The cell surface-expressed HSC70-like molecule preferentially reacts with the rat T-cell receptor Vdelta6 family.

We previously showed that the cell surface-expressed Mr 70,000 heat shock cognate (hsc70, a constitutively expressed member of the hsp70 family) protein-like molecule (#067 molecule) interacts with rat CD3+, CD4-, CD8-, T-cell receptor (TCR)alphabeta-, natural killer recetor-P1- T cells. This 70hsc-like molecule was also suggested to present cellular peptide antigens to these T cells. In the present study, we identified the genetic structure of the TCR by establishing T-cell hybridomas between these T cells and mouse BW5147 cells. Our data indicated that these T cells preferentially used TCRs with the Vdelta6 family. Analysis of the nucleotide sequence of the CDR3 junctional portion showed that there are substantial diversities, with insertion of seven to nine amino acid residues. These data provide indirect evidences for our hypothesis that an hsc70-like molecule could be presented together with cellular peptide antigens to particular T cells with TCR gammadelta chains. Since the expression of this hsc70-like #067 antigen on the cell surface is usually induced along with cell transformation by activated oncogenes, T cells with the TCR Vdelta6 family are likely to contribute to host resistance to tumor cells.

Insulin production in a neuroectodermal tumor that expresses islet factor-1, but not pancreatic-duodenal homeobox 1.

We studied a 60-yr-old female with a brain tumor who showed severe symptoms of hypoglycemia (plasma glucose, 2.2 mmol/L) and hyperinsulinemia (1.28 nmol/L) after radiotherapy. The cystic brain tumor contained proinsulin and insulin at concentrations of 13.6 and 1.22 nmol/L, respectively. Immunohistochemical studies showed the tumor cells were ectodermal in origin but not endodermal, based on three diagnostic features of neuroectodermal tumors 1) pseudorosette formation noted under light microscopy, 2) finding of a small number of dense core neurosecretory granules on electron microscopy, and 3) positive immunostaining for both neuronal specific enolase and protein gene product 9.5. These cells also expressed the transcription factor, neurogenin-3, NeuroD/beta 2, and islet factor I, which are believed to be transcription factors in neuroectoderm as well as in pancreatic islet cells, but not pancreatic-duodenal homeobox 1, Pax4, or Nkx2.2. In addition, they did not express glucagon, somatostatin, or glucagon-like peptide-1. Our results show the presence of proinsulin in an ectoderm cell brain tumor that does not express the homeobox gene, pancreatic-duodenal homeobox 1, but expresses other transcription factors, i.e. neurogenin3, NeuroD/beta 2, and islet factor-1, which are related to insulin gene expression in the brain tumor.

Medicinal foodstuffs. XVIII. Phytoestrogens from the aerial part of Petroselinum crispum MIll. (Parsley) and structures of 6"-acetylapiin and a new monoterpene glycoside, petroside.

In the course of our screening for natural estrogenic compounds from Occidental medicinal herbs, the extracts of several herbs were found to show proliferative activity in MCF-7 (an estrogen-sensitive breast cancer cell line). Among these active herbs, the methanolic extract from the aerial parts of Petroselinum crispum (parsley) showed potent estrogenic activity, which was equal to that of isoflavone glycosides from soybean. Through bioassay-guided separation, we isolated several flavone glycosides and a new flavone glycoside, 6"-acetylapiin, with estrogenic activity together with a new monoterpene glucoside, petroside. The structures of 6"-acetylapiin and petroside were characterized by the chemical and physicochemical evidence. Estrogenic activities of these flavone glycosides were found to be enhanced by removal of their glycoside moieties. The EC50 values (concentration needed to enhance the MCF-7 proliferation 50% compared to non-estrogen treated cell) of their aglycones are as follows, apigenin (1.0 microM), diosmetin (2.9 microM), and kaempferol (0.56 microM). The estrogenic activities of these flavones are nearly equal to those of the isoflavones, daidzein (0.61 microM) and genistein (0.60 microM). The methanolic extract of parsley, apiin, and apigenin restored the uterus weight in ovariectomized mice when orally administered for consecutive 7 days.

Effects of preoperative chemotherapy and radiation therapy on human bronchial blood flow.

