Effect of acupuncture on atrial fibrillation stratified by CHA2DS2-VASc score-a nationwide cohort investigation.

OBJECTIVE: This research aimed to make statements regarding the reduction in atrial fibrillation (AF) risk due to acupuncture, stratified by CHA2DS2-VASc score. METHODS: The Kaplan-Meier method was performed to calculate cumulative incidence of outcomes for each group, and the log-rank test were performed to compare differences between groups. Incidences and hazard ratios (HRs) were estimated by univariate Cox proportional hazards models, and adjusted HRs (aHRs) were estimated by multivariate Cox proportional hazards models including demographic covariates and comorbid status. RESULTS: In CHA2DS2-VASc scores of 0-1, 2-3, 4-5 and >5, cases with acupuncture were all associated with decreased incidence of AF (aHR 0.46 with 95% CI 0.42-0.51, P < 0.001 in the CHA2DS2-VASc scores of 0-1; aHR 0.53 with 95% CI 0.50-0.57, P < 0.001 in the CHA2DS2-VASc scores of 2-3; aHR 0.56 with 95% CI 0.52-0.61, P < 0.001 in the CHA2DS2-VASc scores of 4-5; and aHR 0.64 with 95% CI 0.55-0.74, P < 0.001 in the CHA2DS2-VASc scores of >5). CONCLUSION: Protective effect of acupuncture on AF was observed in this study, and the effect was more obvious for those with fewer comorbidities.

Efficacy and safety of high-dose vs low-dose leucovorin in patients with colorectal cancer: systematic review and meta-analysis.

AIM: The clinical benefits of a combination of leucovorin and fluorouracil have been established in the treatment of colorectal cancer. Due to a leucovorin shortage in 2008, many institutions revised their protocols to reduce the dose of leucovorin. After the shortage was resolved, some hospitals still maintained their modified protocols. Thus, we conducted a systematic review to evaluate the efficacy and safety of low- vs high-dose leucovorin in the treatment of colorectal cancer. METHOD: The PubMed, Embase and Cochrane databases were searched for studies published before May 2019. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcomes were median survival time and tumour response rate. Secondary outcomes were haematological and nonhaematological toxicities. RESULTS: Eight randomized controlled trials and four retrospective studies were reviewed. The pooled median survival time was similar between the two dose levels (standard mean difference -0.06, 95% CI -0.19 to 0.08). The pooled tumour response rate was comparatively higher in the high-dose leucovorin regimen (OR 0.81; 95% CI 0.55-1.18). No statistically significant difference was found between the haematological and nonhaematological toxicities of the two groups. However, there were fewer diarrhoea events in the low-dose leucovorin regimen. CONCLUSION: Low-dose leucovorin regimens seemed feasible approaches for colorectal cancer treatment when the shortage happened, because both regimens manifested comparable outcomes in survival time and tumour response rate.

Herb formula enhances treatment of impotent patients after penile venous stripping: a randomised clinical trials.

Herbs have been regarded as aphrodisiacs in treating impotence for many centuries despite little true scientific evidence. Our latest refined penile venous stripping (PVS) technique is effective in treating impotence, although this procedure remains controversial. A synergic effect of PVS and oral herbs was confirmed in our practice but lacked rigorous scientific proof. The objective of this report was to review our experience with this combination. From August 2010 to May 2014, 263 males underwent PVS. Among these, 67 unsatisfied men chose additional salvage therapy and were randomly assigned to oral herbs (n = 35) or placebo treatment (n = 32) which replaced herb eventually. All were evaluated with the international index of erectile function (IIEF-5) scoring and our dual pharmaco-cavernosography. The pre-op IIEF-5 score for the herb group was 9.7 ± 3.7, post-operative 13.9 ± 3.3 and post-herb 19.6 ± 3.4, while the control group scores were as follows: pre-op 9.3 ± 4.1, post-op 14.5 ± 3.6, post-placebo 15.1 ± 3.5 and post-herb 19.9 ± 3.2. Although there was no significant difference between the two groups pre-operatively, post-operatively and post-herb, a statistically significant difference was found post-salvage therapy (19.6 ± 3.4 versus 15.1 ± 3.6, P < 0.001). It appears that the combination of oral herbs and PVS treatment provides an enhanced outcome to impotent patients refractory to medicine and unsatisfied with PVS monotherapy alone.

