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本学の６つの基本理念の中には，｢ものづくりに直結する実技・実務教育の重視｣がある．技術を理論からのみ学ぶのではなく，実際に「もの」に触れてその本質を感じ取り，自分の体を使い五感を通してものづくりを体験・体得し，ものづくりに興味や問題意識を持ち，自ら学習し改善策や問題点の解決策を考える．そのような体験技能から技術を生み出す授業を実践している．筆者はその中の機械加工実習の授業を担当してきた． 筆者は，大手電機メーカ（日立製作所）の研究所で，研究用の設備や開発・試作装置などを製作する現場において，三十数年間にわたり機械加工に従事してきた．その間，技能五輪国際大会に参加し，旋盤職種部門で金メダルを獲得した．それらの実績から平成13 年の開学と同時に，本学の機械工作実習（1 年次・2 年次の旋盤加工）の教員として就任した．

To clarify the histopathological characteristics of pulmonary hypertension (PH) in Japan, and to clarify the role of serotonin and endclthelin in monocrotaline induced PH, human histopathologiical studies and experimental studies were carried out. An epidemiological study based on the Annual of the Pathological Autopsy Cases in Japan, and a morphological study on autopsy cases of congenital heart disease and idiopathic PH were performed. Plasma levels of serotonin and endothelin, vascular responsiveness to serotonin, and the effects of a selective serotonin antagonist, DV-7028, were investigated after monocrotaline injection. Plexogenic pulmonary arteriopathy was prevalent, and recurrent pulmonary thromboembolism and pulmonary veno-occlusive disease extremely rare among primary pulmonary hypertension in Japan. In secondary PH, systemic lupus erythematosus and mixed connective tissue disease were frequent and showedl particularly severe intimal and medial thickening. After an injection of monocrotaline, plasma serotonin and endotheliii levels were raised, and pulmonary arteries showed hyperreactivity to serotonin. DV-7028 (5-HT2 receptor antagonist) attenuated the rise in pulmonary artery pressure and the various effects of monocrotaline. There may be some genetic difference between PH in Japan and other countries. Roles far serotonin and endothelin in the initiation and progression of monocrotaline induced PH are suggested.

The addition of water to tetrabutylammonium bromide (TBABr)/benzene/sodium bromide ternary component systems induced the separation of TBABr-rich liquid phase (L phase) prior to the appearance of an aqueous phase (W phase). The L phase was assumed to be a bicontinuous phase similar to a microemulsion based on the phase composition. TBABr catalyzed the “solid–liquid” phase-transfer reaction of decyl methanesulfonate with sodium bromide either when the L phase was fully hydrated or after a distinct W phase was formed. The phase-transfer catalytic activity was correlated to the phase behavior of TBABr/benzene/water/NaBr four-component system. The difference and similarity between TBABr and tetrabutylphosphonium bromide (TBPBr) were discussed based on the microstructure of the phases formed by TBABr and TBPBr under the phase-transfer catalytic reaction conditions.

We previously reported that the reductive activities of yeast protein-disulfide isomerase (PDI) family proteins did not completely explain their contribution to the viability of Saccharomyces cerevisiae (Kimura, T., Hosoda, Y., Kitamura, Y., Nakamura, H., Horibe, T., and Kikuchi, M. (2004) Biochem. Biophys. Res. Commun. 320, 359-365). In this study, we examined oxidative refolding activities and found that Mpd1p, Mpd2, and Eug1p exhibit activities of 13.8, 16.0, and 2.16%, respectively, compared with Pdi1p and that activity for Eps1p is undetectable. In analyses of interactions between yeast PDI proteins and endoplasmic reticulum molecular chaperones, we found that Mpd1p alone does not have chaperone activity but that it interacts with and inhibits the chaperone activity of Cne1p, a homologue of mammalian calnexin, and that Cne1p increases the reductive activity of Mpd1p. These results suggest that the interface between Mpd1p and Cne1p is near the peptide-binding site of Cne1p. In addition, Eps1p interacts with Pdi1p, Eug1p, Mpd1p, and Kar2p with dissociation constants (KD) in the range of 10(-7) to 10(-6). Interestingly, co-chaperone activities were completely suppressed in Eps1p-Pdi1p and Eps1p-Mpd1p complexes, although only Eps1p and Pdi1p have chaperone activity. The in vivo consequences of these results are discussed.

The phase behavior and component composition of the coexisting phases in the tetrabutylammonium bromide (TBABr)/benzene/water/NaBr four-component system were strongly influenced by the temperature, TBABr content, and NaBr concentration. The phase-transfer catalytic activity of TBABr for the reaction of decyl methanesulfonate with sodium bromide was closely related to the phase behavior. Under O (oil-rich phase) + L (TBABr-rich liquid phase) + W (aqueous phase) triphase conditions, the influences of temperature and stirring speed on the phase-transfer catalytic activity were small compared with those under O + W biphase conditions. The addition of other quaternary salts that were able to form w/o aggregates in the O phase enhanced the TBABr catalytic activity even under O + W conditions. The relationship between phase behavior and catalytic activity of tetrabutylammonium chloride or iodide (TBACl or TBAI) was also examined. The results strongly suggested that the catalysis of TBAX was attributable to the interfacial reactions of TBAX with the substrate. The interface includes the water-oil microinterface formed in the microemulsion-like L phase as well as the bulk water-oil interface.

