Gastric cancer

With the development of related instruments and techniques, laparoscopic surgery has come to be applied to treatment of gastrointestinal malignancies as a minimally invasive surgery. For early gastric cancers with negligible risk of lymph node metastasis, endoscopic mucosal resection (EMR), laparoscopic wedge resection (LWR), and laparoscopic intragastric mucosal resection (IGMR) have been performed. For those with fairly sizable risk of lymph node metastasis, laparoscopy-assisted distal gastrectomy (LADG) is applied. Our studies have suggest that LADG is more useful than open distal gastrectomy in the management of patients with gastric cancer from the viewpoints of curability, minimal invasiveness, and quality of life of patients.     

Difficult ventilation during induction of anesthesia in a patient with Arnold-Chiari malformation type II

Arnold-Chiari malformation is a congenital disorder with caudal displacement of the cerebellar tonsils through the foramen magnum into the cervical canal. We report difficulty with ventilation during the induction of anesthesia due to apnea and laryngospasm in a 5-year-old female with Arnold-Chiari malformation type II diagnosed at birth. She had had short periods of apnea during infancy, but was asymptomatic recently. Slow induction of anesthesia was performed using sevoflurane, but just after induction, the patient developed apnea and we could not ventilate her due to laryngospasm. We woke her up, and induced anesthesia with barbiturates. The operation was performed without complications, but she had another apnea attack with laryngospasm at extubation. This case suggests that it is important to be aware of the possibility of apnea due to disorder of the respiratory center in patients with Arnold-Chiari deformity.     

An immunohistochemical examination of basaloid squamous cell carcinoma of the esophagus: report of a case

We recently encountered a patient with basaloid carcinoma of the esophagus with extensive node involvement. The patient died of hematogenous metastasis 6 months after surgery. The tumor expressed cytokeratin but did not express either Type IV collagen or laminin. Both tumor cells and metastatic lesions in the regional lymph nodes expressed p53, Bcl-2, and Ki-67 proteins, but did not express cyclin D1 proteins. Received: July 3, 2000 / Accepted: March 6, 2001     

Differential expression of GABA(A) receptor subunit mRNAs and ligand binding sites in rat brain following phencyclidine administration

Recent biochemical observations have suggested the abnormalities in the gamma-amino-butyric acid (GABA)ergic system in schizophrenic brains. In the present study, we investigated the subunits gene expressions and ligand binding of the GABA(A) receptor following acute and chronic administration of phencyclidine (PCP), which induces schizophrenia-like symptoms, in rats using in situ hybridization and in vitro quantitative autoradiography. PCP i.p. administration at a daily dose of 7.5 mg/kg resulted in a significant decrease in expression of alpha 1 subunit mRNA in cerebral cortices (cingulate (-13%) and temporal cortex (-6%)) and hippocampal formation (CA1 (-11%), CA2 (-10%), CA3 (-11%) and dentate gyrus (-12%)) 1 h after a single treatment. In the repeated PCP administrations for 14 days, the expression of beta 2 mRNA in the cerebellum (-10%) and of beta 3 mRNA in the cerebral cortices (cingulate (-12%), parietal (-16%) and temporal cortex (-16%), caudate putamen (-18%), inferior colliculus (-18%), and cerebellum (-15%) were significantly decreased. In addition, [(35)S]t-butylbicyclophosphorothionate (TBPS) binding was also reduced in layer IV of the frontoparietal cortex (-14%), inferior colliculus (-17%), and cerebellum (-12%) following chronic PCP treatment, while no changes were observed following acute PCP treatment. These results indicate that single and repeated administrations of PCP independently regulate the expression of GABA(A)/benzodiazepine (BZD) receptor subunits mRNA and its receptor binding in the brain.     

Perspectives on tetrahydrobiopterin research]

Tetrahydrobiopterin ((6R)-L-erythro-tetrahydrobiopterin, BH4) is de novo synthesized from GTP. Enzymes involved in its synthesis are the rate limiting enzyme GTP cyclohydrolase I, 6-pyruvoyl tetrahydropterin synthase (PTPS) and sepiapterin reductase. Abnormalities in the metabolism of BH4 have been demonstrated in some diseases affecting the central nervous systems such as atypical phenylketonuria, hereditary progressive dystonia (Segawa's disease). Furthermore, BH4 has been shown to be involved in vascular protection. It is suggested that the dysfunction of endothelial BH4 leads to atherosclerosis. Recently we established BH4-deficient mice by disrupting the PTPS gene to investigate the effects of BH4 depletion on the animals and the involvement of BH4 in regulating biological functions including neural systems. Investigation utilizing this model animal can contribute to the development of new therapeutic strategies toward various diseases involving neurological and vascular systems. Pterin derivatives other than biopterin may also be involved in the regulation of a variety of biological functions. We found that ciliated protozoan Tetrahymena pyriformis synthesizes tetrahydromonapterin, isomer of BH4, and its levels alter according to the progress of the cell cycle. How pterin derivatives are related to the human physiology and diseases is an interesting subject of investigation.     