Subablative Er:YAG laser effect on enamel demineralization.

OBJECTIVES: To characterize the cariostatic potential of a low-energy Er:YAG laser treatment. METHODS: Twelve sound premolars were selected. Two 2 × 1 mm windows were created on each tooth and randomly assigned to L(1) and L(2) groups. Three sites in each window were chosen with the middle site as the control and the left and right ones receiving Er:YAG laser treatment of 5.1 J/cm(2) (L(1)) or 2.0 J/cm(2) (L(2)), respectively. The teeth were further subjected to 4-day pH cycling to create caries-like lesions. After mineral quantification using a micro-computed tomography scanner, the preventive effects (ΔML = mineral loss of the control area minus that of the lased area) of L(1) and L(2) treatments were calculated based on the difference in the gray value of the control and lased sites. RESULTS: Significant inhibitory effects of L(1) and L(2) on enamel demineralization were demonstrated (both p ≤ 0.001), with the L(1) treatment having a greater effect (45.2%) than the L(2) treatment (25.2%, p = 0.004). CONCLUSIONS: Subablative low-energy Er:YAG laser irradiation can significantly prevent enamel demineralization potentially through the retardation of enamel diffusion. This study confirmed that high-energy laser treatment, which may damage the peripheral and underlying tissues, may not be needed for caries prevention.

Potential mechanism for the laser-fluoride effect on enamel demineralization.

Laser-induced prevention of dental caries has been studied extensively. However, the cariostatic mechanisms of a combined fluoride-laser treatment are not well-understood. Using micro- computed tomography (micro-CT), we quantified the effect of fluoride and/or Er:YAG laser treatment on enamel demineralization. The mean mineral loss (%/V) for each group was 4,870 ± 1,434 (fluoride followed by laser treatment), 6,341 ± 2,204 (laser treatment), 7,669 ± 2,255 (fluoride treatment), and 10,779 ± 2,936 (control). The preventive effect of the laser (p < 0.001) and fluoride (p = 0.010) treatment was statistically significant. Characterized by micro-x-ray diffraction (XRD) analysis, the significant contraction in the a-axis after both laser and combined laser/fluoride treatment was revealed (both p < 0.05). In conclusion, subablative low-energy Er:YAG laser irradiation following fluoride treatment may instantaneously transform enamel hydroxyapatite into fluoridated hydroxyapatite to reduce enamel solubility as a preventive treatment for enamel demineralization.

Promoting positive health behaviours--'tooth worm' phenomenon and its implications.

UNLABELLED: 'Tooth worm' is a traditional belief about the pathogen of dental caries (tooth decay). Nevertheless, in our previous study, parental 'tooth worm' belief was linked to a reduced caries risk of their children. OBJECTIVES: This study aimed to further characterize the impact of parental 'tooth worm' belief on their children's caries experience and its psychobehavioural mechanisms. BASIC RESEARCH DESIGN: analytic observational study. SETTING: Thirteen randomly selected kindergartens in Singapore. PARTICIPANTS: 1,782 preschoolers aged 3-6 years. METHODS: Each child received an oral examination and microbiological tests. Parents completed a self-administered questionnaire on their socio-demographic background, oral health knowledge/attitude and child's oral health habits. RESULTS: Multivariate analysis confirmed a reduced chance of 'high caries rate' (number of affected teeth > 2) among children whose parents held the 'tooth worm' belief (Odds Ratio = 0.41; 95% Confidence Interval = 0.19-0.89). With such perception among parents, children brushed their teeth more frequently (p = 0.042). Since no difference in oral hygiene was observed, the health benefit of the "tooth worm" perception may be acquired through the delivery of fluoride (an agent with proven anti-caries effect) during frequent toothbrushing episodes. CONCLUSIONS: This study revealed a 'tooth worm' phenomenon, indicating that parental 'tooth worm' belief is associated with early establishment of regular toothbrushing habit and reduction of dental caries in children. This phenomenon and its psychobehavioural mechanisms, enriching our understanding of oral health behaviours, have implications for effective health education.

