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PubMed2003

Wound infiltration with ropivacaine and fentanyl: effects on postoperative pain and PONV after breast surgery.

STUDY OBJECTIVE: To determine whether postoperative wound infiltration with local anesthetics combined with fentanyl improves analgesia following breast surgery; and to investigate awakening and postoperative nausea/vomiting. DESIGN: Prospectively randomized clinical study. SETTING: University hospital. PATIENTS: 45 ASA physical status I and II patients scheduled for breast surgery. INTERVENTIONS: Patients were prospectively randomized and assigned to one of three treatments during general anesthesia: postsurgical wound infiltration with ropivacaine 0.375%; wound infiltration with ropivacaine 0.375% combined with fentanyl 0.5 microg/kg; and intravenous (i.v.) fentanyl 0.5 microg/kg before skin incision and no wound infiltration. Time to first verbal response, pain at rest, postoperative nausea and vomiting, and ketobemidone and dixyrazine utilization were compared. MEASUREMENTS AND MAIN RESULTS: Time to first verbal response was significantly shorter in the i.v. fentanyl group compared to both infiltration groups (8.1 +/- 4.5 min vs. 15.3 +/- 4.3, and 12.0 +/- 5.0 min; p < 0.05, respectively). Postoperative pain at rest, and nausea and vomiting occurred with similar frequencies in the groups. Ketobemidone utilization in both infiltration groups, (2.4 +/- 1.8 mg and 3.1 +/- 1.8 mg, respectively) was not different compared to the i.v. fentanyl group (2.9 +/- 2.0 mg; NS). There were no differences in postoperative antiemetic requirements during the first, second and third two-hour periods postoperatively. The dixyrazine consumption was similar in the three groups, (0.9 +/- 1.5 mg, 0.8 +/- 1.3 mg, and 1.4 +/- 1.8 mg, respectively; NS). CONCLUSION: Postsurgical ropivacaine wound infiltration, with or without adding fentanyl, demonstrates no differences in postoperative pain relief and nausea/vomiting compared to a balanced general anesthetic including i.v. fentanyl.

Amides↗

PubMed2000

Squamous cell carcinoma of the esophagus infiltrating the respiratory tract is less sensitive to preoperative concurrent radiation and chemotherapy.

BACKGROUND: The prognosis of upper thoracic esophageal cancer is poor when compared with middle and lower thoracic esophageal cancer because the tumor easily infiltrates the respiratory tract and surgical en-bloc resection is difficult. Recently, preoperative chemoradiation therapy has been shown to lead to down-staging of the disease and improve prognosis. But the benefit of this therapy for tumors infiltrating the respiratory tract remains unknown. STUDY DESIGN: Fifty-six patients with thoracic esophageal cancer infiltrating neighboring organs, but with no hematogeneous metastasis, were given preoperative concurrent chemotherapy (5-fluorouracil and cisplatin) and radiation (40 Gy) therapy. When a clinical response was observed, making a curative resection potentially possible, patients were scheduled for esophagectomy with extended lymphadenectomy. Patient prognosis with respect to the organs infiltrated by the tumors was estimated by calculating survival curves using the Kaplan-Meier method and comparing the curves by the log-rank test. RESULTS: The prognosis was significantly poorer for patients with tumors infiltrating the respiratory tract (T) or aorta plus respiratory tract (A + T) than for patients with tumors infiltrating the aorta alone (A) or other organs (Oth) (p < 0.05 for Oth versus T; p < 0.05 for Oth versus A + T; p < 0.0001 for A versus T; p < 0.0001 for A versus A + T by log-rank test). Patients positive for respiratory tract invasion (T, T + A), compared with those negative for respiratory tract invasion (A, Oth), showed a poorer clinical response to chemoradiation (3.0%, 45.5%, 39.4%, and 9.1% versus 4.3%, 82.6%, 4.3%, and 8.7% in complete response (CR), partial response (PR), nonresponse (NC) and progressive disease (PD), respectively, p = 0.0156) and surgical resectability (36.4% vs. 87.0%, p = 0.0003). Histologic effectiveness (8.3%, 50.0%, and 41.7% versus 25.0%, 70.0%, and 5.0% in grade 3, grade 2, and grade 1, respectively, for patients with respiratory tract invasion versus those without it, p = 0.0189) and histologic stages (8.3%, 8.3%, 8.3%, 8.3%, 25.0%, and 41.7% versus 20.0%, 0%, 15.0%, 25.0%, 40.0%, and 0% in pathologic CR, stage I, stage IIA, stage IIB, stage III, and stage IV, respectively, for patients with respiratory tract invasion versus those without it, p = 0.0496) were significantly better in patients negative for respiratory tract invasion; the percentages of patients with lymph node metastasis did not differ significantly between the two groups. Comparison of the recurrence patterns showed that local failure was most common in patients with respiratory tract invasion, and distant failure was the leading cause of recurrence in patients without it. CONCLUSIONS: Because the prognosis of patients with thoracic esophageal cancer infiltrating the respiratory tract is extremely poor, partially because of the low local effectiveness of preoperative concurrent chemotherapy and radiation therapy, caution is needed when deciding on salvage surgery.

