High Positive Incidence Research Articles

Computational and experimental investigation into aerodynamic interference between slender bodies in supersonic flow

Aerodynamic interference can occur between high-speed bodies when in close proximity. A complex flowfield develops where shock and expansion waves from a generator body impinge upon the adjacent receiver body and modify its aerodynamic characteristics. The aims of this paper are to validate a computational prediction method, to use the predicted solutions to interpret the measured results and to provide a deeper understanding of the associated flow physics. The interference aerodynamics for two slender bodies were investigated through a parametric wind tunnel study where the effect of axial stagger was investigated for different receiver body incidence angles. Measurements included forces and moments, surface pressures and shadowgraph visualisations. Supporting computational predictions provided a deeper understanding of the underlying aerodynamics and flow mechanisms. Good agreement was found between the measured and predicted interference loads and surface pressures for all configurations. The interference loads are strongly dependent upon the axial impingement location of the primary shockwave. These induced interference loads change polarity as the impingement location moves aft over the receiver. Distinct interference characteristics are observed when the receiver is placed at high positive incidence, where the impinging shock has a strong effect on the crossflow separation location. Overall, the observed interference effects are expected to modify the subsequent body trajectories and may increase the likelihood of a collision.

Therapeutic response to induction chemotherapy and prognosis of patients with inflammatory breast cancer in respect to HER2 and hormonal status.

e11517 Background: IBC presents the most aggressive form of BC with high incidence of HER2 positivity (+) and low rate of complete remission to induction chemotherapy (iCT). It is initially inopera...

Large Eddy Simulation of a Controlled Diffusion Compressor Cascade

In this research a Controlled Diffusion (CD) compressor cascade stator blade is simulated at a Reynolds number of ∼700,000, based on inflow velocity and chord length, using Large Eddy Simulation (LES). A wide range of flow inlet angles are computed, including conditions near the design angle, and at high negative and positive incidence. At all inlet angles the surface pressure distributions are well-predicted by the LES. Near the design angle the computed suction side boundary layer thickness agrees well with experimental data, whilst the pressure side boundary layer is poorly predicted due to the inability of LES to capture natural boundary layer transition on the present grid. A good estimation of the loss is computed near the design angle, whilst at both high positive and negative incidences the loss is less well predicted owing to discrepancies between the computed and experimental boundary layer thickness. At incidences above the design angle a laminar separation bubble forms near the leading edge of the suction surface, which undergoes a transition to turbulence. Similar behaviour is noted on the pressure surface at negative incidence. At high negative incidence contra-rotating vortex pairs are found to form around the leading edge in response to an unsteady stagnation line across the span of the blade. Such structures are not apparent in time-averaged statistical data due to their highly-transient nature.

Upper aerodigestive tract lymphoma in Taiwan

AimTo better understand the spectrum of primary lymphomas in the upper aerodigestive tract, a common site of extranodal lymphoma.Materials and methodsLymphoma cases diagnosed at an institution in southern Taiwan from...

Observations of Transition Phenomena on a Controlled Diffusion Compressor Stator With a Circular Arc Leading Edge

Laminar-turbulent transition behavior is studied near the leading edge of an outlet stator blade in a low-speed 1.5-stage axial-flow research compressor. The stator is a typical controlled diffusion design with a circular arc leading edge profile. Slow-response surface pressure distribution measurements are compared with numerical predictions from the quasi-two-dimensional flow solver, MISES. These both show a strong flow acceleration around each side of the circular arc, followed by a rapid deceleration near each blend point of the arc to the main surface profile. The relative magnitude of the localized overspeeds varies significantly over the wide range of stator flow incidence investigated. The unsteady boundary layer behavior on the stator is studied using a midspan array of surface-mounted hot-film sensors. On the suction surface, wake-induced transitional and turbulent strips are observed to originate close to the leading edge. The boundary layer approaches separation near the leading edge blend point on the suction surface, but this does not always lead to localized turbulent breakdown or continuous turbulent flow: a significant portion of the flow on the forward part of the surface remains laminar between the wake-induced transitional strips. At high positive incidence the wake-induced transitional strips originate near the leading edge blend point, but their growth is suppressed by the strong flow acceleration. On the pressure surface, a small separation bubble forms near the leading edge blend point resulting in almost continuous turbulent flow over the whole incidence range studied.

