The synthetic cannabinoid 5F-MDMB-PICA: A case series.

5F-MDMB-PICA has been detected in products sold on the internet as well as in biological samples since 2016. It is associated with serious adverse health and behavioral effects and even death. Herein we report on twelve cases with proven 5F-MDMB-PICA consumption, including three fatalities, four cases of driving under the influence of drugs and five other criminal acts. In these cases, 5F-MDMB-PICA was detected in postmortem blood or serum. Concentrations ranged from 0.1-16ng/mL. In some blood (serum) and urine samples, the hydrolysis metabolite of 5F-MDMB-PICA (M12) could also be detected. In this case series, co-consumption with other drugs occurred in 9 of 12 cases, most commonly alcohol, cannabis and other contemporary SCs. In five cases, 4F-MDMB-BINACA was also detected. The described cases demonstrate various adverse effects that might be associated with 5F-MDMB-PICA. Observed physical adverse effects were mainly balance deficiencies and ocular effects such as reddened conjunctivae, glassy eyes and delayed or unresponsive pupil light reactions. Observed mental and behavioral effects were mainly changing moods, aggression, confusion, erratic behavior, mental leaps, disorientation, slowed reaction, logorrhea and slurred speech. Due to the fast changing market of synthetic cannabinoids, data on such new appearing substances are basically scarce. Because of the limited number of studies on pharmacological properties of synthetic cannabinoids, reports of findings in human samples along with corresponding case history descriptions can be valuable for the interpretation of upcoming routine cases.

[The mammalian oviduct revisited]. / L'oviducte de mammifère : un organe revisité

The oviducts, or uterine tubes, support the transport and final maturation of gametes, and harbour fertilization and early embryo development. The oviduct environment is finely regulated by ovarian steroids as well as by gametes and embryos that interact with it. Previously regarded as a simple transit zone, the oviduct is now regarded as a complex organ with multiple functions in these various processes. The tubal fluid, now better characterized, is to be regarded as the first interface between the mother and the embryo. It may play a major role in the quality of the conceptus.

[Polyovular follicles]. / Les follicules polyovocytaires.

Folliculogenesis covers the sequential steps in the development of a follicle, from primordial to preovulatory. Most of the time, one follicle contains a single oocyte, but some follicles are polyovular in that they contain several. These follicles were considered earlier as pathological, but they are, actually, fairly common in several species, from mice to humans. The frequency of polyovular follicles (number of polyovular/total number of follicles) varies among species, <0.1% to 14% in the dog, and with age (more polyovular follicles during the prepubertal period). More than 20 oocytes (and even more than 100 in the marsupials like the opossum) may be present in a single follicle. These follicles may form during the earliest stages of follicle formation, due to an imbalance between somatic and germinal cells, which induces an incomplete germ cell cyst breakdown. In polyovular follicles, the quality (size and maturity) of the various oocytes is often heterogeneous. Numerous authors reported that polyovular follicles are able to reach ovulation and ovulate. Polyovular follicles, naturally found in several species, may also be induced by exposure to therapy or agents in the environment, especially with estrogen activity such as pesticides or diethylstilbestrol/DES. Polyovular follicles are also observed in the ovaries of mutated rodents.

Changes in intestinal electrical activity during ischaemia correlate to pathology.

The gastrointestinal tract possesses an omnipresent electrical slow wave called the basic electrical rhythm (BER). It has been shown that the frequency of the BER falls during intestinal ischaemia. The correlation between changes in the BER and pathology that occur during acute ischaemia are not completely understood. To study this, the electrical activity of the ileum in 14 adult male rabbits was recorded during ischaemia. At baseline, 60, 120 and 210 minutes of ischaemia, segments of bowel were resected for histopathologic evaluation. The BER frequency was determined using the Fast Fourier Transformation (FFT) spectral analysis. The BER amplitude and FFT spectral power were also determined. The results showed significant decrease (p<0.05, Student's T-test) in the BER frequency, amplitude, and spectral power at all time points. Between 60 and 120 minutes, while there was a decrease in BER activity the pathologic grade remained the same (focal loss of surface epithelium). By 210 minutes of ischaemia when the BER could not be recorded, there was diffuse mucosal infarction. The results indicate that changes in the electrical activity of the bowel during acute mesenteric ischaemia occurred prior to the pathologic changes. The presence of electrical activity indicates that there was viable bowel. Thus it should be possible to use recordings of electrical activity to evaluate bowel viability during acute ischaemia.

