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L Mazzucchelli

Publications and source records attributed to L Mazzucchelli.

At least 37 records · Page 2Linked to original sources
PubMed1998

Activated CD4+ and CD8+ cytotoxic cells are present in increased numbers in the intestinal mucosa from patients with active inflammatory bowel disease.

The contribution of cell-mediated cytotoxicity to the pathogenesis of inflammatory bowel disease (IBD) is controversial, and results of in vitro assays vary according to experimental procedures. Therefore, we compared the frequency of cytotoxic effector cells in situ. On tissue sections of controls (n = 11), low frequencies of granzyme A and perforin mRNA-expressing cells are found in the lamina propria (1.77 +/- 0.15% and 1.46 +/- 0.12%, respectively) and in the epithelial cell layer (0.76 +/- 0.12% and 0.66 +/- 0.10%, respectively). In patients with IBD (n = 33), corresponding values were significantly (P < 0.02) higher, 6.1 +/- 0.40% and 5.92 +/- 0.57% for granzyme A and perforin expression in the lamina propria and 2.50 +/- 0.19% and 2.59 +/- 0.28%, respectively, in the epithelial compartment. Differences between ulcerative colitis and Crohn's disease are statistically not significant (P > 0.33). Activated cytotoxic cells are preferentially found at sites facing the intestinal lumen. Perforin mRNA-expressing cells are mainly CD8+ T cells. CD4+ T cells expressing perforin mRNA are mainly isolated from affected areas of patients with Crohn's disease. Immunostaining for perforin protein generally coincides with perforin mRNA in situ. These data demonstrate that cytotoxic cells are vigorously activated in situ in the intestinal mucosa of patients with active IBD.

Adult↗
PubMed1997

The C-X-C chemokine ENA-78 is preferentially expressed in intestinal epithelium in inflammatory bowel disease.

BACKGROUND & AIMS: Secretion of chemokines by epithelial cells may represent a crucial event in the pathogenesis of inflammatory bowel disease (IBD). Expression of the chemokine epithelial neutrophil-activating peptide 78 (ENA-78) was monitored in patients with IBD and normal controls. METHODS: In situ hybridizations were performed on 41 tissue specimens from 15 patients with IBD and 10 controls to detect ENA-78 messenger RNA (mRNA). Immunofluorescence stainings were used to localize ENA-78 protein. RESULTS: Intestinal epithelial cells expressing ENA-78 mRNA at detectable levels are found at comparable frequencies in patients with Crohn's disease and ulcerative colitis. Tissue specimens with mild to moderate histological signs of disease activity show slightly higher frequencies of ENA-78 mRNA-expressing epithelial cells than areas with signs of severe disease activity (P = 0.14). Immunofluorescence stainings showed presence of the ENA-78 protein in > 90% of preserved epithelial cells in IBD, in control tissues, ENA-78 mRNA was not detectable, and ENA-78 protein was detectable in 0%-30% of epithelial cells. CONCLUSIONS: The observations are in agreement with a role of the C-X-C chemokine ENA-78 in the pathogenesis of IBD.

Acute Disease↗
PubMed1997

In situ stromal expression of the urokinase/plasmin system correlates with epithelial dysplasia in colorectal adenomas.

An increase of urokinase-type plasminogen activator (uPA) and a decrease of tissue-type PA (tPA) have been associated with the transition from normal to adenomatous colorectal mucosa. Serial sections from 25 adenomas were used to identify PA-related caseinolytic activities by in situ zymography, blocking selectively uPA or tPA. The distribution of uPA, tPA, and type 1 PA inhibitor mRNAs was investigated by nonradioactive in situ hybridization, and the receptor for uPA was detected by immunostaining. Low- and high-grade epithelial cell dysplasia was mapped histologically. Results show that 23 of 25 adenomas expressed uPA-related lytic activity located predominantly in the periphery whereas tPA-related activity was mainly in central areas of adenomas. In 15 of 25 adenomas, uPA mRNA was expressed in stromal cells clustered in foci that coincided with areas of uPA lytic activity. The probability of finding uPA mRNA-reactive cells was significantly higher in areas with high-grade epithelial dysplasia. uPA receptor was mainly stromal and expressed at the periphery. Type 1 PA inhibitor mRNA cellular expression was diffuse in the stroma, in endothelial cells, and in a subpopulation of alpha-smooth muscle cell actin-reactive cells. These results show that a stromal up-regulation of the uPA/plasmin system is associated with foci of severe dysplasia in a subset of colorectal adenomas.

