[Renal vascular lesions and the occurrence of hypertension in patients with IgA nephropathy]. / Lésions vasculaires rénales et développement d'une HTA chez les patients atteints d'une glomérulonéphrite à dépôts mésangiaux d'IgA. Une histoire familiale d'hypertension artérielle.

Worse prognosis of IgA nephropathy (IgAN) is associated to hypertension, high proteinuria, glomerular and vascular sclerosis. A family story of hypertension (FHT) in relatives could be a strong predictor of the occurrence of hypertension (HT) in children. Renal vascular lesions (RVL) are often observed in normotensive patients with IgAN. In order to evaluate a possible association between FHT and LVR in patients with IgAN, we investigated two groups of 73 IgAN patients, sex (56 males and 17 females) and age matched, according to the presence or not of FHT. FHT was diagnosed if relatives and/or at least one child under 60 years of age had treatment for HT or systolic and diastolic BP over 140/90 mmHg at the time of the survey. Patients entering into the study were followed during an average period of 5 to 8 years. At the end of the study, all patients were explored for HT and renal function. Creatinine clearance (CrCl) was evaluated by Cockcroft and Gault formula and renal failure was defined as CrCl<60mL/min. The results were as follow: at the time of renal biopsy, RVL were observed in 73% of males with FHT vs 16% of males without FHT (p<0.0001) and 70.6% of females with FHT vs 29.4% of females without FHT (p<0.001); at the end of the study period, HT was significantly associated to FHT in 89.6% of patients group with FHT vs 22.6% of HT patients in the group without FHT (p<.0001). Renal failure was present in 45.2% of patients with FHT vs 4.1% of patients without FHT (p<0.0001). These data suggest: VRL could be dependent of genetic factors; FHT should be an early predictor of VRL in patients with IgAN; FHT might be a risk factor for renal failure in patients with this renal disease.

[Epidemiologic description of amyloidosis diagnosed at the University Hospital of Rennes from 1995 to 1999]. / Epidémiologie descriptive des amyloses diagnostiquées au CHU de Rennes de 1995 à 1999.

INTRODUCTION: The frequency of amyloidosis is not well known in France. We compiled a register of amyloidosis diagnosed from 1995 to 1999 in the University Hospital of Rennes. PATIENTS AND METHODS: This retrospective study was performed between 01 January 1995 and 31 december 1999. Diagnosis was assessed on positivity of red Congo by anatomopathology. Immunohistochemistry allowed the definition the type of amyloidosis. Clinical data, staging and outcome of patients were analysed. RESULTS: Forty-three amyloidosis were diagnosed (27 women, 16 men) with an incidence of 8,6 new cases per year. Mean age was 63.7 years. Five diagnosis were realised in 1995, six in 1996, six in 1997, 12 in 1998, 14 in 1999. Twenty amyloidosis were AL type (46.5%), seven AA (16.3%), 1 beta2 microglobulin type, 15 (35%) remained of undetermined type. Thirty-three amyloidosis (77%) were systemic, 10 were localized to one organ (23%). When diagnosis was made, biopsies concerned affected organs in 86% of the cases, accessory sites (labial salivary glands, bone marrow) in only 14% of the cases. Twenty-five patients died (58%). Two deaths were treatment-related, 16 to amyloidois, seven patients died of another complaint. CONCLUSION: Increased incidence of amyloidosis needs to be confirmed. We emphasize the importance of immunohistochemical typing on frozen samples, the value of accessory biopsies and the need for complete extension staging.

Expression of Po66-CBP, a galectin-8, in different types of primary and secondary broncho-pulmonary tumors.

