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Biomedical subjects

R Nilsen

Publications and source records attributed to R Nilsen.

At least 37 records · Page 2Linked to original sources

The Swedish snus and the Sudanese toombak: are they different?

In Sweden, snuff (locally known as snus), was introduced since the year 1637. Presently, Sweden has the highest per capita consumption and sale figures of snuff in the world, and the habit is becoming increasingly popular. Snus is manufactured into a dry form used in the nasal cavity and a moist form used in the oral cavity. Snus manufactured for oral use is a moist ground tobacco of Dark Kentucky or Virginia species mixed with an aqueous solution of water and other blending ingredients. This form of snuff is found in two types: (1) loose and (2) portion-bag-packed. These are the most widely used. The loose moist form (1-2 g a quid) is the most popular type consumed by 73% of the males, followed by the portion-bag-packed form (0.5-1 g a quid), consumed by 13% of the males, while 14% of the males are mixed users. The majority of snus users place the quid in the vestibular area of the upper lip, and the prevalence among persons 15 years of age or older in 15.9% among males and 0.2% among females. The pH of snus has declined from a previous range of 8-9 to a range of 7.8-8.5, moisture content ranges 35-60% and nicotine content is in the order of 5-11 mg/g dry wt tobacco-specific N-nitrosamines (TSNAs) in micrograms (N'-nitrosonornicotine: NNN 5-9; 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone: NNK 1-2; N'-nitrosoanatabine: NAT 2-5). In the Sudan, snuff, locally known as toombak, was introduced approximately 400 years ago. It is always processed into a loose moist form, and its use is widespread in the country. Tobacco used for manufacture of toombak is of the species Nicotiana rustica, and the fermented ground powder is mixed with an aqueous solution of sodium bicarbonate. The resultant product is moist, with a strong aroma, highly addictive and its use is widespread particularly among males. Its pH range is 8-11, moisture content ranges 6-60% and nicotine content is from 8 to 102 mg/g dry wt, and TSNAs contents in micrograms (NNN 420-1 550; NNK 620-7 870; NAT 20-290). Snus and toombak dippers develop a clinically and histologically characteristic lesion at the site of dipping. Probably due to control of the TSNAs in snus, this type of snuff is associated with a lower risk of cancer of the oral cavity (relative risk: RR 5-6-fold), whereas the risk for cancer of the oral cavity among toombak users was high (RR 7.3-73.0-fold). In conclusion, the two snuff products significantly differ in many aspects. Most notable differences are tobacco species, fermentation and ageing, nicotine and TSNAs content, pH, expression of the p53 tumour suppressor gene, and keratin types 13, 14, and 19. It was, therefore, the object of the present study to highlight the oral health hazards of toombak, and to compare it with snus regarding the aforementioned differences.

Carcinogens↗

A glycosylated Bence Jones protein and its autologous amyloid light chain containing potentially amyloidogenic residues.

Amyloidosis is characterized by deposition of protein fibrils in various tissues. The wide variety of sequences of both amyloidogenic and non-amyloidogenic immunoglobulin light chains makes them a unique tool for addressing the importance of primary structure in the formation of insoluble fibrils. In this study, we have determined the primary structure of the kappa I immunoglobulin light chain from both the urinary Bence Jones protein and the deposited amyloid fibrils of a patient (MH) with primary amyloidosis. The sequence identity of urinary-excreted and tissue-deposited light chains excluded biclonality and somatic mutations and confirmed that the light chain existed in both a soluble and an insoluble form. Several residues have been previously reported to be significantly associated with amyloidogenic kappa chains. Many of these were found in the MH sequence, including Asp31, Asn45, Phe49, Gln55, His70, Asn/Gly93 and ProN/Val96, thereby supporting their potential role in fibrillogenesis. In addition, Asn20 and Pro60 of protein MH replaced the normally conserved Thr20 and Ser60. Asn20 was glycosylated in both the Bence Jones and the amyloid fibril protein MH. Cumulative effects of amyloid-associated residues and glycosylation might have rendered the immunoglobulin light chain MH prone to fibril formation.

Amino Acid Sequence↗

A mouse model for latent tuberculosis.

