Morphometric abnormalities in spleen and kidney of the progeny of mice fed American cranberry extract (Vaccinium macrocarpon) during pregnancy and lactation.

Cranberries and cranberry-derived diet supplements are often recommended for the treatment of urinary tract infections, also during pregnancy. These products contain strongly anti-angiogenic chemical compounds which could not be indifferent to the developing fetus. In the present work we evaluated the effect of feeding pregnant and lactating mice American cranberry extract (daily dose 0.88 mg) on the morphology and some parameters of spleen and kidney function of their adult progeny. Six weeks after delivery the morphometry of spleen and kidney, cytometric analysis of spleen lymphocytes, evaluation of humoral response to SRBC (Sheep Red Blood Cells), and examination of serum creatinine/urea concentration, were performed in the offspring. Spleens of progeny from experimental (E) group differed from the spleens of progeny of control mice in the lower number of lymphatic nodules and their larger diameter. Cytometry of spleen cells from progeny of E mothers revealed more CD19+ and CD8+ lymphocytes than in the control group. No difference was seen in the response to immunization by red blood cells of sheep (SRBC) between control and E offspring. An increase in the diameter of glomeruli was observed in the kidneys of the experimental group in comparison with the control group. No abnormalities in creatinine and urea serum level were observed. A higher concentration of VEGF and bFGF in E offspring sera in comparison to the controls was seen. CONCLUSION: Although the observed differences between the control and experimental group were not large, caution is recommended in using cranberries and their extracts during pregnancy until more research will be done on this topic.

Verification of the anatomy and newly discovered histology of the G-spot complex.

OBJECTIVES: To expand the anatomical investigations of the G-spot and to assess the G-spot's characteristic histological and immunohistochemical features. DESIGN: An observational study. SETTING: International multicentre. POPULATION: Eight consecutive fresh human female cadavers. METHODS: Anterior vaginal wall dissections were executed and G-spot microdissections were performed. All specimens were stained with haematoxylin and eosin (H&E). The tissues of two women were selected at random for immunohistochemical staining. MAIN OUTCOME MEASURES: The primary outcome measure was to document the anatomy of the G-spot. The secondary outcome measures were to identify the histology of the G-spot and to determine whether histological samples stained with H&E are sufficient to identify the G-spot. RESULTS: The anatomical existence of the G-spot was identified in all women and was in a diagonal plane. In seven (87.5%) and one (12.5%) of the women the G-spot complex was found on the left or right side, respectively. The G-spot was intimately fused with vessels, creating a complex. A large tangled vein-like vascular structure resembled an arteriovenous malformation and there were a few smaller feeding arteries. A band-like structure protruded from the tail of the G-spot. The size of the G-spot varied. Histologically, the G-spot was determined as a neurovascular complex structure. The neural component contained abundant peripheral nerve bundles and a nerve ganglion. The vascular component comprised large vein-like vessels and smaller feeding arteries. Circular and longitudinal muscles covered the G-complex. CONCLUSION: The anatomy of the G-spot complex was confirmed. The histology of the G-spot presents as neurovascular tissues with a nerve ganglion. H&E staining is sufficient for the identification of the G-spot complex.

Comparison of pathological staging and grading of urothelial bladder carcinoma in post-transurethral resection and post-radical cystectomy specimens.

Staging and grading of bladder cancer have a substantial impact on patients' prognosis. However, due to the relatively low quality and quantity of specimens from transurethral resection (TUR), initial histopathological examination may not be fully reliable. The aim of this study was to assess the repeatability of staging and grading in post-TUR and post-radical cystectomy (RC) specimens. Staging and grading in TUR and RC specimens were compared in a group of 181 consecutive patients. All microscopic examinations were performed by dedicated uropathologists. Median time from TUR to RC was 45 days. Additionally, an attempt to identify potential clinical variables influencing the risk of discrepancies was made. In post-RC specimens, the disease was down-staged in 13.8% and up-staged in 54.6% of patients (K = -0.03, p < 0.02). Muscle-invasive bladder cancer was diagnosed in 67.6% of patients initially staged as T1. Cancer was down-graded in 10.3% and up-graded in 17.9% of patients (K = 0.44, p < 0.02). Early onset of disease, female sex and time interval from transurethral resection of bladder tumor (TURBT) to RC had no effect on incidence of discrepancies. Pathological post-TUR examination is not predictive for the final stage of cancer. The incidence of under- or overgrading of bladder cancer is significant, and efforts should be made to reduce it.

