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Biomedical subjects

M Frisch

Publications and source records attributed to M Frisch.

At least 91 records · Page 5Linked to original sources
PubMed1996

Mycoplasma fermentans-derived lipid inhibits class II major histocompatibility complex expression without mediation by interleukin-6, interleukin-10, tumor necrosis factor, transforming growth factor-beta, type I interferon, prostaglandins or nitric oxide.

Mycoplasma cause several diseases in man and animals. Some strains can chronically infect humans, leading to fever or inflammatory syndromes such as arthritis, particularly in immunosuppressed patients. A set of pathogenicity factors shared by many mollicutes may be membrane components that activate macrophages to secrete cytokines and other inflammatory mediators. Mycoplasma-derived high molecular weight material (MDHM) is a macrophage-activating amphiphilic lipid which was purified from Mycoplasma fermentans. We studied the influence of MDHM on the expression of major histocompatibility complex (MHC) class II molecules by mouse resident peritoneal macrophages with an ELISA. Highly purified MDHM at 4 ng/ml and 0.8 microgram/ml crude heat-killed M. fermentans (concentrations chosen to give maximal responses) suppressed interferon (IFN)-gamma-dependent class II MHC induction when added simultaneously with IFN-gamma. MDHM was not toxic and did not result in loss of adherent cells. Kinetic data showed that MDHM first up-regulated, then down-regulated the expression of preformed class II MHC molecules, while expression of Mac-1 and F4/80 antigens remained constant. MDHM-dependent suppression of class II MHC molecule expression resulted in impaired antigen presentation to the helper T cell line D10.G4.1. We further attempted to identify hypothetical products of MDHM-stimulated macrophages as secondary mediators of class II MHC suppression such as were described for lipopolysaccharide (LPS)-stimulated macrophages. Type I IFN, prostaglandins and nitric oxide, all reported to cause down-regulation of class II MHC, could be excluded in this context. Of the cytokines tumor necrosis factor, interleukin (IL)-6, IL-10 and transforming growth factor-beta, only IL-10 inhibited class II MHC expression, although less effectively than MDHM. The involvement of IL-10 was ruled out, as no evidence for its MDHM-dependent formation could be found. Our data suggest that MDHM interferes with class II MHC expression by up-regulating its turnover, and at the same time, inhibits the formation of new class II MHC molecules.

Animals↗
PubMed1996

Rheumatoid arthritis and cancer risk.

The aim of this study was to examine the cancer pattern in a large group of patients with rheumatoid arthritis (RA). A follow-up study of cancer incidence in RA was conducted within a cohort of 20,699 patients recorded in the Danish Hospital Discharge Register during 1977-1987 by linkage with the Danish Cancer Registry through 1991. There were consistent excesses of non-Hodgkin's lymphoma and Hodgkin's disease in both sexes and during both early and late periods of follow-up. Risks for lung cancer and non-melanoma skin cancer were also increased, with no predilection for any specific histological subtype, while risks for colorectal cancer and female breast cancer were reduced. The cancer pattern seen among Danish RA patients largely supports findings from two earlier Nordic investigations. Thus, there seem to be consistent positive associations between RA and non-Hodgkin's lymphoma, Hodgkin's disease and lung cancer and a consistent negative association with colorectal cancer.

Adolescent↗
PubMed1996

Recent increase in the incidence of non-Hodgkin's lymphoma among young men and women in Denmark.

Time-related trends in the incidence of non-Hodgkin's lymphoma (NHL) in Denmark were analysed for the period 1943-89. A total of 13 822 patients (7565 men and 6257 women) were included in the study. In men, world-standardised incidence rates per 100 000 population increased from 2.5 in 1943-47 to 9.3 in 1988-89. In women, a similar increase was seen, i.e. from 1.9 in 1943-47 to 6.5 per 100 000 population in 1988-89. For all birth cohorts, the male-to-female incidence ratio was highest among young subjects and fell significantly after the age of 29 years. Trends in age-specific incidence were analysed separately for two periods, i.e. 1943-77 and 1978-89, reflecting an early, pre-AIDS period and a later period possibly influenced by AIDS. In both periods, the incidence of NHL increased in all age groups. However, in recent years a noticeable increase in incidence averaging 8% annually was observed in men and women aged 40-49 years. A number of factors including changes in the perception of NHL and in the diagnostic methods available are considered insufficient to explain the observed increase. The remarkable and parallel time trends observed in young men and women in recent years indicate that factors other than AIDS must be considered.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Epidemiology of Kaposi's sarcoma in the Nordic countries before the AIDS epidemic.