The aim of the study was to establish a reproducible murine model for latent tuberculosis. We propose an operational definition of latent murine tuberculosis as a stable Mycobacterium-tuberculosis count in lungs and spleens without clinical signs or obvious histopathological changes in the lungs over a long period of time and without spontaneous reactivation of disease. B6D2F1Bom mice were inoculated with a wide range of Mycobacterium tuberculosis doses intraperitoneally or intravenously and followed for a long period to determine suitable conditions to produce latent infection. No anti-tuberculosis drug treatment was used. Microbiological and histopathological studies were carried out. Corticosterone challenge was used to reactivate the latent infection. Mice infected with 4 x 10(4) and 4 x 10(5) bacilli i.p. were followed up to 107 weeks without spontaneous reactivation. The present model is discussed in comparison with previous latent tuberculosis mouse models as well as the possible mechanisms of shift to stationary phase from multiplying bacilli.

Animals↗

Characterization of an amorphous deposit in the lamina propria in oral snuff users in the Sudan as collagen.

Histological and ultrastructural features of 25 oral snuff dipper's lesions with distinctive subepithelial hyaline deposits were investigated. Periodic acid-Schiff reaction with and without diastase digestion demonstrated the presence of glycogen and other carbohydrates, but histochemical stains for normal collagen, elastin and fibrin showed a weak variable reactivity of the deposit. Although in 7/25 cases the deposit was in close proximity to labial salivary glands and on occasions ducts were found within the deposit, the presence of mucin was not a consistent feature. Congo red staining and immunohistochemical investigation with an anti-amyloid antibody did not support the previous contention that such deposits were amyloid in nature. Immunohistochemically, collagen antibodies also provided negative results, but ultrastructural features of three biopsies studied suggest that the bulk of this deposit is made up of collagen, as typical cross-striated fibrils were found. The pathogenesis of this deposit could therefore be interpreted as over-production and/or reduced turnover of collagen by resident fibroblasts, which is further altered by the ingredients of toombak. The deposit does not appear to be a secretory product.

Adult↗

Expression of keratin 13, 14 and 19 in oral squamous cell carcinomas from Sudanese snuff dippers: lack of association with human papillomavirus infection.

In stratified squamous epithelia, altered expression of keratins (Ks) is one possible marker of malignant potential. In the epithelium of the uterine cervix, presence of human papillomaviruses (HPVs) is increasingly regarded as a marker of risk for cervical cancer. However, a similar role in oral cancer and precancer remains controversial. To address these questions, formalin-fixed, paraffin-embedded oral carcinomas from Sudanese snuff dippers (n=14) and oral carcinomas from Sudanese (n=14), Swedish (n=19) and Norwegian (n=41) non-snuff dippers were examined by immunohistochemistry for expression of K types 13, 14 and 19 using monoclonal antibodies. HPV infection was searched for in all the carcinomas by in situ hybridization (ISH) using the cocktail HPV OmniProbe and the ViraType probe. Carcinomas from Sudanese (snuff dippers/non-snuff dippers) were also examined for HPV infection by polymerase chain reaction (PCR) using the general HPV primers GP5+/GP6+. For the oral carcinomas from snuff dippers, moderate to intense expression of K13 (71%; 10/14), K14 (86%; 12/14) and K19 (93%; 13/14) was found. For the oral carcinomas from non-snuff dippers, weak to moderate expression of K13 (64%; 47/74), K14 (43%; 32/74) and K19 (45%; 33/74) was found. HPV DNA was not detected in any of the carcinomas from three countries when examined by ISH. The Sudanese (from snuff dippers/non-snuff dippers) oral carcinomas were also negative for HPV DNA with the PCR. The present study shows that (i) there is a high level of expression of K13, K14 and K19 in oral carcinomas from snuff dippers compared to those from non-snuff dippers, (ii) this high level of expression may arise from dysregulation of keratinocyte proliferation and maturation caused by damaging effects of snuff, (iii) the HPV genome is not found in Sudanese (snuff dippers/non-snuff dippers), Swedish or Norwegian oral carcinomas, and (iv) this may suggest that these viruses do not play a prominent role in the aetiology of oral carcinomas from these countries.

