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Biomedical subjects

C Kittas

Publications and source records attributed to C Kittas.

At least 127 records · Page 7Linked to original sources

Immunocytochemical demonstration of a1-Antitrypsin and a1-Antichymotrypsin in human gastrointestinal tract.

a1-Antitrypsin and a1-Antichymotrypsin were demonstrated by the peroxidase--antiperoxidase (PAP) technique in paraffin sections from various parts of the normal adult gastrointestinal tract. Thus, positive reaction for these two proteinase inhibitors was given by the absorptive epithelial cells of the small intestine and epithelial cells of Brünner's duodenal glands and the glands of the pyloric antrum. Our findings suggest that the presence of a1-Antitrypsin and a1-Antichymotrypsin in epithelial cells of the small intestine, may represent a self-protecting mechanism against the pancreatic proteolytic enzymes of the intestinal juices. The significance of our observation and its possible role in the previously reported a1AT deficiency associated with coeliac-like disease is also discussed.

Brunner Glands↗

Osmiophilic cytoplasmic inclusions in the lymph node post-capillary venules of the guinea pig.

A hitherto unknown pleomorphic osmiophilic inclusion was found in te endothelial cells of the guinea pig lymph node post-capillary venules; its diameter ranges from 0.4 to 2.2 micrometers, it is bound by a single membrane and consists of heavily dense granular area interrupted by irregularly spaced light bands. Occasionally, irregularly arranged membranous profiles in the granular matrix are also seen. It appears that the formation of this unique inclusion is related to the sex hormonal environment but its significance is yet unknown.

Animals↗

BCG-induced changes in the post capillary venules of the guinea pig lymph node.

The post capillary venules (PCV) of the regional lymph nodes of BCG-injected male and female guinea pigs were examined under light and electron microscopy. The endothelial cells showed increased height and pyroninophilia. Their cytoplasm contained increased numbers of ribosomes and polyribosomes and prominent rough endoplasmic reticulum with occasionally dilated cisternae. The number of lymphocytes migrating through the PCV wall was also increased. The activation of the endothelial cells of PCV induced by BCG may increase the recirculation of lymphocytes from the blood stream. These may be of importance in the antitumour activity of BCG. In control guinea pigs the height of the endothelial cells of PCV was significantly greater in the female than in the male. After BCG injection this sex difference was still apparent.

Animals↗

Ultrastructural effects of sex hormones and infection on lymph node post-capillary venules.

The ultrastructure of the lymph node post-capillary venules (PCV) was studied in control, gonadectomised and gonadectomised-Hexoestrol treated male and female mice, infected or not with Toxoplasma gondii. The percentage of the cytoplasmic area of the endothelial cells occupied by Golgi apparatus was estimated by quantitative stereology. The endothelial cells of the PCV are higher and contain more Golgi elements in female than male controls. Oophorectomy decreases the percentage of Golgi apparatus and the height of the endothelial cells while orchidectomy does not affect the former but increases the latter. The endothelial cells react to Hexoestrol similarly in male and female mice, by increasing their height and becoming more heavily structured, with an effect particularly on the Golgi apparatus. All groups of mice infected with Toxoplasma gondii, show increased numbers of lymphocytes passing through the wall of the PCV. The endothelial cells of the latter show increased numbers of ribosomes both free and attached to rough endoplasmic reticulum. Golgi elements are decreased. In view of these findings the mechanisms for selective lymphocyte migration through the walls of the PCV are discussed.

Animals↗

Effect of sex hormones on the response of mice to infection with Toxoplasma gondii.

Groups of male and female mice were gonadectomized and some implanted with a pellet of hexoestrol. Half of the animals in each group, including controls, were infected with a low-virulence strain of Toxoplasma gondii. The animals were killed 6 weeks after infection. Gonadectomy increased the relative thymic weight in both sexes, but more so in the male, and the paracortical area of the lymph node was enlarged, as was the thymus-dependent area of the spleen. Hexoestrol administration induced almost complete thymic atrophy and partial involution of the peripheral lymphoid tissues. Greater resistance to toxoplasmic infection was found in the gonadectomized mice than in controls of both sexes, possibly due to a better cell-mediated immunity in the gonadectomized animals. Overwhelming toxoplasmosis with increased mortality was found in the hexoestrol-treated mice after infection, probably resulting from a depression of cell-mediated immunity caused by hexoestrol. It is postulated that the cellular immune response is of greater importance than the formation of antibody in resistance to toxoplasmic infection. The role of the thymolmphatic--sex hormonal interrelation on the age--sex differences seen in the incidence of toxoplasmic lymphadenopathy is also discussed.

