Biomedical subjects

J Olofsson

Publications and source records attributed to J Olofsson.

At least 19 recordsLinked to original sources

PubMed1998

[Retrospective analysis of selected tumor markers (p53, PCNA, Ki67; DNA ploidy) and ultrastructure in patients with larynx carcinomas].

A comparison was made of the staining intensities of selected immunohistochemical proliferating antigens (p53, PCNA, Ki67), DNA flow-cytometry and ultrastructures of neoplastic cells from 120 cases of laryngeal cancers. Clinically very advanced tumors were in the majority (T3, 43%; T4, 18%). A 5-grade scale was adopted to evaluate the level of immunohistochemical staining of the carcinoma cell nuclei. Positive staining was obtained in 70% for p53, 57% for Ki67 and 80% for PCNA. Sixty-two percent of the cases were DNA-diploid and 38% DNA-aneuploid. The DNA-diploid carcinomas were accompanied by enlargement of the cell nuclei, preservation of wide margins of nuclear heterochromatin, enlargements of the nuclear areas and increases in the number of nuclei. In the aneuploid-polyploid cancers the nuclei had a substantial polymorphism, with large cleaved nuclei showing significant variations in size and having a nuclear envelope. A frequent finding was euchromatization of chromatin. Dense chromatin appeared in the form of small clumps spread over the whole area of these irregular nuclei. Enlargement and activation of nucleoli were found. There was a positive (chi-square) correlation between T- and N-stage and immunohistochemical staining. There was also a positive correlation in staining intensity between p53, Ki67 and PCNA markers and strong correlation between these markers for proliferative activity and the degree of aggressiveness of a tumor.

Biomarkers, Tumor↗

PubMed1998

Melanotic neuroectodermal tumour of infancy arising in the maxilla.

Melanotic neuroectodermal tumour of infancy is an uncommon neoplasm that usually occurs in children aged one year or less. Difficulty in deciding the cellular origin of this tumour has led to numerous names, including congenital melanocarcinoma, melanotic epithelial odontoma, melanotic ameloblastoma, and retinal anlage tumour. Electron microscopy and histochemical studies, however, have now established the neural crest origin. The most frequent site of occurrence is the maxilla followed by the skull, the brain and the mandible. The genital organs are the most frequent extracranial site. We present two cases of melanotic neuroectodermal tumour of infancy arising in the maxilla.

Humans↗

PubMed1997

Correlates of latent and productive HIV type-1 infection in tonsillar CD4(+) T cells.

Correlates of virus load and characteristics of virus-producing cells in tonsillar tissue were investigated. Our results suggest that when less than 1:100 tonsillar CD4(+) T cells from individuals infected with HIV type-1 (HIV-1) contain replication competent provirus, the level of CD4(+) T cells in tonsils is comparable to that observed in uninfected individuals. Virus load at or above this level was associated with low CD4 cell numbers in tonsillar tissue. Only a few percent of all infected T cells in tonsillar tissue were active virus producers, with minor differences observed between individuals. Plasma viremia was found to correlate with infectious virus load in tonsillar tissue. With less than 1:1,000 of CD4 cells in lymphoid tissues being involved in active virus production, direct cytopathic effect by HIV-1 on infected CD4 cells is unlikely to fully explain the immunodeficiency seen in AIDS.

Adult↗

PubMed1997

Alteration of p53 gene structure and function in laryngeal squamous cell cancer.

The p53 gene is known as an anti-oncogene that manifests its function by controlling the cell cycle and is responsible for apoptosis of cells with unrepaired DNA. An accelerated p53 protein synthesis is the first response of a cell following DNA damage. However, mutations of the p53 gene can disturb protein synthesis or may be responsible for synthesis of a changed protein unable to control the cell cycle. Laryngeal tissue specimens from 120 patients were tested by immunohistopathological staining to detect mutated wild-type p53 protein. It was found that p53-positive specimens correlated with TNM staging and histopathological grading. Another indication of entering the cell cycle and undertaking an active proliferation by laryngeal cells was shown by detection of proliferating cell nuclear antigen (PCNA) and Ki67 nuclear antigen, which appeared in proliferating cells (late G1, S-G2 and M phase), but was absent in resting cells. Scoring of the staining for p53 protein, PCNA and Ki67 correlated with each other. DNA from 40 specimens was then isolated, amplified by polymerase chain reaction and analysed by single-strand conformation polymorphism and DNA sequencing for mutation in the p53 gene. Fifteen DNA samples were found to be positive, while mutations were detected in exons 5-8 in 13 samples. The majority of mutations were found in tissue specimens from T3 and T4 tumors. A possible explanation is almost half was attributable to genotoxic effects of tobacco smoking. Changes in the p53 gene and its products may also reflect early changes in laryngeal carcinogenesis and be of prognostic value.

