Tumor cell-conditioned medium stimulates expression of the urokinase receptor in vascular endothelial cells.

We have previously reported that culture medium conditioned by human SK-Hep1 hepatoma cells or mouse S180 sarcoma cells induces in vitro angiogenesis and stimulates production of urokinase plasminogen activator (uPA) in vascular endothelial cells. These activities are mediated by a 3.5-10 kDa, heparin-binding peptide that upregulates endothelial cell expression of basic fibroblast growth factor (bFGF; Peverali et al., 1994, J. Cell. Physiol. 161:1-14.) We now report that SK-Hep 1 or S180 cell-conditioned medium rapidly induces a 4- to 5-fold increase in cell-bound uPA activity and in the high-affinity binding of 125I-prouPA to vascular endothelial cells. Ligand blotting and purification experiments show an equivalent increase in the synthesis of a cell surface protein corresponding to the endothelial cell uPA receptor (uPAR) on the basis of M, (45-50 kDa) and sensitivity to phosphatidylinositol-specific phospholipase C (PI-PLC). The tumor cell-conditioned media also upregulate uPAR mRNA levels in endothelial cells. Thus, the increase in uPA binding capacity of endothelial cells is mediated by an increased expression of uPAR. The uPAR-inducing activity of SK-Hep 1 or S180 cell-conditioned medium is not neutralized by antibodies to bFGF, and is associated with a peptide that has a M, higher than 10 kDa and no affinity for heparin. Therefore, it appears to be distinct from the bFGF/uPA-inducing factor secreted by the same cells, and from other heparin-binding cytokines that upregulate uPAR expression in endothelial cells.

Tumor cells secrete an angiogenic factor that stimulates basic fibroblast growth factor and urokinase expression in vascular endothelial cells.

Culture medium conditioned by human SK-Hep1 hepatoma cells or mouse S180 sarcoma cells rapidly up-regulates endothelial cell expression of basic fibroblast growth factor (bFGF) and induces formation of capillary-like structures by vascular endothelial cells grown on three-dimensional fibrin gels (in vitro angiogenesis). Incubation of endothelial cells with the tumor cell-conditioned media also results in increased expression of urokinase plasminogen activator (uPA), a key component of the proteolytic system required for cell invasion and capillary formation. Although the tumor cell-conditioned media contain no bFGF, addition of anti-recombinant bFGF IgG abolishes the up-regulation of uPA and blocks in vitro angiogenesis. This indicates that both the increase in uPA production and formation of capillary-like structures are mediated by endogenous bFGF expressed by the endothelial cells. Both the bFGF/uPA-inducing activity and the angiogenic activity of SK-Hep1 cell-conditioned medium copurify with a relatively acid-resistant peptide that has moderate affinity for heparin and M(r) < 18 kDa > 3.5 kDa. Known cytokines with similar biochemical features do not possess the same biological activity. These findings indicate that angiogenesis can be mediated by endothelial cell bFGF through an autocrine mechanism and that the bFGF-inducing peptide may represent a novel tumor-derived angiogenic factor that modulates in endothelial cells the concerted expression of cytokines and proteolytic enzymes required for capillary formation.

Cytomegalovirus infection of the larynx in the acquired immunodeficiency syndrome.

CMV is the most important viral opportunist in patients with AIDS. Nearly all patients with AIDS have been exposed to CMV and the virus can be isolated from many. When CMV-related disease occurs in AIDS, it has usually involved the eye or gastrointestinal tract. In lesions in which CMV is the suspected etiology, evidence of direct pathogenicity of the virus should be obtained, usually histologically. Accurate diagnosis is essential because long-term therapy with a relatively toxic drug (ganciclovir) is indicated. We have presented a case of CMV infection of the larynx that responded, albeit slowly, to ganciclovir. Additional cases may arise as the prevalence of AIDS increases. Because of the potential for airway compromise and the tendency toward chronicity, CMV infection of the larynx should be of a significant concern both for the patient and the otolaryngologist.

[Soft tissue pain and psychiatric evaluation]. / Weichteilschmerzen und psychiatrische Begutachtung.

Attention is drawn to the special position of the psychiatric assessor. In his evaluation, the assessor takes into consideration psychic and somatic findings and also social factors. Precisely in connection with the assessment of soft-tissue pain there is a growing recognition that the Ancient Greek dualism of "psyche and soma" is already obsolete. Psychic and somatic factors are mutually dependent, and psychosomatic illness has a multifactorial origin involving predisposition, the development of the personality in early childhood and later, and finally the development of environmental influences in the individual sphere and in the social sphere in general. A subject of special discussion are personality factors which are correlated with a developmental impairment of aggressive motivation. The inhibition of aggression seems to play a decisive role in determining the symptoms. The loss of constructive aggressivity is presented as a trigger for soft-tissue pain.

[Gingival changes in pregnancy]. / Alterazioni gengivali in gravidanza.

Pregnancy represent a particular sistemic condition able to induce, because the tissutal metabolism is upset, an increase replay of the gingival tissues, caused by local factors as plaque and tartar. In this study are described effects determined from the increment ormone on the periodontal tissues, the alterations of the salivar components in pregnancy and the therapy to follow to reach as soon as possible the recovery.

Effects of general anesthesia on the human blink reflex.

The blink reflex was studied in 10 patients undergoing elective procedures under general anesthesia. Anesthetic agents were isoflurane, halothane, nitrous oxide, methohexital, and thiopental in various combinations. At induction, blink reflexes were diminished by low-dose thiopental (1-1.5 mg/kg) and abolished by high-dose thiopental (4-8 mg/kg) and methohexital (1.5 mg/kg). Blink reflexes were absent during halogenated volitile inhalational anesthesia and did not return until patients were in the recovery room, well after end-tidal anesthetic levels were zero by mass spectroscopy. Recovery of consciousness and the ability to blink on command often preceded return of any blink reflex activity, indicating that the blink reflex is not useful as a postoperative test of facial nerve function in the operating room after anesthesia. In six patients, blink reflexes were still diminished 2-3 hours after cessation of anesthesia, at a time when patients were fully oriented and corneal and eyelid reflexes were clinically normal. This finding suggests that the blink reflex might be a sensitive test of subtle CNS dysfunction after inhalational anesthesia and potentially could serve as a useful objective indicator of recovery from anesthesia for outpatient surgery.