Search PubMed⌕ Search

Biomedical subjects

B Rose

Publications and source records attributed to B Rose.

At least 37 records · Page 2Linked to original sources
PubMed1995

Clustering of Cx43 cell-to-cell channels into gap junction plaques: regulation by cAMP and microfilaments.

Cell-to-cell channels are often seen clustered at cell-cell contacts into the so-called gap junction plaques. The mechanism of this clustering is unknown. We show that the clustering of cell-to-cell channels composed of connexin43 is induced by elevation of cyclic AMP. The cAMP-induced clustering is enhanced by inhibition of glycosylation and abolished by disruption of microfilaments. Channel clustering thus seems to be regulated by cAMP and glycosylation and to involve microfilaments.

Actin Cytoskeleton↗
PubMed1994

Groin dissection in malignant melanoma.

BACKGROUND: There is controversy about the extent of groin dissection necessary (whether superficial or radical) and about its utility when the deep nodes are affected. METHODS: A total of 198 groin dissections (1977-1991) were reviewed; 94 (48%) were superficial and 104 (52%) were radical dissections. Of 72 patients with palpable positive inguinal nodes, 31 (43%) had involvement of the deep nodes; of 39 patients with nonpalpable, histologically positive inguinal nodes, seven (18%) had or later manifested involvement of the deep nodes. RESULTS: The mean number of positive nodes (median) in the group with clinically palpable disease was six (two), and in the group with occult disease the number was two (one). The estimated overall (disease-free) 5-year and 10-year survival rates for patients with negative nodes were 73% (67%) and 64% (58%), respectively, and for those with positive nodes they were 36% (27%) and 30% (23%), respectively. Survival was significantly poorer for patients with positive nodes (p < 0.0001). The respective 5-year and 10-year survival rates for patients with positive nodes and involvement of the inguinal nodes only were 41% (33%) and 36% (29%), and for those with involvement of the inguinal and deep nodes the rates were 28% (17%) and 19% (13%). Survival was significantly poorer for patients with deep node involvement (p = 0.006). CONCLUSIONS: The survival rates after therapeutic groin dissection are substantial and unattainable with any other treatment at the present time. Incontinuity dissection of the deep nodes is advisable in the presence of palpable inguinal nodes, since the incidence of deep node involvement is considerable and the survival rate appreciable after removal of involved deep nodes.

Adult↗
PubMed1994

Barbiturate therapy for status epilepticus in the postanesthesia care unit.

Although rare, status epilepticus refractory to conventional therapy may require the initiation of pentobarbital anesthesia and intensive monitoring in the PACU. Barbiturate therapy mandates that the nurse be able to perform mechanical ventilation and advanced cardiopulmonary monitoring as well as be familiar with electroencephalographic monitoring. Careful attention to the potential side effects of barbiturate therapy and anticipation of end-organ complications can increase the likelihood of seizure termination and recovery of status epilepticus patients.

Barbiturates↗
PubMed1993

Gap-junction protein gene suppresses tumorigenicity.

Prompted by the notion that the membrane channels in gap junctions conduct growth-regulating signals from cell to cell, we transferred the alpha 1 gene for the channel protein (connexin43) of rat heart to tumorigenic mouse MCA-10 cells. Upon incorporation into the cell genome, this exogenous gene was expressed, resulting in functional channels and normal growth regulation: cell-cell communication, determined with a channel-permeant 400-dalton fluorescent tracer, was increased and tumorigenicity, determined in nude mice, was suppressed.

Animals↗
PubMed1992

A chimeric mouse/human anti-IL-2 receptor antibody with enhanced biological activities.

A chimeric mouse/human MAb against the human p55 IL-2R was constructed from Ig genes isolated from a mouse hybridoma cell line, designated AHT107. AHT107 binds to a different epitope on p55 than IL-2, and similar to observations made for other rodent anti-IL-2R antibodies that do not recognize the same or spatially related epitope as IL-2, murine AHT107 did not efficiently inhibit proliferation of T-lymphocytes in mitogen and MLR PBMC stimulation assays. In contrast, the chimeric AHT107 antibodies containing a human IgG-1 constant region had substantially more anti-proliferative activity than their murine IgG-I counterparts. Our results indicated that the human constant region of the chimeric antibodies interacted more efficiently than the murine constant region with effector components present in the PBMC cultures. This conclusion was supported by our observation that F(ab')2 generated from the chimeric antibodies did not efficiently inhibit proliferation in the PBMC assays, and the chimeric antibodies did not inhibit proliferation of an antigen specific, IL-2 dependent human T-cell clone stimulated in the absence of PBMC.

Amino Acid Sequence↗
PubMed1992

The cell-cell channel in the control of growth.

Several lines of evidence indicate that the cell-cell channels in gap junction are conduits for growth-regulating signals. Experimental upregulation of the channels by retinoids causes inhibition of cellular growth and, conversely, their downregulation by oncogenes, e.g. activated src, stimulates growth. In either direction, the extent of growth correlates tightly with the degree of communication. Cogent evidence of the channel's function in growth regulation is now on hand: incorporation of a channel-protein gene into the genome of a transformed communication-deficient cell line normalizes communication and growth. The current data conform to a model of growth control with discrete regulatory centers.