Suppression of inflammation-associated factors by indole-3-carbinol in mice fed high-fat diets and in isolated, co-cultured macrophages and adipocytes.

AIMS: This study investigated the effects of indole-3-carbinol (I3C), a compound from cruciferous vegetables, on various parameters related to obesity, in particular, the parameters of infiltration by macrophages and of inflammatory cytokines expressed during the co-culture of adipocytes and macrophages. METHODS: Male C57BL/6 mice were fed with a control diet (C group), high-fat diet (HF group) and HF+5 mg kg(-1) I3C (HFI group). The I3C was intraperitoneally injected (HFI group) for 12 weeks. Epididymal adipose tissue (AT) was collected and stained for F4/80, a marker of macrophages. RESULTS: The immunohistochemical staining for F4/80 indicated a greater presence of macrophages in the HF group than in AT from the control and HFI groups. Furthermore, I3C treatment, in an in vitro cell culture system, decreased expression of inducible nitric oxide synthase (iNOS), decreased nitrite content and enhanced expression of peroxisome proliferator-activated receptor (PPAR-γ). Moreover, in vitro cell culture studies revealed that I3C inhibited intracellular lipid accumulation in hypertrophied adipocytes. In macrophage and primary adipocyte co-culture, I3C inhibited expression of interleukin-6 (IL-6). CONCLUSIONS: In vivo treatment with I3C reduced the infiltration of macrophages in AT, and in vitro addition of I3C to co-cultured macrophages and adipocytes reduced nitrite production and IL-6 expression. With cultures of adipocytes only, I3C inhibited accumulation of intracellular lipid, either by disrupting differentiation, or by directly inhibiting triglyceride synthesis.

The novel anti-hyperglycemic effect of Paeoniae radix via the transcriptional suppression of phosphoenopyruvate carboxykinase (PEPCK).

The antidiabetic actions of Paeoniae Radix involve stimulating glucose uptake and reducing glucose absorption. However, the importance of this herb in the transcriptional regulation of hepatic gluconeogenesis has not previously been investigated, although hepatic gluconeogenesis contributes the most to fasting hyperglycemia. Using rats with streptozotocin-induced diabetes and db/db mice, the dose- and time-dependent suppressive effects of the ethanol extract of Paeoniae Radix (PR-Et) on diabetic hyperglycemia and phosphoenopyruvate carboxykinase (PEPCK) transcription are first demonstrated. Second, by employing H4IIE cells, the inhibitory action of PR-Et on both dexamethasone- and 8-bromo-cAMP-induced-PEPCK expression was also confirmed without causing any cytotoxicity. In addition, this inhibitory effect could be sustained for over 24 h with repeated treatment. Most importantly, PR-Et's action was unaffected by either insulin desensitization or palmitate stimulation. Finally, paeonol and paeoniflorin, two well-known constituents in Paeoniae Radix, did not suppress PEPCK expression at testing concentration. In conclusion, it was clearly demonstrated that transcriptional inhibition of gluconeogenesis is one of the important antidiabetic actions of Paeoniae Radix. Future development of this herb as a dietary supplement or drug should bring substantial benefits for the diabetic population.

Community-based incidence of acute renal failure.