The present study attempts to better understand the mechanism of injuries associated with direct lightning strikes. We reviewed the records of 256 individuals struck by lightning between 1965 and 1999, including 56 people who were killed. Basal skull fracture, intracranial haemorrhage, pulmonary haemorrhage, or solid organ rupture was suspected in three men who died. Generally these lesions have been attributed to current flow or falling after being struck. However, examination of surface injuries sustained suggested that the true cause was concussion secondary to blast injury resulting from vaporization of water on the body surface by a surface flashover spark. To investigate this hypothesis, an experimental model of a lightning strike was created in the rat. Saline-soaked blotting paper was used to simulate wet clothing or skin, and an artificial lightning impulse was applied. The resultant lesions were consistent with our hypothesis that the blast was reinforced by the concussive effect of water vaporization. The concordance between the clinical and experimental evidence argues strongly for blast injury as an important source of morbidity and mortality in lightning strikes.

The solubility of tetrabutylammonium salt (TBAX; X = Cl, Br, or I) in benzene was examined as a function of temperature. The solubility curve had specific features, which were characterized by critical values corresponding to the Krafft point and the critical micelle concentration of ionic surfactants in water. Above the critical concentration, TBAX was assumed to aggregate in benzene, based on NMR analyses. A slight difference of the oil structure exerted a significant effect on the solubility behavior. In the presence of sodium halides, TBACl or TBABr with water exhibited a specific temperature that was similar to the cloud point. Above that temperature, TBAX was liberated as a liquid to form a liquid-liquid two-phase. The solubility of TBAI in water was poor. It gave a liquid-solid two-phase at low temperatures or a liquid-liquid two-phase above 69 °C, unless the TBAI concentration was too low. The solubility of TBAX in aqueous solution was also dependent on the metal cation of the inorganic salts.

The phase behavior of four-component systems composed of tetrabutylammonium halide (TBAX; X = Cl, Br, or I), nonpolar benzene, water, and sodium halide (NaX) has been examined in detail. According to their constituents, compositions, and temperatures, the four-component systems afforded from single- to four-phase states. There were at least three kinds of liquid phases: a TBAX-rich phase (M), an aqueous solution phase (W), and an oil solution phase (O). In the M phase, TBAX was assumed to form aggregates, like microemulsions, while, in the latter two solution phases, TBAX was present without any aggregated form. When these three liquid phases coexisted, an O-M-W three-liquid-phase equilibrium state occurred. Depending on the temperature and NaX concentration in the W phase, the system changed its state from the O-M-W to the O-M or M-W two-liquid-phase. In some cases, a solid TBAX phase (Q) or solid NaX phase (S) coexisted with these liquid phases. In the presence of excess sodium halide, an O-M-W-S four-p...

Twy mice are autosomal recessive mutant mice that develop multiple progressive abnormal calcification, mainly of the cartilage or tendons of the spine and limbs. They finally succumb to severe deformation and ankylosis. We carried out an ultrastructural study on the growth plate as well as the articular and spinal disc cartilage of twy mice and control ICR mice. Knee and spinal specimens were obtained from the animals, then prepared using standard procedures. Ultrastructural observations were made on uranyl lead-stained sections and elemental analysis was carried out on unstained sections. In both twy and ICR mice, linked granules (chain granules) were observed at the pericellular matrix, but there was no remarkable difference between their presence in the growth cartilage. In the twy mice, however, chain granules were observed in the pericellular matrix, cytoplasm, and nucleus of the articular and spinal disc cartilage. These chain granules disappeared after decalcification. Elemental analyses revealed significant amounts of calcium and phosphorus in these granules. It may be significant for abnormal calcification that such chain granules were observed in the articular and spinal disc cartilage of twy mice.

Angiogenesis is an indispensable process in the chronic proliferative synovitis and pannus formation of rheumatoid arthritis (RA). This study examined the expression of vascular endothelial growth factor (VEGF) isoforms and VEGF receptors, Flt-1, KDR and neuropilin-1, in RA and osteoarthritis (OA) synovia, and studied the relationship between their expression and the synovial angiogenesis. By RT-PCR analysis, the isoform VEGF(121) was constitutively expressed in all the RA (17/17 patients) and OA (8/8 patients) synovia. In contrast, the expression of the isoform VEGF(165) was observed in 41% of the RA synovia (7/17 patients), but was undetectable in the OA samples (0/8 patients). The receptor Flt-1 was almost constitutively expressed in RA (15/17 patients) and OA (8/8 patients) synovia, while the expression of KDR was detected in the synovia of six RA patients (6/17 patients; 35%) but none of the OA patients (0/8 patients). The expression of neuropilin-1, an isoform-specific receptor for VEGF(165) which enhances the binding of VEGF(165) to KDR, was also up-regulated in the same RA synovia that expressed KDR. Furthermore, there was a close correlation between the expression of isoform VEGF(165) and that of its receptors KDR and neuropilin-1. Morphometric analysis demonstrated that the vascular density is significantly higher in the RA synovial tissues with expression of VEGF(165), KDR, and neuropilin-1 than in those without their expression (p

