A putative “ribonucleic acid migration factor” in serum

Summary The processing of ribosomal ribonucleic acid (RNA) and the migration of newly synthesized RNA of several types from nucleus and nucleolus to the cytoplasm are restricted at 27°C. The previously reported failure of efforts to induce, glutamine synthetase at that temperature may be due to the retention by the nucleus of the specific RNA required for induction. At the normal temperature of 37°C serum macromolecules appear to be required for RNA migration. Cohn fraction III of bovine serum restores the RNA distribution pattern observed with whole serum. The exchange of lysine-labeled proteins between the cytoplasm and the nucleus is also altered by low temperature and in serum-free medium at 37°C. Supported by American Cancer Society Grant E-348 and United States Public Health Service Grant AI-00957     

The ultrastructure of the “difference factor” in the myelin

Summary Electron-microscopic studies of peripheral nerves as prepared by the freezeetching method show the myelin lamella to be 185 Å thick. This is the same dimension found by x-ray diffraction analysis of natural myelin. In contrast to the appearance of osmiumfixed material, the cytoplasmic surfaces of the paired membranes in the myelin lamella are apposed to two fine, separate lines, while the outer membrane sides are fused into a broader single line. The finding of a decidedly different structure for the outer and for the inner membrane surfaces appears to be the cause of the difference factor.This work was supported by the Swiss National Foundation (Nr. 4065). — Acknowledgement: We thank the Balzers AG. (9496 Balzers, Fürstentum Liechtenstein) for providing us with the High Vakuum Device.     

Nonbenzamidine acylsulfonamide tissue factor–factor VIIa inhibitors

Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P′ binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype.     

“Suppressor factor” of neutrophils: A short story of a long-term misconception

A large body of evidence obtained during the last decade has demonstrated that neutrophils suppress T cell proliferation in different models of inflammation and cell interaction. The commonly used method for assessing cell proliferation and proliferation inhibition is measuring [³H]thymidine incorporation into cells. Earlier, we observed inhibition of [³H]thymidine uptake in experiments on neutrophil-mediated regulation of T cell response in tuberculosis immunity. Here, we used different types of proliferating cells to analyze the nature of the soluble “neutrophil factor” by a variety of methods (dialysis, HPLC, mass spectrometry, and NMR) and unambiguously demonstrated that neutrophils do not synthesize a specific factor inhibiting cell proliferation, but secrete high concentrations of extracellular thymidine that competitively inhibit [³H]thymidine incorporation. Although the physiological significance of thymidine secretion by neutrophils remains unknown, this phenomenon should be carefully considered when designing test systems for studying cell–cell interactions.     

Beobachtungen einer Familie mit Galaktosämie und “Duarte-Variante”

Zusammenfassung Die Familienuntersuchungen einer galaktosämischen Patientin ergaben bei 5 Verwandten das gleichzeitige Vorkommen eines galaktosämischen Merkmals und eines varianten Enzyms (Duarte-Variante). Aktivität der Gal-1-Phosphat-Uridylyltransferase wurde mit Hilfe eines modifizierten UDPG-Verbrauchstests nach Beutler u. Baluda bestimmt.

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Summary 5 relatives of a patient with galactosemia showed a simultaneous occurence of the characteristic sign of galactosemia and of a variant enzyme (Duarte variant). The activity of Gal-1-Phosphat-Uridylyltransferase was determined by a modification of the UDPG-consumptiontest of Beutler and Baluda.

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With the aid of: Landesamt für Forschung des Landes Nordrhein-Westfalen und Landschaftsverband Westfalen Lippe.     

Sauerstoffoptimum und Nährböden “aerober” Bakterien

Ohne Zusammenfassung     

„Pontische“ und „pannonische“ Flora

Ohne Zusammenfassung     

Comparison of transforming growth factor β and a human tumour-derived suppressor factor

Summary Serum-free supernatants from the human melanoma cell line G361 contain a factor that can potently suppress the generation of tumouricidal lymphokine-activated killer (LAK) cells in response to interleukin-2. To characterise the suppressive factor of tumour origin we performed a number of physicochemical and functional comparisons with another immunosuppressive protein, transforming growth factor (TGF). The bioactivity of tumour-derived suppressor factor (TDSF), assayed by suppression of LAK cell generation, was unaffected by a reducing agent but lost when denatured with a chaotropic agent. In contrast, TGF was inactivated by reduction but not denaturation. TDSF lost bioactivity in conditions of pH less than 4, whereas TGF showed no loss of activity. The TDSF moiety has an estimated pI of 4.3 and a molecular mass of 69–87 kDa. This differs from published values of pI 9.5, and 25 kDa molecular mass for TGF. Anti-TGF antiserum reversed the effects of TGF but did not affect the suppression of LAK cell generation caused by TDSF. These findings provide compelling evidence that the TDSF moiety is not TGF, and may be a novel immunoregulatory cytokine.     

Elevated Krüppel-like factor 4 transcription factor in canine mammary carcinoma

Background

Krüppel-like factors (KLFs) are critical regulators of biological and physiological systems and have been extensively studied for their roles in cell proliferation, differentiation and survival in the context of cancer. Among the KLFs, KLF4 is highly expressed in human breast cancers and plays an oncogenic role. The present study examined the expression of KLF4 and assessed its significance in canine mammary carcinoma.

