Functional selectivity of interhemispheric connections in cat visual cortex.

The functional specificity of callosal connections was investigated in visual areas 17 and 18 of adult cats, by combining in vivo optical imaging of intrinsic signals with labeling of callosal axons. Local injections of neuronal tracers were performed in one hemisphere and eight single callosal axons were reconstructed in the opposite hemisphere. The distributions of injection sites and callosal axon terminals were analyzed with respect to functional maps in both hemispheres. Typically, each callosal axon displayed 2 or 3 clusters of synaptic boutons in layer II/III and the upper part of layer IV. These clusters were preferentially distributed in regions representing the same orientation and the same visuotopic location as that at the corresponding injection sites in the opposite hemisphere. The spatial distribution of these clusters was elongated and its main axis correlated well with the preferred orientation at the injection site. These results demonstrate a specific organization of interhemispheric axons that link cortical regions representing the same orientation and the same location of visual stimuli. Visual callosal connections are thus likely involved in the processing of coherent information in terms of shape and position along the midline of the visual field, which may facilitate the fusion of both hemifields into the percept of a single visual scene.

Transforming growth factor-beta and ovarian carcinoma cells: regulation of proliferation and surface antigen expression.

Transforming growth factor-beta (TGF-beta) is a multifunctional peptide regulating several processes in ovarian cells. The growth of ovarian carcinoma cell lines (OVCAR-3, HTB-77, 2780 and CRL-1572) was reduced by TGF-beta in a dose related manner. The antiproliferative activity was not improved by combination with other biological response modifiers. Treatment with TGF-beta augmented the expression of interferon-gamma induced class I and II antigens of the major histocompatibility complex. The presentation of another antigen namely the tumor marker CA-125 on the cell surface was markedly reduced by TGF-beta.

Neurotoxic aminoglycoside antibiotics are potent inhibitors of [125I]-Omega-Conotoxin GVIA binding to guinea-pig cerebral cortex membranes.

[125I]-Omega-Conotoxin GVIA, a blocker of neuronal (N-type) calcium channels labelled 295 +/- 121 fmol per mg protein of high affinity sites (apparent half-saturation at 1.5 to 2.5 pmol/l) in guinea-pig cerebral cortex membranes. Divalent cations (Cd2+ greater than Ni2+ greater than Co2+ greater than Ca2+ greater than Sr2+ = Ba2+ greater than Mg2+) and La3+ were potent inhibitors of Omega-Conotoxin GVIA binding, whereas monovalent cations (Na+, K+, Li+) were ineffective up to 50 mmol/l. Aminoglycosides (neomycin greater than gentamycin = tobramycin greater than streptomycin greater than amikacin greater than kanamycin) and polymyxin B also inhibited [125I]-Omega-Conotoxin GVIA binding with IC50 values in the mumolar range. All other antibiotics tested were ineffective up to 1 mmol/l. With the exception of polymyxin B, which partially inhibited the binding of the 1,4-dihydropyridine (+)-[3H]PN 200-110 and of (-)-[3H]desmethoxyverapamil, the aminoglycosides and the other antibiotics had no effect on the L-type calcium channel labelling. It is suggested, that inhibition of neurotransmitter release by aminoglycosides is mediated via blockade of the N-type calcium channel to which [125I]-Omega-Conotoxin GVIA binds selectively in a quasi irreversible manner.

Solution phase synthesis of the 14-residue peptaibol antibiotic trichovirin I.

The 14-residue peptaibol antibiotic trichovirin I 4A of the structure Ac-Aib-L-Asn-L-Leu-Aib-L-Pro-L-Ala-L-Val-Aib-L-Pro-Aib-L-Leu-Aib-L-Pro-L-Leuol (Aib = alpha-aminoisobutyric acid, Leuol = leucinol) was synthesized by stepwise conventional solution phase synthesis using the Z/O tBu(OMe) strategy and HOBt/EDC as coupling reagents. Intermediates were fully characterized and the identity of the synthetic peptide with the component 4A of the natural, microheterogeneous peptide mixture was proven by electrospray mass spectrometry, HPLC, and bioassay.

[Prognostically relevant factors in malignant mixed Müllerian tumor]. / Prognostisch relevante Faktoren beim malignen Müllerschen Mischtumor.

In a retrospective analysis of 429 endometrial carcinoma and 29 malignant mixed Müllerian tumour (MMMT) patients, the prognostic factors were evaluated. More than 80% of endometrial carcinomata were staged as I or II, whereas about 30% of MMMT's already in stage III or IV (p less than 0.05). MMMT patients were 10 years older than the carcinoma group (73a vs 63a; p less than 0.001). The risk factors parity, adipositas, and diabetes were equally distributed in the two groups, the survival was worse in MMMT (p less than 0.0001). Applying univariate analysis stage, grading, myometrial invasion and type of therapy significantly affected the survival of endometrial carcinoma patients. After a Cox regression, only stage and grading remained significantly associated with the prognosis. For MMMT's, the survival was also influenced by stage, myometrial invasion, and kind of therapy. Moreover, the parity was found to affect markedly the course of disease. Cox regression of our data excluded all but stage and parity. The beneficial influence of parity on the prognosis of MMMTs, despite a latency of more than 20 years from the last birth to tumour appearance, is unique in oncology.