Histopathologic changes during mesenteric ischaemia and reperfusion.

The basic electrical rhythm (BER) of the intestine is known to decrease during mesenteric ischaemia. Some studies have reported the relationship between the BER and the pathologic changes that occur in the bowel during vascular injury. However, these changes have not been completely elucidated. This study describes the histopathologic pattern when the rabbit small intestine was subjected to ischaemia of varying time lengths (30-150 minutes) and subsequent reperfusion for six hours. Intestinal biopsies were taken at baseline, at the end of ischaemia, and at hourly intervals during reperfusion. Microscopic examination of the biopsies revealed evidence of progressive infarction of the mucosa during ischaemia. There was an acute worsening of the pathology during reperfusion, the severity being greater when reperfusion was preceded by longer periods of ischaemia. These changes were statistically significant. The observed pattern in this study shows clearly that reperfusion injury is reflected in the histopathologic response and that this is worse in severity than the response to ischaemia. Studies of longer duration should further clarify the picture during recovery in ischaemia/reperfusion injuries of the bowel.

Cyclooxygenase-2 expression in Barrett's esophagus.

Barrett's epithelium is a recognized premalignant condition for esophageal adenocarcinoma. Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the relative risk of colon cancer in humans and the esophageal tumor load in carcinogen-treated mice. Previous studies provided conflicting results for COX-2 activity in Barrett's mucosa. Pinch mucosal biopsies were collected from Barrett's and adjacent normal esophageal mucosa from 17 patients with Barrett's esophagus. Low-grade dysplasia was found in seven patients. COX-2 protein was undetectable in normal esophageal mucosa. COX-1 protein expression did not vary between normal and Barrett's epithelium. Increased COX-2 protein was detected in Barrett's epithelium in seven patients (41%) but did not differ with or without dysplasia (43% vs 40%). In conclusion, COX-2 protein is increased in 41% of patients with Barrett's epithelium compared to normal esophageal mucosa but did not differ with or without dysplasia. COX-2 induction may be an early event in the development of Barrett's esophagus.

Provider attitudes and use of alternative medicine in a midwestern medical practice in 2001.

OBJECTIVE: To determine the current level of use, referral and desire for service of different complementary and alternative (CAM) therapies among Gundersen Lutheran Medical Center providers. METHODS: A survey was conducted in January of 2001 of all medical and associate staff. RESULTS: The response rate was 79%; 55% reported using 1 or more of 18 therapies for themselves. Over 25% of providers used nutritional supplements, herbal medicines, or hydrotherapy with a patient. Over half of providers had referred a patient for biofeedback or chiropractic care. Over half of providers would like to offer acupuncture, biofeedback, chiropractic care, hydrotherapy, nutritional supplements, or massage to patients in the future. Associate staff, female staff, primary care providers, and those who had personally used CAM therapies were more likely to have used, referred, or wish to offer more therapies in the future. There was little support for aromatherapy, magnetic field therapy, naturopathic medicine, or ethnic healing methods. CONCLUSIONS: Use of and desire for complementary therapies at Gundersen Lutheran was higher than expected by the Integrative Medicine Oversight Committee. Health care organizations should consider having a process in place to manage the increasing demands for complementary and alternative therapies.

Methylene blue staining and endoscopic ultrasound evaluation of Barrett's esophagus with low-grade dysplasia.

This study was performed to determine if either methylene blue staining or endoscopic ultrasound helped direct biopsies in patients with a history of Barrett's esophagus with low-grade dysplasia. Patients underwent radial endoscopic ultrasound scanning to measure esophageal wall thickness, followed by endoscopy with methylene blue staining and biopsies. Mean esophageal wall thickness for squamous mucosa (2.3 +/- 0.2 mm), nondysplastic Barrett's (2.6 +/- 0.2 mm), and Barrett's with dysplasia (2.9 +/- 0.3 mm) were similar. With staining, Barrett's mucosa stained blue more often than gastric epithelium (68% vs 15%, respectively; P < 0.001). The sensitivity and specificity for strong staining detecting Barrett's were 68% and 85%, respectively. Barrett's with low-grade dysplasia stained blue less frequently (52%) than nondysplastic Barrett's (74%; P < 0.05), but the positive predictive value for poor staining indicating dysplasia was 41%. Endoscopic ultrasound was not helpful in directing biopsies in these patients. The utility of methylene blue for detecting dysplasia needs further investigation.

