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Hepatic epithelioid hemangioendothelioma (HEH) is a very rare vascular tumor of the liver. It usually affects adult women and presents as multiple hepatic nodules with mainly peripheral distribution. It poses special difficulties for clinicians in its diagnosis and treatment because of its non-specific clinical manifestations and findings on imaging, and it is easy to be misdiagnosed pathologically. Its clinical course and prognosis are variable but supposed to be intermediate between hemangioma and angiosarcoma. The primary treatments of choice are radical resection or liver transplantation. We report a 62-year-old man with right upper quadrant abdominal pain of several days' duration, who was initially misdiagnosed as having a liver abscess. Finally, HEH was diagnosed on the basis of positive immunohistochemical staining for factor VIII-related antigen in tumor cells. This case could serve to highlight the pitfalls in diagnosing this rare tumor. Increasing the index of suspicion and familiarity with the radiological and histological characteristics of this tumor would facilitate the accurate diagnosis and thus avoid unnecessary interventions.

Acute radiation exposure of humans was observed to induce various forms of cytogenetic damage, including increased frequencies of micronuclei and chromosomal aberrations. However, the cytogenetic effects of chronic low dose radiation exposure in vivo needs further characterization. Sixteen subjects with chronic low dose rates of gamma-radiation exposure from 60Co-contaminated steel in radioactive buildings were compared with seven non-exposed reference subjects for micronucleus frequencies after they relocated. By in situ hybridization using a digoxigenin-labeled anti-alpha all human centromere probe, the exposed subjects were shown to have a significant increase in cytochalasin B-modulated micronucleus (CBMN) frequencies, as well as a significant increase in centromere-positive (C+) CBMN, centromere-negative (C-) CBMN, total C+signals, single C+ MN signals and multiple C+ signals/1000 binucleated cells (BN). However, decreases in the ratios C+MN/C- MN and C+MN/total CBMN (%) were also noted in the exposed subjects. By mixed effects analysis, considering individuals from the same families, the C- MN and single C+ MN/1000 BN were both positively and moderately associated with previous cumulative exposure. When the time period of relocation post-exposure (relocation time or RT) was considered, total C+MN and multiple C+MN/1000 BN were negatively and significantly associated with RT. Moreover, the C+MN, C- MN, C+MN/C- MN ratio and single C+MN/1000 BN were all negatively and moderately associated with RT, but not with exposure dose. This suggested that acentromeric and single or multiple centromeric CBMN cytogenetic damage seems to disappear differentially in human subjects post chronic low dose radiation exposure.

Hepatic angiosarcoma is a rare malignant tumor with a rapidly fatal course. It has become a subject of interest because of its intimate relationship with environmental carcinogens, such as thorium dioxide (Thorotrast), vinyl chloride monomer, and arsenic. We describe a case of a chronic hepatitis B surface antigen carrier, with a 20-year history of environmental exposure to arsenical-containing agricultural herbicides and bactericides, who developed a hepatic angiosarcoma. He died due to rupture of the hepatic angiosarcoma with acute hemoperitoneum 9 weeks after initial diagnosis. This is a rare case of primary hepatic sarcoma, especially in Taiwan where hepatocellular carcinoma is endemic. This case not only serves to give more evidence of the relationship between hepatic angiosarcoma and arsenical exposure, but also demonstrates the key point in the differential diagnosis of liver tumors. Increased familiarity with this disease will facilitate correct diagnosis and help to improve management of the condition in the future.

