrow and a few marrow elements, and focally capped by cartilage. The adjacent soft tissue contained proliferating fibrous tissue. The osteochondral junctions in the latter two specimens were irregular. We believe that the documentation of this tumor at different stages of development has helped in the further understanding of this rare entity.

Adult

Experimental structural scoliosis in rabbits.

Structural scoliosis was produced by purely posterolateral mechanical tethering of the spine with ligation of the scapula to the opposite pelvic bone in rabbits during the growing period. It is a simple and easy method without direct trauma to the spine. When the tethering force occurred discontinuously or only in the coronal plane by drawing of the scapula to the ipsilateral pelvic bone in 17 rabbits, spinal deformity could not be produced. The model provided evidence of biplanar deformity as one of the initial factors for the development of structural scoliosis.

Animals

A new goniometer.

A newly designed goniometer is presented for rapid and accurate measurement in the orthopaedic practice. This new instrument consists of two extensible arms with special calibrations. With proper adjustment of these arms, common and specific angles, such as the Cobb angle, can be measured easily and accurately. Specific calculations of various indices can be done quickly with special calibrations on the arms. This new instrument is simple, convenient, and accurate.

Calibration

Residual damage to hematopoietic system in mice exposed to a mixture of groundwater contaminants.

To assess the potential health effects of chemically contaminated groundwater, we initiated a toxicological program on a mixture of 25 frequently-detected groundwater contaminants derived from hazardous waste disposal sites. As part of this program, myelotoxicity studies were conducted. Bone marrow parameters were examined in mice exposed to 0, 1, 5 or 10% of a simulated chemical mixture stock solution of groundwater contaminants in drinking water for 108 days. Mice treated with 5 or 10% of chemical mixture stock solution for 108 days showed suppressed marrow granulocyte macrophage progenitors (CFU-GM); however, this suppression disappeared in 10 weeks following the cessation of treatment. The possible toxicological interaction of groundwater contaminants and radiation on hematopoiesis was investigated by using the number of bone marrow CFU-GM as an index. When mice were exposed to 200 rads whole body irradiation at 2 and 9 weeks during this 10-week recovery period, the combined treatment (i.e., chemical mixture followed by irradiation) group showed a significantly slower recovery of bone marrow progenitors as compared with the control group (i.e., radiation but without prior chemical mixture treatment). This study showed that even 10 weeks after the cessation of chemical mixture treatment when all hematological parameters were normal, a residual effect of the chemical mixture may still be demonstrated as lower progenitor cell numbers following irradiation. Thus, residual damage of hematopoiesis in mice exposed to groundwater contaminants for 108 days renders the mice more sensitive to subsequent irradiation-induced injury.

Animals

Plate fixation for anterior cervical interbody fusion.

From April 1989 to April 1990, 13 patients with cervical spinal fracture/dislocation, spondylosis or metastasis were treated at the respective hospitals. There were 4 women and 9 men whose ages ranged from 25 to 70 years (mean 45 years). All of them were treated with neural decompression, bone grafting and anterior spinal interbody fusion. All iliac crest or fibular bone grafts were anchored to the vertebral bodies with plates and screws. The clinical outcomes were evaluated retrospectively. The results showed that all had improvement of neurological symptoms and signs. The radiographic evaluation revealed satisfactory alignment and sound union of the cervical spine in all 13 patients. No serious complications were found except screw loosening in two instances without impairment of clinical results. We concluded that anterior cervical plates provide effective stabilization which is essential for good results. Furthermore, from this study and a review of the literature, we advocated that it was not necessary for the tip of the screws to reach or even penetrate the posterior cortex of the vertebral body.

Adult

Traumatic dislocation of the hip.

Of 125 patients with traumatic dislocation of the hips treated, 96 were reviewed retrospectively; 80 were males and 16 females with an age range from seven to 81 years (mean, 33.5 years). Motorcycle accidents were the leading cause of traumatic dislocation in this series (40 cases, 42%). Associated injuries were found in 68 cases (70.8%). Seventy-seven hips (80%) were reduced within 24 hours. In follow-up periods ranging from 15 months to 18 years (mean, 7.5 years), 56 patients had excellent or good results (58.3%). Statistical analysis of the clinical results showed that those patients with simple dislocations had better functional recovery. The earlier the reduction, the better the results. Associated injuries affected prognoses. Good results were obtained in patients with early, stable, and accurate reductions by either closed or open methods.

Accidents, Traffic

Supracondylar fractures of the femur.

