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Biomedical subjects

G N Martinelli

Publications and source records attributed to G N Martinelli.

At least 19 recordsLinked to original sources

Concurrent EGFr and Cox-2 expression in colorectal cancer: proliferation impact and tumour spreading.

BACKGROUND: Many reports were produced on single epidermal growth factor receptor (EGFr) and cyclo-oxygenase-2 (Cox-2) evaluation using immunohistochemical techniques (IHC), but very few works considered concurrent expression of these two proteins in the light of their impact on proliferation and tumour spreading. At least three molecular pathways (EGFr, Cox-2, and APC/beta-catenin molecular cascade) may interact in this malignancy giving rise to cross talking effects on proliferation and cancer spreading. PATIENTS AND METHODS: To better detail these two latter aggressive features, we studied 205 sporadic colorectal cancer patients, comparing concurrent expression of EGFr, Cox-2, Ki-67, Cyclins D1-A, and E, with tumour spreading (budding) (BUD) and pN status. RESULTS: Our results point to a different aggressive molecular profile due to Cox-2 expression. Cox-2 High expressing cases showed a clear EGFr proliferation-promoting role. On the contrary, EGFr seems directly involved in cancer cells spreading rather than in promoting cancer proliferation in Cox-2 Low/Negative cases. CONCLUSIONS: Immunohistochemical profiling of colorectal cancer seems to be a promising approach, not only to define prognostic impact, but also to detail proliferation-related molecular interplays between EGFr and Cox-2 pathways, with these two latter proteins, at present, being the hottest pharmacological targets for colorectal cancer (CRC) chemoprevention and therapy.

Adult↗

Seropositivity to HCV in Macaca fascicularis.

Several non-human primate species are used as laboratory animals for research purposes. Non human primates represent a potential hazard for laboratory animal handlers as they exceed all other species in importance as potentiators of disease in laboratory personnel (Quist K.D., 1972). Hepatitis viruses cause some of the prevalent diseases in man which constitute an important public health problem. The first outbreak of the infection was related to non human primates and occurred in 1958-1960 in USA, with more then 200 human cases. Chimpanzee is the main species that has been implicated but others have also been involved. We report a case of seropositivity to HCV antigens in Macaca fascicularis using a third generation RIBA assay. The nature of reactivity of the positive samples could not be resolved as no animal in the breeder colony had been exposed to an HCV source. Furthermore, Macaca spp. did not appear to be a susceptible species in previous studies.

Animals↗

Silent oophoritis due to cytomegalovirus in a patient with advanced HIV disease.

A case of isolated necrotizing cytomegalovirus (CMV) oophoritis disclosed only by necropsy studies in a patient with AIDS, is described. This unusual case report is discussed with a review of the literature dealing with CMV involvement of genital organs in the immunocompromised host, and in patients with HIV infection and AIDS.

AIDS-Related Opportunistic Infections↗

Primary endocervical extraosseous Ewing's sarcoma/PNET.

A 36-year-old woman presented with intermenstrual spotting and was found to have a cystic mass involving the uterine cervix on a pelvic ultrasound examination. A necrotic and hemorrhagic tumor was excised by hysterectomy and processed for light and electron microscopic investigation and molecular analysis. Microscopic examination revealed a small round cell tumor that immunohistochemical studies (including staining for the highly restricted surface antigen p30/32MIC2) and ultrastructural studies indicated was an extraosseous Ewing's sarcoma (EES)/primitive neuroectodermal tumor (PNET). This diagnosis was established by detection of EWS/ERG fusion transcript through reverse transcription polymerase chain reaction (RT-PCR) with nested primers. Full body computed tomography failed to detect any extrauterine tumor, and the patient is clinically free of disease 18 months after hysterectomy. This case represents the first report of a primary EES/PNET arising in the uterine cervix.

Adult↗

[Clear cell sarcoma of soft tissues. Clinico-pathological and ultrastructural analysis of a case in the head-neck region and a literature review].

