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Cholesterol transport in mesenteric lymph of the preruminant calf: contribution of cholesterol transposition from blood to lymph.

Eight preruminant male calves were prepared surgically with lymphatico-venous shunts and re-entrant gallbladder to proximal duodenum shunts. Liquid diets were formulated to contain 12.5% dried skim milk (SM) or 10.5% SM to which was added 2% soybean oil (SBO), milk fat (MF) or beef tallow (T). Two calves were assigned to each dietary treatment. Transposition of cholesterol from blood capillaries to intestinal lymph was determined by injection of 100 microCi [4-14C]-cholesterol into the blood of calves at feeding time. To avoid recirculation of [4-14C]-cholesterol via the enterohepatic circulation, bile was diverted and replaced with bile from a donor calf fed an identical diet. For the SM, SBO, MF and T diets, respectively, cholesterol transposed from capillaries was 44, 61, 36 and 48% of the cholesterol transported in the mesenteric lymph. When cholesterol synthesis in response to test diets was calculated, we found that intestinal cholesterol synthesis is less when calves are fed SM or SBO than when fed T or MF.

Absorption↗

The architecture of rat lymph nodes. II. Lymph node compartments.

Although lymph nodes are conventionally regarded as composed of superficial cortex, deep cortex, and medullary cords merge gradually into each other, the sinuses, the interstitium, and the germinal centres are separated by cellular borders that seem sufficiently complete to limit the rate of exchange of cells and molecules. Accordingly, the cellular composition shows distinct differences on either side of these borders. These compartments show further division into regions, the sinuses into superficial and deeply situated sinuses, the interstitium into superficial interstitium, follicles, paracortical nodules, and medullary interstitium, characterized by differences in densities of various cell types. Mechanisms behind the different distribution of cells within the different lymph node compartments and regions are discussed.

Animals↗

Gene expression profiling reveals a massive, aneuploidy-dependent transcriptional deregulation and distinct differences between lymph node-negative and lymph node-positive colon carcinomas.

To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P < 1e-7). A significant proportion of these genes mapped to chromosome 20 (P = 0.01). Seventeen genes had a >5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node-negative and lymph node-positive tumors (P < 0.001), the functional annotation of which revealed a preponderance of genes that play a role in cellular immune response and surveillance. The microarray-derived gene expression levels of 20 deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/beta-catenin signaling cascade, suggesting similar pathogenic pathways.

Adenocarcinoma↗

Utility fo gallium-67 in determining the radicality of lymph node dissections of the neck for metastatic lymph nodes with extranodal spread in patients affected by carcinoma of the head and neck.

AIMS AND BACKGROUND: Based on the fact that scintigraphy more readily reveals uptake of a radioisotope in a superficial position owing to incomplete surgical radicality, the authors examined by 67Ga scintigraphy a group of patients who had undergone dissection of lymph nodes of the neck from carcinoma with extranodal spread. They then checked the follow-up to ascertain the efficacy of 67Ga scintigraphy in relation to the eventual recurrences in the soft tissues of the neck. METHODS: A group of 136 patients were examined by 67Ga scintigraphy and followed for a minimum of 3 years after complementary radiotherapy. A group of 20 patients with no lymph node metastases was used as control to evaluate eventual false positives or false negatives. RESULTS: Recurrences in the soft tissues of the neck occurred in 35 (42.7%) of the 82 patients positive at 67Ga scintigraphy and in 6 (11.1%) of the 54 patients negative at the examination (P = 0.0001). All the patients in the control group were negative at 67Ga scintigraphy and without recurrences. CONCLUSIONS: 67Ga scintigraphy can give reliable information on the risk of recurrences in the soft tissues of the neck. Since in spite of postoperative radiotherapy the percentage of local recurrences in cases with positive 67Ga scintigraphy was rather high (42.7%), the authors propose a scheme of radiotherapy based on administration of a higher dose per fraction on the scintigraphically positive area.

Adult↗

Size of breast cancer metastases in axillary lymph nodes: clinical relevance of minimal lymph node involvement.