The monoclonal antibody Po66 is an IgG1 immunoglobulin isolated from a human bronchial squamous carcinoma and directed against a carbohydrate binding protein, Po66-CBP, belonging to the galectin family involved in neoplastic processes. This Po66 antibody has been shown to be useful for immunoscintigraphic detection of squamous cell carcinoma metastasis. We examined the expression of Po66-CBP in a wider range of primary or secondary malignant tumors of the lung of various histological types. We studied 52 specimens of broncho-pulmonary tumors including 41 primary squamous, glandular or neuro-endocrine tumors and 11 secondary tumors of glandular, connective tissue, melanocytic or germinal origin as well as 9 extra-pulmonary primary tumors with histological types similar to lung metastases. An immunohistochemical study was performed using an amplification system on paraffin-embedded sections. All histological types were positive for Po66 antibody, the cell origin giving no influence on the expression of Po66-CBP. There was however a relation between Po66-CBP expression and the degree of differentiation notably for squamous cell cancer and neuro-endocrine tumors. The metastatic character of the tumor tissue did not affect Po66-CBP expression.

Clinical significance of cell proliferation, microvessel density, and CD44 adhesion molecule expression in renal cell carcinoma.

Renal cell carcinoma (RCC) is known to have a wide variation in clinical outcome despite the use of conventional prognostic factors, such as staging or grading. A better knowledge of the biologic aggressiveness of RCC could facilitate the selection of patients at high risk of tumor progression. The aim of this study was to determine if use of measurements of vascular density, cell proliferation, and cell adhesion could better predict the biologic behavior of RCC. We immunohistochemically analyzed CD34, Ki-67, and CD44H expression on formalin-fixed, paraffin-embedded tissues from 73 RCCs for quantifying microvessel density (MVD), Ki-67 labeling index (LI), and CD44H LI, respectively. Univariate cancer-specific survival analysis showed that tumor stage (P < .01), tumor size (P < .001), nuclear grade (P < .01), metastasis (P < .001), MVD (P < .03), Ki-67 LI (P < .001), and CD44H LI (P < .0001) were predictors of tumor-related death. There was a statistical correlation between CD44H LI and both Ki-67 LI (r' = .3) and MVD (r' = -44). Ki-67 LI (P < .04) and CD44H LI (P < .02), as well as metastasis (P < .008), emerged as independent predictors of cancer-specific survival in multivariate analysis in patients with metastases (P < .04 and P < .02, respectively) and in patients without metastases (P < .006 and P < .00001, respectively). Our study suggests that vascular density, cell proliferation, and cell adhesion represent a complex tumor-host interaction that may favor progression of RCC. Cell proliferation and CD44H expression appear to be powerful markers to identify patients with an adverse prognosis.

Detection of early gamma-postirradiation effects in murine spleen by proton NMR relaxation times.

BACKGROUND: It was our aim to evaluate the potential of proton relaxation times for the early detection of radiation-induced spleen changes. MATERIALS AND METHODS: Female Swiss mice were irradiated with doses ranging from 0.05 Gy to 4 Gy. The body weight, the spleen weight and the spleen water content of single animals were determined. Measurements of longitudinal (T1) and transversal (T2) proton relaxation times of the spleen samples were performed in a 0.47 T spectrometer. Histological examinations of the control and irradiated organs were performed. RESULTS: NMR measurements during the first five days after irradiation showed that total body gamma-irradiation with doses from 1.5 Gy to 4 Gy results in decreasing T1 of the murine spleen. Significant shortening in T2 was observed for the spleen of animals irradiated with a dose of 4 Gy. Histological examinations demonstrated subnormal architecture in slices derived from animals irradiated with 2 Gy and 4 Gy. CONCLUSION: The fluctuations of the spleen T1 and T2 of irradiated mice are correlated with relative spleen weight and can be used to estimate radiation induced changes in this organ.

Hemodynamic and histomorphometric characteristics of dilated cardiomyopathy of Syrian hamsters (Bio TO-2 strain).