Adult↗

PubMed2001

Is the infiltration-centrifugation technique appropriate for the isolation of apoplastic fluid? A critical evaluation with different plant species.

The suitability of the infiltration-centrifugation method for collection of apoplastic fluid from intact leaves was evaluated for different plant species. Large differences with respect to infiltrability of the leaves, which correlated inversely with stomatal and mesophyll resistance, became apparent. Osmolality of infiltration medium (deionised water, 0.2 mM CaCl2, 10 mM KCl, 180 mM 2-[N-morpholino]ethane-sulphonic acid) and incubation time, time passed between onset of infiltration and end of centrifugation, revealed relatively little influence on the composition of the apoplastic washing fluid (AWF). In contrast, the pH of the infiltrated solution highly influenced the concentration of sucrose and hexoses. With increasing centrifugation force, hexosephosphate isomerase (HPI) activity in the AWF, which was taken as an indication for cytoplasmic contamination, increased. At the same time, Ca2+ concentration in the AWF increased even more. Since Ca2+ cannot originate from the cytoplasm, the suitability of HPI as marker for cytoplasmic contamination is questioned. From the composition of the AWF, it is concluded that, if centrifugation force does not exceed 1 000 g, cytoplasmic contamination is negligible and that the infiltration-centrifugation technique reveals an easy and inexpensive way to study apoplastic solutes. The infiltration-centrifugation method was also suitable to determine apoplastic air volume (Vair) and apoplastic water volume (Vwater), which are necessary for the calculation of the ion concentration in the leaf apoplast. It could be shown that the leaves of different species and the apical and basal leaves of single plants differ in Vair and Vwater.

Journal Article↗

PubMed1987

Natural killer activity of lymphocytic infiltrates in mouse mammary lesions.

Tissue infiltrating lymphocytes were isolated from BALB/c line C4 preneoplastic hyperplastic alveolar nodules (HAN) and spontaneous tumours that arose from the HANs. NK activity of the lymphocytic infiltrates was tested in a 4 h chromium release assay using 51Cr labelled YAC cells. In situ lymphocytes of C4 HAN expressed 3-4 fold greater relative lytic activity (Pross et al., 1981) than did normal spleen cells whereas the relative lytic activity of C4 tumour infiltrates was equivalent or less than that of normal spleen cells. Spleen cells of all lesion bearers had reduced cytolytic capacity. YAC cell lysis by spleen cells and HAN infiltrates correlated with increasing E/T ratios. The degree of YAC lysis by C4 tumour infiltrates, however, either decreased, stayed the same, or increased non-exponentially with increasing E/T ratios especially at E/T greater than 50. Indeed, C4 tumour infiltrates from animals pretreated with anti-asialo GM1 (ASGM) could suppress the NK activity of normal spleen cells. The lytic activity of both C4 HAN and tumour infiltrates could be enhanced or depressed by in vivo treatment with poly IC or anti-ASGM, respectively. These results indicate that NK cells are activated or recruited into C4 preneoplastic lesions but their lytic activity wanes and suppressive activity arises with progression to neoplasia.