Adenoma↗
PubMed1997

Differentiated thyroid carcinoma in children and adolescents: a 37-year experience in 85 patients.

UNLABELLED: This study reports on 85 differentiated thyroid carcinoma (DTC) (72 papillary, 13 follicular) patients, younger than 18 yr of age at the time of diagnosis, consecutively treated during the period 1958-1995. METHODS: Follow-up (median: 111 mo, range 1-324 mo) consisted of clinical examination, serum thyroglobulin (Tg), 131I whole-body scintigraphy (whole-body scan) and other imaging procedures. RESULTS: Forty-six patients had undergone total thyroidectomy, 38 partial thyroidectomy and 1 thyroid biopsy. In 47 patients, lymph-adenectomy was also performed. Five patients were treated after surgery by external radiotherapy, 59 by 131I therapy and 16 by both modalities. Iodine-131 therapy was successful in ablating thyroid remnants in 35/48 cases, lymph node metastases in 8/11 cases and lung metastases in 12/16 cases. Among the patients with scintigraphic-confirmed disappearance of lung metastases, serum Tg was still detectable in 10 cases, but continued to decrease spontaneously even without further therapeutic doses of 131I. All patients were still alive after a median period of 137 mo (range 5-444 mo). Six patients experienced a recurrence of the disease in the neck. Sixty-seven patients were free of disease, 3 had lymph node metastases, 4 lung metastases and 11 had detectable levels of Tg without demonstrable metastases. No impairment of female fertility or untoward genetic effects were noticed. One male patient, treated with 3.33 GBq of 131I, was infertile due to oligospermia. One case of gastric cancer and one of breast cancer occurred 8 and 19 yr, respectively, after 131I therapy. CONCLUSION: Iodine-131 therapy is highly effective in reducing lung metastases, but undetectable levels of Tg are seldom achieved. Total thyroidectomy and 131I therapy is an effective and safe treatment for the majority of patients with DTC diagnosed in childhood or adolescence.

Adenocarcinoma, Follicular↗
PubMed1996

Differential in situ expression of the genes encoding the chemokines MCP-1 and RANTES in human inflammatory bowel disease.

Two chemotactic cytokines, monocyte chemoattractant protein-1 (MCP-1) and RANTES, possibly contribute to the recruitment and activation of leukocytes in inflamed tissues. The expression of these cytokine genes was evaluated in tissue sections from resected bowel segments of 14 patients with inflammatory bowel disease (IBD) and seven control patients by use of 35S-labelled antisense RNA probes. MCP-1 and RANTES transcripts were generally increased in the intestinal mucosa of patients with IBD, compared with controls. Whereas MCP-1 gene expression in the mucosa was restricted to the lamina propria, the gene coding for RANTES was expressed in intraepithelial lymphocytes and in the subepithelial lamina propria. Furthermore, MCP-1 mRNA, but not RANTES mRNA, was abundant in vessel-associated cells, such as endothelial cells, medial smooth muscle cells, and intraluminal cells; in smooth muscle cells of the intestinal tunica muscularis; and in cells of the myenteric plexus. Compared with controls, a significant increase of MCP-1-expressing cells was observed in tissue specimens from patients with IBD, in endothelial cells of venules, and in cells present in the lumen of intestinal vessels. Conversely, the expression of MCP-1 mRNA in smooth muscle cells and myenteric plexus cells appeared to be comparable in control and diseased intestines. The increased number of MCP-1 and RANTES mRNA-expressing cells in mucosa from patients with IBD suggests that these cytokines play a role in the pathogenesis of mucosal inflammation. Furthermore, the expression of the MCP-1 gene in vessel-associated cells may indicate its involvement in mechanisms regulating the adhesion of blood monocytes to endothelial cells.

