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Under high shear stress, the binding of von Willebrand factor (VWF) A1-loop domain to platelet glycoprotein (GP) Ib alpha occurs as the earliest event in thrombus formation. Therefore recombinant VWF A1-loop fragments could be of therapeutic use in blocking this interaction as competing ligands. We have prepared three homodimeric VWF A1-loop fragments [315 kD Fr III (a homodimer of amino acid [aa] residues 1-1365 of the subunit), 220 kD Fr (a homodimer of aa residues 1-708 of the subunit), and 116 kD Fr (a homodimer of aa residues 449-728 of the subunit) and two monomeric fragments [39/34 kD Fr (a monomer of aa residues 480/481-718 of the subunit] and His-rVWF465-728 (a monomer of aa residues 465-728 of the subunit)], and assessed their potency as inhibitors of botrocetin-induced VWF binding to GPIb alpha and high shear stress induced platelet aggregation mediated by intact VWE All these fragments completely inhibited botrocetin-induced VWF binding to GPIb alpha at a final concentration of 40-200 microM. The homodimeric A1-loop fragments also totally inhibited high shear stress induced platelet aggregation at a final concentration of 0.45-2.0 microM in the following order: 315 kD Fror = 220 kD Fr116 kD Fr. In contrast, the monomeric A1-loop fragments were only partial inhibitors of high shear stress induced platelet aggregation even at a final concentration of 20 microM, and their IC50s were 13-39 times higher than those of the homodimers. These results indicate that the homodimeric structure of the A1-loop fragment is important for optimal molecular interaction with GPIb alpha under high shear stress.

The cDNA clones of two isoforms (enzymes I and II) of human placental ecto-ATP diphosphohydrolases have been isolated based on the N-terminal amino acid (aa) sequence of the immunopurified 82 kDa protein and characterized. The cDNA clone encoding enzyme I consists of 2081 nucleotides and the predicted enzyme I consists of 517 aa residues. Enzyme I has a 5'-UTR and an N-terminal 11 aa sequence that differ from CD39, but the rest of the sequence is the same as CD39. The hydropathy plot indicated that enzyme I has two hydrophobic regions near the N- and C-termini of the molecule. In contrast, enzyme II consists of 1814 nucleotides and the predicted protein consists of 306 aa residues. The sequence of 1-1018 nucleotides of enzyme II is identical to that of enzyme I, but the 1019-1814 nucleotide sequence is different from both enzyme I and CD39. The hydropathy plot indicated that enzyme II has one hydrophobic region near the N-terminus, suggesting that enzyme II is also anchored to the cell membrane. It is, however, likely that some of enzyme II exists as a soluble form in plasma, possibly after proteolytic processing.

An apatite layer was formed on polyethyleneterephthalate (PET) substrates by the following biomimetic process. PET substrates were placed on granular particles of a CaO-SiO2-based glass in simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma to form apatite nuclei on their surfaces (first treatment). They then were soaked in modified SBFs, the ion concentrations of which were changed to give a variation in ionic activity product of apatite (IP), in order to make the apatite nuclei grow (second treatment). The Ca/P atomic ratio and the lattice constant c of the formed apatite decreased from 1.54 to 1.40 and from 6.880 to 6.838 A, respectively, with increasing ion concentrations from 0.75 to 2.00 times those of SBF, that is, with increasing IP from 10(-96.6) to 10(-91.9). This was attributed to an increase in the concentration of HPO4(2-) ion substituting for the PO4(3-) ion sites, which gave an increase in the Ca2+ in the apatite. Even the apatite formed in 1.00 SBF showed a Ca/P ratio of 1.51 and lattice constants a of 9.432 A and c of 6.870 A. The Ca/P ratio and lattice constant c were smaller and the lattice constant a was larger than those of the bone apatite; its Ca/P ratio and its lattice constants a and c, were 1.65, 9.419 A, and 6.88 A, respectively. This was attributed to the lower content (2.64 wt%) of the CO3(2-) ion substituting for the PO4(3-) ion sites of the apatite compared to that of the bone apatite (5.80 wt%). The lower content of the CO3(2-) ion in the apatite might be caused by the lower concentration of HCO3- ion in 1.00 SBF compared to that in human blood plasma.

Gastrointestinal radiographs were reviewed with pathological correlation in 18 patients with histologically proven esophageal adenocarcinoma arising from Barrett's epithelium. Comparison was also made with postoperative radiographs of resected esophageal specimens from 3 of the patients. Esophageal carcinoma could be observed in the gastrointestinal radiographs in 17 of the 18 patients. In 14 of the 17, the classification based on the gastrointestinal radiographs was consistent with the gross classification. In 10 of the 18 patients, rough mucosa was seen on gastrointestinal radiographs in the same area in which Barrett's epithelium was observed in the histopathological specimens. Sliding esophageal hiatus hernia was present in 12 of the 18 patients, a relatively high incidence. Regular granular or reticular shadows were observed on the mucosal surface of the esophagus on the postoperative radiographs of 3 patients. It is believed that a diagnosis of Barrett's epithelium can be made from gastrointestinal radiographs if these mucosal patterns are present. Although a definitive diagnosis of Barrett's epithelium based on upper gastrointestinal radiographs is considered difficult, the presence of rough mucosa in the esophagus around the carcinoma in combination with esophageal hiatus hernia are suggestive of esophageal adenocarcinoma arising from Barrett's epithelium.

