A gastric carcinosarcoma with neuroendocrine cell differentiation and undifferentiated spindle-shaped sarcoma component possibly progressing from the conventional tubular adenocarcinoma; an immunohistochemical and ultrastructural study

A 56-year-old Japanese man underwent total gastrectomy with lymph-node dissection for a gastric tumor. In the oral rim of the excised large ulcerated tumor, a small nodular mass demonstrated a unique histology of a carcinosarcoma composed of more than three distinctive components. A major part of the large ulcerated tumor tissue consisted of conventional tubular adenocarcinoma, with the coincidental focal distribution of solid cell nests of poorly differentiated or neuroendocrine cell (small cell) carcinoma. Sarcoma cells were another of the constituents of the small nodular tumor with atypical spindle-shaped cells. All the excised lymph-node metastasis demonstrated the histology of tubular adenocarcinoma. In the sarcoma cells, many of the lineage-specific immunohistochemical markers were negative. Only vimentin was positive. Electron microscopy revealed that the neuroendocrine cell carcinoma contained cells with abundant small aggregations of neurosecretory-type granules in their cellular cytoplasm. Primitive cellular junctions and incomplete basal lamina were seen in the sarcoma cells. No transitional or hybrid-type cells were seen between carcinoma and sarcoma cells. The interfaces between the cancer cell nests and the proliferation of sarcoma cells are clearly discerned. It was speculated that the unique histology of carcinosarcoma might have progressed from the conventional type of pre-existing advanced tubular adenocarcinoma.     

Mutation analysis of two Japanese patients with Fanconi-Bickel syndrome

Fanconi-Bickel syndrome (FBS), or glycogen storage disease type XI, is a rare autosomal recessive disorder characterized by hepatorenal glycogen accumulation, Fanconi nephropathy, and impaired utilization of glucose and galactose. Recently, this disease was elucidated to link mutations in the glucose transporter 2 (GLUT2) gene. Only three mutations in three FBS families have been reported. Therefore, it is important to elucidate mutations in the GLUT2 gene in FBS by answering the question of whether the syndrome is a single gene disease. In this report, we describe two patients in two unrelated families clinically diagnosed with FBS. No mutation in the entire protein coding region of the GLUT2 gene was detected in patient 1, which suggested that no mutation existed in the GLUT 2 gene, or that some mutations had affected the expression of the GLUT 2 gene. In patient 2, a novel homozygous nonsense mutation (W420X, Trp at codon 420 to stop codon) was detected. These results support the correlation between GLTU2 gene mutation and FBS syndrome. However, many patients must be analyzed to determine whether other genes are involved in FBS. Received: July 16, 1999 / Accepted: September 3, 1999     

Determination of plasma bromvalerylurea and its main metabolite by a simple high-performance liquid chromatographic method and quantitation of bromide by energy dispersive X-ray spectrometry in carbon tetrachloride-intoxicated rats

In the present study, small volumes of plasma were used for the measurement of bromvalerylurea (BVU), its metabolite, 3-methylbutyrylurea (MVU), and bromide in carbon tetrachloride (CCl4)-treated rats by HPLC-UV and energy dispersive X-ray spectrometry. A liquid-liquid extraction system was also investigated. BVU and MVU were extracted from 100 microl plasma samples in a single-step involving deproteination with 1 M hydrochloric acid using ethenzamide as internal standard. Samples were separated by HPLC in an acetonitrile-8 mM potassium dihydrogenphosphate buffer (35:65, v/v) mobile phase at a flow-rate of 0.4 ml/min on a 15 cm octadecylsilyl column at room temperature. Analytes were detected at a wavelength of 210 nm. The limits of quantitation for BVU, MVU and bromide are 0.1, 0.1 and 50 microg/ml, respectively. The intra-day accuracies over the range of concentrations were 95.8 to 121.1%, 97.2 to 119.7% and 96.2 to 105.8% for BVU, MVU and bromide, respectively. The inter-day accuracies were 97.7 to 115.1%, 98.3 to 111.6% and 98.3 to 102.9% for BVU, MVU and bromide, respectively. The absolute recoveries using tert.-butyl methyl ether are 96-98% for BVU and 95-98% for MVU. The decline in the plasma concentrations of BVU in olive oil-treated rats fitted a one-compartment model and the plasma MVU level reached a peak at around 1.5-2 h and then decreased gradually. The elimination of BVU in CCl4 (1 ml/kg)-treated rats was delayed and MVU production was less than that in the olive oil-treated group. However, there was no difference in the plasma levels of bromide between CCl4-treated rats and control rats. rights reserved.     

P16-immunostaining pattern as a predictive marker of lymph node metastasis and recurrence in early uterine cervical cancer.

OBJECTIVES: We investigated the relationship between P16-immunostaining patterns and clinicopathological factors in early uterine cervix cancers and assessed whether P16-immunostaining patterns predict the prognosis of the patients with early uterine cervix cancers. METHODS: Twenty-nine early squamous cell carcinoma (SCC) specimens of the uterus were examined using immunohistochemistry for P16 expression. The P16-immunostaining pattern was classified into two groups: the homogeneous type and the heterogeneous type. P16-immunostaining patterns were evaluated in different parts of the carcinoma in situ (CIS): the center of the tumor and the front interface of the infiltrating tumor. RESULTS: All specimens were of the homogeneous type in CIS. The P16-immunostaining pattern was significantly of the heterogeneous type in the front interface of the infiltrating tumor with lymphatic invasion, vascular invasion, lymph node metastasis, and recurrence. Regarding the P16-immunostaining patterns in the front interface of the infiltrating tumor, the patients with the heterogeneous type showed a significantly worse prognosis than the patients with the homogeneous type. CONCLUSIONS: The prognosis of patients with early uterine cervical SCC may be predicted by evaluating the P16-immunostaining pattern in the front interface of the infiltrating tumor.     