OCORRÊNCIA DA TUBERCULOSE EM REBANHO BOVINO DE UMA PROPRIEDADE DO MUNICÍPIO DE SANTA RITA, MARANHÃO, BRASIL

Bovine tuberculosis is a chronic debilitating disease caused by Mycobacterium bovis and can also infect humans. An important step against it is to determine its frequency in herds. This study assesses the occurrence of bovine tuberculosis in a farm located in the municipality of Santa Rita, Maranhao, Brazil. We evaluated 264 dairy cows, of which 43 were Gir breed and 221 were Girolando breed. The method used was the comparative cervical tuberculin test (CCT). Results revealed that 6,06% were suspect cases and 12,12% of animals were positive, which were most frequent in Girolando breed (11,74%). As regards age, there was a higher incidence of positivity (5,68%) as well as suspect cases (4,54%) among females with more than 7 years old, although tuberculosis was detected in all age groups. Therefore, the prevalence of bovine tuberculosis in this region was higher than the national average.

Results of a multicenter pilot study of weekly nab-paclitaxel, carboplatin with bevacizumab, and trastuzumab as neoadjuvant therapy in HER2+ locally advanced breast cancer with SPARC correlatives

527 Background: The addition of targeted therapies to standard chemotherapy has resulted in improved outcomes in metastatic, neoadjuvant and early stage breast cancer. A phase III study in MBC demonstrated improved efficacy with nab paclitaxel (nab-P) compared with standard solvent-based paclitaxel. The secreted protein acidic rich in cysteine (SPARC) is a poor prognostic factor for survival and may mediate enhanced intratumoral accumulation of nab-P via an interaction with albumin. This multicenter phase II pilot study was designed to evaluate the feasibility, safety, and preliminary efficacy of dual VEGF and HER-2 monoclonal antibodies of bevacizumab (B) and trastuzumab (T) administered in with neoadjuvant nab-P and carboplatin (C) with SPARC tumor correlatives. Methods: Eligibility: clinical T1c-T4d and/or N0–3, M0 (T1N0M0 excluded) chemo naive, ECOG PS 0–2, normal LVEF, adequate organ function. Treatment: nab-P 125 mg/m2 D1, 8, 15 with C AUC 6 D1 q28 days plus T 4 mg/kg load followed by 2 mg/kg/wk and B 5 mg/kg/wk x 6 cycles followed by surgery. Post surgery T and B continued for 52 wks. SPARC tumor expression was measured by immunohistochemistry. Results: 29 pts are enrolled and evaluable for safety. Median age: 52 years (29–76), ECOG PS 0–93%, median tumor size 3.2 cm, 54% ER-/PR-, 72% node positive. G3/4 neutropenia was 38% with no febrile neutropenia. Nonheme toxicity: G3/4 hyperglycemia 10%, proteinuria and hypertension, each in 7%. 8 pts were hospitalized (infection-4, ↓LVEF-1, wound dehiscence-1 pt, other-2). 5 pts did not complete neoadjuvant therapy (↓LVEF-1, noncompliance-1, pt request-3) and 10 pts did not complete post op therapy ((pt request-2, toxicity-3, wound-2, unk-3). Pathologic responses are available for 20 pts. pCR was noted in 13/20 pts (65%) and PR was noted in 7/20 pts (35%). 77% of the pCR pts (10/13) and 86% of the PR pts (6/7) were positive for SPARC. Conclusions: Neoadjuvant B, T with nab-P and C is feasible and highly active with a remarkable pCR of 65%. SPARC tumor correlations with pathologic response data reveal a concordance between the high response rate and high incidence of SPARC positivity. [Table: see text]