The natural history of the disease of the dilated strain Bio TO-2 of cardiomyopathic hamsters (CMH) is not totally characterized. We investigated its hemodynamic and histomorphometric characteristics at 140, 180, 220, 260, and 300 days of age. Forty CMH and 40 controls were investigated (8 at each stage). Mean arterial pressure (MAP, carotid artery catheter) and cardiac output and femoral blood flow (CO, FBF, transit time method) were measured in anesthetized animals. Systemic (SVR) and femoral (FVR) vascular resistances were calculated. Atria, left and right ventricles (LV, RV), lungs, and liver were weighed. LV cavity area, LV and RV wall thicknesses and collagen densities were determined (computer-assisted image analyzer). Pulmonary and hepatic congestion were assessed (arbitrary scales). Compared with controls, MAP, CO and FBF were significantly lower in CMH throughout the study (on average: -22%, -34%, -33%, respectively), FVR was significantly increased (+15%), but SVR was not significantly modified. Concerning histomorphometric characteristics, differences between groups significantly increased with age for most variables: at 300 days, atria (+292%), RV (+13%), lungs (+44%), and liver (+23%) weights, LV cavity area (+130%), LV (+364%) and RV (+181%) collagen densities were significantly increased in CMH vs controls, whereas LV (-40%) and RV (-23%) wall thicknesses were significantly decreased. At 260 and 300 days, CMH showed significant pulmonary congestion without hepatic alteration. Bio TO-2 CMH progressively develop an alteration of cardiac function leading to decreased MAP and musculo-cutaneous blood flow associated with cardiac remodeling including atria hypertrophy and LV dilation, wall thinning and a rise in collagen density.

Increased sensitivity of vascular smooth muscle to nitric oxide in dilated cardiomyopathy of Syrian hamsters (Bio TO-2 strain).

We assessed the evolution with time of the responsiveness of three vascular beds in dilated cardiomyopathic hamsters of the Bio TO-2 strain. Eight cardiomyopathic hamsters and 8 control hamsters were investigated at 180 and 300 days of age. Thoracic aorta and mesenteric and renal artery rings were studied in isolated organ baths. Cumulative concentration-response relations to phenylephrine, acetylcholine, sodium nitroprusside, and angiotensin II were established for each ring. Maximum effect (Emax) and concentration inducing 50% of Emax (EC50) were determined from each concentration-response curve and pD2 was calculated as -log(EC50). Compared with control hamsters, in cardiomyopathic hamsters, Emax of phenylephrine was not modified in aorta, whereas it was significantly lower in mesenteric (-6% and -33% at 180 and 300 days, respectively) and renal (-17% and -24%) arteries. Emax of acetylcholine was significantly higher in aorta (+57% and +30%), mesenteric (+42% and +34%), and renal (+168% and +70%) arteries. Emax of sodium nitroprusside was significantly higher in aorta (+26% and +16%) and tended to be higher in mesenteric (+25% and +23%) and renal (+27% and +10%) arteries. Emax of angiotensin II was not modified in aorta and tended to be lower in mesenteric artery at 300 days. The pD2 of phenylephrine was significantly increased in aorta and the pD2 of sodium nitroprusside was significantly increased in aorta and renal artery. In conclusion, in dilated cardiomyopathic hamsters, endothelium-dependent and -independent vasodilations are enhanced early, demonstrating increased sensitivity of vascular smooth muscle to nitric oxide. This abnormality may be involved in the decreased responsiveness to phenylephrine and angiotensin II.

Immunohistochemical expression of the intracellular component of galectin-8 in squamous cell metaplasia of the bronchial epithelium in neoplastic and benign processes.

Specified galectins are known to play a role in regulating cell proliferation, differentiation, adhesion and migration. Po66, a mouse IgG1 monoclonal antibody produced by immunization against squamous cell cancer, reacts against a carbohydrate-binding protein (Po66-CBP), recently shown to be a member of the galectin family with a strong homology with galectin-8 (PCTA-1), identified as a human tumor-associated antigen. We studied Po66 in squamous metaplasia of the bronchi in order to determine whether it could be specifically involved in neoplastic conditions and if so, if it would be helpful in distinguishing metaplasia at risk of cancer. Twenty-eight formalin-fixed, paraffin-embedded archival tissues of 17 metaplasias with SCC, 3 metaplasia with distant neoplastic disease and 8 metaplasias with an inflammatory process, were immunostained using a streptavidin biotin peroxydase method. The squamous metaplasias were positively stained in non-neoplastic disease as well as in neoplastic processes. Expression was also observed in stromal and normal cells. Po66-CBP was not associated with a pre-neoplastic character. We discussed the expression of this intra-cellular component of galectin-8 according to the functions of galectins in cellular differentiation, host reaction against tumor, and inflammation.