Animals↗

Effect of gonadectomy and oestrogen administration on the response of lymph-node post-capillary venules to infection with Toxoplasma gondii.

The effects of gonadectomy and oestrogen administration on the response of lymph-node post-capillary venules to infection with Toxoplasma gondii have been studied in mice. The endothelial cells of the post-capillary venules were significantly higher in the female than in the male controls. Oophorectomy had no significant effect while orchidectomy increased the height of the cells. However, hexoestrol administration resulted in a rise of the height to maximum levels in the female and in the male gonadectomised animals. The endothelial cells of male and female control and gonadectomised mice were higher after infection with Toxoplasma while in the infected hexoestrol-treated animals, lower cells were seen. The number of lymphocytes passing through the post-capillary venule wall was increased by gonadectomy and decreased by hexoestrol administration in both sexes. The same pattern was seen in the infected groups. The influence of sex hormones on the post-capillary venules and its possible contribution to the differences seen in the immune response between the two sexes is discussed.

Animals↗

An electron microscopic study of the changes induced by oestrogens on the lymph-node post-capillary venules.

The changes induced in the lymph-node post-capillary venules of male and female mice, 1, 2, 4, 7, 10 and 14 days after oestrogen administration were studied in 1 micron sections and with the electron microscope. The endothelial cells of the post-capillary venules are higher in female than in male control mice. On the first and second days after Hexoestrol administration there is an increase in the number of ribosomes and polyribosomes lying free in the cytoplasm of the endothelial cells. These cells were significantly increased in height between day 2 and day 7, in both male and female Hexoestrol-receiving mice, remaining at high levels thereafter. The increase in height was accompanied by an increase in the Golgi elements which occupied the major part of the cytoplasm of the endothelial cells. Lysosomes, multivesicular bodies and signs of phagocytosis were more often seen. In contrast, the numbers of lymphocytes passing through the post-capillary venule wall were significantly decreased, probably due to a direct effect of Hexoestrol on the thymus. The relation of an oestrogenic effect on the ultrastructure of the post-capillary venules to the sex differences seen in the immune response is discussed. The possibility that this may constitute a part of a general oestrogenic effect on the reticuloendothelial system is also considered.

Animals↗

A light and electron microscope study on the origin of Foà-Kurloff cells.

Numerous Foà-Kurloff (FK) cells have been found in the circulation, spleen, bone marrow, thymus and placenta of guinea pigs under endogenous or exogenous oestrogenic stimulation. The origin of these cells is obscure. In the present experiment, the distribution of FK cells in organs other than those stated above was studied following gonadectomy and hexoestrol administration in guinea pigs of both sexes for either 1 or 10 weeks. More FK cells than those expected from the vascularity of the organ were found in the liver and lungs of male and female animals. The number of FK cells in these organs was larger after the long-term treatment with hexoestrol and it was accompanied by a significant decrease in the number of Kupffer cells of the liver. The latter observation is in contrast to previous reports of increased numbers of Kupffer cells in the liver of oestrogen-receiving mice, a species not producing FK cells. These observations suggest a relation between the two types of cells. No transformation of mature Kupffer cells into FK cells was seen with the electron microscope. However, other findings suggest that both Kupffer cells and FK cells may well be derived from a common precursor of MPS in the bone marrow.

Animals↗

Effect of sex hormones on the immune system of guinea-pigs and on the development of toxoplasmic lesions in non-lymphoid organs.

The role of cell-mediated immunity in the pathogenesis of toxoplasmic lesions in non-lymphoid organs and its significance in resistance to infection with Toxoplasma gondii were studied in guinea-pigs. Alteration of the sex hormonal environment in both sexes has significant effects on the immunological status of the guinea-pig, changing its reaction to toxoplasmic infection. Thus, gonadectomy appears to enhance delayed hypersensitivity, leading to a greater prominence of lesions in the non-lymphoid organs of gonadectomized male and female animals than in controls. This observation supports the possibility that delayed hypersensitivity plays a major role in the pathogenesis of non-lymphoid, toxoplasmic lesions. Hexoestrol administration for a long period of time induces complete thymic atrophy and severe involution of the thymus-dependent areas of the lymph nodes and spleen, leading to the suppression of cell-mediated immunity and overwhelming disease in those animals infected with Toxoplasma gondii, suggesting that cell-mediated immunity is of importance in resistance to toxoplasmic infection. In view of these findings, the difficulties in the treatment of non-lymphoid toxoplasmic lesions, such as ocular ones, by depressing cellular immunity, are discussed.