Based on data from the Nordic cancer registries, time-related trends in incidence of Kaposi's sarcoma (KS) were analysed in four ethnically similar populations before the AIDS epidemic. Data were available for different time periods in Denmark (1970-79), Sweden (1958-79), Finland (1953-79) and Norway (1953-79). KS was more common among men than among women aged 60 years or more, whereas no differences were observed for younger persons. The incidence of KS differed significantly between the four countries (P = 0.0001); Sweden having the highest and Denmark the lowest rates. Similarly, regional differences in incidence were observed within Sweden, rates being higher in the northern than in the southern areas (Ptrend = 0.002). Overall, in Nordic men the world standardised incidence rose from 0.5/1,000,000 person-years in the period 1953-57 to 1.8/1,000,000 person-years in 1978-79; in Nordic women, the corresponding rates were 0.2/1,000,000 person-years and 0.8/1,000,000 person-years respectively. The rate of increase was similar in Sweden, Finland and Norway (P = 0.14), whereas the short period of observation in Denmark precluded precise assessment of time-related incidence trends. These observations cannot be explained by registrational procedures or known risk factors for KS, and argue that environmental factors play an important role in the development of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1996

HPV-16-positive anal and penile carcinomas in a young man--anogenital 'field effect' in the immunosuppressed male?

This report presents the unusual occurrence of metachronous perianal and penile carcinomas in a young, immunosuppressed man. Both anogenital cancers were HPV-16-DNA-positive by the polymerase chain reaction. DNA in situ hybridization analysis of the penile carcinoma revealed HPV-16 in most neoplastic cells. HPV-16 appears to have played a central role in both anogenital cancers in this patient, suggesting that, like in immunologically susceptible women, a carcinogenic 'field effect' may exist in the anogenital area of the immunosuppressed male.

Adult↗
PubMed1995

Risk of lung cancer in pre- and post-menopausal women with ano-genital malignancies.

Women diagnosed during the period 1943-1990 and reported to the Danish Cancer Registry with invasive squamous-cell carcinomas of the uterine cervix, vulva, vagina or anus, together with those having pre-cancerous lesions (CIN III or carcinoma in situ) of the uterine cervix diagnosed in the period 1958-1990, were followed for the occurrence of subsequent lung cancer over 762,000 person-years. Overall, these patients developed 2 to 2 1/2 times more lung cancers than women in the general Danish population. Women in whom cervical cancer was diagnosed recently, and before the age of 45 years, had a 4.6 times elevated risk of developing lung cancer, while young women with vulvar or vaginal cancer were at a 4.0-fold elevated risk. Similarly, women in whom anal cancer was diagnosed before the age of 60 years were at a 3.5-fold increased risk of developing lung cancer. The present study supports the hypothesis that smoking is involved in the aetiology of ano-genital malignancies. The particularly high risk of developing subsequent lung cancers seen in women who were pre-menopausal (< 45 years) at the time of the ano-genital cancer diagnosis suggests that the effect of smoking in ano-genital carcinogenesis might be partly mediated through alterations in oestrogen metabolism. Alternatively, patients who developed their initial ano-genital cancer at a young age might harbour some genetic susceptibility which could explain their excess lung-cancer risk.

Adult↗
PubMed1995

Carcinoid tumors in Denmark 1978-1989 and the risk of subsequent cancers. A population-based study.