[Intraluminal renal metastasis from a rectal adenocarcinoma: an unusual site]. / Métastase pyélocalicielle d'un adénocarcinome d'origine rectale: une localisation inhabituelle.

Primary adenocarcinoma of the urinary tract are uncommon. But secondary involvement of pyelocalyceal system by metastasis of colorectal origin is rare. We report a case of late rectal metastasis with renal pelvis growth presenting as a pyonephrosis. This study emphasizes the relevance of cytokeratin 7 and 20 immunostaining in such differential diagnosis.

[An uncommon tumor of the urinary bladder: the small cell carcinoma]. / Une tumeur vésicale rare: le carcinome à petites cellules.

Primary small cell carcinoma of the urinary bladder is an uncommon tumor, compared to the frequency of urothelial tumors. Fifty percent of cases are combined with a non endocrine carcinomatous component. We report six new cases of this tumor, three of pure, and three associated with an urothelial carcinoma. Diagnosis is easy established by the immunohistochemical study which show the neuro-endocrine differentiation of these aggressive tumors. Pathologist needs to look for a neuro-endocrine part in all bladder cancer, as its presence modify the treatment. Chemotherapy is used in these cancers, due to their high metastatic power. Places of radical surgery and radiotherapy need to be specified.

[Unusual variety of bladder urothelial carcinoma: "nest type" microlobular carcinoma: report of an anatomoclinical case and review of the literature]. / Une variété rare de carcinome urothélial de la vessie: le carcinome microlobulaire "à type de nids": à propos d'un cas anatomo-clinique avec revue de la littérature.

We report a case of nested cell carcinoma, an uncommon transitional tumor. These tumors are composed of regular cuboidal transitional cells forming small nests with minimal cytologic atypia. Despite the benign course, this tumor resembling proliferation of Brunn's nests or inverted papilloma, must be considered as an aggressive transitional tumor. Thus, morphologic criteria are needed to make the diagnosis. Because of its aggressive behaviour, the surgical therapy depends on the tumor's infiltration.

Value of immunohistochemical Ki-67 and p53 determinations as predictive factors of outcome in renal cell carcinoma.

OBJECTIVES: Nuclear grade and tumor stage are important prognostic factors in renal cell carcinoma, but tumors of similar stage and grade can exhibit a wide variation in biologic behavior and clinical outcome. In this retrospective study, we evaluated the immunologic markers, Ki-67 (MIB1) and p53, in 73 cases of conventional (clear cell) renal cell carcinoma and compared these markers with the accepted prognostic features of grade, stage, and tumor size in predicting outcome. METHODS: Specimens of 73 renal cell carcinomas of different nuclear grade (20 Furhman I/II, 32 Fuhrman III, and 21 Fuhrman IV) and different stage (10 pT1, 23 pT2, 36 pT3, and 4 pT4) were immunostained with monoclonal antibodies against Ki-67 and p53. RESULTS: Univariate statistical analysis showed that tumor size (P <0. 001), nuclear grade (P <0.01), tumor stage (P <0.01), Ki-67 index (P <0.001), and p53 immunostaining (P <0.03) correlated significantly with a poor prognosis. A Ki-67 index of 20% was a powerful predictor of survival in all patients (P <0.00001), with strong predictive values. On multivariate analysis, the Ki-67 index and metastases were significant independent prognostic factors (P <0.02 and <0.01, respectively). CONCLUSIONS: Ki-67 immunostaining appeared to be an additional prognostic indicator of biologic aggressiveness in renal cell carcinoma. Immunohistochemical assessment of tumor antigens could be used to identify patients at high risk of tumor progression in addition to conventional prognostic factors.

Primary liver hemangiopericytoma associated with hypoglycemia: report of a second case.

