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Biomedical subjects

S Stenman

Publications and source records attributed to S Stenman.

At least 37 records · Page 2Linked to original sources

Enhancement of radiation effects by alpha interferon in the treatment of small cell carcinoma of the lung.

The effects on lung tissue and tumor of natural human alpha interferon (IFN) and radiotherapy were investigated in a multimodality treatment program for selected patients with small cell carcinoma of the lung (SCLC). Interferon was given first as a single agent, then concomitantly with radiotherapy to 12 previously untreated patients with limited disease. At disease progression outside the chest, interferon was discontinued and combination chemotherapy was initiated. In the first series, 7 patients received a high interferon induction dose (800 X 10(6) IU i.v. over 5 days) followed by low-dose maintenance therapy (6 X 10(6) IU i.m. TIW), median total dose 1380 X 10(6) IU (range 794-2074). At local progression, split-course radiotherapy, 55 Gy/20 F/7 wk, was added to interferon therapy. In the second series, 5 patients received low-dose interferon from the start (6 X 10(6) IU i.m. daily) combined with twice-a-day fractionated radiotherapy 44 Gy/40 F/4 wk. Median total dose of interferon in this series was 698 X 10(6) IU (range 354-828). Tumor response and normal tissue reactions were evaluated by monthly chest X rays, 3-monthly CT scans, restaging bronchoscopies and by serial respiratory function tests. Autopsy specimens from both lungs within and outside the radiation field were systematically evaluated when available. After the completion of radiotherapy, there were 4/7 CR in the high-dose IFN group compared to 3/5 CR in the low-dose IFN group. Rapid shrinkage of huge tumor masses was observed. At 2 months post radiotherapy radiological grade III fibrosis occurred in 4/7 patients in the high-dose and 1/5 patients in the low-dose group. Lung function studies showed a significant decrease in diffusing capacity and in lung volumes. Seven patients died within 12 months from start of interferon treatment, one of them from treatment complication. At autopsy the tumor area was in most cases replaced by severe fibrosis. Outside the radiation field lung fibrosis was mild. Our results suggest enhancement of radiation effect by interferon with a possible dose and/or schedule dependence of interferon and radiotherapy and call for more clinical studies of IFN and radiotherapy in combination.

Carcinoma, Small Cell↗

Radiation pneumonitis and fibrosis following split-course radiation therapy for lung cancer. A radiologic and physiologic study.

Radiographic signs of radiation pneumonitis and fibrosis were assessed and pulmonary function monitored in lung cancer patients after two different split-course radiation therapy schedules, one with a rest interval of 3 weeks and the other with a rest interval of 5 weeks, the total radiation dose being the same in both treatments (55 Gy/20 fractions/7 or 9 weeks). Post-mortem findings were analysed when available. Spirometric measurement of vital capacity, determination of diffusing capacity for carbon monoxide (DL) and alveolar volume with the single breath technique, and determination of regional distribution of lung perfusion by two different techniques, radiospirometry and gamma camera digital display following intravenous injection of 133Xe, were carried out before and at various times after the completion of irradiation. Of the physiologic parameters, only DL showed a significant decrease 6 as well as 9 months post-treatment (p less than 0.05). No difference between the two treatment schedules could be shown with regard to grade or time pattern of radiologic changes or decrease in DL. The findings suggest that measurement of DL may be of value in monitoring patients included in research protocols for radiation therapy of lung cancer as well as in selection of patients for this treatment.

Aged↗

Collagens, laminin, fibronectin, and cytoskeletal composition of cells in syngeneic aortal vein grafts in the rat.

The supradiaphragmatic vena cava of the rat was transplanted to the abdominal aorta in syngeneic recipients. The cells and the connective tissue matrix of these grafts were studied 3 days to 12 weeks after transplantation by immunofluorescence staining of the cytoskeletal proteins desmin, vimentin, and myosin. The matrix proteins, collagen Types I and III, laminin, fibronectin, and fibrin(ogen) were similarly demonstrated. Blood coagulation Factor VIII was used as a marker for endothelial cells. Inflammatory cells invaded the graft during Week 1, but later on the grafts were crowded with cells containing vimentin. Intimal thickenings developed already after 1 week. Smooth muscle cells containing desmin proliferated in these thickenings. After transplantation collagen Type I increased in the graft, but collagen Type III rather decreased. During the phase of intense proliferation of smooth muscle cells the media contained a rich matrix of diffusely distributed laminin. The laminin of older grafts was confined mostly to the subintimal zone and to the intimal plaques.

Animals↗

Relation between serum group II pepsinogen concentration and the degree of Brunner's gland hyperplasia in patients with chronic renal failure.