There is limited information about the true incidence of acute renal failure (ARF). Most studies could not quantify disease frequency in the general population as they are hospital-based and confounded by variations in threshold and the rate of hospitalization. Earlier studies relied on diagnostic codes to identify non-dialysis requiring ARF. These underestimated disease incidence since the codes have low sensitivity. Here we quantified the incidence of non-dialysis and dialysis-requiring ARF among members of a large integrated health care delivery system - Kaiser Permanente of Northern California. Non-dialysis requiring ARF was identified using changes in inpatient serum creatinine values. Between 1996 and 2003, the incidence of non-dialysis requiring ARF increased from 322.7 to 522.4 whereas that of dialysis-requiring ARF increased from 19.5 to 29.5 per 100,000 person-years. ARF was more common in men and among the elderly, although those aged 80 years or more were less likely to receive acute dialysis treatment. We conclude that the use of serum creatinine measurements to identify cases of non-dialysis requiring ARF resulted in much higher estimates of disease incidence compared with previous studies. Both dialysis-requiring and non-dialysis requiring ARFs are becoming more common. Our data underscore the public health importance of ARF.

High rate of clinical complete response to weekly outpatient neoadjuvant chemotherapy in oral carcinoma patients using a new regimen of cisplatin, 5-fluorouracil, and bleomycin alternating with methotrexate and epirubicin.

BACKGROUND: A Phase II trial was initiated to evaluate the response to and toxicity of a new regimen of weekly outpatient neoadjuvant chemotherapy in patients with oral carcinoma. METHODS: Patients with previously untreated squamous cell carcinoma of the oral cavity were eligible for this trial. The neoadjuvant chemotherapy was comprised of cisplatin, 25 mg/m2, 5-fluorouracil, 1000 mg/m2, and bleomycin, 10 mg/m2, mixed in normal saline as a 24-hour intravenous (i.v.) infusion, alternating with methotrexate, 30 mg/m2, and epirubicin, 30 mg/m2, as an i.v. bolus (PFB/ME) on a weekly schedule for 8-12 weeks. In patients with American Joint Committee on Cancer Stage IV disease who completed neoadjuvant chemotherapy, surgery was preferred to radiotherapy, unless patients refused surgery. RESULTS: A total of 40 patients (82.5% with Stage IV disease) with previously untreated oral carcinoma were enrolled. The median size of the primary tumor was 7 cm (range, 3-13 cm). Fifty percent of patients had tumor penetrating through the oral mucosa to the cheek skin and 62.5% had bony destruction. Detectable cervical lymph nodes were noted in 77.5% of patients. After neoadjuvant weekly chemotherapy, 22 patients (55%) showed complete response (CR) and 15 patients (37.5%) showed partial response, for an overall response rate of 92.5%. World Health Organization Grade 3/4 toxicity included mucositis (7.5%), leukopenia (25%), anemia (10%), and thrombocytopenia (2.5%). Eleven of 33 patients with Stage IV disease underwent surgery, and pathologic CR (2 patients) or microscopic residual tumor (4 patients) was noted (54.5%). CONCLUSIONS: The results of the current study indicate that a weekly PFB/ME neoadjuvant chemotherapy regimen is highly effective for the treatment of patients with oral carcinoma. In addition, this regimen has low toxicity. The authors believe that implementation of this regimen into a multimodality therapy protocol deserves further study.

Outpatient weekly chemotherapy in patients with nasopharyngeal carcinoma and distant metastasis.