Animals↗

PubMed2004

Retinoblastoma protein function and p16INK4a expression in actinic keratosis, squamous cell carcinoma in situ and invasive squamous cell carcinoma of the skin and links between p16INK4a expression and infiltrative behavior.

p16INK4a is involved in many important regulatory events in the cell and the expression and function is closely associated with the retinoblastoma protein (Rb). Earlier, we have in colorectal cancer and in basal cell carcinoma showed that p16INK4a is upregulated at the invasive front causing cell cycle arrest in infiltrative tumor cells via a functional Rb. This role for p16INK4a as a regulator of proliferation when tumor cells infiltrate might besides a general cyclin-dependent kinase (cdk) inhibitory effect explain why p16INK4a is deregulated in many tumor forms. The expression pattern of p16INK4a in relation to Rb-function in squamous cancer and precancerous forms of the skin has not been fully detailed. We therefore characterized the expression of p16INK4a, Rb-phosphorylation and proliferation in actinic keratosis, squamous cell carcinoma in situ and invasive squamous cell carcinoma with special reference to infiltrative behavior. The expression of p16INK4a varied between the lesions, with weak and cytoplasmic p16INK4a expression and functional Rb in actinic keratosis. Strong nuclear and cytoplasmic p16INK4a expression was observed in all carcinomas in situ in parallel with lack of Rb-phosphorylation but high proliferation indicating a nonfunctional Rb. Invasive squamous carcinoma showed a mixed p16INK4a expression pattern where some tumors had strong cytoplasmic p16INK4a expression, large fraction of Rb-phosphorylated cells and high proliferation. Interestingly, despite this disability of p16INK4a to inhibit proliferation there was an upregulation of cytoplasmic p16INK4a in infiltrative cells compared to tumor cells towards the tumor center. A similar scenario but strong and combined nuclear and cytoplasmic p16INK4a expression in infiltrative cells, was observed in other invasive squamous cancers. This suggests that the p16INK4a upregulation in infiltrative cells is governed independently of the subcellular localization or of the potential to affect proliferation via Rb, and suggests a potentially proliferation independent function for p16INK4a in infiltrative behavior.

Blotting, Western↗

PubMed2002

Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma.

In the present study, epithelium derived lesions of various pathological manifestations were examined histologically and immunohistochemically for mononuclear cell infiltration. The infiltrate under the transformed epithelium of oral lesions, was examined for differences in the composition of immune mononuclear cells as the epithelium moves from hyperkeratosis through various degrees of dysplasia to squamous cell carcinoma. The study was performed on 53 human tongue tissues diagnosed as hyperkeratosis (11 cases), mild dysplasia (nine cases), moderate and severe dysplasia (14 cases) and squamous cell carcinoma (19 cases). A similar analysis was performed on 30 parotid gland tissues diagnosed as pleomorphic adenoma (14 cases) and carcinoma ex-pleomorphic adenoma (16 cases). Immunohistochemical analysis of various surface markers of the tumour infiltrating immune cells was performed and correlated with the transformation level as defined by morphology and the expression of p53 in the epithelium. The results revealed that, in the tongue lesions, the changes in the epithelium from normal appearance to transformed were accompanied by a corresponding increase in the infiltration of CD4, CD8, CD14, CD19+20, and HLA/DR positive cells. The most significant change was an increase in B lymphocytes in tongue lesions, that was in accordance with the transformation level (P<0.001). In the salivary gland, a significant number of cases did not show an infiltrate. In cases where an infiltrate was present, a similar pattern was observed and the more malignant tissues exhibited a higher degree of immune cell infiltration.

Carcinoma↗

PubMed2001

Extremely high Langerhans cell infiltration contributes to the favourable prognosis of HPV-infected squamous cell carcinoma and adenocarcinoma of the lung.