Glycopeptides containing the N-linked oligosaccharide from human serum IgA1 were analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS). Two glycopeptides, GP1 and GP2, prepared from the endoproteinase Asp-N digest of the IgA1 heavy chain, were derived from the CH2 domain (N-glycan site at Asn263) and the tailpiece portion (N-glycan site at Asn459), respectively. The structure of the attached sugar chain was deduced from the mass number of the glycopeptide and confirmed by a two-dimensional mapping technique for a pyridylaminated oligosaccharide. GP1 was composed of two major components having a fully galactosylated bianntena sugar chain with or without a bisecting N-acetylglucosamine (GlcNAc) residue. On the other hand, the GP2 fraction corresponded to the glycopeptides having a fully galactosylated and fucosylated bianntena sugar chain partly bearing a bisecting GlcNAc residue. Thus, the site-specific fucosylation of the N-linked oligosaccharide on the tailpiece of the alpha1 chain became evident for normal human serum IgA1.

Background: To describe computed tomographic (CT), magnetic resonance (MR), ultrasonographic (US), and angiographic findings of retroperitoneal malignant mesenchymoma with emphasis on CT findings. Methods: Five CT, four US, four angiography, and two MR studies were obtained in five patients with pathologically proven retroperitoneal malignant mesenchymoma. Results: Tumors were larger than 10 cm (n = 4), well-cimcumscribed and heterogeneous (n = 4), and with massive intratumorous calcifications (n = 3) on plain CT or US. Tumors showed heterogeneous enhancement on contrast-enhanced CT scans (n = 4) and moderate hypervascularity with heterogeneous staining on angiography (n = 3). Tumors were essentially hypointense on T1-weighted MR images (n = 2) and heterogeneous hyperintense on T2-weighted MR images (n = 2). Plain CT showed a fat-dense structure in a tumor in one patient. Conclusions: The radiologic findings of large expansile heterogeneous masses in the retroperitoneum, especially with massive calcifications, were considered to be typical of malignant mesenchymomas. RID=""ID="" Correspondence to: S. Suzuki

To assess tissue changes responsible for enhancement of the meninges adjacent to meningiomas on magnetic resonance (MR) images, the authors correlated the MR imaging characteristics of meningeal lesions seen before and after administration of gadolinium diethylenetriamine-pentaacetic acid (DTPA) with the appearance of these lesions on contrast material-enhanced computed tomographic (CT) images and with histopathologic findings in four patients. Histopathologic examination of meninges showed increased loose connective tissue, hypervascularity, and dilated vessels. There was neoplastic infiltration of the dura mater in two patients but it was restricted to the immediate junction of neoplasm and dura mater, with maximum peripheral extension within 1 mm of the tumor margin. In both patients the meninges were enhanced far beyond the neoplastic infiltration. The other two patients showed no infiltration of dura mater. These findings suggest that pathologic enhancement of meninges adjacent to meningioma after administration of Gd-DTPA mainly represents reactive changes to the neoplasm and does not necessarily indicate neoplastic involvement.

We propose a method for representing common concepts by fusing conceptual fuzzy sets (CFS) with ontology. We also describe a method of conceptual matching for retrieving information that meets a user's intentions. The matching is done based on the region of the ontological structure covered by the CFS representing the user's intention as well as on the original keywords. We apply the proposed conceptual-matching method to an agent, which selects music matching the tone of a text composition. Selection of music for two e-mail notes shows that the proposed system can select music that matches human feelings.

We have investigated the applicability of a simple and inexpensive osteoclastic assay system using bone-like apatite-coated polyethyleneterephthalate (PET) disks. A 1 microm thick apatite layer, uniform and homogeneous bone-mineral-like with no organic components, was made on PET disks using a biomimetic process. As substrates for an osteoclastic assay, these coated disks were compared with dentine as well as with bone-like or heat-treated apatite of various thicknesses on apatite- and wollastonite-containing glass ceramic (A-W GC) disks. The unfractionated bone cells, including osteoclasts, of a neonatal rabbit were seeded onto these substrates. By scanning electron microscopic examination, the resorption lacunae of the thick bone-like apatite clearly showed track-like shapes at various depths, similar to those of dentine although the border between the A-W GC and the apatite was unclear. In contrast, those of heat-treated apatite showed small and shallow shapes with irregular margins, quite different from those of dentine. By reducing the thickness of bone-like apatite to 1 microm as well as using PET as its substrate, the margins of the resorption lacunae became quite clear, and with the use of phase-contrast microscopy during culture, osteoclasts and resorption pits could be precisely observed. The resorbed area, easily measured with the aid of bright-field microscopy and an image analyzer, was found to have increased in a time-dependent manner and at the end of 4 days of culture was not statistically different from that of dentine.