[Comparison of conventional radium and high dose rate afterloading brachytherapy in cervix cancer]. / Vergleich der konventionellen Radium-mit einer High-dose-rate-Afterloading- Brachytherapie beim Zervixkarzinom.

The combination of intracavitary and external-beam radiation is the treatment of choice in advanced cervical cancer. Low-dose regimens using radium were widely abandoned in favour of high-dose-rate afterloading systems. We compared in this retrospective analysis of 550 patients the 2 different treatment modalities. We could observe neither in overall survival, nor in the incidence of side effects, any significant difference. Although the change from low- to high-dose-rate radiation therapy was not accompanied by a benefit in survival, the latter modality displayed several advantages e.g. a reduced exposure of personnel to radiation and shorter duration of confinement to bed. Patient survival rate was dependent mainly on parameters of tumour burden (FIGO stage), i.v. pyelogram or CT scan of paraaortic lymph nodes. On the other hand, neither the histological classification as epidermoid or adenocarcinoma nor the WHO grading, were useful predictors of patient outcome.

[The value of etoposide (VP-16) in the therapy of refractory ovarian cancer]. / Die Wertigkeit von Etoposid (VP-16) in der Therapie des refraktären Ovarialkarzinoms.

In analogy to Kühnle et al. (1984) the role of etoposide in patients with cisplatin-refractory ovarian cancer was evaluated. 45 patients were treated with 150-200 mg of etoposide per sa. m. on days 1-3. Acute toxicity was tolerable except alopecia grade III. Remarkable, however, was the induction of two fatal cases of leukaemia following etoposide treatment. The first patient, who was 27 years old, with FIGO stage IIb serous cystadenocarcinoma, which was treated with cisplatin/epirubicin and after a latent period of 45 months, a local recurrence was treated with 8 cycles of etoposide. Twenty-three months after discontinuation of etoposide therapy, the patient showed acute myelogenous leukaemia (AML) of M5b-subtype according to the FAB classification. Two days after diagnosis, the patient died of the disease. The second patient, a 55-year old woman with FIGO stage IIa serous cystadenocarcinoma, was treated with cisplatin/cytoxan; 8 cycles of etoposide were given as a second line therapy. This patient, 21 months after discontinuation of etoposide therapy showed a pre-pre-B-acute lymphocytic leukaemia with coexpression of the myeloid antigens. Two months after diagnosis, the patient died of the disease. In 4 out of 38 patients, a complete and in 7 patients a partial remission was induced by etoposide treatment and survival of these responding patients was prolonged in comparison with the nonresponder. The survival was also dependent on CA-125 serum level and the cumulative dose of etoposide administered. Etoposide treatment is an acceptable option as salvage therapy in refractory ovarian cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased production of immune activation marker neopterin by colony-stimulating factors in gynecological cancer patients.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been introduced in the treatment of chemotherapy-induced neutropenia. Effects of these CSFs on the cellular immune system were evaluated in 38 neutropenic gynecological cancer patients during chemotherapy. In addition to restoring the leukocyte count, GM-CSF--to a greater extent than G-CSF--also induced neopterin, a sensitive marker of macrophages activated by interferons. This effect was confirmed in vitro by investigating the effects of these CSFs on interferon-gamma-mediated pathways in THP-I human myelomonocytic cells. The results suggest activation of immune effector cells by GM-CSF.

Vascular endothelial growth factor in serum and in the follicular fluid of patients undergoing hormonal stimulation for in-vitro fertilization.

A cross-sectional study regarding endocrine and cytokine parameters in human follicular fluid (FF) as compared to serum values following hormonal stimulation for in-vitro fertilization was conducted. The patients (n = 32) were treated sequentially with the luteinizing hormone-releasing hormone (LHRH) agonist buserelin followed by a combination of buserelin plus highly purified follicle stimulating hormone and finally human chorionic gonadotrophin, in order to induce ovulation. The FF content of pro-inflammatory (IL-1, IL-6), and anti-inflammatory (IL-1ra, IL-10) cytokines, of the immune response-related soluble interleukin-2 receptor (sIL-2R), as well as the mitogens vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) were determined. Routine evaluation included peripheral blood cell counts, morphological data of the ovary and ova, ovarian steroids, prolactin concentrations and thyroid function parameters [free thyroxine (fT4), thyroglobulin]. The concentrations of IL-6, IL1-ra, sIL-2R, VEGF and bFGF in the FF compartment were higher than in serum in the majority of cases. Regression analysis showed a significant association between the serum and FF concentrations of fT4 (P = 0.04; y = 0.37 + 0.34x) and IL-6 (P = 0.002; y = 0.78 + 0.5x). Multiple regression analysis revealed that progesterone played a role in determining VEGF concentrations in the FF (P = 0.07; y = 0.37 + 0.86x). Thyroglobulin concentrations within the FF were extremely low, whereas fT4 concentrations in the FF were similar to those in serum. Patients with a previously diagnosed hypothyroidism tended to have lower serum oestradiol and higher serum progesterone when compared to euthyroids. We conclude that the human FF represents a functional compartment that integrates endocrine, immunological, and mitogenic signalling that is unique for each ovarian follicle. The close association between progesterone and VEGF within the FF suggests a close association of this mitogen to gonadotrophin stimulation, confirming the ovary as a production site of VEGF.