Three-dimensional reconstruction of the antennal lobe in Drosophila melanogaster.

We present the first three-dimensional map of the antennal lobe of Drosophila melanogaster, based on confocal microscopic analysis of glomeruli stained with the neuropil-specific monoclonal antibody nc82. The analysis of confocal stacks allowed us to identify glomeruli according to the criteria shape, size, position, and intensity of antibody labeling. Forty glomeruli were labeled by nc82, eight of which have not been described before. Three glomeruli previously shown exclusively by backfills were not discernible in nc82 stainings. We distinguish three classes of glomeruli: (1) "landmark" glomeruli that are constant in all four criteria mentioned above, (2) less well-demarcated glomeruli that deviate in a single criterion, and (3) poorly defined glomeruli that vary in more than one criterion. All class 2 and 3 glomeruli can be identified by comparison with landmark neighbors. To further aid identification, our model assigns glomeruli to five arrays, each of which is defined by a prominent landmark glomerulus. Six glomeruli consist of distinct, but contiguous structural units, termed "compartments." Glomerular variability observed occasionally between males and females is in the same range as between individuals of the same sex, suggesting the lack of a significant sexual dimorphism in the glomerular pattern. We compare the new model with a previous map and address its potential for mapping activity and expression patterns. An important goal of this work was to create three-dimensional reference models of the antennal lobe, which are accessible on-line.

Dysplastic gastroesophageal junction nodules--a precursor to junctional adenocarcinoma.

Adenocarcinoma of the gastroesophageal junction is a disease rapidly increasing in prevalence. The origin of these tumors is unclear. Barrett's esophagus, gastric cardia lesions, and mucus glands of the distal esophagus have been implicated. This case report presents two cases of patients who had chest pain leading to esophagogastroduodenoscopy. Both had small, benign-appearing nodules at the gastroesophageal junction in the absence of Barrett' s esophagus or gastric lesions. Biopsies revealed intestinal metaplasia with dysplasia in one patient and dysplasia of the mucus glands of the esophagus in the other. The first patient was followed for 8 months with serial biopsies, during which time the lesion became progressively more dysplastic, culminating in invasive cancer. These cases are presented to show that 1) benign-appearing gastroesophageal junction nodules may have malignant behavior, and 2) junctional cancer and high grade dysplasia can occur in the absence of Barrett's esophagus or gastric cardia lesions. Gastroesophageal junctional dysplasia/carcinoma may occur in small foci of intestinal metaplasia or in the mucus glands of the distal esophagus.

The seroprevalence of cagA-positive Helicobacter pylori strains in the spectrum of gastroesophageal reflux disease.

BACKGROUND & AIMS: The role of Helicobacter pylori in the pathogenesis of gastroesophageal reflux disease (GERD) is unknown. We determined the prevalence of cagA-positive (cagA+) H. pylori strains in patients with GERD or its complications compared with controls of similar age. METHODS: A total of 153 consecutive patients with GERD, Barrett's esophagus, and Barrett's esophagus complicated by dysplasia or adenocarcinoma were compared with 57 controls who underwent upper endoscopy for reasons other than GERD. H. pylori infection and CagA antibody status were determined by histology and enzyme-linked immunosorbent assay. RESULTS: H. pylori prevalence was lower (34%) in patients with GERD and its sequelae than in the control group (45.6%)(P = 0.15). Regardless of the group, increasing age was associated with higher prevalence of H. pylori (P = 0.003). When compared with controls (42.3%), the prevalence of cagA+ H. pylori strains decreased (P = 0.008) in patients with more severe complications of GERD (GERD, 36.7% [nonerosive GERD, 41.2%; erosive GERD, 30.8%]; Barrett's esophagus, 13.3%; and Barrett's with adenocarcinoma/dysplasia, 0%). CONCLUSIONS: Prevalence of H. pylori in patients with GERD and its sequelae was lower but not significantly different than that of a control group. However, patients carrying cagA+ strains of H. pylori may be protected against the complications of GERD, especially Barrett's esophagus and its associated dysplasia and adenocarcinoma.

