Biomedical subjects
Publications and source records attributed to J Pan.
A case of successful replantation of multiple digits and circular palm amputation caused by an industrial punch force is reported. The two-level amputation was reconstructed by first replanting the severed fingers to the palmar segment and then connecting the palm segment to the hand stump. An arterial crisis was treated with urokinase, and postoperative functional recovery is described.
Previous work in our laboratory demonstrated that cytochrome P450 2B1 in rat liver was induced, but P450 2E1 was inhibited and inactivated, by diallyl sulfide (DAS), a compound derived from garlic. Such a selective effect on P450 enzymes is of considerable interest toward the understanding of dietary effects on xenobiotic metabolism. In the present study, the mechanism of P450 2B1 induction by DAS was investigated. Following a single dose of DAS (200 mg/kg body weight, ig), liver microsomal pentoxyresorufin dealkylase (PORd) activity, a representative activity of P450 2B1, was induced 3-, 16-, 26-, and 43-fold at 6, 12, 18, and 24 h after the treatment, respectively. A corresponding increase in the level of P450 2B1/2 protein was observed by immunoblot analysis. The level of P450 2B1/2 mRNA in rat liver also increased markedly, reaching a maximum at 12 h after the DAS treatment. Hybridization with the isozyme-specific oligonucleotide probes revealed that the mRNA levels of both P450s 2B1 and 2B2 were induced. In contrast, the level of P450 2E1 mRNA in the liver of DAS-treated rats was not changed. The results of nuclear run-on assay revealed that the transcriptional rate of P450 2B1/2 genes in the rat liver increased 13-fold at 6 h after DAS administration and returned to the control value at 24 h. The transcription of P450 2B1/2 genes was blocked completely by alpha-amanitin, an inhibitor of RNA polymerase II. These results clearly demonstrate that the induction of P450 2B1/2 in rat liver by DAS is mainly due to transcriptional activation. In the DAS-treated rats, P450 2B1/2 mRNA was also markedly induced in the stomach and duodenum. The maximal induction was found at 12 h after the treatment while the levels of P450 2B1/2 mRNA increased 66-fold in the duodenum and 23-fold in the stomach. DAS treatment, however, did not change the levels of P450 2B1/2 mRNA in the lung and nasal mucosa.
Nitric oxide is thought to play an important role in the mediation of the cardiovascular features of septic shock. We determined plasma levels of nitrite and nitrate (not differentiated in measurement) in neonates with sepsis and found these levels to be elevated at the time of entry compared with those of control subjects (p < 0.05); the levels were significantly higher in the patients with sepsis and shock than in those without shock (p < 0.05). Elevations of nitrite plus nitrate were correlated with tumor necrosis factor and severity of illness judged by pediatric risk of mortality (PRISM) scores at onset (p < 0.05). Of 8 newborn infants with a nitrite-plus-nitrate value > 200 mumol/L, 6 had septic shock; none of 12 not reaching that cutoff value had septic shock (p < 0.05). Levels of nitrite plus nitrate were elevated as much in gram-positive as in gram-negative sepsis. We conclude that the determination of circulating plasma levels of nitrite plus nitrate may be useful in forecasting the severity of illness and the occurrence of septic shock; therapeutic approaches associated with inhibition of nitric oxide synthesis may be worth trying in infants with septic shock.
In a rat model of fatal infection caused by Pseudomonas aeruginosa, the circulating level of nitrite/nitrate (NO2-/NO3-), a good indicator for nitric oxide production, was remarkably increased after elevation of circulatory tumor necrosis factor (TNF). Anti-TNF MAb cotreatment was shown to blunt hypoglycemia and hyperlacticemia and was associated with decreased mortality of septic animals. Moreover, anti-TNF MAb significantly reduced not only plasma TNF but also plasma NO2-/NO3- levels. Dexamethasone had a similar effects, and when anti-TNF MAb was used in combination with dexamethasone, the suppression of nitric oxide production and the protective efficacy were more remarkable compared with therapy with either anti-TNF MAb or dexamethasone alone. Our present data suggested that the protective efficacy of anti-TNF MAb may correlate with the suppression of nitric oxide production and also with a modulation in metabolic abnormalities in the septic newborn rats.
Myocardial revascularization by Nd: YAG laser used in rats with myocardial infarction was studied. The left coronary artery was ligated and the laser channels with a diameter of 300 microns were made immediately by 2.5-4.2 W lasersonics YAG unit. After 24 hours, the rats were killed. Evaluation included hemodynamics, lactate dehydrogenase of myocardium and myocardial infarct size. The results showed that laser myocardial revascularization reduced myocardial infarct size and enzyme leakage, and improved left ventricular function. The study may provide theoretical basis for the clinical applications of this new technique in the treatment of ischemic heart disease.
