Treatment of carcinoma in situ of the bladder with BCG

Summary Although carcinoma in situ conveys the idea of an early neoplasm, such lesions in the bladder mucosa commonly exhibit a very aggressive behavior and carry a grave prognosis. Seven patients with in situ carcinoma of the bladder have been treated with intravesical and systemic administration of Bacillus Calmette-Guérin. Elimination of tumor was documented by endoscopy, histology and cytology in five patients. These five patients have remained tumor-free for periods ranging between 12 and 33 months (mean: 22.6). This preliminary study indicates that regional and systemic immunotherapy is an alternative worth additional investigation in patients with carcinoma in situ of the bladder.     

In vivo binding of 2,3,6,2′,3′,6′-hexachlorobiphenyl and 2,4,5,2′,4′,5′-hexachlorobiphenyl to mouse liver macromolecules

The role of metabolic activation in the binding of polychlorinated biphenyls (PCBs) to cellular macromolecules was investigated in vivo by comparing the relative binding of 2,4,5,2′,4′,5′-[U-¹⁴C]hexachlorobiphenyl (2,4,5), a slowly metabolized PCB, with that of 2,3,6,2′,3′,6′-[U-¹⁴C]hexachlorobiphenyl (2,3,6), a rapidly metabolized PCB, and the appropriate controls. Each hexachlorobiphenyl was administered to mice, orally for 5 days (7.28 mg/kg/day). Following the dosing schedule, animals were killed at 1, 5 and 8 days. The concentration of each PCB was determined in liver, muscle and kidney and in purified macromolecules isolated from those tissues. The concentration of 2,4,5 was consistently higher than the concentration of 2,3,6 in all tissues studied. However, the amount of 2,3,6 bound to the purified macromolecules was consistently at least one order of magnitude greater than that of 2,4,5. The greatest binding was observed in RNA followed by protein and DNA, respectively. The purity of the macromolecules and the presence of PCB-derived radioactivity at the monomer level were confirmed. This is the first report of ¹⁴C-labeled PCB being bound to purified RNA, DNA, and proteins isolated from the tissues of animals treated in vivo. The binding is thought to be covalent and to be the result of metabolic activation.     

The capybara (Hydrochoerus hydrochaeris) as a reservoir host for Trypanosoma evansi

Discovery of two ill horses and three dogs naturally infected with Trypanosoma evansi near an experimental station in the Eastern Plains of Colombia led to a search for reservoir hosts of the parasite. Infection was detected in 8/33 healthy capybaras (Hydrochoerus hydrochaeris), none of the remaining 14 horses, and none of 32 Zebu cattle (Bos indicus), 18 paca (Cuniculus paca) and 20 spiny rats (Proechimys sp.). Contrary to common opinion, the results indicated a carrier state in the capybara. Diagnosis was based on morphology, behaviour in albino rats, and pathogenicity and host range in domestic animals.     

States of myosin subfragment-1 studied by catalyzed ascorbate reduction of bound spin label.

The second-order rate constant, k, whereby ascorbate reduces spin label, N-(1-oxyl-2, 2,6,6-tetramethyl-4-piperidyl) iodoacetamide, bound to the fast-reacting (SH₁) thiol groups of heavy meromyosin (HMM) has been compared with the k whereby ascorbate reduces free spin label in the same solvent. It is clear that the k of protein-bound spin label is primarily determined by conditions “on-board” subfragment-1 (S-1), rather than by properties of the solvent. First, in saturating [STP] the k of HMM-bound spin label was much greater than the k of free spin label, and both k's were independent of [KCl], from 0.05 to 1 m. Second, in the absence of ATP, or even in the presence of ADP, the k of HMM-bound spin label was less than the k of free spin label at l m KCl, and much more in a 0.05 m KCl. The organized structure of S-1 is required for observing the change of k with ATP, because the change of k disappeared on denaturing HMM with either guanidine hydrochloride or urea.Measuring k can be a “probe” to specify HMM states. However, the parameter, k, is conceptually dissimilar to measuring peak heights on an EPR spectrum. Experimentally we have observed that when [KCl] is increased, while [MgATP] = 0, spectral peak height is constant, but k varies remarkably. At no [KCl] did excess F-actin affect k. Quantitative examination of metal contamination (e.g., Cu, Fe) in HMM showed that changes in the k of HMM-bound spin label cannot arise from changes in proximity to contaminating metal redox catalysts bound to HMM.An intramolecular participant in the reaction of ascorbate with bound nitroxyl half inhibits the Ca²⁺-ATPase of spin labeled HMM, so signal annihilation and ATPase activity are closely correlated in time. The rate of signal annihilation is unaffected by prior reaction of the “SH₂” thiols with N-ethylmaleimide.     

Defining the "fast-reacting" thiols of myosin by reaction with 1, 5 IAEDANS.

