Anisotropic Bladder Planning Target Volume in Bladder Radiation Therapy

Purpose

This study aimed to investigate 3 planning target volume (PTV) margin expansions and determine the most appropriate volume to be used in bladder preservation therapy when using daily cone beam computed tomography (CBCT). We aimed to establish whether a smaller PTV expansion is feasible without risking geographical miss.

Chronic treatment with scopolamine and physostigmine changes nerve growth factor (NGF) receptor density and NGF content in rat brain

Nerve growth factor (NGF) and NGF receptors were measured in cortex and hippocampus of rats treated with drugs affecting cholinergic neurotransmission. High (K_d= 0.045nM) and low (K_d= 21nM) affinity¹²⁵I-NGF binding sites were present in both cortical and hippocampal membranes with hippocampus containing higher numbers of both sites than cortex. Chronic treatment of rats with the muscarinic receptor antagonist scopolamine (5 mg/kg, twice daily) decreased the density of high- and low-affinity sites by 50–90% in cortical and hippocampal membranes. These changes were seen after 7 days, but not 3 days, of scopolamine treatment. Chronic infusion of physostigmine (1 mg/kg/day) using minipumps increased the number of high- and low-affinity sites in cortex 3- and 6-fold, respectively. The changes in receptor-binding parameters induced by physostigmine were transient as they were evident after 3 days of treatment, but returned to control levels after 7 days. NGF content in cortex and hippocampus was reduced by about 50% following 7, but not 3, days of chronic physostigmine infusion. In contrast, scopolamine treatment failed to change NGF levels in the cholinergic neuronal target regions but it decreased NGF content in the septal area. The content of NGF mRNA in the cortex measured by Northern blot analysis failed to change following either scopolamine or physostigmine treatment. The results suggest that levels of NGF and NGF receptors in the target regions of cholinergic neurons are regulated by the extent of cholinergic neurotransmitter activity.     

Inhibition of growth of PC-82 human prostate cancer line xenografts in nude mice by bombesin antagonist RC-3095 or combination of agonist [D-Trp6]-luteinizing hormone-releasing hormone and somatostatin analog RC-160.

The effects of treatment with a bombesin receptor antagonist [D-Tpi6, Leu13 psi (CH2NH) Leu14]BN(6-14)(RC-3095) and the combination of an agonist of luteinizing hormone-releasing hormone [D-Trp6]-LH-RH and somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val- Cys-Trp-NH2 (RC-160) were studied in nude mice bearing xenografts of the hormone-dependent human prostate tumor PC-82. During the 5 weeks of treatment, tumor growth was decreased in all treated groups compared with controls. Bombesin antagonist RC-3095 and the combination of [D-Trp6]-LH-RH and RC-160 caused a greater inhibition of tumor growth than [D-Trp6]-LH-RH or RC-160 alone as based on measurement of tumor volume and percentage change in tumor volume. The largest decrease in tumor weight was also seen in the groups treated with the bombesin antagonist and with the combination of RC-160 and [D-Trp6]-LH-RH. Serum prostatic-specific antigen levels were greatly decreased, and insulin-like growth factor I (IGF-I) as well as growth hormone levels were reduced in all treated groups. Specific binding sites for [D-Trp6]-LH-RH, epidermal growth factor (EGF), IGF-I, and somatostatin (SS-14) were found in the tumor membranes. Receptors for EGF were significantly down-regulated by treatment with the bombesin antagonist or RC-160. Combination of LH-RH agonists with somatostatin analog RC-160 might be considered for improvement of hormonal therapy for prostate cancer. The finding that bombesin antagonist RC-3095 inhibits the growth of PC-82 prostate cancer suggests the merit of further studies to evaluate the possible usefulness of antagonists of bombesin in the management of prostatic carcinoma.     

Detection of massive pulmonary embolism by transesophageal echocardiography.

Transesophageal echocardiography is a new echocardiographic technique with indications that are still expanding and being redefined. Recently, the usefulness of transesophageal echocardiography in pulmonary embolism has been demonstrated in several case reports. In this article, we present 3 cases with pulmonary embolism diagnosed by transesophageal echocardiography and discuss its diagnostic value in this clinical setting.     

Growth inhibition of estrogen independent MXT mouse mammary carcinomas in mice treated with an agonist or antagonist of LH-RH,an analog of somatostatin,or a combination

Summary Female BDF₁ mice inoculated with MXT (3.2) estrogen independent mouse mammary carcinoma were treated for three weeks with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp⁶]LH-RH, the antagonist SB-75, the somatostatin analog RC-160, or combinations. The lack of estrogen dependence of the tumor was proved by bilateral surgical ovariectomy, which had no effect. In two experiments, treatment with 25µg/day doses of each analog alone resulted in a significant inhibition of tumor growth as shown by a 40–53% inhibition of tumor volumes, 38–43% decrease in tumor weights, and histological signs of tumor regression. However, the combination of SB-75 or [D-Trp⁶]LH-RH with somatostatin analog RC-160 caused greater reduction of tumor volume (68 and 61%) or tumor weights (59 and 56%), than single analogs, and histologically the occurrence of apoptosis and decrease in AgNOR numbers was more pronounced in the groups receiving combination therapy. Specific binding sites for [D-Trp⁶]LH-RH, EGF, and IGF-I were demonstrated in the tumor membranes. The binding capacity of LH-RH receptors was decreased by treatment with the analogs, the greatest down-regulation being caused by combination therapy. A significant decrease in EGF binding capacity was observed after treatment with the LH-RH analogs, alone or especially in combination with somatostatin analog RC-160. The combination of these analogs also caused a reduction in IGF-I receptors. The finding that LH-RH agonists and antagonists and somatostatin analogs inhibit the growth of estrogen independent mammary tumors, and that combinations are more effective than single analogs, might be of practical importance in human breast cancer therapy.     