Comparison of the inhibitory effects of glucocorticoids on the expression of eotaxin in airway epithelial cell line BEAS-2B]

OBJECTIVE: Inhaled corticosteroids play a pivotal role in the treatment of asthma. To observe the mechanisms of glucocorticoids, we focused our study on the comparison of several glucocorticoids' effects on eotaxin expression in the airway epithelial cells. METHODS: Airway epithelial cell line BEAS-2B was cultured in vitro. Cells were preincubated with or without glucocorticoids (becromethasone dipropionate; BDP, budesonide; BUD, fluticasone propionate; FP) and stimulated with TNFalpha and/or IL-4. Protein levels of eotaxin in the supernatants of the cultured cells were determined by ELISA. RESULTS AND CONCLUSIONS: TNFalpha and IL-4 increased the levels of eotaxin in BEAS-2B cells. Combination of these cytokines synergistically upregulated the eotaxin expression as reported previously. Each glucocorticoid significantly inhibited the expression of eotaxin protein induced with TNFalpha and IL-4 and the compared efficacy was in order of FP>BUD>BDP. FP seemed most potent and the inhibitory effect was also observed with relatively low concentration such as 10 (-10)M. Taken together, the comparison of the potency of each glucocorticoid using airway epithelial cells may reflect the efficacy of these drugs in asthmatics.     

The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization

Choroidal neovascularization (CNV) is directly related to visual loss in some eye diseases, such as age-related macular degeneration. Although several human histological studies have suggested the participation of macrophages in CNV formation, the precise mechanisms are still not fully understood. In this study, we elucidated the role of ocular-infiltrating macrophages in experimental CNV using CCR2 knockout (KO) mice, wild-type mice, and C57BL/6 (B6) mice. CCR2 is the receptor of monocyte chemoattractant protein-1, and the number of infiltrating macrophage and the area of CNV were significantly reduced in CCR2 KO mice. Enriched ocular-infiltrating macrophages from B6 mice actually showed angiogenic ability in a dorsal air sac assay. Moreover, their expression of class II, CD40, B7-1 and B7-2 molecules, and the mRNA for potential angiogenic factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor alpha, was also observed. Collectively, we conclude that ocular-infiltrating macrophages play an important role in CNV generation.     

Construction of a standard rating scale to estimate sleep onset and the analysis of influencing factors

In this study, we developed a ratings scale for estimating sleep onset that would be capable of providing quantitative evaluations of the quality of the sleep onset process. We also examined factors affecting sleep onset using a questionnaire consisting of two separate clusters of items: the first, consisting of 9 items, related to the quality of sleep onset; and the second, consisting of 56 items, related to factors with apparent effects on sleep onset. The questionnaire was administered to 515 day-workers (range: 25-44 years old) for standardization. Each item was weighted based on the distribution of subject responses to determine discrimination. The reliability coefficient alpha for the questionnaire was high, exceeding 0.8. Of 41 items set out as potential factors affecting sleep onset, the results of the questionnaire indicated that five factors consisting of 26 items could be isolated as most likely affecting sleep onset. Path analysis indicated that sleep onset is more commonly affected by factors present at bedtime than factors related to sleep quality the previous night, or to daytime activities.     

Catastrophic antiphospholipid syndrome: CAPS]

Antiphospholipid syndrome (APS) is well known as an autoimmune thrombotic syndrome with recurrent thromboses. In APS, thromboses occurs both artery and vein, and from large to micro vessels. In contrast, so called catastrophic antiphospholipid syndrome, CAPS, develops multiple thromboses at microvessels mainly within a few weeks and induces to poor prognosis. CAPS often occurs in patients with SLE or primary APS after a change of antithrombotic therapy, infection, and operation. Treatments for CAPS have not established although plasma exchange is carried out usually as well as intensive anticoagulation and immunosuppressive therapy. We treated with immunoadsorption plasmapheresis (IAPP) for 5 CAPS patients and they improved their clinical symptoms and ameliorated their titers of antiphospholipid antibodies. IAPP could be an useful treatment skill for CAPS and we have started prospective study.     

Skin vascular response in the hand during sinusoidal exercise in physically trained subjects

The effect of physical training on the cutaneous vascular response during transient exercise load is unclear. We determined the phase response and amplitude response of cutaneous vascular conductance (CVC) in the hand during sinusoidal exercise in endurance exercise-trained and untrained subjects. Subjects exercised on a cycle ergometer with a sinusoidal load for 32 min. The load variation ranged from 10% [23 (1) W in the trained group, 19 (1) W in the untrained group] to 60% [137 (4) W, 114 (6) W] of peak O₂ uptake, and five different time periods (1, 2, 4, 8, and 16 min) were selected. Skin blood flow in the dorsal hand and palm were monitored by laser-Doppler flowmetry. CVC was evaluated from the ratio of blood flow to mean arterial pressure. During sinusoidal exercise, the amplitude of CVC was smaller in the dorsal hand than palm for shorter periods (1, 2, and 4 min) (P<0.05). The phase lag of CVC was smaller in the dorsal hand than palm for longer periods (8 and 16 min) (P<0.05). The amplitude response did not differ significantly between the two groups. The phase lag of CVC in the dorsal hand (P<0.05) and palm (P=0.06) was larger in the trained group than untrained group. These findings suggest that glabrous and nonglabrous skin vascular responses in the hand differ during transient exercise load, and physically trained subjects show a slower vascular response in the two skin areas to exercise stimulation than do untrained subjects.