AIMS: The infiltration of Langerhans cells in adenocarcinomas and squamous cell carcinomas of the lung was examined in relation to prognostic implications and human papillomavirus (HPV) infection. METHODS AND RESULTS: Samples from 62 adenocarcinoma and 59 squamous cell carcinoma patients in 1995-97, the prognosis of which had been followed up, were used. The Langerhans cells were demonstrated immunohistochemically using anti S100a and CD1 antibodies. Human papillomavirus (HPV) infection was examined by polymerase chain reaction (PCR) and nonisotopic in-situ hybridization (NISH) methods. Statistical analysis was carried out using the Kaplan-Meier method (Wilcoxon analysis) and multiple regression analysis. HPV infection was demonstrated in 12 cases (19.4%) of adenocarcinoma. The HPV-infected adenocarcinomas had abundant faintly eosinophilic cytoplasm, and were immunohistochemically positive for the surfactant apoprotein A. In the 59 cases of squamous cell carcinomas 19 were of the well differentiated form, and 29 and 11 were moderately and poorly differentiated cases, respectively. HPV was detected in 29 cases (49.2%) (13 well and 16 moderately differentiated cases). In all HPV-infected adenocarcinoma and squamous cell carcinoma cases, extremely large numbers of Langerhans cells (more than 100 per high-power field) were demonstrated in the tumour nests. In contrast, in the non-HPV-infected adenocarcinomas and squamous cell carcinomas, only a few (less than about 10 per high-power field) Langerhans cells were observed. The squamous cell carcinoma cases with high Langerhans cell infiltration, which were also infected with HPV, showed a significantly good prognosis (P = 0.007). The adenocarcinoma cases with high Langerhans cell infiltration tended to have a better prognosis than the cases with low Langerhans cell infiltration, but the difference was not statistically significant. The low number of highly infiltrated cases was insufficient for an adequate statistical analysis. Furthermore, there was no significant correlation between either Langerhans cell infiltration and smoking, or HPV infection and smoking, in either squamous cell carcinoma or adenocarcinoma cases. CONCLUSIONS: It was considered that the extremely high Langerhans cell infiltration in the tumours was caused by HPV infection. The extremely large number of Langerhans cells in the tumours contributes to the favourable prognosis for HPV-infected lung cancer.

Adenocarcinoma↗

PubMed2002

Effectiveness of intra-operative wound infiltration with long-acting local anaesthetic.

BACKGROUND: Postoperative pain relief is of importance to both patients and surgeons. One of the simpler techniques is infiltration of the surgical incision with long acting local anaesthetic. The literature is confusing, with numerous reports attesting to the value of this approach and a similar number disputing the demonstrable benefits. METHODS: A prospective, 'blinded', randomized trial was undertaken involving 18 females undergoing uncomplicated bilateral sapheno-femoral ligation. They received intraoperative bupivacaine infiltration into one or the other of their groin incisions. Postoperatively these patients were asked to assess a number of variables relating to their postoperative pain, each patient thereby acting as their own control. RESULTS: There was no significant difference in the postoperative pain experience between groins infiltrated with bupivacaine and those not infiltrated. Two patients developed wound infections and both of these occurred on the sides which had been infiltrated with bupivacaine, however this was not statistically significant. There was no difference found in pain experience with respect to pre- versus post-incision infiltration. CONCLUSION: Intraoperative wound infiltration with bupivacaine is widely employed as a method of minimizing postoperative pain. This study was unable to demonstrate a benefit of employing the technique in terms of a reduction in the patient's perception of pain. By having each patient act as their own control, we have avoided one of the major deficiencies of previous studies, namely, interpatient variability in assessment and perception of pain.

Adult↗

PubMed2000

Pattern of distribution of intraductal and infiltrating ductal carcinoma: a three-dimensional study using serial coronal giant sections of the breast.