Adult↗

PubMed1997

In vitro T-lymphocyte function in head and neck cancer patients.

T-lymphocyte cell function was studied in vitro in peripheral blood mononuclear cells (PBMC) from 61 male patients with head and neck squamous cell carcinomas compared to 46 control patients. Patients older than 80 years or with reduced tumor-related performance status as measured by Karnofsky score less than 75 were excluded. In contrast to previous similar studies, control subjects ensured a minimum stress load by sampling all patients on the day of either diagnostic or therapeutic surgery. PBMC were separated by density-gradient centrifugation and subsequently cultured with autologous sera in vitro. The mitogen concanavalin A (Con A), which stimulates all T-cell clones, was employed. Findings showed that increased Con A stimulation and PBMC proliferation occurred with PBMC from cancer patients compared to that from control patients. In contrast, no differences could be detected with respect to the stimulated supernatant level of interleukin-2, interleukin-4 or interferon-gamma between the groups. These results suggest that T-lymphocytes from PBMC are generally affected by neoplastic disease through either a supporting cell or serum factor.

Analysis of Variance↗

PubMed1997

[Significance of p53, PCNA and Ki-67 in the prognosis of squamous cell carcinoma of the oral cavity].

BACKGROUND: A common gene alteration in human malignancies is the mutation of the p53 gene. Through mutation p53 loses its function as a tumor suppressor and enables the tumor to proliferate. Ki-67 and PCNA are proliferation markers. The aim of this study was to find a reference to the prognostic significance of p53, Ki-67, and PCNA in squamous cell carcinoma (SCC) of the oral cavity. MATERIAL AND METHODS: Samples from 64 patients of the Department of Otolaryngology/Head and Neck Surgery, University of Bergen, Norway, with histologically proven SCC of the oral cavity were submitted to immunohistochemical procedure. All carcinomas were untreated. RESULTS: 59.3% of the patients showed a positive reaction for p53.Ki-67 and PCNA were expressed in about 68% of the cases, but with less staining intensity. No correlation could be found between the expression of the three antibodies and tumor factors such as tumor size, lymph nodes, degree of differentiation, recurrence and survival rate, the occurrence of second primaries, or the smoking habits of the patient. CONCLUSIONS: The expression of the tumor suppressor gene p53 and the proliferation marker PCNA and Ki-67 seem to have no prognostic significance in SCC of the oral cavity.

Adult↗

PubMed1997

Barrier between the supraglottis and the glottis: myth or reality?

Controversial opinions on the existence of a "barrier" between the supraglottic and glottic regions of the larynx are reported. Even if the two areas have different embryological derivations, there is no anatomic evidence of a "barrier" that could prevent supraglottic cancer from extending downward to the glottis. Numerous adequate pathologic studies, including whole organ sections, confirm that for advanced cancers, anatomic compartments delimiting the spread of the neoplastic process from the supraglottis to the glottis do not exist. Therefore, supraglottic laryngectomy should be performed not on the basis of embryological considerations, but on the basis of the actual extension of the neoplastic lesion.

Glottis↗

PubMed1997

[Chaos theory and otoneurologic diagnosis].

Current interpretation of signals obtained from ENG (electronystagmography) of patients suffering from vertigo is based on methods developed before computers became standard laboratory equipment. New signal processing methods, based on the use of fast computers, can increase our knowledge of the mechanisms involved in the regulation of the vestibular system. Preliminary results suggests that new analyzing tools from the field of chaos theory may yield information of clinical relevance. At present this would appear to be a promising approach to research in this field.

Humans↗

PubMed1996

Bcl-2 immunoreactivity in salivary gland neoplasms is unrelated to the expression of mRNA for natural killer cell stimulatory cytokines interleukin (IL)-2 and IL-12.