Chondrocytes from 21-day-old rat fetal nasal cartilage were cultured in alginate beads for up to 20 days. It was found that chondrocytes retained their spherical shape and typical chondrocytic appearance. During the culture time, chondrocytes underwent differentiation, as demonstrated by the alkaline phosphatase-specific activity and rate of proteoglycan synthesis. Morphological data confirmed chondrocyte differentiation with the appearance of hypertrophic chondrocytes scattered in the alginate gel and a dense extracellular matrix containing filamentous structures and matrix vesicles. In addition, Northern blot analysis performed on day 8 of culture showed that chondrocytes cultured in alginate beads expressed type II collagen mRNA. The alginate bead method also appeared to be suitable for testing biomaterials, and the ready dissolution of the alginate beads by chelating agents provided a simple means for the rapid recovery of encapsulated chondrocytes. Powdered glass-ceramic particles entrapped in the alginate gel were colonized by chondrocytes, which then proliferated and formed a tissue similar to a true calcified cartilaginous structure. These results indicate that the alginate system represents a relevant model for studies of chondrogenesis and endochondral ossification. Furthermore, the encapsulation method could prove useful for studies of tissue-biomaterial interactions in an in vitro environment which more closely mirrors the cartilage matrix than other culture methods.

General transcription factor TFIID consists of TATA box-binding protein (TBP) and TBP-associated factors (TAF(II)s), which together play a central role in both positive and negative regulation of transcription. The N-terminal region of the 230 kDa Drosophila TAF(II) (dTAF(II)230) binds directly to TBP and inhibits TBP binding to the TATA box. We report here the solution structure of the complex formed by dTAF(II)230 N-terminal region (residues 11-77) and TBP. dTAF(II)230(11-77) comprises three alpha helices and a beta hairpin, forming a core that occupies the concave DNA-binding surface of TBP. The TBP-binding surface of dTAF(II)230 markedly resembles the minor groove surface of the partially unwound TATA box in the TBP-TATA complex. This protein mimicry of the TATA element surface provides the structural basis of the mechanism by which dTAF(II)230 negatively controls the TATA box-binding activity within the TFIID complex.

Evolution of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) into aggressive B cell lymphoma is thought to be a rare event and the cause of this transformation has not been fully elucidated. We describe two patients with AILD that progressed to aggressive large-cell lymphoma with a B cell phenotype. At presentation, the lymph nodes of both patients showed the typical features of AILD by hematoxylin-eosin staining. Immunohistochemical staining with monoclonal antibodies revealed positive staining of atypical cells with UCHL-1 and negative staining with L-26. In situ hybridization of EBV RNA showed rare positive cells in one patient and was negative in the other patient. At relapse, both patients showed systemic lymph nodes swelling, which is characteristic of diffuse large immunoblastic lymphoma. Single-cell analysis with monoclonal antibodies and immunohistochemical staining showed the monoclonal proliferation of B cells. Southern blot analysis of the lymph nodes showed a rearrangement in both patients of the Ig heavy chain gene and germ line configuration of the T cell receptor beta chain gene. Southern blot analysis using the EBV terminal repeat region probe detected clonal proliferation of EBV in the lymph nodes of both patients. In situ hybridization studies identified considerable EBV mRNA in both patients. These observations suggest that EBV proliferation plays an important role in the development of B cell lymphoma that arises from AILD. We suggest that infection or reactivation of EBV may occur in some patients with AILD, probably due to their immunodeficient state, and that this infection or reactivation is directly involved in the development of B cell lymphoma.

Tyrosinase is an antigen that is expressed by normal melanocytes as well as melanoma cells, against which responses by autologous T cells have been detected. Although CD4+ T cells play an important role in tumor immunity in animal tumor models, little information about CD4+ T-cell immunity against human tumors exists. Here, we report that CD4+ T cells from the peripheral blood of a patient with melanoma respond to synthetic peptides derived from nonmutated tyrosinase. T-cell clones were generated that recognized the tyrosinase p386-406 peptide when it was presented by the HLA-DR15 (DRB1*1501) molecule. The CD4+ T-cell clone also recognized autologous EBV-transformed B-lymphoblastoid cell lines that had been pulsed with the lysate of melanoma cells. The synthetic tyrosinase p386-406 peptide was capable of binding to HLA-DR15 (DRB1*1501) molecules on cell surface of DR15 homozygous cells. Thus, the finding that nonmutated tyrosinase peptides are immunogenic in a melanoma patient may provide the basis for the development of cancer immunotherapy, based on knowledge of synthetic tumor-associated peptide antigens.