A variety of free-tissue transplantations are available for oropharyngeal (lining) reconstruction. The most commonly used flap, the radial forearm flap, is relatively thin, adaptable, and reliable but does not provide lubrication. In this study, the potential of the transverse colon to provide a lubricating tissue for replacement of oral lining was investigated. Eleven patients requiring replacement of oral lining received transverse colon flap transplantation between November of 1993 and December of 1995. There was one complete flap loss and one partial loss. Flap size used for reconstruction averaged 40.4 cm2, and average vessel length and diameter were 7 cm and 2.0 mm, respectively. In a follow-up period from 15 to 48 months, all colon flaps proved to be durable with continuous lubrication function. Histologic assessment of the transplanted colon flaps at various postoperative times showed an adequate amount of mucus-secreting goblet cells even after irradiation. There was no donor-site morbidity. The main disadvantage seemed a tendency to transplant too much tissue, which resulted in formation of redundant pockets affecting food handling. Thus, 8 out of 10 patients with flap survival required one to three debulking procedures. Given an accurate estimation of the area of mucosa defect and adequate trimming of the colon flaps, the transverse colon flap offers a good alternative for reconstruction of the oral lining, especially when lubrication is desirable in cases with large defects and preoperative or postoperative irradiation, or in case a radial forearm flap is not available.

We describe the first case of isolated nasopharyngeal Castleman's disease mimicking juvenile angiofibroma. Castleman's disease may appear as a local or generalized tumor-like condition, usually in the chest or abdomen, and may involve both the lymph nodes and non-nodal tissues. Since the nasopharyngeal roof is the residence of the pharyngeal tonsils (adenoids) which are rich in lymphoid tissues, such an appearance is predictable. It is emphasized that careful interpretation of radiographs may help to distinguish Castleman's disease from other tumor conditions, such as lymphoma, neurogenic tumor, or even angiofibroma, etc. But the exact diagnosis must be made on the basis of histologic confirmation. In addition to histologic classifications, clinical distinction between the localized and multicentric forms is important in selecting appropriate management. Surgical excision is the first choice and is curative in cases of localized Castleman's disease, but provides little benefit for cases of the multicentric form because of systemic manifestations and rapid deterioration. Thus, antineoplastic agents and steroids may offer an alternative form of therapy for patients with the multicentric form.

Since human papillomavirus (HPV) infection is strongly associated with cervical neoplasia and tumor hypoxia has prognostic significance in human cervical carcinomas, we examined the relationship between hypoxia and apoptosis in human cervical epithelial cells expressing high-risk HPV type 16 oncoproteins. In vitro, hypoxia stimulated both p53 induction and apoptosis in primary cervical epithelial cells infected with the HPV E6 and E7 genes but not in cervical fibroblasts infected with E6 and E7. Furthermore, cell lines derived from HPV-associated human cervical squamous cell carcinomas were substantially less sensitive to apoptosis induced by hypoxia, indicating that these cell lines have acquired additional genetic alterations that reduced their apoptotic sensitivity. Although the process of long-term cell culturing resulted in selection for subpopulations of HPV oncoprotein-expressing cervical epithelial cells with diminished apoptotic potential, the exposure of cells to hypoxia greatly accelerated the selection process. These results provide evidence for the role of hypoxia-mediated selection of cells with diminished apoptotic potential in the progression of human tumors and can in part explain why cervical tumors that possess low pO2 values are more aggressive.

Precise assessment of the extent of nasopharyngeal carcinoma (NPC) represents the basic step towards optimal treatment. We compared the capacity of CT and MRI in assessing the extent of NPC in 67 patients. MRI was superior to CT in demonstrating lesions in the retropharyngeal node, skull base, intracranial area, carotid space, longus colli muscle and levator palatini muscle. Of 25 cases in which retropharyngeal adenopathy was recognised only on MRI, seven had been reported as showing oropharyngeal involvement and 18 as primary extension to the carotid space on CT. MRI showed skull-base involvement in 40 patients compared with 27 on CT and intracranial involvement in 38 patients versus 24 on CT. There was not a single case in which skull base invasion was seen on CT but not on MRI. MRI enabled improved recognition of tumour infiltration of longus colli muscles (34 cases compared with 15 on CT). It allowed us to clarify 12 questionable sinonasal opacities on CT. Overall, T-staging was changed in 18 of 67 patients (26.9%), including upstaging in 15 cases and down-staging in 3 cases, after comparing CT with MRI. The nodel status was changed from negative on CT to positive on MRI in 4 of 67 patients (6%). We believe that MRI allows more accurate evaluation of the extent of NPC than CT and should be the primary mode of investigation.