Certain cytokines are involved in the generation of natural killer (NK) cells and participate in the regulation of the proto-oncogene bcl-2. We aimed to study the mRNA expression of interleukin (IL)-2, IL-4 and IL-5, the composition of the tumour infiltrating lymphocytes (TIL), and the expression of bcl-2 in 14 benign and malignant human parotid tumours. T IL were predominantly composed of T lymphocytes and NK cells. We found evidence for the homing of T cells, and for generation of NK cells in the vicinity of the tumours. mRNA for IL-2 and IL-12, were identified but IL-4 mRNA was not found. The cytokine profiles and the composition of TIL of the two tumour categories were indistinguishable, suggesting that these host-response variables do not explain the differences in biological behaviour of these particular tumours. The results support a shift towards Th 1 (T helper 1) cells and interferon-gamma production, and that IL-12 also in vivo may play an important role in the regulatory interaction between innate resistance and adaptive immunity in tumour diseases. Most infiltrating lymphocytes showed strong expression of bcl-2; an interesting observation with regard to lymphocytic apoptosis in neoplastic diseases. The immunoreactivity for the bcl-2 protein varied considerably between and within tumours, and almost all benign tumours showed strong bcl-2 positively whereas several of the malignant tumours showed weak or absent staining. The variable expression of bcl-2 protein suggests a different susceptibility of tumour cells to apoptosis. The results also indicate that bcl-2 cannot pla a major role as protective agent in the specific apoptotic pathway induced by NK cells.

Humans↗

PubMed1996

Regulation of the inducible form of prostaglandin endoperoxide synthase in the perfused rat ovary.

The regulation of the two isoforms of prostaglandin endoperoxide synthase (PGS-1 and PGS-2) and prostaglandin synthesis by luteinizing hormone (LH)/3-isobutyl-1-methylxanthine (IBMX) and progesterone was examined in granulosa cells and residual ovarian tissue of rat ovaries perfused in vitro. The endogenous progesterone synthesis was blocked by an inhibitor of 3 beta-dehydroxysteroid-dehydrogenase, compound A (CA), previously shown to reversibly inhibit ovulation in the in vitro perfused rat ovary. Preovulatory ovaries were perfused for 7 h, and soluble extracts from granulosa cells and residual ovarian tissue were obtained for immunoblotting and determination of the tissue contents of PGS-1/PGS-2. The tissue concentrations of prostaglandins (PGE2, PGF2 alpha and 6-keto-PGF1 alpha) were measured. The ovaries were perfused with medium alone (control) or medium containing LH (0.1 microgram/ml) and IBMX (0.2 mM), LH+IBMX+CA (10 micrograms/ml) or LH+IBMX+CA+progesterone (10 micrograms/ml). PGE2, PGF2 alpha and 6-keto-PGF1 alpha tissue concentrations were increased by LH+IBMX, with highest values detected for PGE2. The addition of CA alone or CA in combination with exogenous progesterone, did not change the values of prostaglandins increased by LH+IBMX. The content of PGS-1 was only marginally changed in both granulosa cells and residual ovarian tissue in the different treatment groups, compared to the control group. In contrast, PGS-2 was markedly increased by LH+IBMX, especially in the granulosa cells. The addition of CA, in combination with LH+IBMX, resulted in a small decrease of PGS-2, and progesterone further decreased its content. In the residual ovarian tissue, only minor changes of PGS-2 were detected. These results demonstrate that LH and progesterone selectively regulate the expression of PGS-2 in rat granulosa cells, whereas the hormonal regulation of PGS-1 is less pronounced. Progesterone inhibits PGS-2 in granulosa cells but has negligible effects on the total ovarian synthesis of prostaglandins during the ovulatory period.

Animals↗

PubMed1996

Positive identification in situ of mRNA expression of IL-6, and IL-12, and the chemotactic cytokine RANTES in patients with chronic sinusitis and polypoid disease. Clinical relevance and relation to allergy.

Interleukins 6 (IL-6) and 12 (IL-12), and the chemoattractant chemokine RANTES were studied in ethmoidal mucosa, using reverse transcriptase polymerase chain reaction. The 49 patients had chronic sinusitis or nasal/paranasal polyposis, and some also allergy. To the best of our knowledge, this is the first study that demonstrates RANTES and IL-12 on mRNA level in human sinonasal mucosa in situ. mRNA for IL-6, IL-12 and RANTES were detected in 2, 8 and 6 patients with chronic sinusitis, respectively, and in mucosa from patients with polyposis a positive expression was observed in 4, 14 and 10 cases. There were no statistically significant differences. Analysing the entire group of 49 patients, disregarding type of mucosal disease, the number of patients with positive RANTES was significantly higher than that for IL-6. Similarly, IL-12 positivity was more frequently expressed than IL-6. mRNA for IL-6 was expressed in only 2 of the allergic patients. The cytokine production studied thus seems to be unrelated to the clinically defined entities. There is thus a local production in human diseased sinonasal mucosa of RANTES, as well as of IL-6 and IL-12. The local production of RANTES is an important prerequisite for recruitment and migration of inflammatory cells into the tissue. IL-12 is a co-stimulator of antigen-specific responses of established T helper 1 (Th1) clones, and regulates the responsiveness of the clones to a number of T cell growth factors. The study supports a shift towards Th1 cells in these disease entities.