The twy (tiptoe walking Yoshimura) mouse is an autosomal recessive mutant manifesting multiple osteochondral lesions characterized by pathologic calcium deposition. To elucidate the pathophysiology of the limb joint lesions and the intervertebral disk lesions of the twy mouse, we assessed the mRNA expression of noncollagenous bone matrix proteins such as osteocalcin, osteonectin, osteopontin, and matrix Gla protein (MGP) by in situ hybridization, but only expression of MGP was observed in association with the pathologic calcium deposits in twy mice. Mild degeneration and abnormal growth of the cartilage in contact with the joint capsule was observed at 5 weeks in the articular cartilage of the ankle joint of the twy mouse, and MGP gene expression was observed at the same time. Simultaneous growth of synovial membrane cells and relatively undifferentiated articular cartilage cells in the knee joint, and of cartilage-like cells near the insertion of the cruciate ligament was observed in the twy mouse, and MGP gene expression was found to be present at the same time. Hypertrophy of abnormally proliferated chondrocyte-like cells, which are different from fibrocartilaginous cells of the annulus fibrosus, was observed in the intervertebral disks of the twy mouse at 3 weeks of age, and MGP gene expression was noted at the same time. These findings suggest that abnormal expression of MGP plays a major role in the pathologic calcification of the twy mouse.

Spontaneous occlusion of the circle of Willis (cerebrovascular Moyamoya disease; SOCW) was first described by Japanese surgeons and is thought to have a high incidence in the Japanese population. SOCW is characterized by the angiographical findings of the obstructive vascular lesions around the terminal portions of the internal carotid arteries and the formation of abnormal vascular networks visualized in the arterial phase without any definite underlying conditions. Here, we present a detailed histopathological observation of 31 autopsy cases with SOCW to discuss its etiology which is still a matter of dispute. The obstructive vascular lesion around the terminal portions of the internal carotid arteries which is thought to be the primary site affected in SOCW is due to multilayered eccentric intimal fibrous thickening suggestive of organized mural thrombi. In fact, we found thrombotic lesions frequently in the major cerebral arteries, including those of the circle of Willis, of autopsy cases with SOCW. This fact supports the idea that thrombi play an important role in establishment of the vascular lesions. Extracranial vessels are also shown to be involved and it is conceivable that the systemic etiologic factor, such as the systemic background to form thrombi, exists in patients with SOCW.

Background The aim of the present study was to morphologically characterize the structure of the subepithelial blood vessels in the dark cell area of the human vestibular organs, and to determine whether immunocompetent cells such as macrophages and lymphocytes could be found around these small blood vessels. Materials and Methods All 31 surgical specimens (semicircular canals and utricles) were obtained from patients with vestibular schwannoma. Formalin fixed specimens were stained with hematoxylin and eosin (H&E), and with antibodies to von Willebrand Factor (vWF), leukocyte common antigen (LCA), and UCHL-1, and were examined with light microscope. Specimens fixed with glutaraldehyde were examined with a transmission electron microscope (TEM). Observations: Subepithelial blood vessels stained positive for vWF. By TEM observation, these blood vessels were observed to be capillaries that consisted of non-fenestrated endothelium, occasional pericytes, and a basement membrane. They were usually accompanied by melanophages with a number of secondary lysosomes containing phagocytosed degraded melanosomes and lipid droplets. Moreover, melanocytes and their cell processes directly surrounded these subepithelial capillaries. The fact that cells which were positively stained with LCA and UCHL-1 were present both in the intra- and subepithelial layer of the specimens, and that by TEM the intra- and subepithelial mononuclear cells with a lymphoid appearance had clustered dense bodies in their cytoplasm, suggested that they were a population of T lymphocytes. Conclusions Results suggested the possibility of a T lymphocyte-melanophage (macrophage) interaction, both originating from and harbored around subepithelial capillaries, which suggests the presence of an immune surveillance system in the human vestibular organs. Anat. Rec. 249:153–162, 1997. © 1997 Wiley-Liss, Inc.

Primary leiomyosarcoma of the thyroid gland is extremely rare, and to the best of our knowledge only five well-documented cases have been reported in the world literature. We herein report a 58-year-old female patient with primary leiomyosarcoma of the thyroid who was successfully treated by total thyroidectomy with a modified neck dissection. Immunohistochemically, the tumor cells showed positive reactivity to alpha-smooth muscle actin and vimentin. Radical surgery was thus considered to be essential in the treatment of this rare but rather aggressive malignancy.

The expression of matrix metalloproteinase-1 (MMP-1) gene and the presence of MMP-1 protein in gastric cancer were examined by in situ hybridization and immunohistochemistry. Expression of the interstitial collagenase (MMP-1) gene was detected within the stroma of the neoplastic glands, and infiltration of eosinophils was observed to be associated with regions of MMP-1 gene expression. The degree of eosinophilic infiltration correlated with the level of MMP-1 mRNA expression. Immunostaining showed localization of MMP-1 protein in the stromal cells, and additionally in the neoplastic glands. These findings indicate that the stromal cells may play an important role in the expression of MMP-1, and suggest a pathophysiological role for MMP-1 in the invasion and metastasis of gastric cancer.