Birch pollen is a very common cause of nasal allergy (pollinosis) not only in Scandinavia, Europe, Canada, and the northern part of the United States but also in Hokkaido, Japan. We have previously reported a positive association between the HLA-DR9 phenotype and the development of birch pollen allergy in Japanese subjects. However, there is little information about T cell epitopes of birch pollen which are presented by HLA class II molecules other than HLA-DR9. Therefore, we analyzed the difference in T cell epitope usage in patients who had HLA-DR9 versus those who did not. Seven Japanese patients with birch pollinosis were studied. Some groups of peptides representing T cell epitopes (Betula verrucosa; Bet VI peptides, p7-33, p23-46, p138-160) appeared to be shared by the majority, while another peptide (Bet VI p72-95) was recognized predominantly by patients who expressed HLA-DR9 and/or HLA-DQ3 molecules. Moreover, seven T cell clones and eight T cell lines were generated from two patients who did not have HLA-DR9 or HLA-DQ3. Using some of these T cell clones/lines, we investigated the relationship between HLA class II molecules and antigenic peptides. One of these T cell clones recognized antigenic peptides in the context of the HLA-DQ1 molecule. To our knowledge, this is the first indication that the epitope on Bet VI can be presented by the HLA-DQ molecule.

Human cathepsin K is a novel cysteine protease previously reported to be restricted in its expression to osteoclasts. Immunolocalization of cathepsin K in breast tumor bone metastases revealed that the invading breast cancer cells expressed this protease, albeit at a lower intensity than in osteoclasts. In situ hybridization and immunolocalization studies were subsequently conducted to demonstrate cathepsin K mRNA and protein expression in samples of primary breast carcinoma. Expression of cathepsin K mRNA was confirmed by reverse transcription PCR and Southern analysis in a number of human breast cancer cell lines and in primary human breast tumors and their metastases. As this protease is known to degrade extracellular matrix, including bone matrix proteins, it is possible that cathepsin K may contribute to the invasive potential of breast cancer cells, including those that metastasize to bone. Thus, cathepsin K may be a potential target leading to the design of novel drugs for cancer therapy.

Three types of bioactive bone cement (designated AWC, HAC, and TCPC), each consisting of bisphenol-alpha-glycidyl methacrylate (Bis-GMA)-based resin and a bioactive filler of apatite and wollastonite containing glass-ceramic (AW-GC), sintered hydroxyapatite (HA), or beta-tricalcium phosphate (beta-TCP) powder were made in order to evaluate the influence of the bioactive filler on the mechanical and biological properties of bone cement. The proportion of filler added to the cements was 70% w/w. The compressive, bending, and tensile strengths and the fracture toughness of AWC were higher than HAC and TCPC under wet conditions. The cements were evaluated in vivo by packing them into the intramedullary canals of rat tibiae. An affinity index that equalled the length of bone in direct apposition to the cement was calculated for each cement and expressed as a percentage of the total length of the cement surface. Histological examination of rat tibiae up to 8 weeks after implantation revealed that AWC had higher bioactivity than HAC and TCPC. New bone had formed along the AWC surface within 2 weeks, and at 4 weeks newly formed bone surrounded the cement surface almost completely. In HAC- and TCPC-implanted tibiae, immature bone had formed directly toward but not along the cement surface at 2 weeks. Observation of cement-bone interfaces showed that AWC had bonded to the bone via a so-called "Ca-P-rich layer"; the cement-bone interface remained stable, and the width of the CA-P-rich layer became thicker with time. On the other hand, in HAC- and TCPC-implanted tibiae, the cement surface fillers were surrounded by new bone and were absorbed gradually to become bone matrix. The cement-bone interfaces went inside the cement with time. Our results indicate that stronger interstitial bonding between the inorganic filler and the organic matrix resin in AWC lead to higher mechanical properties; results also indicate that the more stable cement-bone interface and higher bioactivity of AWC are due to early and uniform apatite formation on the cement surface.

To evaluate the usefulness of MIBI scintigraphy (MIBI) for parathyroid lesions, the detectability of lesions by MIBI was compared with that by Tl-Tc subtraction imaging, ultrasonography, CT and MRI in 56 histologically proved lesions. In neck lesions, ultrasonography (92%) and MIBI (85%) showed better detectability than those by the other three modalities. With MIBI, detectability was decreased for smaller parathyroid lesions that coexisted with thyroid disease. Among the five modalities, MIBI showed the highest detectability (88%) for ectopic or metastatic lesions. The smallest parathyroid lesions detected by MIBI were a parathyroid adenoma weighing 220mg and a parathyroid hyperplasia weighing 200mg. MIBI was thought to be more valuable for ectopic or metastatic parathyroid lesions.

