In vitro growth inhibition of neoplastically transformed cells by non-transformed cells: requirement for gap junctional intercellular communication

We examined whether the inhibition of neoplastically transformedcell growth by co-cultured non-transformed cells involved gapjunctional intercellular communication (GJIC). The growth ofpoorly communicating (     

HPLC和1HNMR分析确定cis-A-和cis-B-羟甲芬太尼的组成和构型

羟甲芬太尼(1)是一个强效的镇痛剂和高亲和、高选择性的阿片μ受体激动剂。通过HPLC和¹HNMR分析,cis-A-l被确定为由等量的cis-(+)-(3R,4S,2'S)-l和:cis-(—)-(3S,4R,2'R)-1组成的外消旋体,cis-B-l被确定为由等量的cis-(—)-(3R,4S,2'R)-1和cis-(+)-(3S/,4R,2'S)-1组成的外消旋体。     

Segmental intestinal muscular thinning: a possible cause of intestinal obstruction in the newborn

Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant.     

Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats

The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5. The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site-specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-2, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy.     

Cerebellar Golgi cells in the rat receive multimodal convergent peripheral inputs via the lateral funiculus of the spinal cord

We recently showed that the activity of cerebellar Golgi cells can be powerfully modulated by stimulation of peripheral afferents, in a pattern different to local Purkinje cells. Here we have examined the pathways underlying these responses. Graded electrical stimulation of muscle and cutaneous nerves revealed that long-lasting depressions and short-lasting excitations of Golgi cells were evoked by stimulation of cutaneous nerves at stimulus intensities that activated large mechanoreceptive afferents, and grew as additional afferents were recruited. In contrast, none of the neurones responded to stimulation of muscle nerves at intensities that activated group I afferents, although about half responded with long-lasting depressions, but not excitations, to stimuli that recruited group II and III afferents. Selective lesions of the spinal dorsal columns did not affect either of these types of response. After lesions of one lateral funiculus in the lumbar cord the responses evoked by stimulation of the hindlimb contralateral to the lesion were reduced or abolished, leaving responses evoked by ipsilateral hindlimb afferents unaltered. Since both ipsi- and contralateral afferents generate responses in Golgi cells, the convergence from the two sides must occur supraspinally. It is difficult to reconcile these properties with any of the direct spinocerebellar pathways or spinoreticulocerebellar pathways that have been described. Instead, it is likely that the responses are evoked via the multimodal 'wide dynamic range' neurones of the anterolateral system. Golgi cell activity may thus be powerfully enhanced or depressed during arousal via the anterolateral system.     

Ontogenetic transition in fetal wound transforming growth factor-beta regulation correlates with collagen organization

Fetal rat skin transitions from scarless fetal-type repair to adult-type repair with scar between day 16 (E16) and day 18 (E18) of gestation (term = 21.5 days). Deficient transforming growth factor (TGF)-beta 1 and -beta 2 injury response has been proposed as a mechanism for scarless fetal-type repair. However, previous fetal studies have inconsistently reported the degree of TGF-beta induction after injury. To minimize developmental variables in fetal versus adult TGF-beta regulation, we narrowed our study to wounded fetal animals. We hypothesize that TGF-beta ligand and receptor expression will be differentially regulated during the transition from early gestation (E16) wounds manifesting scarless fetal-type repair to late gestation (E19) wounds manifesting adult-type repair with scar. In this study, decreased and rapidly cleared TGF-beta 1 and -beta 2 expression accompanied by increased and prolonged TGF-beta 3 levels in wounded E16 animals correlated with organized collagen deposition. In contrast, increased and prolonged TGF-beta 1 and -beta 2 expression accompanied by decreased and delayed TGF-beta 3 expression in wounded E19 animals correlated with disorganized collagen architecture. Similarly, expression of TGF-beta receptors type I and II were also increased or prolonged in E19 animals. Our results implicate increased TGF-beta 1, -beta 2, and decreased TGF-beta 3 expression, as well as increased type I and II receptor expression in late gestation fetal scar formation.     

Functionally distinct monoclonal antibodies reactive with enzymatically active and binding domains of Pseudomonas aeruginosa toxin A.

Monoclonal antibodies (MAbs) are described which react with two discrete structural domains of Pseudomonas aeruginosa toxin A and which have two distinct functional profiles. The MAbs designated T3-1C7 and T4-1F2 reacted with a 46,000-dalton peptide similar to the putative B or binding fragment of toxin A. These antibodies neutralized the cytotoxic and lethal properties of toxin but had no effect on its ADP-ribosyl transferase activity. T4-1F2 interfered with the binding of toxin A to membrane receptors on mouse fibroblasts (L cells), although the epitope for the antibody appears to be distinct from the actual receptor binding site. The MAb designated T2-1H2 reacted with intact toxin A and with a cloned, enzymatically active carboxy-terminal polypeptide similar to the toxin A fragment. This MAb neutralized the ADP-ribosyl transferase activity of activated holotoxin and of the cloned peptide, but inhibited neither binding of toxin to membrane receptors nor its cytotoxic and lethal actions. The complementary specificity and function of these MAbs confirm the functional specialization of discrete structural domains within the toxin A molecule. Our findings suggest the greater antitoxic potential of antibodies that block binding, compared with those which inhibit the enzymatic activity of toxin A.