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Biomedical subjects

S J Li

Publications and source records attributed to S J Li.

At least 73 records · Page 4Linked to original sources

t(13q;17p) and del(5q): possibly specific changes in Chinese patients with colorectal cancers.

Cytogenetic study of 18 colorectal carcinomas confirmed the extensive heterogeneity and the complexity of the karyotypic picture in this type of tumor. Karyotypic analysis showed that chromosomes 17p and 5q, in both numerical and structural aspects, were the most frequently involved chromosomes and prone to losses. The most common structurally rearranged forms were translocations of 17p with other chromosomes, especially t(13q;17p), which constituted over 50% of all 17p rearrangements, and an interstitial deletion of 5q that made up as much as 73% of all structural abnormalities of 5q. According to the results, we conclude that chromosomes 17 and 5 may play important roles in the evolution of colorectal cancer and t(13q;17p) and del(5q) may be possibly specific to Chinese patients with colorectal cancer.

Adult↗

Age-related changes in opioid peptide concentrations in brain and pituitary of spontaneously hypertensive rats. Effect of antihypertensive drugs and comparison with deoxycorticosterone acetate and salt hypertension.

The relationship of age-dependent changes in concentrations of various opioid peptides in the brain and pituitary to the development of hypertension was studied in the spontaneously hypertensive rat (SHR). Normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats served as controls. Opioids determined were dynorphin A (1-8) [DN-A(1-8)], beta-endorphin (BE) and Met-enkephalin (ME). Three approaches were used: (1) temporal correlations of opioid concentrations with the onset of hypertension in 4-, 8-, 12- and 16-week-old rats; (2) study of opioid changes when hypertension development was prevented with antihypertensive drugs and (3) determination of possible opioid peptide changes in another rat model of hypertension, the deoxycorticosterone acetate (DOCA) + salt model. Opioid peptide concentration differences (SHR/WKY) found were as follows. There were much lower DN-A(1-8) levels in the SHR hippocampus and hypothalamus at all ages studied. At 12 and 16 weeks, coincidently with the onset of hypertension, lower levels of BE were found in the anterior lobe of the pituitary, but there were higher BE and ME levels found in the neurointermediate lobe (NIL). Prevention of hypertension in SHR by 8 weeks of oral therapy with guanethidine and hydralazine reversed the BE and ME changes in the NIL but not in the anterior lobe. There were no brain or pituitary changes in opioid peptide concentrations associated with DOCA-salt hypertension. The results are interpreted as supporting a role for altered concentrations of brain and pituitary opioids in the genesis of SHR hypertension.

Aging↗

Lipid-free total parenteral nutrition and macrophage function in rats.

Certain lipids are immunosuppressive when used for nutritional support, while other lipids and nutritional additives may enhance immunologic function. We hypothesized that total parenteral nutrition (TPN) may be immunosuppressive irrespective of lipids. Twenty-four rats underwent central vein catheterization and received either intravenous saline solution and oral chow or TPN alone. At 7 or 14 days, the animals were killed. Splenic and bone marrow macrophages were isolated and cultured in either M199 medium alone or were stimulated with Escherichia coli lipopolysaccharide. The supernatants were tested for prostaglandin E2 and C3. The splenic prostaglandin E2 levels were significantly higher in the TPN group following lipopolysaccharide stimulation at 7 days but not at 14 days. Administration of TPN to rats, even without lipids, may be immunosuppressive through the release of prostaglandin E2 from splenic macrophages following a septic challenge. This effect appears to be abolished after 14 days of TPN infusion.

Animals↗

Clinical spectrum of fungal infections after orthotopic liver transplantation.