Carcinoma, Squamous Cell↗

[Sick leave II for backache--municipality of Kristiansand. A one-year follow up with and without an outpatient program].

186 patients from Kristiansand who had been certified as sick for more than eight weeks because of low back pain were recruited consecutively and studied over a period of one year. 91 of these patients participated for three weeks in an out-patient programme involving physical activity and theoretical education. The control group (95 patients) consisted of 65 patients recruited before the treatment group and 30 recruited after the treatment group. The duration of certified sick leave was reported by the national Insurance Office of Kristiansand. The subjective ratings of low back pain, function and quality of life were stated by all subjects at the time of inclusion in the study and again after six and 12 months. The treatment group also stated their subjective assessment after the three weeks of intervention. The results show a significant improvement of low back pain, function and quality of life in the treatment group only, both following the intervention and after one year. 15% of the treatment group were still certified as unfit for work after one year, as against 23% of the one and 26% of the other control group. These differences were not, however, statistically significant.

Adult↗

Species differences in V1a receptor gene expression in monogamous and nonmonogamous voles: behavioral consequences.

Arginine vasopressin modulates a number of species-typical social behaviors, including social memory in rats, scent marking and aggressive behavior in hamsters, and partner preference formation and paternal behavior in monogamous rodents. The distribution of V1a receptor binding sites in the brain varies greatly among species. Using in situ hybridization in 2 species of voles with strikingly different patterns of V1a binding sites and social behaviors, the authors demonstrate that differences in V1a receptor binding sites are due to species differences in regional V1a receptor gene expression. It is then demonstrated that the differences in receptor gene expression are associated with species differences in behavioral response to centrally administered vasopressin. Together, these data suggest that the phylogenetic plasticity of central neurohypophyseal peptide receptor expression may contribute to the evolution of species-typical social behaviors.

Amino Acid Sequence↗

Immunohistochemical detection of p53 in archival formalin-fixed tissues of lip and intraoral squamous cell carcinomas from Norway.

We investigated the expression of p53 in 82 formalin-fixed, paraffin-embedded archival tissue specimens of lip and intraoral squamous cell carcinomas (SCCs) from the period 1930-1995, by immunohistochemistry using three monoclonal antibodies (MAbs DO-7, DO-1 and 1801). Before incubation, sections were pretreated with 0.1% Protease enzyme at 37 degrees C for 10 min followed by 5 + 5 min microwave oven heating at 700 W and 425 W, respectively. Formalin-fixed tissues of 10 carcinomas of the uterine cervix positive for p53 were used as controls. With one or more of the three MAbs, p53 was expressed in 73% of the 82 SCCs examined. With only protease enzyme pretreatment or microwave oven heating, p53 was expressed in 9/82 and 12/82 of the SCCs, respectively. Of the 82 SCCs, 60%, 45% and 23% expressed p53 with DO-7, DO-1 and 1801, respectively. The kappa coefficient indicated poor agreement between these results for the antibodies, and for lip and intraoral SCCs, except for p53 expression in intraoral SCCs demonstrated by DO-1/1801, which showed fair agreement. The present study suggests that combined protease pretreatment and microwave oven heating of tissue sections improved unmasking of p53 antigenic sites in archival material stored for up to 65 years.

Adult↗

Immunohistochemical detection of p53 in non-malignant and malignant oral lesions associated with snuff dipping in the Sudan and Sweden.

