Identification of myoglobin in human smooth muscle

Myoglobin (Mb) has been believed to be absent generally from mammalian smooth muscle tissue. Examination of human rectal, uterine, bladder, colon, small intestine, arterial, and venous smooth muscle by immunohistochemical techniques shows that each of these tissues is immunopositive for both smooth muscle myosin and human Mb. Mb-specific primers were used for the polymerase chain reaction to generate cDNA from smooth muscle tissues. Southern hybridization with a Mb-specific probe gave a very strong signal with the cDNA from rectum, weaker signals from small intestine and uterus, a faint signal from colon, and no signal from bladder tissue. High performance liquid chromatography analysis coupled with sequence determination has shown that contaminating heme-binding serum albumin as well as hemoglobin in extracts of smooth muscle seriously compromise any heme-based or spectrophotometric assay of Mb. Combined affinity and size exclusion chromatography, however, provide the necessary resolution. The cDNA-derived amino acid sequence of human smooth muscle Mb was found to be identical to that of Mb from striated muscle.     

Antiphospholipid syndrome complicated by thrombosis of the superior mesenteric artery, co-existence of smooth muscle hyperplasia

A 37-year-old woman underwent an emergency operation at our hospital because of severe abdominal pain and ileus. Most of her small intestine and ascending colon were observed to have become necrotic due to occlusion of her superior mesenteric artery (SMA). Pathological findings of the resected intestine revealed that her SMA was completely thrombosed 2 cm distal from its origin with smooth muscle proliferation. Post-surgical blood analysis of her pre-operative serum was positive for lupus anticoagulant and antinuclear antibodies. She noticed vaginal bleeding due to missed abortion on the 31st day after the operation. We diagnosed her acute abdominal pain to be that of antiphospholipid syndrome associated with her pregnancy.     

Esophageal conduit in nearly hopeless corrosive esophageal stricture patient

The case report of a 28 year old woman with strictured esophagus from corrosive esophagitis for 4 months is presented. Barium swallowing showed a strictured esophagus extending from T2 to the aortic knob and needed frequent dilatations. The patient had a perforated thoracic esophagus and mediastinitis on last dilatation. Cervical esophagostomy, transabdominal esophageal bandaging and jejunostomy feeding were done along with intravenous broad spectrum antibiotics. On esophagoscopy, there was complete stenosis of the cervical esophagus 2 cm from the postcricoid area. The large intestine from the caecum, transverse colon and descending colon was chosen as the esophageal conduit because of adequate length to pass subcutaneously. The caecum was anastomosed to the cervical esophagus and descending colon to the stomach. Seven days postoperatively, the patient could take liquids and soft porridge orally. There was a small leakage from the cervical anastomosed, spontaneous closure was achieved 3 weeks postoperatively. We chose the right side colon as the esophageal conduit because of adequate length to pass subcutaneously. Mediastinal and transhiatal routes could not be passed because of previous mediastinitis from thoracic esophageal perforation. This may be an alternative choice of operation for high cervical esophageal stenosis with previous mediastinitis.     

Effect of the novel T-selective calcium channel antagonist mibefradil on kidney function in comparison with amlodipine

BACKGROUND: The pathogenesis of intestinal dysfunction induced by stress has not been established. We tried to clarify possible causal mechanisms of irritable bowel syndrome. METHODS: An experimental model of intestinal dysfunction was designed using loading restraint stress in rats. A cannula was inserted into the origin of the duodenum or colon, with the other end leading to the skin. To provide intestinal content, a semi-solid colored marker was used for monitoring intestinal transit. After 1 week the marker was injected into the intestine through the cannula under unanesthetized wakefulness. RESULTS: Under restraint stress, transit in the small intestine was suppressed, but actual suppression took place only in the upper half, where the contents normally moved fast. Transit time in the colon was reduced by restraint stress. This reduction was attributed to the disappearance of the stagnant region, which was present under normal conditions. CONCLUSIONS: These results suggested that restraint stress affects the function of the pacemaker site of the intestine.     