BACKGROUND: Overt ipsilateral axillary lymph node metastases of breast cancer are the most significant prognostic indicators for women who have undergone surgery, yet the clinical relevance of minimal involvement (isolated tumor cells and micrometastases) of these nodes is uncertain. PATIENTS AND METHODS: We evaluated biologic features, adjuvant treatment recommendations, and prognosis for 1,959 consecutive patients with pT1-3, pN0, minimal lymph node involvement (pN1mi or pN0i+), or pN1a (single positive node) and M0, who were operated on and counseled for medical therapy from April 1997 to December 2000. RESULTS: Patients with pN1a and pN1mi/pN0i+, when compared with patients with pN0 disease, were more often prescribed anthracycline-containing chemotherapy (39.1% v 33.2% v 6.1%, respectively; P < .0001) and were less likely to receive endocrine therapy alone (9.8% v 19.4% v 41.9%, respectively; P < .0001). At the multivariate analysis, a statistically significant difference in disease-free survival (DFS) and in the risk of distant metastases was observed for patients with pN1a versus pN0 disease (hazard ratio [HR] = 2.04; 95% CI, 1.46 to 2.86; P < .0001 for DFS; HR = 2.32; 95% CI, 1.42 to 3.80; P = .0007 for distant metastases) and for patients with pN1mi/pN0i+ versus pN0 disease (HR = 1.58; 95% CI, 1.01 to 2.47; P = .047 for DFS; HR = 1.94; 95% CI, 1.04 to 3.64; P = .037 for distant metastases). CONCLUSION: Even minimal involvement of a single axillary node in breast cancer significantly correlates with worse prognosis compared with no axillary node involvement. Further studies are required before widespread modification of clinical practice.

Adult↗

Sentinel lymph node tumor load: an independent predictor of additional lymph node involvement and survival in melanoma.

BACKGROUND: Even though 60% to 80% of melanoma patients with a positive sentinel lymph node (SLN) have no positive additional lymph nodes (ALNs), all these patients are subjected to an ALN dissection (ALND) with its associated morbidity. The aim of this study was to predict the absence of ALN metastases in patients with a positive SLN by using features of the primary melanoma and SLN tumor load. METHODS: Of 71 SLN-positive patients, 52 had metastasis limited to the SLN (group 1), and 19 had > or =1 positive ALN after ALND (group 2). The tumor load of the SLN was assessed by measuring the total surface area by computerized morphometry. Breslow thickness, ulceration and lymphatic invasion of the primary tumor, and total SLN metastatic area were tested as covariates predicting the absence of positive ALNs. RESULTS: The mean SLN metastatic area was 1.18 mm(2) (group 1) and 3.39 mm(2) (group 2) (P = .003) and was the only significant and independent factor after multivariate analysis (P = .02). None of the patients with both a Breslow thickness <2.5 mm and an SLN metastatic area <.3 mm(2) had a positive ALN. CONCLUSIONS: SLN metastatic area can be used to predict the absence of positive ALNs in melanoma patients. In this study, patients with a Breslow thickness <2.5 mm and an SLN tumor load <.3 mm(2 )seemed to have no positive ALN and had excellent survival. We hypothesize that this subgroup might not benefit from ALND. Prospective larger trials, using this model and randomizing between ALND and no ALND, should confirm this hypothesis.

Adolescent↗

Role of the regional lymph node in neoplasia: cellular mediated reactivity in vitro by autologous regional or distant lymph nodes or peripheral blood lymphocytes of dogs with spontaneous neoplasms.

This report concerns the in vitro reactivity of lymphocytes obtained from regional (draining) lymph nodes, distant nodes and peripheral blood against autochthonous spontaneous neoplasms. Tumors, blood and lymph nodes were collected aseptically prior to necropsy. Primary tumor cultures were established. Viable tumor cells were first incubated with media or autologous sera and then various numbers of lymphocytes were added. The mixtures were rotated for 60 minutes and then plated. Two and/or five days later cultures were terminated and viable target cells counted. The results of the tests were similar regardless of the lymphocyte source utilized. In vitro tumor cell cytotoxicity by high numbers (1000:1 lymphocytes to tumor cells) of any autologous lymphocytes and interference of such reactivity by autologous sera were demonstrated. Low numbers (100:1) of any lymphocyte source lead to tumor growth stimulation. Animals with spontaneous neoplasms are probably the best model for the study of human clinical oncology. Our data demonstrate that in these animals lymphocytes obtained from regional nodes were not unique in their reactivity to tumors. It is possible that early in the disease the draining node may play a vital role in initiation of host response; however, later its importance probably diminishes.

Adenocarcinoma↗

[Foreign proteins in the blood and lymph after oral administration. Giant molecular foreign proteins in the blood and lymph of adult animals and men and their biological effectiveness after enteral administration].