Immunohistochemistry was used to examine the expression of p53 in pre-malignant oral lesions and oral squamous-cell carcinomas (SCCs) from Swedish and Sudanese snuff-dippers, as well as in pre-malignant oral lesions and oral SCCs from non-snuff-dippers from the Sudan, Sweden and Norway. Of the 14 SCCs from Sudanese snuff-dippers, 21% (3/14) expressed p53. Of the 14, 60 and 41 SCCs from non-snuff-dippers from the Sudan, Sweden and Norway, 64% (9/14), 65% (39/60) and 68% (28/41) expressed p53, respectively. A statistically significant difference in expression of p53 was found in SCCs from Sudanese snuff-dippers compared to those from non-snuff-dippers from all/or any of the 3 countries. None of the suspected pre-malignant oral lesions from Sudanese snuff dippers or non-snuff-dippers expressed p53. Only 2 out of the 15 oral fibro-epithelial hyperplastic lesions from Swedish snuff-dippers expressed p53. Some of the oral epithelial dysplastic lesions, as well as the carcinoma in situ lesions from Norwegian non-snuff-dippers, expressed p53, while the oral fibro-epithelial hyperplastic lesions did not. The low relative frequency of p53 expression found in oral SCCs from snuff-dippers compared to those from non-snuff-dippers might suggest differences in mechanisms of oncogenic action induced by snuff. Alternatively, the pathogenesis of malignant oral lesions from snuff-dippers may follow a p53-independent pathway. In view of the unusually high levels of the tobacco-specific nitrosamines (TSNA) found in the type of snuff used in the Sudan, investigations of p53 mutations or oncogenes are needed.

Adolescent↗

Species differences in central oxytocin receptor gene expression: comparative analysis of promoter sequences.

The distribution of oxytocin binding sites in the brain is highly variable among mammals. Using two species of microtine rodents (voles) with strikingly different patterns of oxytocin binding sites in the brain, we demonstrate that these differences are due to differences in region specific gene expression and not post-translational processing. The distribution of oxytocin receptor mRNA closely resembles the distribution of oxytocin receptor binding sites in both species. Analysis of the 5' flanking region of the oxytocin receptor gene from both species reveals few differences in potential regulatory elements which could explain the differences in gene expression. These data suggest that species differences in oxytocin receptor binding are due to species differences in: i) distant DNA sequences further upstream or downstream which may influence expression; ii) the distribution of regulatory proteins such as transcription factors in the brain or iii) epigenetic factors, such as prenatal and perinatal environment which may affect gene expression in the adult.

Amino Acid Sequence↗

Treatment of relapsing-remittent multiple sclerosis with recombinant human interferon-alfa-2a: design of a randomised, placebo-controlled, double blind trial in Norway.

A multicentre, randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of 4.5 and 9.0 MIU recombinant human interferon alfa-2a (Roferon-A) given thrice weekly in patients with relapsing-remittent multiple sclerosis is described. The patients are treated for 6 months followed by a 6 months drug-free period. The primary objective is to determine new disease activity analysed by monthly MRI with gadodiamide (GdDTPA-BMA, Omniscan). The study is conducted at eight centers in Norway and is completed in January 1996.

Contrast Media↗

[Introduction and evaluation of HIV tests in the North-East part of Tanzania].

The MUTAN (Tanzanian Norwegian AIDS Project) virology programme has comprised research, intervention, surveillance and education as part of the Tanzanian National AIDS Control Programme. HIV testing of blood donors was introduced in 1988 in the regions Arusha and Kilimanjaro. Simple and rapid HIV-tests have been evaluated continuously, as well as the possible use of alternative specimen samples for testing. The polymerase chain reaction for detection of HIV proviral DNA was established at the Northern Zone Reference Hospital, The Kilimanjaro Christian Medical Centre in Moshi, in 1993.

AIDS Serodiagnosis↗

Spontaneous gingival antibody production to Fusobacterium nucleatum outer membrane in patients with adult periodontitis.

The local antibody response to Fusobacterium nucleatum outer membrane (FnOM) was analyzed in patients with adult periodontitis (AP) at the single cell level. Furthermore, we analyzed whether periodontal hygienic treatment could alter the antibody response. The number of IgG- and IgM-producing cells were investigated in gingival samples collected from 20 patients with AP. The patients were divided into 2 groups, before (BT, n = 9) and after (AT, n = 11) periodontal hygienic treatment. Four healthy gingival samples were used as controls. The results obtained showed that local antibody production against FnOM occurred in gingiva of patients with AP, but not in healthy gingiva. The IgG anti-FnOM was the predominant isotype observed. However, there was no statistically significant difference between the BT and AT groups. These results indicate that periodontal hygienic treatment was not sufficient to alter significantly the number of IgG- and IgM-secreting cells present in gingival tissue of AP patients, but it promoted a reduction of IgG anti-FnOM secreting cells. The presence of anti-FnOM antibodies in AP but not in control patients indicates that this bacteria may play a role in the pathogenesis of periodontal disease.

