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Biomedical subjects

S Olling

Publications and source records attributed to S Olling.

At least 19 recordsLinked to original sources

Reactivity of monoclonal antibodies with ganglioside antigens in human small cell lung cancer tissues.

Gangliosides on tumor cells have been suggested as potential target antigens for specific immunotherapy in various types of cancer including small cell lung cancer (SCLC). In this study we have compared the expression of three gangliosides that have been described as tumor-associated antigens, FucGM1, GM2 and GD3 in SCLC tissue specimens collected at autopsy, using a double-layer immunofluorescence staining method and specific monoclonal antibodies (Mabs) directed against these ganliosides. We found expression of FucGM1, GD3 and GM2 in (70% (n=20), 60% (n=15) and 40% (n75% of the tumor cells in all lesions from the same patient (five of eight cases). Our results indicate that FucGM1 is a relevant ganglioside antigen in SCLC, and suggest that specific immunotherapy involving more than one ganglioside antigen in SCLC should at least include FucGM1 and GD3.

Antibodies, Monoclonal↗

Ifosfamide in malignant mesothelioma: a phase II study.

Malignant mesothelioma is a rare malignancy with a median survival, ranging from 4 to 18 months in untreated patients. In a phase II study of patients with mesothelioma, the efficacy and toxicity of ifosfamide and mesna was evaluated. Twenty-nine previously untreated patients, with histologically proven and unresectable mesothelioma, entered the study. Three patients were later excluded from the study due to revision of the diagnoses. The patients had to have bidimensionally measurable disease by CT scans and a WHO performance status < or = 3. Eligible patients received ifosfamide 3000 mg/m2 per day for 3 days as a 1-h infusion and mesna 1800 mg/m2 per day for 3 days every third week. Dose modifications were made according to the degree of hematologic, neurologic and renal toxicity. Response to treatment was evaluated in accordance with WHO criteria. The median age of patients was 59 years (range 39-68), 18 patients (69%) had a history of asbestos exposure and the median of treatment cycles was four (range 1-10). No complete responses were observed. One patient obtained a partial response after five cycles with a duration of response of 25 months. Nine patients (35%) had stable disease, while 13 (54%) progressed. The median survival for all patients was 10 months. The toxicity of the treatment was considerable. Thirteen patients (50%) had grade 4 leucopenia, ten patients (38%) had grade 3 or 4 reversible neurotoxicity and ten patients (38%) had grade 3 or 4 nausea and vomiting. Eleven patients (42%) went off the study due to the toxicity of the treatment. In conclusion, ifosfamide did not show any substantial activity of relevance in malignant mesothelioma at the dose level investigated, in spite of considerable toxicity.

Adult↗

Lack of interferon-gamma receptor does not influence the outcome of infection in murine schistosomiasis mansoni.

Studies of vaccine-induced immunity in experimental schistosomiasis in mice have suggested that interferon-gamma (IFN-gamma) is an important factor for the induction of protective immunity against schistosomiasis. The present study compares some parameters during primary schistosome infection in IFN-gamma receptor deficient mice and wild type mice. No significant difference in worm burden between the two groups was found. Almost the same number of eggs in the liver as well as typical granulomas with numerous macrophages and eosinophils were observed in both groups of mice. Furthermore, IFN-gamma receptor deficient mice infected with S. mansoni displayed a significant reduction in the number of IgG2a secreting cells in the spleen and a significant enhancement of IgA secreting cells in the spleen and in the lungs. These findings suggest that the lack of IFN-gamma activity may result in an enhanced dominance of Th2 cells which, however, does not influence the development of a primary schistosome infection.

Animals↗

Lung cancer in West Sweden 1976-1985. A study of trends and survival with special reference to surgical treatment.

We reviewed 3 285 consecutive cases of lung cancer diagnosed in West Sweden during the period 1976-1985. Data were collected from the regional cancer registry, the Swedish National Population Registry, and medical records. During the study period, the annual female/male ratio increased from 0.29 to 0.42. In females, there was an increase primarily in the incidence of tobacco-related morphologic tumour types (i.e. squamous and small cell lung cancers). In males, a moderate increase of adenocarcinomas was seen, although squamous cell cancer remained the most common tumour type. The overall 5-year survival rate was 8.3%. In 641 patients (20%) a surgical tumour resection was carried out. The 5-year survival rate following resection was 38%, and the probability of 10-year survival was estimated at 25%. In a multifactorial model including gender, age, histology, pTNM stage and extent of resection, pTNM stage and, to a lesser degree, age were statistically significant independent predictors of postoperative survival. The five-year survival was 57% in stage 1, 21-27% in stage II and IIIa, and 10% in stage IIIb. Of all resected patients, 4.2% died within two months after resection. In males, early postoperative mortality was predicted by preoperative bicycle ergometry. The prognosis in non-resected patients was poor, with only 2% surviving 5 years or longer. In conclusion, the results indicate that some progress has been made with regard to surgical management of lung cancer, but they also point to the fact that the vast majority of patients are not amenable to curative treatments, and that the overall survival in lung cancer has improved only marginally during the last decades.