BACKGROUND: Previous studies have suggested an excess cancer risk in patients with carcinoid tumors. This association was reexamined using truly population-based data. METHODS: By means of data from the Danish Cancer Registry all carcinoid tumors diagnosed in Denmark between 1978 and 1989 were identified. All patients with primary carcinoid tumors were studied for the occurrence of subsequent cancers. The numbers of subsequent cancers observed in the follow-up period were compared with the expected numbers calculated from population rates. RESULTS: A total of 1029 patients with carcinoid tumors were identified (464 men and 565 women). The annual age-adjusted incidence rates (world standardized) for carcinoid tumors during 1978-1989 were stable at about 1.1 per 100,000 person-years for both men and women. The patients were followed for the occurrence of subsequent cancers over a period comprising 2512 person-years. Thirty subsequent cancers were identified in 29 patients. The overall relative risk of subsequent cancers was 1.1 (95% CI, 0.8-1.6). Subsequent cancers of the thyroid were in excess (RR, 21.4; 95% CI, 2.4-77.1; n = 2), as were tumors of the brain and nervous system (RR, 5.4; 95% CI, 1.1-15.9; n = 3) and non-Hodgkin's lymphomas (RR, 5.8; 95% CI, 1.2-16.9; n = 3). CONCLUSIONS: Overall, this population-based study does not support previous studies of an excess cancer risk in patients with carcinoid tumors. Increased risks of cancers of the thyroid, tumors of the brain and nervous system, and non-Hodgkin's lymphomas were observed, but these findings were based on few cases.

Aged↗
PubMed1995

Evidence of an association between non-Hodgkin's lymphoma and skin cancer.

OBJECTIVE: To investigate a possible link between exposure to ultraviolet light and the almost epidemic increase in non-Hodgkin's lymphoma worldwide. Because ultraviolet light is known to cause skin cancers, the association between non-Hodgkin's lymphoma and skin cancer was studied. DESIGN: Secondary occurrence of either malignant melanoma or squamous cell skin cancer in cohorts of patients with a first diagnosis of either non-Hodgkin's lymphoma or chronic lymphocytic leukaemia, and vice versa, were studied. Expected numbers of subsequent cancers were calculated by sex, age, and period specific national incidence rates multiplied by the person years under observation in the cohorts. SETTING: Denmark (1943-89) and Sweden (1958-89). SUBJECTS: Four population based cohorts identified in the nationwide cancer registries (34,641 people with non-Hodgkin's lymphoma, 17,400 with chronic lymphocytic leukaemia, 34,989 with malignant melanoma, 25,980 with squamous cell skin cancer). A total of 562,085 person years were accrued for the analysis. MAIN OUTCOME MEASURES: The ratios of observed to expected cancers (the standardised incidence ratio) served as a measure of the relative risk. RESULTS: The relative risk for developing squamous cell skin cancer was 5.5 (95% confidence interval 4.6 to 6.6) among patients with non-Hodgkin's lymphoma and 8.6 (7.2 to 10.3) among patients with chronic lymphocytic leukaemia. The relative risks remained high over more than 15 years of follow up. Relative risks for malignant melanoma were 2.4 (1.8 to 3.2) for patients with non-Hodgkin's lymphoma and 3.1 (2.1 to 4.4) for patients with chronic lymphocytic leukaemia. After squamous cell skin cancer had been diagnosed there was a twofold excess risk for non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. By contrast, in each of the cohorts the general cancer risks excluding skin and lymphoproliferative malignancies were close to the expected. CONCLUSIONS: The occurrence of non-Hodgkin's lymphoma and skin cancer are strongly associated; this supports the hypothesis that the secular increase in exposure to ultraviolet light may have contributed to the increasing incidence of non-Hodgkin's lymphoma in recent decades.

Age of Onset↗
PubMed1995

New primary cancers after squamous cell skin cancer.