Background: Identifying the factors predicting response to chemotherapy is important for patients with head and neck squamous cell carcinoma (HNSCC). It allows more rational selection of subsets of patients who may benefit from multidisciplinary treatment. Correlation of lymph node density in contrast-enhanced computed tomographic (CT) scans of HNSCC with response to chemotherapy was observed in the recent literature. This prospective study was designed to validate this clinical issue., Methods: From January 1992 to March 1995, 71 patients with untreated HNSCC were included in this study in which the following criteria were met: 1) a lymph node > 3 cm by physical examination or > or = 2 cm by scanographic examination; 2) clinically evaluable disease treated by cisplatin-based neoadjuvant chemotherapy; and 3) availability of a pretherapeutic contrast-enhanced CT scan showing the cross-sections of relevant lymph node metastases. The density of the largest lymph node was compared with that of the nuchal muscles by a radiologist blinded to the patient's therapeutic outcome. A lymph node was classified as hypodense if more than 33% of the lymph node surface area was comprised of a hypodense zone, and isodense if less than a third of the lymph node surface area was comprised of a hypodense zone., Results: Fifty-one patients (72%) had the largest lymph node classified as hypodense, and 63 patients (89%) were found to have extranodal spread (ENS) in the relevant lymph nodes. Fifty-nine patients were betel quid chewers. Lymph node density was not related to T classification, primary site, or histologic differentiation of the primary tumor. There was also no correlation between lymph node density and lymph node N classification. The lymph node chemotherapy response rate was 35% (7 of 20) of the isodense group and 47.1% (24 of 51) of the hypodense group (P = 0.36). ENS was found to have no impact on the chemotherapy response., Conclusions: Computed tomographic density of lymph node metastases did predict chemotherapy response in the HNSCC patients in the current study from an area in which betel quid chewing is prevalent.

A 19-year-old male was admitted to our clinic because of nasal obstruction and intermittent postnasal drip of 3 to 4 years' duration. Physical examination revealed a wide-based, smooth-surfaced nasopharyngeal tumor which was suspected to be a nasopharyngeal angiofibroma after examination of computed tomographic scans and an angiogram. However, after the tumor was removed by surgical excision via a transpalatal approach, the pathologic examination revealed Castleman's disease of the hyaline-vascular type. There was neither evidence of recurrence nor nasal problems at 4 years' follow-up. To our knowledge, Castleman's disease, or angiofollicular lymph node hyperplasia, may present as a local or generalized tumor-like condition, usually in the chest or abdomen, and may involve both the lymph nodes and non-nodal tissues. A review of previous articles reveals that there has not been any report of Castleman's disease found in the nasopharynx. This rare disorder is presented and discussed.

Due to the development of anesthetic drugs and techniques, and the progress of monitor system. The rate of cardiac arrest during anesthesia has declined during the last decades. We report two cases of sudden cardiac arrest which happened during transurethral resection of the prostate, and discuss the mechanism, treatment, and the methods of prevention.

Inhalation of foreign body in children is extremely hazardous, since the caliber of the tracheobronchial tree is small in children and the technique of bronchoscopic extraction is very demanding. The problem is even more complicated in handling rare foreign bodies, since the bronchoscopic procedure may be prolonged and inaccurate. Presented here is a case of pin aspiration. The long and pointed pin is quite impossible to remove. In this article, the course of bronchoscopy removal of the pin was described and the technical aspects of rigid bronchoscopy in handling pointed objects were cited in detail.