Age Distribution↗

L3p40-50--a new lung-tumor-associated 40- to 50-kDa antigen defined by a monoclonal antibody (L3).

A monoclonal antibody (MAb), designated L3, was raised against a human-lung-adenocarcinoma-derived cell line, A549. Immunohistological studies showed reactivity of MAb L3 with 70 to 90% of lung tumors representing the 4 major histotypes. Strongest reactivity was seen with squamous-cell cancer and adenocarcinoma, with strong intracellular staining of the tumor cells. In small-cell lung cancer, staining was seen in a minority of tumor cells. Normal tissue staining was seen with thyroid follicular cells and focally with epithelial cells of the bronchi, the colon and the small intestine. Normal liver parenchyma was negative, whereas hepatocytes surrounding metastatic lesions were strongly stained. This pattern of staining was also seen for connective tissue. Western-blot analysis showed that the antigen defined by MAb L3 has an apparent molecular weight of 40 to 50 kDa, and hence is denominated L3p40-50. Our results suggest that L3p40-50 represents an undescribed tumor antigen.

Adenocarcinoma↗

Quantitative importance of asbestos as a cause of lung cancer in a Swedish industrial city: a case-referent study.

We wanted to assess the quantitative importance of asbestos as a cause of lung cancer. In a case-referent study, the exposure to asbestos, tobacco smoke and some other occupational exposures were compared between 147 cases of lung cancer (100 men, 47 women), 111 hospital referents, and 109 population referents, all below the age of 75 yrs and living in an industrial city. The attributable risk of lung cancer due to asbestos exposure was 16% in men (95% confidence interval 1-31%). No woman had occupational exposure to asbestos. We conclude that in the mid 1980's tobacco smoking was the major attributable risk, being 95% for men and 78% for women, but that in men asbestos was an appreciable contributing factor in the general population of a Swedish industrial city.

Adult↗

Coexpression of ganglioside antigen Fuc-GM1, neural-cell adhesion molecule, carcinoembryonic antigen, and carbohydrate tumor-associated antigen CA 50 in lung cancer.

With the aid of specific monoclonal antibodies, tumor tissues from 68 patients with lung cancer were examined for their expression of two small cell lung carcinoma (SCLC) antigens, Fuc-GM1 (fucosyl GM1; IV2FucII3NeuAc GgOse4) and neural-cell adhesion molecule (NCAM), and two broader tumor antigens, carcinoembryonic antigen (CEA) and carbohydrate cancer-associated antigen CA 50. Expression of Fuc-GM1 was seen in 75% and NCAM in 78% of the SCLC specimens, but also in 12 and 20% of non-SCLC. Either or both of these antigens were expressed in more than 90% of SCLC and in 25% of non-SCLC. CEA was found in more than 80% of SCLC and non-SCLC. Expression of CA 50 was seen in 65-68% of non-SCLC and SCLC, showing preference for SCLC and lung adenocarcinoma. In SCLC, cellular expression of Fuc-GM1 was generally seen together with NCAM and CA 50, but rarely with CEA. There was considerable inter- and intratumor heterogeneity in the expression of all four antigens. The results suggest that CEA is the antigen of choice for the detection of lung cancer regardless of histotype. In combined analysis of CEA, CA 50, Fuc-GM1 and NCAM, two patterns of antigen expression were recognized that appear to discriminate between SCLC and non-SCLC tumors, respectively. A considerable fraction of SCLC and non-SCLC tumors, however, exhibited similar patterns of antigen expression. The biological and clinical significance of these observations remains to be investigated.

Antibodies, Monoclonal↗

Immunohistochemical detection of two small cell lung carcinoma-associated antigens defined by MAbs F12 and 123C3 in bronchoscopy biopsy tissues.