In a search for clues to the origin of squamous cell skin cancer (SCC), the authors investigated the pattern of new cancers in a cohort of 5,100 SCC patients whose tumors were diagnosed during the years 1978-1989 and recorded in the Danish Cancer Registry. Subsequent cancer experiences in SCC patients were compared with the cancer incidence in the Danish population using ratios of observed cancers to expected cancers as a measure of the relative risk. Overall, patients with SCC were at increased risk of new malignancies (relative risk (RR) = 1.6, 95% confidence interval (CI) 1.5-1.7). Significantly elevated risks were found for cancers of the respiratory organs (RR = 1.7, 95% CI 1.4-2.0); cancers of the lip, buccal cavity, and pharynx (RR = 3.1, 95% CI 2.1-4.5); non-Hodgkin's lymphoma (RR = 2.3, 95% CI 1.4-3.5); leukemia (RR = 2.5, 95% CI 1.7-3.5); malignant melanoma (RR = 2.6, 95% CI 1.5-4.3); and cancer of the small intestine in men (RR = 4.1, 95% CI 1.1-10.6). The risk of new cancers (other than nonmelanoma skin cancers) was higher in patients diagnosed with SCC before the age of 60 years (RR = 1.9, 95% CI 1.5-2.5) than in those diagnosed with SCC at or after that age (RR = 1.3, 95% CI 1.2-1.4). The data confirmed previous strong associations between SCC and malignant melanoma and cancers of the major salivary glands. A previously undocumented significant excess of smoking-related cancers was observed after an SCC diagnosis, suggesting that smoking may be involved in the development of SCC. Since a variety of other squamous cell cancers have already been linked to smoking, the authors speculate that some general effect of smoking might act on all human squamous epithelia. The observed significant associations with lymphoma and leukemia and the high risk of subsequent malignancies in young SCC patients merit further attention.

Aged↗
PubMed1995

Cancer in patients with ulcerative colitis.

A cohort of 5,546 ulcerative colitis patients was identified from the Danish Hospital Discharge Register for 1977-1989. Patients not included in the cohort comprised those with proctitis, those treated in outpatient clinics and those for whom follow-up was less than 1 year. The cohort was linked to the Danish Cancer Registry in order to assess the risks for colorectal and other cancers. The linkage revealed a significant increase in the number of colorectal cancers over that in the general population (RR = 1.8; n = 42; 95% CI = 1.3-2.4) with consistent relative risks during early and late follow-up. The relative risk was considerably higher among younger (20-39 years: RR = 22; n = 8; 95% CI = 9.7-44) than older patients (> or = 60 years: RR = 1.3; n = 25; 95% CI = 0.8-1.9), but the risk difference between patients and the general population was approximately constant across all ages. In addition, we observed a significant increase in the relative risk of hepatobiliary cancers (RR = 2.3; n = 9; 95% = 1.0-4.3) and a slight but significant increase in the relative risk of non-melanoma skin cancer (RR = 1.4; n = 37; 95% CI = 1.0-1.9). In summary, our population-based study confirms the increased risk of colorectal cancer among patients with ulcerative colitis and provides new leads suggesting that hepatobiliary cancer and non-melanoma skin cancer should be considered as possible sites for future patient monitoring.

Adult↗
PubMed1994

Benign anal lesions and the risk of anal cancer.

BACKGROUND: Benign anal lesions are often considered to cause a predisposition to anal cancer. To reexamine this association, we linked national data on hospital discharge and cancer in Denmark. METHODS: After making certain exclusions, we used the Danish Central Hospital Discharge Register to identify 68,549 patients hospitalized with benign anal lesions between 1977 and 1989. Through computerized linkage to the Danish Cancer Registry, all incident cases of epidermoid anal cancer and colorectal cancer among these patients were identified. Follow-up for the occurrence of cancer started the month after the date of the first hospital discharge and continued until the patient died (10.6 percent of the sample), emigrated (0.7 percent), or was lost to follow-up (0.04 percent) or until December 31, 1989 (88.6 percent), whichever came first. RESULTS: The median follow-up period was 6.2 years. There were 23 epidermoid anal cancers and 416 colorectal cancers. The overall relative risk of anal cancer (observed vs. expected cases) was 4.4 (95 percent confidence interval, 2.8 to 6.6). The relative risk was 12.0 (95 percent confidence interval, 5.2 to 23.6) within the first year after hospitalization for benign lesions, 4.6 (95 percent confidence interval, 2.3 to 8.3) from one to four years after hospitalization, and 1.8 (95 percent confidence interval, 0.5 to 4.7) five or more years after hospitalization. The risk of colorectal cancer was significantly increased only during the first year after hospitalization (relative risk, 2.6; 95 percent confidence interval, 2.1 to 3.1). CONCLUSIONS: There is a strong temporal association between the diagnosis of benign anal lesions and the diagnosis of anal cancer. Although we could not exclude the possibility of a moderate increase in the long-term risk of anal cancer, our data do not support the view that benign anal lesions cause anal cancer.