The purpose of this study was to establish the 3-dimensional (3D) structure of the breast tissue and to study the distribution and relationship between the intraductal and infiltrating components of ductal carcinoma and other proliferative epithelial lesions of the breast. Thirty mastectomy specimens with infiltrating carcinoma less than 3.0 cm in diameter were serially cut in the coronal plane. Each giant section was divided into small sections for routine processing. Using Photoshop (Adobe) and PowerPoint (Microsoft) software programs, the routinely stained sections were scanned and assembled to reestablish complete giant sections of the breast and subsequently the 3D structure. Intraductal and infiltrating ductal carcinomas, epithelial hyperplasia with atypia, and marked epithelial hyperplasia without atypia were mostly confined to a single duct (27 cases), resulting in an increase in size of the involved breast segment. Three remaining cases included a case of Paget's disease with tumor appearing to spread from one duct system to another system through the epidermis and two cases with multiple separate foci of carcinomas located in different quadrants and accompanied by ductal spread in different lactiferous ducts. Both intraductal and infiltrating carcinomas were often located in the superficial segments (near the subcutaneous tissue) (28 cases). The infiltrating components were often located adjacent to area of pure intraductal carcinoma and were often peripheral (nearer the chest wall than the nipple). Intraductal carcinomas showed a "fanned out" pattern of distribution, frequently extended toward the nipple (with involvement of the nipple or subareolar tissue in 7 cases), and occasionally were seen in the breast tissue peripheral to the infiltrating carcinoma. Multiple ducts with intraductal carcinoma could be seen to be connected with each other with serial sections. However, in at least 6 cases, foci of intraductal carcinomas were separated from each other by segments of duct with benign epithelium. Breast carcinoma often arise from the breast segment close to the subcutaneous tissue. Infiltrating carcinoma lesser than 3.0 cm in diameter is usually located adjacent to the area of pure intraductal. The pattern of spread of intraductal carcinoma has a pyramid-like shape, with the summit toward and occasionally extending up to the nipple. These findings should be considered in the surgical strategy for segmental resections of breast carcinomas.

Adult↗

PubMed2001

The clinical and pathologic implications of plasmacytic infiltrates in percutaneous renal allograft biopsies.

Plasmacytic infiltrates in renal allograft biopsies are uncommon and morphologically distinctive lesions that may represent variants of acute rejection. This study sought significant clinical and pathologic determinants that might have influenced development of these lesions and assessed their prognostic significance. Renal allograft biopsies (n = 19), from 19 patients, with tubulointerstitial inflammatory infiltrates containing abundant plasma cells, composing 32 +/- 8% of the infiltrating mononuclear cells, were classified using Banff '97 criteria. Clonality of the infiltrates was determined by immunoperoxidase staining for kappa and lambda light chains and polymerase chain reaction for immunoglobulin heavy-chain gene rearrangements, using V(H) gene framework 3 and JH consensus primers. In situ hybridization for Epstein-Barr virus encoded RNA (EBER) was performed in 17 cases. The clinical features, histology, and outcome of these cases were compared with kidney allograft biopsies (n = 17) matched for time posttransplantation and type of rejection by Banff '97 criteria, with few plasma cells (7 +/- 5%). Sixteen of 19 biopsies (84%) with plasmacytic infiltrates had EBER-negative (in 14 cases tested) polyclonal plasma cell infiltrates that were classifiable as acute rejection (types 1A [4], 1B [10], and 2A [2]). These biopsies were obtained between 10 and 112 months posttransplantation. Graft loss from acute and/or chronic rejection was 50% at 1 year and 63% at 3 years, and the median time to graft failure was 4.5 months after biopsy. There was no significant difference in overall survival or time to graft failure compared with the controls. Three of 19 biopsies (16%) had EBER-negative polyclonal plasmacytic hyperplasia, mixed monoclonal and polyclonal polymorphous B cell hyperplasia, and monoclonal plasmacytoma-like posttransplantation lymphoproliferative disease (PTLD) and were obtained at 17 months, 12 weeks, and 7 years after transplantation, respectively. Graft nephrectomies were performed at 1, 19, and 5 months after biopsy, respectively. Plasmacytic infiltrates in renal allografts comprise a spectrum of lesions from acute rejection to PTLD, with a generally poor prognosis for long-term graft survival.

Adult↗

PubMed2005

[Estimation of diffuse bone marrow infiltration of the spine in multiple myeloma: correlation of MRT with histological results].

PURPOSE: To determine the detection of diffuse bone marrow infiltration with MRI in comparison with histopathological findings. MATERIALS AND METHODS: MRI was performed on 45 patients with histologically proven multiple myeloma and on 30 healthy individuals. Three experienced radiologists read separately Tl-weighted SE sequences, STIR sequences and the combination of Tl-weighted SE and STIR sequences of the spine. Additionally, Tl-weighted SE sequences were obtained after gadolinium administration and the percentage increase in signal intensity was calculated. Bone marrow histology was used as gold standard for assessing the grade of infiltration. A dichotomous decision (infiltration yes/no) was made when assessing the MRI examinations. RESULTS: For the visual detection of diffuse infiltration, the best sensitivity was found with Tl-weighted SE sequences, achieving 71 % on average. The specificity was 89 %. The STIR sequences showed a sensitivity of 61 % and a specificity of 98 %, and the combination of Tl-weighted/STIR-sequences achieved a sensitivity of 65 % and a specificity of 94 %. In comparison with the histological findings, the sensitivity of the Tl-weighted sequences was 35 % for low-grade, 89 % for moderate and 100 % for high-grade infiltration. The application of contrast material with calculation of the percentage signal increase improved the detection by 7 %. CONCLUSION: The sensitivity of the visual detection of diffuse multiple myeloma with unenhanced MRI is limited for low-grade or moderate infiltration, whereas the sensitivity for high grade infiltration is reliable. The specificity is high and the diagnostic confidence improves after application of contrast material with calculation of the percentage increase in signal intensity.

