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Biomedical subjects

G Monga

Publications and source records attributed to G Monga.

At least 19 recordsLinked to original sources

Karyomegalic interstitial nephritis: report of 3 new cases and review of the literature.

Karyomegalic interstitial nephritis is a rare, but perhaps an "underdiagnosed" condition. Peculiar nuclear changes characterize it, involving mainly tubular cells along with glomeruli and blood vessels. Herein, 3 bioptically proven new cases of patients with chronic renal failure are discussed. The first case had a recently diagnosed karyomegalic nephritis which, to date, still does not require dialysis. The other 2 (brother and sister) required dialysis 4 and 1 years after diagnosis. Karyomegalic changes were found not only in the skin and duodenal biopsies of the male, in skin and liver biopsies of the female and in the urine cells of both patients, but also in several organs (brain, thyroid, lung, esophagus, arteries) as shown at the autopsy of the female. There was a fatal outcome for both patients. The data reported in this study emphasize the usefulness of pathologic investigation of both tissue and urine samples in the identification of this disease. Moreover, as karyomegalic interstitial nephritis is strongly suspected to have a genetic background, its identification may well not only be of clinical relevance, due to its ominous outcome, but may also bear eugenetic value.

Adult↗

Altered patterns of the interferon-inducible gene IFI16 expression in head and neck squamous cell carcinoma: immunohistochemical study including correlation with retinoblastoma protein, human papillomavirus infection and proliferation index.

AIMS: To investigate whether the expression of interferon (IFN)-inducible gene IFI16 is inversely related to proliferative activity in vivo, we compared immunohistochemical reactivity of IFI16 in a series of head and neck squamous cell carcinomas (HNSCCs) with their proliferation index and the cell cycle regulator pRb. As human papillomavirus (HPV) infection is manifested by changes in the function or expression level of host genes such as IFN-inducible genes, we also investigated the presence of HPV DNA to determine whether head and neck cancers associated with HPV DNA can be distinguished from tumours that are presumably transformed by other mechanisms. METHODS: Thirty-six HNSCCs were evaluated for IFI16, pRb and Ki67 expression by immunohistochemistry. The presence of HPV was also detected by polymerase chain reaction. Nine tumours were located in the oropharynx (tonsillar area) and 27 in the larynx. RESULTS: HPV DNA was found in 14 of 25 (56%) laryngeal SCCs and in five of nine (56%) tonsillar SCC specimens examined; 17 out of the 19 HPV-DNA-positive cases showed high-grade IFI16 expression. Overall, proliferative activity was significantly related to tumour differentiation and histological grading. IFI16 protein expression was significantly inversely correlated with Ki67 (P = 0.039). Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. CONCLUSIONS: To our knowledge, this is the first expression analysis of the IFN-inducible IFI16 gene in HNSCC. Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index.

Aged↗

Molecular characterization and sequence analysis of polyomavirus BKV-strain in a renal-allograft recipient.

The significance of polyomavirus (PV) infection was investigated in a 53-year-old patient who underwent renal transplantation and was treated with triple immunosuppressive therapy (tacrolimus, prednisone, and azathioprine). A renal biopsy taken because of the suspicion of acute rejection showed focal inflammatory interstitial infiltration, tubulitis, and tubular cell nuclear changes consistent with the hypothesis of viral infection. Both the tubular and decoy cells identified by means of urinalysis positively stained for anti-SV40 antibody. Polymerase chain reaction performed on the DNA extracted from renal tissue and isolated from urine showed the presence of an antigenic variant (AS) of the BKV archetype after sequence analysis of the transcription control region (TCR). On the basis of the diagnosis of BKV infection, immunosuppressive therapy was reduced. The patient's renal function improved and was still stable 8 months later when urinalysis showed only a few decoy cells, which were found to be infected by JC but not BK virus. These data suggest that only the BKV, probably favoured by immunosuppressive therapy (tacrolimus), causes renal damage. It is worth underlining that even small and sporadic viral genome mutations may lead to pathologic effects.

BK Virus↗

Distribution of alpha-chains of type IV collagen in glomerular basement membranes with ultrastructural alterations suggestive of Alport syndrome.

