Proton beam irradiation for treatment of experimental human retinoblastoma.

Proton beam irradiation was used to treat human retinoblastoma (Y-79 cell line) grown subcutaneously in the athymic "nude" mouse. Thirty-four tumors were included in the experimental groups, of which twenty-three were irradiated and eleven served as controls. Tumors were irradiated with protons produced at the 160 megavolts Harvard cyclotron. The dose delivered to the tumor ranged from 7.5 to 27.5 proton gray in a single treatment, and 25.0 proton gray delivered in two fractions separated by 24 hours. Reduction of tumor growth was significantly greater than controls (p less than 0.001) with treatment doses greater than or equal to 17.5 proton gray. Histologic examination revealed a marked decrease of mitotic activity in all specimens examined 48 hours after treatment at these higher doses. Total regression without evidence of remaining malignant cells was noted in three tumors treated at 17.5 proton gray or above. Our results indicate that human retinoblastoma in a murine host, with a tumor mass similar to that seen in a clinical setting, is sensitive to radiation by high energy protons.     

Alkaline phosphatase and peptidase levels in invertebrate cartilage

Summary Cartilage is encountered in the skeletons of many advanced invertebrates, yet it never calcifies or is replaced by bone. In an attempt to account for the absence of bone in invertebrates, we tested a hypothesis proposing that absence or inadequate quantities of several enzymes associated with vertebrate osteogenesis may underlie the failure of the invertebrates to evolve bone. The enzymes examined were alkaline phosphatase, alanyl -naphthylamidase, and neutral protease. Their activities were measured in the gill cartilage of the Atlantic horseshoe crab, Limulus polyphemus, and the odontophore cartilage of the marine whelk, Busycon canaliculatum. Animals were collected from the Cape Cod area. Samples of cartilage of Limulus perichondrium, various nonskeletal tissues, and neonatal rat calvaria, the latter as a reference standard, were homogenized in 0.1 M phosphate buffer (pH 7.1) and analyzed for protein content and the above-mentioned enzyme activities. Alkaline phosphatase specific activity was readily detected in most tissues except the invertebrate cartilage specimens in which it was present only at near-trace levels. Naphthylamidase and protease activities were present in all tissues. In a single experiment, higher phosphatase values were recorded for Limulus cartilage retaining perichondrium, but in a subsequent trial assaying cartilage retaining perichondrium, denuded cartilage, and isolated perichondrium separately, it was demonstrated that phosphatase activity resided primarily within the perichondrium. Exposure of thick cryostat sections to p-nitrophenyl phosphate confirmed the suspicion that alkaline phosphatase activity was present principally in the perichondrium. In view of the strong association between alkaline phosphatase and vertebrate cartilage mineralization it is proposed that extremely low levels of this enzyme may contribute to the failure of invertebrate cartilage to be replaced by bone.     

Hepatic abscess

Hepatic abscess—amebic or pyogenic—can be diagnosed with great accuracy by either ultrasonography or computed tomographic (CT) scanning. Ultrasound is the modality of choice and will detect almost 100% of abscesses. Confirmation of a diagnosis of amebic liver abscess is made by the indirect hemagglutination test that should be positive in almost 100% of cases. Cultures of pus from the abscess and from the blood must be obtained in cases of pyogenic liver abscess. A positive culture of pus from the abscess has been achieved in 90% of cases. Ultrasound or CT guidance is utilized in aspiration of a hepatic abscess. In the treatment of an amebic liver abscess, metronidazole is the amebicide of choice. Open drainage is contraindicated. For cases that fail to respond to therapy with amebicides, closed drainage guided by CT or ultrasound is performed. Secondary bacterial infection of an amebic liver abscess is an extremely rare event. The identification and determination of the antibiotic sensitivity of organisms responsible for pyogenic liver abscess is a crucially important step. Unless a celiotomy is necessary to correct an intraabdominal process or the abscess is extremely large, the initial treatment of pyogenic liver abscess is a 2 week course of appropriate antibiotics followed by a 1 month course of oral antibiotics. The majority of pyogenic liver abscesses will respond to such treatment. If drainage of a pyogenic abscess is required, the preferable technique is with a percutaneous CT- or ultrasound-directed catheter. Open surgical drainage should be reserved for those cases in which a celiotomy is required for other purposes or for the patient who has failed a course of appropriate antibiotic therapy and closed percutaneous drainage is not feasible. The mortality for treatment of amebic liver abscess should be approximately zero and for pyogenic liver abscess should be less than 10%.