Adult↗

PubMed1996

[Infiltration patterns of plasmacytomas in magnetic resonance tomography].

PURPOSE: To define the different infiltration patterns in the spine in multiple myeloma, in correlation with histological and clinical findings. Quantitative signal evaluation with contrast media (Gd-DTPA). To compare the results in MRI with X-ray films. MATERIAL AND METHODS: 61 patients with proven multiple myeloma and 50 controls were examined (1.0 Tesla, T1-w SE, opposed phase GE images). RESULTS: Five infiltration patterns with different clinical stages were detected: normal bone marrow (11%) in cases of low interstitial marrow infiltration (biopsy), pure diffuse infiltration (25%), focal involvement (33%), combined diffuse/focal infiltration (23%) and a "salt-and pepper" pattern (8%). In diffuse plasmacytoma the 40% signal intensity increase was modification of diffuse infiltration. MRI proved to be more sensitive than radiography. CONCLUSION: MRI is able to show the type and the extension of bone marrow infiltration in multiple myeloma. Diffuse involvement can be objective with gadopentetate dimeglumine.

Adult↗

PubMed2001

Lymphoid cell infiltration into Epstein-Barr virus-positive nasopharyngeal carcinomas.

OBJECTIVES: A pilot study was designed to analyze lymphoid cell infiltration in Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinomas (NPCs) and to determine whether this pattern of infiltration is consistent with non-EBV+ head and neck carcinomas or with solid EBV+ tumors in other locations. STUDY DESIGN: We performed a retrospective analysis of archived NPCs and oral cavity carcinomas. METHODS: Immunohistochemical staining of the archive material for various markers (CD3, CD8, UCHL-1, S-100, and intercellular adhesion molecule) was performed. Polymerase chain reaction techniques to establish the presence of the EBV genome were used. Cells in different locations were counted under a light microscope by 2 of the authors. RESULTS: The infiltration pattern of NPCs was different from that of oral cavity carcinomas. Stromal infiltration was significantly denser in oral cavity carcinomas. Tumor nest infiltration was more pronounced in NPCs. The pattern of infiltration was comparable with what has been described for other solid EBV+ tumors. CONCLUSIONS: The immune response to NPCs is likely to be strongly influenced by the presence of the EBV genome. The pattern of infiltration is similar to that of other non-head and neck EBV+ solid tumors and different from that of EBV- head and neck carcinomas.

Antigens, CD↗

PubMed1989

Comparative features of ductal carcinoma in situ and infiltrating ductal carcinoma of the breast on fine-needle aspiration biopsy.

To evaluate the usefulness of fine-needle aspiration biopsy of the breast in separating ductal carcinoma in situ (DCIS) from infiltrating ductal carcinoma, the authors reviewed 16 preoperative fine-needle aspiration biopsies from biopsy-proven exclusive DCIS and 39 fine-needle aspiration biopsies from infiltrating ductal carcinomas with or without an in situ component. Seven (44%) of the DCIS and eight (21%) of the infiltrating ductal carcinomas had inadequate material for diagnosis on the aspiration biopsy. Five (32%) of the DCIS and 29 (74%) of the infiltrating ductal carcinomas caused suspicion or had positive results for malignancy. Four (25%) of the DCIS and two (5%) of the infiltrating ductal carcinomas showed atypical cells. Morphologic features of the atypical or malignant cells in the adequate specimens from these two lesions were similar except that the cells from the infiltrating ductal carcinomas showed more irregular nuclear spacing (94% vs. 44%, P less than 0.01) and more pronounced nuclear overlapping (65% vs. 33%) than those from the DCIS. In addition, the fine-needle aspiration biopsies of the DCIS tended to be hypocellular (less than 10 cells/10X) (44% vs. 6.5%, P less than 0.05) and to contain benign epithelial cells (22% vs. 6.5%) and macrophages (33% vs. 13%). Although the suspicion of DCIS might be raised when hypocellularity, benign epithelial cells, and macrophages are noted in a fine-needle aspiration biopsy of the breast that has positive results or causes suspicion for malignancy, fine-needle aspiration biopsy cannot be relied upon to distinguish DCIS from infiltrating ductal carcinoma.