Serum concentrations of group I and II pepsinogens (PG I and PG II) were determined in 15 patients with chronic renal failure. Gastroduodenoscopy with biopsy and acid secretion tests were also performed. Five patients had histologically confirmed severe Brunner's gland hyperplasia manifesting as multiple polyps in the duodenal bulb. Five patients had a mild form of Brunner's gland hyperplasia which was evident only by histological analysis. Five had no signs of such alterations. The three groups of patients were comparable in age, sex, mean level of serum creatinine, mean duration of dialysis treatment, distribution of non-dialysed and dialysed patients, and gastric histology. In patients with severe Brunner's gland hyperplasia the mean serum PG II concentration was significantly higher than in the other patients. Both the serum PG I and the serum PG II concentrations decreased after receiving a well functioning renal transplant in the two patients who underwent transplantation.

Adult↗

Chronic gastritis and gastric acid secretion in uraemic and renal transplant patients.

Upper gastrointestinal endoscopy with biopsies from the antrum, body and duodenum, as well as tests for acid secretion were performed on 43 uraemic patients, 17 women and 26 men, (mean age 49.7 years) and on 46 patients with well-functioning renal transplant received 10 months earlier (12 women and 34 men, mean age 40.6 years) in order to study the background of peptic lesions in uraemic patients. Eighty-nine age- and sex-matched subjects selected from a random population sample consisting of 434 persons served as a control group. All groups of renal patients were similar with respect to the prevalence and severity of antral or body chronic gastritis. Compared with control subjects their antrum had significantly less advanced chronic gastritis, which was due to the lack of atrophic changes. Furthermore, the gastric body tended to show fewer alterations than that of the controls. The acid secretion capacity in the renal patients decreased with the increasing severity of atrophic changes in the body mucosa. However, definite hypoacidity was found in some of the renal patients with normal body mucosa. Thus, a true "state of hypoacidity" seems to occur in chronic uraemia.

Adult↗

Tuberculosis of the colon in a kidney transplant patient.

A 58-year-old woman experienced recurrent fever episodes after kidney transplantation. She was treated with antibiotics because of suspicion of staphylococcus infection. Abdominal pain combined with haemorrhagic diarrhoea occurred eight months after transplantation. A barium enema revealed a stenotic process in the middle part of the ascending colon mimicking carcinoma, and hemicolectomy was consequently performed. Histological examination revealed tuberculosis with little granuloma formation and abundant acid-fast tubercle bacilli in the mucosa and submucosa, and only slight perigranulomatous reactions. The patient was successfully treated with triple antituberculous chemotherapy without deterioration of allograft function. Tuberculosis should be suspected in immunosuppressed patients suffering from pyrexia of unknown origin, even when chest X-ray is normal.

Colonic Diseases↗

Multiple duodenal polyps in uraemia: a little known clinical entity.

Multiple duodenal polyps were found by endoscopy in five out of 33 patients with chronic renal failure and in one of 300 controls. In the uraemic cases the polyps were caused by circumscribed nodular hyperplasia of Brunner's glands. One of these five patients later underwent surgery for duodenal obstruction caused by the polyps; the other patients were asymptomatic. One of the controls had multiple duodenal polyps. The recorded incidence of multiple duodenal polyps was significantly higher among patients with chronic renal failure than in patients without renal disease. Patients with chronic renal failure and polyps did not differ significantly from the other renal patients in the comparison of variables such as gastric acid secretion, serum concentrations of gastrin and group I pepsinogens or mean length of dialysis treatment. The mean pH of gastric resting juice was significantly higher, however, in uraemic patients with polyps than in those without. Uraemic patients displayed a gastric acid secretion capacity within normal range, and significantly raised serum gastrin and group I pepsinogen concentrations.

Adolescent↗

Expression of a neural type of intermediate filament as a distinguishing feature between oat cell carcinoma and other lung cancers.

Expression of intermediate filaments was studied immunohistologically in oat-cell (6 cases), epidermoid (9 cases), adeno- (7 cases), large-cell anaplastic (3 cases), and bronchioalveolar carcinoma (3 cases), of lung. Affinity-purified antibodies against epithelial (anti-keratin), neural (anti-neurofilament), muscle (anti-desmin) and mesenchymal (anti-vimentin) intermediate filaments were used. In indirect immunofluorescence microscopy of oat-cell carcinomas a positive cytoplasmic fluorescence was seen only with antibodies against neural intermediate filaments, neurofilaments, while no staining of the tumor cells was observed with antibodies against other types of intermediate filaments. On the other hand, all the epidermoid, adeno, anaplastic, and bronchioalveolar carcinomas showed constantly a strong reaction with anti-keratin antibodies in a varying number of cells but no decoration with anti-neurofilament antibodies. The results show that expression of neural intermediate filaments is a major distinguishing feature between oat-cell carcinomas and other lung cancers and suggest that anti-neurofilament antibodies can be used as a diagnostic aid in the surgical pathologic study of pulmonary neoplasms.

Adenocarcinoma↗

Connective tissue changes and collagen metabolism in syngeneic vena caval grafts in rats.