Animals↗

Prognostic factors in advanced stage Hodgkin's lymphoma: the significance of the number of involved anatomic sites.

BACKGROUND: Advanced Hodgkin's lymphoma (HL) is curable by conventional chemotherapy in 60--70% of patients. The pretreatment identification of a sizeable subgroup of patients with sufficiently low failure-free survival (FFS) to be eligible for investigational treatment is necessary. OBJECTIVES: To determine the prognostic significance of the number of involved sites (NIS) in patients with advanced HL and its relationship to the International Prognostic Score (IPS). METHODS: A retrospective review of patients with advanced HL, defined as Ann Arbor stage (AAS) IB, IIB, III or IV, treated with anthracycline-based regimens. The end-point was FFS. RESULTS: We identified 277 patients with a median age of 32 yr (14--78), 57% of whom were males. AAS was I in 4% of patients, II in 29%, III in 38% and IV in 29%. B-symptoms were recorded in 81%. Most patients had nodular sclerosis (64%) and mixed cellularity (26%) histology. IPS was greater-than-or-equals 3 in 44% of 242 evaluable patients. The NIS was greater-than-or-equals 5 in 32% of the patients and 20% of all patients had both greater-than-or-equals 5 involved sites and IPS greater-than-or-equals 3. The 10-yr FFS was 67%, being 76% vs. 50% for patients with less-than-or-equals 4 vs. greater-than-or-equals 5 involved sites (P < 0.0001). The NIS (greater-than-or-equal 5), AAS IV and anemia were independent predictors of FFS in multivariate analysis. The NIS remained significant along with IPS, when the latter was included in the analysis. Patients with greater-than-or-equals 5 involved sites and IPS greater-than-or-equals 3 had 10-yr FFS overall, and relapse-free survival of 41%, 45% and 49%, respectively. CONCLUSIONS: The NIS was associated with FFS in advanced HL, was independent of IPS, and led to the identification of a sizeable subgroup of patients with 10-yr FFS of approximately 40%. This factor should be evaluated during the development of prognostic systems.

Adolescent↗

Modulation of wild-type p53 activity by mutant p53 R273H depends on the p53 responsive element (p53RE). A comparative study between the p53REs of the MDM2, WAFI/Cip1 and Bax genes in the lung cancer environment. WAFI/Cip1 = WAF1/Cip1.

Wild-type (wt) p53 is a tumor-suppressor protein which acts via transcriptional and transcriptional-independent mechanisms. The transcriptional function of p53 is mediated by specific responsive elements (REs). The MDM2, WAF1/Cip1 and Bax genes possess p53REs and their activation by wt p53 induces cell cycle progression, arrest and programmed cell death (apoptosis), respectively. Mutations of the p53 gene are detected in more than 50% of the human malignant tumors. p53 mutants seem to have a more stable conformation and are suggested to exert dominant-negative inhibition of wt p53 in cells containing both wt and mutant (mt) alleles. However, recent studies show that certain mt p53 proteins posses a "gain of function" phenotype. In the present study, we examined the effects of the second most frequent p53 mutant R273H on the p53REs of the MDM2, WAF1/Cip1 and Bax genes in the H1299 non-small cell lung carcinoma cell line. Although mt p53 R273H alone was unable to bind and transactivate the corresponding p53REs, it enhanced the MDM2-p53RE mediated gene transcription of wt p53 (positive-dominant effect) and prevented the wt p53 transactivation of the p53REs of WAF1/Cip1 and Bax genes (negative-dominant effect). Our data suggest that in the appropriate environment, differential transcription of critical p53 target genes by certain p53 mutant proteins may illustrate another mechanism implicated in tumor development.

Cyclin-Dependent Kinase Inhibitor p21↗

Human papilloma virus DNA detection in oral lesions in the Greek population.

HPVs (Human Papilloma Viruses) are small DNA "epitheliotropic" viruses, implicated in cervical carcinogenesis, particularly the "high-oncogenic-risk" types HPV-16 and HPV-18. Data concerning oral carcinogenesis are however, contradictory. We examined the presence of HPV and subsequently HPV-16 and HPV-18 in 102 specimens of paraffin-embedded oral tissue blocks--81 oral squamous cell carcinomas and 21 oral hyperplasias--using PCR technique followed by agarose gel electrophoresis. Our results demonstrated that 49% (50/102) of the samples were HPV positive. Subsequent analysis of HPV positive lesions revealed 22% positivity for HPV-16 and 44% for HPV-18. HPV-18 was detected only in carcinomas, while HPV-16 was more abundant in papillomatous hyperplasias and in a small percentage of carcinomas. These findings may probably indicate a contributing role for HPV-18 as a potent co-carcinogen in oral epithelial carcinogenesis in the Greek population.