To assess the time course of alterations in pulmonary endothelial vasodilator functions during pathological development of pulmonary hypertension (PH) and right ventricular hypertrophy (RVH), we examined changes in serotonin (5-HT) removal rates and the production of prostacyclin (PGI2) and nitric oxide (NO) in isolated rat lungs harvested at various times after single exposure to monocrotaline (MCT). We assessed the generation of vasodilator substances under conditions of both the absence and the presence of 5-HT in lungs perfused with blood-free solution. Major findings included: (i) remodeling of the pulmonary vasculature associated with RVH evident 14 days after MCT injection; (ii) the capacity for 5-HT removal was suppressed at day 1 and 7 but had been restored by day 14 after MCT exposure; (iii) basal PGI2 production in the absence of 5-HT was augmented at day 1 but had returned to control levels in lungs harvested 7 or 14 days postinjection of MCT; (iv) PGI2 production evoked by 5-HT was suppressed in MCT lungs obtained at all time points examined; (v) basal NO production was suppressed at day 1 but enhanced at day 7 and 14 in MCT lungs; (vi) NO production elicited by 5-HT stimulation in 1-day-MCT lungs was obviously suppressed while that in 7- and 14-day-MCT lungs had been restored to the control level. These findings suggest that transitional changes in endothelial functions including 5-HT removal and production of vasodilators in MCT lungs do not follow the same time course.

BACKGROUND Hexamethylene bisacetamide (HMBA), a potent differentiating agent of transformed cell lines, has been reported to affect phenotypic modulation and suppress proliferation of vascular smooth muscle cells (VSMCs). The effects of HMBA on the growth of VSMCs were studied in the rat carotid injury model. METHODS HMBA was added to culture medium of VSMCs explanted from aorta of Sprague Dawley rats and the cell number was counted after 5 days of incubation. The carotid artery of Sprague Dawley rats was denuded with a balloon embolectomy catheter. The rats were treated with continuous infusion of HMBA (1 g/day) or saline for 7 days after injury. RESULTS HMBA inhibited VSMC proliferation in a dose-dependent manner (at a HMBA concentration of 1-5 mM). Plasma concentration of HMBA during continuous infusion was in the range 0.8-1.0 mM. Immunohistochemistry of proliferating cell nuclear antigen showed that HMBA inhibited VSMC proliferation after vascular injury. Cell number in the intima and neointimal thickening were significantly reduced in HMBA-treated rats at 14 days after injury. CONCLUSIONS Systemic administration of HMBA inhibited VSMC proliferation in the rat carotid injury model.

Haemangioma of the thyroid gland is extremely rare. We report a case of a cavernous haemangioma of the neck that was located both inside and outside the thyroid gland of a 21-year-old man. Ultrasonography of the neck revealed numerous calcified nodules. Computed tomography (CT) showed a large calcified soft tissue mass in the right lobe of the thyroid. Based on the imaging findings a papillary thyroid carcinoma was suspected, but examination of the surgical specimen revealed a huge cavernous haemangioma containing numerous phleboliths.

An autopsy case of a 74-year-old man suffering from edema in the legs and diagnosed as protein-losing enteropathy due to intestinal lymphangiectasia is presented. He underwent a radical operation and radiotherapy for esophageal carcinoma at age 65 years and the onset of protein-losing enteropathy was at age 70. Postmortem examination disclosed widespread abnormalities of the duodenal and small intestinal lymphatics and mesenteric lymph node fibrosis. The mucosal lymphatic capillaries were markedly dilated. In the submucosal and serosal layers, the lymphatic vessels showed marked dilatation in some areas and fibrous occlusion with very thick muscle layers in others. All these lymphatic changes were presumed to be attributable to a reactive process secondary to lymph congestion, which it is suggested, was caused by the mesenteric lymph node fibrosis.

Thirteen cases of tall-cell variant of papillary thyroid carcinoma (PTC) showing extensive lymphocyte and plasma cell infiltration within the fibrous stalks of the papillary architecture were compared with age-, sex-, and tumor size-matched cases of ordinary tall-cell variant without extensive lymphocyte infiltration and also with cases of PTC of the conventional type. All cases of the tall-cell variant of PTC with extensive lymphocyte infiltration exhibited the histologic features of chronic thyroiditis. Dissemination of tumor cells with the thyroid was significantly less frequent than in control cases, but there was no difference between the incidences of lymph node metastasis. Immunohistochemically, the lymphocytes infiltrating the carcinoma focus were mainly CD20+, CD45+, and CD45RO+ cells, that is, basically the same as those found in foci of chronic thyroiditis. No tumor recurrence was observed during the mean follow-up period of 3 years 8 months. The results of this study suggest that the tall-cell variant of PTC with extensive lymphocyte infiltration has less aggressive characteristics and a more favorable prognosis.

Vascularization between vestibular schwannomas and the adjacent eighth cranial nerve was examined in order to elucidate the angiogenic effect of these tumours. Specimens from 12 patients were examined by light microscopy and immunohistochemistry (series 1), while specimens from another 17 patients were examined by light and transmission electron microscopy (series 2). Slight to marked angiogenesis was found in 5 patients from series 1 and 7 patients from series 2. Ultrastructural examination indicated that these blood vessels were more fragile than those in the normal eighth cranial nerve. These findings suggested that sudden hearing loss in vestibular schwannoma patients may be related to the disruption of such blood vessels. In addition, surgical injury to these blood vessels may cause postoperative hearing loss despite preservation of the cochlear nerve.