BACKGROUND: Clear cell sarcoma of soft tissues (CCSST), even synonymically termed malignant melanoma of soft tissues, is a peculiar malignant tumor with both a prolonged clinical course and a final poor prognosis. Whilst its neuroectodermal histogenesis is most likely, its nosological position is still a matter of debate. Light microscopy (LM), immunocytochemistry (ICC), and electron microscopy (EM) investigations have shown both a melanocytic and schwannian differentiation. Recent findings from cytogenetic analysis documenting a reciprocal translocation between the long arms of chromosomes 12 and 22 [t(12:22)(q13;q12.2)] not seen in cutaneous melanomas nor in other neurogenic sarcomas support CCSST as a distinct entity. MATERIALS AND METHODS: A case of CCSST arising in the preparotid region of a young man with a clinical history of two previous surgical interventions was admitted in 1994 and is herein reported. This patient was previously cured twice in different institutions: the first time he was diagnosed with a "melanoma, NOS" of the face and surgically treated 10 years earlier. The second time--meaning one year earlier the admission--this patient was again surgically treated for a local recurrence which was interpreted as a myoepithelioma (clear cell type) of salivary gland origin. A morphological, immunocytochemical, and ultrastructural analysis performed on the last recurrence is herein presented. RESULTS: On LM the tumor exhibited the classic morphological appearance comprised both of clear and eosinophilic cells with prominent nucleoli, focally containing cytoplasmic granules of melanin pigment. At ICC expression of vimentin and S-100 protein was diffusely demonstrated as well as the melanoma associated antigen HMB-45 was even albeit focally documented.

Adult↗

Microcolposcopic topographic endocervical assessment before excisional treatment of cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate whether microcolposcopic topographic endocervical assessment reduces the failures of excisional treatment of cervical intraepithelial neoplasia (CIN). METHODS: Three hundred fifty patients with colposcopic and histopathologic findings of endocervical CIN were recruited for excisional treatment. Three hundred forty-eight of these were randomized to have or not have microcolposcopy before excisional treatment. Measurement of endocervical lesion was the only aim of microcolposcopic evaluation. When an endocervical extension was available, the cone biopsy was cut according to microcolposcopic measurement. Excision status was evaluated and related to presurgical management on operative specimens. After excision, patients were followed-up for at least 5 years after treatment. Three hundred thirty (171 and 159 with and without preoperative microcolposcopy, respectively) patients completed the study. Disease persistences were defined by cytologic, colposcopic, and histologic results. Microcolposcopic value was defined as completeness of excision and/or lack of persistent disease. RESULTS. On surgical specimens, involved margins were detected in 19 (5.4%) cases. Presurgical microcolposcopy was performed in only one of these cases. The difference of incomplete excision between cases with or without microcolposcopy was statistically significant (P < .001). In patients who were followed-up, persistent disease was detected in one (0.6%) woman in the microcolposcopy group and in 16 (10%) women in the control group. Comparison between the two groups showed a significantly lower risk of persistent disease when presurgical microcolposcopy was performed (P < .001). CONCLUSION: By measuring endocervical extension of the lesion, preoperative microcolposcopy allows individualized cones, thus improving the prognosis after excisional treatment of CIN.

Adolescent↗

Presurgical assessment and therapy of microinvasive carcinoma of the cervix.

Retrievable pathological specimens and clinical data on 70 patients with microinvasive carcinoma diagnosed on surgical specimens from cone biopsy or hysterectomy (Stage IA) were reviewed and compared to pertinent findings in the literature with the intent of evaluating diagnostic criteria and defining pathological features that may influence the outcome by therapy. Emphasis was given to the preoperative assessment emphasizing that both an accurate colposcopic evaluation and a detailed pathological analysis may reliably point to a conservative therapeutic approach. Increasing depth of stromal invasion was associated with lesion width as well as with endocervical extension, as measured on colposcopy, microcolpohisteroscopy, and histology. Lymph-vascular space involvement was significantly related to depth of invasion. Two patients of 28 with dissected nodes had node metastases as well as lymph-vascular space involvement. Both developed a pelvic recurrence. One had a > 1- to < or = 3-mm invasion depth, the other a > 3- to < or = 5-mm lesion invasion. While advocating a conservative procedure for Stage IA1, we suggest discrimination with regard to Stage IA2 because we believe that lymph-vascular involvement should be meticulously evaluated. In fact, > 1- to < or = 3-mm lesions without lymph-vascular space involvement can be conservatively treated, while for any other lesion falling within the Stage IA2 category a modified radical histerectomy plus pelvic lymphadenectomy should be recommended.

