Biomedical subjects

J C Yu

Publications and source records attributed to J C Yu.

At least 37 records · Page 2Linked to original sources

PubMed2000

Direct growth suppressive activity of interferon-alpha and -gamma on human gastric cancer cells.

BACKGROUND AND OBJECTIVES: Interferons (IFNs) exhibit anti-tumor activities through either immune modulation or direct anti-tumor effects. We have investigated the activity and mechanisms of IFN-alpha and IFN-gamma on the growth of TSGH9201, TMK-1 and AGS gastric cancer cells in vitro. METHODS: Activities of IFNs on cell growth were analyzed by measuring total cellular DNA. Effects of IFNs on apoptosis was evaluated by formation of in situ DNA breakage and DNA ladders. Effects of IFNs on cells cycle phase distribution were analyzed using flow cytometry. Levels of Bcl-2 family proteins after treatment with IFNs were analyzed using Western blot. RESULTS: Both IFN-alpha and IFN-gamma were active in suppressing the growth of TSGH9201 and TMK-1 cells, while AGS cells were resistant to treatment with IFNs. The IC(50)s of IFN-alpha for TSGH9201 and TMK-1 cells were 300 and 500 U/ml, respectively, and the IC(50)s of IFN-gamma were 40 and 2.0 U/ml, respectively. Both IFN-alpha- and IFN-gamma-induced cell cycle arrest in sensitive cells. IFN-gamma also increased cellular apoptosis, demonstrated by increasing in situ DNA damage and DNA fragmentation. IFN-gamma increased BAK protein levels and decreased Bcl-2 and Bcl-X(S) protein levels in TSGH9201 cells. CONCLUSIONS: IFN-alpha suppressed growth of gastric cancer cells through induction of cell cycle arrest. IFN-gamma suppressed cell growth through induction of both cell cycle arrest and apoptosis. IFN-gamma-mediated apoptosis was associated with the alteration in protein levels of Bcl-2, Bcl-X(S) and BAK.

Antineoplastic Agents↗

PubMed2000

Preincisional dextromethorphan treatment for postoperative pain management after upper abdominal surgery.

Previous studies showed that ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, provides a preemptive analgesic effect and preemptive analgesia improves postoperative pain management. The aim of this study was to examine whether premedication with dextromethorphan (DM) improves postoperative pain management after upper abdominal surgery. Sixty (American Society of Anesthesiologists class 1 and 2 of either gender) patients scheduled for upper abdominal surgery were included in the study. Patients were randomly assigned to one of four groups: control, DM-10, DM-20, and DM-40. In the control group, chlorpheniramine maleate (CPM, 20 mg) was injected immediately before induction of anesthesia intramuscularly (IM). In the DM-10, DM-20, and DM-40 groups, patients were premedicated with DM 10 mg, 20 mg, and 40 mg IM, respectively. After operation, patient-controlled analgesia (PCA) with morphine was given for pain relief. The time to the first PCA trigger, morphine consumption, pain scores, and analgesic-related side effects were recorded at 1, 2, 4, 24, 48, and 72 hours after surgery. The time to first PCA trigger for the control group was 17.8 +/- 1.4 minutes, for group DM-10 20.2 +/- 1.6 minutes, for group DM-20 32.4 +/- 1.9 minutes, and for DM-40 77.9 +/- 6.5 minutes. The morphine delivered and PCA triggering frequency were 5.5 +/- 0.5/11.3 +/- 0.8 times for the controls, 5.5 +/- 0.4/ 14.1 +/- 1.3 times for DM-10, 3.1 +/- 0.3/6.3 +/- 1.2 times for DM-20, and 0.2 +/- 0.1/0.3 +/- 0.2 times for DM-40 during the first hour after operation. For the first day, the figures are 19.9 +/- 1.2/23.9 +/- 1.4 for the controls, 15.6 +/- 1.2/17.3 +/- 2.4 for DM-10, 12.6 +/- 0.7/15.9 +/- 1.6 for DM-20, and 5.0 +/- 0.21/5.6 +/- 0.9 for DM-40. On the first day, the cough pain scores were 6.67 +/- 0.23, 6.53 +/- 0.16, 6.67 +/- 0.23, and 5.73 +/- 0.18 for the controls, DM-10, DM-20, and DM-40 groups, respectively. All data showed dose-dependent better pain relief in DM-premedicated patients. We conclude that DM premedication offers preemptive analgesia and reduces postoperative pain and morphine requirement.

