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Biomedical subjects

J J Yang

Publications and source records attributed to J J Yang.

At least 127 records · Page 7Linked to original sources

LINKERS: a simulation programming system for generating populations with genetic structure.

Significant features are described of a Monte Carlo simulation system, LINKERS, that generates nuclear family data conforming to one locus and two loci genetic models. Software engineering techniques help to produce a user friendly environment for studies of genetic ascertainment. LINKERS' 39 code modules are maintained and optimized using VAXset. Within a VAX/VMS workstation environment LINKERS generates a useful population of 10,000 families in 1 min. An example is presented to illustrate the use of LINKERS. Generated data were analysed using the segregation program POINTER. Likelihood ratio tests showed the effects of multiple alleles, gene frequency and incorrect specification of disease prevalence.

Computer Simulation↗

Pathologic findings associated with interleukin-2-based immunotherapy for cancer: a postmortem study of 19 patients.

The use of interleukin-2 (IL-2), either alone or in combination with lymphokine-activated killer cells, tumor infiltrating lymphocytes, or other immunotherapeutic agents has added a new list of alternatives to conventional antineoplastic regimens. Little information is available about the pathologic changes occurring in patients treated with these agents. In this study, we reviewed the necropsy materials from 19 patients, 12 men and 7 women, with a variety of malignancies including melanoma, renal cell carcinoma, gastrointestinal and pulmonary adenocarcinoma, and metastatic gastrinoma, who died after receiving IL-2-based immunotherapy. Death occurred at intervals ranging from less than 1 hour to 143 days following the last dose of therapy. All patients dying at or less than 43 days following cessation of therapy had lymphoid infiltrates of varying intensity in residual tumor. At necropsy, the major cause of death unrelated to the presence of metastatic tumor was bacterial sepsis. In addition, we found evidence of significant cardiac and pulmonary toxicity: two patients with acute myocardial infarction, one with and one without significant coronary artery disease, two cases of unexplained lymphocytic myocarditis, and one case of fatal pulmonary capillary plugging following an infusion of lymphokine-activated killer cells. Thus, not unlike other forms of therapy for cancer, IL-2-based immunotherapy does not appear to be without significant toxicity.

Adult↗

Primary renovascular effects of erythromycin in the rat: relationship to cyclosporine nephrotoxicity.

Erythromycin is known to exacerbate cyclosporine nephrotoxicity. This has been attributed to the potential of erythromycin to reduce the hepatic microsomal metabolism and clearance of cyclosporine. Erythromycin may also be nephrotoxic. We tested the hypothesis that erythromycin may have direct effects on the renal vasculature which are additive or synergistic with the effects of cyclosporine. Sprague-Dawley rats were administered graded doses of either erythromycin, 2.5, 5, 7.5, and 10 mg/kg BW/min i.v. over consecutive 10-min intervals; cyclosporine, 1, 2, 3, and 4 mg/kg BW/min i.v. over consecutive 10-min intervals; or both drugs simultaneously. In separate experiments, identical doses of erythromycin or cyclosporine were infused intravenously following acute unilateral renal denervation. Infusion of erythromycin led to an initial decline in arterial blood pressure whereas infusion of cyclosporine resulted in a dose-related increase in arterial blood pressure. Despite these different systemic effects, each drug alone produced a striking decrease in renal blood flow. This effect was more pronounced when the drugs were infused concomitantly. The reduction in renal blood flow occurred in an additive manner as a direct consequence of increased renal vascular resistance. Prior renal denervation did not modify the response to either erythromycin or cyclosporine. These results demonstrate that cyclosporine-induced vasoconstriction is exacerbated by erythromycin and suggest that the decline in renal function observed in patients coadministered these drugs may be due in part to additive renovascular toxicity.

Adult↗

[Synthesis of ganoderma alkaloid A and B].

Ganoderma alkaloid A (IA, 1-isopentyl-2-formyl-5-hydroxymethylpyrrole) and B (IB, 1-phenylethyl-2-formyl-5-hydroxymethylpyrrole) were discovered in the hypha of deep fermented Ganoderma capense. Both are new pyrrole alkaloids. In order to provide samples for bioassay, we completed the synthesis of these new alkaloids and their acetyl derivatives. The route of synthesis included six steps. The whole yields were 20.7% for IA and 24.7% for IB. Synthetic IA and IB were found to be identical with the natural compounds by comparison of spectral data. IA and IB showed some antiinflammatory activity in animal experiments.

Alkaloids↗

[Chemical constituents of Armillaria mellea mycelium. VI. Isolation and structure of armillaripin].