The specificity of the fluorescent reagent N-iodoacetyl-N-(5-sulfo-1-naphthyl)ethylenediamine (1,5 IAEDANS) for a specific thiol group of myosin has been characterized by a comparison with iodoacetamide (IAA) and by observing maximal enhancement of the Ca²⁺-ATPase activity and inhibition of the K⁺-EDTA-ATPase activity of myosin. The stoichiometry of the [³H]1,5 IAEDANS bound to myosin indicates the presence of two fast-reacting thiols which correspond to the “SH₁” groups responsible for the catalytic properties of myosin. Moreover, it has been unequivocally demonstrated by gel electrophoresis that the fast-reacting thiol is located on the myosin heavy chain. A single radioactivity-labeled thiol peptide obtained from tryptic digests of myosin labeled with [³H]1,5 IAEDANS or iodo[1-¹⁴C]acetamide indicates strongly that the identical thiol was labeled by both reagents.     

A synaptic model for the kindling effect

In this work we present a model of the kindling effect based on the Hopf bifurcation for a system of ordinary differential equations. The model shows how quantitative changes in the physiological parameters at the microscopic, synaptic scale, produce the afterdischarge which is a macroscopic effect at the neuronal network scale. The presynaptic mechanisms are based on the vesicular hypothesis, or more generally on the quantal theory of synaptic transmission. The postsynaptic processes rely on Granit's law. This model gives a consistent framework which organizes and explains several experimental observations.     

Asynchrony of labyrinthine receptors as a physical factor in motion sickness

Evidence is presented to show that despite their effectiveness in producing motion sickness the actual frequencies and accelerations involved in ship motion are rather low. It is suggested that the disparity is due to the fact that ship motion is such as to cause an asynchrony between signals from the labyrinth and those from other motion receptors.     

Mouse model systems of autism spectrum disorder: Replicability and informatics signature

Phenotyping mouse model systems of human disease has proven to be a difficult task, with frequent poor inter‐ and intra‐laboratory replicability, particularly in behavioral domains such as social and cognitive function. However, establishing robust animal model systems with strong construct validity is of fundamental importance as they are central tools for understanding disease pathophysiology and developing therapeutics. To complete our studies of mouse model systems relevant to autism spectrum disorder (ASD), we present a replication of the main findings from our two published studies of five genetic mouse model systems of ASD. To assess the intra‐laboratory robustness of previous results, we chose the two model systems that showed the greatest phenotypic differences, the Shank3/F and Cntnap2, and repeated assessments of general health, activity and social behavior. We additionally explored all five model systems in the same framework, comparing all results obtained in this three‐yearlong effort using informatics techniques to assess commonalities and differences. Our results showed high intra‐laboratory replicability of results, even for those with effect sizes that were not particularly large, suggesting that discrepancies in the literature may be dependent on subtle but pivotal differences in testing conditions, housing enrichment, or background strains and less so on the variability of the behavioral phenotypes. The overall informatics analysis suggests that in our behavioral assays we can separate the set of tested mouse model system into two main classes that in some aspects lie on opposite ends of the behavioral spectrum, supporting the view that autism is not a unitary concept.     

单孔、两孔及三孔胸腔镜下早期非小细胞肺癌根治术的效果比较研究

目的:通过比较不同胸腔镜手术方式治疗早期非小细胞肺癌根治术术后的相关临床指标,为临床手术方式提供经验。方法:收集我院2017年1月～2019年12月收治的行肺癌根治术的早期非小细胞肺癌病例共100例,分别采用单孔胸腔镜(40例),两孔胸腔镜(32例)及三孔胸腔镜(28例)手术方式,比较三组手术术中及术后的相关指标。结果:单孔胸腔镜组术中出血量、术后引流量明显少于两孔胸腔镜组和三孔胸腔镜组(P0.05),而两孔胸腔镜组明显少于三孔胸腔镜组(P0.05);单孔胸腔镜组术后胸管留置时间和术后住院时间均短于两孔胸腔镜组和三孔胸腔镜组(P0.05),而两孔胸腔镜组明显短于三孔胸腔镜组(P0.05)。三组组内疼痛评分术后24h低于术后12h,术后48h低于术后24h,差异均有统计学意义(P0.05)。三组组间不同时间点疼痛评分比较发现,单孔胸腔镜组疼痛评分低于两孔胸腔镜组和三孔胸腔镜组(P0.05),而两孔胸腔镜组低于三孔胸腔镜组(P0.05)。三组清扫淋巴结数目、淋巴结站数和术后并发症发生率差异均无统计学意义(P0.05)。结论:单孔胸腔镜早期非小细胞肺癌根治术与两孔、三孔胸腔镜手术相比优势明显,且不会显著增加术后并发症,可作为临床首选。