c-kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract

In vivo injection of a neutralizing, monoclonal antibody (ACK2) to the receptor tyrosine kinase (c-kit) disrupts the normal motility patterns of the mouse small intestine. Immunohistochemical studies showed that cells expressing c-kit-like immunoreactivity (c-kit-LI) decreased in numbers in response to ACK2, but the identity of these cells is unknown. We investigated the identity and development of the cells that express c-kit-LI in the mouse small intestine and colon. Cells in the region of the myenteric plexus and deep muscular plexus of the small intestine and in the subserosa, in the myenteric plexus region, within the circular and longitudinal muscle layers, and along the submucosal surface of the circular muscle in the colon were labeled with ACK2. The distribution of cells that express c-kit-LI was the same as that of interstitial cells (ICs). In whole-mount preparations cells with c-kit-LI were interconnected, forming a network similar to the network formed by cells that stained with methylene blue, which has been used as a marker for ICs in the mouse gastrointestinal tract. Immunocytochemistry verified that ICs were labeled with ACK2. Multiple injections of animals with ACK2 between days 0 and 8 post partum (pp) caused a dramatic reduction in the number of ICs compared to control animals. From an ultrastructural point of view, the proliferation and development appeared to be suppressed in some classes of ICs, while others displayed an altered course of development. Functional studies showed that the decrease in ICs was accompanied by a loss of electrical rhythmicity in the small intestine and reduced neural responses in the small bowel and colon. Morphological experiments showed that c-kit-positive cells are ICs, and physiological evidence reinforced the concept that ICs are involved in generation of rhythmicity and translation of neural inputs in gastrointestinal smooth muscles. Controlling the development of ICs provides a powerful new tool for the investigation of the physiological role of these cells.     

Small intestinal sarcoidosis with massive hemorrhage: report of a case

Sarcoidosis of the small intestine is a rarely described complication of systemic sarcoidosis. Although bleeding from sarcoidosis of the esophagus, stomach, and colon has been reported, massive bleeding from this condition in the small intestine has not been previously described. We present here the first case of hemorrhage from a jejunal sarcoid lesion that was unsuspected and undiagnosed until laparotomy with resection was performed. As with most pathologic conditions of the small intestine, preoperative diagnosis is difficult. Furthermore, the refractory nature of bleeding from this lesion made resection necessary in this patient, suggesting the need for similar therapy in other affected patients.     

Acute ethanol inhibits calcium influxes into esophageal smooth but not striated muscle: a possible mechanism for ethanol-induced inhibition of esophageal contractility

In both humans and cats, EtOH administered in vivo and acutely decreases contractility of smooth muscle of lower esophageal sphincter (LES) and lower esophagus (LE), but not striated muscle of upper esophagus. To see if these effects are associated with perturbation of Ca++ homeostasis, esophageal muscle slices were incubated in vitro with EtOH and then 45Ca++. At steady-state Ca++ uptake, some slices were exposed to 1 microM carbachol (CCH). Although 100 mM EtOH had no effect on Ca++ uptake into resting or stimulated striated muscle of upper esophagus, it significantly inhibited Ca++ uptake into smooth muscle of LES and LE. For unstimulated LE and resting LES, 100 mM EtOH significantly inhibited both initial uptake and steady-state levels, whereas lower doses had no significant effect. EtOH at 100 mM also affected changes in Ca++ content induced by CCH stimulation. CCH increased total exchangeable tissue Ca++ content in LE, whereas it decreased Ca++ content in LES. EtOH at 100 mM blunted these CCH-induced effects in both LES and LE. In contrast to resting muscle, inhibition of CCH-stimulated LE muscle was not limited to 100 mM EtOH, because substantial and significant inhibition was also seen at EtOH doses of 25 and 50 mM, doses which are relevant even in social drinking. Thus, EtOH inhibition of Ca++ influx into esophageal muscle is selective for smooth muscle, can occur at pharmacologically relevant EtOH doses and could be the underlying mechanism for EtOH's inhibition of contractility of esophageal smooth muscle.     

Ethical review of multi-centre research: a survey of local research ethics committees in the south Thames region

We reported a 63-year-old woman with myotonic dystrophy (MD), who had frequent swallowing disturbances and died from suffocation asphyxia. Her esophagus on CT image 30 minutes after taking semi-solid meal showed dietary remnants in the middle portion of esophagus with entire esophageal dilatation. At autopsy, there was marked atrophy in the striated muscles in the upper part and smooth muscles in the lower part of the esophagus. The site of dietary stagnation on CT image was identical to the atrophic smooth muscle layer seen at autopsy. We speculate that one of the causes of esophageal motor dysfunctions is smooth muscle atrophy. The dietary stagnation in the esophagus may increase a risk of the asphyxia. Therefore we need to keep patients at the straight position during and after dietary ingestion to prevent respiratory problems.     