Carcinoma, Squamous Cell↗

Cytotoxic protein expression in non-Hodgkin's lymphomas and Hodgkin's disease.

Recent studies have shown that some peripheral T-cell lymphomas (PTCL) could be derived from lymphocytes with cytotoxic potential. Therefore, we have investigated by immunohistochemistry 34 cases of PTCL including 2 cases of hepatosplenic gamma delta PTCL and 5 cases of sinonasal NK-cell lymphomas as well as 7 cases of T-lymphoblastic lymphomas (T-LBL) for the expression of the cytotoxic proteins TIA-1 and granzyme B. In addition, 50 cases of Hodgkin's disease (HD) were investigated in order to see if these cytotoxic proteins are expressed by Hodgkin and Reed-Sternberg (HRS) cells. Expression of the TIA-1 is characteristic of cytotoxic cells regardless of their activation status whereas expression of granzymes is highly increased in activated cytotoxic cells. All the five cases of sinonasal NK-cell lymphomas expressed TIA-1 and granzyme B in most tumour cells. The two gamma delta PTCL cases expressed TIA-1 protein in most tumour cells but not granzyme B. Of the 32 other PTCL, 9 cases showed cytotoxic protein expression in tumour cells. These cases comprised 2 pleomorphic medium large cell (PML) (1 nodal and 1 intestinal) and 7 CD30 positive anaplastic large cell lymphomas (ALCL) (5 nodal and 2 cutaneous). Cytotoxic protein expression in our series appeared to be related to the location since 10/18 (55%) extranodal PTCL and NK-NHL and only 6/21 (28%) nodal PTCL expressed TIA-1, and related to histology since, in nodal PTCL, this pattern was observed in most anaplastic (5/6 cases) and in a few pleomorphic (1/9 cases) lymphomas, but not in AILD-type NHL (0/6 cases). The 7 cases of T-LBL did not express cytotoxic proteins in tumour cells. EBV was detected by EBER RNA in situ hybridization (RISH) in tumour cells in all 5 sinonasal NK-NHL and in scattered atypical cells in all 6 cases of AILD. Two of the 50 cases of HD weakly expressed TIA-1 and granzyme B in a proportion of HRS cells. EBV was detected by RISH in 19/50 cases of HD but no correlation was found between EBV status and expression of cytotoxic proteins in HRS cells. However, the finding that granzyme B positive cells were found very rarely in close vicinity of HRS cells suggests that the function of activated cytotoxic cells is locally inhibited by the HRS cells and/or the reactive cells in the vicinity of HRS cells. Taken together our data suggest that: a) sinonasal NK-cell NHL represent tumours of activated cytotoxic NK-cells, b) the hepatosplenic gamma delta PTCL represent tumours of nonactivated cytotoxic gamma delta T-cells, c) a small proportion of other PTCL, mostly anaplastic large cell lymphomas represent tumours of cytotoxic T-cells and d) only very few cases of HD expressing cytotoxic proteins in a proportion of tumour cells, could be derived from activated cytotoxic cells.

Granzymes↗

Aberrant p16 expression is correlated with hemizygous deletions at the 9p21-22 chromosome region in non-small cell lung carcinomas.

The p16 protein is encoded by the CDKN2 gene, and functions as an inhibitor of cyclin-dependent kinase 4 and 6 (CDK4/6). Phosphorylation of the retinoblastoma protein (pRb) by CDK4/6 represents a vital step in cell cycle progression. Alterations of p16INK4A are frequent events in human malignancies. In non-small cell lung carcinoma (NSCLC) the data concerning the mechanisms of p16INK4A inactivation suggest that point mutations and aberrant methylation of its promoter can only account for a proportion of the cases with abnormal p16 immunoexpression. The role of deletions in this procedure is not yet clarified. In order to gain more insight into the role of deletions in p16INK4A deregulated expression, we investigated the state of the chromosomal region 9p21-22 in a series of 57 NSCLCs, by performing a detailed mapping analysis, using a tight cluster of highly polymorphic microsatellite markers, and correlating the findings with p16 immunostaining. Abnormal p16 expression was observed in 46% of the NSCLCs examined. No relationship was observed between p16 abnormal staining and various clinicopathological parameters. Abnormal p16 protein staining was strongly associated with hemizygous deletions at the IFNA and D9S171 microsatellite loci, which demarcate the region encoding the p16INK4A gene (P = 0.002). These findings suggest that deregulated expression of p16 is involved in the multistage process of NSCL carcinogenesis and that deletions may represent a predominant mechanism of p16INK4A inactivation. A significant percentage also of LOH was noticed at the D9S162 (35%) and D9S126 (38%) loci which lie 6cM and 4cM, respectively, far from the area which encodes p16INK4A, implying that other tumor suppressor genes (TSGs) may reside in this region. Although the overall incidence of LOH at the examined region was high (58%), we did not observe any correlation with smoking habits, histology and lymph node status. Another noteworthy finding was the existence of microsatellite instability (MI) in 11% of the patients. MI provides a marker for replication error phenotype (RER+), a recently defined manifestation of genetic instability observed in a wide range of tumors. In conclusion, alterations (LOH + MI) at the 9p21-22 chromosome region are frequent events in NSCLCs and may affect directly or indirectly the expression of p16.