Risk and Therapeutic Outcomes in a Multiethnic Group of Acute Lymphoblastic Leukemia Patients Treated at a Large Public Hospital

Despite improvements in the treatment of adults with acute lymphoblastic leukemia (ALL) during the last decade, most patients will relapse and ultimately die of disease. Although some factors that affect risk of disease and treatment outcome are known, our ability to predict response and tailor treatments is far from perfect. In particular, we observed that the majority of the ALL patients treated at our large public hospital in Houston, TX were Hispanic. In order to more closely examine this trend and attempt to identify characteristics that would predict risk or therapeutic response, we performed a retrospective analysis of all patients with precursor B-cell ALL, T-cell ALL, and Burkitt lymphoma treated at our hospital over a fifteen year period. One hundred thirteen patients were identified, including sixty-one with precursor B-cell ALL, thirty-two with Burkitt lymphoma, sixteen with T-cell ALL, and four patients with additional features. All patients were treated with HyperCVAD, alternating with methoxtrexate and cytarabine, although some patients had therapeutic modifications because of disease characteristics, particularly in the first course. The median overall survival for all patients was 357 days. Patients with precursor B-cell ALL had the poorest outcome in both overall survival and progression-free survival, and a less favorable outcome than expected from the literature with a 38% two-year survival (95% CI: 54–92%). In contrast, patients with Burkitt lymphoma had an 80% 2-year survival (95% CI: 54%–92%) and those with T-cell ALL had a 63% 2-year survival (95% CI: 32%–83%). The outcomes for Burkitt lymphoma and T-cell ALL are similar to those reported in the literature. Nearly 80% of the patients with precursor B-cell ALL were Hispanic, and most were older than thirty (mean age 36.4 years) with few comorbidities. In contrast, only about 40% of the other high grade leukemia/lymphoma patients were Hispanic, reflecting more closely the racial/ethnic distribution of the population served by the hospital. While our precursor B-cell ALL patients were predominantly Hispanic, there was no statistical difference in overall survival or progression-free survival for Hispanic versus non-Hispanic patients. Hispanic patients with pre-B ALL had a 38% 2-year survival (95% CI: 20%–55%) while non- Hispanic patients had a 41% 2-year survival (95% CI: 12%–69%). Patients younger than thirty with precursor B-cell ALL had a statistically significant survival benefit compared to older patients. Fourteen patients (22.6%) with precursor B-cell ALL had a white blood cell count greater than 50,000, and these patients had significantly poorer outcomes. There was no correlation between cytogenetic abnormalities and outcome; however, very few patients were found to harbor the 9:22 translocation. There was a high incidence of CD20 positivity (55.7%) in patients with precursor B-cell ALL; however, there was no statistically significant correlation with overall survival or progression-free survival. Thus in our multiethnic patient population, patients with precursor B-cell ALL had significantly poorer outcomes than those reported in the literature, while patients with T-cell ALL or Burkitt lymphoma had outcomes to those reported in the literature using the identical chemotherapy regimen. The older age of the precursor B-cell ALL patients may have contributed to this poorer outcome. As noted above, our precursor B-cell ALL patients were predominately Hispanic as compared to the other leukemia patients we studied. Although Hispanic ethnicity did not clearly contribute to outcome, risk of developing precursor B-cell ALL appears to be greater in the Hispanic population.

Expression of S100A6 protein in a broad spectrum of cutaneous tumors using tissue microarrays