Adult↗
PubMed1996

Local up-regulation of neuropeptide receptors in host blood vessels around human colorectal cancers.

BACKGROUND & AIMS: Neuropeptide receptors, expressed at high density by neoplastic cells, can be instrumental for diagnosis and therapy. However, little is known about neuropeptides and neuropeptide receptors in the tumor bed. The aim of this study was to study the expression of two neuropeptide receptors in peritumoral blood vessels. METHODS: Somatostatin and substance P receptors were measured using in vitro receptor autoradiography in well-defined submucosal and subserosal vessels located in the immediate surroundings of human colorectal carcinomas or in normal colon taken at increasing distances from the tumor. RESULTS: Both receptors were 3-5-fold overexpressed in the host veins within a 2-cm-wide area surrounding human primary colorectal carcinomas compared with veins located at 5-10-cm distance in normal gut tissue. The expression of peritumoral vascular somatostatin receptor and substance P receptor appears independent of receptor expression in the tumor, of tumor stage, and of the grade of local inflammation. CONCLUSIONS: These biochemical alterations of veins in the immediate vicinity of tumors represent a novel tumor-related site of expression for the two receptors and may point to a new biological principle of host-tumor interaction. Thus, vascular regulatory mechanisms in the tumor bed may be important for tumor development and metastasis and may be used as a target for tumor therapy.

Aged↗
PubMed1996

Monocyte chemoattractant protein-1 gene expression in prostatic hyperplasia and prostate adenocarcinoma.

Human monocyte chemoattractant protein-1 (MCP-1) has been shown to act as a chemokine in the recruitment of monocyte/macrophages during inflammation states. Furthermore, there is increasing evidence that MCP-1 is involved in the recruitment of tumor-associated macrophages. In vivo, one of the major cellular sources of MCP-1 are the smooth muscle cells. As MCP-1 gene expression and/or protein production in these cells is not necessarily correlated with the accumulation of inflammatory cells, there might possibly be additional functions of this cytokine. In the present study, we investigated by use of 35S-labeled antisense RNA probes whether the MCP-1 gene is expressed in tissue specimens of benign prostatic hyperplasia (n = 13) and specimens of prostate carcinoma (n = 8), both of which are characterized by a prominent fibromuscular stroma and inconspicuous inflammatory infiltrates. MCP-1 transcripts were located in stromal smooth muscle cells and, additionally, in basal cells of benign prostatic glands. In prostate carcinoma, the number of MCP-1 mRNA-expressing cells was significantly less than in benign prostatic hyperplasia. MCP-1 transcripts were located in preserved fibromuscular stroma and in basal cells of entrapped non-neoplastic glands but not in carcinomatous cells. Immunohistochemical staining with polyclonal antibodies raised against MCP-1 revealed strong reactivity in the fibromuscular stroma surrounding both benign and malignant glands. MCP-1 gene expression or immunoreactivity for anti-MCP-1 antibodies was not related to the rare, lymphocytic interstitial infiltrates. The results show that 1) in the absence of significant leukocyte accumulation, it is unlikely that MCP-1 exerts chemotactic functions in the prostate and 2) that MCP-1, in contrast to previous findings in a wide variety of other human neoplasms, is not expressed in carcinomatous cells of the prostate.

Adenocarcinoma↗
PubMed1996

Extensive extramedullary hematopoiesis in a thyroid nodule.

We describe a case of extramedullary hematopoiesis in a hyperplastic thyroid nodule from a patient with primary myelofibrosis. The presence of extensive extramedullary hematopoiesis in the thyroid gland was suspected as a result of fine-needle aspiration cytologic examination and was confirmed by histo- and immunomorphologic examination of the resected nodule. The diagnosis of myelofibrosis was established on the basis of clinical findings, hematologic laboratory results, and bone marrow morphologic characteristics.