Carcinoma, Non-Small-Cell Lung↗

Diagnostic value of anti-alpha FP antibody levels in a metastatic germ cell tumor of unknown primary site.

BACKGROUND: A 21 year old man with a metastatic germ cell tumor of unknown primary not responding to chemotherapy was scheduled to have a blind bilateral orchiectomy to eradicate the possible primary site although palpation and ultrasonography of the testicles had always been normal. METHOD: The patient underwent a radioimmunoscintigraphy with Anti-alpha FP antibody scan (AFP-Scan). RESULTS: On the basis of the scintigraphic results the patient underwent a left orchiectomy and additionally removal of the lymph node metastases. Histology revealed the presence of an in situ carcinoma in the left testis and a mixed tumor present in the abdominal lymph node metastases. Fluorescent in situ hybridization on tumor cells did not show any abnormalities related to chromosome 12, a finding connected with the somatic type of germ cell tumors. CONCLUSION: Anti-alpha FP antibody scan was helpful in detecting the primary site and saving the life of the patient without resulting in hypogonadism.

Adult↗

Recent advances in early prostatic cancer.

Early prostatic carcinoma is a slowly progressing, localized malignant tumor which has been recently discovered with increased frequency due to the use of improved diagnostic methods. The combination of digital rectal examination, serum PSA level and transrectal ultrasound is currently the best available diagnostic tool, although other putative diagnostic markers and techniques are being investigated. Core needle biopsy may follow if there is suspicion of malignancy and in doubtful cases the most useful antibody for the immunohistochemical diagnosis of early, low grade prostatic carcinoma is clone 34 beta E12. Cytogenetic techniques and molecular biological methods are increasingly being used for further investigating localized prostate carcinomas in order to identify early molecular targets and alterations, which may lead to progression. Chromosome abnormalities, cell to cell and cell to matrix interactions, changes in the status of steroid hormone receptors, oncogenes and tumor suppressor genes, as well as other, as yet unclear, events may be of importance in prostate carcinogenesis and the progression of early malignant tumors to aggressive phenotypes. A variety of putative prognostic markers, apart from serum PSA levels, histological grade and tumor volume, such as neuroendocrine differentiation, angiogenesis, cell proliferation labeling index and ploidy analysis may prove useful in evaluating tumor progression in early prostatic carcinomas. The final and most important goal of all investigations related to early prostate cancer is to contribute to the best therapeutic management of the individual patient.

Biomarkers, Tumor↗

New frontiers in liver surgery. Two-stage liver surgery for the management of advanced metastatic liver disease.

BACKGROUND/AIMS: To assess the value and the safety of main portal branch transection combined with transarterial targeting locoregional neo and adjuvant immunochemotherapy, 32 patients suffering from advanced metastatic liver disease underwent two-stage hepatectomy. METHODOLOGY: From September 1995 to June 1999, 32 consecutive patients underwent two-stage surgery for advanced metastatic liver disease. Firstly we performed ligation and transection of the main portal branch corresponding to the liver lobe occupied by the tumor and introduction of an arterial jet port catheter towards the hepatic artery. After a locoregional transarterial targeting immunochemotherapy regimen the patient had a 2nd laparotomy for hemihepatectomy. Following surgery, locoregional targeting immunochemotherapy was carried out in all patients via the arterial port of the gastroduodenal artery as an adjuvant treatment. RESULTS: There were no operative deaths. Mean survival was 27 +/- 8 months. CONCLUSIONS: Two-stage liver surgery is an appealing alternative that increases the resectability rate and overall survival in patients with advanced metastatic liver disease and is associated with excellent quality of post-operative life.

Adult↗