Magnetic resonance guided localization and biopsy of suspicious breast lesions

Nausea, vomiting, and abdominal pain are common symptoms that suggest many diagnoses. The patient's symptoms may be related to an anatomical defect such as a peptic ulcer or a mechanical small bowel obstruction. However, no anatomical abnormality may be identified despite radiological, endoscopic, or laboratory studies. The cause of the patient's symptoms may have significant impact on the patient's quality of life (nonulcer dyspepsia) and life span (intestinal pseudo-obstruction). Abnormal antroduodenal motility may be the underlying cause of the patient's symptoms. Normally, coordinated phasic contractions in the stomach and small intestine maintain digestion and absorption of food. A prolonged set of phasic contractions (phase 3 of the migrating complex) begins in the stomach and propagates down the small intestine to excrete nondigestible foods, bacteria, and dead cells. Any disturbance in the normal motility pattern can lead to maldigestion and symptoms of upper intestinal dysfunction. Objective tests of motility disturbances in the stomach and small intestine include measurement of gastric emptying, intestinal transit, contractions of the stomach and duodenum, and electrogastrography. Abnormal antroduodenal motility may be secondary to an abnormality in the smooth muscle (myopathy) or the nerves in controlling smooth muscle contractions (neuropathy). Antroduodenal motility measurements may help identify a partial small bowel obstruction, the cause of small intestinal overgrowth, and the cause of chronic abdominal visceral pain. Motility studies may suggest useful drugs for correcting the underlying pathophysiology and relieving symptoms.     

Critical study of electric activity of the small intestine in the dog

Thanks to a cross-circulation, the authors caused to survive in the abdomen of a sacrificed dog, the whole of the small intestine, the motor activity of which was analysed by electro-enterography. This experimental preparation thus eliminates polygraphic recordings of all potential variations outside the small intestine, e.g. stomach, colon, diaphragm, muscle, myocardium. One thus obtains very pure tracings of the variations of potential originating in the small intestine, recorded from bipolar serous intestinal electrodes, they show the activity of the small intestine, consisting of a permanent basal electric rhythm on which are grafted spikes contemporary of motor phenomena. In the abdominal skin there were recorded only a cutaneous slow wave which was contemporary with the deep motor phenomena.     

Capsaicin-resistant vagal afferent fibers in the rat gastrointestinal tract: anatomical identification and functional integrity

The presence and distribution of vagal fibers and terminals throughout esophagus and gastrointestinal tract that could be anterogradely labeled by nodose ganglion tracer injections was quantitatively assessed in capsaicin- and vehicle-pretreated adult rats, in order to identify the capsaicin-resistant population. Up to 90% of the intraganglionic laminar endings (IGLEs), in the myenteric plexus of the esophagus, and 70-90% in the stomach, as well as 57% of the intramuscular endings or arrays (IMAs) in the fundic stomach survived the capsaicin treatment, while in the upper small intestine only few and in the lower small intestine, the cecum and colon, virtually no IGLEs survived capsaicin treatment. Intramucosal terminals were not assessed. Furthermore, gastric balloon distension-induced c-Fos expression in the dorsal vagal complex was not significantly decreased in capsaicin-treated rats. It is concluded that among primary vagal afferents there is a capsaicin-resistant population that primarily innervates the esophagus and upper gastrointestinal tract, and a capsaicin-sensitive population that innervates mainly the lower tract. At least vagal gastric tension-sensitive afferents also seems to be functionally intact in that they may be capable of synaptically activating second-order neurons in the brainstem.     

Muscle architecture and function in humans

We describe a 58-year-old woman who developed Wegener's granulomatosis (WG) complicated by a perforation of the transverse colon caused by necrotizing granulomatous vasculitis. In addition, her colon lesion continued in spite of high dose corticosteroid and cyclophosphamide therapy. She was admitted to our hospital because of her severe tonsillitis in Dec., 1994. She was diagnosed as having WG because she had oral ulcer, antibiotics-resistant lung infiltration, renal dysfunction and positive C-ANCA. Just after we started high dose steroid therapy, the transverse colon was perforated because of vasculitis, and she underwent emergency operation. Many vasculitic lesions were found in the small intestine, colon, and mesenterium. The disease was improved by corticosteroid and cyclophosphamide therapy except for a sustained ulcer with necrotizing vasculitis in the sigmoid colon region even 1 year after the operation. Although WG rarely complicates digestive tract lesions as initial manifestations, they reach 12% of the causes of death of WG in Japan. Therefore, we should take care of digestive tract lesions when we follow-up patients with WG.     

Gastrointestinal manifestations of scleroderma

Gastrointestinal involvement is commonly found in scleroderma. Gastrointestinal symptoms may be the presenting symptoms for the diagnosis and may precede the actual diagnosis by months to years. The esophagus is the most frequently affected, but functional problems of the anorectum, small bowel, colon, and stomach may occur. The pathophysiologic mechanism appears to be one of smooth muscle atrophy and, to a lesser degree, fibrosis. These changes result in gastrointestinal motility disturbances and may cause GERD, pseudo-obstruction, bacterial overgrowth, and defecatory disorders. Malnutrition may be a serious consequence. The evaluation of a particular symptom in a patient with scleroderma may lead to treatment strategies that improve the patient's sense of well-being and quality of life.     

CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance

Our laboratory recently described a new human cytochrome P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3), both of which were expressed in extrahepatic tissues. Northern analysis of RNA prepared from the human and rat intestine demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed primarily in the small intestine and colon. In contrast, immunoblotting studies using a polyclonal antibody raised against recombinant CYP2J2 showed that CYP2J proteins were expressed throughout the gastrointestinal tract. Immunohistochemical staining of formalin-fixed, paraffin-embedded intestinal sections using anti-CYP2J2 IgG and avidin-biotin-peroxidase detection revealed that CYP2J proteins were present at high levels in nerve cells of autonomic ganglia, epithelial cells, intestinal smooth muscle cells, and vascular endothelium. The distribution of this immunoreactivity was confirmed by in situ hybridization using a CYP2J2-specific antisense RNA probe. Microsomal fractions prepared from human jejunum catalyzed the NADPH-dependent metabolism of arachidonic acid to epoxyeicosatrienoic acids as the principal reaction products. Direct evidence for the in vivo epoxidation of arachidonic acid by intestinal cytochrome P450 was provided by documenting, for the first time, the presence of epoxyeicosatrienoic acids in human jejunum by gas chromatography/mass spectrometry. We conclude that human and rat intestine contain an arachidonic acid epoxygenase belonging to the CYP2J subfamily that is localized to autonomic ganglion cells, epithelial cells, smooth muscle cells, and vascular endothelium. In addition to the known effects on intestinal vascular tone, we speculate that CYP2J products may be involved in the release of intestinal neuropeptides, control of intestinal motility, and/or modulation of intestinal fluid/electrolyte transport.     

Mathematical coupling in medical research: lessons from studies of oxygen kinetics

BACKGROUND: Smooth muscle hamartoma is an uncommon lesion. Diagnosis is usually made at birth in infants presenting a plaque with minimal or no infiltration and covered with long dark hairs. Congenital forms with multiple plaques are rarely reported. CASE REPORT: A 5-day-old infant (normal pregnancy and delivery) had plaques localized on the buttocks, the left thigh, leg and shoulder and the right ankle. The plaques were minimally infiltrative and covered with long black hairs. Histology examination showed hyperplastic smooth muscle bundles with varying orientation. The diagnosis was smooth muscle hamartoma. The rest of the clinical examination was normal. CONCLUSION: This case of congenital smooth muscle hamartoma showed a particular form with partially regressive multiple plaques.     

Genome search in celiac disease

Celiac disease (CD), a malabsorption disorder of the small intestine, results from ingestion of gluten. The HLA risk factors involved in CD are well known but do not explain the entire genetic susceptibility. To determine the localization of other genetic risk factors, a systematic screening of the genome has been undertaken. The typing information of 281 markers on 110 affected sib pairs and their parents was used to test linkage. Systematic linkage analysis was first performed on 39 pairs in which both sibs had a symptomatic form of CD. Replication of the regions of interest was then carried out on 71 pairs in which one sib had a symptomatic form and the other a silent form of CD. In addition to the HLA loci, our study suggests that a risk factor in 5qter is involved in both forms of CD (symptomatic and silent). Furthermore, a factor on 11qter possibly differentiates the two forms. In contrast, none of the regions recently published was confirmed by the present screening.     

Coordination of peristalsis in pharynx and esophagus

When a swallowed liquid bolus is followed from mouth to stomach in man by contrast studies or manometry, it traverses its course without hesitation even though the bolus is propelled by striated muscle contraction in the first part of its journey and smooth muscle in the latter part. The striated muscle is innervated by excitatory cholinergic nicotinic cranial nerves whereas the smooth muscle of the esophagus is innervated by the enteric nervous system (ENS) through excitatory and inhibitory nerves. These differences can be demonstrated by observing the inhibitory effects of curare and atropine, the first blocking nicotinic receptors and the second muscarinic receptors. Early students of esophageal motility recognized that peristalsis could be initiated in two ways. The first is initiated by a swallow and is called primary peristalsis and the second called secondary peristalsis is initiated by distension of the esophagus. It was proposed that primary peristalsis was initiated by a single sensory input activated by the bolus entering the pharynx which in turn activated a motor program in the brain stem. Secondary peristalsis was believed to be stimulated by multiple afferent impulses arriving from the esophagus as the bolus passed down the esophagus. More recent studies using manometric techniques have suggested that the only difference between primary and secondary peristalsis is the afferent stimuli and the effector mechanism is the same. Subsequent studies of carefully timed, paired swallows, transection of vagus nerves and esophagus, and single nerve recordings suggest that the answer lies between the two extremes noted above.(ABSTRACT TRUNCATED AT 250 WORDS)