OBJECTIVE: We investigated the relationship between bronchial mucosal blood flow around the area of lung resection and the state of healing of the bronchial stump in patients after chemotherapy with or without radiation therapy. METHODS: Ninety patients with primary lung cancer were divided into the following 3 groups: group A, 72 patients who had no preoperative therapy; group B, 10 patients who had chemotherapy; and group C, 8 patients who had chemoradiation (60 Gy) therapy. Bronchial mucosal blood flow was measured preoperatively, intraoperatively, and postoperatively (days 8-10) with a laser Doppler flowmeter. RESULTS: In groups A and B bronchial mucosal blood flow was preserved sufficiently around the surgical site, and the healing of the bronchial stump was satisfactory. On the contrary, preoperative blood flow in group C was 70% of the preoperative value in group A and decreased further intraoperatively. Healing of the bronchial stump was poor, and a bronchopleural fistula occurred in one patient of group C. CONCLUSION: Preoperative chemoradiation therapy may adversely affect bronchial mucosal blood flow and healing of the bronchial stump, although lymphadenectomy and preoperative chemotherapy had little effect. It is recommended that the bronchial stump should be covered with pedicled viable tissue after chemoradiation therapy for prophylaxis against bronchial complications.

Acquired digital arteriovenous malformation: a report of six cases.

Arteriovenous malformation (AVM) is usually congenital, but an acquired type is also known, of which most are due to a previous injury. We report six patients with acquired digital AVM, all having a small patch of AVM localized to the tip of one finger, and therefore quite different from ordinary AVM which consists of a large pulsatile mass. Histologically, dilated venous and arterial vessels were present in the dermis. Tumour-like growth was absent; thus, these six cases could be differentiated from arteriovenous haemangioma. Because of the characteristic anatomical site, unique clinical manifestations and histology, this appears to be a new and distinctive entity.

Malignant solitary fibrous tumor in the pleura.

We present a case of malignant solitary fibrous tumor of the pleura in an asymptomatic 75-year-old man. A needle biopsy specimen revealed a solitary fibrous tumor of the pleura with suspected. The tumor was resected and the final diagnosis was a malignant solitary fibrous tumor. At one-and-a-half years later, the patient has no clinical or radiological evidence of recurrence. The propriety of a needle biopsy for preoperative diagnosis is discussed.

Neuroblastoma resection in an adult with a 10-year history of chest-mass shadow.

Neuroblastoma is rare in adults. We encountered this tumor in an asymptomatic 21-year-old man with a 10-year history of a mass-like shadow in chest radiography. Diagnosis was confirmed after resection, and 60 Gy radiation therapy was started. One year later, the patient has no clinical or radiological evidence of recurrence.

[Thoracoscopic pleural biopsy under local anesthesia using a 2 mm laparoscope].

Thoracoscopy is indicated in patients with undiagnosed effusion after conventional methods. It has been usually performed under general anesthesia or using a thoracoscope with a thoracoscope with a diameter over 5 mm. However, it is an invasive diagnostic technique. We evaluated the feasibility of thoracoscopic pleural biopsy under local anesthesia using a 2 mm laparoscope. Six patients with a pleural effusion of unknown etiology after conventional methods, underwent thoracoscopy under local anesthesia. A 2 mm laparoscope and biopsy forceps (2 mm Minisite, United States Surgical Corp., USA) was used in all patients. Pleural fluid was removed, and the thoracic cavity was inspected. Thoracoscopic intercostal blocks were performed with 1% lidocaine, and then a biopsy was performed. The biopsy specimen was sent for histopathology. Three patients were shown to have carcinomatous pleurisy, two of them with localized lesions less than 10 mm. In the remaining three patients, non-specific diagnoses were made, but long-term follow-up revealed no malignant pleural disease. Although the pictures obtained using a 2 mm laparoscope were inferior in quality, they were adequate for the detection of malignant lesions in the pleural cavity. There were no procedure-related complications. These findings suggest that thoracoscopy using a 2 mm laparoscope is (1) a useful diagnostic tool in cases of pleural malignancy; (2) a minimally invasive method with the advantage of being easily performed under local anesthesia. Thus, thoracoscopic pleural biopsy using a 2 mm laparoscope appears to be useful for undiagnosed pleural effusion.

Loricrin gene mutation in a Japanese patient of Vohwinkel's syndrome.