S100A6, a calcium-binding protein in the S100 family, has been observed in melanocytic nevi, neural tumors, fibrohistiocytic tumors and is overexpressed in melanoma. Previous studies reported S100A6 expression in atypical fibroxanthomas (AFX) but not in a small number of desmoplastic melanomas (DM). Limited data on S100A6 expression in cutaneous epithelial tumors exists in the literature. The goal of this study was to determine the specificity and sensitivity of S100A6 protein in a spectrum of cutaneous mesenchymal or epithelial tumors. Tissue microarrays of cutaneous epithelial neoplasms, mesenchymal neoplasms, DM and malignant peripheral nerve sheath tumors (MPNST) were stained with S100A6 antibody. Eleven basal cell carcinomas (BCC) failed to express S100A6, whereas all 10 squamous cell carcinomas (SCC) expressed S100A6. Four of seven microcystic adnexal carcinomas (MAC) stained for S100A6. Tumors with duct differentiation variously expressed S100A6 protein, with two hidradenomas showing the strongest staining. Malignant spindle cell tumors, with the exception of 13 of 30 MPNST, had a high incidence of S100A6 positivity. S100A6 expression may distinguish SCC from BCC, MAC from BCC and hidradenoma from other adnexal tumors. S100A6 expression favors DM over MPNST but overlap limits its diagnostic use.

Does acute promyelocytic leukemia in Indian patients have biology different from the West?

Acute promyelocytic leukemia (APML) is a well-characterized malignancy with typical clinico-hematological and molecular features. However, Indian data on this malignancy are limited. This study was conducted to determine the clinico-hematological profile of APML in India. Thirty-five patients with APML presenting to Hematology Department, AIIMS, New Delhi, between July 2003 and June 2005 were evaluated for presenting clinical features, hemogram, peripheral smear, bone marrow morphology and cytochemistry. Reverse transcriptase PCR (RT-PCR) for PML-RARalpha was done in all cases. Male-to-female ratio was 0.9:1 (males--17 and females--18) with median age 25 years (range 11-57 years). Presenting features included anemia, bleeding, fever, gum hypertrophy and scrotal ulceration. All cases showed hypergranular abnormal promyelocytes. Median hemoglobin was 6.3 g/dL (range - 3.0-9.0 g/dL), total leukocyte count (TLC) was 33.88 x 10(9) /L (range - 1-170 x 10(9) /L). Platelet count was 28 x 10(9) /L (range - 4-170 x 10(9) /L). All cases were positive for myeloperoxidase and sudan black (SB), whereas 60% cases also showed non specific esterase (NSE) positivity with 40% cases being fluoride sensitive. RT-PCR showed PML-RARalpha in 33/35 cases with the bcr3 isoform being present in 24/33 positive cases (72.7%). The two cases negative for PML-RARalpha showed typical morphology and responded to ATRA. On statistical analysis, no correlation was found between bcr isoform and TLC, platelet count, age sex and early death. Unusual features included gum hypertrophy and scrotal ulceration at presentation and high median presenting TLC (33.8 x 10(9) /L). There was, however, no microgranular variant. Another interesting feature was a high incidence of NSE positivity (60%), which was fluoride sensitive in 40%. Moreover, the bcr3 isoform was significantly overexpressed (72.7%) in comparison to other studies. APML in India has certain unusual features, which may reflect a different biology.

Frequent Expression of Cancer/Testis Antigens CT7 and LAGE-1 in Advanced Stage Multiple Myeloma: Are They Possible Targets for Immunotherapy?.