With isotopic and immunological methods it could be demonstrated that: 1. Rabbit- and horse-proteins can be absorbed from the gut into blood and lymph of rats and dogs in highmolecular form. 2. The highmolecular part after the passage of the intestinal wall was calculated between 5 and 20%. 3. The increase of the lymphocytotoxicity in the lymph of rats from 1:2 to 1:16 after enteral application of horse-antihuman-lymphocyte-gammaglobulin indicates the biological activity of the protein after the penetration through the gut. Furthermore the immunosuppressive effect of ALS after oral application could be demonstrated on the survival time of allogeneic skin transplants. A significant lymphopenia could be induced in dogs after the oral application of horse-antidog-gammaglobulin. From these findings far reaching consequences must be drawn concerning nutritional and immunological aspects. By the enteral absorption of proteins for example a natural tolerance must be induced which is broken in food allergies. Furthermore it is conceivable that the immunocompetent cells of the gastro-intestinal tract can be manipulated for the purpose of immunization or desensibilization within therapeutical programs of prophylactic medicine.

Administration, Oral↗

Simultaneous occurrence of medullary and papillary carcinomas of the thyroid gland with metastases of papillary carcinoma to the cervical lymph nodes and the coinciding small B-cell lymphocytic lymphoma of the lymph nodes--a case report.

We report a case of a simultaneous occurrence of medullary and papillary carcinomas of the thyroid gland with metastases of a papillary carcinoma to the cervical lymph nodes and a concurrent small B-cell lymphocytic lymphoma revealed in the lymph nodes examined in a 71-year-old woman. The diagnosis was based on microscopic examination of surgical specimens and supported by immunohistochemistry. Additionally, P53 and RET mutation analysis was performed. In this case, the coincidence of medullary and papillary carcinomas of the thyroid gland may account for a true composite tumor. The coexistence of a small B-cell lymphoma in our patient may be explained by irradiation treatment undergone during the adolescence.

Aged↗

Induction of lymph follicle formation with several mitogens and adjuvants in the mouse popliteal lymph node.

The formation of lymph follicles in draining popliteal nodes was investigated in young adult male mice which had been injected in the rear footpad with several mitogens and adjuvants, and killed after 3-21 days. PPD (100 micrograms-1 mg) and PHA (25-500 micrograms) induced germinal centers in association with existing follicles and mild plasmacytosis, but failed to produce new follicles in draining nodes. Endotoxin LPS (50-200 micrograms), Con A (50 micrograms-1 mg) and PWM (50 micrograms-1 mg) induced germinal centers within existing follicles and plasmacytosis, and also produced new follicles which soon developed germinal centers. Both Freund's complete and incomplete adjuvants (FCA and FICA, 25 microliters) induced virtually no germinal centers and plasmacytosis, but produced a significant number of new primary follicles. Poly (A, U) (600 micrograms) produced neither germinal centers nor plasmacytosis, and did not induce new follicles. Analysis of the distribution of lymphoid cells which had incorporated 3H-thymidine in the draining nodes at 3 days after the injection of test substances indicated that PPD, PHA, LPS, Con A and PWM preferentially stimulated in vivo the same types of lymphocytes as they do in vitro. FCA triggered lymphocyte activation in the deep cortex, whereas Poly (A, U) appeared not to stimulate lymphocytes in vivo. In further experiments, induction of lymph follicles with artificially precipitated PPD and PHA was studied. The draining nodes treated with alum-precipitated PPD or PHA were found to produce a significant number of new follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Pharmaceutic↗

Pathways of lymph flow to and from the medulla of lymph nodes in sheep.

Medullary sinuses are continuous with penetrating afferent lymphatics, and with the trabecular and tubular sinuses which penetrate through the cortex. Tubular sinuses are often associated with blood vessels, especially in the deep cortex, and they appear to be important in the transport of lymphocytes. The subcapsular sinus is continuous over the cortex and the medulla, although trabeculae and reticular processes appear to restrict the flow of afferent lymph to the subcapsular sinus over the medulla. Lymph leaves the medulla through up to 100 or more initial efferent lymphatics, some only 60 micron across. Almost all of these arise from sinuses adjacent to the capsule lining the hilus. Some efferents remain associated with the capsule for a short distance whereas others, especially in nodes with a deep hilar depression, leave immediately at an angle of 30-90 degrees.

Animals↗

[Antigen-specific lysis in vitro of lymph node cells of intact mice injected with RNA from viable lymph node cells of immunized animals].