Ninety-three supracondylar fractures of the femur treated with 95 degrees angulated condylar plates were retrospectively evaluated. Seventy-one patients were males and 22 were females; ages ranged from 15 to 80 years (mean, 46.9 years). Seventy-two patients were involved in traffic accidents; 44 of them were victims of motorcycle accidents. Twenty patients sustained open fractures. Fifty patients had associated injuries, 41 of them had multiple fractures. There were 13 patients referred for management of complications. The followup periods ranged from 1 to 10 years (4.6 years). Seventy-nine patients had excellent/good results. Eighty-one patients achieved sound union. Stiffness of knee, nonunion, delayed union, and infection were the major complications. Careful selection of the patients, adherence to the principles of anatomic reduction and rigid fixation, and early mobilization are essential for satisfactory outcomes.

Adolescent

Approaches used by the US National Toxicology Program in assessing the toxicity of chemical mixtures.

The US National Toxicology Program has made a definite commitment towards improving the understanding and predictability of the toxicity of chemical mixtures. The commitment has consisted of a thorough review by the National Research Council of the state of the art of complex mixture testing and strategy for in vivo tests as well as a series of laboratory studies to better characterize the toxicity of selected chemical mixtures and research programmes to improve our ability to predict the toxicological properties of other mixtures.

Animals

Toxicity and mutagenicity of a mixture of 25 chemicals found in contaminated groundwater.

A defined mixture of 25 chemicals that are often found in contaminated groundwater was prepared as an aqueous solution and studied for mutagenicity in bacteria, for prophage induction in bacteria, for palatability and effect on weight-gain in rats and mice, and for cytogenetic effects in bone marrow cells of rats and mice. The bacterial mutation and prophage induction tests were negative. Exposure to the mixture in drinking water for two weeks resulted in a concentration-related decrease in water consumption in male and female rats and mice. Concentration-related decreases in weight gain were observed in male and female mice; in rats, only the high-dose groups showed decreased weight gains. A small but significant increase in sister chromatid exchanges was seen in male mice and a similar weak effect on micronucleated polychromatic erythrocytes (PCE) in the bone marrow of males and females. Also in bone marrow of male and female mice, an increase in mitotic index and a decrease in average cell generation time was observed. The %PCE in bone marrow was decreased in female mice only, while the %PCE in peripheral blood was increased in both sexes. In rats, the only effects observed in the cytogenetic studies were increased PCE frequencies in the peripheral blood of males and in the bone marrow of males and females. These results indicate that the 25-chemical mixture studied is not genotoxic in bacteria and that a concentration-dependent effect on its palatability to rodents leads to reduced water consumption, food consumption and weight gain. Although the bone marrow effects may be associated with disruptions of normal erythropoiesis that, in turn, alter the cytogenetic end-points reported, elevations of SCE and MN-PCE in mice suggest the 25-chemical mixture, under the conditions of administration, leads to cytogenetic damage in the bone marrow. Such damage may indicate a potential health hazard.

Animals

Thirteen-week toxicity study of n-hexane in B6C3F1 mice after inhalation exposure.

B6C3F1 mice were exposed to n-hexane 6 h/day, 5 days/week for 13 weeks at concentrations of 0, 500, 1000, 4000, and 10,000 ppm and at 1000 ppm 22 h/day, 5 days/week for 13 weeks (1000C group). Toxicological endpoints assessed included clinical signs, body and organ weight changes, gross and histopathology, neuropathology, and a battery of neurobehavioral tests. All mice survived the treatment. Exposure-related effects of n-hexane included sneezing at 10,000 ppm and body weight gain depression at 1000C and 10,000 ppm. Histopathologic changes included mild inflammatory, erosive and regenerative lesions in the olfactory and respiratory epithelium of the nasal cavity at 1000C, 4000, and 10,000 ppm. The only neurobehavioral parameter affected was a decrease in locomotor activity in female mice at 1000C and 10,000 ppm. In teased fiber preparations of tibial nerve, paranodal axonal swellings were observed at 1000C or at 10,000 ppm, but not in the control groups. The severity of the peripheral nerve lesion was mild. These studies show that n-hexane has minimal toxicity to the nervous system and respiratory system of mice.

Administration, Inhalation

Toxicology studies of a chemical mixture of 25 groundwater contaminants. I. Chemistry development.

As part of an effort to evaluate the toxicology of a chemically defined mixture of 25 frequently detected groundwater contaminants, we report here the formulation and analytical chemistry of this mixture. Many problems were anticipated, including limitation of solubility, chemical interactions, and extreme volatility in the aqueous solution of 25 chemicals. The final technically achievable stock solution was prepared based on EPA survey concentrations of these chemicals in groundwater around hazardous waste disposal sites, their toxicity information, and solubility of the individual compounds in the matrix of the aqueous solution of these 25 chemicals. Because the anticipated animal studies were to be conducted at various laboratories, for ease of handling and maximum stability, the stock solution was stored or shipped as two substock solutions: an organic substock with 18 neat organic chemicals in a glass vial sealed with minimum headspace and an aqueous substock solution with 6 metals of various salt forms and phenol. The concentrations of the solutions were such that direct mixing of the organic and aqueous substocks produced the desired high dose level for the animal experiments. Analyses of all 25 chemicals in the drinking water mixture required six different chromatographic and spectroscopic methods. Some loss of organic volatiles during mixing of the substocks and during the first 24 hr following preparation did occur. However, the concentrations of acetone, phenol, and all the metals remained constant during preparation. Solutions held under simulated animal cage conditions for 96 hr showed losses of the organic volatiles; the majority of which occurred within the first 24 hr. This study shows that it is possible to conduct animal experiments on an aqueous mixture containing 25 groundwater contaminants. Furthermore, a reasonable estimate of intake of individual chemicals can be achieved provided that dosing solutions are prepared fresh at frequent intervals (e.g., 48 to 72 hr) and that comprehensive analyses are carried out.