Seven cases with Osteosarcoma (OS) of the jaw were retrospectively reviewed. There were five female and two male patients. Their ages ranged from 14 to 57 years with a mean of 39 years. Seventy-one percent of the patients were older than 30 years old. Jaw swellings were the most frequent complaints occurring on an average of 3 months before diagnosis. Four cases occurred in mandible and three cases developed from maxilla. Most cases were lytic lesions on roentgenography. Four were osteoblastic, 2 were chondroblastic, and 1 was histologic classification. Six of the 7 cases received surgery. Postoperatively, 3 of them received both radiotherapy and chemotherapy, 1 received chemotherapy only and 1 received radiotherapy only. One case received palliative chemotherapy only because of the locally far advanced disease. Four cases died of regional failure without any metastatic lesions (survival ranged from 5 months to 22 months). Two cases survived more than 4 years without any recurrence. The median survival time was 22 months. We concluded that OS of the jaw has different natural courses from OS of the long bones and the regional failure seems to be the main problem in jaw OS.

Electron transfer flavoproteins (ETF) are alpha beta-heterodimers found in eukaryotic mitochondria and bacteria. We have identified currently sequenced protein members of the ETF-alpha and ETF-beta families. Members of these two families include (a) the ETF subunits of mammals and bacteria, (b) homologous pairs of proteins (FixB/FixA) that are essential for nitrogen fixation in some bacteria, and (c) a pair of carnitine-inducible proteins encoded by two open reading frames in Escherichia coli (YaaQ and YaaR). These three groups of proteins comprise three clusters on both the ETF-alpha and ETF-beta phylogenetic trees, separated from each other by comparable phylogenetic distances. This fact suggests that these two protein families evolved with similar overall rates of evolutionary divergence. Relative regions of sequence conservation are evaluated, and signature sequences for both families are derived.

We have investigated the expression and regulation of rab3C in rat tissues and rat pheochromocytoma PC12 cells by using a polyclonal antibody that specifically recognizes this protein. Rab3C was expressed in the neuroendocrine systems, as is its highly homologous family member, rab3A. Strong immunoreactivity of rab3C was also observed in testis, heart and 3 different adipose tissues. In addition, induction of neuronal differentiation in PC12 cells, which causes an increase in catecholamine secretion, also led to an increase in rab3C expression. In summary, our data demonstrate a defined pattern of rab3C expression in the rat; such expression is not limited to the neuroendocrine systems. Regulated secretion of various hormones occurs from all of these rab3C-containing tissues. Our results provide important insight into understanding the potential role of rab3C in regulated exocytosis.

Thirty patients with external laryngeal trauma were analysed retrospectively. Injuries were mostly caused by motor vehicle accidents (car = 36.7 per cent; motorcycle = 23.3 per cent). The main presenting symptoms and signs were hoarseness, neck tenderness, dysphagia, and neck emphysema. Sites of laryngeal injury included arytenoid swelling, vocal fold injury, soft tissue contusion or superficial mucosal laceration, cricoarytenoid dislocation, thyroid fracture, epiglottic fracture and mixed injuries. Treatment was varied depending on the severity of the injuries. Sixteen cases were managed conservatively by medical treatment; two cases received intubation; four cases were treated initially by tracheostomy; eight cases received surgical repair and/or reconstruction; cases made a full recovery of the voice and 18 cases fair voice recovery due to either sustained vocal fold swelling or limitation of vocal fold movement. One case was graded as poor. Twenty-eight cases had good airway patency and two cases fair airway patency. A delay in the early detection of laryngeal trauma may precipitate into life-threatening airway problems, therefore prompt and accurate diagnosis should be followed immediately by skillful airway management.