Abdomen↗

PubMed2000

Pre-incisional epidural ketamine, morphine and bupivacaine combined with epidural and general anaesthesia provides pre-emptive analgesia for upper abdominal surgery.

BACKGROUND: Previous studies have shown that N-methyl-D-asparate (NMDA) receptor antagonists provide a pre-emptive analgesic effect in humans. This study investigated the benefits of pre-emptive analgesia for upper abdominal surgery, using pre-incisional epidural ketamine + morphine + bupivacaine (K+M+B) treatment for achieving postoperative pain relief. METHODS: Sixty ASA 1-2 patients scheduled for upper abdominal surgery were allocated to three groups in a randomized, single-blinded study. Patients in the control group (I) received general anaesthesia followed by an infusion of normal saline. Group II and III patients received general anaesthesia with a continuous epidural infusion of 2% lidocaine. Thirty minutes after the incision in groups I and II, an epidural pain control regimen was administered using ketamine (10 mg) and morphine (1 mg) in 10 ml of 0.085% bupivacaine (K+M+B). Group III patients also received K+M+B, but it was administered 10 min after the 2% lidocaine injection and 30 min before skin incision. All patients received an epidural pain control regimen (q12 h) for 3 days after their first injection. Patient-controlled analgesia (PCA) with morphine was used to control subsequent postoperative pain. During the 3-day period following surgery, duration to PCA trigger (h), morphine consumption (mg), pain intensity at rest and when coughing/moving, and analgesic-related adverse effects were recorded. The VAS scale (0-10) was used to assess pain intensity. RESULTS: Median times to first PCA trigger were 1.2 (0.5-2.0) h, 3.0 (0.7-4.2) h, and 4.0 (2.5-7.5) h for groups I, II, and III, respectively. Both the incident and resting pain scores were consistently lower for group III patients than groups I and II. The number of PCA triggers (all attempts/successful triggers) during the day following surgery were 14.0 (3-30)/8.0 (3-24) times, 10.0 (3-23)/6.0 (2-20) times, and 7.0 (3-12)/4.5 (1-10) times for groups I, II, and III. Total morphine consumption for the 3-day observation period was 12.5 (3-42) mg, 10.5 (2-29) mg, and 6.0 (1-20) for groups I, II, and III, respectively. CONCLUSION: Pre-incisional epidural K+M+B treatment combined with continuous epidural anaesthesia and general anaesthesia provides an ideal pre-emptive analgesic therapy, exhibiting better postoperative pain relief than general anaesthesia and post-incisional K+M+B treatment.

Abdomen↗

PubMed2000

Reconstruction of the Achilles tendon and overlying soft tissue using antero-lateral thigh free flap.

Reconstruction of combined loss of the Achilles tendon and overlying soft tissue was performed using an antero-lateral thigh free flap in three patients. The cutaneous portion is used to cover the open wound, and a piece of fascia lata is utilised to replace the missing segment of the Achilles tendon. The skin defect ranged from 5 x 2.5 to 7 x 5 cm, and the tendon loss measured from 3.5 to 5.5 cm in length. All of the patients showed satisfactory functional results with a follow-up period from 3 to 9 months. The advantages of the procedure are that: it is a single-staged operation; it promotes rapid healing of the tendo Achilles since the tendon substitute is well vascularised; it is adaptable to a wide range of defect sizes and shapes; it can be performed in the supine position without the need for postural change; and it can restore good contour and causes minimal morbidity at the donor site.

Achilles Tendon↗

PubMed2000

A simplified pneumotachometer for the quantitative assessment of velopharyngeal incompetence.

By applying pipe flow rate mechanics, the authors have developed a simple and inexpensive device that can measure oral and nasal airflow and pressure quantitatively. It allows clinicians to document objectively the degree of velopharyngeal incompetence and nasal airway obstruction. This device is a modified U-manometer with a Y-connector to a collection bag. This prototype is being used in the authors' cleft palate clinic and they have found it useful in documenting quantitatively the amount of nasal air escape from either nostril with the corresponding pressure and flow. The primary measurement, which is reproducible and reliable, is the product of a cross-sectional area of oronasal communication and the pressure differential between the oral and nasal cavity. With some modifications, this device can be adapted to estimate the size of the oronasal communication.

Airway Obstruction↗

PubMed2000

Free anterolateral thigh flap for reconstruction of head and neck defects following cancer ablation.