Results

Immunohistochemistry was employed to investigate the expression of KLF4 in 142 cases of canine mammary tumor. 75 of the 142 (52.8%) cases were histologically confirmed as mammary carcinoma. Quantification of immunohistochemistry was carried out using Quick score which multiply the staining intensity by the percentage of positive cells. High KLF4 expression was identified in 44 of the 75 (59%) dogs with mammary carcinoma and none in the benign cases. High KLF4 expression occurred only in the tumor cells and not the adjacent normal cells in mammary carcinoma (P < 0.001). Moreover, the high expression level of KLF4 expression was statistically associated with poor grade, late stage, histological subtypes of simple and complex carcinoma, and shorter 24-month survival. The Kaplan-Meier survival analysis also indicated that dogs with high nuclear KLF4 expression had a significantly shorter survival than those with low/moderate KLF4 expression (P = 0.011).

Conclusions

KLF4 is highly and frequently expressed in canine mammary carcinoma and correlates with a more aggressive phenotype.

     

Histologische und autoradiographische Untersuchungen zur „Präspermatogenese“ und „Spermatogenese“ der Ratte

Zusammenfassung An den Hoden 15–21 Tage alter Feten sowie 0–64 Tage alter Jungtiere (Wistarratten) wurden histologische und autoradiographische Untersuchungen durchgeführt. Auf Grund dieser Untersuchungen wird die Entwicklung des Samenepithels in zwei große Etappen gegliedert, die Präspermatogenese und die Spermatogenese. In der Präspermatogenese proliferieren hauptsächlich die Stützzellen, die Gonocyten vermehren sich nur während des 15.–17. Schwangerschaftstages. Der Prozentsatz der Gonocyten an der Gesamtzahl der Zellen in den Keimsträngen bzw. Samenkanälchen nimmt während dieser Zeit von 70% am 15. Schwangerschaftstag bis auf 4% am 4. Lebenstag ab. Mit Hilfe der Methode der markierten Mitosen wurden die Generationszeit und die Teilphasen der Stützzellen zwischen Lebenstag 0 und Lebenstag 1 bestimmt. Die Generationszeit T und die S-Phase S der Stützzellen liegen mit 38 Std für T und 20 Std für S in der gleichen Größenordnung wie T und S der A-spg. Ein Teil der Gonocyten geht vor allem während der ersten Lebenstage zugrunde. Der andere Teil der Gonocyten tritt nach einer langen Ruheperiode von 8 bis 11 Tagen am 3.–6. Lebenstag in die S-Phase und in die Mitose. Die Tochterzellen der Gonocyten wandeln sich in der Peripherie der Kanälchen in A-spg um. Mit dem Auftreten der ersten A-spg endet die Präspermatogenese und beginnt die Spermatogenese. Die ersten A-spg treten am 3. und 4. Lebenstag auf, am 5. Lebenstag erscheinen die ersten Im-spg, am 6. Lebenstag die ersten B-spg und am 7. Lebenstag die ersten ruhenden Spermatocyten. Erst während des ersten Schubs sich differenzierender Zellen erfolgt die weitere Proliferation der A-spg, die die Matrix des Samenepithels bilden. Vom Beginn der Spermatogenese an bzw. einen bis zwei Tage nach dem Beginn der Spermatogenese kann somit bereits eine Reihe sich differenzierender Keimzellen (Im-spg, B-spg, Spermatocyten usw.) von einer proliferierend regenerierenden Reihe (A-spg) unterschieden werden.

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Summary Testes of wistar rats from the fifteenth to the twenty-first day of gestation and from zero to sixty-four days after birth were investigated histologically and autoradiographically. The development of the seminiferous epithelium is subdivided into two phases: the prespermatogenesis and the spermatogenesis. In prespermatogenesis there mainly is a proliferation of the supporting cells, whereas the gonocytes only proliferate from the fifteenth to the seventeenth day of gestation. The percentage of gonocytes in the total number of cells in the sex cords or seminiferous tubules decreases from 70% at the fifteenth day of gestation to 4% at the fourth postnatal day. By the method of labeled mitoses the generation time and the subphases of supporting cells are determined from zero to one postnatal days. The generation time T and the S-phase S of the supporting cells (38 hours for T and 20 hours for S) are almost identical with T and S of A-spg. Part of the gonocytes degenerate, above all during the first postnatal days. The other part of the gonocytes undergoes the S-phase and mitosis from the third to the sixth postnatal day after a long period of rest. Near the basal membran of the tubules the derivates of the gonocytes become A-spg. With the appearence of the first A-spg prespermatogenesis ends and spermatogenesis starts. The first A-spg are found at the third and fourth postnatal days, the first Im-spg at the fith day, the first B-spg at the sixth day, and the first resting spermatocytes at the seventh day. During the first wave of differentiation of cells further proliferation of A-spg takes place. So from the outset of spermatogenesis respectively one to two days later a line of differentiating germinal cells (Im-spg, B-spg, spermatocytes, etc.) is separated from a proliferating and regenerating one (A-spg).