During a 50-month period, we identified 91 episodes of fungal infection in 72 liver transplant recipients (23.8%). Candida species accounted for 83.5% of cases. Clinical patterns of fungal infections included disseminated infection (19), peritonitis (17), pneumonitis (15), multiple sites of colonization (13), fungemia (11), and other sites (16). The diagnosis of fungal infection was usually made in the first 2 months (84.7% of cases), at a mean time of 16 days after transplantation. Risk factors for fungal infections included retransplantation, Risk score, intraoperative transfusion requirement, urgent status, Roux limb biliary reconstruction (in adults), steroid dose, bacterial infections and antibiotic therapy, and vascular complications. Fungal infections were successfully treated with amphotericin B in 63 cases (74.1%) but were associated with diminished patient survival (50% vs 83.5%). Fungal infection is a frequent source of early morbidity and can be related to well-defined risk factors, suggesting the need for effective prophylaxis.

Adolescent↗

Tumor bioenergetics and blood flow in RIF-1 murine tumors treated with 5-fluorouracil.

Treatment of RIF-1 solid tumors with 5-fluorouracil (5-FU, 100 or 200 mg/kg, ip) caused substantial regression of the tumors, with regrowth initiated on Day 6 (100 mg/kg) or Day 9 (200 mg/kg). Blood perfusion in the tumor, estimated by uptake of 86Rb+, was significantly increased after treatment with 5-FU, while Rb+ uptake in normal tissues (skin, muscle) was unaffected. The increase in tumor perfusion during the first few days following treatment was significantly greater in animals treated with the higher dose of 5-FU. Perfusion-dependent 86Rb+ uptake returned to control levels by the 9th day after treatment with 100 mg/kg of 5-FU, but remained elevated on Days 9-12 after the higher dose. By the 1st day following treatment with 5-FU, in vivo 31P NMR spectra of treated tumors indicated significantly higher ratios of phosphocreatine to Pi, higher pH, and lower ratios of Pi to nucleoside triphosphates compared to untreated age-matched controls. These changes persisted for 9 days following the lower 5-FU dose and for at least 12 days following the higher dose. Treatment with 5-FU induces profound, dose-dependent changes in tumor bioenergetics, which may result, at least in part, from changes in tumor perfusion after cytoreduction.

Animals↗

Hepatic allograft rescue following arterial thrombosis. Role of urgent revascularization.

Hepatic artery thrombosis is a continuing source of morbidity and mortality following orthotopic liver transplantation. The cornerstone of therapy has been urgent retransplantation that is limited by organ availability. For this reason we developed a policy of urgent revascularization for allograft rescue. Hepatic artery thrombosis developed following 15 transplants of which 11 underwent urgent rearterialization. The diagnosis was made a mean of 4.8 days (range 1-10) following transplantation. Duplex ultrasonography was diagnostic in all patients and confirmed by angiography in 4 (36%). Three patients with hepatic artery thrombosis were identified following screening ultrasonography and were clinically unsuspected. Upon reexploration, a specific technical reason for hepatic artery was found in 4 patients (36%). Twelve arterial revascularization procedures were performed in 11 patients including: thrombectomy alone (n = 4); revision of anastomosis with thrombectomy (n = 5); and thrombectomy with placement of vascular conduit (n = 3). Following revascularization, 8 patients maintained hepatic artery patency. Three patients eventually required retransplantation secondary to biliary sepsis. Biliary tract complications developed in 6 patients, at a mean of 23 days following revascularization and included: breakdown of the biliary anastomosis (n = 4); stricture (n = 1); and sludge formation (n = 1). The overall graft and patient survival are 74% and 82% respectively, with a mean follow-up of 6.8 months. Hepatic allograft rescue with the use of urgent revascularization following hepatic artery thrombosis appears to be an effective means of either avoiding retransplantation or providing a bridge until a suitable donor becomes available.

Adult↗

Prediction of tumor radiosensitivity by hexafluoromisonidazole retention monitored by [1H]/[19F] magnetic resonance spectroscopy.

