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A case of malignant lymphoma associated with complete heart block in a 30-year-old woman is reported. The patient progressively deteriorated despite temporary pacing and died 24 days after being admitted. Microscopic examination of the heart revealed marked infiltration by lymphoma cells in the atrioventricular node and the bundle of His. A diffuse lymphoma (large cell type, B cell) was diagnosed. This case is considered to be rare, since complete heart block was the first and only manifestation of the malignant lymphoma.

Eradication of immunologically-syngeneic tumors was achieved by adoptive chemotherapy using effector cells induced by Corynebacterium parvum-Pyridine Extract Residue (CP-PER). A mixture of 2 X 10(6) Meth A cells and 0.1 mg CP-PER was subcutaneously inoculated into the back of donor BALB/c mice, with the result that their spleen cells showed an antitumor effect 10 to 13 days after the inoculation. These cells were used as immune cells. Recipient mice were inoculated with 1 X 10(6) Meth A cells, and 2 days later were administered cyclophosphamide. On the following day, 1 X 10(8) immune cells were adoptively transferred into the recipient mice. As a result, the tumor began to regress 7 to 12 days after the adoptive transfer. An immuno-histochemical study of the donors' spleens and the recipients' regressing tumors revealed that the ratio of L3T4+ T cells to Lyt-2+ T cells in the donors' spleens was increased and that the infiltrating cells in the recipients' tumors were mainly composed of L3T4+ T cells. This confirmed that the transfer of L3T4+ T cells led to the infiltration of L3T4+ T cells into the recipients' tumors, causing their eradication.

The interosseous and lumbrical muscles in twenty-five hands of Japanese adult cadavers were dissected. The palmar and dorsal interosseous muscles continued, with few exceptions, into the wing tendons. The dorsal interosseous muscles gave off tendons which pierced the transverse laminae or passed deep to the transverse laminae, and attached to the bases of the proximal phalanges. The palmar interosseous muscles seldom had such attachments. The palmar and dorsal interosseous muscles sometimes gave off additional tendons which passed superficial to the transverse laminae and attached to the bases of the proximal phalanges. These latter attachments were typical in the contrahentes muscles. Thus, the present findings suggest that the human dorsal interosseous muscles are composite muscles derived from the dorsal abductor, flexor brevis and contrahens muscles, and that the human palmar interosseous muscles are composite muscles derived from the flexor brevis and contrahens muscles. The lumbrical muscles rarely gave off accessory slips with atavistic attachments to the proximal phalanges.

Isolated rat glomerular basement membrane was treated with elastase and observed by transmission electron microscopy. The treatment with elastase revealed the fundamental structure of the glomerular basement membrane quite clearly, and enabled the observation of a sieve structure within the glomerular basement membrane. This sieve structure may play a major role in the filtration of blood as well as in the production of urine. Treatment with antibody showed that the sieve was mainly constituted of type IV collagen.

A mixture of glycol methacrylate (GMA) and Quetol 523 was examined as an embedding medium for atrial tissue to be selectively stained for specific atrial granules. Semi-thin sections of rat atrial tissue embedded in this resin were stained with lead hematoxylin and observed under a light microscope. Atrial granules were found to be specifically stained blue black with lead hematoxylin. The same semithin sections stained with OsO4 vapor were examined electron microscopically and the atrial granules could be distinguised clearly from other cytoplasmic components. The GMA-Quetol 523 mixture is a useful embedding medium for studying the distribution of specific atrial granules by light and electron microscopy.

A method has been developed for the rapid preparation of single-cell suspensions from rat hepatocyte primary cultures on collagen substratum. Hepatocytes were adequately dissociated into single cells when the cultures were first treated with a combination of trypsin and ethylenediaminetetraacetic acid (EDTA) and then with collagenase. However, when the order was reversed, hepatocytes were inadequately dispersed. The possible mechanism of cell dissociation is discussed on the basis of the experimental data obtained.