Biopsy, Needle↗

PubMed2003

Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: a quantitative MRI study.

Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, the precise sequence of these events and their role in lesion formation and disease progression remain unknown. Here we provide quantitative evidence that blood-brain barrier leakage is an early event and precedes massive cellular infiltration in the development of acute experimental allergic encephalomyelitis (EAE), the animal correlate of multiple sclerosis. Cerebrovascular leakage and monocytes infiltrates were separately monitored by quantitative in vivo MRI during the course of the disease. Magnetic resonance enhancement of the contrast agent gadolinium diethylenetriaminepentaacetate (Gd-DTPA), reflecting vascular leakage, occurred concomitantly with the onset of neurological signs and was already at a maximal level at this stage of the disease. Immunohistochemical analysis also confirmed the presence of the serum-derived proteins such as fibrinogen around the brain vessels early in the disease, whereas no cellular infiltrates could be detected. MRI further demonstrated that Gd-DTPA leakage clearly preceded monocyte infiltration as imaged by the contrast agent based on ultra small particles of iron oxide (USPIO), which was maximal only during full-blown EAE. Ultrastructural and immunohistochemical investigation revealed that USPIOs were present in newly infiltrated macrophages within the inflammatory lesions. To validate the use of USPIOs as a non-invasive tool to evaluate therapeutic strategies, EAE animals were treated with the immunomodulator 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitor, lovastatin, which ameliorated clinical scores. MRI showed that the USPIO load in the brain was significantly diminished in lovastatin-treated animals. Data indicate that cerebrovascular leakage and monocytic trafficking into the brain are two distinct processes in the development of inflammatory lesions during multiple sclerosis, which can be monitored on-line with MRI using USPIOs and Gd-DTPA as contrast agents. These studies also implicate that USPIOs are a valuable tool to visualize monocyte infiltration in vivo and quantitatively assess the efficacy of new therapeutics like lovastatin.

Animals↗

PubMed1996

Platelet-derived endothelial cell growth factor in human colon cancer angiogenesis: role of infiltrating cells.

BACKGROUND: Development of new blood vessels is essential for tumor growth and metastasis and depends on the production of angiogenic factors by tumor and/or infiltrating cells. We previously showed that vascular endothelial growth factor (VEGF) expression and vessel count correlate with metastasis in human colon cancer. Although most tumors with high vessel counts express high levels of VEGF, some do not. Recently, platelet-derived endothelial cell growth factor (PD-ECGF), another potent angiogenic factor, has been reported to be expressed in colon cancer. PURPOSE: In this study, we examined the role of PD-ECGF in colon cancer angiogenesis and whether PD-ECGF is derived from the tumor or infiltrating cells. METHODS: Immunostaining for PD-ECGF was performed on 96 colon cancer specimens, some of which were previously stained for VEGF and factor VIII, a marker that is specific for endothelial cells. Double staining was done by using antibodies to PD-ECGF and to CD68 (macrophage specific) or CD3 (lymphocyte specific) to confirm which infiltrating cells produce PD-ECGF. Northern blot analysis for PD-ECGF messenger RNA (mRNA) was performed on four colon cancer specimens and corresponding normal colon mucosae (same patients) and four human colon cancer cell lines (KM12SM, SW620, HT29, and NCI-H508) to determine whether colon cancer epithelium expresses PD-ECGF. RESULTS: Immunohistochemical analysis demonstrated that PD-ECGF was expressed in infiltrating cells in most of the colon cancer specimens (80 [83%] of 96) but rarely in tumor epithelium (five [5%] of 96). Double staining demonstrated that infiltrating cells staining positive for both PD-ECGF and CD68 were more predominant than those staining positive for both PD-ECGF and CD3. The intensity of staining for PD-ECGF in infiltrating cells correlated with vessel counts (Spearman's rank correlation coefficient (R) = .29; P = .004), but did not correlate with the intensity of VEGF staining (R = .176, P = .086) or metastasis (Mann-Whitney U test, P = .253). PD-ECGF staining intensity was higher in specimens with a high vessel count (> 50 at high magnification) and low VEGF-staining intensity (< or = 2+) than in specimens with a high vessel count (again, > 50) and high VEGF-staining intensity (3+). Northern blot analysis revealed that colon cancer specimens and normal mucosae expressed relatively high levels of PD-ECGF mRNA, whereas PD-ECGF mRNA transcripts were not detectable in colon cancer cell lines. CONCLUSIONS AND IMPLICATIONS: PD-ECGF expression in human colon cancer specimens is associated with vessel count and may be responsible for tumor vascularity in those tumors with low VEGF expression. Infiltrating cells expressing PD-ECGF may contribute to angiogenesis, thus providing an additional mechanism for tumor neovascularization.