A study was undertaken in rabbit tibiae to determine the effects of chemical treatments and/or surface-induced bonelike apatite on the bone-bonding ability of titanium (Ti) implants. Smooth-surfaced plates (10 x 10 x 2 mm) of pure Ti, alkalil- and heat-treated Ti, and bonelike apatite-formed Ti after the treatments were implanted into the tibial metaphyses of mature rabbits. The tibiae containing the implants were harvested at 4, 8, and 16 weeks after implantation and subjected to a tensile testing and histologic evaluation. Biomechanical results showed that both treated implants exhibited significantly higher failure loads compared with untreated Ti implants at all time periods. Histologic examination by Giemsa surface staining, contact microradiography (CMR), and scanning electron microscopy (SEM) in backscatter mode revealed that both treated Ti implants directly bonded to bone tissue during the early postimplantation period, whereas untreated Ti implants formed direct contact with the bone only at 16 weeks. SEM-electron-probe microanalysis (EPMA) examination showed a Ca-P-rich layer at the interface between the treated implants and bone, although the Ca-P-rich layer was not detected on the surface of untreated implants during observation periods. The results of this study suggest that chemical treatments may accelerate the bone-bonding behavior of titanium implants and enhance the strength of bone-implant bonding by inducing a bioactive surface layer on Ti implants.

Computed tomographic (CT) scans were performed in 179 patients with esophageal carcinoma to evaluate mediastinal lymph node metastasis. Histopathologic findings were compared with CT findings in a total of 7,218 resected lymph nodes. First, the criterion for lymph node metastasis on CT scans was 10 mm or more in long transverse diameter. The overall sensitivity and positive predictive value (PPV) were 19% (60 of 317 nodes) and 33% (60 of 180 nodes), respectively. Analysis of each of the eight subgroups of mediastinal nodes revealed that the PPV was more than 70% in node Nos. 105, 108, 110, and 112. In other subgroups, however, the PPV was less than 60%. Sensitivity was less than 50% in all eight subgroups. Second, the criterion for metastasis was 10 mm or more in short transverse diameter. The overall sensitivity and PPV were 8% (26 of 317 nodes) and 63% (26 of 41 nodes), respectively. Analysis of subgroups showed that the PPV in No. 106 nodes increased to 92%. In No. 106 nodes, use of a 5 mm criterion in long transverse diameter increased sensitivity to only 55%. Of the 317 histopathologically proven metastatic lymph nodes, 90 nodes (28%) were 10 mm or more in size, 112 (35%) were 5-10 mm, and 115 (36%) were less than 5 mm. Of the 6,901 non-metastatic lymph nodes, 473 nodes (7%) were 10 mm or more in size. Small (less than 5 mm in size) metastatic nodes were present in all eight subgroups. Among No. 107 and 109 nodes, large (10 mm or more in size) nonmetastatic nodes were prominent, resulting in low sensitivity and PPV. We conclude that CT does not provide an accurate assessment of metastatic versus non-metastatic mediastinal lymph nodes in patients with esophageal carcinoma.

The present authors previously showed that titanium metal forms a bone-like apatite layer on its surface in a simulated body fluid (SBF), when it has been treated with a NaOH solution to form a sodium titanate hydrogel layer on its surface. This indicates that the NaOH-treated Ti metal bonds to living bone. The gel layer as-formed is, however, mechanically unstable. In the present study, the NaOH-treated Ti metal was heat treated at various temperatures in order to convert the gel layer into a more mechanically stable layer. The gel layer was dehydrated and transformed into an amorphous sodium titanate layer at 400-500 degrees C, fairly densified at 600 degrees C and converted into crystalline sodium titanate and rutile above 700 degrees C. The induction period for the apatite formation on the NaOH-treated Ti metal in SBF increased with the transformation of the surface gel layer by the heat treatment. Ti metal heat treated at 600 degrees C, however, showed a fairly short induction period as well as high mechanical stability, since it was covered with a fairly densified amorphous layer.

Papillary adenoma of type II pneumocytes is a rare tumour. It is considered to be a benign neoplasm and is derived from immature cells in the bronchioloalveolar epithelium, however, its biological nature has not been elucidated. We report a case of an adenomatous tumour; a papillary adenoma of type II pneumocytes, which we regard as possessing malignant potential. Light microscopically, as well circumscribed, papillary tumour of predominantly cuboidal cells resembling type II pneumocytes was found, but Clara type and ciliated cells were also present. Immunohistochemically, the tumour cells reacted positively with antibodies to surfactant apoproteins (A, B), carcinoembryonic antigen, cytochrome P-450 1A1-2 and 2B1-2. Ultrastructurally, many osmiophilic lamellar bodies and electron-dense granules were demonstrated. Semi-serial sections revealed signs of transbronchial dissemination and vascular invasion. Morphometry using 12-dimensional cluster analysis disclosed features of the tumour cells which resembled those of pneumocyte type II adenocarcinoma. These findings suggest that the present case has some malignant characteristics and originates from immature bronchiolar or alveolar cells, with a potential to develop into both type II pneumocyte and Clara cell type adenocarcinomas.