The clinical, hemodynamic and pathological findings of 13 patients with aortic regurgitation due to aortic valve prolapse caused by advanced myxomatous degeneration were evaluated. Eleven patients showed a favorable outcome with no complications resulting from surgery. One patient died from aortic dissection, and another died suddenly from an unknown cause. Five patients had mitral valve prolapse as a complication. Ten patients (77%) had a long-standing history of hypertension. Twelve patients (92%) were male. None of the patients had the stigmata of Marfan's syndrome. All patients had marked myxomatous degeneration of the aortic valves without any inflammatory changes. Two patients showed microcalcification; 7 demonstrated moderate fibrosis. Five patients showed severe fragility of the cusps which appeared redundant, gelatinous and softened by degenerative changes. Myxomatous degeneration of the aortic valve is not rare, and, in fact, it may be one of the most common pathologic and clinical entities associated with pure aortic insufficiency.

The deep palmar muscles in monkey hands were studied. The contrahentes muscles mainly arose from the capitate bone, descended palmar to the deep palmar branch of the ulnar nerve and the palmar metacarpophalangeal nerves, and attached to the proximal phalanges or wing tendons of the second, fourth and fifth fingers. In relation to the deep palmar branch of the ulnar nerve and the palmar metacarpophalangeal nerves, the contrahentes muscles are homologous with the adductor pollicis and flexor indicis radialis muscles. The contrahentes muscles occasionally gave off some accessory slips which blended with the interosseous muscles. These findings suggest that the human adductor pollicis muscle is a well-developed remnant of a contrahens muscle, and that the human interosseous muscles contain some remnant of the contrahentes muscle. In fact, a well-developed remnant of a contrahens muscle was found in the fourth finger of a human hand. It is further considered that the human adductor pollicis muscle contains an element of the interosseous muscle of the thumb.

Two distinct human papillomavirus (HPV) DNAs (MY-1 and MY-2) were molecularly cloned from the benign skin lesions of a patient with epidermodysplasia verruciformis. The restriction map of MY-1 was the same as that of HPV 3a. The map of MY-2 appeared to be different from those of any HPVs reported in the literature. MY-2 did not cross-hybridize with MY-1 or the DNAs of HPV types 1, 2 and 4 under stringent conditions.

The direct determination by gas chromatography of blood levels of anesthetic agents has been difficult because of the water content of blood. In the present study, the method of Yokota et al. (1967) was modified by improving the packing materials of the column, the blood sample vaporizer and the flow-path during analysis. As a result, accurate and reproducible determination of halothane, enflurane and isoflurane dissolved in blood was achieved. With this system, blood in which halothane, enflurane and isoflurane had been dissolved could be analyzed without changing the column between samples. Moreover, each sample was prepared in less than 10 min, and more than 100 consecutive determinations could be made with excellent reproducibility. The coefficient of variation was less than 3.8%.

Phalloidin, a toxin from the plant Amanita phalloides, irreversibly polymerizes actin filaments and causes cholestasis. Three-dimensional structural changes induced by phalloidin in the bile canaliculi and the intra-acinar localization of these changes were studied in the rat liver by scanning and transmission electron microscopy. After 3 days of treatment, canalicular changes appeared mainly in zones 2 and 3 of Rappaport's acinus, but after 7 days of treatment changes occurred in bile canaliculi of the whole acinus. The changes in the bile canaliculi included tortuosity, saccular dilatation, loss of microvilli, bleb formation and elongation of canalicular side branches. Some side branches extended near to Disse's space, leaving only a thin cytoplasmic rim between the canalicular lumen and Disse's space. Kupffer cells were occasionally situated near such extended bile canaliculi and protruded their processes into the hepatic cord. These results suggest that bile canaliculi in zone 3 are more susceptible to phalloidin toxicity than those in zone 1 and that biliary constituents may leak from such altered bile canaliculi.

To clarify the mode of secretion of specific atrial granules, rat atrial muscle cells were examined by transmission electron microscopy. Atrial granule formation and exocytotic features of granules were clearly seen. Abrupt breaks in the unit membrane structure of mature granules were observed in thin sections, but these breaks were not detected in freeze-fracture replicas. These findings support the concept that the granule contents are released to the extracellular space by exocytosis.