Introduction: Recently, Jungbluth and collaborators (Blood 2005; 106(1):167) demonstrated that CT7 and MAGE-A3/6 are frequently expressed in advanced stage MM patients and that higher levels of CT7 and MAGE-A3/6 proteins also correlate with elevated plasma-cell proliferation index. These findings suggest a possible pathogenic role of such proteins in MM and also show that they could be attractive targets for immunotherapy.Objectives: To analyze global expression of 13 CTs (MAGE-A1, MAGE-A2, MAGE-A3/6, MAGE-A4, MAGE-A10, MAGE-A12, BAGE-1, CT7, GAGE family, LAGE-1, PRAME, SP17 and SSX-1) in a panel of normal tissues and monoclonal gammopathies.Material and Method: We studied 13 normal tissues (skeletal muscle, bladder, lung, spleen, heart, brain, thymus, uterus, stomach, mammary gland, pancreas, prostate and colon, Clontech), six normal bone marrow aspirates (donors for allogeneic stem-cell transplants), one pool of 10 normal bone marrow samples (Clontech), three monoclonal gammophaties of undertermined significance (MGUS), five solitary plasmacytomas, 39 multiple myeloma samples (two Durie-Salmon stage II and 37 stage III) and MM cell line U266. Normal testis was used as positive control. Total RNA was extracted using Trizol reagent (Invitrogen). After cDNA synthesis, the expression of CTs was evaluated by RT-PCR and 2% agarose gel electrophoresis.Results: SP17 was positive in all seven normal bone marrow samples and in the 13 normal tissues tested. Thus, it was excluded from further analyses. CT7 was positive in one MGUS and in one plasmacytoma. U266 cell line was positive for all CTs, except SSX-1. The frequency of CTs expression in MM patients was: CT7 = 30/39 (77%); LAGE-1 = 18/39 (46%); MAGE-A3/6 = 16/39 (41%); MAGE-A2 = 14/39 (36%); GAGE family = 13/39 (33%); BAGE-1 = 11/39 (28%); MAGE-A1 = 10/39 (26%); PRAME = 9/39 (23%); SSX-1 = 10/39 (26%); MAGE-A12 = 8/39 (20,5%); MAGE-A4 and MAGE-A10 = 0%. It is important to note that from the 18 cases with less CT's positivity (0, 1 or 2 positive-CTs), three were negative for all of them. Twelve of the remaining 15 cases (80%) were positive for CT7. We did not find association between International Scoring System and percentage of expressed CTs in 36 analyzed MM cases.Conclusion: Our results showed high frequency of expression of CT7 in advanced stage MM patients and support its importance as a target for immunotherapy, because it has a high incidence of positivity even in cases without expression of other CTs. As far we know, this is the second study showing high frequency (~ 50%) of LAGE-1 expression in MM (van Baren et al, 1999), also highlighting its importance as therapeutic target.

High Incidence of Thromboembolic Complications and PF4 Positivity in Patients with Ventricular Assist Devices.

Patients with ventricular assist devices (VAD) are at high risk for thromboembolic complications (TEC) probably due to platelet activation and excessive thrombin generation once the device is implanted. This warrants prophylactic use of full dose anticoagulation, usually with unfractionated heparin (UFH), which increases the risk for development of heparin-induced thrombocytopenia (HIT). We retrospectively evaluated the incidence of TEC and PF4 positivity in 50 sequential patients who underwent VAD placement for severe ventricular dysfunction between November 2002 and April 2005. Median age at VAD placement was 52 years (range 18–72), 68% were men, and all patients were on full dose UFH post-VAD insertion. TEC were observed in 22/50 patients (44%), with 8 patients experiencing >1 event. CNS embolic phenomena occurred in 11/22 (50% of TEC), with watershed/non-embolic CNS infarcts being identified in 2 additional patients. Splenic infarcts were identified in 6/22 (27%). Two patients had lower extremity deep vein thromboses (DVT), and two patients had pulmonary emboli. One patient died from complications of multiple infarcts involving his spleen and gut that were attributed to HIT. All patients became thrombocytopenic (<150K) at some point during VAD/UFH use. 44 patients (88%) dropped the platelet count below 100K with an average nadir of 56K. Antibodies to the PF4/heparin complex were checked using a standard enzyme immunoassay (EIA) in 38 (76%) patients, and found to be positive in 17 (44.7%). PF4 antibodies were detected using the EIA in 50% of patients with TEC and in 25% of patients with no documented TEC. A functional antibody assay was checked in a total of 17 patients, the serotonin release assay (SRA) in 13 and heparin-induced agglutination (HIA) in 4 cases. The SRA was only positive in 2/13 cases, and concordant with the PF4 result both times. The HIA was positive once, and concordant with the PF4 result. These results highlight the high incidence of TEC in patients with a VAD, despite anticoagulation therapy. There is a particularly high rate of embolic stroke in this patient population, and better ways of preventing this complication need to be explored. Thrombocytopenia is also extremely common post-VAD placement, prompting evaluation of HIT in over ¾ of the patients, often necessitating use of direct thrombin inhibitors. The frequent detection of PF4 antibodies in this patient group and lack of correlation with functional assays illustrates the need for more specific laboratory means to quickly confirm those patients with HIT.