Hemangiopericytoma is an uncommon vascular tumor which usually develops in soft tissues. It has been exceptionally described in the liver and only one case associated with hypoglycemia has been reported in this organ. A giant hemangiopericytoma which was revealed by life-threatening hypoglycemia is described. Imaging and pathological features are presented. The patient, a 73 year-old woman, was treated by hepatectomy. She is perfectly well after a 3-year follow-up, without any evidence of recurrence.

Analysis of Ki-67, p53 and Bcl-2 expression in the dysplasia-carcinoma sequence of Barrett's esophagus.

The grading of dysplasia in Barrett's esophagus has prognostic importance, however observer variation limits the reliability of simple histological analysis alone. We investigated Ki-67, p53 and Bcl-2 expression in Barrett's esophagus, in the sequence from Barrett's low-grade dysplasia to high-grade dysplasia and infiltrating adenocarcinoma. Forty-four esophagectomy specimens were utilized: 39 specimens with esophageal dysplasia and adenocarcinoma and 5 specimens with esophageal dysplasia only. This gave 83 sections (2 sections for specimens with dyplasia and carcinoma) examined from 44 patients. The sections were examined for Ki-67, p53 and Bcl-2 reactivity by immunohistochemistry. Low-grade dysplasia was present in 14 sections, high-grade dysplasia in 30 sections and carcinoma in 39 sections. Ki-67 expression occurred in 2 out of 14 (14%) sections with low-grade dysplasia, in 22 out of 30 (73%) sections with high-grade dysplasia and in 34 out of 39 (87%) sections with carcinoma (p<0.001). p53 protein expression was found in 1 of 14 (7%) sections with low-grade dysplasia, in 18 of 30 (60%) sections with high-grade dysplasia and in 33 of 39 (85%) sections with carcinoma (p<0.001). Expression of Bcl-2 was found in 11 of 14 (84%) sections with low-grade dysplasia but immunoreactivity was not seen in any section with high-grade dysplasia or Barrett's carcinoma. Our results indicate that overexpression of Ki-67, Bcl-2 protein and p53 mutations can be identified as early events during neoplastic progression in Barrett's esophagus. These data support the hypothesis that, in the progression of Barrett's metaplasia to adenocarcinoma, the balance of proliferation/apoptosis plays an important role.

Meningioma in long-term survivors after allogeneic bone marrow transplantation.

Late complications occurring after allogeneic bone marrow transplant (BMT) are increasingly reported, since more patients survive. Among these late complications, solid tumors are of particular clinical concern. Only malignant brain tumors have been reported (astrocytoma, glioblastoma). We describe two cases of meningiomas developing 13 and 15 years after the graft. Occurrence of such benign tumors has been described after treatment of ALL, but not following allogeneic BMT. It is important to consider the diagnosis of meningioma in long-term survivors presenting with neurological symptoms.

[Ischemic renal diseases have become the most frequent causes of end stage renal disease in the elderly]. / La néphroangiosclérose et la néphropathie ischémique athéromateuse sont devenues les causes les plus fréquentes d'insuffisance rénale terminale chez le sujet âgé de plus de 60 ans.

In the 80s it was established that atherosclerotic renal artery stenosis (ARAS) is a leading cause of renal insufficiency and that this condition ranks among the rare etiologies of chronic renal failure amenable to improvement or stabilization particularly in the white. Nephroangiosclerosis (NAS) is an increasing cause of ESRD in the western countries, especially in blacks. Epidemiological data on the vascular nephropathies leading to ESRD are still rare. In this study, we compare annual incidence of ESRD due to ARAS and NAS during two five-year periods: period A = 1982-1986, period B = 1992-1996. The region of the survey comprised 410,664 inhabitants (99.6% of Caucasians), of whom 100,230 were aged over 60 years. Diagnosis of ARAS required arteriography and that of NAS a renal biopsy. Undetermined vascular nephropathy was diagnosed when ESRD patients had had previously no arteriography or no histological examination. Major results were as follow (A vs B, incidence = n/million inhabitants): 1) Increasing incidence of ESRD due to all causes: 76 vs 95 per million, mean age at ESRD 56 vs 62 yrs, percentage of patients over 65 yrs 28 to 59% (p < 0.001). 2) Increasing incidence of ESRD due to vascular nephropathies: 5.5 vs 27.5 per million (p < 0.0001) in general population and 22 vs 110 per million (p < 0.0001) in population aged over 60 years, mean age at ESRD 68 vs 73 yrs. 3) Increasing incidence of different types of ischemic renal diseases leading to ESRD: ARAS 2.5 vs 15 per million (p < 0.0001) in general population and 10 vs 60 per million (p < 0.001) in those aged over 60 yrs, mean age 69 vs 74 yrs, NAS: 1 vs 8 and 4 vs 32 per million (p < 0.001), mean age 67 vs 72 yrs, undetermined VN 0.5 vs 2.5 and 2 vs 10 per million, 65 vs 73 yrs. Our study demonstrates that ischemic renal diseases 1) have become the most frequent causes of ESRD (27% of all patients and 43% of those aged over 6C years) in the Caucasian elderly. 2) are the only cause of increasing incidence of ESRD in this French region.