Deleted in liver cancer protein family in human malignancies (Review).

The Deleted in Liver Cancer (DLC) protein family comprises proteins that exert their function mainly by the Rho GTPase-activating protein (GAP) domain and by regulation of the small GTPases. Since Rho GTPases are key factors in cell proliferation, polarity, cytoskeletal remodeling and migration, the aberrant function of their regulators may lead to cell transformation. One subgroup of these proteins is the DLC family. It was found that the first identified gene from this family, DLC1, is often lost in hepatocellular carcinoma and may be involved as a tumor suppressor in the liver. Subsequent studies evaluated the hypothesis that the DLC1 gene acts as a tumor suppressor, not only in liver cancer, but also in other types of cancer. Following DLC1, two other members of the DLC protein family, DLC2 and DLC3, were identified. However, limited published data are available concerning the role of these proteins in malignant transformation. This review focuses on the structure and the role of DLC1 and its relatives in physiological conditions and summarizes data published thus far regarding DLC function in the neoplastic process.

The effect of undecanones and their derivatives on tumor angiogenesis and VEGF content.

The in vivo effects of some derivatives of aliphatic ketones (2-undecanone, 3-undecanone, 4-undecanone and their derivatives) on L-1 sarcoma tumor angiogenesis and VEGF content were studied in Balb/c mice. Mice that inhaled 10% solution of 3-undecanone(3-on) or 1% solution of 2-undecanone propylene acetal (Acpr2) for 3 days after tumor cells implantation, presented lower neovascular response measured by tumor-induced cutaneous angiogenesis test (TIA) and lower tumor VEGF content in 5-days tumors, than non-inhaled controls. Other substances presented various effects on tumor VEGF concentration and angiogenesis. Histological examination of lesions collected from mice inhaled Acpr2, or non-inhaled controls, revealed small diffused areas of necrosis in the former group. In both groups, slight to moderate inflammatory infiltrations were seen at the tumor's margin. In Acpr2 group, there were less small blood vessels at tumor's margin than in the control group.

The effect of Chinese medicinal herb Rhodiola kirilowii extracts on cellular immunity in mice and rats.

UNLABELLED: Rhodiola kirilowii (RK) roots and rhizomes are traditionally used in China as a tonic, adaptogen, antimicrobial and anti-inflammatory drug. The aim of this work was to study the in vivo and in vitro effects of aqueous and 50% hydro-alcoholic extracts of RK rhizomes on some parameters of cellular immunity in H-2d mice and rats. We show for the first time that in vitro both extracts stimulated granulocyte activity and increased lymphocyte response to mitogens, and in vivo they enhanced the ability of lymphocytes derived from parental strain mice fed R. kirilowii aqueous and hydro-alcoholic extracts, to induce local cutaneous graft-versus-host reaction (GVH) in F1 hybrids. CONCLUSION: Rhodiola kirilowii extracts are cellular immunity enhancers.

The influence of Rhodiola quadrifida 50% hydro-alcoholic extract and salidroside on tumor-induced angiogenesis in mice.