From March 1977 to October 1989, 85 patients with early stage glottic cancer were treated with either radiotherapy or surgery at Chang Gung Memorial Hospital (CGMH). Patients were excluded from the analysis of local control if they died or remained disease-free with a follow-up period of less than two years. Of the 26 patients treated with definitive radiotherapy, initial control of the primary lesions was achieved in 100% of stage T1s, 76% of T1, and 57% of T2 patients. Surgical salvage of radiation failure was achieved in 83% of the patients, giving the ultimate local control of 100% for T1s, 94% for T1, 86% for T2 patients. Of the 44 patients treated with definitive surgery, initial control of the primary lesions was achieved in 100% for T1s, 95% for T1, and 78% for T2 patients. Salvage of the surgical failure was 50%, giving the ultimate control in this group of 100% for T1s, 95% for T1, 83% for T2. There was no difference in either initial or ultimate control of T1 and T2 lesions between patients treated with primary radiotherapy and primary surgery. Voice preservation rates were 73% and 34% in the radiotherapy and surgery group, respectively. When divided into two groups according to the times they were being treated, we found that surgery preserved a comparable number of larynges as radiotherapy did after 1988 (60% vs 77%, p = 0.33). It is concluded that radiotherapy and surgery could achieve the same good local control results and long-term survival and comparable functional results of early stage glottic cancer, if conservative surgery is carefully selected for each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of severe hypoglycemia (30 mg/dL) after resection of unilateral pheochromocytoma is reported. Consciousness regained after 20 gm dextrose water was given intravenously. Rebound insulin storm is highly suspected as the main mechanism for the development of post-operative hypoglycemia. Administration of alpha and beta adrenergic blockers may also contribute to the severity of the hypoglycemia. Closely monitoring blood sugar level during the perioperative period is the only way to prevent the occurrence of such a catastrophe.

Pure red cell aplasia (PRCA) is an unusual early manifestation of systemic lupus erythematosus (SLE). Review of the 13 cases in literature revealed that the immune system played a significant role in disease pathogenesis. Immunosuppression has been thought to be the cause of the efficacy of corticosteroids in treatment. The case of a 28-year-old woman with SLE is described. She presented with PRCA, but has had good response to corticosteroid therapy.

The safety and efficacy of patient-controlled analgesia used for postoperative pain relief were evaluated. Cumulative 24-hour requirements were analyzed for possible correlation with patient characteristics. All patients who used a patient-controlled analgesia device for postoperative pain relief were reviewed from June to October 1991. The device Baxter's basal/bolus infusor with patient control module, was used to deliver fentanyl in 379 patients. The fentanyl requirement, verbal analog pain score, first passage of flatus, side effects, sedative score, and degree of satisfaction were examined. The fentanyl requirement during the first 24 hours after operation was analyzed with regard to age, body weight, and sex. The daily fentanyl consumption in the first three postoperative days was 928 +/- 352 micrograms (n = 338), 553 +/- 259 micrograms (n = 220), and 490 +/- 222 micrograms (n = 71), respectively. The requirement for fentanyl during the first 24 hours after surgery was significantly higher than for the next two days (p-value < 0.001). Fentanyl consumption correlated well with body weight, and inversely with age. No difference was found between fentanyl consumption and sex (p-value = 0.4687). The mean time to the first passage of flatus in patients with abdominal surgery was 54.6 +/- 26.4 hours. The incidence of nausea, vomiting, and dizziness was similar, about 20% of patients. Itching was noted in 7% of patients. Oversedation (class 4) was found in three patients during the first operative day, the sedative score for other patients were around class 1-3. No patient exhibited signs of respiratory depression or withdrawal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