Expression of major histocompatibility complex of lung cancer was examined to study the malignant potential of the tumor using immunochemical staining (anti-HLA class I monoclonal antibody; w6/32). Nuclear DNA contents and the labeling index of proliferating cell nuclear antigen (PCNA) were measured as well. Forty three advanced (p-stage IIIa) lung cancers resected by lobectomy (33 cases), pneumonectomy (9 cases), and segmentectomy (1 case) entered the study. Mediastinal lymph node dissection was performed in every case during the operation. Of the 43 cases, expression of HLA class I was positive in 17 and negative in 26. The patients with positive HLA expression showed significantly better prognosis than those with negative HLA expression in terms of 5 year survival (p0.01). The patients with aneuploid pattern and positive HLA class I expression had the best prognosis on the survival curve (p0.01). When the PCNA positive rate was high, the prognosis was poor. And the patients with negative PCNA and positive HLA class I expression had significantly better prognosis than the others (p0.01). These findings suggest that the expression of HLA class I on the tumor cells is an important prognostic factor in the patients with NSCLC.

This study was undertaken to clarify the effect of corticosteroids on the long-term clinical course of the early stage of progressive IgA nephropathy. The early stage of progressive IgA nephropathy was defined as having moderate proteinuria between 1 and 2 g/day, creatinine clearance values of 70 ml/min or more, and a histological severity score of 7 or more. The number of patients who fulfilled these three conditions during 12 years from 1972 and then were continuously followed up for 10 years or more in our renal unit was 46. Twenty of them received steroid treatment for an average period of 18 months, and the remaining 26 patients had no steroid treatment. The initial data of proteinuria, creatinine clearance values, frequency of hypertensive cases, and histological scores of 7 or more were not different between the two groups: 1.4 +/- 0.4 vs. 1.3 +/- 0.3 g/day, 85 +/- 14 vs. 88 +/- 13 ml/min, 25 vs. 38%, and 10.7 +/- 2.5 vs. 11.0 +/- 3.0, respectively. During the follow-up period of 10 years, the renal survival rate was significantly different between the two groups (100 vs. 84% 5 years after starting therapy and 80 vs. 34% 10 years later; p0.001). The final creatinine clearance values were significantly different between the two groups (54 +/- 35 vs. 20 +/- 29 ml/min; p0.005). On the other hand, the patient groups with mild histological changes or decreased renal function due to moderate proteinuria showed no significant differences in the final outcome. These results indicate that corticosteroids are beneficial in stabilizing the renal function for a long time during the early stage of progressive IgA nephropathy, although this study was not a randomized one.

A 68-year-old woman who had a history of Recklinghausen neurofibromatosis from 1964 showed nephrotic syndrome in 1989. Renal biopsy revealed membranous nephropathy. Various suspected causes of secondary membranous nephropathy were not found. Coexistence of Recklinghausen neurofibromatosis and membranous nephropathy has rarely been reported.

The most reliable factors predicting a long-term prognosis in individual progressive IgA nephropathy patients were evaluated. Ninety-eight cases who showed moderate to severe histological alterations (total score of 7 or more) and were continuously followed up for 10 years or more from the first biopsy were the subjects of this study. During the follow-up period of 10 years, 52 of the 98 cases went into hemodialysis treatment (HD). All 24 cases who had a higher total score of 17 or more, or severe renal dysfunction of less than 60 ml/min in their initial Ccr values went into HD. The remaining 74 cases who showed both a total score below 16 and initial Ccr values of 60 ml/min or more were divided into two groups in their clinical courses: 28 (group I) of the 74 cases went into HD and the other 46 (group II) did not. The degree of initial proteinuria was significantly different between groups I and II, but the degree of individual proteinuria was in a similar range from 0.5 to 2.5 g/day in most cases of both groups. Therefore, in order to clarify a more precise factor associated with the individual prognosis, the % duration of massive proteinuria (% DP) was calculated in individual cases. The % DP was more significantly different between groups I and II (82.6 +/- 26.1 vs 19.6 +/- 27.3%, p0.01). Moreover, all cases but one in group I showed 30% or more in % DP and 35 of 46 cases in group II showed 30% or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Release experiments with four drugs using representative pressure-sensitive adhesive (PSA) matrices were performed at 37 degrees C, and drug-PSA polymer interaction was determined by the Williams, Landel, and Ferry (WLF) equation. Two acrylic-type [2-ethylhexylacrylate and acrylic acid copolymer (2EHA/AA) or acrylamide copolymer (2EHA/AAm)], one rubber-type (a mixture of high and low molecular weight polyisobutylene), and one silicone-type PSA were used, and dipropylphthalate (PP), aminopyrine (AMP), ketoprofen (KP), and lidocaine (LC) were selected as model drugs because of their molecular size and functional groups. PSA containing acrylic acid (2EHA/AA) strongly interacted with the amide LC, with the tertiary amine AMP, and with the carboxylic acid KP; PSA-containing acrylamide (2EHA/AAm), however, did not interact with LC or AMP, although it markedly interacted with KP. The rubber-type and silicone-type PSAs, composed of no or only a few polar functional groups, did not interact with any of the drugs used in this experiment. Therefore, the diffusion coefficient of the drugs through PSA was influenced by the drug-PSA polymer interaction, and the extent of this interaction can be estimated by the relationship between the drug concentrations in the PSA and their diffusion coefficients.