A new protoilludane sesquiterpenoid aromatic ester, named armillaripin, C24H30O6, mp 202-204 degrees C, [alpha]D15 + 130 degrees (c 0.055, CHCl3), was isolated from the petroleum ether extract of the artificially cultured mycelium of Armillaria mellea (Vahl. ex Fr.) Quel. (Tricolometaceae) by silica gel chromatography. On the basis of spectral (UV, IR, 1HNMR 13CNMR and MS) analysis its structure was deduced as I and confirmed by single-crystal X-ray analysis.

Agaricales↗

Pre- and postoperative sequential study on the immunosuppressive activity of serum and cell-free skin bleb fluid of patients with lung cancer and esophageal cancer.

Serial changes of immunosuppressive activity of serum and cell-free skin bleb fluid that can suppress the activity of acid a-naphthyl acetate esterase (ANAE) of lymphocytes and phagocytosis of macrophages were detected by immunoregulatory tests in vitro in 50 lung cancer and 42 esophageal cancer patients. In comparing these tests with those of 53 cases of noncancerous thoracic lesion and 69 normal adults, the immunosuppressive activity of serum and skin bleb fluid from cancer patients is significantly higher than that of noncancerous thoracic lesions and normal individuals (P less than .01). The activity is related to the stages of cancer, the size of primary tumor, the presence of lymph node metastasis, and tumor resect-ability, but not to histological classification, sex, and age. The immunosuppressive activity of serum and skin bleb fluid decreased gradually after the removal of the tumor and was eliminated on the 30th postoperative day. These results suggest that serum and skin bleb fluid from cancer patients may contain immunosuppressive factors that can suppress the immune responsive functions of lymphocytes and macrophages in vitro in a manner similar to that seen in vivo. Therefore, complete surgical removal of cancer is likely the most effective immunotherapy.

Adult↗

Functional and psychosocial effects of multimodality limb-sparing therapy in patients with soft tissue sarcomas.

We have documented functional and psychosocial changes in patients with extremity soft tissue sarcomas who have undergone multimodality limb-sparing treatments. In 88 patients, parameters related to economic status, sexual activity, pain, limb function, and global quality of life (QOL) were recorded prior to surgery and every 6 months postoperatively. Changes from the preoperative assessment for every parameter were analyzed in each patient. Six months after surgery, there was a decrease in employment status, sexual activity, and in limb function in a significant number of patients. At 12 months, these decreases were still evident. Despite these changes, global QOL measured by a standardized test showed at least some improvement in a significant proportion of patients at 12 months. These findings highlight the difficulty in defining QOL. It could not be ascertained if radiation therapy and/or chemotherapy were causative factors in specific changes because of the small numbers of patients in each subgroup. However, among 60 patients with high-grade sarcomas, significant wound problems developed in 10 of 33 who received postoperative radiation therapy in combination with adjuvant doxorubicin and cyclophosphamide chemotherapy compared with one of 27 patients who received adjuvant chemotherapy alone (P = .016). Also, among high-grade sarcoma patients with 12-month follow-up, six of 19 patients who received radiation therapy and chemotherapy developed joint contractures compared with zero of 15 patients who received chemotherapy alone (P less than .04). The combination of postoperative radiation therapy and chemotherapy appeared to be associated with significantly more tissue-related injury in patients with high-grade sarcomas compared with chemotherapy alone.

Adolescent↗

[Surgical treatment of primary pulmonary cryptococcal granuloma--report of 4 cases].

Primary pulmonary cryptococcal granuloma is not common in Sichuan. The diagnosis of this disease is difficult to make because the patient has no characteristic symptoms and the chest X-ray findings of the mass are not easily differentiated from carcinoma of the lung. The incidence of this disease is apparently increasing. Pulmonary cryptococcosis may be disseminated hematogenously to the meninges and cryptococcal meningitis is very difficult to treat. If the pulmonary lesion is localized, the patient's general condition is good with no evidence of systemic lupus erythematosis, diabetes, leukemia or lymphoma, partial resection of the lung is indicated. But, if the patient has a history of recent cryptococcal meningitis, surgery must be deferred. Four cases of primary pulmonary cryptococcal granuloma have been treated surgically supplemented with medical therapy in the First Affiliated Hospital from 1986 to 1987. Follow-up of more than one year showed good results in each case.

Adult↗

Order of response surfaces for representation of a Monte Carlo epidemic model.