The human vestibular dark cell (DC) areas of the utricle and ampulla of the lateral semicircular canal were investigated ultrastructurally in 7 patients with acoustic neurinoma. Two types of DCs mainly constituted the epithelial cells of the DC area. One type of DC had basolateral infoldings that were closely interwoven with the melanocyte processes, and the pinocytotic vesicles were frequently found within the basolateral infoldings and the melanocyte processes. The other type of DC had basolateral infolsings stacked upon each other. The former type of DC was more frequently found than the latter type in the DC area adjacent to the sensory epithelium and in the mid portion of the DC area. However, the latter type of DC was more predominant in the DC area distant from the sensory epithelium. These findings suggest that the activity of DCs is modulated by the melanocytes and that the former type of DC has a more active role in ion and/or fluid transport than the latter type of DC. Thus, the DC area near the sensory epithelium might be more actively engaged in the production and regulation of vestibular endolymph than that distant from the sensory epithelium.

This report illustrates a case of the phyllodes tumor of the breast with intracytoplasmic inclusion bodies that are diffusely distributed over the tumor. The inclusion bodies were identified as aggregated actin filaments by modified immunohistochemical and ultrastructural analyses. These structures are thought to be identical to those of the characteristic intracytoplasmic inclusion bodies observed in the case of infantile digital fibromatosis. To date, tumors with such intracytoplasmic inclusion bodies have been recognized exclusively as infantile digital fibromatosis. Although a few rare cases in which the infantile digital fibromatosis-like tumor occurred outside the digit or in adulthood, all these cases were in the category of fibromatosis or fibroma. This case is the first instance of the tumor containing intracytoplasmic inclusion bodies identical with the infantile digital fibromatosis other than fibromatosis or fibroma.

The central-peripheral transitional region (TR) of the eighth nerve root was obtained from 8 patients with cerebellopontine angle schwannoma and investigated by light microscopy, electron microscopy, and immunohistochemistry. As a control, the TRs of 6 autopsy patients without any otologic disease were studied. Astrocytic proliferation at the TR was more prominent in the schwannoma patients than in the normal controls. Mild gliosis of the mantle zone of the TR was found in 5 schwannoma patients and moderate gliosis was noted in 3. The distribution of capillaries at the TR differed between the schwannoma patients and the normal controls. In the schwannoma patients, capillaries were rarely found in the mantle zone of the TR but were densely clustered at the glial fringe zone, especially near its border with the peripheral nervous tissue. Stasis of the capillaries in the glial fringe zone was frequently noted. These histological findings may indicate the occurrence of gliosis in response to eighth nerve degeneration. We suggest that there is increased susceptibility of the eighth nerve to injury at the TR in patients with schwannoma.

To investigate the central-peripheral transitional region (TR) of the eighth nerve in elderly humans and to determine the reasons for its fragility, the eighth nerve root was studied by light and electron microscopy and by immunohistochemistry. Central and peripheral nervous tissue showed complex interdigitations at the TR. Slight proliferation of central glial tissue accompanied with disarranged course of the nerve fibers was also seen in this region. These findings were thought to be age-related changes of the eighth nerve. The capillaries ran in various directions at the TR and formed anastomoses with capillaries in the peripheral portion of the nerve. The density of capillaries in the peripheral nervous tissue was twice as high as that in the central nervous tissue. These findings indicated that the capillaries at the TR provide a connection between the blood supply to the central and peripheral portions of the eighth nerve. The occurrence of the age-related changes and complex course of the capillaries at the eighth nerve TR appeared to be related with the fragility of this region.

Vascular casting has so far been used mainly for observation of the vascular system of the inner ear in experimental animals. In the present study, this method was applied to analysis of the three-dimensional vascular structure in the inner ear in humans. To date there has been no comparative study of overall pictures of blood vessels in the human inner ear. Seven cases were observed mainly by means of scanning electron microscopy. Even with this new method, the results in many respects obtained confirmed those of previous reports. However, the following findings which have not been previously reported or are currently in dispute, were observed: i) In two cases, spring coil-like structures of blood vessels were found in the internal auditory canal; ii) We corroborated the pattern of arrangement of cochlear arteries previously described in words and schemata, i.e., the following two types were confirmed: the first type showing the cochlear branch of vestibulocochlear artery and the spiral modiolar artery running into the cochlea, and the second type showing the cochlea supported by arteries derived from the artery corresponding to the vestibulocochlear artery, alone; and iii) A right-angled arteriolar branch of the spiral modiolar artery was found to further bifurcate to form radiating arterioles extending in two directions: both over the scala vestibuli and along the spiral lamina.

The histogenesis and clinical significance of solid cell nests (SCN) of the thyroid are not fully understood. From August 1987 to December 1989 a total of 2544 patients with thyroid and parathyroid diseases underwent surgery at Ito Hospital, and SCN were revealed within the thyroid parenchyma in 21 (0.8%). Distribution of SCN was not limited to the upper one-third of the lateral lobe, and SCN were found even in the isthmus lobe. In 5 cases microcysts were also noted within SCN, and their content was thought to be acidic proteoglycan. Immunohistochemical study revealed that SCN were negative for thyroglobulin and calcitonin but positive for carcinoembryonic antigen. Thirteen of 21 cases showed positive immunostaining with cytokeratin. Scattered calcitonin-positive cells were noted around the SCN. It is suggested from these findings that SCN of the thyroid are closely related to certain cells of ultimobranchial body vestiges which may be not of neuroectodermal origin but of endodermal origin.