Thirty-seven consecutive free anterolateral thigh flaps in 36 patients were transferred for reconstruction of head and neck defects following cancer ablation between January of 1997 and June of 1998. The success rate was 97 percent (36 of 37), with one flap lost due to a twisted perforator. The anatomic variations and length of the vascular pedicle were investigated to obtain better knowledge of anatomy and to avoid several surgical pitfalls when it is used for head and neck reconstruction. The cutaneous perforators were always found and presented as musculocutaneous or septocutaneous perforators in this series of 37 anterolateral thigh flaps. They were classified into four types according to the perforator derivation and the direction in which it traversed the vastus lateralis muscle. In type I, vertical musculocutaneous perforators from the descending branch of the lateral circumflex femoral artery were found in 56.8 percent of cases (21 of 37), and they were 4.83 +/- 2.04 cm in length. In type II, horizontal musculocutaneous perforators from the transverse branch of the lateral circumflex femoral artery were found in 27.0 percent of cases (10 of 37), and they were 6.77 +/- 3.48 cm in length. In type III, vertical septocutaneous perforators from the descending branch of the lateral circumflex femoral artery were found in 10.8 percent of cases (4 of 37), and they were 3.60 +/- 1.47 cm in length. In type IV, horizontal septocutaneous perforators from the transverse branch of the lateral circumflex femoral artery were found in 5.4 percent of cases (2 of 37). They were 7.75 +/- 1.06 cm in length. The average length of vascular pedicle was 12.01 +/- 1.50 cm, and the arterial diameter was around 2.0 to 2.5 mm; two accompanying veins varied from 1.8 to 3.0 mm and were suitable for anastomosis with the neck vessels. Reconstruction of one-layer defect, external skin or intraoral lining, was carried out in 18 cases, through-and-through defect in 17 cases, and composite mandibular defect in two cases. With increasing knowledge of anatomy and refinements of surgical technique, the anterolateral thigh flap can be harvested safely to reconstruct complicated defects of head and neck following cancer ablation with only minimal donor-site morbidity.

Adult↗

PubMed2000

Postoperative intramuscular dextromethorphan injection provides pain relief and decreases opioid requirement after modified radical mastectomy.

BACKGROUND: Narcotics are still the therapeutic mainstay for postoperative pain relief. However, many unwanted side effects are accompanied. NMDA antagonists have been demonstrated to produce analgesic and antihyperalgesic effects, moreover, to possess potentiated effect of narcotics on postoperative pain management. AIMS: To examine whether postoperative dextromethorphan (DM), an antitussive and also an NMDA antagonist, intramuscular injection (I.M.) reduced pain and analgesic requirement after modified radical mastectomy (MRM). METHODS: Sixty-one patients scheduled for MRM were included and randomly allocated into two groups. For the control group (n=31), patients received chlorpheniramine maleate (CPM, 20 mg) I.M., while in the DM group (n = 30), 40 mg DM containing 20 mg CPM (I.M.) was given at the end of surgery. Meperidine (1 mg/kg, I.M.) was prescribed for postoperative pain relief, if ask. The time to first meperidine injection, total meperidine consumption, worst pain score, bed-rest time, and meperidine-related side effects were recorded for 48 hours postoperation. RESULTS: A longer time to first meperidine injection (20.3 +/- 1.4 vs 1.5 +/- 0.2 hr, p < 0.001) and lower meperidine consumption (10.7 +/- 4.0 vs 70.7 +/- 8.9 mg, p < 0.001) were observed in the DM group than the control group. The average bed rest time was significantly shorter in the DM group than in the control group (18.9 +/- 1.5 vs 23.4 +/- 1.6 hr, p < 0.001). The number of patients who required meperidine injection (6 vs 27, p < 0.005) and meperidine-related side effects were significantly lower in the DM group than in the control group (1 vs 7, p < 0.025). No difference was noted in worst VAS pain score between the DM and the study groups. CONCLUSION: Postoperative DM I.M. injection provided an analgesic effect and reduced meperidine requirement after MRM.

Analgesics, Opioid↗

PubMed1999

Biochemical and functional characterization of nitric oxide synthase III gene transfer using a replication-deficient adenoviral vector.

