Pathological analysis of hypertrophic cardiomyopathy simulating dilated cardiomyopathy

The pathomorphologic features of hypertrophic cardiomyopathy simulating dilated cardiomyopathy in the late stage (HCM-DCM) were compared with those of ordinary hypertrophic cardiomyopathy (HCM). Seven autopsied hearts with HCM-DCM and 11 with HCM were assessed quantitatively using an image analyzer. Unlike HCM, significant left ventricular enlargement and wall thinning were observed in HCM-DCM, and the percentage areas of massive fibrosis and disarray were significantly greater. In HCM-DCM, the disarray was distributed diffusely, whereas massive fibrosis was distributed more intensively in the ventricular septum and anterior wall than in the lateral and posterior wall. Narrowing of intramyocardial small arteries was observed more frequently in HCM-DCM, especially in the ventricular septum and anterior wall, than in HCM. These results suggest that the enlargement and wall thinning of the left ventricle in HCM-DCM are attributable to non-uniform progression of massive fibrosis, which is closely related to small-arterial lesions.     

Brain creatine functions to attenuate acute stress responses through GABAnergic system in chicks

The involvement of brain creatine in the adaptation to acute stress responses was investigated in chicks. In experiment 1, brain creatine content of chicks exposed to social separation stress was significantly increased compared with control chicks. The effects of i.c.v. injection of creatine (2 mug) on vocalizations, spontaneous activity and plasma corticosterone concentration in chicks under social separation stress were investigated in experiment 2. All measurements were attenuated by the i.c.v. injection of creatine compared with the controls under separation stress. Creatine also significantly decreased the active posture, but increased the motionless eye-opened posture, compared with the control. To clarify the relationship between creatine function and GABA receptors, the i.c.v. co-injection of creatine with picrotoxin, a GABA-A receptor antagonist, or CGP54626, a GABA-B receptor antagonist, was investigated in experiments 3 and 4. The effects of creatine on vocalizations and spontaneous activity were attenuated by co-injection of picrotoxin. In this case, active postures decreased by creatine were recovered by co-injection with picrotoxin. However, these effects were not obtained with CGP54626. The results suggest that central creatine functions within the CNS to attenuate the acute stress response by acting through GABA-A receptors in chicks.     

Evidence of the monoclonal composition of human endometrial epithelial glands and mosaic pattern of clonal distribution in luminal epithelium

The endometrium is a highly regenerative tissue that plays a crucial role in implantation. We examined the clonal constitution of glandular cells as well as the luminal epithelium of this unique tissue. Using collagenase-based digestion techniques with microscopic manipulation, we isolated individual human endometrial glands and examined their clonality using a polymerase chain reaction-based assay for nonrandom X chromosome inactivation with an X-linked androgen receptor gene. Most of the glands analyzed were composed of monoclonal populations of epithelial cells and one of the glands exhibited a loss of heterogeneity in the androgen receptor gene. In addition, adjacent glands within a 1-mm(2) area shared clonality, suggesting that clonality of the luminal epithelium is regionally defined. The clonality of endometrium was further confirmed in a study of female mice that harbor the green fluorescent protein gene on either the maternal or paternal X chromosome. Fluorescent microscopy of uterine sections revealed that individual endometrial glands consisted completely of either fluorescent or nonfluorescent cells and that the surface epithelium exhibited a clear boundary between these cell types. These findings suggest that single or multiple stem cells with uniform clonality exist on the bottom of each endometrial gland and genetic alterations occurring in such cells may play a critical role in endometrial carcinogenesis. The possible association between area-specific X inactivation of the endometrial surface and the endometrial receptivity of embryo implantation remains to be clarified.     

Sources of Ca2+ in relation to generation of acetylcholine-induced endothelium-dependent hyperpolarization in rat mesenteric artery