Adjuvants, Immunologic↗

PubMed1996

Endoscopic endonasal sinus surgery. A long-term follow-up study.

This study presents 230 patients who have been selected for endoscopic endonasal sinus surgery on the basis of a standardised diagnostic procedure. Surgery was performed by one surgeon during the period 1987 to 1991 and the Messerklinger technique (MT) was used exclusively. The selection was made from patients with nasal/paranasal complaints remitted for further treatment. Diagnostic procedures comprised a thorough anamnesis including questions about additional factors such as specific allergy of the upper airways, unspecified hyperreactivity of the nasal/paranasal mucosa, asthma, smoking, exposure to air pollution, heritage and systemic diseases, in addition to a conventional ENT-examination, endoscopy of the nasal/paranasal cavities, and tomography (conventional or computed). The patients were thereafter divided into the following groups: 1) acute recurrent and/or chronic sinusitis, 2) nasal/paranasal polyposis, 3) sinogenic headache, 4) mucoceles, and 5) olfactory dysfunction. More than 90% of the patients were treated on a day care out-patient basis, under local/topical anaesthesia combined with intravenous sedation. The extent of surgery varied in the different groups. There were no serious peroperative complications and no postoperative sequelaes. The patients were closely followed postoperatively for 1-5 years (mean 3 years and 5 months) until the study was closed at the end of 1992. We conclude that endoscopic endonasal sinus surgery demands several postoperative controls. Meticulous postoperative care is one of the basic requisites for securing optimal long-term results.

Adolescent↗

PubMed1996

Alterations in the level of phosphotyrosine signal transduction constituents in human parotid tumors.

Human parotid tumors were evaluated for the activation of the phosphotyrosine signaling pathway by Western blot, enzyme activity assay, and reverse transcriptase-polymerase chain reaction. Warthin's tumor and mucoepidermoid carcinomas had the greatest level of tyrosine phosphorylated proteins identified in plasma membrane fractions. These tumors, along with pleomorphic adenocarcinoma, showed high levels of membrane expression of the tyrosine kinase receptor, c-erbB-2, and phosphatidylinositol-3-kinase. Expression of the epidermal growth factor receptor was confined to normal tissue. The level of mRNA for c-erb was elevated only in mucoepidermoid carcinomas. Messenger RNA levels for ras were unchanged from control levels in all tumors, while the level of src mRNA was higher in the tumor samples than the normal parotid tissue. The activities of several signal transduction kinases, including protein kinase A and C were elevated in tumor tissue (7.7- to 18.9- and 0.4- to 3.7-fold higher, respectively), relative to surrounding normal tissue. While the level of glandular amylase was reduced (22%-0% of normal levels) in the tumor tissue, epidermal growth factor (EGF) and transforming growth factor-alpha (TGFalpha) content was dramatically higher in the neoplastic tissue (10- to 170-fold and 4.6- to 6.0-fold, respectively). These results suggest that with the presence of elevated levels of EGF, TGFalpha, and the oncoprotein receptor c-erbB-2 in the membrane of parotid tumors, cell proliferation and activation of the phosphotyrosine signal transduction pathway may involve autocrine stimulation through the expression of high levels of growth factor and receptor in the same tissue.

Base Sequence↗

PubMed1996

Reduced CD4 cell counts in blood do not reflect CD4 cell depletion in tonsillar tissue in asymptomatic HIV-1 infection.

OBJECTIVE: To investigate whether the loss of CD4 cells seen in peripheral circulation of HIV-1-positive individuals reflects a similar depletion of CD4 cells from lymphoid tissue. DESIGN: CD4 and CD8 cells in tonsillar mononuclear cell suspensions were quantified relative to tonsillar B cells, as these were thought to remain numerically unchanged in the course of HIV infection. Results were related to the CD4 cell counts in blood and to the clinical status of the patients. METHODS: Blood samples and tonsillar tissue were obtained from 13 HIV-1-seropositive individuals and six seronegative controls. B cells and T-cell subsets in mononuclear cells were quantified using a three-colour flow cytometry protocol. Histological sections were morphologically classified and B-cell areas were quantified by morphometry. RESULTS: The B-cell fraction was confirmed to be relatively unchanged in asymptomatic HIV-1-seropositive individuals compared with controls. The tonsillar CD4 : B-cell ratios in asymptomatic individuals was similar to those seen in controls, whereas the CD4 : B-cell ratios in symptomatic HIV-1-infected individuals were greatly reduced. The tonsillar CD4 : CD8 cell ratios in HIV-1-infected individuals were much lower than those seen in controls, in the asymptomatic group due to a considerable expansion of the tonsillar CD8 cell subset, and in the symptomatic group also due to a loss of CD4 cells. CONCLUSIONS: We found no evidence of CD4 cell depletion in tonsillar tissue in asymptomatic HIV-1-infected individuals despite low CD4 cell counts in blood. Loss of CD4 cells from this lymphoid tissue seems to occur as a late-stage phenomenon correlated with the onset of clinical symptoms.