Nitric oxide (NO) produced in endothelial cells has been implicated in the regulation of blood pressure, regional blood flow, inhibition of platelet aggregation, and endothelial and vascular smooth muscle cell proliferation. In a variety of cardiovascular disease states, such as atherosclerosis, arterial hypertension, and restenosis, expression of endothelial NO synthase (NOS-III) and endothelial NO production appear to be altered. Thus, NOS-III is an attractive target for cardiovascular gene therapy for which adenoviral vectors are one of the most effective vector systems. Therefore, a recombinant adenoviral vector expressing NOS-III (adenovirus type 5 [Ad5] cytomegalovirus [CMV] NOSIII) was constructed and biochemically and pharmacologically characterized both in vitro and in intact cells. Ad5CMVNOSIII-derived recombinant NOS-III was successfully expressed, as shown by immunoprecipitation and immunocytochemistry, and biologically active, as shown by functional assays in human primary umbilical vein and EA.hy926 endothelial cells, as well as 293 human embryonic kidney and Chinese hamster ovary cells. The Km values for NADPH and L-arginine and the Ka for tetrahydrobiopterin as well as the enzyme's dependency on other cofactors were similar to recombinant reference enzyme and literature values. NOS-III expression levels correlated linearly with the multiplicity of infection with Ad5CMVNOSIII and lasted for at least 8 days. NOS-III transfection inhibited endothelial cell proliferation. In conclusion, adenovirus-mediated gene transfer of Ad5CMVNOSIII to vascular and nonvascular cells resulted in the dose-dependent expression of intact, physiologically regulated, and functionally active NOS-III.

Adenoviridae↗

PubMed1999

Preincisional dextromethorphan decreases postoperative pain and opioid requirement after modified radical mastectomy.

PURPOSE: To examine whether preincisional dextromethorphan (DM) improved analgesia after modified radical mastectomy (MRM). METHODS: Sixty patients (ASA I-II) scheduled for MRM were included and randomly allocated into two groups. Patients in the treatment group (DM) received 40 mg DM and 20 mg chlorpheniramine maleate (CPM) i.m., and those in the control group received 20 mg CPM i.m. alone 30 min before skin incision. Meperidine, 1 mg x kg(-1) i.m., was given for postoperative pain relief as required. The time to first meperidine injection, total meperidine consumption, worst pain score, bed-rest time, and side effects were recorded every 24 hr for 48 hr after surgery by a resident anesthesiologist on a double-blind basis. RESULTS: A longer time to first meperidine injection (19.2 +/- 1.6 vs 1.5 +/- 0.23 hr, P < 0.001) and lower meperidine consumption (0[10] vs 75[50] mg, median [interquartile range], P < 0.001) were observed in the DM group than in the control group. The bed-rest time was shorter in the DM than in the control group (18.0[4] vs 23.0[19] hr, P < 0.001). No difference was noted in worst VAS pain score. Meperidine-related side effects (nausea, vomiting, pruritus, dizziness, headache) were more frequent in the control (10/30) than in the DM group (3/30, P < 0.05). The number of patients who required meperidine injection for pain relief was lower in the DM (7/30) than in the control group (25/30, P < 0.005). No DM- or CPM-associated side effects were observed. CONCLUSION: Preincisional IM. DM treatment decreased postoperative pain and opioid requirement after MRM surgery.

Analgesics, Opioid↗

PubMed1999

Thoracic epidural anesthesia for pain relief and postoperation recovery with modified radical mastectomy.