A patient with malignant lymphoma suddenly collapsed, and ST segment elevation with complete atrioventricular block was observed on his electrocardiogram during an episode resembling acute myocardial infarction. Cardiac cineangiography revealed posterobasal asynergy of the left ventricle with no significant obstruction in the coronary arterial tree. Autopsy revealed diffuse invasion of the myocardium by lymphoma cells. Left ventricular wall motion was preserved even in the area of massive invasion; there was no true necrosis. Myocardial biopsy may be indicated in patients in whom there is a discrepancy between coronary pathoanatomy and wall motion abnormalities.

Previously, it has been reported that a mammalian protein disulfide isomerase (PDI), when expressed on a single copy number plasmid, can rescue growth of a PDI1-disrupted yeast. However, here, for the first time we demonstrated by tetrad analysis that human PDI (hPDI) is unable to replace yeast PDI (yPDI) when hPDI cDNA is integrated into the yeast chromosome. This observation indicates that hPDI is not functionally equivalent to yPDI. Estimation of the actual copy number of the plasmid, as well as comparison of isomerase and chaperone activities between human and yeast PDI homologues, indicates that one copy of hPDI cDNA is not sufficient to rescue the PDI1-disrupted strain. Notably, the isomerase activities of yPDI family proteins, Mpd1p, Mpd2p, and Eug1p, were extremely low, although yPDI itself exhibited twice as much isomerase activity as hPDI in vitro. Moreover, with the exception of Mpd1p, all hPDI and yPDI family proteins had chaperone activity, this being particularly strong in the case of yPDI and Mpd2p. These observations indicate that the growth of Saccharomyces cerevisiae is completely dependent on the isomerase activity of yPDI.

The transitional region of the eighth cranial nerve, where the central and peripheral nervous tissues are contiguous, was studied by electron microscopy using surgically resected specimens of the human eighth cranial nerve root. The astrocytic glial dome was sharply demarcated by a basement membrane from the peripheral portion of the nerve. Half-desmosomes were found on the edge of the astrocytic glial dome and at the luminal surface of the perivascular glial limiting membrane. Desmosomes and gap junctions were found between the astrocytic processes. These ultrastructural features suggest a weak link between the central and peripheral portions of the nerve which might predispose the transitional region to injury, although the peripheral and central portions have sufficient resistance to external stresses independently.

A case of cystadenocarcinoma of the appendix with a large cystic lesion is reported. A 49-year-old man undergoing a routine ultrasonic scan was incidentally found to have an abdominal mass measuring some 30 cm in size. The clinical presentation was asymptomatic, and the patient underwent a laparotomy without ascertaining a diagnosis preoperatively. The lesion, which derived from the appendix, was removed and was found to be cystic and contained huge amounts of mucin. The histological findings revealed a well-differentiated cystadenocarcinoma of the appendix, and immunohistochemical staining of the epithelium and mucinous implants in the mass demonstrated a positive reaction for carcinogenic antigens, including carcinoembryonic antigen and carbohydrate antigen.

The pulmonary vasculature exhibits various morphological changes in patients with pulmonary hypertension (PH). Among them, the plexiform lesion is one of the most characteristic vascular lesions, although nothing is known about the molecular mechanisms of its formation. In the present study, the expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific angiogenic mitogen, and its receptors, fms-like tyrosine kinase (Flt-1) and kinase insert domain-containing receptor (KDR), in the lungs of five cases with PH, were examined. By in situ hybridization, VEGF expression was found in modified smooth muscle cells inside the plexiform lesions as well as in medial smooth muscle cells of the arteries adjacent to the lesions. The expression of Flt-1 mRNA was observed in endothelial cells of the arteries adjacent to the plexiform lesions, while KDR mRNA was expressed in the endothelial cells inside the plexiform lesions. VEGF was immunolocalized to the endothelial cells expressing its receptors as well as the modified smooth muscle cells producing VEGF. These results demonstrate that VEGF and its receptors are upregulated with a close correlation to the plexiform lesions, and suggest that VEGF expressed by smooth muscle cells may activate the endothelial cells to form the plexiform lesions.

We report the case of a patient with SLE who had repeated ulceration of the small intestine requiring emergency surgery. Pathologic examination revealed microthrombosis and vasculitis at the site of the intestinal ulcers. High levels of antiphospholipid antibodies, thrombocytopenia, and prolonged prothrombin time coincided with the episodes of intestinal ulceration. Antiphospholipid antibodies may be involved in the development of thrombosis resulting in the repeated episodes of intestinal ulceration in this patient. This possibility should be considered in patients with SLE who have intestinal ulceration and appropriate antithrombotic medication should be administered.

A 53-year-old man sustained a 50 Hz, 60 kV electrical injury. The current flowed between his right hand and both feet. There was necrosis of the distal portion of the right forearm, and the fourth and fifth toes on the right foot. The skin on the amputated right upper extremity appeared normal except for an ulcer in the antecubital fossa and some blister scars. However, most of the muscles of the arm at the elbow were necrosed and partially replaced by fatty tissue or fibrosis. These necrotic areas corresponded to minimally increased signal intensities on T1-weighted MRI, and high signal intensities on T2-weighted images. MRI may be employed to predict amputation level after electrical injury.