UNLABELLED: The genus Rhodiola (Crassulaceae) consists of more than 100 species. They grow mainly in Tibet, China and Mongolia and are traditionally used as tonic, adaptogen, antidepressant and anti-inflammatory drugs. The best known is Rhodiola rosea (R. rosea) now cultivated also in Europe and North America, and present on the market as dietary supplement. Some authors reported anti-tumor activity of R. rosea extracts. Recently, we have published some data on immunomodulatory and antiangiogenic properties of R. rosea. Rhodiola quadrifida (R. quadrifida) belongs to the same family, but is almost not known in Europe, and there is no information about its possible anti-tumor as well as immunotropic and angiotropic activity. The aim of this study was to determine the influence of 50% hydro-alcoholic extract from rhizomes of R. quadrifida (Mongolian origin) and its main biologically active compound salidroside on tumor-induced angiogenesis. Angiogenesis was induced in the skin of Balb/c mice by grafting of syngeneic L-1 sarcoma cells. Mice were fed R. quadrifida extract or salidroside in daily doses 40, 200 and 400 microg, or 0.5, 1, 2, and 4 microg, respectively. After 72 hours, mice were sacrificed with lethal dose of Morbital. All newly formed blood vessels were identified and counted in dissection microscope. RESULTS: It was found that R. quadrifida extract and salidroside highly significantly decreased neovascular reaction in all doses applied.

The effect of Rhodiola quadrifida extracts on cellular immunity in mice and rats.

Rhodiola quadrifida (Rq) roots and rhizomes are traditionally used in Asia as a tonic, adaptogen, antidepressant and anti-inflammatory drug. The aim of this work was to study the in vivo effect of aqueous and 50% hydro-alcoholic extracts of Rq rhizomes on some parameters of cellular immunity in mice and rats. The metabolic activity of blood phagocyting cells was determined based on the measurement of intracellular respiratory burst after stimulation by PMA in RBA test. Potential bactericidal activity of phagocyting cells was determined in isolated blood leukocytes stimulated with killed microorganisms, according to the PKA test. Proliferative response of lymphocytes stimulated by mitogen concanavaline A (ConA) or lipopolysaccharide (LPS) were determined by MTT assay. Both extracts stimulated granulocytes activity in vitro and increased lymphocyte response to mitogens. The ability of parental strain mice lymphocytes to induce local cutaneous graft-versus-host reaction (GVH) in F1 hybrids was stimulated by 50% hydro-alcoholic extract only.

Hodgkin-like lymphoma, simulating anaplastic large cell lymphoma in the patient after renal transplantation--unusual case report and literature review.

UNLABELLED: We report the atypical case of posttransplant lymphoproliferative disorder (PTLD) diagnosed in 55-year men 9 years after renal transplantation. It was evaluated only by bone marrow biopsy, which showed its total involvement with malignant lymphoma. It was composed of two populations of lymphoid cells: large RS-like cells and small to medium ones, with slightly angular nuclei without visible nucleoli. Both cellpopulations did not show positive reaction for typical B cell markers (CD20, CD79a). Large RS-like cells were positive with CD30 and EBV-LMP. However, negative reaction with CD15 and positive reactions with UCHL1 and EMA were not consistent with classical type of Hodgkin lymphoma. Morphological picture and immunophenotype had suggested anaplastic T cell lymphoma. Because of negative reaction with ALK1, initial diagnosis was ALCL ALK-negative. Then, additional stains with BOB1 and Oct2 were performed, which were positive. Taking it into account the diagnosis was changed; finally Hodgkin-like B lymphoma was diagnosed. The patient was treated with CHOP regimen with good response. 5 years after primary diagnose of PTLD he is steel free of disease. CONCLUSIONS: 1. Apart from typical forms of PTLD, one may expect cases with nonspecific morphological picture and phenotype. 2. Negative reactions with typical immunohistochemical markers for lymphocytes of B cell line do not exclude the possibility of B-cell proliferation.

Posttransplant lymphoproliferative disorder: morphological picture and diagnostic difficulties.

Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of both solid organ and bone marrow transplantation. It includes a wide spectrum of proliferative changes ranging from reactive hyperplasia, borderline lesions to malignant lymphomas. PTLD develops in 1% to 10% of transplant recipients. We present 10 cases of PTLD. Five developed after renal, four after liver, and one after heart transplantation. Among the early lesions, we diagnosed two reactive plasmacytic hyperplasias; one infectious mononucleosis-like PTLD; one polymorphic lesion; and one "mixed" case of plasmacytic hyperplasia in one tonsil with a polymorphic PTLD in the second one. Among the lymphomas, we observed three diffuse large B-cell lymphoma (DLBCL); one mantle lymphoma; and one Hodgkin lymphoma-like PTLD. The morphological pictures of six PTLD cases were typical and posed no diagnostic problems. In the one case of plasmacytic hyperplasia, the lymph node morphology was atypical with atrophy of lymphoid components accompanying plasma cell proliferation. Contrary to a good prognosis of early, reactive PTLD, this patient experienced a rapid course and succumbed to sepsis. The most difficult case was a rare Hodgkin lymphoma-like PTLD, which was diagnosed only by a bone marrow biopsy. Because of its noncharacteristic immunophenotype, it was primarily diagnosed as an anaplastic lymphoma of the T-cell type. After additional immunohistochemical studies (BOB and OCT2), we established the final diagnosis of Hodgkin lymphoma-like PTLD. Due to the increasing number of organ transplantations, doctors of various specialties may encounter PTLD.

Pathomorphological features of acute rejection in patients after orthotopic liver transplantation: own experience.

INTRODUCTION: Acute hepatic allograft rejection remains an important problem following liver transplantation. Liver biopsy specimens show a combination of characteristic changes, first observed by Snover as a diagnostic triad: portal inflammation, bile duct damage, and central or portal vein endothelial inflammation (endothelitis or endothelialitis). The aim of this study was to describe our histopathological assessment of liver transplants. MATERIALS AND METHODS: In the period between September 2000 and June 2004, we evaluated 150 liver biopsy specimens from 105 liver recipients. RESULTS: Acute rejection was diagnosed in 26.6% of liver biopsies taken from 31.4% patients who demonstrated clinical symptoms of liver damage. In 90% of cases the rejection was described as minimal or mild, and in 10% as moderate. There was no episode of severe acute rejection. Only four biopsies (10%) showed nothing but Snover triad changes. In 9 (22.5%) cases only acute rejection was diagnosed; the remaining showed in addition to acute rejection the possibility of other concomitant pathologies: viral infection in 15 cases (37.5%), biliary flow obstruction in 11 cases (28.5%), functional cholestasis in two cases (5%), and ischemic complications in three cases (7.5%). CONCLUSIONS: Histologically confirmed acute rejection episodes were diagnosed in 14.9% liver recipients. Liver biopsy specimens, aside from Snover triad features, often showed other unspecific morphological changes. Differentiation of acute rejection from other accompanying diseases is sometimes difficult, requiring precise clinical data and pathologist experience.

Morphologic features of hepatitis C recurrence in patients after orthotopic liver transplantation-preliminary analysis of our case observations.

INTRODUCTION: Hepatitis C virus (HCV) recurrence is almost universal in patients after liver transplantation. The diagnosis of reinfection is more difficult than that of a primary process, as shown by our pathomorphologic analysis of cases of HCV recurrence. MATERIAL: During 5.5 years, 240 liver biopsies included 54 obtained from liver transplant recipients with primary HCV infections, among whom 26 (56.5%) had clinical signs and symptoms of hepatitis. Nineteen patients from this population underwent 30 liver biopsies. In addition, seven biopsies were performed in five patients without clinical signs of reinfection. RESULTS: In 44.2% of patients with HCV recurrence and 15% without reinfection, the intensity of the primary process in the native livers was assessed as high. Reinfection was found in all patients with liver carcinoma and 67% with hepatocyte dysplasia. Histologic signs of infection were estimated as minimal (n = 4), mild (n = 19), or moderate (n = 4). In five patients with reinfections and one without recurrence, histologic manifestations of acute rejection were also observed. In conclusion, HCV was the indication for liver transplantation in 22.4% cases. Clinical manifestation of recurrence was found in 56.5% of the patients, who tended to be older than those without disease recurrence. Upon microscopy, lobular lesions predominated over the portal changes. Factors predisposing to HCV recurrence were coexistence of other liver disorders, a high intensity of the inflammatory process, hepatocyte dysplasia, and/or hepatocellular carcinoma in the native liver and acute rejection episodes.