Adult↗

PubMed1996

[p53 oncogene in the laryngeal cancer].

Cancer is a genetic disease and the development of the techniques of molecular biology in recent 10 years contributed to the new understanding of neoplasmatic process. The mutations of gene p53 became one of the most common abnormality in human cancer. The aim of this research was to mark oncoprotein p53 in 120 cases of larynx cancer and the correlation of its appearance with clinical and histopathological parameters. The evaluate the degree of immunohistochemical staining of cell nuclei a 5 degree scale was adopted. The positive staining of cell nuclei was observed in 70% of cases. Positive correlations based on a chi-square test was observed between p53 and T and N as well as between p53 and the degree of histological differentiation.

Adult↗

PubMed1996

p53, PCNA and Ki67 in laryngeal cancer.

Immunohistopathological staining for p53, PCNA and Ki67 was performed in 120 specimens from previously untreated laryngeal carcinomas using the avidin-biotin method with peroxidase as a marker enzyme and diaminobenzidine as a chromogen. A 5-grade staining score system was used. Statistically significant correlations (Chi-square) were seen between T- and N-stage and histopathological grading. p53 and Ki67 scoring correlated with T- and N-stage whereas PCNA with T-stage. All staining correlated with histopathological grading. The score of staining for p53, PCNA and Ki67 correlated with each other. The patients with recurrences within 3 years had mainly carcinomas with higher staining scores. Using Chi-square analysis the p53, PCNA and Ki67 staining scores were also independent prognostic indicators.

Adult↗

PubMed1996

[Diagnostic and prognostic value of p53 oncogene and the selected neoplastic markers (Ki67, PCNA, DNA ploidy) of the ultrastructure in patients with laryngeal cancer].

A comparison was performed of staining intensity of immunohistochemical proliferating antigens (p53, PCNA, Ki67), DNA flow cytometry and ultrastructure of the carcinoma cells in 120 cases of laryngeal cancer. Clinically very advanced tumors were in majority (T3 - 43%, T4 - 18%). A 5 graded scale was adapted to evaluate the level of immunohistochemical staining of the carcinoma cell nuclei. A positive staining was obtained in 70% for p53, 57% for Ki67 and in 80(2/3) for PCNA. 62% of the cases were DNA diploid and 38% DNA aneuploid. The DNA diploid carcinomas were accompanied by the enlargement of the cell nuclei, preserving of the nuclei's wide margins of heterochromatine, enlargement of the nuclear area and increase of the number of nuclei. In the aneuploid-polyploid cancer the nuclei had a substantial polymorphism with large cleaved nuclei and with significant variation in size, and with nuclear envelope. A frequent finding was euchromatization of chromatine. Dense chromatine appeared in the form of small clumps spread over the whole area of these irregular nuclei. Enlargement and activation of nucleoli occurred. There was a positive correlation (Chi-square) between T- and N-stage and immunohistochemical staining. There was also a positive correlation in staining intensity between p53, Ki67 and PCNA. There is also strong correlation between these markers of proliferative activity and the degree of aggressiveness of the tumour.

Adult↗

PubMed1995

[(Adeno)tonsillectomy in children. A follow-up study].

A retrospective study was performed where parents of 246 children who had undergone (adeno)-tonsillectomy received a questionnaire regarding the symptomatology (14 symptoms) before and after surgery. 92% of the parents were satisfied with the surgical outcome. 98% felt that their children were in a better condition after surgery. There was a significant improvement of all symptoms. The expectations of the parents were fulfilled. The major complaint was the waiting time for operation. In order to reduce the cost of health care an increasing number of operations are performed as day-care surgery. Less than 1% of the parents in our study would like to have the tonsillectomy performed on a day case basis. Anyhow, the majority of the patients would have failed to meet the criteria for outpatient surgery because of obstructive sleep apnoea, recent history of upper airway infection or because they were living too far from the hospital.

Adenoidectomy↗