Antibodies, Bacterial↗

Expression of HLA class II antigens in marginal periodontitis of patients with Down's syndrome.

The expression of HLA Class II antigens on the surfaces of immunocompetent cells and the presence of CD1a+ cells (Langerhans cells) are important components of antigen presentation. Quantitative variations in HLA class II expression on antigen-presenting cells play a role in immune regulation. An indirect immunofluorescent technique was used on cryostat sections to reveal such differences qualitatively or quantitatively between chronic marginal periodontitis (CMP) in patients with Down's syndrome (DS) and in otherwise normal patients (NP). We found increased frequency of HLA Class II (HLA-expression on inflammatory cells and on keratinocytes of the oral gingival epithelium) in CMP of DS patients compared to sections from NP. The expression of HLA-DR was more frequent on the keratinocytes of the pocket epithelium in NP than in DS. There were significantly higher numbers of CD1a+ cells and ratios of HLA-DR+/CD1a+ cells and HLA-DP+/CD1a+ cells in the DS group compared to the NP group. Our conclusion is that there is a more pronounced inflammatory process in the gingival sites with CMP of DS patients compared to CMP in NP. The findings also indicate that there is a highly activated immune response in CMP of DS patients.

Adolescent↗

Analysis of T-cell receptor expressing lymphocytes infiltrating squamous cell carcinomas of the upper aerodigestive tract.

T-lymphocytes expressing T-cell receptors (TCRs) of the gamma/delta type have been suggested to play an important role in mucosal defense against infection and neoplastic transformation. In this study, an immunohistochemical investigation was performed on the distribution of alpha/beta and gamma/delta TCRs among tumor-infiltrating lymphocytes. Thirteen patients with squamous cell carcinomas of the upper aerodigestive tract were studied, using monoclonal antibodies and an avidin-biotin-peroxidase technique. Most of the T-cells had an alpha/beta TCR. Only 1.6% of the T-cells within the cancer tissue and 1.2% of the T-cells in the parenchyma adjacent to the cancer tissue expressed gamma/delta TCRs. These results are consistent with the results of similar studies in bronchial and breast carcinomas. Biopsies from normal oral mucosa in nine healthy individuals showed that 1.3% of the T-cells within the epithelium and 1.0% of those in the lamina propria adjacent to the epithelium expressed gamma/delta TCRs. Quantitatively the results do not support the theory that gamma/delta T-cells play an important role in the immunological response against cancer tissue in the mucosa of the upper aerodigestive tract. The functional role of these cells in the mucosa and in response to carcinomas is, however, still uncertain.

Adult↗

Comparative detection frequency of 6 putative periodontal pathogens in Sudanese and Norwegian adult periodontitis patients.

Twenty-five sudanese and 18 norwegian adult periodontitis patients were selected to participate in this study. The purpose was to compare cultivation results of Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, and Capnocytophaga species as well as various enteric rods in both populations. In addition, DNA probe analysis was used to identify P. gingivalis, P. intermedia, A. actinomycetemcomitans, F. nucleatum, and Bacteroides forsythus in the Sudanese patients and results were compared with those obtained by cultivation. The paper point technique was used to sample 99 sites in the Sudanese group (4 paper points/site) and 119 sites in the Norwegian patients (3 paper points/site). In the Sudanese subjects, the fourth paper point was used for the DNA probe analysis. The chi-square test and the Wilcoxon signed rank test were used to test for statistically significant differences between Sudanese and Norwegian cultivation results as well as between cultivation and DNA results in the Sudanese group. Cultivation results indicated that the Sudanese subjects had significantly lower prevalence of P. gingivalis, P. intermedia, and F. nucleatum (P < 0.01), significantly higher prevalence of Capnocytophaga species (P < 0.05), and similar prevalence of A. actinomycetemcomitans. Almost all Sudanese subjects tested positive for various enteric rods, while none of the Norwegians did so. The extent to which unrestricted use of antibiotics and transport media influenced the levels of enteric species is not known, however.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