Adult↗

Smooth muscle differentiation in normal human ovaries, ovarian stromal hyperplasia and ovarian granulosa-stromal cells tumors.

An immunohistochemical and ultrastructural investigation on the presence of "smooth muscle differentiation" in stromal ovarian tissue was carried out in 10 adult granulosa cell tumors, six juvenile granulosa cell tumors, six thecoma/fibrothecomas, six cases of stromal hyperplasia, and in 10 normal ovaries. For immunohistochemistry, formalin-fixed paraffin-embedded tissues were processed using anti-alpha smooth muscle actin (alpha-SM actin) and anti-desmin as primary monoclonal antibodies. All adult granulosa cell tumors and juvenile granulosa cell tumors showed an intense alpha-SM actin immunoreaction, but weaker for desmin. Immunostain was diffuse in six out of 10 and five out of six adult granulosa cell tumors and juvenile granulosa cell tumors, respectively. Ultrastructurally, intermediate filaments focally converging into well developed desmosomes as well as peripheral bundles of myofilaments were documented both in adult granulosa cell tumors and juvenile granulosa cell tumors. In thecoma/fibrothecomas and stromal hyperplasia, alpha-SM actin and desmin expression was minimal or absent; on electron microscopy some "myoid" features and myofibroblasts were also seen. In normal ovaries, alpha-SM actin was found intensely expressed in the theca externa, focally identified in cortex-medulla, and unstained in the theca interna layer. Immunoreaction increased during folliculogenesis, going from a thin positive alpha-SM actin layer around secondary follicles to a strong diffuse stain in mature follicles. Our immunohistochemical and ultrastructural results indicate that a "smooth muscle differentiation" is a typical component of the specialized gonadal stromal tissue. A diffuse and focally alpha-SM actin is constantly present in granulosa cell tumors and thecoma/fibrothecomas, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

The morphology of elastin in non-specific and inflammatory abdominal aortic aneurysms. A comparative transmission, scanning and immunoelectronmicroscopy study.

The maintenance of the mechanical properties of the vessels results from the correct arrangement of smooth muscle cells and extracellular fibrous proteins (elastin and collagen) in their wall. The morphology of extracellular matrix modifications, particularly of elastin, was investigated in inflammatory (IA) and non specific (NSA) abdominal aortic aneurysms by scanning (SEM), transmission (TEM) and immunoelectron microscopy. Both NSAs and IAs were significantly characterized by extensive extracellular matrix remodelling, including different patterns of elastin degradation. Elastic and collagen fibres distribution appeared to be extensively altered in IAs, while it conformed more to a normal pattern in NSAs. With respect to NSAs, the morphology of elastic fibres in IAs was modified to such an extent that their identification by TEM had a rely on immunocytochemical methods and by SEM on back-scattered electron analysis. The observed ultrastructural changes are indicative of the central role of extracellular matrix modifications in the pathogenesis of IAs and NSAs.

Aortic Aneurysm, Abdominal↗

Gastro-intestinal stromal tumors: an ultrastructural reinterpretation of the clear cell component.

The histology, immunohistochemistry and ultrastructure of six gastro-intestinal stromal tumors of the stomach (GSTs) showing a focal to diffuse clear cell component are reported. At light microscopy, all GSTs had typical histopathological features with one case additionally displaying stromal myxoid changes and scattered multinucleated giant cells. Immunohistochemically, 6 of 6 GSTs stained positive for vimentin, 2 of 6 for smooth muscle specific actin and 1 of 6 for desmin. At electron microscopy, GSTs showed microfilaments with focal densities as well as other smooth muscle features, such as subplasmalemmal linear densities and foci of external lamina. Ultrastructural appearances of tumor cells with clear cell features showed these not to be an artifact of fixation, but the expression of an unusual cytophagocytic activity. Inclusions of auto- and heterophagocytic nature were found responsible for the origin of the large, mostly lipidic vacuoles which displaced cell nuclei peripherally in a signet-ring fashion. It is concluded that such previously unrecognized features are ultrastructural aspects of GSTs with smooth muscle differentiation.