The vasculature of the peripheral portion of the human eighth cranial nerve (VIIIN) was investigated by light and transmission electron microscopy. Arterioles and venules running longitudinally around the VIIIN formed the extrinsic vascular system. The anatomical relationship between these extrinsic vessels and the VIIIN sheath was similar to that between blood vessels on the surface of the brain and the pia mater. In the endoneurium, postcapillary venules and large capillaries were sparsely distributed and longitudinally arranged, and these microvessels formed the intrinsic microvascular system, which was supported by the extrinsic vascular system via anastomosing vessels. The ultrastructural features of the internal auditory artery and its main branches were the same as those of other intracranial arteries. Ultrastructural study also revealed myo-endothelial junctions in anastomosing arterioles, and endothelio-pericytic junctions in extrinsic and anastomosing venules. Microvascular endothelial cells were connected by tight junctions in both the vestibular ganglion and the rest of the VIIIN. These features of the vasculature were considered to be effective for maintenance of the endoneurial fluid and regulation of the circulation in the peripheral portion of the human VIIIN.

Background The purpose of the present study was to obtain additional information about the ultrastructural characteristics of gap junctions between melanocytes in human vestibular organs by using various ultrastructural techniques. Methods All materials were obtained from patients with vestibular schwannoma. Glutaraldehyde-fixed specimens and specimens treated with fixative containing glutaraldehyde and tannic acid were processed for conventional ultrathin transmission electron microscopic (TEM) examination. Others were prepared for freeze-fracture replica and examined by TEM. Results Gap junctions were present between adjacent subepithelial melanocytes. The gaps between the inner leaflets of the apposed plasma membranes at the gap junctions were 10–12 nm, and the gaps between the outer leaflets were 2–4 nm. The intercellular space between the apposed plasma membranes of gap junctions showed the deposition of high electron-dense material in specimens prepared with fixative containing glutaraldehyde and tannic acid. At the highest magnification specimens fixed by glutaraldehyde with or without tannic acid and cut obliquely to the plasma membranes showed periodic substructures with constant repeating lattices or a small porous structure at the junctions. Study by freeze fracture revealed that these gap junctions between melanocytes consisted of 100–200 aggregations of connexon particles that were approximately 8.8 nm in diameter. Conclusions We suggest that melanocytes may construct a cellular network involved in the maintenance of the homeostasis of human vestibular organs through the intimate transmission of various signals or intercellular informations via well-developed gap junctions. © 1996 Wiley-Liss, Inc.

Rheumatoid nodule is a frequent and characteristic extra-articular manifestation of rheumatoid arthritis (RA). Its involvement of central nervous system is a rare occurrence with only a few reported cases. A 78-year-old man with severe arthritis showing the formation of rheumatoid nodule-like granulomas in the dura and subarachnoid space along with the spleen is presented. The characteristic morphological finding of the granulomas was the presence of neutrophils and the absence of definite fibrinoid necrosis, which differed from the typical features of rheumatoid nodules previously described. The diagnosis should be based on the exclusion of diseases that may cause similar granulomatous reactions including infectious diseases. Additionally, there was systemic necrotizing vasculitis in the dura and multiple cerebral infarcts, although the association between vasculitis and cerebral infarcts was not clear.

Background: The possibility of interaction between epithelial dark cells and melanocytes in the mammalian inner ear has been pointed out because of their morphological and biochemical characteristics, although very few studies have dealt directly with communication between these two types of cells. We investigated the dark cell area of human vestibular organs in order to clarify the ultrastructual evidence for cell interaction between epithelial dark cells and melanocytes. Methods: All of the material was obtained from vestibular schwannoma operations. Paraffin sections were stained with hematoxylin and eosin (H&E) and by the Fontana-Masson technique. Other paraffin sections were also stained immunohistochemically for S-100 protein. Glutaraldehyde fixed specimens were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: Light microscopy revealed melanin pigment granules in the cytoplasm of epithelial dark cells. Melanocytes in the subepithelial layer stained positively for S-100 protein. The presence of intraepithelial melanocytes was confirmed by the presence of cell profiles with a large number of melanin pigment granules and S-100 protein in the cytoplasm. SEM showed that the dark cells had a pentagonal surface with microvilli on the apical surface edge. They had complicated structures at the basal portion of their cytoplasm. Melanocytes extending cytoplasmic processes to adjacent areas were observed under the dark cells. TEM showed that the dark cells were tightly linked by junctional complexes in the upper lateral portion of their cytoplasmic membrane and interdigitated by lateral infoldings. Compound melanosomes (phagosomes or secondary lysosomes) found in the cytoplasm of the dark cells contained poorly pigmented melanosomes with a periodic internal structure. Gap junctions were clearly showed between adjacent melanocytes in the subepithelial layer. Conclusions: The characteristic substructures of dark cells and melanocytes suggested the presence of intimate cell interaction between these two types of cells in the vestibular organs of the human inner ear, although it is not clear at this stage whether such cell interaction is specific only for patients with vestibular schwannoma. Dark cells and melanocytes form a cell community that serves to maintain homeostasis in vestibular organs through communication in which cell information obtained by both dark cells and melanocytes serves to facilitate the system. © 1995 Wiley-Liss, Inc.