The cytoskeletons of two established chick embryo cell (CEC) lines were examined by fluorescence and electron microscopy and compared with those of control cells and cells transformed by Rous sarcoma virus (RSV). In normal CEC, many stress fibers were observed. On the other hand, stress fibers were disorganized in nontransformed spontaneously established CEC, non-tumorigenic CEC partially transformed with a chemical carcinogen, and tumorigenic RSV-transformed CEC. In the normal CEC, actin filaments formed several bundles along the processes of the cell. Stereo-images of the peripheral region revealed bundles of filaments which were located along the attached side to the substrate. A fine well preserved network of filaments was also observed. On the other hand, in spontaneously established, partially transformed and RSV-transformed CEC, a fine network of filaments, but no actin cables, was found. These results support previous evidence that the cytoskeletal changes themselves are not directly related to the transformation or tumorigenicity of cells.

Seasonal distribution of the birth dates of 405 pre-menopausal and 285 post-menopausal breast cancer patients was investigated in order to determine whether or not the season of their birth was related to various reproductive risk factors of breast cancer, including nulliparity, late age at first birth, early age at menarche, late age at menopause, and a history of benign breast diseases. The seasonal distributions of births were compared between groups of patients categorized according to whether they possessed each risk factor or not, separately for pre- and post-menopausal patients. Patients with the same menopausal status generally had the same seasonal distribution of births, irrespective of whether or not they possessed a risk factor. Moreover, low-risk patients exhibited more deviation in the seasonal distribution of birth from general births than the high-risk patients. These results suggest that the distinctive seasonal distribution of birth observed in breast cancer patients is basically a phenomenon independent from the effect of the reproductive history on the occurrence of breast cancer, and that specific seasonal factors are involved at the fetal or neonatal stage in the etiology of breast cancer.

The arylsulfatase activity and histamine concentration of bronchoalveolar lavage fluid (BALF) were examined in patients with bronchial asthma in relation to the eosinophil count and asthma type (atopic and non-atopic). The BALF arylsulfatase activity and histamine concentration were significantly higher in atopic asthmatics than in non-atopic asthmatics. In atopic asthmatics, the activity of arylsulfatase was significantly increased in patients with a higher eosinophil count (10% or more). However, the BALF histamine concentration did not correlate with the eosinophil count. In non-atopic asthmatics, there was no significant correlation between arylsulfatase activity and the eosinophil count. The results show that arylsulfatase participates in IgE-mediated allergic reactions.

Upper gastrointestinal bleeding is a major adverse event of non-steroidal anti-inflammatory drugs (NSAIDs), and co-administration of proton pump inhibitors and H2 receptor antagonists has been established as a means of preventing such an eff ect. However, the incidence of bleeding associated with NSAID-induced ulcers under conditions where such strong anti-acid agents are used for prevention has yet to be clarified. We aimed to determine the annual incidence of serious upper gastrointestinal ulcer bleeding among Japanese patients in whom NSAIDs were used in our hospital. Before commencing the study, we recommended to all the physicians in our hospital the best method for caring for NSAID users, focusing on the concomitant use of proton pump inhibitors or H2 receptor antagonists. We conducted a cohort study involving 17,270 patients for whom NSAIDs had been newly prescribed. Bleeding from gastric ulcers was observed in 8 of the 17,270 patients using NSAIDs (0.05%). The pooled incidence rate for bleeding was calculated as 2.65 (95% confidence interval, 2.56-2.74) and 1.29 (1.27-1.31) per 1,000 patient years for low-dose aspirin and non-aspirin NSAID users, respectively. None of the bleeding ulcer patients required blood transfusion or were in serious condition. In conclusion, gastric ulcer bleeding occurred in low-dose aspirin or non-aspirin NSAID users, but its incidence was low and outcomes were not serious when adequate preventive measures were taken.