An Empirical Prediction Method for Secondary Losses in Turbines—Part I: A New Loss Breakdown Scheme and Penetration Depth Correlation

Despite its wide use in meanline analyses, the conventional loss breakdown scheme is based on a number of assumptions that are known to be physically unsatisfactory. One of these assumptions states that the loss generated in the airfoil surface boundary layers is uniform across the span. The loss results at high positive incidence presented in a previous paper (Benner, M. W., Sjolander, S. A., and Moustapha, S. H., 2004, ASME Paper No. GT2004-53786.) indicate that this assumption causes the conventional scheme to produce erroneous values of the secondary loss component. A new empirical prediction method for secondary losses in turbines has been developed, and it is based on a new loss breakdown scheme. In the first part of this two-part paper, the new loss breakdown scheme is presented. Using data from the current authors’ off-design cascade loss measurements, it is shown that the secondary losses obtained with the new scheme produce a trend with incidence that is physically more reasonable. Unlike the conventional loss breakdown scheme, the new scheme requires a correlation for the spanwise penetration depth of the passage vortex separation line at the trailing edge. One such correlation exists (Sharma, O. P., and Butler, T. L., 1987, ASME J. Turbomach., 109, pp. 229–236.); however, it was based on a small database. An improved correlation for penetration distance has been developed from a considerably larger database, and it is detailed in this paper.

High incidence of HER-2 positivity in inflammatory breast cancer

HER-2 is over-expressed in around 25% of human breast cancers, and is associated with poor outcome. We examined the incidence of HER-2 status in inflammatory breast cancer (IBC). Forty-nine newly diagnosed IBCs were studied. Formalin-fixed paraffin-embedded pre-treatment tissue biopsies were examined immunohistochemically for the over-expression of the HER-2 protein and gene using the HercepTest™ and FISH assay. Clinical outcome was compared between the HER-2 positive (HercepTest™ score 3+and FISH positive) and negative groups. Fifty-two per cent of the IBCs examined were HER-2 positive. The HER-2 positive group were demographically comparable to the HER-2 negative group. Ninety-six per cent of the HER-2 positive patients responded to primary chemotherapy compared to 76% of the HER-2 negative ( P=0.09). No significant differences in outcome emerged between the two groups. In conclusion, this study found the incidence of HER-2 protein over-expression in IBC is higher than previously reported in non-IBC. Early HER-2 directed therapy (such as the monoclonal antibody trastuzumab) as a part of multimodal treatment may improve outcome in this poor prognosis cancer.

Renal cell carcinoma (RCC) and telomerase activity: relationship to stage

Limited information is available on the correlation of telomerase activity and the clinical and pathological characteristics, in patients with renal cell carcinoma (RCC). Telomerase repeat amplification protocol (TRAP) was used to measure telomerase activity in frozen RCC specimens from partial/radical nephrectomies performed between 1987 and 1991. Presence of tumor tissue was verified by a pathologist using hematoxylin and eosin stained sections. RNA was measured to ensure the presence of intact protein necessary for telomerase expression. Data on demographics, tumor type, and stage at presentation, local recurrence, distant metastasis, disease-free survival (DFS), and overall survival (OS) was collected, and telomerase activity was correlated with each of these variables. Forty-nine of 67 patients (73%) were telomerase positive (+ve). Gender and stage were the only variables that appeared to be associated with telomerase positivity. Tumors were telomerase +ve in 12/21 females (57 %) vs. 37/46 males (80%) ( P = 0.07). Tumors were telomerase +ve in 85% of Stage IV, 76% of Stage III, and 70% of Stage I/II patients ( P = 0.12). Five-year survival was 0% for Stage IV, 57% for Stage III, and 77% for Stage I/II patients ( P < 0.001), DFS 54% for stage III and 84% for Stage I/II patients ( P = 0.05). Telomerase activity, however, was not related to survival in either univariate or multivariate analysis. In patients with telomerase +ve tumors 5-year survival was 55%, and with telomerase −ve tumors 58% ( P = 0.56). Stage was the only variable associated with OS or DFS in clear cell RCC patients. In patients with advanced disease, there is a high incidence of telomerase positivity was found, within this limited sample, however, no correlation with survival was found.