Vohwinkel's syndrome (VS) is a rare, dominantly inherited keratoderma with pseudoainhum. Recently, a mutation in loricrin gene has been reported in two VS families of British extraction. In the present study, we examined the loricrin gene mutation in a Japanese VS patient. The patient was a 20-year-old woman. She had palmoplantar keratoderma, constricting bands encircling all the fingers, fifth toes, wrist, and neck. She also had generalized mild ichthyosis and suffered from acoustic impairment. Her parents and a brother showed no skin abnormality. Histopathology of the patient revealed hyperkeratosis with parakeratosis, together with hypergranulosis. The clinical and histopathological findings were consistent with an ichthyotic (or Camisa) variant of VS. The sequence analysis of the loricrin gene revealed that the patient had a heterozygous mutation identical to that described in previous reports, i.e. a G insertion producing a frameshift at codon 231 with an abnormal C-terminus. These results clearly demonstrate that a common loricrin gene mutation underlies VS in different ethnic groups.

Differential interleukin 12 responsiveness for interferon gamma production in advanced stages of cancer patients correlates with performance status.

Interleukin 12 (IL-12) has been shown to exhibit potent antitumor activity in murine tumor models through various mechanisms including the capacity to stimulate IFN-gamma production by T cells and natural killer cells. The aim of the present study was to examine the efficacy of IL-12 in inducing IFN-gamma secretion in cancer patients. A comparison was made between healthy individuals who served as controls and cancer patients for IFN-gamma production induced after the stimulation of whole blood samples with 1000 pg/ml IL-12. Samples from all healthy individuals showed positive IL-12 responsiveness. Approximately half of the samples from patients displayed levels of IFN-gamma production comparable to those observed for controls, whereas the rest of the samples exhibited almost-null responses. The incidences for reduced capacity of IFN-gamma production and null IL-12 responsiveness in cancer patients at all cancer stages or at a given advanced stage (stage IV) increased along with performance status. However, these correlated with neither the number of lymphocytes contained in the blood samples nor the tumor types. When peripheral blood mononuclear cells were isolated from patient blood samples showing null/marginal responses, and their responsiveness was examined, 7 of 13 samples exhibited positive responses. Whereas enhanced tumor necrosis factor alpha production was also observed in some patients after IL-12 stimulation, the elevation of tumor necrosis factor alpha was induced only in blood samples that showed IL-12-stimulated IFN-gamma production. These observations indicate that a remarkable difference exists in IL-12 reactivity among cancer patients, and that differential IL-12 responsiveness depends largely on performance status.

Susceptibility to Infection Due to Diminished Interferon-α-Producing Capacity in Patients with Refractory Anemia with Excess of Blasts or Refractory Anemia with Excess of Blasts in Transformation.

Peripheral whole blood cells from normal subjects and from 8 patients with refractory anemia with excess of blasts (RAEB) and one patient with RAEB in transformation (RAEB-t) were studied to ascertain their interferon (IFN)-α-producing capacity. This capacity was determined by time-resolved immuno-fluoroassay 20 hrs after the blood cells had been incubated with 500 HA/ml of Sendai virus. The mean IFN-α-producing capacity in the peripheral whole blood cells of 35 normal males was 8718 ± 4683 IU/ml, while that of 49 normal females was 7549 ± 4731 IU/ml; not a significant difference. All of the RAEB and RAEB-t patients examined showed a significantly low (<2500 IU/ml) IFN-α-producing capacity in the peripheral whole blood cells. In addition, the levels of IFN-α-producing capacity in 1 ml cell suspension containing 1 x 10(6) peripheral mononuclear blood cells were markedly lower in all 5 RAEB patients and the RAEB-t patient examined than those in the normal subjects, when 5 HA of Sendai virus was used. The activities of natural killers were lower in the RAEB/RAEB-t patients than those in the normal subjects. These findings suggest that IFN-α-producing capacity is diminished in the peripheral whole blood cells of RAEB and RAEB-t patients, and great care is advised regarding infection by virus and bacteria in treatment of these patients.

Determination of interferon-alpha-producing capacity in whole blood cultures from patients with various diseases and from healthy persons.

To assess the clinical value of determination of the interferon (IFN)-producing capacity of patients, IFN production induced by Sendai virus (HVJ) in vitro was measured in cell cultures of whole blood from patients with various diseases. IFN production in patients with lung cancer, myelodysplastic syndromes, noninsulin-dependent diabetes mellitus, pulmonary tuberculosis, and asymptomatic HIV-1 infection was lower than that in healthy persons. Furthermore, periodic measurements of IFN production revealed decreasing IFN producing capacities in patients with lung cancer with progression of the tumor stage. However, increased IFN-producing capacities were observed in patients with tuberculosis after standard therapy. Further experiments showed that the main type of IFN induced in whole blood cultures was IFN-alpha, and decreased IFN production in patients did not result from a decreased number of leukocytes but rather from an impairment of cellular IFN production. The evaluation of IFN production in whole blood cell cultures may be a feasible method of assessing the impaired immune status.