We have studied MAbs* for their ability to detect SCLC and differentiate this tumor type from the other lung tumor histotypes in cryostat sections of biopsy specimens taken at bronchoscopy from patients with suspected primary lung tumor disease. MAb F12, specific for the ganglioside fucosyl-GM1, reacted with 58% of the cases with SCLC (n = 19) and with less than 3% of those with non-SCLC (n = 38). MAb 123C3, specifically reactive with NCAM, reacted with 78% of the SCLC cases (n = 23). With this MAb no positive staining was seen in the non-SCLC cases (n = 41). None of the two MAbs reacted with tissue sections without tumor. In combined analysis with MAbs F12 and 123C3, all SCLC cases (n = 15) were positive with either and 47% with both of the MAbs. Our results show that both MAbs F12 and 123C3 are highly specific for SCLC in bronchoscopic biopsy tissue specimens, whereas the sensitivity for this histotype tends to be higher with MAb 123C3 than with F12 (P = 0.14). When used in combination, all SCLC cases could be identified. These MAbs may therefore be valuable as complements to current histopathologic characterization and differentiation of lung cancer.

Adenocarcinoma, Bronchiolo-Alveolar↗

Amebic colitis presenting as acute inflammatory bowel disease. Case report.

A 41-year-old woman who had lived in the tropics for 23 years developed a clinical picture of inflammatory bowel disease 4 years after resettlement in Sweden. Search for ova and trophozoites in stools was negative. As medical treatment was unsuccessful, total colectomy was considered. Repeated colonic endoscopy with multiple biopsies initially failed to show amebiasis, but subsequently the trophozoites were identified in biopsies from the rectosigmoid mucosa. The diagnosis was serologically confirmed. Metronidazole treatment was rapidly and lastingly effective.

Acute Disease↗

99mTechnetium dimercaptosuccinic acid scintigraphy in the diagnosis of acute pyelonephritis in rats.

The use of 99mtechnetium dimercaptosuccinic acid (99mTc-DMSA) scintigraphy for the early diagnosis of pyelonephritis has been evaluated in a study performed on adolescent female Sprague-Dawley rats exposed to an ascending Escherichia coli infection. The rats were studied with DMSA scintigraphy either before and 5 days after the infection or 5 and 28 days after the infection. One group of rats received anti-microbial treatment during days 6-11. After the last DMSA scintigraphy the rats were sacrificed and the kidneys prepared for light microscopy study. Kidney morphology was normal and DMSA uptake was high and homogeneous in all control rats. The majority of the rats exposed to E. coli developed inflammatory changes, on light microscopy which extended to various degrees in the renal parenchyma. Five days after the infection the DMSA uptake was consistently reduced, if the inflammatory lesion on light microscopy involved more than 15% of the renal cortex. Twenty-eight days after infection the inflammatory changes were less extensive than at 5 days. The DMSA uptake had usually improved. At this time, however, areas of decreased DMSA uptake could be detected even if the light microscopy changes involved less than 15% of the parenchyma. Microscopical lesions were less frequent and less extensive in the treated than in the untreated rats. The complete return to normal of previously abnormal DMSA uptake was only observed in treated rats. In a few untreated rats cortical scars had formed by day 28. The scars appeared in areas with decreased DMSA uptake at 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Ear discharge after insertion of transmyringeal tubes.

The peroperative bacteriology and cytology of the middle ear have been studied in 103 ears in 65 children operated on due to longstanding secretory otitis media. Within one month postoperatively, 12 ears (12%) showed signs of infection with discharge from the tube. Ten out of these 12 ears showed peroperative growth of Hemophilus influenzae, Branhamella catarrhalis, pneumococci or staphylococci in the middle ear effusions, a significant difference compared to ears without postoperative discharge. The peroperative cytological evaluation of the middle ear effusions from 10 out of the 12 patients with postoperative ear discharge showed presence of phagocytes as a sign of infection. It is concluded that pre-existing bacteria in the middle ear effusion of patients with longstanding secretory otitis media might increase the risk of postoperative infection within the first month after insertion of transmyringeal tubes.

Bacteria↗

Follicular cystitis in girls with untreated asymptomatic or covert bacteriuria.

Nodular changes of the bladder mucosa, that is cystitis follicularis or cystitis cystica, are found in 2 to 9% of all children with urinary tract infections. The nodules are composed of lymphoid aggregates, resembling Peyer's patches in the intestine. Children with this finding are considered to have a poor short-term prognosis with a marked tendency for recurrent infections. Screening programs for bacteriuria have revealed that a few per cent of the female population are bacteriuric without symptoms of overt disease. Of 59 girls followed with untreated asymptomatic bacteriuria 52 had nodular changes of the bladder mucosa at cystoscopy. Biopsy was performed in 22 girls, and revealed lymphocytic infiltration in 19 and follicular formation in 11. The nodular changes persisted when bacteriuria continued but disappeared in patients who became abacteriuric. This finding demonstrates the reversibility of the changes, and supports the assumption that they are secondary to the presence of bacteria and not a primary lesion.