Response hypersurfaces for two selected outcomes and for 6 model features were generated for Latin Hypercube (LH) samples of the parameter space of a discrete, micro-population, Monte Carlo model of an epidemic of an infectious disease agent. SAS stepwise, multivariate regression routines were used to generate response hypersurfaces of first, second and third order in the model features for each outcome. These are used as illustrative examples to examine the appropriateness of the order of the polynomial describing the response hypersurface. The response hypersurfaces are very dependent on the model outcomes and also on the selected ranges of the model features. Results indicate that there is little reason to prefer any particular order for the response hypersurfaces. Further, it is suggested that apparent interaction terms found when using quadratic and cubic response hypersurfaces may represent artifacts of the choice of a particular order for the response hypersurface. Nonetheless, the comparison of the 3 orders of response hypersurfaces can, under some circumstances, reveal basic characteristics of the sensitivity of the outcome to the model features.

Computer Simulation↗

Percutaneous and oral absorption of chlorinated paraffins in the rat.

Parallel percutaneous absorption studies of two 14C-labelled chlorinated paraffins (C18, 50-53% chlorination; C28, 47% chlorination) were carried out in the Sprague-Dawley rat. The dermally applied dose (66 mg/cm2) was approximately equivalent to 2.0 g/kg of body weight. An oral absorption study with the C18-chlorinated paraffin (0.5 g/kg) was carried out in rats for comparison. Less than 1% of the dermally applied dose of [1-14C]polychlorooctadecane (50-53% chlorination) and less than 0.1% of the applied dose of [14,15-14C]polychlorooctacosane (47% chlorination) were recovered in excreta, expired air and tissues after 96 hours. In contrast, approximately 86% of the orally administered dose of [1-14C]polychlorooctadecane (0.5 g/kg) was recovered. These results indicate that rat skin acts as an effective barrier to chlorinated paraffins containing eighteen or more carbons and more than 40% chlorine by weight. The oral absorption of the C18 chlorinated paraffin can be estimated to be nearly 100 times greater than its dermal absorption. Based on current toxicity results from rodent experiments and these present findings, chlorinated paraffins of the type tested would be expected to have little or no effect in animals as a result of dermal exposure. It is reasonable to assume that such chlorinated paraffins are unlikely to be systemically toxic to humans by skin contact under normal conditions of production and use.

Administration, Cutaneous↗

Percutaneous absorption of benzo[a]pyrene in the rat: comparison of in vivo and in vitro results.

Percutaneous absorption of 14C-labeled benzo[a]pyrene (BaP) was studied in five-day in vivo and in vitro experiments with female Sprague-Dawley rats following single topical doses of 9-10 micrograms/cm2. The in vivo percutaneous absorption was measured by the presence of 14C radioactivity in urine, feces and tissues. In vitro percutaneous absorption was measured with excised (non-viable) skin in Franz-type diffusion cells. Several modifications of standard diffusion cell techniques which are known to enhance the transport of lipophilic compounds were evaluated. In vitro penetration was determined by directly measuring the level of 14C radioactivity in the receptor fluid. BaP was observed to readily penetrate in vivo with a total of 46.2% (n = 4, SD = 3.4%) of the applied dose being absorbed over five days. In in vitro experiments using an approximately 350 micronthick skin section and normal saline receptor solution, only 2.1% of the applied BaP diffused into the receptor fluid over five days. In in vitro experiments using full-thickness skin and a 6% solution of nonionic surfactant receptor fluid, 28.0% of the applied BaP diffused into the receptor fluid over five days. When both an approximately 350 microns-thick skin section and a 6% surfactant receptor solution were used in vitro, 49.9% (n = 4, SD = 3.1%) of the BaP dose was found in the receptor fluid after five days. The results show that the modified in vitro method is suitable for studying percutaneous absorption of lipophilic compounds such as BaP.

Administration, Cutaneous↗

Percutaneous absorption of anthracene in the rat: comparison of in vivo and in vitro results.

The present study was conducted to evaluate the applicability of in vitro percutaneous absorption techniques to estimate in vivo absorption of polynuclear aromatic (PNA) compounds commonly found in mineral oils. The percutaneous absorption of 14C-labeled anthracene, a three-ring PNA, was compared in a six-day in vivo and in vitro experiment with female Sprague-Dawley rats following a single topical dose (9.3 micrograms/cm2). In vivo absorption was measured by the presence of 14C radioactivity in urine, feces and tissues and in vitro absorption by penetration of radioactivity through excised skin into the receptor fluid of Franz-type diffusion cells. Several modifications of standard diffusion cell techniques were used which are known to enhance the absorption of lipophilic compounds. Anthracene was observed to readily penetrate the skin in both experiments and the total amounts absorbed in vivo and in vitro were seen to gradually coalesce over time. Within six days after application, 52.3 and 55.9% of the administered anthracene was absorbed in vivo and in vitro, respectively.

Administration, Cutaneous↗