Hexafluoromisonidazole (CCI-103F) is a hypoxic cell label that can be measured by in vivo [1H]/[19F] magnetic resonance spectroscopy (MRS). The retention of CCI-103F in SCCVII tumors was found to be correlated with tumor size, with larger tumors retaining more label. Such a correlation was anticipated, as larger SCCVII tumors have larger hypoxic fractions. A significant but less strong correlation was also found between CCI-103F retention and the fraction of tumor cells surviving after 10 Gy irradiation, with tumors that retained larger amounts of CCI-103F having higher surviving fractions. These results indicated that non-invasive MRS measurement of CCI-103F retention could predict radiosensitivity in SCCVII tumors. The lack of a strong correlation between CCI-103F retention and radiosensitivity, however, indicated that hypoxic fraction was not the only factor influencing radiosensitivity in these tumors.

Animals↗

A new device of incentive spirometry.

Incentive spirometry is a feedback system to encourage patients to take a deep breath and produce a sustained maximal inspiration (SMI) for the primary purpose of opening and stabilizing atelectatic areas of the lung. However, currently available incentive devices are not reusable, expensive, and emphasize inspiratory effort only. We have designed a new device of incentive spirometer based on pursed-lip breathing technique. The device consists of a piece of paper hanging on a frame. The patient is instructed to take a deep and slow inspiration followed by holding the breath for 5 seconds. Then, using pursed-lip technique, the patient generates a flow to keep the paper attached to a bar as long as possible. The duration of paper blowing is recorded and is compared with vital capacity. In the present study 96 cases were recorded. Vital capacity was correlated well with paper blowing time (multiple regression test r = 0.87, p less than 0.0001). The advantages of our device include (1) reusibility and less cost, (2) equal emphasis of both inspiration and expiration, and (3) being especially helpful for patients with chronic obstructive lung disease (COPD). This is a preliminary result and further clinical study is needed.

Breathing Exercises↗

Effect of ischemia on protein synthesis in the septic liver.

The effect of ischemia on hepatic protein synthesis during sepsis is not known, but is of clinical relevance, since hepatic blood flow decreases during the late phase of sepsis. In this study, synthesis of acute-phase proteins was measured in perfused livers of rats 16 hours after sham operation or cecal ligation and puncture. Livers from each group had 45 minutes of complete ischemia or control perfusion. Protein synthesis was measured during two hour perfusion after the ischemia or control period, by determining incorporation of 3H-leucine into total secreted trichloracetic acid precipitated proteins, immunoprecipitated complement component C3 and albumin and phosphotungstenate-precipitated alpha 1-acid glycoprotein. Lactate, glutamine-oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels in the perfusate were measured during preischemic and postischemic perfusion. Tissue glutathione levels were measured at the end of the perfusion. Synthesis of alpha 1-acid glycoprotein was increased by 100 per cent and albumin synthesis decreased by 46 per cent in septic livers, consistent with an acute-phase response and apparent downregulation of albumin synthesis during early sepsis. Synthesis rates were reduced by 50 to 60 per cent after ischemia in perfused livers from sham operated rats and 70 to 80 per cent in livers from septic rats. Hepatic production of interleukin-1 was not different between the groups during perfusion. GOT and GPT levels increased significantly during ischemia of both nonseptic and septic livers and rapidly returned toward baseline during reperfusion. Lactate levels were higher in perfusate of septic than of nonseptic livers before ischemia and increased further during ischemia. The results suggest that ischemia inhibits production of secreted hepatic proteins similarly in nonseptic and septic livers, but perhaps to a slightly greater extent in septic livers.

Acute-Phase Proteins↗

Diagnosis and differentiation of HTLV-I and HTLV-II infection by enzyme immunoassays using synthetic peptides.