For hospital personnel, transmission of virus is a common and serious occupational hazard. Other than suffering from physical discomfort, these infected hospital staffs may also transmit the disease to patients through their blood, mucous or secretion contamination. The purpose of this study is intended to understand the condition of hepatitis B virus infection between anesthetists and hospital administration staffs. Forty-six anesthetists (study group) and 90 hospital administration staffs (control group) were volunteers of the study. Blood samples for serologic and biochemical test of hepatitis B virus infection in each participant were proceeded from October to December 1990. To investigate personal recognition about hepatitis B infection, each was requested to fill up a questionnaire after blood sampling. We also retrieved the chart of all participators for their annual hepatitis B serologic result in order to find out the incidence of seroconversion. Among the 136 participators, 20 (14.7%) were HbsAg carriers. Only 28 (20.6%) of all the participators were free from infection and seronegative. However, it was found that there was no significant difference (P greater than 0.05) between the two groups, no matter in HbsAg positive or seronegative incidence. There was 10 (1.27%) incidence of seroconversion during 790 times of person-year observation. Though not significant (P less than 0.05), there was a double fold (2.2 times) seroconversion rate in the study group than that of the control group. Twenty (19.9%) seropositive participators knew that they are hepatitis B carrier or had been infected. Generally, anesthetists seemed better than hospital administration staffs in realizing that they were infected or carrier from the data of serological test.(ABSTRACT TRUNCATED AT 250 WORDS)

Three proteins, GTPase activating protein (GAP), neurofibromatosis 1 (NF1) and the yeast inhibitory regulator of the RAS-cAMP pathway (IRA2), have the ability to stimulate the GTPase activity of Ras proteins from higher animals or yeast. Previous studies indicate that certain lipids are able to inhibit this activity associated with the mammalian GAP protein. Inhibition of GAP would be expected to biologically activate Ras protein. In these studies arachidonic acid is shown also to inhibit the activity of the catalytic fragments of the other two proteins, mammalian NF1 and the yeast IRA2 proteins. In addition, phosphatidic acid (containing arachidonic and stearic acid) was inhibitory for the catalytic fragment of NF1 protein, but did not inhibit the catalytic fragments of GAP or IRA2 proteins. These observations emphasize the biochemical similarity of these proteins and provide support for the suggestion that lipids might play an important role in their biological control, and therefore also in the control of Ras activity and cellular proliferation.

The use of a disposable non-electronic patient-controlled analgesia (PCA) device (Baxter) was evaluated in this study. Every patient under trial was instructed thoroughly how to use the PCA device before operation. The PCA device delivers a 25 mg IV injection of pethidine upon patient demand with a delay of 15 min between allowable administrations. The degree of patient satisfaction, the drug consumption, and the duration of using analgesia were compared with those in IM pethidine group. The results showed that, in the PCA group, the duration of using analgesic was longer; the drug consumption was greater (especially during the first 20 h after operation); and the degree of patient satisfaction was higher. The series comprised a total of 54 patients, 14 of whom complained of mild dizziness or nausea which did not require specific treatment. In sum, giving analgesic by the Baxter PCA device was a safe and effective alternative for IM analgesic in postoperative pain control.

The physical interaction between GTPase-activating protein (GAP) and lipids has been characterized by two separate analyses. First, bacterially synthesized GAP molecules were found to associate with detergent-mixed micelles containing arachidonic but not with those containing arachidic acid. This association was detected by a faster elution time during molecular exclusion chromatography. Second, GAP molecules within a crude cellular lysate were specifically retained by a column on which certain lipids had been immobilized. The lipids able to retain GAP on such columns were identical to those which were shown previously to be most active in blocking GAP activity. The association between lipids and GAP was dependent upon magnesium ions. Lipids unable to inhibit GAP activity were also unable to physically associate with GAP. The tight association of GAP with these lipids was predicted by and helps to rationalize their ability to inhibit GAP activity.

Quiescent NIH 3T3 cells were stimulated with serum prior to the extraction of total cellular lipids. These lipids were fractionated on thin-layer chromatography plates, and individual fractions were tested for the ability to inhibit GTPase-activating protein (GAP) activity. Two separate GAP inhibitory lipids were produced. One behaved similarly to arachidonic acid during silica gel chromatography, whereas the other was related to a phosphoinositide. Further study of the arachidonic acid-related material indicated that it was produced between 1 and 5 min after serum addition but was never observed in high-density, contact-inhibited cultures. The identity of these lipids is under investigation. The possibility raised by these results, that a metabolite of arachidonic acid is involved in mitogenic signaling, was supported by the finding that several lipoxygenase products of arachidonic acid efficiently inhibited GAP activity. These results provide further support for the hypothesis that lipids, GAP, and ras activity function together in the control of cellular proliferation.