The purpose of this study was to investigate whether thoracic epidural anesthesia (TEA) provides better postoperative pain relief and recovery than general anesthesia (GA) for modified radical mastectomy (MRM) surgery. Sixty-four patients rated as American Society of Anesthesiologists (ASA) 1 to 3 who underwent MRM surgery were included in the study. In TEA group patients, 2% lidocaine (15-20 ml) was administered via the epidural route as primary anesthesia, in conjunction with midazolam (5-10 mg) and fentanyl (<250 microg) for amnesia. The GA patients were maintained with isoflurane and 50% nitrous oxide in oxygen. After operation the patients were given pethidine (1 mg/kg IM) as required for pain relief. The time to first pethidine requirement, total pethidine consumption, worst pain score, bed rest time, satisfaction score, and anesthesia-related side effects were recorded for 2 days after surgery. The results show that TEA provided a more prolonged analgesic effect than GA after operation. A longer time to first pethidine requirement (19.2 +/- 1.5 vs. 7.6 +/- 2.5 hours) (p < 0. 001) and decreased pethidine consumption (17.2 +/- 7.0 vs. 76.3 +/- 17.4 mg) (p < 0.001) were observed in the TEA group than in the GA group, respectively. A worse visual analog scale (VAS) pain score was observed in the GA group (5.7 +/- 0.6) than in TEA patients (4.3 +/- 0.4) (p < 0.01). The average bed rest time was significantly shorter in the TEA group (16.9 +/- 0.9 hours) (p < 0.01) than in the GA group (27.1 +/- 4.1 hours). Overall satisfaction scores were significantly higher in the TEA group (4.4 +/- 0.1) (p < 0.01) than in the GA group (3.5 +/- 0.2). Side effects were observed at a higher frequency in the GA group (16/32) (p < 0.0001) than in the TEA group (3/32). The frequency of pethidine injection for pain relief was significantly lower in the TEA group (8/32) (p < 0.0001) than in the GA group (24/32). The total hospital cost (NT 64,392 +/- 3,523 vs. NT 53,806 +/- 2,817) (p = 0.0342) and anesthesia cost (NT 7,968 +/- 246 vs. NT 5,268 +/- 262) (p < 0.0001) are also significantly lower in the TEA group than the GA group. In conclusion, TEA provided better postoperative pain relief and recovery and lower cost than GA for MRM surgery.

Analgesics, Opioid↗

PubMed1999

Expression of nuclear retinoid receptors in normal, premalignant and malignant gastric tissues determined by in situ hybridization.

Retinoids exhibit multiple functions through interaction with nuclear retinoid receptors and have growth-suppressive activity on gastric cancer cells. To better understand the roles of nuclear retinoid receptors during gastric carcinogenesis, we have used in situ hybridization to investigate expression of retinoic acid receptors (RARs) and retinoid x receptors (RXRs) in premalignant and malignant formalin-fixed paraffin-embedded gastric tissues. Histological sections of eight normal, 17 distal normal and nine gastric cancer tissues were hybridized with non-radioactive RNA probes for subtypes of RAR and RXR. Expression of RAR alpha, RAR beta, RAR gamma, RXR alpha and RXR beta was found in most cell types in gastric mucosa tissues from normal individuals as well as in distal normal tissues from cancer patients. Expression of RAR alpha and RAR beta were found in three and seven cancer tissues, respectively, and levels of RXR alpha mRNA were significantly decreased in poorly differentiated cancer tissues. Among the five investigated nuclear retinoid receptors, only expression of RAR alpha mRNA was significantly decreased in intestinal metaplasia, dysplasia and cancer tissues when compared to adjacent normal tissues. In conclusion, normal gastric mucosa expressed both RARs and RXRs, which supports the physiological role of retinoic acid on normal gastric mucosa. The decrease in RAR alpha expression in premalignant and malignant gastric tissues suggests a significant role of RAR alpha during gastric carcinogenesis.

Gastric Mucosa↗

PubMed1999

Preincisional dextromethorphan treatment decreases postoperative pain and opioid requirement after laparoscopic cholecystectomy.

UNLABELLED: In the present study, we examined whether preincisional treatment with dextromethorphan (DM) provides preemptive analgesia. Ninety patients scheduled for laparoscopic cholecystectomy were included. Patients receiving chlorpheniramine maleate (CPM) 20 mg via an IM injection 30 min before skin incision were designated as the control group. Patients in Group A received DM 40 mg (containing CPM 20 mg) IM after removal of the gallbladder, whereas in Group B, DM 40 mg (containing CPM 20 mg) was administered IM 30 min before skin incision. Meperidine (1 mg/kg IM) was given for postoperative pain relief as required. Times to first meperidine injection, total meperidine consumption, worst pain score, bed rest time, and side effects were recorded for 48 h after surgery. Times to first meperidine injection were 9.3+/-15.9, 17.4+/-3.4, and 28.6+/-3.9 h for the control group and Groups A and B, respectively. The total meperidine consumption was 90.7+/-11.9, 77.5+/-12.7, and 20.0+/-4.4 mg for the control group and Groups A and B, respectively. The worst visual analog pain scores were 6.0+/-0.2, 6.0+/-0.2, and 4.0+/-0.4 for the control group and Groups A and B, respectively. The bed rest times were 21.0+/-0.5, 20.0+/-0.5, and 19.0+/-0.4 h for the control group and Groups A and B, respectively. The number of patients who required meperidine injection was 26, 22, and 12 for the control group and Groups A and B, respectively. We conclude that DM is more effective in producing postoperative analgesia when it is administered preincision rather than after the gallbladder removal treatment, which suggests a preemptive analgesic effect. IMPLICATIONS: Preincisional dextromethorphan (40 mg IM) treatment offers a preemptive analgesic effect, thus improving the postoperative pain management.