Pulmonary complications from impaired airway secretion clearance mechanisms are major causes of morbidity and mortality for post-poliomyelitis individuals. The purpose of this study was to review the long-term use of manually assisted coughing and mechanical insufflation-exsufflation (MI-E) by post-poliomyelitis ventilator-assisted individuals (PVAIs) and to compare the peak cough expiratory flows (PCEF) created during unassisted and assisted coughing. Twenty-four PVAIs who have used noninvasive methods of ventilatory support for an average of 27 years, relied on methods of manually assisted coughing and/or MI-E without complications during intercurrent respiratory tract infections (RTIs). Nine of the 24 individuals were studied for PCEF. They had a mean forced vital capacity (FVC) of 0.54 +/- 0.47L and a mean maximum insufflation capacity achieved by air stacking of ventilator insufflations and glossopharyngeal breathing of 1.7L. The PCEF were as follows: unassisted, 1.78 +/- 1.16L/sec; following a maximum assisted insufflation, 3.75 +/- 0.73L/sec; with manual assistance by abdominal compression following a maximum assisted insufflation, 4.64 +/- 1.42L/sec; and with MI-E, 6.97 +/- 0.89L/sec. We conclude that manually assisted coughing and MI-E are effective and safe methods of airway secretion clearance for PVAIs with impaired expiratory muscle function who would otherwise be managed by endotracheal suctioning. Severely decreased maximum insufflation capacity but not vital capacity indicate need for a tracheostomy.
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Our previous studies demonstrated that the sex-related difference in renal metabolism of N-nitrosodimethylamine in C3H/HeJ mouse was due to the sexual dichotomy of cytochrome P450 2E1 (P450 2E1) and that renal P450 2E1 in female mouse was inducible by testosterone. The present study demonstrates that the sex-related difference in renal P450 2E1 and the testosterone-mediated regulation also occurred in other mouse strains studied. The time- and dose-responses in the testosterone-mediated regulation of P450 2E1 were characterized. 19-Nortestosterone, an analog of testosterone, was shown to have an effect on the regulation of mouse renal P450 2E1 similar to that of testosterone. Testicular feminized mice (Tfm, a mouse strain devoid of functional androgen receptors) had about only one-tenth the renal P450 2E1 mRNA level as the wild-type male mice and testosterone treatment of the Tfm mice had no effect on the level of renal P450 2E1 mRNA. The result suggests that androgen receptor plays an important role in the sex- and testosterone-related regulation of mouse renal P450 2E1. To study the mechanism of the sex-related and testosterone-mediated regulation of P450 2E1 mRNA in mouse kidney, the transcription rate of the P450 2E1 gene was measured by a nuclear run-on transcription assay. Although the kidneys of male and testosterone-treated female mice had much higher steady-state levels of P450 2E1 mRNA, their transcription rates of the P450 2E1 gene were not higher than the kidneys of untreated female mice. This result suggests that the sex- and testosterone-related regulation of mouse renal P450 2E1 is predominantly at the post-transcriptional level.
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In embryogenesis, ovarian surface epithelial cells and ovarian granulosa cells arise through divergent differentiation from a common mesenchymal precursor, the urogenital ridge. In the adult rat, ovarian surface epithelial cells are nonsteroidogenic and keratin positive, while ovarian granulosa cells are steroidogenic and keratin negative. In culture, Kirsten murine sarcoma virus-transformed, tumorigenic ovarian surface epithelial cells continued to express keratin but also became steroidogenic. Transformed ovarian granulosa cells remained steroidogenic but also acquired keratins. Mesodermally derived cells from other sources did not show these differentiation-related changes in response to transformation. The results suggest that v-ras oncogenes may cause the reversion of adult, developmentally related cells to the phenotype of a common, multipotential precursor. They also demonstrate the capacity of v-ras to either induce or reduce the same differentiated characteristic, depending on the developmental history of the target cells.