BACKGROUND: Distant metastasis is a more common pattern of failure than locoregional recurrence after adequate radiotherapy in patients with nasopharyngeal carcinoma (NPC). The objective of this Phase II study was to assess the efficacy and toxicity of weekly chemotherapy in NPC patients with distant metastasis. METHODS: Patients with a histologic diagnosis of NPC and documented distant metastasis were eligible, including those who 1) had metastatic disease at presentation; 2) had developed metastatic disease during or at any time after local radiotherapy; or 3) had developed progressive disease or recurrence of metastasis after prior chemotherapy. The weekly chemotherapy regimen was comprised of 5-fluorouracil (5-FU), 1250 mg/m2, plus cisplatin, 25 mg/m2, as a 24-hour continuous intravenous infusion via a subcutaneous implanted port, using an ambulatory pump in an outpatient setting for the first 19 patients. Because of the low incidence and reduced severity of toxicity, the dosage of chemotherapy was escalated to 5-FU, 1667 mg/m2, plus cisplatin, 33.3 mg/m2, for the subsequent 25 patients. RESULTS: Between October 1992 and June 1996, a total of 44 patients with metastatic NPC were studied. They were 36 males and 8 females with a median age of 48 years (range, 30-72 years). Poorly differentiated epidermoid carcinoma or undifferentiated carcinoma were the major pathologic types. Twenty-six patients had single organ metastasis, whereas 18 patients had multiple organ involvement. Locoregional disease existed simultaneously in 16 patients. The majority of patients had received previous radiotherapy (33 patients) and chemotherapy (23 patients: 16 as concurrent therapy for localized disease, 6 as salvage therapy for metastatic disease, and 1 for a postradiation adjuvant purpose). Among 38 patients with measurable disease, 8 obtained a complete response (CR) (21.1%), 12 obtained a partial response (PR) (31.6%), 17 had stable disease (SD) (44.7%), and 1 had progressive disease (2.6%). The median duration of CR, PR, and SD were 6.5 months, (range, 2-12 months), 5.5 months (range, 2-9 months), and 2.5 months (range, 1-6 months), respectively. Toxicity was found to be very mild. Only one patient developed a World Health Organization (WHO) Grade 1 mucositis. No visible alopecia and no treatment-related deaths occurred. WHO Grade 3-4 hematologic toxicities occurred in 1.0% of patients for leukopenia, 4.1% for anemia, and 2.9% for thrombocytopenia. CONCLUSIONS: Data from the current study indicate that 24-hour weekly infusion of 5-FU plus cisplatin has moderate activity but very low toxicity for NPC patients with distant metastasis. Further study is necessary to find more effective therapy.

Partially hyperfractionated accelerated radiotherapy and concurrent chemotherapy for advanced nasopharyngeal carcinoma.

PURPOSE: A newly designed concomitant chemoradiotherapy was undertaken to assess the feasibility and efficacy for advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Sixty-three patients with biopsy-proven NPC were entered in this Phase II trial from March 1992 to November 1993. Most patients present with Stage IV disease (93.4%) and poorly differentiated epidermoid carcinoma or undifferentiated carcinoma were the major pathologic type. Radiotherapy was delivered using a telecobalt unit and 10 MV x-rays and by altered fractionation (72-74 Gy/45 fractions/6 weeks). Chemotherapy with cisplatin 75 mg/m2, 2 h infusion at day 1, followed by 5-FU 400 mg/m2/day, continously infused for 4 days was given concurrently during the first and fifth weeks of radiotherapy. RESULTS: The major toxicity was mucositis (61% belong to Grade 3, 31% to Grade 2). Weight loss, leucopenia, and skin reaction were frequently encountered. Three patients withdrew from treatment at 15, 25, and 55.5 Gy, three patients interrupted the radiotherapy for 1-4.5 weeks, and two patients refused the second cycle of concomitant chemotherapy due to toxicities. The initial tumor response showed 100% overall response rate, with 90.5% complete response. After a median follow-up time of 38 months, five patients failed at the primary and/or neck (four recurrent and one persistent), and 14 patients developed distant metastases alone. The 3-year primary disease-free, regional disease-free, distant disease-free, and overall survival rates are 89.1, 92.8, 74.3, and 73.6%, respectively. The late complication rate is acceptable so far. CONCLUSIONS: Our data indicates that concurrent chemoradiotherapy for advanced NPC is both feasible and effective, with acceptable toxicities. Distant metastases are the major site of treatment failure. Postradiation adjuvant chemotherapy to eradicate subclinical distant metastasis should be further studied.

Preliminary report of outpatient weekly adjuvant chemotherapy for high-risk nasopharyngeal carcinoma.