The use of histological and immunohistochemical markers to distinguish pleural malignant mesothelioma and in situ mesothelioma from reactive mesothelial hyperplasia and reactive pleural fibrosis.

Distinguishing malignant mesothelioma from reactive mesothelial hyperplasia and reactive fibrosis can be a diagnostic problem in small pleural biopsies, made more difficult by the recent recognition of mesothelioma-in-situ. Antibodies to epithelial membrane antigen (EMA), p53, and bcl-2 have all been advocated for differentiating reactive from neoplastic conditions, but reports are inconsistent. These antibodies have therefore been applied to 31 cases of malignant mesothelioma, 34 cases of reactive pleural disease (20 reactive mesothelial hyperplasia and 14 reactive pleural fibrosis) and four small biopsies that were initially coded as suspicious, from patients who later developed frank mesothelioma. Thirty out of 31 (97 per cent) cases of mesothelioma showed positive nuclear staining for p53, with a higher incidence of positivity in epithelioid than in sarcomatoid elements and 30/31 (97 per cent) showed diffuse linear membrane staining for EMA, again more intense in the epithelioid elements. No mesothelioma was positive for bcl-2. In seven cases that contained both in situ and invasive mesothelioma, the in situ elements showed similar staining patterns to the invasive epithelioid elements. Thirteen out of 20 (65 per cent) cases of reactive mesothelial hyperplasia showed occasional nuclear positivity for p53 and 5/20 (25 per cent) cases showed focal weak membrane staining for EMA. Three out of 14 (21 per cent) cases of reactive pleural fibrosis showed positive nuclear staining for p53 and 6/14 (43 per cent) cases showed focal membrane staining with EMA. No reactive cases stained for bcl-2. All four suspicious cases showed diffuse linear staining with EMA and three showed focal staining for p53. It is concluded that strong diffuse linear staining for EMA is a good marker of malignancy when differentiating epithelioid malignant mesothelioma and mesothelioma-in-situ from reactive mesothelial hyperplasia, although weak focal staining may occur in reactive conditions. Nuclear staining for p53 is also suggestive of epithelioid mesothelioma, but should be regarded as no more than suspicious. The antibodies used in this investigation are less helpful in differentiating sarcomatoid mesothelioma from reactive pleural fibrosis.

Expression of cathepsin-D, CA125 and epidermal growth factor receptor in imprint smears of ovarian carcinoma.

One hundred primary ovarian cancers were studied for the expression of cathepsin-D, CA125 and epidermal growth factor receptor (EGF-R) by staining of imprint smears from freshly obtained surgical specimens. Estrogen and progesterone receptors of the primary tumor, lymph node invasion, menopausal status of the patients and primary tumor size were also noted. The polymorphism of the antigenic characteristics of ovarian carcinomas was noted and significant associations of EGF-R positivity and lymph node negativity, EGF-R positivity and serous carcinomas, EGF-R positivity and cathepsin-D positivity, cathepsin-D positivity and CA125 positivity, and CA125 positivity and serous carcinomas were observed. The high incidence of cathepsin-D positivity makes it a possible complementary method to CA125 for following up patients. It is suggested that complete antigenic profiles of individual tumors are more likely to provide accurate prognostic information in individual cases.

Breast carcinomas occurring in young women (< 35 years) are different.