Supernatant fluid obtained after centrifugation of the suspension of viable lymph node cells of immunized animals proved to induce in vivo in the lymph node cells of intact mice sensitivity to lysis with a specific antigen in vitro. This property was possessed after chromatography of the supernatant fluid on Sephadex G-200 by the 3rd fraction (MW about 30000 dalton). DNA-ase, trypsin or deproteinization failed to influence whereas RNA-ase inactivated this fraction in respect to the inducing properties.

Animals↗

[Studies on the lymph drainage of the eye. 2. Drainage of lymph-dependent radioactive substances from the anterior chamber. (author's transl)].

In order to study lymph drainage from the eye colloid solutions (198Au-colloid and 99mTc-sulfur-colloid) were injected into the right anterior chamber of the eye in 12 rabbits. The distribution of the radioactivity was measured in vivo with an Anger-type camera and in vitro with a sodium iodine crystal well-counter after dissection. The drainage of radioactivity from the anterior chamber had an average half-life of 36 min. The drained activity could be found mainly in blood, liver, kidney, and bone tissue. Moreover, a concentration of radioactivity significantly surpassing the concentration in blood was measured in the right retrobulbar space in 75% of the cases and in the cervical lymph nodes in 50% of the cases. These findings substantiate a communication between the anterior chamber of the eye and the retrobulbar space in the form of a lymphatic or a prelymphatic-lymphatic flow.

Animals↗

Migration inhibition of lymph node lymphocytes as an in vitro assay for cell-mediated immunity in the draining lymph nodes of parenterally immunized mice.

This paper describes a method for in vitro measurement of specific cell-mediated immunity in the mouse. Animals were immunized parenterally with ovalbumin in Freund's incomplete or complete adjuvant, and a direct migration inhibition assay was performed, using lymphoid cells from the draining lymph nodes. Migration inhibition was found to be antigen specific, correlated with systemic delayed-type hypersensitivity measured in vivo by skin testing, and had a high degree of sensitivity for ovalbumin. The migrating cells were identified as lymphocytes. Lymph node lymphocyte migration inhibition provides a reliable in vitro assay for regional CMI in the mouse.

Animals↗

[Lymph drainage routes and variability in preoperative efferent lymph flow scintigraphy in malignant melanoma of the trunk].

Malignant melanoma of the skin has become a real problem due to the increasing number of cases. No other tumor is induced by long term UV-radiation of the skin. Excision of the primary tumor is the treatment of choice in this disease. Before excision of the tumor lymphoscintigraphy is the first choice in diagnosis to demonstrate the draining lymph vessels and lymph node groups of an malignant melanoma for later operation. This work current the status quo of lymphoscintigraphy in malignant melanoma of the trunk.

Adult↗

[Lymph node eosinophilic granuloma. Apropos of 2 cases of Langerhans-cell histiocytosis with isolated lymph node involvement].

The authors report two cases of isolated lymph node involvement by Langerhans' cell histiocytosis which affected two young children. The histologic aspect reveals that lymph nodes have been modified by a proliferation of large histiocyte-like cells, associated with eosinophils. An immunohistochemical study on paraffin sections and for one case on frozen sections, reveals the usual phenotype of Langerhans' cells: these cells stain positively with S 100 protein and CD1 and are negative for both lysozyme and al antichymotrypsine. After a period of two years for one child and four years for the other, these children are in total remission, one spontaneously, the other after chemotherapy.

Child, Preschool↗

Results of extended lymph node dissection for gastric cancer cases with N2 lymph node metastasis.

The therapeutic value of extended lymph node dissection (D2) for gastric cancer remains controversial. Limited lymph node dissection, however, leaves cancer cells in the second tier of nodes (N2) in patients with N2 metastasis. This retrospective study was, therefore, undertaken to clarify which patients would be most likely to benefit from D2 dissection, even with N2 metastasis. Two groups, N2 cases with (n = 40) and without (n = 24) the development of recurrence after curative surgery, were compared. Borrmann type IV and serosal invasion were significantly related to recurrence. The number of metastatic nodes did not differ significantly between the two groups. All (7/7) of the Borrmann type IV cases with N2 metastasis developed recurrence and died. However, one quarter (7/30) of the cases with serosal invasion and N2 metastasis showed no sign of recurrence. D2 dissection is a surgical treatment which offers the potential to cure gastric cancers, other than Borrmann type IV tumor, with N2 metastasis.

Female↗