Distant metastasis has become the most frequent failure site-more so than locoregional relapse-after adequate radiotherapy in nasopharyngeal carcinoma (NPC). A prospective study was initiated to test the role of postradiation adjuvant chemotherapy using a weekly schedule for selected patients with high-risk NPC (N3, T4N2b-2c, and N2b-2c, with one of nodal size > 4 cm, or residual disease after radiotherapy). Through July 1993 to August 1994, a total of 20 patients were entered into the study: 16 men and four women, with a median age of 49 years and age range of 27-75 years. Pathology showed WHO type I:II:III = 2:13:5. Previous treatment consisted of concurrent chemoradiotherapy (16 patients), radiotherapy alone (two), and neoadjuvant chemotherapy followed by radiotherapy (two). Postradiation adjuvant chemotherapy was usually started 2 months after radiotherapy, using a weekly FP schedule (5-fluorouracil 1,250 mg/m2 + cisplatin 25 mg/m2, mixed in 100 ml saline, 24 h continuous i.v. infusion) for 18 weeks. The treatment of five patients was at 5, 6, 10, 14, and 15 weeks because of leukopenia-induced mortality, sudden death unrelated to adjuvant chemotherapy, a patient's refusal, and distant metastasis (the last two cases) during adjuvant chemotherapy. The major toxicity was leukopenia (grade I, 20%; grade II, 45%; grade III, 15%; and grade IV, 10%). Ten patients (50%) developed distant metastasis after a median follow-up time of 20 months. Our preliminary data indicate that postradiation adjuvant chemotherapy with a weekly FP regimen at our dosage is not recommended for high-risk NPC.

Local massage after vaccination enhances the immunogenicity of diphtheria-tetanus-pertussis vaccine.

The effect of local massage on adverse reactions and immunogenicity of diphtheria-tetanus-pertussis vaccine was investigated. After diphtheria-tetanus-pertussis vaccination 327 infants were either massaged or not, and adverse reactions were evaluated. Local pain and fever were more frequent in the massage group. The extra febrile episodes from massage were mild (38-39 degrees C). For evaluation of the antibody responses, 124 infants were recruited into massage or nonmassage cohorts and antibody production was measured at 2, 6, 7, 18 and 19 months of age, respectively. Subjects in the massage group developed significantly higher antibodies against filamentous hemagglutinin at 6 and 7 months of age, pertussis toxin at 6, 7, 18 and 19 months of age, pertussis agglutinogen at 18 and 19 months of age and those in the nonmassage group. Local massage after diphtheria-tetanus-pertussis vaccination was associated with better immunogenicity and more adverse reactions, including low grade fever and local pain, which were mild and not particularly disturbing.

Effects of fish oil supplementation on acute ischemic brain injury in the rat.

We studied the effects of long-term fish oil (FO) dietary supplementation on brain edema, polymorphonuclear neutrophil (PMN) infiltration, and infarct size in a rat stroke model. Rats were given regular rat chow with or without FO supplement (20% of total calories) for 7 weeks. Body weight did not differ between the two groups. In the FO group, an increase in eicosapentaenoic acid and a decrease in arachidonic acid content in hepatic phospholipids were significant in the phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine but not in the phosphoinositol fraction. Platelet activity reflected by serum thromboxane B2 levels was reduced in the FO group. Postischemic brain edema and PMN infiltration were not different between the two groups. The infarct volume was significantly greater in the FO group (controls: 96 +/- 7 mm3, n = 49; FO group: 124 +/- 6 mm3, n = 53; p = 0.0036). The greater ischemic brain injury in the FO-supplemented animals is probably related to the intraischemic hyperglycemia, which was worse in the FO group than in the control group (controls: 265 +/- 19 mg/dl, n = 14; FO group: 340 +/- 18 mg/dl, n = 16; p = 0.0079).

Angiodysplasia as a source of intestinal bleeding: report of seven cases.