Effects of single and repeated phencyclidine administration on the expression of metabotropic glutamate receptor subtype mRNAs in rat brain.

Recent animal studies regarding phencyclidine (PCP), which induces psychotic symptoms in humans, have suggested that group II metabotropic glutamate receptors (mGluRs) represent a novel target for the treatment of PCP psychosis. In the present study, we used in situ hybridization to investigate the gene expressions of the mGluR 1-5 subtypes following single and repeated administration of PCP in rats. A single administration of PCP (7.5mg/kg, i.p.,) resulted in a significant decrease in the mGluR5 mRNA expression of group I mGluR in the subcortical regions (thalamus (-15%), central gray (-23%), inferior colliculus (-23%), and nucleus accumbens (-10%)) and hippocampal formation (CA1 (-14%), CA2 (-15%), CA3 (-18%), and dentate gyrus (-18%)). After repeated PCP administration for 14 days, the mGluR2 mRNA expression of group II mGluR in the anterior cingulate cortex (-23%) and the mGluR4 mRNA expression of group III mGluR in the cortical regions (parietal (-11%), temporal (-13%) and entorhinal cortices (-18%)), the caudate putamen (-12%), thalamus (-17%), and subiculum (-25%) were significantly decreased. These results indicate that PCP affects not only group II mGluR but also group I and III of mGluR, and it is of particular interest that mGluR2 subtype is involved in a development of behavioral abnormality following repeated PCP administration. Single and repeated administrations of PCP independently regulate the expression of mGluR subtypes of mRNA in the brain.     

An investigation of radiologists' perception of lesion similarity: observations with paired breast masses on mammograms and paired lung nodules on CT images

RATIONALE AND OBJECTIVES: We conducted an observer study to investigate whether radiologists can judge similarities in pairs of breast masses and lung nodules consistently and reproducibly. MATERIALS AND METHODS: Institutional review board approval and informed observer consent were obtained. This study was compliant with the Health Insurance Portability and Accountability Act. We used eight pairs of breast masses on mammograms and eight pairs of lung nodules on computed tomographic images, for which subjective similarity ratings ranging from 0 to 1 were determined in our previous studies. From these, four sets of image pairs were created (ie, a set of eight mass pairs, a set of eight nodule pairs, and two mixed sets of four mass and four nodule pairs). Eight radiologists, including four breast radiologists and four chest radiologists, compared all combinations of the eight pairs in each set using a two-alternative forced-choice (2AFC) method to determine the similarity ranking scores by identifying which pair was more similar than the other pair based on the overall impression for diagnosis. RESULTS: In the mass set and nodule set, the relationship between the average subjective similarity ratings and the average similarity ranking scores by 2AFC indicated very high correlations (r = 0.91 and 0.88). Moreover, in the two mixed sets, the correlations between the average subjective similarity ratings and the average similarity ranking scores were also very high (r = 0.90 and 0.98). Thus, radiologists were able to compare the similarities for pairs of lesions consistently, even in the unusual comparison of pairs of completely different types of lesions. CONCLUSION: The subjective similarity of a pair of lesions in medical images can be quantified consistently by a group of radiologists. The concept of similarity of lesions in medical images can be subjected to rigorous scientific research and investigation in the future.     