Specific binding of [3H]mepyramine to histamine H1-receptors in vascular smooth muscle membranes

The antagonist-sensitive binding of [³H]mepyramine to beef aortic membranes was as expected for binding to histamine H₁-receptors. [³H]mepyramine binds rapidly and in saturable fashion to the specific receptor sites, specific binding reaching equilibrium in 3 min at 37°CScatchard's analysis of the binding data gave a dissociation constant of 3.0 nM for the radioligand-receptor complex and maximal number of binding sites: 31 fmol/mg protein. In the competition studies histamine H₁-antagonists are more potent inhibitors of radioligand binding than H₂-antagonist. They inhibit [³H]mepyramine binding in the following order: mepyramine >triprolidine     

Identification and characterization of a conserved,stage-specific gene product of Plasmodium falciparum recognized by parasite growth inhibitory antibodies

We have identified a novel conserved protein of Plasmodium falciparum, designated D13, that is stage-specifically expressed in asexual blood stages of the parasite. The predicted open reading frame (ORF) D13 contains 863 amino acids with a calculated molecular mass of 99.7 kDa and displays a repeat region composed of pentapeptide motives. Northern blot analysis with lysates of synchronized blood stage parasites showed that D13 is highly expressed at the mRNA level during schizogony. The first N'-terminal 138 amino acids of D13 were expressed in Escherichia coli and the purified protein was used to generate anti-D13 monoclonal antibodies (MAbs). Using total lysates of blood stage parasites and Western blot analysis, these MAbs stained one single band of approximately 100 kDa, corresponding to the predicted molecular mass of ORF D13. Western blot analysis demonstrated further that D13 is expressed during schizogony, declines rapidly in early ring stages and is undetectable in trophozoites. D13 protein is localized in individual merozoites in a distinct area, as demonstrated by indirect immunofluorescence analysis. After subcellular fractionation, D13 was confined to the pelleted fraction of the parasite lysate and its extraction by alkaline carbonate buffer treatment indicated that D13 is not a membrane-integral protein. Inclusion of certain anti-D13 MAbs into in vitro cultures of blood stage parasites resulted in considerable reduction in parasite growth. The N'-terminal domain encompassing 158 amino acids is 94 and 95%, respectively, identical at the amino acid level between Plasmodium knowlesi, Plasmodium yoelii, and P. falciparum. In summary, we describe a novel stage-specifically expressed, highly conserved gene product of P. falciparum that is recognized by parasite growth inhibitory antibodies.     

Short-term and long-term stimulation of Na+−H+ exchange in cortical brush-border membranes during compensatory growth of the rat kidney

The effect of unilateral nephrectomy on Na⁺–H⁺ exchange in rat renal cortical brush-border membrane vesicles (BBMV) was studied by the method of acridine orange fluorescence quenching. The exchanger activity in BBMV from remnant kidney increased rapidly by 70–75% within first 30 min following uninephrectomy. Only a slight further increase was found in later stages of renal growth, i.e. 30 min to 7 days following uninephrectomy. The changes in antiporter activity were restricted toV _max, whereas theK _m for Na⁺ was similar in control and compensatory growing kidney. The increase of Na⁺–H⁺ exchange at 15 min was not affected by actinomycin D in vivo, whereas the increase at 48 h was completely abolished indicating that protein synthesis could be involved in the late, but not in the initial stimulation of renal Na⁺–H⁺ exchange. The late, but not the initial stimulations of Na⁺–H⁺ exchange were associated with elevated activities of cortical (Na⁺+K⁺)-ATPase indicating that changes in antiporter activity precede those in the (Na⁺+K⁺)-pump. The early stimulation of Na⁺–H⁺ exchange in BBMV in one kidney was induced also by the occlusion of blood flow through the contralateral kidney for 15 min, without removing it. Thirty min after the occlusion was removed and the reflow established, the Na⁺–H⁺ exchange in BBMV from the intact kidney decreased to the control values. The observed modulations in renal Na⁺–H⁺ exchanger may be regulated by phosphorylation-dephosphorylation events. In support, the concentration of a well known protein kinase C activator, 1,2-diacylglycerol, in the cortical tissue of the remnant kidney increased up to 100% within 5 min following unilateral nephrectomy and preceded the increase in Na⁺–H⁺ exchange. The early stimulation of Na⁺–H⁺ exchange may be a trigger in initiating the kidney growth.