Acetone

Toxicology studies of a chemical mixture of 25 groundwater contaminants. II. Immunosuppression in B6C3F1 mice.

Concern over the potential adverse health effects of chemically contaminated groundwater has existed for many years. In general, these studies have focused on retrospective epidemiological studies for cancer risk. In the present studies, immune function was monitored in female B6C3F1 mice exposed to a chemical mixture in drinking water for either 14 or 90 days. The mixture consisted of 25 common groundwater contaminants frequently found near toxic waste dumps, as determined by EPA surveys. None of the animals developed overt signs of toxicity such as body or liver weight changes. Mice exposed to the highest dose of this mixture for 14 or 90 days showed immune function changes which could be related to rapidly proliferating cells, including suppression of hematopoietic stem cells and of antigen-induced antibody-forming cells. Some of these responses, e.g., granulocyte-macrophage colony formation, were also suppressed at lower concentrations of the chemical mixture. There were no effects on T cell function or T and B cell numbers in any of the treatment groups. Altered resistance to challenge with an infectious agent also occurred in mice given the highest concentration, which correlated with the immune function changes. Paired-water studies indicated that the immune effects were related to chemical exposure and not to decreased water intake. These results suggest that long-term exposure to contaminated groundwater may represent a risk to the immune system in humans.

Animals

Toxicology studies of a chemical mixture of 25 groundwater contaminants. III. Male reproduction study in B6C3F1 mice.

A mixture of chemicals has been developed that models contaminated groundwater around hazardous waste sites. We investigated the effects of this mixture on spermatogenesis in B6C3F1 mice. The animals consumed three different concentrations of this mixture for 90 days, after which time they were euthanatized. Although there was a concentration-related decrease in the amount of fluid consumed at the higher two concentrations, there were no differences in body weight among the groups. Similarly, there was no effect of mixture consumption upon the histology of liver, kidney, testis, epididymis, or seminal vesicles or upon the absolute organ weights of these organs. Kidney weight relative to body weight was increased in the high dose group. Epididymal sperm number and testicular spermatid count were not affected by treatment. These studies show that, at exposure levels that decrease fluid intake and increase adjusted kidney weight, there were no effects of this mixture on gametogenesis in male mice.

Animals

Toxicology of chemical mixtures: experimental approaches, underlying concepts, and some results.

The toxicology of chemical mixtures will be the toxicology of the 1990s and beyond. While this branch of toxicology most closely reflects the actual human exposure situation, there is yet no standard protocol or consensus methodology for investigating the toxicology of mixtures. Thus, in this emerging science, experimentation is required just to develop a broadly applicable evaluation system. Several examples are discussed to illustrate the different experimental designs and the concepts behind each. These include the health effects studies of Love Canal soil samples, the Lake Ontario Coho salmon, the water samples repurified from secondary sewage in the city of Denver Potable Water Reuse Demonstration Plant, and the National Toxicology Program (NTP) effort on a mixture of 25 frequently detected groundwater contaminants derived from hazardous waste disposal sites. In the last instance, an extensive research program has been ongoing for the last 2 years at the NTP, encompassing general toxicology, immunotoxicology, developmental and reproductive toxicology, biochemical toxicology, myelotoxicology, genetic toxicology, neurobehavioral toxicology, and hepato- and renal toxicology.

Animals

Experimental allograft in spinal fusion in dogs.

Fifty-six dogs were used for the comparison of the allogenous and autogenous bone graft in anterior interbody and posterior spinal fusion. Excluding 7 cases with wound infections, the end results of the allograft and autograft in anterior interbody and posterior spinal fusion were nearly the same, provided that the rules of technique for the spinal fusion were strictly followed, especially in the allograft group. Grossly, there was a reduction tendency in the fusion mass of the allograft group that was proven by roentgenographic examination of the harvested spinal block. Histologically, there was no evidence of regeneration of the allograft that can be readily detected in the autograft. In the allograft group, osteogenesis can only be seen in the recipient sites, the allograft transplants become sequestrated and resorbed.

Animals