BACKGROUND: In Alport syndrome (AS) impaired production and/or assembly of col IV alpha-chain isoforms results in abnormal structure of glomerular basement membrane (GBM), haematuria and, frequently, progressive renal disease. We investigated the relationship between col IV alpha-chains expression and morphology of GBM, as a possible key to the better understanding of the pathogenesis of renal disease in AS. METHODS: GBM distribution of col IV alpha1-, alpha3-, and alpha5-chain was investigated by immunohistochemistry in 32 patients (21 males and 11 females, mean age at biopsy of 11.5 years) with ultrastructural findings suggestive of AS. Ten patients had a proven COL4A5 mutation. Based on the severity of ultrastructural findings, the biopsies were grouped in three (I-III) electron microscopy (EM) classes. Significant EM changes of GBM (thinning, thickening, splitting, basket weaving of the lamina densa) were singularly evaluated using a semiquantitative scale (0-3). RESULTS: Col IV alpha1-chain was demonstrated in GBM of all patients. Three patterns of staining for col IValpha3- and alpha5-chains were observed: positive, negative, and alpha3(IV)-positive/alpha5(IV)-negative. By chi(2)-test, EM class III lesions and complete loss of alpha3(IV)- and alpha5(IV)-antigen were significantly more frequent (P<0.05 and P<0.01) in male patients, but no significant relation was observed between EM classes and immunohistochemical patterns. GBM alterations did not correlate with staining for alpha5(IV)-chain. Intensity of alpha3(IV)-chain staining, however, had a negative correlation (P<0.05) with the severity of GBM basket weaving. CONCLUSIONS: Our results suggest that the alpha3(IV)-chain-containing col IV-network plays a fundamental role in structural and, possibly, functional organization of GBM. Absence of alpha3(IV)-chain in GBM could indicate a more severe renal disease in AS.

Adolescent↗

Molecular characterization and sequence analysis of polyomavirus strains isolated from needle biopsy specimens of kidney allograft recipients.

We retrospectively examined 29 renal allograft biopsy specimens from 42 kidney transplant recipients by means of molecular biologic techniques (nested polymerase chain reaction), immunohistochemical analysis (anti-SV40 antibody), and histologic examination to evaluate the presence of polyomaviruses (PVs), viral genotypes, genomic mutations, and their pathologic significance. PV genomes were found in six cases (21%); restriction fragment length polymorphism analysis characterized 4 as JC virus (JCV) and 2 as BK virus (BKV). The latter also were positively stained immunohistochemically and showed histologically typical intranuclear viral inclusions; JCV cases were negative. DNA sequence analysis revealed only minor changes in the 4 JCV cases (3 archetypes and 1 JCV type 3, not associated with a known pathogenic genotype) but identified 2 specific variants in the BKV isolates (AS and WW strains). Given the different histologic findings (mixed inflammatory infiltration in the AS and no inflammation in the WW strain), we speculate that different BKV strains may cause differential damage in transplanted kidneys. Finally, the negative histologic and immunohistochemical JCV results, as well as the absence of viral mutations, indicate that JCV renal infection is latent in transplant recipients.

BK Virus↗

Lymphoepithelioma-like carcinoma of the breast. An unusual pattern of infiltrating lobular carcinoma.

A case of breast carcinoma, showing both lymphoepithelioma-like and lobular infiltrating carcinoma, is described, which must be distinguished from the medullary carcinoma with which it shares some features, such as the strong lymphocytic infiltration, but not sharp circumscription, syncytial growth pattern, nuclear pleomorphism, and high mitotic rate. Unlike the lymphoepithelial carcinoma of the nasopharynx and some lympho-epithelioma-like carcinomas of the lung, stomach, salivary glands, and thymus, it does not seem to be connected with Epstein-Barr virus (EBV) infection, as shown by negative results of both in situ hybridization and polymerase chain reaction. This neoplasia may be defined as a peculiar form of lobular carcinoma, therefore, more representative of an unusual microscopic pattern than a distinctive clinicopathologic entity in itself.

Breast Neoplasms↗

JC virus in human glial-derived tumors.

To investigate the presence and the role of polyomaviruses JC (JCV), BK (BKV), and the simian polyomavirus (SV40) in human brain tumors, samples from 25 glial-derived tumors (10 astrocytomas, 5 ependymomas, 5 oligodendrogliomas, and 5 glioblastomas) were examined by means of molecular biology and immunohistochemistry. Nested PCR of the large T (LT) region and its sequence analysis showed JCV in 6 cases (4 astrocytomas, 1 oligodendroglioma, and 1 ependymoma), while the transcriptional control region (TCR) was amplified only in 1 astrocytoma, the oligodendroglioma, and the ependymoma, one of which (astrocytoma) also stained positively by immunohistochemistry (JCV LT). TCR sequence analysis of the oligodendroglioma showed a JCV rearranged structure not related to a known viral strain, while the astrocytoma and the ependymoma disclosed a JCV Mad-4 strain that is known to induce brain tumors in animals. We suggest that JCV could have played a role in the pathogenesis of these brain tumors.