Anus Diseases↗
PubMed1994

Malignancies that occur before and after anal cancer: clues to their etiology.

With the use of two different approaches to study multiple primaries in anal cancer patients, the authors sought clues to the etiology of anal cancer. Based on data from the Danish Cancer Registry for 1943-1989, previous cancers in 831 anal cancer patients were compared with cancers in 12,376 matched population controls, and subsequent cancers in 955 anal cancer patients were compared with expected numbers based on population rates. Overall, previous cancers were in excess among anal cancer patients (odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.3-2.1). Elevated risks were observed especially for the vulva/vagina (OR = 15.4, 95% CI 4.9-48.0), cervix (OR = 4.3, 95% CI 2.7-6.9), and lymphoma/leukemia (OR = 3.9, 95% CI 1.5-10.4). Subsequent cancers were also in excess (relative risk (RR) = 1.4, 95% CI 1.1-1.7), particularly for the lung (RR = 2.3, 95% CI 1.3-3.7), bladder (RR = 2.3, 95% CI 1.0-4.6), breast (RR = 2.0, 95% CI 1.2-3.3), vulva/vagina (RR = 12.3, 95% CI 4.0-28.7), and small intestine (two cases) (RR = 10.8, 95% CI 1.2-39.0). Colorectal cancers were reduced (RR = 0.3, 95% CI 0.1-0.9). The data support a multifactorial etiology for anal cancer, in which an infectious agent and smoking may be involved. The association with lymphatic/hematopoietic cancers may indicate a possible role for immunodeficiency in anal cancer development. Multiple cancers occurred predominantly in patients diagnosed with anal cancer at a young age (< 60 years), which raises the possibility of a genetic predisposition for some cases. The authors recommend that, in future hypothesis generating and hypothesis testing multiple cancer studies of rare malignancies, the combined study of cancer events both prior to and following an index cancer should be considered.

Age Factors↗
PubMed1994

Changing patterns of anal cancer incidence in the United States, 1940-1989.

Anal cancer has been hypothesized to be associated with a sexually transmitted agent and, more recently, with the epidemic of human immunodeficiency virus (HIV). The authors used a descriptive incidence study to evaluate these hypotheses based on US data from the Surveillance, Epidemiology, and End Results (SEER) program for 1973-1989 and from the Connecticut Tumor Registry for 1940-1988. Since 1960, anal cancer incidence in Connecticut increased 1.9-fold among men and 2.3-fold among women. Based on information from SEER, the incidence was lowest among white men (1973-1989 average: 0.41/100,000) and highest among black women (1973-1989 average: 0.74/100,000). Residents of the metropolitan areas had a twofold risk of anal cancer compared with populations in less densely populated areas. The most dramatic change in incidence was observed for white men in the San Francisco Bay area, among whom the incidence increased from 0.5/100,000 in 1973-1975 to 1.2/100,000 in 1988-1989 (p trend < 0.001). The relative risks (95% confidence intervals) of anal cancer among never married men compared with ever married men in the urban areas rose from 5.8 (0.9-8.7) in 1973-1978 to 6.7 (4.7-9.5) in 1979-1984 and 10.3 (7.5-14.1) in 1985-1989 (p trend = 0.02). No significant difference was observed among women. In conclusion, anal cancer incidence in the United States has increased significantly during the past 30 years and is now higher in women than men, in blacks than whites, and in residents of metropolitan rather than rural areas. Some of this changing pattern clearly relates to the period prior to the acquired immunodeficiency syndrome (AIDS) epidemic and argues that behavioral changes are important in anal cancer development. However, the recent remarkable change in rates among never married men and men living in the San Francisco Bay area suggests that homosexual men are at special and increasing risk. The authors speculate whether part of this recent increase could be attributed to the AIDS epidemic.