Involvement of peptide antigens in the cytotoxicity between 70-kDa heat shock cognate protein-like molecule and CD3+, CD4-, CD8-, TCR-alpha beta- killer T cells.

We previously reported that the 70-kDa heat shock cognate protein-like molecule (hsc70) is expressed on the cell surface along with the neoplastic transformation of rat fibroblast and that this molecule is recognized by CD3+, CD4-, CD8-, NKR-P1-, and TCR-alphabeta- T (DNT) killer cells in an MHC class I-unrestricted fashion. We investigated the mechanism of interaction between hsc70 and DNT cells. H-ras oncogene-transformed rat fibrosarcoma W31 cells expressed hsc70 on the cell surface in almost the same density when the cells were growing in a conventional 5% FCS (5% W31) as when the cell growth was inhibited in the cultivation with 1% FCS (1% W31). However, DNT cells lysed only 5% W31, but not 1% W31. Since these observations suggest that certain peptide Ags of the fast growing W31 cells may play a role in the interaction between hsc70 and DNT cells, we pulsed 1% W31 cells with trifluoroacetic acid (TFA)-extracted fast growing W31 tumor Ags of less than 3000 Da in molecular size. We also pulsed 1% W31 with TFA-extracted Ags from moderate growing W14 tumors and whole fetus tissues. Our data indicated that DNT cells were clearly cytotoxic to 1% W31 pulsed only with TFA-extracted Ags from W31 tumors. Anti-rat hsc70 mAb completely blocked this cytotoxicity. In addition, pronase K treatment of Ags clearly inhibited the cytotoxicity by DNT cells. Taken together, these data suggest that the complex of peptide Ag and hsc70 is involved in the cytotoxic mechanism between hsc70 and DNT cells.

Hyaline cell-rich chondroid syringoma: epithelial nature of the hyaline cells.

We report a case of hyaline cell-rich chondroid syringoma arising in the skin on the left side of the neck. The tumor was composed exclusively of hyaline cells arranged in a predominantly thick trabecular pattern. Ductal structures of various sizes in the tumor were composed of eosinophilic cuboidal cells showing transition to hyaline cells. Immunohistochemically, the hyaline cells were positive for cytokeratin, S-100, and vimentin, although the best marker for myoepithelial differentiation, alpha-smooth muscle actin, was negative. As is the case with plasmacytoid monomorphic adenomas of the salivary gland and some reported cases of hyaline cell-rich chondroid syringoma, hyaline cells in the present tumor similarly lacked any evidence of myoepithelial differentiation. These immunohistochemical findings reveal that the hyaline cells in the present tumor were epithelial.

Induction of erythroid-specific gene expression in lymphoid cells.

Erythropoietin (Epo) is a cytokine which specifically regulates differentiation and proliferation of erythroid progenitor cells. We report here that Epo receptor expressed in interleukin 3-dependent lymphoid Ba/F3 cells transmits both differentiation and growth signals. Epo stimulation of these cells leads to activation of transcription and/or translation of the erythroid-specific transcription factors GATA-1 and SCL, followed by the accumulation of both alpha- and beta-globin chains. These results suggest that expression and activation of the Epo receptor regulates erythroid-specific gene expression and might play a role in determining a cell lineage in vivo and that GATA-1 and SCL may exert their effects after Epo binds to its receptor. It was further found that chimeric receptors composed of extracellular domains of Epo receptor and cytoplasmic domains of interleukin 2 or interleukin 3 receptors could also induce erythroid-specific gene expression in Ba/F3 cells. Taking these data together with previous observations, we conclude that interaction of the extracellular domains of the Epo receptor with other membrane components is essential for transmission of both the erythroid differentiation and the growth signals.

Cellular stress- and transformation-associated cell surface antigens expressed on human and rodent tumor cells.