Synthetic peptides from the major envelope protein of HTLV-I (ENV-I, amino acid 177-213) and HTLV-II (ENV-II, amino acid 173-209) and a conserved region of the transmembrane protein (TM, amino acid 378-402) were used as antigens in microtiter plate enzyme immunoassays (EIA) to detect and discriminate antibodies to HTLV-I and II. The ENV-I and ENV-II peptide EIAs were able to correctly discriminate HTLV-I and II infections in 17 of 18 subjects whose infections were determined by a gene amplification method. Sera from 100 of 107 subjects with serologically confirmed infection with HTLV-I/II and 0 of 218 seronegative controls reacted with one or more of the peptides (sensitivity, 93.5%; specificity, 100%). Ninety-six of the 100 peptide positive sera reacted exclusively with either the ENV-I or the ENV-II peptide, thereby differentiating the two viral infections. The pattern of reactivity to the ENV peptides was distinct in different populations. Patients attending an Emergency Department, who had a history of drug abuse, and male inmate entering a correctional facility only had antibody reactivity to the ENV-II peptide. Subjects from Haiti and patients with HTLV-associated neurological disease only had antibody reactivity to the ENV-I peptide. Peptide-based enzyme immunoassays that distinguish antibodies to HTLV-I and HTLV-II will facilitate studies of the epidemiology of HTLV.

Amino Acid Sequence↗

Hippocampal levels of dynorphin A (1-8) in neonatal and 16-week-old spontaneously hypertensive rats: comparisons with DOCA-salt hypertension.

In this study the possible role of hippocampal dynorphin in the development of hypertension in spontaneously hypertensive rats (SHR) was investigated by determining dynorphin A (1-8) (DN A (1-8] levels in hippocampus in 16 week old SRH, Wistar Kyoto (WKY) controls and SHR treated with antihypertensive drugs as well as DOCA-salt hypertensive Sprague Dawley (SD) rats, using radioimmunoassay (RIA). We found that DN A (1-8) was decreased significantly in both dorsal (-68%) and ventral (-58%) hippocampus in SHR compared with WKY rats. Treatment with hydralazine and guanethidine (25 mg/kg/24 hr of each drug in drinking water) for 8 weeks to prevent the development of hypertension in young SHR had no effect on this low hippocampal dynorphin level. We failed to find significant changes in hippocampal DN A (1-8) level in DOCA-salt hypertensive rats. The low level of hippocampal dynorphin existed before the development of hypertension in 6 day neonatal SHR (-73%). Hippocampal Met-enkephalin was unchanged in all experimental groups except for a slight decrease in neonatal SHR. The results establish a genetic difference in the hippocampal dynorphin system of SHR compared with WKY, the significance of which, for the development of hypertension, remains to be investigated.

Animals↗

Addition of L-glutamine to total parenteral nutrition and its effects on portal insulin and glucagon and the development of hepatic steatosis in rats.

Infusion of total parenteral nutrition (TPN) with excess carbohydrate calories leads to hepatic steatosis in rats and is associated with an elevated portal insulin/glucagon molar ratio. Previously we have shown that adding glucagon to TPN prevents and reverses hepatic steatosis in rats, possibly by increasing hepatic lipid export. It has been reported that steatosis is eliminated in rats by the addition of L-glutamine to TPN. In this study, we examined the effect of glutamine on portal insulin and glucagon levels and the development of hepatic steatosis. Adult rats (n = 19) received internal jugular catheters: Group 1 (n = 6), saline (3 cc/hr) and chow ad libitum; Group 2 (n = 7), 25% dextrose base TPN; Group 3 (n = 6), 25% dextrose base TPN with 2% glutamine. The infusion rate of TPN was 1.2 cc/100 g body wt/hr. Daily nitrogen balance was determined and at 7 days, portal venous blood was drawn for insulin and glucagon radioimmunoassay, livers were removed for histology and lipid content determination, and the small intestines were removed for mucosal protein and DNA content determination. Panlobular vacuolization of the hepatocytes was noted on histology in Group 2 (TPN) while Group 1 (chow) and Group 3 (TPN + glutamine) showed normal liver morphology. Hepatic lipid content was significantly elevated in Group 2 (P less than 0.05). The portal insulin/glucagon molar ratio was increased because of excessive portal venous insulin in Group 2 (TPN). In contrast, portal glucagon was significantly elevated while the insulin/glucagon ratio and hepatic lipid content did not increase above control levels in the glutamine-supplemented Group 3 rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of nigrostriatal dopaminergic tone on the biosynthesis of dynorphin and enkephalin in rat striatum.