Primary lymphoma of the liver -- morphological and clinical analysis of 6 cases. Success of aggressive treatment.

Histological, clinical and immunohistochemical analysis of 6 cases of primary liver lymphomas (PLL) are presented. PLL represents 4.3% of primary malignant liver tumors diagnosed in our department. The patients were relatively young people, who despite the presence of a large tumor, were in good general health status. There were no signs of scirrhosis, and cancer markers were normal. All lymphomas were CD20, CD79a, BAX positive, CD3, CD30, EMA, CD10, CD5, CD59, c-myc, Bcl2, EBV(LMP), CK negative. The proliferation index (Ki67) was high, ranging from 50-100%. In two cases positive staining for Bcl6 and in another one for cyclin D1 was obtained. The major histological type of the tumor was diffuse large B-cell lymphoma. Positive immunohistochemical results with BAX and the lack of Bcl2, c-myc and CD59 are associated with better prognosis. We have not confirmed the value of Bcl6 and CD10 stains as a predictor of poor outcome. Despite clinically advanced stage at the time of diagnosis, if treated appropriately, the primary lymphoma of the liver has relatively good prognosis (five of our patients are alive).

Fluid consumption, electrolyte excretion and heart remodeling in rats with myocardial infarct maintained on regular and high sodium intake.

The purpose of the study was to determine effect of high sodium intake on fluid and electrolyte turnover and heart remodeling in the cardiac failure elicited by myocardial infarction (MI). The experiments were performed on four groups of Sprague Dawley rats maintained on food containing 0.45% NaCl and drinking either water (groups 1, 2) or 1% NaCl (groups 3, 4). Groups 1 and 3 were sham-operated while in groups 2 and 4 MI was produced by the coronary artery ligation. In each group food and fluid as well as sodium intake, urine (Vu), sodium (UNaV), potassium (UKV) and solutes (UosmV) excretion were determined before and four weeks after the surgery. Size of the infarct, left ventricle (LV) weight and diameter of LV and right ventricle (RV) myocytes were determined during post-mortem examination. Before the surgery groups 3 and 4 ingested significantly more fluid and sodium, had higher Vu, UNaV, UKV and UosmV than the respective groups 1 and 2. In groups 2 and 4 MI resulted in significant decrease in Vu, UNaV and UosmV in comparison to the pre-surgical level. In Group 4 MI resulted also in a significant decrease of food and sodium intake. The MI size did not differ in groups 2 and 4 while diameter of LV myocytes was significantly greater in groups 2 and 4 than in groups 1 and 3, and in group 4 than in group 2. The study reveals that prolonged high sodium consumption increases fluid and electrolyte turnover both in the sham and in the MI rats and that the MI causes decrease in food and sodium intake in rats on high but not on regular sodium intake. In addition high sodium diet promotes development of greater post-MI hypertrophy of the LV myocytes.

Do all well-differentiated thyroid cancers constitute a definite contraindication to obtaining organs for transplantation? A case report.

In this case a thyroid gland tumor was diagnosed with fine needle aspiration (FNA) in a 34-year-old female donor of a liver fragment for living related liver transplantation. This diagnosis disqualified her as a donor. The increased incidence of thyroid cancer in Poland presents the possibility of their occurrence in potential donors. Well-differentiated thyroid papillary carcinomas larger than 1 cm in diameter, as well as follicular and medullary carcinomas (regardless their size and or clinical staging), present absolute contraindication to donation. Papillary microcarcinoma restricted to the thyroid gland (with no metastases in local lymph nodes) because of its specific behavior and almost always benign course, requires an individualized approach. It seemed that when a recipient is in a life-threatening condition, we should consider taking organs from a donor suffering of papillary microcarcinoma restricted to the thyroid gland.