[Intravascular malignant B-cell lymphomatosis with renal glomerular involvement: a case]. / Lymphomatose maligne intravasculaire de type B avec atteinte rénale glomérulaire: une observation.

We report a case of intravascular malignant lymphomatosis observed in a 71 year-old male and characterised by the presence of a proteinuria in relation to the specific intraglomerular localisation. This malignant lymphoma, usually of the B phenotype, is rare and affects predominantly the central nervous system and the skin. Neoplastic cells home selectively to endothelium. Histological renal infiltration is frequent but a glomerular localisation, with proteinuria, is rare. The mechanism whereby lymphocytes home to endothelium cells is unclear but it could be related to the expression of lymphocyte-endothelium adhesion molecules. When present the nephrotic syndrome is associated with minimal change disease.

Laminin isoforms in non-tumoral and tumoral human livers. Expression of alpha1, alpha2, beta1, beta2 and gamma1 chain mRNA and an alpha chain homologous to the alpha2 chain.

BACKGROUND/AIMS: Laminins, the major non-collagenous basement membrane components, are involved in various biological processes. Laminin isoforms have never been characterized in human livers. The expression of five laminin mRNA was investigated in livers with or without cancer and in hepatoma cells and, by comparison, in both rat hepatoma and hepatic stellate cells. METHODS: Laminin alpha1, alpha2, beta1, beta2 and gamma1 mRNA was detected by northern blot and/or RT-PCR in livers without chronic disease (n=5), in both tumoral and non-tumoral areas of livers with hepatocellular carcinomas (n=13) or metastases (n=18), in human HBGC2 and rat Faza-567 hepatoma cell lines, and in 6-day-old rat hepatic stellate cell cultures. RESULTS: Laminin alpha1, alpha2 and beta1 mRNA were found in 25-33% and gamma1 mRNA in 58% of the livers, the signal for laminin beta2 mRNA being faint in all the samples. Laminin alpha2, beta1, beta2 and gamma1 mRNA were expressed in hepatoma and stellate cells. The laminin alpha2 cDNA probe recognized a 3.5 kb mRNA different from the expected 9 kb mRNA. Using degenerated oligonucleotides, RT-PCR products from both rat hepatoma and stellate cells revealed 90% identity with the alpha2 chain sequence. Antibodies against peptide deduced from the conserved C-terminal domain of both alpha1 and alpha2 chains recognized polypeptides corresponding to the degradation products of alpha2 chain in liver extracts and both media and cell layers from hepatoma and stellate cells. In addition, a Mr=130000 polypeptide was revealed by these antibodies in liver extracts and cell layers, which was consistent with the expected size deduced from the 3.5 kb mRNA. CONCLUSIONS: This first report on laminin isoforms in human livers indicates that laminin 1 (alpha1-beta1-gamma1), 2 (alpha2-beta1-gamma1), 3 (alpha1-beta2-gamma1) and 4 (alpha2-beta2-gamma1) mRNA and a polypeptide homologous to the alpha2 isoform, which could correspond to a truncated form of this chain, are usually expressed in non-tumoral and/or tumoral livers.