One hundred and sixty-three breast carcinomas occurring in women aged between 26 and 44 years were examined for pathological features, oestrogen and progesterone receptor status, proliferation as determined by Ki-67 labelling and the presence of c-erbB-2 and p53 protein, and were compared with a control group of carcinomas from women in the 50-67 years age group. Carcinomas occurring in women aged under 35 years had a significantly high incidence of being poorly differentiated and of having high proliferation rates. This group also had a significantly high incidence of p53 protein staining. Carcinomas in the under 30 years age group had a lower incidence of oestrogen and progesterone receptor positivity. No differences were found in c-erbB-2-positive staining between the groups. Infiltrating lobular carcinomas were only identified in women aged 40 years and over. There was a higher incidence of a family history in the 35-44 years age group (18%) than in the under 35 years age group (11%). Breast carcinomas occurring in women aged under 35 years are more aggressive. An important finding is the high incidence of p53 positivity, which may indicate genetic instability.

Ascitic Positive Cytology and Intraperitoneal Metastasis in Ovarian Dysgerminoma

To verify the pattern of the spread of tumors in ovarian dysgerminoma, with special reference to intraperitoneal metastasis, and to assess clinicopathologic factors for predicting tumor extension. Detailed data regarding ascitic cytology, macroscopical findings at surgery, and the histopathology of the surgical specimens were retrospectively reviewed in 12 patients with dysgerminoma who were treated at Kyoto University Hospital. The relationships between the tumor extension and the period of symptoms, the serum lactic dehydrogenase (LDH) level, and the operative findings also were analyzed. Ascitic cytology revealed a high incidence of positivity in 6 of the 10 (60%) cases examined. Extraovarian metastases were present in 4 of the 6 (67%) cases with positive cytology, and in 1 of the 4 (25%) cases with negative cytology. Intraperitoneal metastatic nodules were detected in 5 of the 12 (42%) patients either by inspection during surgery or by postsurgical histological examination. In addition, these metastatic lesions were 5 or fewer in number and 7 mm or less in diameter, except in 1 patient with widespread disease. The presence or absence of extraovarian spread of the tumor was not significantly correlated with the period of symptom, the serum LDH level, the size of the primary tumor, or the volume of the ascitic fluid. The incidence of intraperitoneal spillage and/or metastases of dysgerminoma cells might be higher than previously reported. These findings indicate the importance of ascitic cytology and careful inspection at the time of operation, as well as the rationale of postsurgical chemotherapy for dysgerminoma of an apparently early stage.

Screening of baboons as potential liver donors for humans

Abstract: The baboon could supply organs for humans, and there may be a particular role for baboon livers in “bridging” patients in terminal hepatic failure who are awaiting a human liver. We have investigated 10 healthy adult baboons in regard to i) hepatic metabolism and ii) the presence of infections that might be transferred to a human recipient with a transplanted organ. Blood was drawn for a general profile of hematologic, metabolic, and biochemical parameters and compared with standard values for humans. All baboons were i) examined by a veterinarian, ii) tuberculin tested, iii) virologically screened, and iv) screened for bacterial, protozoal, helminth, and fungal infections. Tests i–iii were repeated after a 3‐month interval. BUN, LDH, and SGOT levels were higher than in the human in &gt;50% of the cases. Fasting blood glucose, uric acid, cholesterol, albumin, and total bilirubin levels were frequently lower. Serology was positive both for HTLV1 and STLV in three baboons. All baboons were positive for foamy virus, but this was not thought to exclude them as organ donors. There was a high incidence of positivity for DNA viruses (SA8, SA6, HSV, CMV, and EBV) but generally indicated past, rather than active, infection. Hepatitis A serology, but not IgM, was positive in four baboons, but hepatitis B and C were negative in all (except in two where there was transient positivity to hepatitis B). SA11 rotavirus serology was positive in six. No evidence for mycobacterial, protozoal, helminth, or fungal infection was found, although one baboon had positive serology for toxoplasma IgG. We would conclude that six or possibly seven of the 10 baboons would be acceptable as donors of organs for humans. Only the three with positive serology for the retroviruses HTLV1 and STLV would be definitely excluded. A case could be made for also excluding the baboon positive for Toxoplasma IgG.