Karl-Ove Söderström

RNA synthesis in different stages of rat seminiferous epithelial cycle.

In vitro RNA synthesis has been analyzed using autoradiographic and electrophoretic methods in isolated 1-2 mm segments of rat seminiferous tubules. The cellular composition of each segment was accurately identified using microscopic analysis of the transillumination pattern of the freshly isolated, unstained, seminiferous tubules combined with phase-contrast microscopy of the living spermatogenic cells. The RNA synthesized in the seminiferous tubules was found to be mostly heterogenous nuclear RNA (HnRNA), which appeared to have a long lifetime. It was most actively formed in the stages which contain mid-pachytene spermatocytes. Formation of rRNA was slow in all stages and it was first observed when a 2-h pulse with [3H]uridine was followed by a 6-h chase. A very low RNA synthetic rate was observed in the stage containing the meiotic reduction divisions. The function of the meiotic RNA in regulation of spermiogenesis is discussed.

Detection of Residual Tumours in Postchemotherapy Testicular Cancer by FDG-PET

The aim of this study was to investigate whether 2-(F-18)-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) could reliably detect testicular cancer in patients following chemotherapy. Twenty FDG-PET studies were performed on 15 patients with metastatic seminoma or non-seminoma. Tracer uptake in the PET study was measured by calculating the standardised uptake value (SUV) for the tracer. Nine lesions out of 20 were judged to be positive based on high FDG uptake. Three proved to represent inflammatory changes in non-cancerous tissue. Eleven PET studies were negative. In one of these, viable tumour was found at retroperitoneal lymphadenectomy. The median SUV values of metastatic tumours and benign residual tumours were 2.7 (range 1.6-9.5, n = 10) and 1.7 (range 0.7-5.5, n = 15), respectively. The large overlap of SUVs between these groups was due to the relatively high FDG uptake in inflammatory tissue (median 4.2, range 2.0-5.5, n = 4). The results indicate that FDG imaging of metastatic testicular cancer after chemotherapy has limited value because of a potentially high accumulation of FDG in inflammatory tissues.

Transport of material between the nucleus, the chromatoid body and the golgi complex in the early spermatids of the rat

SummaryThe movement and transport of material between intranuclear dense particles, the chromatoid body and the Golgi complex have been studied in early spermatids of the rat. The analyses involved observation of living accurately identified cells, time-lapse cinemicrography and electron microscopy.The chromatoid body establishes transient contacts with intranuclear material during early spermiogenesis. The chromatoid body also makes contacts with the Golgi complex. It is suggested that the chromatoid body receives material from the nucleus during the postmeiotic period and participates in the early formation of the acrosomic system.

MMP-1 expression has an independent prognostic value in breast cancer

AbstractBackgroundBreast cancer consists of a variety of tumours, which differ by their morphological features, molecular characteristics and outcome. Well-known prognostic factors, e.g. tumour grade and size, Ki-67, hormone receptor status, HER2 expression, lymph node status and patient age have been traditionally related to prognosis. Although the conventional prognostic markers are reliable in general, better markers to predict the outcome of an individual tumour are needed.Matrix metalloproteinase-1 (MMP-1) expression has been reported to inversely correlate with survival in advanced cancers. In breast cancer MMP-1 is often upregulated, especially in basal-type breast tumours. The purpose of this retrospective study was to analyse MMP-1 expression in breast cancer cells and in cancer associated stromal cells and to correlate the results with traditional prognostic factors including p53 and bcl-2, as well as to patient survival in breast cancer subtypes.MethodsImmunohistochemical analysis of MMP-1, ER, PR, Ki-67, HER2, bcl-2, p53 and CK5/6 expression was performed on 125 breast cancers. Statistical analyses were carried out using Kruskal-Wallis and Mann-Whitney -tests. In pairwise comparison Bonferroni-adjustment was applied. Correlations were calculated using Spearman rank-order correlation coefficients. Kaplan-Meier survival analyses were carried out to compare breast cancer-specific survival curves. Factors significantly associated with disease-specific survival in univariate models were included in multivariate stepwise.ResultsPositive correlations were found between tumour grade and MMP-1 expression in tumour cells and in stromal cells. P53 positivity significantly correlated with MMP-1 expression in tumour cells, whereas HER2 expression correlated with MMP-1 both in tumour cells and stromal cells. MMP-1 expression in stromal cells showed a significant association with luminal A and luminal B, HER2 overexpressing and triple-negative breast cancer subtypes.ConclusionsThe most important finding of this study was the independent prognostic value of MMP-1 as well as Ki-67 and bcl-2 expression in tumour cells. Our study showed also that both tumoural and stromal MMP-1 expression is associated with breast tumour progression and poor prognosis. A significant difference of MMP-1 expression by cancer associated stromal cells in luminal A, luminal B and triple-negative breast cancer classes was also demonstrated. Please see related commentary articlehttp://www.biomedcentral.com/1741-7015/9/95