Analgesics, Opioid↗

PubMed1999

Treatment of posttraumatic ocular dysmotility using autogenous buccal fat grafts in a porcine model.

Diplopia occurring after orbital trauma is a complex and difficult clinical problem. Numerous potential mechanisms exist by which it may occur. Restrictive ocular dysmotility caused by intraorbital scarring is a major component in diplopia's pathogenesis. The current large animal study was conducted to develop an experimental model of restrictive ocular dysmotility that would quantitatively characterize the biomechanical properties of the globe rotations. Using this model, a novel method of restoring the low-friction milieu within the orbit by interposing a buccal fat graft was tested. In the initial stage, the baseline force duction was measured in 20 pig eyes using a highly sensitive, digital tensiometer. Traumatic violation of Tenon's fascia with electrocautery into the extraconal fat and the periorbita was followed by direct suturing of the extraocular muscle to the nearest orbital periosteum. After 6 weeks, the measurements (again in the field of the traumatized muscle) were repeated, and the eyes were divided into two treatment groups (n = 10 eyes per group). The left eye received the standard lysis of adhesion, whereas the right eye received lysis and buccal fat interposition grafting. The third and final force measurements were performed 6 weeks after treatment. The results showed a baseline linear load-displacement curve of 0 to 8 mm, with the globe rotating 400 microm for every 1000 mg of tensile load. Surgical trauma increased the slope as defined by load/displacement but, surprisingly, the relationship remained linear in the entire range from 2 to 8 mm. This linear relationship was seen in all stages: baseline, after trauma to Tenon's fascia, after surgical lysis alone, and after lysis with buccal fat interposition. The difference was in the slope, or stiffness. Lysis alone partially reduced the slope, but it was still higher than baseline. Lysis and buccal fat grafting returned the slope to near baseline. This, however, did not reach the level of statistical significance. It seems that a focal intervention along the course of an extraocular muscle altered the composite behavior of orbital resistance to globe rotation. Although buccal fat grafting did not significantly improve motility, it did not worsen it.

Adipose Tissue↗

PubMed1999

Molecular studies into the role of CD44 variants in metastasis in gastric cancer.

CD44, an integral membrane glycoprotein expressed by many cell types, serves as the principal transmembrane hyaluronate receptor and might be a determinant of metastatic and invasive behaviour in carcinomas. The generation of CD44 splice variants might be linked closely with gastric carcinoma tumorigenesis and differentiation. Some studies have reported that the magnitude of CD44 variant synthesis at the protein level correlates with lymph node metastasis. A number of studies have examined the possible mechanism of involvement of the CD44 variant in tumour metastasis. Most studies have reported that the regulation of CD44 binding to hyaluronate results from glycosylation of variably spliced exons. Direct hyaluronate binding studies of CD44 V4-V7 isoforms transfected into the human gastric carcinoma cell line, SC-M1, have indicated that the V4-V7 isoforms themselves, in addition to glycosylation, can alter hyaluronate binding.

DNA, Complementary↗

PubMed1998

Allelic loss of the BRCA1 and BRCA2 genes and other regions on 17q and 13q in breast cancer among women from Taiwan (area of low incidence but early onset).

We have examined the role of the breast cancer susceptibility genes BRCA1 and BRCA2 and other loci in the vicinity of these 2 genes on the long arms of chromosomes 17 and 13 (17q and 13q) for the presence of genomic deletions in breast cancer among Taiwanese women. Breast cancer in Taiwan is particularly characterized by its low incidence rate and its early age of tumor onset. Twelve microsatellite markers spanning the region 17q12-21 and 8 microsatellite markers spanning the region 13q12-14 were analyzed for allelic loss or loss of heterozygosity (LOH) in 90 patients with primary infiltrating ductal carcinoma. Compared with the background LOH level (10-12%) estimated by LOH at 4 unrelated loci, 17 markers (11 at 17q and 6 at 13q) demonstrated a significantly increased frequency (21-42%) of allelic loss (p < 0.05). Subsequent construction of deletion maps based on LOH at these significant loci localized the 6 smallest regions of overlap, including those harboring BRCA1, BRCA2, the retinoblastoma gene and 3 novel regions (the 1st located approximately 0.5 to 1 cM telomeric to BRCA1, the 2nd centromeric to BRCA1 flanked by D17S857/D17S846 and the 3rd closely adjacent to BRCA2), suggesting sites of susceptibility genes. Allelic loss at BRCA1 and BRCA2 was specifically associated with poorly differentiated tumors.