A patient is described with severe IgA nephropathy associated with psoriatic arthritis, idiopathic interstitial pneumonia and brain hemorrhage that developed serially over one and a half years. The histological findings of the renal biopsy showed severe endo- and extracapillary proliferative glomerulonephritis. Massive IgA deposits were observed by immunofluorescence not only in the mesangium but also along the capillary walls. Electron microscopy revealed abundant electron-dense deposits in the mesangial and subendothelial areas. The overlapping or coexistence of these conditions has rarely been reported.

A TATA box-binding initiation factor, TFIID, plays a central role in the transcriptional regulation by activators. Using anti-TFIID tau (a TATA box-binding component of native TFIID) immunoaffinity chromatography, nine polypeptides (230, 110, 85, 62, 58, 42, 28, 22, and 21 kDa) were identified as native Drosophila TFIID components that are tightly associated with TFIID tau. To verify the functional activity of the purified TFIID complex, template DNA and other transcription factors were reconstituted with purified TFIID bound to the antibody-Sepharose matrix. Immobilized TFIID mediated not only basal transcription but transcriptional activation by upstream stimulatory factor (USF). On the other hand, recombinant TFIID tau immobilized on the same antibody-Sepharose matrix could not mediate activation by USF. These results suggest that one or more of these additional polypeptides are required as functional TFIID subunits for activator-dependent transcription in conjunction with TFIID tau. As further evidence of the relevance of the Drosophila TFIID components identified in this analysis, including the previously unrecognized p230 (Dynlacht, B. D., Hoey, T., and Tjian, R. (1991) Cell 66, 563-576), protein blot analysis showed that TFIID tau interacts specifically and exclusively with p230. This suggests that p230 is an integral subunit of TFIID and that it may play a major role in tethering other subunits to TFIID tau.

A strain of Aeromonas hydrophila was found to show prolyl endopeptidase activity. The enzyme gene was cloned and expressed in Escherichia coli JM83. A 12 kbp EcoRI fragment containing the enzyme gene was subcloned at the HincII site of pUC19 to construct plasmid pAPEP-3 with a 3.5 kbp insert. E. coli JM83 transformed with this plasmid showed about 100-fold higher activity than the parent Aeromonas. Analysis of the nucleotide sequence of the insert revealed that the mature enzyme-encoding sequence starts just after the ATG initiation codon of the open reading frame. The enzyme was a single polypeptide composed of 689 amino acid residues with a molecular weight of 76,383. It showed properties very similar to those of Flavobacterium prolyl endopeptidase, except that the isoelectric point was 5.5. The amino acid sequence was 56 and 41% homologous to those of Flavobacterium and porcine brain prolyl endopeptidases, respectively. From a survey of sequence homology with other members of the prolyl endopeptidase family, the amino acid residues involved in the catalytic triad were deduced to be Ser-537, His-656, and Asp-512 (or Asp-621).

Magnetic resonance (MR) images and conventional radiographs were compared in 142 hips with avascular necrosis, and a staging system for the disease based on MR imaging was developed. MR images were classified into three patterns: class I: a band of low signal intensity, class II: an area of low signal intensity with internal spot (s) of high signal, and class III: an area of low signal intensity without internal spots of high signal. Most MR class I lesions were in radiographic stage I (normal) or II (sclerotic or cystic changes without collapse). Most MR class II lesions were in radiographic stage III (segmental collapse), and most MR class III lesions were in stage III or IV (secondary degenerative changes). The MR image classification was closely correlated with radiographic staging (p0.01, using chi square test). We considered that this classification closely reflected the different stages of the disease according to the histopathology of the bone marrow.

For the purpose of an effective management of patients at high risk for nontraumatic avascular necrosis of the femoral head (ANFH), it is expedient to examine the femoral heads of patients most likely to undergo subsequent segmental collapse. The purpose of this study was to evaluate the ability of magnetic resonance imaging (MRI) and radionuclide bone scanning (RS) to predict segmental collapse of the femoral head at the roentgenographically normal stage. Fifty-five hips in 37 patients at risk for ANFH and having normal roentgenograms were included in this study. Magnetic resonance imaging was performed in all hips and RS in 29 hips. The patients were observed during a period of more than two years without any invasive intervention, and nine femoral heads manifested collapse during this period. Predictive values for subsequent segmental collapse of a positive test of MRI and RS were 31% and 13%, respectively, whereas those indicative of a negative test were 100% and 76%, respectively. Magnetic resonance imaging was more useful than RS in detecting patients in need of intensive follow-up examination. In particular, a bandlike area of low intensity that traversed the femoral head in midcoronal slices on MR images seemed to be a significant indicator of subsequent collapse.