Adolescent↗

BK virus renal infection in a patient with the acquired immunodeficiency syndrome.

BACKGROUND: We describe herein a patient with the acquired immunodeficiency syndrome and renal failure due to biopsy-proven BK virus (BKV) infection. Three months after the diagnosis of the renal viral infection, his condition remained unchanged. Although BKV has previously been shown to be associated with ureteral stenosis and renal damage in renal transplant patients, to our knowledge, the literature contains only 3 cases describing the presence of BKV lesions in the kidneys of immunosuppressed patients who had not undergone transplantation. METHODS: The presence of BKV infection was demonstrated by means of histology, immunohistochemistry with polyclonal anti-SV40 antibody, immunoelectron microscopy, polymerase chain reaction, and enzymatic cleavage with BamHI. RESULTS: Histologic examination revealed interstitial inflammatory infiltrates and tubules with enlarged and eosinophilic nuclei. CONCLUSIONS: The high frequency of latent BKV infection and its reactivation during immunosuppression suggest that the possibility of its involvement in renal damage should be considered in immunocompromised patients.

Acquired Immunodeficiency Syndrome↗

Demonstration of multiple HPV types in laryngeal premalignant lesions using polymerase chain reaction and immunohistochemistry.

Recent evidence has shown that human papillomavirus (HPV) is involved in both the development of carcinoma and in premalignant mucosal lesions of the oral cavity. This study examined the relationship of HPV infection to some pathological features in precancerous lesions of the larynx, not examined extensively so far. Fifty formalin-fixed paraffin-embedded tissue sections containing human laryngeal precancerous lesions were screened for the presence of HPV infection by polymerase chain reaction, and for capsid protein expression by immunohistochemistry with polyclonal antibody directed against the L1 protein. The presence of HPV DNA was detected in 28 of 50 specimens (56%), including 9/12 cases with mild dysplasia (75%), 3/6 cases with moderate dysplasia (50%), and 7/11 cases with severe dysplasia (64%). Multiple HPV infections, containing two or three types, were detected in 17 of the 28 HPV-positive lesions (60%). Of 21 cases with keratosis and no dysplasia, 11 were positive for HPV DNA (52%) and 4 showed L1 staining (36%). By contrast, L1 positivity was revealed only in two lesions with moderate dysplasia, confirming that fully productive HPV infection is strictly dependent on epithelial differentiation and surface keratinization. The probability that HPV is a cofactor in the malignant progression of these lesions is suggested by the fact that 3/4 patients who developed cancer within 50 months were positive for HPV DNA.

Adult↗

Renal Encephalitozoon (Septata) intestinalis infection in a patient with AIDS. Post-mortem identification by means of transmission electron microscopy and PCR.

We describe the occurrence of renal Encephalitozoon (Septata) intestinalis infection in a 35-year-old AIDS patient who died with disseminated tuberculosis. The patient did not complain of specific symptoms involving the kidney or lower urinary tract during life, but at autopsy, light microscopic examination of the kidney revealed numerous small round or oval bodies in the tubules and tubular cell cytoplasm that were interpreted as intracellular protozoa. Transmission electron microscopy of tissue retrieved from paraffin-embedded samples identified these organisms as microsporidia belonging to the Encephalitozoonidae family, but did not allow definitive identification of the species of infecting parasite. This was made possible only by means of Southern blot hybridization after the polymerase chain reaction, which recognized the micro-organism as E. intestinalis.

AIDS-Related Opportunistic Infections↗

Ultrastructural and immunohistochemical findings in Alport's syndrome: a study of 108 patients from 97 Italian families with particular emphasis on COL4A5 gene mutation correlations.