Blotting, Northern↗

PubMed2003

Induction of resistance and expression of defense-related genes in tobacco leaves infiltrated with Ralstonia solanacearum.

Ralstonia solanacearum 8107 (8107) is non-pathogenic to tobacco and elicits the hypersensitive response (HR). In Nicotiana tabacum cv. Samsun NN leaves infiltrated with 8107, acquired resistance to challenging tobacco mosaic virus (TMV) was induced 2-6 d after 8107-infiltration. hsr203J and hin1 genes were expressed only in the 8107-infiltrated area. On the other hand, the expression of PR-1a and PR-1b genes was not detected in the 8107-infiltrated area, but in areas other than that developing the HR. Expression of these PR-1 genes was regulated simultaneously and the kinetics of the expression was dependent on the distance from the infiltration area. Therefore, diffusible signal(s) might be produced in HR-causing cells and transmitted to peripheral cells resulting in expression of PR genes. In NahG10 tobacco infiltrated with 8107, the HR was induced but resistance to TMV was not. Analysis using NahG10 tobacco also showed that the salicylic acid (SA)-dependent signal regulated the expression of hsr203J and PR-1a, but not that of hin1 and PR-1b. These results suggest that resistance of tobacco to 8107 is SA-independent and involves a quite different mechanism from acquired resistance to TMV induced by 8107-infiltration which is SA-dependent.

Amino Acid Sequence↗

PubMed1996

Dissociation in the control of cervical eosinophilic infiltration and collagenolysis at the end of pregnancy or after pseudopregnancy in ovariectomized steroid-treated rats.

Previous studies have demonstrated that during parturition the physiological ripening that permits dilation of the cervical canal is due to a widespread collagenolysis that follows a heavy polymorphonuclear leukocyte invasion of the uterine cervix. The aim of this study was to investigate whether there is any association between the ovarian steroid hormones involved in rat parturition and this phenomenon. Pregnant or pseudopregnant rats were ovariectomized (OVX) at Day 9 and then given a hormonal treatment (sufficient to maintain fetal viability) until Day 23. Cervical biopsies, taken from animals killed intrapartum or 1 h before expected parturition, were studied for eosinophilic infiltration and collagen birefringence. Intrapartum or sham-OVX pregnant rats showed a massive eosinophilic infiltration and a widespread collagenolysis as indicated by a loss of collagen birefringence. Ovariectomized pregnant rats treated with estrogen plus progesterone or with progesterone alone showed neither infiltration nor collagenolysis. In rats OVX during pseudopregnancy, estrogen given alone induced a significant infiltration of eosinophils in the cervical stroma; however, treatment with the combination of estrogen and progesterone was not able to promote eosinophilic infiltration. Collagenolysis was absent in all pseudopregnant animals. These results show that estrogen induced a cervical eosinophilic infiltration in rats but that when progesterone was added to the estrogen treatment the infiltration was not present; in addition, none of the steroid hormones assessed were responsible for the collagenolysis found in the cervical tissue at term.

Animals↗