An attempt was made to determine if changes occurring in connective tissue and collagen metabolism of vein-to-artery grafts arose from the trauma of transplantation as such or from the higher pulsatile pressure. Segments of the supradiaphragmatic inferior vena cava were therefore transplanted to the infrarenal vena cava in syngeneic pairs of rats. The sequential changes in hydroxyproline concentration, 3H-proline incorporation and the histologic appearance of collagen, elastic fibres and fibronectin were noted. Comparisons were made with previously reported changes in syngeneic venoartery grafts in rats. The initial changes, probably resulting from the transplantation trauma, were similar in the veno-vein and veno-artery grafts. Subsequent changes, however, were less pronounced in veno-vein than in veno-artery grafts. The study thus suggests that these changes in vein-to-artery grafts are due partly to the transplantation trauma, but mainly to the increased pressure in the new environment.

Animals↗

Expression of fibronectin matrix in cybrids of fibroblasts and epithelial cells.

The pericellular fibronectin matrix of human fibroblasts is lost when they are fused with normal or malignant cells, which do not produce fibronectin matrix. In the present study we have investigated whether also the cytoplasmic fraction of fibronectin-negative HeLa or MDCK cells can cause this effect. Enucleated epithelial cells (cytoplasts) were therefore fused with norman human fibroblasts. Fibronectin expression of the resulting cytoplasmic hybrids (cybrids) was studied by the indirect immunofluorescence technique. Three hours after fusion cybrids formed between fibroblasts and enucleated epithelial cells showed fibronectin matrix expression clearly weaker than that seen on the intact fibroblasts. An accumulation of fibronectin matrix was observed in the cybrids, analogously to the intact fibroblasts, and already 12-24 h after fusion the cybrids showed a fibronectin matrix expression similar to that of the fibroblasts. No fibronectin matrix was detected in the epithelial cells or their cytoplast. Our results indicate that cytoplasmic factors from epithelial cells are able to cause an initial suppression in the formation of fibronectin matrix. However, the cytoplasts are not capable of causing a long-term effect on the fibroblasts.

Animals↗

Expression and distribution of vimentin and keratin filaments in heterokaryons of human fibroblasts and amnion epithelial cells.

The expression of intermediate filaments of the keratin- and the vimentin-type was studied in heterokaryons of human fibroblasts and amnion epithelial cells by immunofluorescence microscopy. Fibroblasts and their homokaryons showed a fibrillar, vimentin-specific fluorescence throughout the cytoplasm but were negative when stained for keratin. Amnion epithelial cells and their homokaryons, on the other hand, showed a keratin-specific fibrillar staining, and only some of them contained also detectable vimentin. When suspended epithelial cells were fused with adherent fibroblasts, keratin fibrils spread within 3 h into the fibroblasts, intermixing with the vimentin fibrils. 1-3 d after fusion, both vimentin and keratin filaments were expressed as typical fibrillar cytoplasmic arrays, and the distribution of keratin in heterokaryons resembled closely that of vimentin. A typical cell-to-cell arrangement of keratin fibrils, seen in cultures of amnion epithelial cells, could also be found between heterokaryons. Treatment of the cultures with vinblastine sulphate induced coiling of the vimentin filaments in both homo- and heterokaryons, whereas the keratin organization was only slightly affected. Our results show that both vimentin and keratin filaments are incorporated into the cytoskeleton of heterokaryons formed between fibroblasts and epithelial cells, and that they behave in the same way as in their parental cells. Both epithelial and fibroblastic characteristics thus appear to the coexpressed in such heterokaryons.

Cell Fusion↗

Immunohistological studies on valvular vegetations in nonbacterial thrombotic endocarditis (NBTE).

Thrombi and thrombus formation in nonbacterial thrombotic endocarditis (NBTE) were studied using light microscopy and immunohistology. Samples from vegetations on cardiac valves were taken at autopsy from five patients with NBTE and adenocarcinoma as an underlying disease. Morphological studies disclosed proliferative changes underneath the thrombi. In immunofluorescence microscopy, focal deposits of immunoglobulins and complement components Clq and C3 were found. The results suggest that immune complexes, elicited by the underlying malignant process, may play important role in the pathogenesis of the thrombus formation in NBTE.

Adenocarcinoma↗

Fibronectin in human solid tumors.

Fibronectin in human solid tumors was studied by indirect immunofluorescence staining of biopsy material. Altogether 73 tumors were examined, comprising 12 sarcomas, 3 melanomas 1 reticulum cell sarcoma, 39 carcinomas, 6 benign soft-tissue tumors and 12 benign epithelial tumors. In all sarcomas the individual tumor cells were surrounded by a network of fibronectin which was continuous with the stroma. The distribution of fibronectin was similar in the benign soft-tissue tumors. In contrast, no fibronectin was detected in the individual carcinoma cells or in their periphery. However, the reactive connective tissue stroma of carcinomas was strongly connective tissue stroma of carcinomas was strongly positive for fibronectin. This was true also for the stroma of benign epithelial tumors. These results show that, contrary to the situation in cell culture, in vivo sarcoma cells and benign soft-tissue tumor cells contain fibronectin in their pericellular matrix. On the other hand, fibronectin can be used to distinguish carcinomas from sarcomas in vivo.

Carcinoma↗