Adult↗

Immunocytochemical study of epidermal growth factor receptor, transforming growth factor alpha, and "squamous differentiation" in human endometrial carcinoma.

The expression of epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) was compared with the presence of "squamous differentiation" (SD) visualized in various histotypes of endometrial carcinoma by using a panel of monoclonal antibodies. The results of the current study demonstrate that EGFr and TGF-alpha are present in routinely processed endometrial carcinoma. The highest positive EGFr and TGF-alpha expression was seen in the group of adenocarcinomas with SD. The more intense EGFr and TGF-alpha immunoreactivity was observed in "squamous" foci both in adenoacanthomas (AA) and in adenosquamous carcinomas (AS). These EGFr- and TGF-alpha-positive squamous areas prevalently displayed a "stratification-related" cytokeratin (CK) immunoprofile characterized by the expression of CKs 1, 4, 5, 10, 13, 14, and 16. No correlation was found between EGFr- and TGF-alpha-positive status and depth of myometrial invasion or surgical stage. These results clearly demonstrate that EGFr and TGF-alpha expression is related remarkably to endometrial carcinoma with "squamous" areas both morphologically and immunophenotypically. This specific association leads us to suggest that EGFr and TGF-alpha expression in endometrial carcinoma may be prevalently involved in the equilibrium of cell differentiation of the "squamous" foci commonly observed in this group of neoplasias.

Adenocarcinoma↗

Expression of intermediate filaments in normal and neoplastic exocrine pancreas.

The intermediate filament (IF) proteins present in the normal and pathological exocrine human pancreas were studied by immunolocalization using antibodies to cytokeratins (CKs) and vimentin. Acinar cells of normal pancreas showed a presence of simple CKs 8 and 18. Duct epithelium consistently expressed CKs 7, 8, 18 and 19 whereas centroacinar cells were rather low in CK 7. A subpopulation of CK 4 cells was detected in inter-intralobular ducts. In addition, some ducts contained individual cells or groups of cells that were positive for the stratification-related CKs (CKs 4, 5, 13, 15, 16). All pancreatic ductal adenocarcinomas regularly expressed CKs 7, 8, 18, 19 and were also positive for the 34 beta E12 antibody. Cytokeratin 4 was detected in a minor population of tumor cells. Pancreatic carcinoma also contained minor amounts of stratification-related CKs in variable combinations. Mucinous cystoadenocarcinoma showed the presence of CKs 7, 8, 18, 19 and was also positive for 34 beta E12, whereas the serous microcystic tumor presented CKs 8, 18, 19 and a variable amount of CKs 4 and 7. The duct-ductular alterations of the exocrine pancreas contained a different combination and distribution of CK isoforms similar to normal pancreatic ductal system. Mucinous hypertrophy and pyloric gland metaplasia reacted with antibodies to CKs 7, 8, 18 and 19. Vimentin was focally present both in normal and neoplastic tissue. Our results indicate that pancreatic ducts are characterized by an intrinsic "biliary-pancreatic duct type" immunoprofile (CKs 7, 8, 18 and 19), in contrast to acinar cells expressing exclusively CKs 8 and 18. We also detected a subpopulation of ducts regularly expressing CK 4. Surprisingly, several stratification-related CKs were detected both in normal and neoplastic exocrine pancreas. Moreover, the differentiation phenotypes of pancreatic tumors were reminiscent of normal cellular compartments.

Adenocarcinoma↗

[Wash and non-wash system in the perioperative recovery of blood in prosthetic surgery: ultrastructural assessment of corpuscular blood components].