The purpose of this study was to obtain direct evidence that the nigrostriatal dopamine (DA) pathway modulates the metabolism of striatal dynorphin and [Met5]-enkephalin. This was achieved by repeated injections of apomorphine (APO) or D-amphetamine (AMP) in unilateral nigral 6-hydroxydopamine (6-OHDA)-lesioned rats. Three weeks after a 6-OHDA lesion, dynorphin A(1-8)-like immunoreactivity (DN-LI) and the level of mRNA encoding prodynorphin in the striatum on the lesioned side were decreased compared with the contralateral control side. Activation of DA receptors by 7 daily injections of APO (5 mg/kg, Bid, s.c.), however, caused a large increase (3- to 4-fold of saline control) in striatal levels of DN-LI and prodynorphin mRNA on the 6-OHDA lesioned side, which is far greater than the increase on the contralateral side (2-fold of saline control). Presumably, the potentiated effect of APO in 6-OHDA lesioned rats is due to hypersensitivity of DA receptors resulting from DA denervation. Seven daily injections of AMP (5 mg/kg, Bid, s.c.), a DA-releasing agent, increased striatal DN-LI (187% of saline control) on the non-lesioned side, but not on the 6-OHDA-lesioned side. Taken together, the data indicate that the nigrostriatal pathway exerts a tonic excitatory influence over the biosynthesis of dynorphin and that this influence is not maximal since an additional increase in dopaminergic tone further increases the expression of dynorphin. In contrast, [Met5]-enkephalin-like immunoreactivity (ME-LI) in the striatum was increased by a 6-OHDA-lesion (145% of contralateral control), which was blocked by repeated administration of APO but not AMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dynamic measurements of hexafluoromisonidazole (CCI-103F) retention in mouse tumours by 1H/19F magnetic resonance spectroscopy.

Selective retention of hexafluoromisonidazole, CCI-103F, in RIF-1 and SCCVII tumours of C3H/Km mice has been measured by 1H/19F magnetic resonance spectroscopy (MRS) on a Bruker AM-400 multinuclear spectrometer. CCI-103F concentrations in tumours and in normal tissues were measured using an MRS technique in which the water component in the tissues serves as an internal concentration reference. The biodistribution and elimination half-life of the drug in the tissues after i.p. injections were determined. The plasma half-life of the drug (41 min) was measured by high-pressure liquid chromatography. The two tumour lines and liver have longer retention times with half-lives of 47, 129 and 81 min, respectively, while normal tissues, muscle and brain have little retention of CCI-103F and clear the drug very quickly. Dynamic measurements of CCI-103F retention in tumours by MRS may provide a non-invasive probe for assessing tumour hypoxia.

Animals↗

Effects of ischemia and reperfusion on protein synthesis in livers with different glutathione levels.

The role of oxygen-free radicals for metabolic derangements in the ischemic and reperfused liver is controversial. The effect on hepatic protein synthesis of a 60-minute period of ischemia followed by two hours of reperfusion was studied in four groups of rats with different hepatic contents of the oxygen free radical scavenger glutathione (GSH): group 1, fed rats; group 2, fed rats treated with diethylmaleate (DEM) one hour before use (0.69 mL/kg, i.p.); group 3, 48-hour fasted rats; and group 4, 48-hour fasted rats treated with cobalt-chloride (45 mg/kg, s.c.) ten hours before use. Protein synthesis rates were determined by measuring incorporation of U-14C-leucine into protein in incubated liver slices. Treatment of fed rats with DEM and fasting for 48 hours significantly reduced liver GSH content. The effect of fasting on liver GSH was reversed by treatment with cobalt-chloride. The protein synthesis rate was reduced to approximately 30% of initial value at the end of the ischemic period and recovered to 70% to 100% of initial value after two hours of reperfusion with no differences between the experimental groups. Thus the effect of liver ischemia and reperfusion on protein synthesis was similar in groups of rats with different hepatic GSH contents at the onset of ischemia. The data suggest that oxygen free radicals do not play a major role for the impairment of protein synthesis in the ischemic and reperfused liver.

Animals↗