Adult↗
PubMed1994

Examination for intratubular germ cell neoplasia at operation for undescended testis in boys.

A total of 843 consecutive boys (median age 12.7 years) who had undergone testicular biopsy at operation for undescended testis was followed into adulthood (median age 25.2 years) to examine for testicular germ cell neoplasia. Five cases of testicular germ cell neoplasia were identified, including 1 nonseminoma of the contralateral testis, which had been treated before surgery for an undescended testis, 1 nonseminoma found at followup, 1 seminoma and 2 intratubular germ cell neoplasms. Of the later 3 patients 1 had a 45,X/46,XY karyotype and 2 had abnormal external genitalia. Previous testicular biopsy from the patient in whom nonseminoma was noted at followup showed Sertoli cells only. We recommend that testicular biopsy be performed at operation for undescended testis in boys with abnormal sex chromosomes, particularly 45,X/46,XY karyotype, and in those with abnormal external genitalia. The pattern of Sertoli cells only in biopsies from boys does not preclude the occurrence of testicular cancer in adulthood.

Biopsy↗
PubMed1994

Effects of beta-adrenergic antagonists on salivary secretory function in individuals of different ages.

The purpose of this study was to assess the effects of chronic beta-adrenergic antagonists on parotid and submandibular gland secretions in men and women of different ages. Unstimulated and stimulated saliva flow rates, total protein concentrations, and protein secretion rates were compared from medicated (various beta-antagonists, n = 25) and control (n = 60) subjects. Age-related decreases were found in unstimulated parotid saliva flow rate (p = .011) and protein secretion rate (p = .04), unstimulated submandibular salivary flow rate (p = .005) and protein secretion rate (p = .010), and in stimulated submandibular flow rate (p = .002) and protein secretion rate (p = .006). A drug-related effect was observed only in unstimulated parotid salivary flow (p = .033) and protein secretion rate (p = .04) from medicated subjects. Results from this study indicate that age and beta-adrenergic blockade alter salivary glandular function, but their effects differ with the type of salivary secretion examined.

Adrenergic beta-Antagonists↗
PubMed1994

Purification and partial biochemical characterization of a Mycoplasma fermentans-derived substance that activates macrophages to release nitric oxide, tumor necrosis factor, and interleukin-6.

Mycoplasmal products may exert a number of diverse in vitro effects on cells of the immune system. A macrophage-activating substance from Mycoplasma fermentans was described in this laboratory and named mycoplasma-derived high-molecular-weight material (MDHM). Using synthesis of nitric oxide by peritoneal cells from endotoxin low-responder mice as an assay system, MDHM was purified as follows. After freeze-thawing of M. fermentans, MDHM activity was sedimented with the membrane fraction. Membranes were delipidated with chloroform-methanol, and MDHM activity was extracted with octyl glucoside. Coextracted proteins were degraded by proteinase K. MDHM was further purified by reversed-phase high-pressure liquid chromatography and eluted in one major and one minor peak of activity. Neither carbohydrates nor amino acids were found as constituents. MDHM had the following properties: it partitioned into the phenol phase upon phenol-water extraction and into the Triton phase after extraction with Triton X-114. MDHM was not inactivated by either phospholipase A2 or triglyceride lipases. However, mild periodate treatment led to a > 95% loss of activity. Also, alkaline hydrolysis at 25 degrees C completely abolished MDHM activity with a half-life of 2 min. MDHM activity was spread out over a wide molecular weight range upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membranes, whereas after proteinase treatment MDHM activity migrated close to the front. These features of MDHM, taken together, speak in favor of an amphiphilic molecule with a lipid moiety carrying fatty acids in ester linkage and a polyol moiety of unknown character. MDHM was active in the nanogram-per-milliliter range, activating macrophages to release nitric oxide, interleukin-6, and tumor necrosis factor.

Animals↗