The prolyl endopeptidase [EC 3.4.21.26] gene of Flavobacterium meningosepticum was cloned in Escherichia coli with the aid of an oligonucleotide probe which was prepared based on the amino acid sequence. The hybrid plasmid, pFPEP1, with a 3.5 kbp insert at the HincII site of pUC19 containing the enzyme gene, was subcloned into pUC19 to construct plasmid pFPEP3. The whole nucleotide sequence of an inserted HincII-BamHI fragment of plasmid pFPEP3 was determined by the dideoxy chain-terminating method. The purified prolyl endopeptidase was labeled with tritium DFP, and the sequence surrounding the reactive serine residue was found to be Ala (551)-Leu-Ser-Gly-Arg-*Ser-Asn(557). Ser-556 was identified as a reactive serine residue. The enzyme consists of 705 amino acid residues as deduced from the nucleotide sequence and has a molecular weight of 78,705, which coincides well with the value estimated by ultra centrifugal analysis. The amino acid sequence was 38.2% homologous to that of the porcine brain prolyl endopeptidase [Rennex et al. (1991) Biochemistry 30, 2195-2203] and 24.5% homologous to E. coli protease II, which has substrate specificity for basic amino acids [Kanatani et al. (1991) J. Biochem. 110, 315-320].

Eighteen patients with the predisposing factors for aseptic necrosis of the femoral head were followed up for more than two years after the initial magnetic resonance (MR) imaging. At the time of the initial examination, 24 femoral heads showed abnormal low-intensity areas on MR images without abnormal findings on plain radiographs. Among them, six femoral heads collapsed in the follow-up period. The initial mid-coronal T1-weighted MR images of these femoral heads had shown characteristic findings, that is, band-shaped low-intensity areas with the lateral end not covered by the acetabulum. Subchondral fracture of the femoral head occurred in the vicinity of the lateral end of the band. The findings of initial MR imaging seem to predict subsequent collapse of the femoral head.

An apatite- and wollastonite-containing glass-ceramic (A.W-GC) has been reported to form a tight bond with living bone through an apatite layer formed on its surface. This layer is considered to be formed by dissolution of Ca2+ and HSiO3- ions from the glass-ceramic into the surrounding body fluids. In order to confirm this proposed mechanism for the surface reaction of A.W-GC, three kinds of glass in the systems CaO-SiO2, CaO-SiO2-CaF2, and CaO-SiO2-P2O5 were implanted into the tibiae of rabbits for 3 or 8 weeks. Contact microradiography and SEM-EPMA showed that all three kinds of glass formed a Ca,P-rich layer in combination with a Si-rich layer on their surfaces within 3 weeks and formed a direct bond with bone via these layers. The detaching test, performed 8 weeks after implantation, showed that the loads required to detach the implants from the bone were almost equal for the phosphorus-free and the phosphorus-containing glasses. It was concluded that even P2O5-free CaO.SiO2 glass formed a Ca,P-rich layer on its surface and bonded tightly with living bone. If glasses and glass-ceramics release at least Ca2+ and HSiO3- ions, this would be sufficient for them to form the Ca,P-rich layer on their surfaces in vivo, enabling them to bond directly with bone.

MRI of four patients with spontaneously ruptured middle cranial fossa dermoids was reviewed. In all patients, MRI clearly demonstrated the primary tumour, and T1-weighted images showed high signal areas with fatfluid levels in the ventricles(3/4) and/or high signal spots in the cerebrospinal fluid (CSF) spaces(4/4). Signal intensity of these areas decreased as images became more heavily T2-weighted, in accordance with the known MRI characteristics of fat. MRI was very sensitive for detection of small fat droplets within CSF and for demonstrating their exact distribution, especially on T1-weighted images.

We present a case of intrahepatic cystic cholangiocarcinoma with unusual radiologic appearance. Computed tomography, ultrasonography, and magnetic resonance imaging showed a cystic mass with thick wall, that mimicked liver abscess, and cystic or necrotic metastasis. The fluid in the cyst was not mucinous and was negative bacteriologically. Histologic examination showed cholangiocarcinoma with large cavities resulting from necrosis.

We successfully controlled hypertension of a 48-year-old female by embolizing metastatic pheochromocytoma of the liver. Although transarterial embolization of the hepatic artery was uneventful, the patient soon developed severe hypertension and tachycardia which were controlled medically. Symptoms subsided within 10-20 days. Follow-up CT showed reduction of the liver mass.

The coronary vein has few variations. We describe a case of coronary vein with an unusual course. In this case, the coronary vein entered the umbilical portion of the left portal vein directly, whereas it usually flows into the portal trunk or splenic vein. The angiographic appearance is presented.