Stress-induced proteins may have significant roles in anti-tumor resistance. To clarify the immunobiological roles of these proteins, we first developed monoclonal antibody (mAb) H1A that detects the HeLa cell-surface antigens whose expression was enhanced by treatment of the cells with physico-chemical stressors, such as heat, H2O2 and tumor necrosis factor. H1A (IgM) detects several molecules with mol. wt. 30, 43, 75, 90, 100, 120 and 150 kDa in Western blot analysis of HeLa cell lysates. Although the antigen was constitutively expressed on the HeLa cell surface, the cell-surface expression of H1A-defined antigen was rapidly enhanced (within 1 h) after heat treatment of HeLa cells. H1A antigens were also transformation-associated, since 1) the activated oncogene-transformed fibroblasts expressed the antigens, but parental nontransformed cells did not, and 2) certain human neoplastic but not normal cells strongly expressed the antigens. Furthermore, H1A mAb also partly blocked the cytotoxicity of purified protein derivatives-stimulated human T cell receptor gamma delta-type T cells towards HeLa cells. Taken together, these data indicate that H1A-defined stress-inducible proteins may play a vital role in anti-tumor resistance by cytotoxic T cells.

Erythropoietin receptor binds to Friend virus gp55 through other membrane components.

Direct interactions of Friend spleen focus-forming virus glycoprotein gp55 with either erythropoietin receptor (EpoR) or interleukin (IL)2 receptor beta chain (IL2R) (but not with IL3 receptor) have been reported to induce factor-independent prolonged proliferation of erythroid or lymphoid cells. In order to clarify the molecular mechanism by which EpoR-gp55 complex transmits an aberrant growth signal in the absence of erythropoietin, various chimeric receptors constituted with IL2R, EpoR or IL3 receptor were constructed. It was found that coexpression of gp55 and the chimeric receptors containing the cytoplasmic domains of EpoR and the extracellular domains of IL3 (or IL2) receptor in IL3-dependent Ba/F3 cells results in factor-independent growth. Since gp55 in cell membrane has only a two amino acid tail in the cytoplasmic domains and thus cannot interact with EpoR in cytoplasm, our data suggest that gp55 does not bind EpoR directly but interacts with EpoR through third membrane component(s).

Spontaneous hemopneumothorax with aberrant vessels found to be the source of bleeding: report of two cases.

We report herein our experience of two cases of spontaneous hemopneumothorax in which the source of bleeding was found to be aberrant vessels. Both patients were successfully treated by early thoracotomy. Case 1 was a 23-year-old female in whom chest X-ray revealed an air-fluid line and a bulla with a narrow restiform shadow connecting the pleural cupola. Angiography clearly visualized aberrant vessels branching from the costocervical trunk, distributed in and around the bulla in the apex of the lung, being the possible source of bleeding. These aberrant vessels were confirmed at surgery and resected. Case 2 was a 56-year-old male who underwent thoracotomy for persistent bleeding. At surgery, a continuously bleeding vessel from the pleural cupola was seen and ligated. The remnant of the vessel was located in the apex of the lung, and resected with the bulla. Thus, the rare entity of a congenital aberrant vessel lying concealed as a possible source of bleeding should be borne in mind.

[Quality of life for older people under oncological treatment].

Recently, an argument over the medical treatment of older patients has arisen in the field of clinical oncology. In the past oncological treatment has been geared to young and middle-aged people. Currently, oncological treatment takes the peculiarities of older people into consideration. Firstly, it highlights the multidimensionality of Quality of Life (QOL) as an important element, with subjectivity the second element. This notion has gained a worldwide consensus. The domain of "multidimensionality" consists of: 1. Physical status and functional abilities 2. Psychological status and well-being 3. Social interaction 4. Economic status and factors With these factors in mind, different questions are asked, depending on the condition of each patient, in order to let the patient form his/her own judgment on possible medical treatment. However, it is sometimes difficult for older people to make such judgments due to problems such as depression or their diminishing mental ability. Also, it is impossible to define life satisfaction indiscriminately without regard to individual outlook. QOL for older people is generally characterized by "individuality" which includes: 1) A person's integrity; 2) independence; and 3) autonomy. Though these elements are taken into account in adopting the above-mentioned methodology, the field of clinical oncology's two concepts of QOL still apply in principle. Flexibility to put emphasis on different elements of the domain will be necessary. Even though QOL for older people is a matter of subjective judgment, the "sound judgment of professionals" (objective and scientific judgment of caregivers) can be adopted in cases when there is difficulty in communication.(ABSTRACT TRUNCATED AT 250 WORDS)