From October 1978 to April 1991, seven patients presenting at the National Taiwan University Hospital with gastrointestinal tract hemorrhage were diagnosed by colonofibroscopy or angiography as having angiodysplasia of the colon and small intestine. There were two men and five women; their ages ranged from 23 to 65 years, with a mean age of 50.3 years. None of these patients were diagnosed by barium enema. Only two patients were diagnosed by colonofibroscopy, and six patients were diagnosed by angiography. Therefore, angiography was the most effective method for diagnosing angiodysplasia. A vascular tuft was the most frequent finding. Six patients with lesions on the right side of the colon underwent a right hemicolectomy, one patient with a lesion on the jejunum underwent a right hemicolectomy initially with segmental resection of the jejunum later. The postoperative courses were smooth, and there has been no further evidence of gastrointestinal blood loss or anemia in the follow-up period. A right hemicolectomy is the treatment of choice because these lesions are frequently multiple; the lesions are found primarily on the right side of the colon.

CT myelography for differential diagnosis between intramedullary and intradural-extramedullary spinal tumors in the region of the conus medullaris.

We reviewed the myelograms and computed tomographic myelograms of 12 cases of intraspinal tumor with a "cupping sign" on the myelogram in the region of the conus medullaris from 1986 to 1988. There were 5 intramedullary tumors, 4 of them having an exophytic component, and 7 intradural-extramedullary tumors. The myelograms revealed that 4 of the 5 intramedullary tumors showed expansion and the outline of the conus medullaris was irregular, whereas 1 of the tumors showed smooth compression (crescent-shaped) and displacement of the conus medullaris. Six of the 7 intradural-extramedullary tumors showed smooth compression and displacement of the conus medullaris, while 1 of the tumors had caused expansion of the conus medullaris. Complete blockage of the passage of the contrast medium was noted in 3 of the 5 intramedullary tumors, while a partial block was noted in 3 of the 7 intradural-extramedullary tumors. Two of the 7 intradural-extramedulllary tumors showed an extradural tumor component, such as a dumb-bell tumor and a enlarged intervertebral neural foramen. Tumor calcification was noted in 1 of the 7 intradural-extramedullary tumors. Dural ectasia was noted in 2 of the 7 intradural-extramedullary tumors which were later proven to be neurofibromatosis. We conclude that smooth compression (crescent-shaped) and displacement of the conus medullaris, existence of an extradural tumor component, and eroded intervertebral neural foramina favor intradural-extramedullary tumors, while expansion and a conus medullaris with an irregular outline favors intramedullary tumors.

Generation of recombinant cytoplasmic domain of epidermal growth factor receptor with intrinsic protein tyrosine kinase activity.

We have generated a recombinant baculovirus using the high expression vector pVL941 containing the complementary DNA encoding the intracellular domain of the human epidermal growth factor receptor (EGFR-IC). Upon infection of Spodoptera frugiperda insect cells, protein tyrosine kinase-active EGFR-IC was produced. The expressed protein has a molecular weight of 61,000 and is specifically recognized by antibodies directed against peptides representing different regions of human EGFR-IC. Upon sonication of infected cells, EGFR-IC was detected in both the soluble and insoluble fractions of the cell lysate. About 20-50% of the expressed EGFR-IC was soluble. Metabolic labeling and protein analyses showed that EGFR-IC comprised 7% of newly synthesized proteins in the cytoplasmic lysate and 0.1-0.2% of the total soluble protein. We have used a three-step purification procedure (fast-Q-Sepharose and phenyl-Sepharose column chromatographies and 30% ammonium sulfate precipitation) to purify EGFR-IC to 85% purity with 15-20% recovery from the initial soluble lysate. A yield of 3-4 mg of purified EGFR-IC has been consistently produced from 20 roller bottles with 2-4 x 10(8) infected cells/bottle. The tyrosine kinase activity was retained through purification. The enzyme demonstrated much higher autophosphorylation activity in the presence of Mn2+ than Mg2+. Phosphopeptide mapping revealed the same autophosphorylation sites utilized by EGFR-IC as those identified in wild-type EGFR. EGFR-IC-catalyzed phosphorylation of either a synthetic peptide representing the major autophosphorylation site or angiotensin II showed that the baculovirus-expressed EGFR-IC exhibits similar enzymatic kinetic characteristics to the intact activated EGFR kinase.