1. The aim of the present study was to identify the sources of Ca²⁺ contributing to acetylcholine (ACh)-induced release of endothelium-derived hyperpolarizing factor (EDHF) from endothelial cells of rat mesenteric artery and to assess the pathway involved. The changes in membrane potentials of smooth muscles by ACh measured with the microelectrode technique were evaluated as a marker for EDHF release.
2. ACh elicited membrane hyperpolarization of smooth muscle cells in an endothelium-dependent manner. The hyperpolarizing response was not affected by treatment with 10 μM indomethacin, 300 μM N^G-nitro-L-arginine or 10 μM oxyhaemoglobin, thereby indicating that the hyperpolarization is not mediated by prostanoids or nitric oxide but is presumably by EDHF.
3. In the presence of extracellular Ca²⁺, 1 μM ACh generated a hyperpolarization composed of the transient and sustained components. By contrast, in Ca²⁺-free medium, ACh produced only transient hyperpolarization.
4. Pretreatment with 100 nM thapsigargin and 3 μM cyclopiazonic acid, endoplasmic reticulum Ca²⁺-ATPase inhibitors, completely abolished ACh-induced hyperpolarization. Pretreatment with 20 mM caffeine also markedly attenuated ACh-induced hyperpolarization. However, the overall pattern and peak amplitude of hyperpolarization were unaffected by pretreatment with 1 μM ryanodine.
5. In the presence of 5 mM Ni²⁺ or 3 mM Mn²⁺, the hyperpolarizing response to ACh was transient, and the sustained component of hyperpolarization was not observed. On the other hand, 1 μM nifedipine had no effect on ACh-induced hyperpolarization.
6. ACh-induced hyperpolarization was nearly completely eliminated by 500 nM U-73122 or 200 μM 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate, inhibitors of phospholipase C, but was unchanged by 500 nM U-73343, an inactive form of U-73122. Pretreatment with 20 nM staurosporine, an inhibitor of protein kinase C, did not modify ACh-induced hyperpolarization.
7. These results indicate that the ACh-induced release of EDHF from endothelial cells of rat mesenteric artery is possibly initiated by Ca²⁺ release from inositol 1,4,5-trisphosphate (IP₃)-sensitive Ca²⁺ pool as a consequence of stimulation of phospholipid hydrolysis due to phospholipase C activation, and maintained by Ca²⁺ influx via a Ni²⁺- and Mn²⁺-sensitive pathway distinct from L-type Ca²⁺ channels. The Ca²⁺-influx mechanism seems to be activated following IP₃-induced depletion of the pool.

     

Intravalvular implantation technique for aortic valve replacement in aortitis syndrome

BACKGROUND: Paravalvular leakage is one of the most serious complications of aortic valve replacement in patients with aortitis syndrome. The purpose of this study was to compare the effectiveness of the intravalvular implantation technique in preventing paravalvular leakage with that of the conventional technique. METHODS: Since 1982, 14 patients with aortic regurgitation caused by aortitis syndrome have undergone aortic valve replacement at our institute. An intravalvular implantation technique was applied in 7 of the 14 patients. The technique consists of suturing a prosthetic valve to the aortic annulus and sandwiching the leaflets between exogenous felt pledgets and the inflamed aortic annulus. RESULTS: Paravalvular leakage occurred in 3 of 7 patients in the conventionally treated group and in none of 7 in the intravalvular implantation group. CONCLUSIONS: The intravalvular implantation technique is effective in preventing paravalvular leakage in patients with aortitis syndrome.     

Transthoracoscopic needle biopsy for indeterminate lung nodules

Background: The usefulness of transthoracoscopic needle biopsy for preoperatively indeterminate intrapulmonary nodules was evaluated. Methods: Thoracoscopy was performed on 38 patients with pulmonary solitary nodules suspected to be primary lung carcinomas. When the nodule was localized by simple observation or tactile sensor, a biopsy specimen of the tumor was obtained by a biopsy needle introduced through a trocar. Results: The nodules were 7 to 55 mm in diameter. All were located in the peripheral region of the lung. Biopsy specimens were obtained even from 17 nodules with no associated pleural changes. By cytology, all the malignant tumors were precisely diagnosed, 29 as primary lung cancers and 3 as metastatic lung neoplasms. Five of the remaining six benign nodules were not precisely diagnosed. However, they were cytologically classified as class I. Conclusions: Transthoracoscopic needle biopsy is feasible for diagnosing small intrapulmonary nodules, particularly those of malignant neoplasms. As compared with thoracoscopic excisional biopsy, transthoracoscopic needle biopsy saves time and may reduce the possibility of tumor dissemination during the procedure. Received: 14 March 1997/Accepted: 31 May 1997     

Metastatic seeding of bile duct carcinoma in the transhepatic catheter tract: Report of a case

We describe herein the case of a 51-year-old woman in whom metastatic tumor seeding of the percutaneous transhepatic biliary drainage tract occurred following a pancreatoduodenectomy for carcinoma of the distal common bile, duct. An abdominal computed tomography scan done 6 months after the initial operation detected a hepatic lesion located at the site of the previous percutaneous transhepatic biliary drainage tract. Implantation of bile duct carcinoma in the drainage tract was diagnosed, and the recurrent tumor was successfully resected by performing a subsegmentectomy of segment 3 and removal of the adjacent abdominal wall. At present, 5 years and 4 months after the second resection, the patient is in good health without any signs of recurrence. This case report demonstrates that an aggressive surgical approach should be performed for tumor seeding of a transhepatic biliary catheter tract.     