Functional Consequences of the Mutations in Human Cardiac Troponin I Gene Found in Familial Hypertrophic Cardiomyopathy

Functional consequences of the six mutations (R145G, R145Q, R162W, DeltaK183, G203S, K206Q) in cardiac troponin I (cTnI) that cause familial hypertrophic cardiomyopathy (HCM) were studied using purified recombinant human cTnI. The missense mutations R145G and R145Q in the inhibitory region of cTnI reduced the intrinsic inhibitory activity of cTnI without changing the apparent affinity for actin. On the other hand, the missense mutation R162W in the second troponin C binding region and the deletion mutation DeltaK183 near the second actin-tropomyosin region reduced the apparent affinity of cTnI for actin without changing the intrinsic inhibitory activity. Ca(2+) titration of a fluorescent probe-labeled human cardiac troponin C (cTnC) showed that only R162W mutation impaired the cTnC-cTnI interaction determining the Ca(2+) affinity of the N-terminal regulatory domain of cTnC. Exchanging the human cardiac troponin into isolated cardiac myofibrils or skinned cardiac muscle fibers showed that the mutations R145G, R145Q, R162W, DeltaK183 and K206Q induced a definite increase in the Ca(2+)-sensitivity of myofibrillar ATPase activity and force generation in skinned muscle fibers. Although the mutation G203S also showed a tendency to increase the Ca(2+) sensitivity in both myofibrils and skinned muscle fibers, no statistically significant difference compared with wild-type cTnI could be detected. These results demonstrated that most of the HCM-linked cTnI mutations did affect the regulatory processes involving the cTnI molecule, and that at least five mutations (R145G, R145Q, R162W, DeltaK183, K206Q) increased the Ca(2+) sensitivity of cardiac muscle contraction.     

Effects of vibration and hyaluronic acid on activation of three‐dimensional cultured chondrocytes

Objective

To investigate the effects of vibration (Vib) and hyaluronic acid (HA) on 3‐dimensional cultured cartilage.

Methods

Chondrocytes were obtained from metatarsophalangeal joints of freshly killed 6‐month‐old pigs. Twenty‐four–well plates containing type I collagen sponge disks were used to culture samples. The frequency and the amplitude of the vibration of the well plate were 100 Hz and 0.5 nm, respectively. We produced 3‐dimensional cartilage tissue using HA and vibration with collagen sponge as a carrier. Four different culture conditions were examined: a control HA−Vib− group, an HA−Vib+ group, an HA+Vib− group, and an HA+Vib+ group. Each group was cultured for 2 weeks. After culture days 3, 7, 10, and 14 (every 3.5 days), the levels of chondroitin 4‐sulfate (C4S) and chondroitin 6‐sulfate (C6S) isomers synthesized in each culture medium were measured. Histologic analysis, immunohistochemical analysis, and electron microscopic examination were performed.

Results

Mean C4S and C6S synthesis had increased rapidly after 7 days of culture and continued to increase thereafter. There were significant differences among the 4 groups (P < 0.01). Synthesis of both C4S and C6S was most abundant in the HA+Vib+ group and the lowest in the HA−Vib− group. After 1 and 2 weeks of culture, the chondrocytes had formed stratified structures on the collagen sponges in all groups, although the thickest structure was observed in the HA+Vib+ group and the thinnest in the HA−Vib− group. Under immunofluorescence, the HA+Vib+ group exhibited the strongest chromatic features. Under electron microscopy, the chondrocytes in the HA+Vib+ group exhibited many long and slender prominences on their surface, and extracellular substance could be observed associated with the cells.

Conclusion

Our results indicate that the combination of vibration and HA activates the production of proteoglycan in 3‐dimensional cultured chondrocytes and stimulates MAPK and β‐catenin. This suggests that some mechanoreceptors for vibration exist on the plasma membrane of chondrocytes and activate the intracellular signal transduction system.

     

Inhibition by neuroprotective drug NS-7 of nicotine-induced Na influx, Ca influx and catecholamine secretion in adrenal chromaffin cells

In cultured bovine adrenal chromaffin cells, NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride], a newly-synthesized neuroprotective drug, inhibited nicotine-induced ²²Na⁺ influx via nicotinic receptors (IC₅₀=15.5 μM); the suppression by NS-7 was observed in the presence of ouabain, an inhibitor of Na⁺,K⁺-ATPase, and was not attenuated upon the washout of NS-7. NS-7 decreased nicotine-induced maximum influx of ²²Na⁺ without altering the EC₅₀ value of nicotine. Also, NS-7 diminished nicotine-induced ⁴⁵Ca²⁺ influx via nicotinic receptors and voltage-dependent Ca²⁺ channels (IC₅₀=14.1 μM) and catecholamine secretion (IC₅₀=19.5 μM). These results suggest that NS-7 produces noncompetitive and long-lasting inhibitory effects on neuronal nicotinic receptors in adrenal chromaffin cells, and interferes with the stimulus-secretion coupling.