Nuclear DNA content and its prognostic value in lymphoma of the stomach

Nuclear DNA content of 27 primary lymphomas of the stomach was determined by flow cytometry from paraffin‐embedded tissue. Thirteen (50%) of the 26 non‐Hodgkins lymphomas were aneuploid. The only case with Hodgkins disease was diploid. The mean age of patients with aneuploid lymphoma was less than that of patients with diploid lymphoma (53 years versus 63 years, P = 0.02). DNA aneuploidy was more common in tumors with extragastric spread into the adjacent organs or the upper abdominal lymph nodes than in intragastric lymphomas (73% versus 17%; P = 0.003). Patients with aneuploid lymphoma had both inferior crude recurrence‐free survival rate (P = 0.05) and survival rate corrected for known intercurrent diseases (P = 0.02) than patients with diploid lymphoma. Extragastric spread of lymphoma into the adjacent organs or the upper abdominal lymph nodes was, however, the most important prognostic factor by a multivariate analysis.

Effect of actinomycin D on the structure of the chromatoid body in the rat spermatids.

SummaryThe effect of actinomycin D on the chromatoid body of rat spermatids has been studied by light and electron microscopy, high resolution autoradiography and biochemical methods.Actinomycin D caused structural changes in the chromatoid body of young round nucleated spermatids. The normal irregularily lobulated chromatoid body acquired a ring-like configuration 12 h after an intratesticular injection of 2 μg of the drug. The labelling of the chromatoid body with 3H-uridine which can normally be seen after 12 h was also abolished by actinomycin D.These observations lead to the suggestion that the chromatoid body contains a store of long-lived mRNA molecules that are activated later during spermiogenesis when transcription in the spermatid nucleus has ceased but a high level of protein synthesis still persists.

Characterization of RNA synthesis in mid-pachytene spermatocytes of the rat

Abstract In this paper the RNA synthesis in mid-pachytene spermatocytes of the rat has been studied. The results show that RNA synthesized by these cells is mostly high molecular weight RNA comparable to HnRNA of somatic cells. In comparison with the rapid metabolism of HnRNA in somatic cells, HnRNA in pachytene spermatocytes is stable and remains in the nucleus for a considerable time. About 30% of this HnRNA contains a poly(A) sequence, although no difference in the rate of metabolism between poly(A)+ and poly(A)− RNA was observed. Based on these results it is suggested that at least a part of the RNA which is synthesized by pachytene spermatocytes is stored in the cells and utilized later during spermatogenesis when the RNA synthesis of the spermatids ceases, but protein synthesis is still active for about 2 weeks.

Use of carbon-11 methionine positron emission tomography to assess malignancy grade and predict survival in patients with lymphomas