A cytoplasmic protein has been identified that inhibits the guanosine triphosphatase (GTPase) activity of bacterially synthesized, cellular H-Ras protein. This GTPase inhibiting protein is able to counteract the activity of GTPase activating protein (GAP), which has been postulated to function as a negative regulator of Ras activity. The potential biological importance of the GTPase inhibiting protein is further supported by its interaction with lipids. Phospholipids produced in cells as a consequence of mitogenic stimulation increase the activity of the GTPase inhibiting protein, as well as inhibit the activity of GAP. The interaction of such lipids with each of these two regulatory proteins would, therefore, tend to increase the biological activity of Ras and stimulate cell proliferation.

A 60 year-old hypertensive male was operated with resection of epidermoid carcinoma of buccal mucosa. He was expired postoperation complicated with left middle cerebral artery infarction. The cerebral infarction may be induced by acute hypotension, improper position during operation and underlying disease associated with old age. Prevention methods included preoperative evaluation, immediately injection vasopressor when acute hypotension occurred during anesthesia, and avoidance of improper position to compress vertebral or carotid artery which may leading to cerebral perfusion insufficiency.

1 DL-Muscarine elicited a contraction of the ileal longitudinal muscle of the guinea-pig and the contraction was characterized by an after-response. 2 Physostigmine (20 x 10(8) M) potentiated the contraction of the longitudinal muscle elicited by DL-muscarine. 3 Hemicholinium-3 (HC-3) caused a rightward shift of the dose-response curve to DL-muscarine on the ileal longitudinal muscle of the guinea-pig ileum. 4 beta-Bungarotoxin (10 microgram/ml) significantly (P < 0.025) reduced the contraction elicited by DL-muscarine (2.5 X 10(-8) M) suggesting presynaptic release of acetylcholine as an indirect mechanism of action of DL-muscarine. 5 Morphine (1.0 x 10(-8) M) significantly (P < 0.05) reduced the contractions elicited by DL-muscarine (2.5 x 10(-8) M) further suggesting presynaptic release of acetylcholine as an indirect mechanism of action of DL-muscarine. 6 A subthreshold dose of DL-muscarine (2.0 x 10(-10) M) potentiated the effect of acetylcholine (2.5 x 10(-8) M) and the potentiation was blocked by beta-bungarotoxin.

Bacterially synthesized c-Ha-ras protein (Ras) was incubated with guanosine triphosphatase (GTPase) activating (GA) protein in the presence of various phospholipids. The stimulation of Ras GTPase activity by GA protein was inhibited in some cases. Among the lipids most active in blocking GA protein activity were lipids that show altered metabolism during mitogenic stimulation. These included phosphatidic acid (containing arachidonic acid), phosphatidylinositol phosphates, and arachidonic acid. Other lipids, including phosphatidic acid with long, saturated side chains, diacylglycerols, and many other common phospholipids, were unable to alter GA protein activity. The interaction of lipids with GA protein might be important in the regulation of Ras activity during mitogenic stimulation.

Cellular ras activity has been neutralized in 3T3 cells by microinjection of a specific anti-ras monoclonal antibody. The injected antibody efficiently inhibited proliferation in cells treated with a phorbol ester and a calcium ionophore, or with prostaglandin F2 alpha. These treatments were designed to imitate the action of phospholipase C or of phospholipase A2. In addition, the highly efficient mitogenic potential of phosphatidic acid was inhibited by the injected antibody even more efficiently than was serum-induced proliferation. The close reliance of phospholipid-induced mitogenesis upon ras activity suggests that ras proteins are unlikely to function to control the action of a phospholipase.