Effects of mesenteric ischemia and reperfusion on small bowel electrical activity.

UNLABELLED: Previous studies involving basic electrical rhythm (BER) have not been carried out far enough to fully characterize the relationship between mesenteric ischemia and BER. The phenomenon of reperfusion injury has also not been correlated with BER activity. The goal of this study was to characterize changes in BER during mesenteric ischemia and reperfusion and to correlate them with changes in pathology. METHODS: Serosal electrodes were used to record the electrical activity of rabbit jejunum (n = 20) at baseline, during ischemia (90-210 min), and during reperfusion (120-240 min). BER frequency and amplitude were monitored, and biopsies were taken at the end of ischemia and reperfusion. A pathologist blinded to the specimen identity graded the histology on a scale of 0 (no changes) to 6 (transmural necrosis). Paired t test, the Kruskal-Wallis test of non-parametric ranks, and Fisher's r to z test were used for statistical significance where appropriate. RESULTS: BER frequency and amplitude fell significantly after 15 min of ischemia and became undetectable by 90 min of ischemia in all animals. The likelihood that BER would return during reperfusion was highly correlated with length of ischemia (r = 0.99). Longer periods of reperfusion were associated with increasing pathologic grade. CONCLUSIONS: BER frequency and amplitude are very sensitive to ischemia and their changes occur well before histopathologic changes. The variation in electrical activity of the small bowel during ischemia and reperfusion is a dynamic process that reflects the metabolic state of the smooth muscle. If electrical activity of the bowel is to be used for assessment of viability, continuous recordings more accurately reflect the metabolic state of the smooth muscle.

Superconducting quantum interference device magnetometer for diagnosis of ischemia caused by mesenteric venous thrombosis.

Although mesenteric venous thrombosis carries a better prognosis than arterial thrombosis, mortality and morbidity are still high. Previous studies have shown that the basic electrical rhythm (BER) of the bowel decreases early after induction of arterial ischemia. Furthermore, our studies have shown that these changes occur prior to pathologic changes and that they can be recorded noninvasively using a superconducting quantum interference device (SQUID). SQUIDs measure magnetic fields that are created by the electrical activity of the gastrointestinal smooth muscle and have been used to measure the BER of the small intestine in human volunteers. This study was conducted to determine if a SQUID could be used for early noninvasive detection of mesenteric venous ischemia in an animal model. Simultaneous recordings from serosal electrodes and a SQUID outside the abdomen were taken from anesthetized New Zealand rabbits. Recordings were made for 15 minutes before and 90 minutes after injection of thrombin into the superior mesenteric vein. The basic electrical rhythm of the small bowel dropped from 16.42 +/- 0.69 to 8.80 +/- 0.74 cycles per minute at 30 minutes and to 6.82 +/- 0.722 after 90 minutes (p < 0.0001, paired t-test). The correlation coefficient between the SQUID and electrical recordings was 0.954 (p < 0.0001). These data suggest that the ischemia caused by mesenteric venous thrombosis results in changes in the bioelectrical activity, which can be noninvasively detected using a SQUID.

Expression of surfactant protein B precursor and surfactant protein B mRNA in adenocarcinoma of the lung.

Surfactant protein B (SP-B) is a 79-amino acid, hydrophobic protein that plays important roles in surfactant function and homeostasis. SP-B is produced in the respiratory epithelium by proteolytic processing of a glycosylated precursor (pro-SP-B) of relative molecular mass 42,000 to 46,000. To develop diagnostic markers for pulmonary adenocarcinomas, we examined the incidence and distribution of pro-SP-B and SP-B mRNA in paraffin sections of 35 non-small cell lung carcinomas (15 adenocarcinomas, 15 squamous cell carcinomas, and 5 large cell carcinomas), using immunohistochemical techniques and in situ hybridization. Fifteen nonpulmonary adenocarcinomas were used as controls. Pro-SP-B and SP-B mRNA were detected in 60% and 53% of pulmonary adenocarcinomas, respectively. Expression was seen in adenocarcinomas with acinar, papillary, bronchioloalveolar, and solid growth patterns. Squamous cell and large cell carcinomas of the lung and nonpulmonary adenocarcinomas did not contain pro-SP-B immunoreactivity or SP-B mRNA. The specificity of SP-B gene expression in adenocarcinomas of the lung supports the usefulness of pro-SP-B and SP-B mRNA in the study and diagnosis of these neoplasms.

Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice.

Transgenic mice expressing either the neu proto-oncogene or transforming growth factor (TGF-alpha) in the mammary epithelium develop spontaneous focal mammary tumors that occur after a long latency. Since the epidermal growth factor receptor (EGFR) and Neu are capable of forming heterodimers that are responsive to EGFR ligands such as TGF-alpha, we examined whether coexpression of TGF-alpha and Neu in mammary epithelium could cooperate to accelerate the onset of mammary tumors. To test this hypothesis, we interbred separate transgenic strains harboring either a mouse mammary tumor virus/TGF-alpha or a mouse mammary tumor virus/neu transgene to generate bitransgenic mice that coexpress TGF-alpha and neu in the mammary epithelium. Female mice coexpressing TGF-alpha and neu developed multifocal mammary tumors which arose after a significantly shorter latency period than either parental strain alone. The development of these mammary tumors was correlated with the tyrosine phosphorylation of Neu and the recruitment of c-Src to the Neu complex. Immunoprecipitation and immunoblot analyses with EGFR- and Neu-specific antisera, however, failed to detect physical complexes of these two receptors. Taken together, these observations suggest that Neu and TGF-alpha cooperate in mammary tumorigenesis through a mechanism involving Neu and EGFR transactivation.

Effect of sublethal liver injury on doxorubicin metabolism.

Centrilobular hepatocyte contribution to doxorubicin (DOX) metabolism and myelotoxicity was probed with bromobenzene (BRB), a known centrilobular hepatotoxin. New Zealand White rabbits were given DOX, 3 mg/kg i.v. After 4 weeks, the rabbits were pretreated i. p. with 2.6 ml/kg 40% solution of BRB in corn oil followed 72 h later with a 3-mg/kg dose of DOX. Pharmacokinetics of DOX after BRB pretreatment was mildly changed from control. Significantly increased plasma concentrations of doxorubicinol and its aglycone product, 7-deoxydoxorubicinol aglycone, were detected. Treatment with BRB alone was not lethal; however, in three of seven rabbits, the combination of DOX and BRB was. The mortality appeared to be related to myelosuppression. We conclude that toxin-induced hepato-cellular necrosis causes increased DOX-induced myelotoxicity. Following BRB pretreatment, the relatively small pharmacokinetic changes of parent compound concentrations as compared with greater changes in plasma pharmacokinetics of its alcohol metabolites suggest systemic changes in drug metabolism and distribution in the setting of hepatic disease may be the cause of increased toxicity.

Acceleration of mammary neoplasia in transforming growth factor alpha transgenic mice by 7,12-dimethylbenzanthracene.

A mouse mammary tumor virus enhancer/promoter-transforming growth factor alpha transgenic mouse model has been described in which mammary tumors develop (Y. Matsui et al., Cell, 61: 1147-1155, 1990). In Line 29, spontaneous mammary tumors do not develop before 300 days of age in virgin females. Herein, Line 29 virgin females and their nontransgenic littermates have been treated with 7,12-dimethylbenzanthracene (DMBA) at varying dosages and times. Orogastric instillation of a single dose of DMBA (0.5 mg) dramatically accelerates mammary tumor formation when administered to 21- and 56-day-old virgin transgenic females compared to their nontransgenic littermates. The latency period for tumor formation is significantly shorter in transgenic mice treated with DMBA at 56 days compared to transgenic mice treated with DMBA at 21 days when results are analyzed by time from DMBA administration. To determine whether differences in the proliferative state of the mammary gland may contribute to these findings, bromodeoxyuridine incorporation was examined in the mammary glands of untreated 21- and 56-day-old mice. No differences in bromodeoxyuridine incorporation were detected between 21-day-old transgenic and nontransgenic mice. However, there was a marked increase in bromodeoxyuridine incorporation in the epithelial cells comprising the smaller ducts of 56-day-old transgenic mice compared to their nontransgenic littermates. These data indicate an enhancing interaction between a growth factor and a genotoxic carcinogen in mammary tumorigenesis and provide evidence that the transforming growth factor alpha transgene acts as a tumor promoter in this experimental model.

Pretreatment with vitamin A inhibits transforming growth factor alpha stimulation of human mammary carcinoma cells.