Plasmacytic hyperplasia--the early form of posttransplant lymphoproliferative disorder--with atypical morphology and clinical course in patient after liver transplantation: a case report.

This case report describes an early lesion of posttransplant lymphoproliferative disorder (PLTD)--plasmacytic hyperplasia with atypical morphology. The 54-year-old patient was 4 months after liver transplantation due to alcoholic cirrhosis. The postoperative course had been uneventful without graft rejection episodes. Primary immunosuppressive therapy included tacrolimus and prednisone. On admission to the hospital the patient showed rapidly increasing jaundice, hepatomegaly, anemia, thrombocytopenia, and significant leukocytosis. A biopsy suggested generalized infection. Acute Epstein-Barr virus (EBV) infection was confirmed using serological methods. Despite treatment the patient died. On autopsy we found features of generalized infection. Histological examination of the enlarged lymph nodes showed plasmacytic hyperplasia despite lymph node atrophy. Plasmacytic hyperplasia, an early lesion of PTLD despite usually a good prognosis with multifactor therapy may display a rapid course that leads to death through intensified immunosuppression. In accordance with other reports we confirmed reactivation of EBV infection as the probable cause of plasmacytic hyperplasia. The lymph node morphology of plasmacytic hyperplasia may be atypical with atrophy of lymphoid components accompanying plasma cell proliferation.

Immature hepatic tumor of bimodal differentiation in a young adult patient: a novel lesion expressing beta-catenin and mimicking a distinct phase of hepatogenesis.

PATIENT AND METHODS: A large right-sided liver tumor was incidentally discovered and totally resected in a 21-year-old female patient without chronic liver disease. Histopathologic examination revealed that this malignant tumor does not fit any of the known types of primary liver tumors reported thus far. RESULTS: The lesion chiefly consisted of numerous solid nests composed of immature epithelial cells disclosing a marker profile typical for hepatocytes and strongly expressing beta-catenin. These nests were tightly associated with abnormal duct-like profiles exhibiting features of bile duct cells. CONCLUSIONS: The finding of numerous neoplastic hepatobiliary units ('liverlets') suggests that this tumor may mimic a distinct developmental phase of hepatogenesis close to ductal plate formation.

Carcinoma adenoides cysticum as a primary neoplasm most probably derived from biliary ducts--case report.

UNLABELLED: Adenoid cystic carcinoma is a typical tumor of large and small salivary glands and sometimes of the breast. The aim of this report is presentation of a case of primary liver cancer with adenoid cystic cancer histology in 21-year old female patient. The tumor was discovered accidentally during pregnancy. The patient did not complain of any ailments. In biochemical tests only slightly elevated bilirubin, alkaline phosphatase and GGT concentrations were observed. No focal lesions in other organs were found in imaging examinations. Huge tumor of 30-cm diameter was found during surgery, encompassing almost whole left and right lobe of the liver. The biopsy taken from the tumor revealed histological picture typical for adenoid cystic carcinoma. Additional stainings and immunohistochemical examinations pointed to biliary ducts as possible place of origin of the neoplasm. SUMMARY: Among primary liver tumours of atypical clinical course the possibility of adenoid cystic carcinoma, deriving most probably from the biliary ducts, should be considered.

[Benign clear cell tumor of the lung (sugar tumor). Morphologic, immunohistochemical and ultrastructural evaluation]. / Lagodny, jasnokomórkowy guz pluca ("guz cukrowy"). Ocena morfologiczna, immunohistochemiczna i ultrastrukturalna guza.

Clear cell tumour or "sugar tumour" of the lung is a rare primary neoplasm with unique histologic and electron microscopic features that may resemble those of metastatic renal cell carcinoma. An immunohistochemical studies are useful in a differential diagnosis these tumours: HMB45 in combination with a panel of various antibodies. The authors present a benign clear cell tumour of the lung, diagnosed on the base of its morphological, immunohistochemical and ultrastructural features.