AIM: The authors aimed to perform an ultrastructural morphological analysis of blood recovered using wash and non-wash systems in patients undergoing full cement-free hip replacement in order to evaluate the integrity of the various blood corpuscle components. EXPERIMENTAL PROTOCOL: An open prospective study in patients undergoing full cement-free hip replacement at the Orthopedics Division of S. Orsola-Malpighi Policlinico in Bologna. Materials of S. Orsola-Malpighi Policlinico in Bologna. MATERIALS AND METHODS: Blood recovered postoperatively using a non-wash system was studied in 6 patients. In a further 3 patients perioperatively recovered blood was studied after washing using Cell Saver Haemolite 2 before reinfusion. Red globules, white globules and plaelets were isolated from blood collected using these two different recovery systems and analysed by SEM. RESULTS: Study of the ultrastructural morphology of various corpusculated blood fractions. DISCUSSION AND CONCLUSIONS: From the data in our possession it appears that the ultrastructural morphology of the various corpuscle components of blood in subjects undergoing postoperative recovery is better preserved using a non-wash system. There was no sign of "polluting" material in terms of adipose cells or free bone fragments in either group.

Blood Cells↗

Nuclear bodies associated with core particles of hepatitis B virus in a healthy carrier.

An unusual association of nuclear bodies (NB) with core particles of hepatitis B virus (HBV) is described in a healthy carrier who histologically showed ground glass hepatocytes with occasional sanded-nuclei. Ultrastructurally, many hepatocytes had typical features of HBV infection. Unexpectedly, a few cells contained previously undescribed complexes of NB studded with a number of HBV core particles. The ultrastructural characteristics of these complexes and their possible relation to HBV morphogenesis are briefly discussed.

Carrier State↗

Origin of unreactive hyaline bodies from erythrocytes in genital tumors.

Two genital tumors, one a lipid virilizing cell tumor of the ovary, the other an ovarian Sertoli-Leydig cell tumor with retiform pattern, were studied focusing attention on the numerous eosinophilic hyaline bodies that were present both in the extracellular spaces and within the cytoplasm of the proliferating cells. Histochemistry and immunohistochemistry revealed that they were PAS positive and alpha-1-fetoprotein negative. Under electronmicroscopy these hyaline bodies appeared to correspond to variably altered red blood cells: red blood cell ghosts, erythrocytes with Heinz bodies, phagocytosed erythrocytes. Our findings could explain the origin of at least a part of the hyaline bodies found in similar or in other unrelated pathologies.

Adolescent↗

Immunohistochemistry with antibody to the LA-1 oncogene as a prognostic marker in cervical intraepithelial neoplasia.

Previous studies with antibody to a synthetic peptide designated LA-1 identified a 60-kDa protein in cervical intraepithelial neoplasia and invasive cancer tissues. To determine whether these findings are of clinical significance cervical tissues from 223 patients with squamous intraepithelial lesion (SIL) or invasive carcinoma and 39 normal healthy cervical tissues were stained with antibody to LA-1 using the immunoperoxidase assay. Tissues from 52 patients with squamous carcinomas at other sites were used as controls. Staining was respectively observed in 46.4, 56.5, and 64.7% of patients with low-grade SIL, high-grade SIL, and invasive cancer. It was localized in the atypical epithelium involving a progressively larger extent of epithelium as a function of increased pathologic grade. Only 10.3% of the normal cervical tissues stained with anti-LA-1 antibody. Twenty-five patients that were lost to follow-up for 2-5 years after the original diagnosis were studied at the time of diagnosis (1 degree biopsy) and when they returned to the clinic (2 degrees biopsy). In the follow-up series, LA-1 staining was observed in both biopsies from 9/12 patients that progressed to a higher degree of atypia, while 9/11 patients whose lesions remained stationary were LA-1 negative. Our studies suggest that LA-1 might be a useful biological marker of cervical neoplasia.

Adult↗

A new polychrome stain and simultaneous methods of histological, histochemical and immunohistochemical stainings performed on semithin sections of Bioacryl-embedded human tissues.

We describe a new polychrome stain and simultaneous methods of histological, histochemical and immunocytochemical staining performed on sections from human tissues embedded in the new hydrophilic resin Bioacryl. The polychrome stain involves the sequential use of Harris' Haematoxylin, silver methenamine, Light Green and Eosin or Safranin dyes and provides a highly specific visualization of the overall cytological tissue architecture. When histochemical, immunocytochemical, and polychrome stains are performed together on the same section, crisp images are obtained, yielding simultaneous data of histochemical and immunological reactivities with clear tissue architecture.

Acrylic Resins↗