Vitamin A or retinol is an important agent in the normal differentiation and growth of cells. Retinol is an effective inhibitor of the growth of many transformed cells in vitro and in vivo but its mechanism of action is unclear. Transforming growth factor alpha (TGF alpha) is a known mitogen. We examined the effect of retinol treatment on TGF alpha stimulation of two human mammary carcinoma cell lines, one which is growth inhibited by retinol and one which is not. Pretreatment of both cell lines for 48 hours with retinol resulted in inhibition of TGF alpha stimulation of growth. In the T47D cell line the mechanism was not related to an effect on the cellular content of TGF alpha, epidermal growth factor (EGF) receptor protein, EGF receptor mRNA, or on the binding of TGF alpha to the EGF receptor. However, TGF alpha-induced stimulation of the EGF receptor substrate, phospholipase C-gamma 1, was abrogated in the T47D cell line with retinol pretreatment. In the MDA-MB-468 cell line, pretreatment with retinol resulted in a decrease in tyrosine phosphorylation of the EGF receptor. These results suggest that pretreatment with retinol decreases cellular proliferation seen with TGF alpha treatment by altering phospholipase C-gamma 1 response and/or EGF receptor tyrosine kinase activity. Alteration of phospholipase C-gamma 1 activity does not appear to be responsible for the inhibition of cell growth seen in the absence of TGF alpha stimulation.

Morphologic and functional alterations of intestinal segments following urinary diversion.

The current study was undertaken to determine the effect of chronic urinary diversion on both the morphology and absorptive function of intestine. Adult female Wistar rats (N = 8) underwent urinary diversion by interposing a 10-12 cm. segment of distal ileum between the bladder and sigmoid colon following urethral ligation. Control animals (N = 8) underwent sham laparotomies. Three months later, the diverted segment and a 10-12 cm. segment of distal ileum in control animals were studied. The intestinal segments were studied morphologically by both light microscopy and transmission electron microscopy. By using a previously reported in vivo intestinal perfusion model, the transport properties of the intestinal segments were examined. There were prominent and consistent morphological alterations in the diverted segments when compared with normal ileum. These changes consisted of marked mucosal atrophy evidenced by loss of microvilli with decreased villi-to-crypt ratio in diverted segments. Diverted ileum secreted more sodium and absorbed less chloride than normal ileum though this difference was not statistically significant. Water flux into the intestinal lumen was higher in diverted bowel (p = .06). The absorption of ammonium, potassium, and urea, as well as bicarbonate secretion, was the same in the diverted ileum as in normal ileum. There was also no significant difference in pH change or osmolar flux between the two groups. In conclusion, the results of this study indicate that despite morphological changes as a result of chronic exposure of urine, intestinal segments continue to transport urinary solutes similar to normal nondiverted segments. This represents the first convincing evidence that the reason for the low incidence of metabolic alterations following urinary diversion is not due to decreased absorptive capacity of the intestinal mucosa.

Characterization of HeLa cell vacuoles induced by Helicobacter pylori broth culture supernatant.

Helicobacter pylori broth culture supernatants induce eukaryotic cell vacuolation in vitro, a phenomenon that has been attributed to cytotoxic activity. We sought to characterize further the vacuolation of HeLa cells that occurs in response to H pylori culture supernatant. Nascent vacuoles were detectable by electron microscopy after 90 minutes of incubation with H pylori supernatant and were not associated with any identifiable organelle. After 6 days of incubation with H pylori supernatant, vacuoles were membrane-bound structures filled with electron-dense debris, which resembled secondary lysosomes. Acid phosphatase activity was detected within the vacuoles. The vacuoles induced by H pylori supernatant were then compared with vacuoles induced by trimethylamine, a weak base known to induce lysosomal swelling. Neutral red dye rapidly entered the vacuoles induced by either H pylori supernatant or trimethylamine, and both types of vacuoles were reversible. Compared with trimethylamine-induced vacuoles, the vacuoles induced by H pylori supernatant were larger and typically lacked a limiting membrane. In the early stages of formation, vacuoles induced by trimethylamine were labeled by lucifer yellow, a pinocytotic marker, whereas H pylori cytotoxin-induced vacuoles were not. These data suggest that trimethylamine-induced vacuoles arise directly from endocytic compartments, whereas H pylori cytotoxin induces vacuole formation via an autophagic mechanism.