A total of 108 patients affected by Alport's syndrome, taken from 97 families, were enrolled in a genetic and ultrastructural study. Sixty-four families (75 patients) were X-linked, seven autosomal recessive, two autosomal dominant, five uninterpretable, and 19 sporadic. The ultrastructural features were consistent with Alport's syndrome in 66, doubtful in 20, and not significant for Alport's syndrome in 22 patients in the X-linked, sporadic, and genetically uninterpretable groups (without significant differences), as well as in the autosomal group. Mutations of the COL4A5 gene were present in 36 patients in the first three groups, without significant differences. More severe mutations were more frequently present in patients with an ultrastructural pattern consistent with Alport's syndrome. Nevertheless, there seems to be no strict correlation between mutation and ultrastructure, because a major rearrangement was found in a patient with no significant lesions, and different morphologic patterns were detected in patients Belonging to the same family. Immunohistochemical investigation into 24 patients for alpha (IV) chains showed that both alpha 3(IV) and alpha 5(IV) were lacking in the glomerular basement membrane of 13 patients (five with mutations) and were expressed in another six (three with mutations and one in the autosomal group). On the contrary, in this study the retained expression of alpha 3(IV) chain was found, despite the lack of alpha 5(IV) in the glomerular basement membrane of five patients (two with mutation). These different patterns could be related to both the type and severity of the COL4A5 mutations. All of the ultrastructural patterns were identified in all three immunohistochemical groups. Ultrastructural features and alpha 5(IV) chain production, even if an expression of a genetic mutation, do not strictly correlate. The combined use of analysis of collagen expression and electron microscopy made it possible to diagnose Alport's syndrome in 92% of the cohort, and therefore this approach is advisable. A multidisciplinary approach is recommended in the study of Alport's syndrome in an attempt to achieve a better diagnostic definition of and insight into the pathogenetic mechanisms.

Adolescent↗

PCR detection of JC virus DNA in the brain tissue of a 9-year-old child with pleomorphic xanthoastrocytoma.

Pleomorphic xanthoastrocytoma (PXA) is a rare cerebral tumor of young adults with a slow growth and a good prognosis. Due to its peculiar histopathological findings, the tumor resemble to the lytic phase of progressive multifocal leukoencephalopathy (PML), a JC Virus (JCV) induced disease. For these reasons, the presence of JCV genoma and viral particles were searched for by means of nested polymerase chain reaction (nPCR) and electron microscopy (EM) in a 9-year-old child with PXA. Although EM did not reveal any viral particles, nPCR did reveal genomic sequences of the LT, R, and VP1 regions of JCV. Sequence analysis showed that the R region was mutated with respect to the archetypal form thus yielding the Mad 4 variant of JCV previously reported as being oncogenic in animals. We suggest that JCV may have played a role in the development of this tumor.

Astrocytoma↗

[Assessment of clinical competence of medical school graduates in Italy with standardized patients. The opinion of the examinees].

An international collaborative project for the evaluation of clinical competence at the end of the Medical School curriculum using the ECFMG-CSA (Educational Commission for Foreign Medical Graduates--Clinical Skills Assessment) prototype was started in Italy in April 1996. Faculty representatives from Italian Medical Schools and experts from the ECFMG in Philadelphia participated in the Project. The CSA consists of integrated clinical encounters with 10 standardized patients during which the examinee is asked to obtain a focused history, perform a relevant physical examination and communicate initial diagnoses and management plan to the Standardized Patient (SP). The SP then completes checklists that are scored by Faculty members. The project was concluded in Spring 1998 and a total of 173 new graduates were examined. The data elaborated by the primary site in Chieti University will be available in the Fall 1998 by the ECFMG in Philadelphia. This preliminary communication reports the opinions of the examinees on the ECFMG-CSA, contained in the questionnaires administered after the test. Most of the examinees considered this new methodology as a valid tool for the assessment of clinical competence, especially history-taking and interpersonal skills and stated that the SP simulations were realistic. The 72% of examinees indicated that the Medical School curriculum does not adequately prepare for the CSA examination. Lastly, 68% was in favour of including the SP in the Medical Licensing Examination.

Clinical Competence↗

Hepatic histology of patients with HIV infection and chronic hepatitis C treated with interferon.

AIMS: To evaluate the histological changes seen in liver biopsies after interferon (IFN) treatment in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection. METHODS: Twenty four intravenous drug users with chronic hepatitis C were investigated histologically before beginning a 12 month course of IFN treatment and 18 months later. Twelve were HIV positive, without opportunistic or other viral infections (group A), and 12 were HIV negative (group B). RESULTS: According to alanine amino-transferase concentrations, four sustained responders and eight non-responders were found in group A; six sustained responders, five relapsers, and one non-responder were found in group B. HCV RNA became negative in one sustained responder of group A and in the six sustained responders of group B. When histological findings of biopsies performed before therapy and 18 months later were compared, no significant changes in the mean value of Knodell's index and subindices were found in group A, whereas in group B Knodell's index, piecemeal necrosis, and focal hepatocellular necrosis decreased significantly. CONCLUSIONS: In chronic hepatitis C, coinfection with HIV showed a tendency towards a lower response to IFN, although this did not reach statistical significance; however, none of the HIV positive patients developed cirrhosis during the follow up and this should be considered in clinical management of such patients.

Adult↗