Aged↗
PubMed1995

Assessment of female fertility and carcinogenesis after iodine-131 therapy for differentiated thyroid carcinoma.

UNLABELLED: The aim of this study was to evaluate female fertility, carcinogenic, and genetic effects after treatment with 131I of differentiated thyroid carcinoma. METHODS: A total of 814 females of child-bearing age were studied. The fertility of 627 females who received 131I therapy was compared to 187 untreated females. Birth histories of the children born from these women were registered. The carcinogenic effect was evaluated by comparing the incidence of tumors in 730 patients treated with 131I with an internal control group, as well as with local population incidence. RESULTS: There was no significant difference in the fertility rate, birth weight and prematurity between the two groups. Only one case of a ventricular septal defect was observed in a child born to a women treated with 131I. The overall standardized incidence ratio (SIR) of second tumors was 1.19 (95% CI: 0.76-1.77) in patients treated with 131I. An elevated SIR was registered for salivary gland tumors and melanoma. No case of leukemia was registered. CONCLUSION: The risk of long-term effects of 131I treatment of differentiated thyroid carcinoma is quite low. Iodine-131 may be safely used in treating cases with a high risk of recurrence.

Adolescent↗
PubMed1994

Invasion depth is the most important prognostic factor for transitional-cell carcinoma in a prospective trial of radical cystectomy and adjuvant chemotherapy.

The aim of this prospective study was to examine the prognostic pathomorphological factors in urothelial cancer of the urinary bladder. Clinical and morphological variables were evaluated by univariate and multivariate analysis in 70 patients with invasive transitional-cell carcinoma of the bladder (pTI-pT4a). The patients were treated according to a prospective program consisting of radical cystectomy and pelvic-node dissection, either alone or followed by adjuvant cisplatinum chemotherapy. Nodal status was pN0 in 89% of the patients. The median follow-up time was 5.75 years and the 5-year survival was 58%. Among the morphologic variables, deep invasion of the bladder wall and squamous differentiation indicated a poorer prognosis. Differentiation grade, pattern of growth (infiltrating versus expanding), angioinvasive growth, glandular differentiation and concomitant prostate carcinoma (pT1) were not significative factors for survival. By contrast, a significant reduction in mortality rate was found in patients with concomitant carcinoma in situ. Multivariate analysis confirmed that depth of invasion is an independent prognostic factor of outcome. The results confirm the primary importance of tumor stage in the prediction of survival after radical cystectomy.

Adult↗
PubMed1994

[Cutaneous vasculitis: how to recognize, interpret, treat it?].

Clinical and histopathological features of cutaneous vasculitis are presented by means of 14 case reports. Proof of vasculitis in skin biopsy consecutively demands for a search of a cause and of the extension of the vasculitic process in the sense of a systemic disease. The most frequent form of cutaneous vasculitis is hypersensitivity angiitis, a disease in which always an exogenous (drugs, infections) or an endogenous (malignant neoplasia, connective tissue disease) trigger should be sought if cutaneous vasculitis persists after removal or treatment of the suspected cause. Then, antihistaminic or--particularly in cases with systemic involvement--immunosuppressive drugs (corticosteroids or cyclophosphamide) should be considered.

Adult↗
PubMed1994

Intestinal vessels express a high density of somatostatin receptors in human inflammatory bowel disease.