Animals↗
PubMed1992

Transcription of the gene for the gap junctional protein connexin43 and expression of functional cell-to-cell channels are regulated by cAMP.

We investigated the mechanism by which cyclic AMP (cAMP) induces gap junctional communication via cell-to-cell channels in a communication-deficient rat Morris hepatoma cell line. We found that under basal conditions, the cells transcribe cx43 at a low level but do not transcribe cx26 or cx32. Elevation of intracellular cAMP, which induced communication, increased cx43 mRNA 15- to 40-fold and the rate of cx43 transcription 6-fold. Cx43 protein was detected by immunostaining in junctions of only those cells in which communication had been induced. We found the regulation by cAMP also in other cell lines; namely, in those with a low basal level of cx43 mRNA.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Differential effects of a murine and chimeric mouse/human anti-interleukin-2 receptor antibody on human T-cell proliferation.

The preference for interleukin-2 receptor (IL-2R) expression on activated, compared with resting T lymphocytes makes the IL-2R a promising target for selective immunosuppressive therapy. To increase the potential therapeutic effectiveness of anti-IL-2R monoclonals, a chimeric mouse/human variant was constructed from Ig genes isolated from a murine anti-human IL-2R hybridoma cell line, designated AHT54. AHT54 binds to the same or spatially related epitope as IL-2 on the p55 protein that constitutes the low- and high-affinity forms of IL-2R. Although the murine and chimeric AHT54 antibodies inhibited cell-surface binding of IL-2 to the same extent, the chimeric antibodies containing a human IgG1 constant region had substantially more anti-proliferative activity than their murine IgG1 counterparts. Our results indicated that the human constant region of the chimeric antibodies interacted more efficiently than the murine constant region with effector components present in peripheral blood mononuclear cells (PBMC).

Animals↗
PubMed1991

Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XV: Antithrombotic effect of selected oligoamines in rats.

Oligoamines which exert antiplatelet and anticoagulant properties in vitro show as well antithrombotic effects in mesenteric arterioles and venoles of rats. The formation of thrombi in these vessels was induced by a laser beam and quantified by the thrombus formation index (TFI). The most potent compound RE 1492 already reduced the formation of thrombi after i.v. administration of 1 mg/kg significantly. After oral administration, however, only a minor effect even after a 200 mg/kg dose is observed. This suggests that the oligoamine was poorly absorbed from the gastrointestinal tract. The tricarbamate of RE 1492 (identical to RE 1492 C), however, was a suitable prodrug. Eight hours after a single oral dose of 10 mg/kg significant antithrombotic properties in arterioles and venules were seen. (TFI = 3.63 (A), 1.77 (V); control: 1.76 (A), 1.29 (V).) After p.o. application of 30 mg/kg RE 1492 C the onset of activity is after 2 h (TFI = 3.44/1.48). A maximum effect is reached after 4 h (TFI: 4.43/2.84) and maintained up to 24 h (TFI = 4.49/2.45). After 48 h the effect in arterioles is still significant (p less than 0.05, chi 2-test). The results obtained with five other carbamates (RE 2029 C, RE 1964 C, RE 2120 C, RE 2112 C, and RE 1981 C) 4 h after p.o. administration in general show a stronger effect in arterioles than in venules which is in the same range as in RE 1492 C.

Amines↗
PubMed1991

Incorporation of the gene for a cell-cell channel protein into transformed cells leads to normalization of growth.

Incorporation of the gene for connexin43, a cell-cell channel protein of gap junction, into the genome of communication-deficient transformed mouse 10T1/2 cells restored junctional communication and inhibited growth. Growth was slowed, saturation density reduced and focus formation suppressed, and these effects were contingent on overexpression of the exogenous gene and the consequent enhancement of communication. In coculture with normal cells the growth of the connexin overexpressors was completely arrested, as these cells established strong communication with the normal ones. Thus, in culture by themselves or in coculture, the connexin overexpressor cells grew like normal cells. These results demonstrate that the cell-cell channel is instrumental in growth control; they are the expected behavior if the channel transmits cytoplasmic growth-regulatory signals.

Animals↗
PubMed1990

[Anti-aggregatory and anticoagulant properties of oligoamines. 11. Oligoamines with two primary amine groups].

Ten branched alpha,omega-alkanediamines with two primary amino groups have been synthesized and tested for their antiplatelet and anticoagulant effects. Seven of them inhibited the platelet aggregation induced by collagen at an IC50 ranging from 5-11 mumol/L. In concentrations up to 400 mumol/L the one stage thromboplastin time was only slightly prolonged (delta t less than 7s).

Amines↗
PubMed1990

The action of v-src on gap junctional permeability is modulated by pH.