Dry pleural dissemination in non-small cell lung cancer, defined as solid pleural metastasis of lung cancer without pleural eff usion, is a condition occurring in T4 lung cancer. Positron emission tomography (PET) has been reported to be useful for the diagnosis and staging of lung cancer. It has been reported that positive findings on PET scans of indeterminate pleural abnormalities at computed tomography (CT) are sensitive to malignancy. We encountered two cases of dry small pleural dissemination of adenocarcinoma of the lung preoperatively detected by PET/CT. A 75-year-old man and a 66-year-old man underwent CT scan, which demonstrated solitary tumor in the lung, an enlarged mediastinal lymph node, and a small pleural nodule less than 10 mm in size, all of which were positive findings on the fluorine 18 fluorodeoxyglucose (FDG) PET portion of an integrated PET/CT. Both patients underwent thoracoscopic biopsy of the dry pleural nodule revealing dissemination of adenocarcinoma of the lung (T4). Whereas histological thoracoscopic diagnosis remains mandatory before planning treatment, our cases may suggest that PET/CT will be useful as a screening modality for dry pleural dissemination of lung cancer.

Malignant mesothelioma (MM) is a highly aggressive tumor with a dismal prognosis. The incidence of MM is increasing as a result of widespread exposure to asbestos. As for the molecular alterations that occur in MM, chromosome alterations including homo-deletion of the P16 and P14 genes located in the 9p21 are well known. Mutations are rare in the P53 and Ras genes, which are frequently present in epithelial solid tumors. However, mutations are frequently present in the neurofi bromatosis type 2 gene. Epigenetic alterations including DNA methylation have been found in the MM, the profi le of which is diff erent from that of lung cancer, although differential diagnosis is sometimes clinically difficult. As in other malignant tumors, genes that are related to immortalization, proliferation, metastasis, angiogenesis, and anti-apoptosis are also overexpressed in MM, contributing to its malignant phenotype. It is of interest that simian virus 40 has been implicated to be one of the causative factors of MM in western countries. Although the causative role of asbestos is well-known in MM, much less information is available for MM than for other malignant tumors regarding the molecular alterations that occur in the disease. In terms of future tasks, it will be necessary to apply the knowledge that is learned about molecular alterations to clinical practice and to further elucidate the pathogenesis of MM with extensive research.

The induction of both long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal CA1 region is triggered by the activation of N-methyl-D-aspartate (NMDA) receptors and the subsequent postsynaptic intracellular Ca2+ increase. However, how NMDA receptor activation differs between LTP and LTD induction is unclear. In the present study, we examined the eff ects of the magnitude and duration of NMDA receptor activation on the induction of LTP and LTD. Partial blockage of NMDA receptors by a low concentration of aminophosphonovaleric acid (APV)(2 μM) prevented the induction of LTP, but not LTD. In contrast, a high concentration of APV(25 μM) blocked both LTP and LTD. Tetanus stimulation-induced LTP was impaired when hippocampal slices were given the tetanus stimulation for more than 5 min. Under partial blockage of NMDA receptors, the prolonged-tetanus stimulation induced LTD but not LTP. This phenomenon was mimicked by the application of glutamate to the slices. Finally, LTD induced by prolonged activation of NMDA receptors was not aff ected by inhibition of the desensitization of α-amino-3-hydroxy-5 methylisoxazole-4-propionic acid (AMPA) receptors. These results suggest that critical diff erences exist between the induction of LTP and that of LTD in terms of both the magnitude and the duration of NMDA receptor activation. The duration of the increase in intracellular Ca2+ concentration may be critical for determining whether LTP or LTD induction occurs.

Since clinical document architecture (CDA) became an American National Standards Institute (ANSI)-approved health level seven (HL7) Standard, many countries have begun making an eff ort to make local standards conform to CDA. In order to make CDA compatible with the many diff erent local standards existing in diff erent countries, we designed a prototype model using HL7 CDA R2 with medical markup language (MML), a Japanese medical data exchange standard. Furthermore, a referral letter system based on this model was developed. Archetypes were used to express medical concepts in a formal manner and to make 2 diff erent standards work collaboratively. We share herein the experience gathered in designing and implementing a referral letter system based on HL7 CDA, Release 2 (CDA R2). We also outline the challenges encountered in our project and the opportunities to widen the scope of this approach to other clinical documents.