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Diallyl sulfide (DAS), a component of garlic oil, has been shown to inhibit tumorigenesis by several chemical carcinogens. Our previous work demonstrated that DAS inhibited the metabolic activation of carcinogenic nitrosamines, including the tobacco-specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in rat lung and nasal mucosa microsomes. In the present study, the effects of DAS on the tumorigenicity and the metabolism of NNK in A/J mouse lung were examined. Female A/J mice at 7 weeks of age were pretreated with DAS (200 mg/kg body wt in corn oil, p.o) daily for 3 days. Two hours after the final DAS treatment, the mice were either given a single dose of NNK (2 mg/mouse, i.p.) and kept for an additional 16 weeks for determining the production of pulmonary tumors, or were killed immediately so as to measure the microsomal activity in metabolizing NNK. In comparison to the vehicle control group, DAS pretreatment significantly decreased the incidence of NNK-induced lung tumors (37.9 versus 100%) and the tumor multiplicity (0.6 versus 7.2 tumors/mouse). In pulmonary metabolism of NNK, DAS pretreatment reduced the rates of formation of keto aldehyde, keto alcohol, NNAL-N-oxide, and NNK-N-oxide by 70-90%. In addition, the formation of NNK oxidative metabolites from NNK in the liver microsomes from DAS-pretreated mice was remarkably reduced. DAS also inhibited the metabolism of NNK in mouse lung microsomes in vitro. These results demonstrate that DAS is an effective chemopreventive agent against NNK-induced lung tumorigenesis, probably by inhibiting the metabolic activation of NNK.
Interrelationships between neoplastic progression and the expression of intermediate filaments were examined in primary cultures, immortal lines, and Kirsten murine sarcoma virus (KiMSV) transformed lines of rat ovarian surface epithelial (ROSE) cells. Immunofluorescence microscopy revealed abundant keratin filaments in all cells of primary cultures. In immortal, nontumorigenic lines, keratin filaments were detected in fewer cells, in smaller numbers, and in microscopically altered forms. The percentage of keratin-positive cells ranged from 4 to 54%. Its expression was inversely proportional to cell density. Keratin expression was similar in the two immortal lines, although one had retained a monolayered epithelial growth pattern resembling primary cultures, while in the other the growth pattern of the cells was more atypical. The two KiMSV-transformed lines were previously shown to produce tumors in vivo that resemble human ovarian endometrioid stromal sarcomas. In spite of this histologic appearance, the proportion of keratin-positive cells in these cells was increased over the immortal lines. Keratin expression was unrelated to cell density, and keratin in most virally transformed cells was limited to few, fine filaments. In thymidine-labelled immortal and virus-transformed cultures stained for keratin, no correlation was found between keratin expression and proliferative activity. The keratin profiles of primary and immortal cultures were identical on Western blots, with subtypes ranging from 52 to 66 kDa. The two virally transformed lines lacked some of the subtypes. Vimentin networks were faint or absent in primary cultures. In the immortal and the virus-transformed lines, neoplastic progression was associated with increasing vimentin expression but with no changes in filament morphology and distribution. The results show that the abnormalities in intermediate filament expression that accompany immortalization do not preclude the retention of a normal epithelial morphology and growth pattern in this cell type. Furthermore, the number of intermediate filaments and their intracellular distribution appear to be altered at an earlier stage in neoplastic progression than those mechanisms that select for specific keratin subtypes, or those that respond to regulation by cell density. Finally, the presence of keratin in the KiMSV-transformed lines examined in this study supports the hypothesis that human ovarian stromal sarcomas can arise in the OSE.
The constituents of essential oils obtained from the leaves, stems, and fruits of Perilla frutescens were analysed by GC-MS. 65 compounds including perilla aldehyde, perilla alcohol, trans-caryophyllene and hexadecanoic acid, etc. were identified. Their percentages in the oils were given.
The sensitivity of Western blots is limited by the avidity of antibody-antigen interactions, and by problems of specificity in interactions between antibodies and antigens from different species. Using rat and human keratins as the antigens, and a set of antibodies against human and rat keratins, this study demonstrates that mild treatment of nitrocellulose blots with trypsin and/or pepsin enhances the sensitivity of the assay and permits the cross-species demonstration of antigens that are not otherwise detectable.
Pathologic changes in superficial temporal arteries (STA) and middle meningeal arteries (MMA) biopsied from 15 patients with moyamoya disease (MD) who had undergone cerebro-temporal arterio-synangiosis were studied histologically, ultrastructurally and immunohistochemically. The main pathologic features were: proliferation of smooth muscle cells (SMCs) and thickening of the intima, degeneration and destruction of SMCs in the media and intima, and the presence of condensed organelles in necrosed SMCs or the interstitium among SMCs, or both outside and within the elastica interna (EI). The EI had become thin, porous, fragmented and was even absent in some segments. These changes are different from those of other forms of angiopathy, but identical with those at the ends of internal carotid arteries (ICA) reported by us previously, being pathognomonic for MD. These changes in the STA and MMA reveal that MD involves not only the ICA but also the intra- and extracranial branches of external carotid arteries. The medial necrosis of SMCs seems to be the primary injury of the arterial wall in MD. STA tissue blocks from two cases of MD were stained immunohistochemically. By electron microscopy, IgG-, IgM-, and C3-positive granules were observed on the ER of endothelial and intimal cells. Further studies on more cases are needed to determine whether an immunoreaction has occurred in these arteries.
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