Abstract. The aim of this study was to investigate whether uptake of carbon-11 methionine (MET) is associated with histological grade of malignancy and survival in patients with newly diagnosed or recurrent lymphoma. Thirty-two patients with histologically confirmed lymphoma participated in the study. Twenty-six (81%) were studied before any therapy and six before treatment for recurrent disease. Twenty-eight patients had non-Hodgkin’s lymphoma and four had Hodgkin’s disease. An ECAT 931/08-12 positron emission tomography (PET) scanner was used for PET imaging. After the transmission scan, a median dose of 293 MBq of MET was injected intravenously and dynamic images were acquired for 40 min. The uptake of MET in tumour was measured as the standardized uptake value (SUV) and influx constant (Ki). The SUV formula was also adjusted to the predicted value of lean body mass (SUVlean) and body surface area (SUVBSA). The PET results were correlated with the clinical follow-up data. The median SUV in 32 malignant lesions was 6.6 (range, 1.9–12.4) and the median Ki was 0.116 min−1 (range, 0.025–0.201, n=23). The median SUV was 7.0 (range, 5.4–12.4, n=9) in high, 6.2 (range, 1.9–10.4, n=11) in intermediate and 5.7 (range, 3.8–8.3, n=8) in low grade lymphomas. One intermediate grade lymphoma of the skin was visually negative (SUV 1.9). In Hodgkin’s disease the median SUV was 7.0 (range, 3.2–7.9, n=4). The median Ki value was 0.162 min−1 (range, 0.147–0.197, n=7) in high, 0.099 (range, 0.025–0.152, n=10) in intermediate, and 0.078 (range, 0.056–0.152, n=4) in low grade lymphomas and 0.149 (range, 0.096–0.201, n=2) in Hodgkin’s disease. The difference between high and other grade non-Hodgkin’s lymphomas was significant when using Ki (P<0.001), but not with SUV, SUVlean or SUVBSA. The final outcome of the patients was not related to MET uptake. Lymphomas with a high Ki value tended to have a high S-phase fraction (r2=0.46, P=0.043). It is concluded that MET PET is highly sensitive for the detection of untreated and recurrent lymphomas. Differentation of high grade lymphomas from lower malignancy grades seems to be possible if graphical analysis is applied to calculate Ki for MET. However, prediction of survival is not possible with MET PET.

Selective modulation of collagen gene expression by different isoforms of platelet-derived growth factor in experimental wound healing

Abstract.Subcutaneous sponges in rat were used as a wound model to study the changes in collagen gene expression induced by different isoforms of platelet-derived growth factor (PDGF). The steady state levels of proα1(I) and proα1(III) collagens rose markedly in response to PDGF-AB treatment. In marked contrast to PDGF-AB, PDGF-BB exerted a down-regulatory effect on the expression of type I and III procollagen mRNA levels. In situ hybridisation signal for proα1(I) collagen mRNA was most prominent in the periphery of the sponges in response to PDGF-AB. In PDGF-AA and PDGF-BB treated sponges, however, the hybridisation signal for proα1(I) collagen mRNA was evenly distributed. Immunolabellings demonstrated the presence of type I and III collagen epitopes and thus revealed the deposition of these proteins into developing granulation tissue. The volume of ingrown granulation tissue was estimated by measuring the cross-sectional area of the samples. PDGF-AB and PDGF-BB were both effective resulting in a significant increase in the amount of granulation tissue. However, only a limited enhancement of granulation tissue ingrowth was observed in response to PDGF-AA treatment. To conclude, PDGF-AB and PDGF-BB induced significantly the ingrowth of repair tissue in wounds. PDGF-AB distinctively upregulated collagen gene expression, while PDGF-BB primarily seemed to be mitogenic.

Lectin binding to prostatic adenocarcinoma

The binding of different lectins (concavalin A [Con A], triticum vulgaris [WGA], glycine maximum [SBA], dolichos bilflorus [DBA], ulex europaeus [UEA I], arachis hypogaea [PNA], and ricinus communis [RCA I] to cells of normal prostate glands, hyperplastic glands and adenocarcinoma was studied. The Con A, WGA, DBA, PNA and RCA I bound to both normal and hyperplastic glands. The binding in the malignant glands differed from that of the benign conditions. The SBA, which was not bound by benign cells, was bound to the malignant glandular cells. Also, UEA I was bound to a part of the carcinoma cells. In addition, the binding pattern of Con A and WGA in the cells differed between the malignant and benign conditions. Based on the results of this study, it is suggested that lectin histochemical study might be useful in routine pathologic examination to detect malignant cells in cases which are doubtful with regard to malignancy by routine methods.