Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist

We describe an improved synthesis and properties of fluphenazine-mustard, a potent phenothiazine having an alkylating chlorethylamine chain in its structure. The drug possesses anticalmodulin activity equivalent to the parent compound, but unlike fluphenazine dihydrochloride, the mustard derivative irreversibly antagonizes the ability of calmodulin to activate cyclic nucleotide phosphodiesterase. This property is partially calcium-dependent and can be overcome by coincubation with excess fluphenazine dihydrochloride. The compound irreversibly inactivated calmodulin when incubated with intact cells and caused single-stranded breakage of DNA. Fluphenazine-mustard possesses potent antiproliferative and cytotoxic properties against malignant cell lines that are likely to be mediated through both of these actions.     

Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

Adenocarcinoma Metastasis of the Intertransversarius Cervicis Muscle Eliciting a Right Forelimb Lameness in a Dog

This article describes identification of a metastatic adenocarcinoma to the intertransversarius cervicis muscle using magnetic resonance imaging (MRI) in a dog that presented with chronic lameness of the right forelimb. Magnetic resonance imaging revealed a right sided, ovoid signal abnormality within the intertransversarius cervicis muscle lateral to the sixth cervical (C6) vertebra. The lesion was uniform, hyperintense on T2‐ and isointense on T1‐weighted images to muscle and exhibited uniform contrast enhancement on T1‐weighted images. The MRI findings were consistent with a neoplasia. Surgical excision was performed. Histopathological diagnosis was metastatic fibrous adenocarcinoma. The dog recovered rapidly but 6 months post‐operatively he was killed because of lung metastases. Necropsy was declined and the primary tumour could not be identified.     

Hybridization of laboratory strains of sibling species A and B of Anopheles quadrimaculatus

Adult mosquitoes of the Anopheles quadrimaculatus complex were collected from Montgomery County, AL (MON) and Alachua County, FL, (KBG) and laboratory stocks of species A and B were established through a selection procedure employing isofemale lines. Progeny from a cross of species B females to ORL males were usually semisterile females and sterile males. Progeny of the reciprocal cross were also semisterile females and sterile males, but the sex ratio was variable and ranged from normal to no males because of male mortality during the pupal stage. Conspecific crosses between strains from the two locations resulted in fertile offspring. Crosses between the sibling species from the two locations invariably gave semisterile females and sterile males (or lethal effects). This evidence confirmed previous data from hybridization and electrophoretic analyses of field populations indicating that Anopheles quadrimaculatus is a species complex.     

A new member of the Anopheles quadrimaculatus complex, species C

A new member, species C, of the Anopheles quadrimaculatus complex was recently found in collections from the northwest coast of Florida. This new species cannot be differentiated from the other 2 species with available taxonomic keys. Evidence for this taxon as a sibling species includes data on hybrid sterility and distorted sex ratios in the progeny of crosses to species A and B, chromosomal differences, and diagnostic allozymes.     

Self-regulation of food intake among rural Mexican preschool children

Access to food and the amount consumed were investigated within a group of 45 children aged 33 to 60 months, among whom growth stunting was common. Children were observed throughout 1 day; all foods offered and consumed were weighed, and food-related behaviors noted. Children ate frequently, at least 2 meals and an average of 7.4 +/- 2.6 snacks daily. Children had access to 2029 +/- 575 kcal (8493 +/- 2407 kJ) yet only consumed 1528 +/- 343 kcal (6396 +/- 1436 kJ) daily; thus food availability was not restricting intake. A higher proportion of snacks than meals (85 per cent vs. 71 per cent) was consumed. Children requested foods frequently (x = 9.2 +/- 4.3) and 76 per cent of requests were fulfilled. Neither amount of accessible food nor amount consumed differed by age, gender, or socioeconomic status. The importance of the child's role in determining food intake, and of snacking to overall food consumption, was demonstrated.     

子宫内膜增生性病变与子宫内膜癌的超声诊断价值

目的:探讨子宫内膜增生性病变与子宫内膜癌的超声鉴别诊断及内膜癌肌浸程度的估价.方法:采用术前B超、术后大体标本观察测量,对123例子宫内膜病变患者的声像图资料进行分析并与手术后病理结果对照.结果:①子宫内膜病变者子宫三径之和平均值均大于正常值;②58.6%的子宫内膜增生过长病变患者内膜形态以条形、梭形和正常形态回声;35%的Ⅱ期以上子宫内膜癌患者内膜回声以积液为主兼有其它图像类型;③大于50岁患者不同病理类型病变的子宫内膜平均厚度均超过其正常内膜厚度值,但无明显的规律性.小于50岁的患者内膜增厚主要以子宫内膜增生过长病变为主占48%;④通过超声测量子宫内膜厚度判断子宫内膜癌浅肌层和深肌层浸润符合率均为71.4%.结论:超声检查对判断子宫内膜病变病理类型有一定帮助,内膜厚度、内膜形态、回声特点、及内膜与肌层间的关系等,仅提示病变存在的可能性,要鉴别病变的良恶性、肌层浸润深度,须根据上述回声特点进行综合分析.     

Acetazolamide-responsive myotonia congenita

We have studied 14 patients from a kindred with an autosomal dominant form of myotonia, with features differing from most cases of autosomal dominant or recessive myotonia congenita. All patients had painful muscle stiffness that was provoked by fasting and oral potassium administration and was relieved by carbohydrate-containing foods. Muscle biopsies showed the presence of type 1, 2A, and 2B fibers, as opposed to the absence of type 2B fibers seen in some patients with myotonia congenita. Acetazolamide was dramatically effective in alleviating myotonia in all patients and was more effective than other antimyotonic agents.