BACKGROUND/AIMS: The neuropeptide somatostatin exerts multiple functions in the gastrointestinal tract and may also play a regulatory role in inflammatory bowel disease, as several other neuropeptides do, e.g., substance P or calcitonin gene-related peptide. Therefore, the expression of somatostatin receptors was evaluated in tissue sections of diseased intestines and compared with controls. METHODS: Somatostatin receptors were measured in intestinal samples of 6 patients with Crohn's disease, 3 with ulcerative colitis, and 7 controls using somatostatin receptor autoradiography with 125I-[Tyr3]-octreotide or 125I-[Leu8,D-Trp22,Tyr25]-somatostatin-28 as radioligands. Substance P receptors were measured similarly on adjacent sections. RESULTS: Somatostatin receptors are present in high density in most intramural veins, but not in arteries, of intestines in florid Crohn's disease or ulcerative colitis. The receptors are specific and of high affinity for somatostatin-14 and -28, as well as for octreotide. Somatostatin receptors remain undetectable in the veins of noninflamed control intestine. Substance P receptors are identified in the somatostatin receptor-positive veins and also in arteries. CONCLUSIONS: The expression of receptors for somatostatin in veins of inflamed intestines suggests an active involvement of this peptide in the pathophysiology of inflammatory bowel disease and perhaps of inflammation in general.

Adult↗
PubMed1994

Adjuvant cisplatin chemotherapy following cystectomy for bladder cancer: results of a prospective randomized trial.

Between April 1984 and May 1989, 77 eligible patients with invasive, nonmetastatic (stage M0) transitional cell carcinoma of the bladder were stratified after radical cystectomy and pelvic lymph node dissection on the basis of nodal status (stage pN0 versus pN1-2) and were randomly assigned to either observation or postoperative cisplatin chemotherapy (3 courses of 90 mg./m.2 cisplatin given for 3 consecutive days at monthly intervals). Patient eligibility included a creatinine clearance of greater than 60 ml. per minute. There were 40 eligible patients in the control group (median age 61 years) and 37 in the cisplatin group (median age 64 years). In regard to postoperative tumor stage and nodal status, there was no statistical difference between the 2 patient groups. In the cisplatin group 21 patients received the full dose, 9 required dose reduction and 7 refused treatment. Median followup was 5 years 9 months (range 3 to 8 years). Survival analysis showed no significant difference (log rank p = 0.65) between the 40 patients in the control group and the 37 in the cisplatin group. The survival rate at 5 years was 54% (95% confidence interval 39 to 69%) in the control group and 57% (95% confidence interval 40 to 74%) in the treatment group. Patients with cancer confined to the bladder wall (stage pT3a or less) had a 5-year overall survival rate of 70% and those with tumor growth in the perivesical fat or into the prostate (stages pT3b plus pT4a) had a 5-year overall survival rate of 40%. This difference in survival between the low stage subgroup (stages pT3a or less) and the high stage subgroup (pT3b plus pT4a) is highly significant (p = 0.0043). However, no difference between the controls and the cisplatin group was found within either the low or high stage subgroups. The reasons for failing to show a survival benefit from adjuvant high dose cisplatin monotherapy after radical cystectomy are discussed.

Carcinoma, Transitional Cell↗
PubMed1994

Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation.

Interleukin-8 (IL-8) is a potent cytokine for recruitment and activation of neutrophils. To visualize its distribution in the intestinal mucosa and to understand better its possible role in the induction and promotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn's disease or ulcerative colitis. In situ hybridization with IL-8 anti-sense RNA probes revealed strong and specific signals in the histologically affected mucosa. The number of cells expressing IL-8 gene correlated with the histological grade of active inflammation. In accordance with the characteristic histological signs of active disease, IL-8-expressing cells were diffusely distributed over the entire affected mucosa in patients with ulcerative colitis, whereas in patients with Crohn's disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, in inflammatory exudates on mucosal surfaces, in crypt abscesses, and at the border of fistulae. Analysis of semi-serial sections pointed to macrophages, neutrophils, and epithelial cells as possible sources of this cytokine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments and in normal-appearing control mucosa of patients with colon cancer. In contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays and important but nonspecific role in the pathogenesis of inflammatory bowel disease and that the production of IL-8 messenger RNA is restricted to areas with histological signs of inflammatory activity and mucosal destruction.

Adult↗