By using surgical materials obtained from 7 cases of vestibular schwannoma, the ultrastructure of melanocytes in the dark cell area of human vestibular organs was examined by light microscopy and electron microscopy. Paraffin sections were stained with hematoxylin and eosin. Glutaraldehyde-fixed specimens were observed by electron microscopy. Melanocytes were found in the subepithelial layer of the dark cell area. Melanocytes had round or spindle-shaped nuclei and clear cytoplasm with brown pigment granules which were thought to be melanin granules. Besides melanocytes, there were fibroblasts and small blood vessels. By electron microscopy we found melanocytes with round shaped melanosomes in various stages of pigmentation, well-developed Golgi apparatus and endoplasmic reticulum in the cytoplasm, and many cytoplasmic processes. There were pinocytotic vesicles just under the limiting membrane of the melanocytes, and intermediate filaments were abundant in the cytoplasm. On the other hand long-spacing collagen was found in the connective tissue area around melanocytes.

Structural changes after photodynamic therapy of atherosclerotic lesions of the thoracic aorta were analyzed by scanning electron microscopy. Cholesterol fed atherosclerotic rabbits were injected intravenously with 5 mg/kg of NPe6. At 6 hours after NPe6 loading, a diode laser irradiated angioscopically on the surface of atheroma with the total energy of 200 mJ/cm2. Scanning electron microscopy showed degeneration of atherosclerotic plaques of the thoracic aorta examined at one week after photodynamic therapy. NPe6 could be a potent photosensitizer for photodynamic therapy of atheroma.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Collagenolytic proteinases play an important pathological role in the invasion and metastasis of cancer cells. However, little is known about the role of interstitial collagenase (matrix metalloproteinase-1; MMP-1) in this process. To investigate the expression of the MMP-1 gene in cancer tissues, an in situ hybridization study was carried out in gastrointestinal tract cancers (one esophageal cancer, five gastric cancers, and four colorectal cancers), using a 35S-labeled MMP-1 cDNA probe. The MMP-1 gene was expressed in the stromal cells of fibrous tissue around cancer nests, especially at the margin of invasion and/or within the cancer nest; however, no definite expression within cancer cells was observed. Expression of the MMP-1 gene in the stromal cells was more common in well differentiated gastric adenocarcinoma than in poorly differentiated adenocarcinomas. These findings indicate that expression of the MMP-1 gene is greater in stromal cells that are closely associated with cancer cells, suggesting a pathophysiological role of MMP-1 in the invasion and metastasis of cancer cells.

Squamous cell carcinoma (SCC) of the thyroid is thought to be rare. However, SCC not infrequently occurs in conjunction with other histologic types of tumor. We reviewed 67 thyroid cancer autopsy cases obtained from two institutions from 1969 to 1981 and from 1975 to 1992, respectively. SCC was found in 19 cases (28.4%): 2 SCCs as the only malignancy and of uniform histologic type, 9 cases of tumors mixed with papillary carcinoma, and 8 cases of SCC mixed with papillary and anaplastic carcinomas. In only four of these cases was the SCC component found in the surgical specimens. These results indicate that the presence of SCC component is more likely to be found at the later stage of the disease.

A murine autosomal recessive mutant named twy (tiptoe walking-Yoshimura) mouse showing multiple osteochondral lesions including ankylosis of the vertebral column and limb joints underwent sequential histopathological analysis of posterior limb joint lesions and intervertebral disc lesions. In the articular cartilage, a decrease in alcian blue-positive extracellular matrix and the presence of degenerated collagen fibers were found at the age of around 4-8 weeks. Calcium deposits in the articular cartilage were found at that time and later in the articular space and synovial tissue. Calcium deposits were also found in the intervertebral discs at 4 weeks. Using electron microscopy, some of the crystals were seen inside small vesicles. In both joints, degeneration of, and calcium deposition in, the articular cartilage progressed with age, finally producing bony ankylosis. These histological observations suggest that calcification and degeneration of the articular cartilage are the major factors in the pathogenesis of joint disorders in the twy mouse, and this mutant mouse provides a good model for studying the process and mechanism of osteoarthritic lesions, destructive arthritis and ankylosis.

The nerve root segment where the transition from central to peripheral nervous tissue occurs is referred to as the transitional region (TR). Part of the TR is a continuation of the subpial glial limiting membrane (SGLM) which covers the surface of the brain. To assess the physiological and pathophysiological roles of astrocytes in the TR of the human eighth cranial nerve, electron microscopy was performed on surgically resected specimens of the eight cranial nerve root obtained from patients with cerebellopontine angle tumors. The astrocytic glial dome was sharply bounded by a basement membrane and was mainly composed of the bodies and processes of fibrous astrocytes. Desmosomes and gap junctions were found between these astrocytic processes. Half-desmosomes were found on the edge of the astrocytic glial dome and at the luminal surface of the perivascular glial limiting membrane. These ultrastructural features indicate that the astrocytes of the TR might have some motility capacity that allows adjustment to changes in the pressure exerted by the vessels, the peripheral nervous tissue, and the cerebrospinal fluid. In addition, it is also suggested that lack of structures linking the central and peripheral portions of the nerve and the abrupt change of nerve composition at the TR might predispose this area to injury by tractional forces or pathologic conditions such as tumor or arterial compression.