Pulmonary small cell carcinoma associated with sarcoid reactions: Report of a case

A 45-year-old male was admitted to our hospital for investigation of a nodular shadow in segment 5 of the right lung on a chest computed tomogram. A right middle lobectomy with mediastinal lymph node dissection was performed under a diagnosis of lung cancer, and histologic examination confirmed small cell carcinoma. There were sarcoid reactions in the resected lymph nodes and the lung parenchyma, but no signs of systemic sarcoidosis were evident. Sarcoid reactions are rarely observed in the regional lymph nodes draining malignant tumors. Moreover, while they are most common in squamous cell carcinoma of the lung, they extremely rare in small cell carcinoma. To our knowledge, this is only the third report of this unusual entity in the English and Japanese literature.     

Induction of food intake by a noradrenergic system using clonidine and fusaric acid in the neonatal chick

To clarify noradrenergic systems on food intake of the neonatal chicks, we examined the effects of i.c.v injection of clonidine (CLON), an alpha2-receptor agonist, and fusaric (5-butylpicolinic) acid (FA), a dopamine (DA)-beta-hydroxylase (DBH) inhibitor. Although a high dose (250 ng) of CLON induced a narcoleptic response and reduced food intake, food intake at 30 min post-injection was enhanced by lower doses (25 and 50 ng) of CLON. Central administration of FA (25, 50 and 100 microg) increased food intake in a dose-dependent fashion. It is suggested that feeding behavior is stimulated by low levels of CLON and decreased by further production of norepinephrine (NE), and FA may play the disturbance of sleeping and then enhance food intake.     

Functional regulation by dopamine receptors of serotonin release from the rat hippocampus: in vivo microdialysis study

The functional regulation by dopamine (DA) receptors of serotonin (5-HT) release from the rat hippocampus was investigated by use of in vivo microdialysis. Dialysate 5-HT levels were reduced by co-perfusion of 10 M tetrodotoxin (TTX) and were elicited by K⁺ (60 and 120 mM) stimulation in a concentration-dependent manner. Local perfusion (10 M) and peripheral administration (20 mg/kg, i.p.) of fluoxetine produced increases in 5-HT levels. These results indicate that the spontaneous 5-HT levels in the rat hippocampus can be used as indices of neuronal origin from the serotonergic nerve terminals. The nonselective dopamine (DA) receptor agonist apomorphine (1, 10 and 100 M), when perfused through the probe over a period of 40 min, increased 5-HT release in a concentration-dependent manner. Apomorphine-induced (100 M) increases in 5-HT release was abolished by pretreatment with the selective D₂ receptor antagonist, S(–)-sulphide (1 and 10 M), but not prevented by pretreatment with the selective D₁ receptor antagonist, R(+)-SCH-23390 (R(+)-7-chloro-8-hydroxy-3-methyl-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) (1 M). S(–)-Sulpiride and R(+)-SCH-23390 by themselves did not alter the spontaneous 5-HT levels. The 5-HT release was elevated by perfusion of the selective DA reuptake inhibitor GBR 12909 (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine)(1, 10 and 100 M), indicating the possibility of not only exogenous but also endogenous DA-mediated facilitatory effects on 5-HT release in vivo. The 5-HT release was also elevated by perfused (±)-PPHT ((±)-2-(N-phenylethyl-N-propyl)-amino-5-hydroxytetralin)(1, 10 and 100 M), the selective D₂ receptor agonist, in a concentration-dependent manner. On the other hand, (±)-PPHT (100 M) failed to increase 5-HT release in catecholamine (CA)-lesioned rats pretreated with 6-hydroxydopamine (6-OHDA)(200 g/rat, i.c.v.). The (±)-PPHT-induced (100 M) increase in 5-HT release was prevented not only by pretreatment with 10 M S(–)-sulphide but also by pretreatment with the ₂-adrenoceptor antagonist idazoxan (10 M). These findings suggest that the functional regulation of 5-HT release via D₂ receptors exists in the rat hippocampus. Furthermore our results indicate that the facilitatory effect of 5-HT release via D₂ receptors may be mediated indirectly by noradrenergic neurons, but not mediated directly through D₂ receptors located on serotonergic nerve terminals.