Bacteriuria↗

Cytological and bacteriological aspects of secretory otitis media.

Bacteriological and cytological examinations were performed on 105 middle ear secretions from 66 children with middle ear effusion (MEE) of more than 3 months' duration. The secretions were searched for granulocytes and the activity of these cells was judged by their capacity for random locomotion and their ability to reduce nitroblue tetrazolium. The functional characteristics of the granulocytes were compared with the bacteriological findings on cultures from MEE. Bacteria commonly regarded as pathogens in middle ear infections (Hemophilus influenzae, Branhamella catarrhalis or Streptococcus pneumoniae) were found in 25% of the secretions. Granulocytes with activity or lacking activity, virtually dead, were found in all secretions where these bacteria were isolated. In secretions where bacteria commonly regarded as commensals, mainly staphylococci, were isolated, about two thirds of the secretions showed phagocytes with or without activity. No relation between bacterial growth and the functional state of the granulocytes was observed. In contrast, no phagocytes were found in over 60% of MEE lacking bacterial growth. These findings suggest a role for bacteria in the development and maintenance of secretory otitis media.

Child↗

Immunohistological detection of fucosyl-GM1 ganglioside in human lung cancer and normal tissues with monoclonal antibodies.

With the aid of a highly specific murine monoclonal antibody, F12, an immunofluorescence method was elaborated that allowed sensitive and specific detection of the ganglioside antigen fucosyl-GM1 (IV2FucII3NeuAcGgOse4Cer) in different types of human lung cancer and normal tissues. Nineteen of 21 cases of small cell lung cancer were positive with the F12 immunofluorescence method as compared to 2 of 10 squamous epithelial cell lung cancers and 1 of 5 large cell lung cancer specimens. Specimens of lung adenocarcinoma (8 cases) and bronchial carcinoid (3 cases) were all negative, as were 2 examined cases of neuroblastoma. No fucosyl-GM1 could be detected in normal lung and bronchus. However, in thymus, spleen, and lamina propria of the small intestine sparsely distributed clusters of small round cells were stained as well as intramural ganglionic cells of the small intestine and islet cells of the pancreas. All other normal tissues tested were negative. Results obtained with immunofluorescence closely agreed with immunochemical determination of fucosyl-GM1 in lipid extracts of tissues. Our findings suggest that fucosyl-GM1 is strongly associated with small cell cancer of the lung and demonstrate that this tumor-associated antigen can be detected with high sensitivity and specificity with an immunofluorescence method based on the use of the F12 monoclonal antibody.

Animals↗

Ascending pyelonephritis in young rats retards kidney growth.

Several radiological studies have suggested that pyelonephritis in infancy and childhood may result in kidney growth retardation without renal scarring. In the present study, we induced ascending pyelonephritis in 20-day-old rats with intravesical infusion of E. coli. Four days after infusion, E. coli was cultured from all renal cortex. The rats were either left untreated (PNu) or were treated with trimethoprim-sulfa (PNt). The rats were investigated one month after infection and compared with an age-matched control group (C). Seventy-nine percent of the PNu rats had recovered spontaneously from infection. Body weight was the same in all groups. In PNu rats, kidney weight (KW), kidney area (KA) and glomerular filtration rate (GFR) were significantly decreased. KW, KA and GFR were similar in PNt and C rats. The numbers of filtering nephrons were not reduced by the infection. The total cortical DNA content (index of cell number) was significantly lower in PNu (5.30 +/- 0.32 mg) and PNt (6.62 +/- 0.44 mg) than in C rats (8.48 +/- 0.49 mg). The cortical DNA content was significantly lower in PNu than in PNt rats. The cortical protein/DNA ratio was significantly higher in PNu rats than in C rats. The protein/DNA ratio was similar in PNt and PNu rats. The increase in protein/DNA ratio was interpreted as a sign of cell hypertrophy. The inflammatory process as such did not increase the protein/DNA ratio. The kidneys were also examined for structural lesions. Signs of scarring, inflammation and cell necrosis were almost absent in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

A case of carcinoma in intralobar pulmonary sequestration.

A case of intralobar pulmonary sequestration with the unusual origin of an abnormal artery from the ascending aorta and with cancer localised in the sequestrated lung tissue is presented. The preoperative investigation failed to diagnose the cancer.

Adenocarcinoma↗