The product of the viral src gene (v-src) is the protein tyrosine kinase pp60v-src. Among the known consequences of pp60v-src activity is the reduction in permeability of gap junctions, an effect that is counteracted by the calcium antagonist TMB-8 (8-N,N-[diethylamino]octyl-3,4,5-trimethoxybenzoate). We show here that a decrease in intracellular pH (pHi) also counteracts the v-src effect: junctional permeability of cells containing active v-src kinase rose with decreasing pHi in the range 7.15 to 6.75, whereas junctional permeability of cells containing inactive v-src kinase or no v-src at all was insensitive to pH in that range. Low pH also counteracted the known action of diacylglycerol on junction, but only when pp60v-src kinase was inactive. Immunoblots of whole-cell lysates using an antibody against phosphotyrosine show that phosphorylation on tyrosine of at least one cellular protein, specific for pp60v-src kinase activity, was reduced by low pH but not by TMB-8. These results suggest that TMB-8 does not inhibit v-src action on junctional permeability by interfering with tyrosine phosphorylation of a protein crucial for closure of gap junction channels, but that the inhibition by low pH may be via this mechanism.

Animals↗
PubMed1989

Anogenital warts in childhood.

Fifteen children with anogenital warts are presented. Twelve cases were referred for assessment of sexual abuse which was established in six cases, strongly suspected in one, and excluded in three. In two, the source was unclear. Papillomavirus typing was carried out by HPV DNA dot and Southern blot hybridization using mixed HPV 6/11, 16/18, and 2/3 DNA probes on 15 specimens from 12 of the children. Seven biopsy specimens were positive for HPV 6 or 11 and one hybridized with both HPV 6/11 and 16/18 mixed sets of probes. Two specimens were positive for HPV 2, and a further two hybridized with both HPV 18 and 2. Three wart specimens could not be typed with the available genital or skin probes. The viruses causing genital tract papillomata are the same for children and adults. The identification of HPV 16/18 raises the concern of potential oncogenicity and stresses the need for long-term assessment. The diagnosis of sexual abuse was made on history rather than examination, as only two cases showed additional physical signs of sexual abuse. It is advocated that the presence of anogenital warts alone be sufficient grounds to pursue the possibility of sexual abuse. Nonsexual transmission, although possible, is far less likely.

Adolescent↗
PubMed1988

Hemodynamic and angiographic effects of prostaglandin E1 in coronary artery disease.

The effects of prostaglandin E1 (PGE1) were assessed in 24 patients with coronary artery disease. Quantitative coronary angiography was performed in 15 patients. PGE1 was found to produce dilation of coronary stenoses (6 +/- 12% to intravenous PGE1, difference not significant, 19 +/- 22% to intracoronary PGE1, p less than 0.05), but usually no change in the diameter of angiographically normal segments. In these patients intracoronary nitroglycerin consistently dilated the normal segments not altered with PGE1 and often led to further dilation of the stenoses. In 9 other patients who were undergoing coronary angioplasty, hemodynamics and the time to ischemia induced by coronary occlusion were measured. In both patient groups PGE1 led to decreases in aortic, pulmonary artery and pulmonary arterial wedge pressures and an increase in heart rate (all p less than 0.05). Before coronary occlusion PGE1 produced coronary vasodilation manifested by preservation in coronary sinus flow (130 +/- 41 to 126 +/- 42 ml/min, difference not significant); as aortic pressure declined coronary resistance decreased (0.9 +/- 0.3 to 0.8 +/- 0.3 mm Hg/ml/min, p less than 0.05). During coronary occlusion residual flow to the affected region was usually similar to control occlusions (37 +/- 20 to 36 +/- 25 ml/min, difference not significant) and collateral resistance was decreased (3.2 +/- 2.9 to 2.9 +/- 2.6 mm Hg/ml/min, p less than 0.05). However, time to ischemia usually remained unchanged. PGE1 shows an interesting angiographic and hemodynamic profile in patients with coronary artery disease. Although no obvious clinical benefit was seen, PGE1 was safely administered both intravenously and directly into narrowed coronary arteries.

Adult↗
PubMed1988

Growth factors modulate junctional cell-to-cell communication.

The epidermal growth factor (EGF) and the platelet-derived growth factor (PDGF) inhibit gap junctional communication in the mammalian cell lines NRK and BalbC 3T3: cell-to-cell transfer of a 400-dalton tracer molecule is reduced and junctional conductance is reduced. The inhibition of cell-to-cell transfer is reversible and dose dependent; half-maximal effects are obtained at 10(-9) and 10(-11) M concentrations of EGF and PDGF, respectively. The response of junctional conductance is detectable within 2 min of EGF application and reaches a maximum within 10 min. It is among the earliest cellular responses to this growth factor and may be significant in the regulation of growth. The response is lacking in EGF receptor-deficient NIH 3T3 cells. The transforming factor beta (TGF beta) enhances junctional communication in BalbC 3T3: cell-to-cell transfer is increased over a period of 8 hr. But in NRK cells, where it upregulates EGF receptors, TGF beta reduces junctional communication synergistically with EGF.

Animals↗