Aged↗

PubMed1998

Quantitative forced ductions in an animal model--characterization of passive forces.

PURPOSE: Our purpose was to characterize the passive tissue forces involved in ocular rotation in a controlled animal model and to evaluate the influence of manual versus mechanized ductions, repeated measurements, speed of rotation, and the influence of the nondepolarizing muscle relaxant mivacurium. METHODS: Forced ductions were performed under general anesthesia on 20 eyes of 10 pigs, with or without mivacurium, with use of a highly sensitive force gauge attached to the eye by a traction suture. The eye was moved either manually or at constant speed with a motorized platform. Eyes were rotated a total of 8 mm from their resting position under anesthesia. The force-displacement relationship was analyzed and compared between groups. RESULTS: A linear (elastic) relationship between force and displacement was noted, with a slope of 0.4 g per degree with use of the mechanized technique. Neither speed of rotation, use of mivacurium, nor repeated ductions significantly influenced the shape or slope of the relationship. Hysteresis averaged 2 to 4 g. Measurements performed with use of the motorized platform showed significantly improved reliability over those made manually. CONCLUSIONS: The passive length-tension data correlate well with data reported by others in humans. Within a wide range of eye movement, this force is elastic in nature. For relatively low angular velocities, such as might be produced in smooth pursuit, the passive forces do not change appreciably with changes in velocity. The nondepolarizing muscle relaxant mivacurium has no effect on accurate performance of passive forced ductions under general anesthesia. Studies collecting quantitative data on passive orbital forces should be performed, when feasible, with an automated duction and recording apparatus.

Anesthesia, General↗

PubMed1998

Restricted ocular motility after orbital trauma--studies with an animal model.

OBJECTIVE: Our purpose was to develop a quantitative model of restricted ocular motility (fat adherence syndrome) in the pig orbit to facilitate research into pathogenesis and treatment. METHODS: Twenty eyes of 10 pigs were used in an attempt to create a fibrous adhesion between either the inferior rectus or the medial rectus muscle and the adjacent periorbita. Quantitative forced ductions were performed preoperatively and 6 weeks postoperatively with an electronic force gauge. RESULTS: Forced ductions displayed a linear relationship to displacement over the range tested, both preoperatively and postoperatively. Although increased resistance to forced ductions was produced in 10 of the 20 (50%) eyes, the average changes were not statistically significant. The absolute change in force (Postoperative--Preoperative) was linearly related to the amount of ocular rotation. Reproducibility of measurements was markedly improved by the use of a motorized forced duction apparatus compared with manual rotation. CONCLUSIONS: The results from this study, and those from previous work, suggest that the classic fat adherence syndrome is an uncommon event, even after significant soft tissue injury in the orbit. Further studies are needed to more completely define the risk factors and pathogenesis of the fat adherence syndrome and the suitability of the pig orbit as a model.

Adipose Tissue↗

PubMed1997

Requirement of phosphatidylinositol-3 kinase for activation of JNK/SAPKs by PDGF.

The molecular mechanism by which cell surface receptors stimulate the serine/threonine kinase activity of c-Jun N-terminal kinases (JNKs) was investigated using a transient cotransfection experiments in COS-7 cells. Our data demonstrate that JNK activity is potently induced by platelet derived growth factor (PDGF) upon expression of beta PDGFR wild type (beta RWT). However, PDGF failed to mediate JNK activation in cells expressing beta PDGFR mutant lacking the binding site for phosphatidylinositol-3 (PI-3) kinase but not for phospholipase C gamma (PLC gamma) or Syp. Consistent with this result, a PI-3 kinase inhibitor, wortmannin inhibited activation of JNK by PDGF. Furthermore, overexpression of P110 the catalytic domain of PI-3 kinase was sufficient for activation of JNKs which could be efficiently inhibited by dominant negative forms of Ras, Rac but not of RhoA or Cdc42. Taken together all of these findings suggest that activation of JNK by PDGF involves receptor association with PI-3 kinase activity, which in turn acts on a ras- and rac-dependent pathway.

Androstadienes↗