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Resumen El absceso hepático—amibiano o piogénico—puede ser diagnositicado con gran precisión mediante la ultrasonografía (US) o la tomografía computadorizada (TC). La ultrasonografía es la modalidad de escogencia; détecta casí el 100% de los abscesos. La confirmación del diagnóstico de absceso amibiano del hígado se hace por la prueba de hemaglutinación indirecta, la cual debe resultar positiva en prácticamente el 100% de los casos. Cultivos del pus y de la sangre deben ser realizados en los pacientes con abscesos piógenos. Se logran cultivos positivos del pus del absceso en 90% de los casos. Se utiliza la guía ultrasonográfica o de tomografía computadorizada para la aspiración del absceso.El metronidazol es el agente amebicida de preferencia en el tratamiento del absceso amibiano del hígado. El drenaje abierto está contraindicado. En los casos en que falla la terapia con amibicidos, se realiza el drenaje cerrado guiado por US o por TC. La infección secundaria de un absceso amibiano del hígado es un fenómeno extraordinariamente raro.La identificatión y determinatión de la sensibilidad antibiótica de los microorganismos responsables del absceso piógeno representa un paso crucial en su manejo. A menos que se haga necesario realizar una laparotomía para la correción del algún proceso intraabdominal o porque el absceso es excesivamente grande, el tratamiento inicial del absceso piógeno es un ciclo de antibióticos propiados de 2 semanas, seguidos de tratamiento con antibióticos orales por un mes. La mayoría de los abscesos piógenos del hígado responde a este tipo de tratamiento. Si se requiere drenaje de un absceso piógeno, la técnica de preferencia es la punción percutánea por medio de un catéter guiado por US o TC. El drenaje quirúrgico abierto debe reservarse para aquellos casos en que la laparatomía es necesaria por razones diferentes o en que hay falla en la respuesta a un ciclo de terapia antibiótica adecuada y el drenaje percutáneo no es factible.La mortalidad en el manejo del absceso amibiano del hígado debe ser nula, y para el absceso piógeno de menos de 10%.

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Résumé L'abcès hépatique amibien ou à pyogènes peut être diagnostiqué avec une grande précision soit par l'échographie, soit par la tomodensitométrie. L'échographie est la méthode de choix et détecte presque 100% des abcès. On obtient la confirmation du diagnostic d'abcès amibien par le test d'hémagglutination indirecte qui est positive dans presque 100% des cas. On doit faire des cultures de pus provenan de l'abcès et des hémocultures en cas d'abcès à pyogènes du foie. Ces cultures ont été positives dans 90% des cas. L'échographie et la tomodensitométrie aident à guider le drainage de abcès.Dans le traitement de l'abcès amibien du foie, le métronidazole est l'amibicide de choix. Le drainage à ciel ouvert est contreindiqué. Pour les cas qui ne répondent pas aux amibicides, un drainage percutané guidé par la tomodensitométrie ou l'échographie est indiqué. La surinfection d'un abcès amibien du foie est extrêmement rare.L'identification et la détermination de la sensibilité aux antibiotiques des organismes responsables de l'abcès à pyogènes est une étape extrêmement importante. A moins qu'une laparotomie soit nécessaire pour traiter une infection intraabdominale associée ou que le volume de l'abcès soit extrêmement important, le traitement initial d'un abcès à pyogènes comprend 2 semaines d'antibiotiques adaptés par voie générale suivies d'un mois d'antibiotiques par voie orale. La plupart des abcès à pyogènes répondront bien à ce traitement. Si le drainage d'un abcès à pyogènes s'avère nécessaire, la meilleure technique est percutanée avec un cathéter inséré sous contrôle tomodensitométrique ou échographique. On réservera le drainage chirurgical à ciel ouvert aux cas où une laparotomie est nécessaire pour d'autres raisons et où le malade n'a pas répondu à l'antibiothérapie adaptée et chez qui le drainage percutané est impossible à faire.La mortalité de l'abcès amibien traité devrait approcher 0% et atteindre pour l'abcès à pyogènes moins de 10%.

     

DNA repair in human bronchial epithelial cells

The purpose of this investigation was to compare the responseof human cell types (bronchial epithelial cells and fibroblastsand skin fibroblasts) to various DNA damaging agents. Repairof DNA single strand breaks (SSB) induced by 5 krads of X-raywas similar for all cell types; 90% of the DNA SSB were rejoinedwithin one hour. During excision repair of DNA damage from u.v.-radiation,the frequencies of DNA SSB as estimated by the alkaline elutiontechnique, were similar in all cell types. Repair replicationas measured by BND cellulose chromatography was also similarin epithelial and fibroblastic cells after u.v.-irradiation.Similar levels of SSB were also observed in epithelial and fibroblasticcells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene;benzo[a]pyrene diol epoxidle (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine.Significant repair replication of BPDE-induced DNA damage wasdetected in both bronchial epithelial and fibroblastic cells,although the level in fibroblasts was 40% of that in epithelialcells. The pulmonary carcinogen asbestos did not damage DNA.DNA-protein crosslinks induced by formaldehyde were rapidlyremoved in bronchial cells. Further, epithelial and fibroblasticcells, which were incubated with formaldehyde and the polymeraseinhibitor combination of cytosine arabinoside and hydroxyurea,accumulated DNA SSB at approximately equal frequencies. Theseresults should provide a useful background for further investigationsof the response of human bronchial cells to various DNA damagingagents.     

Experimental measurement of impulse response and noise for an emission computed tomography system

Experimental studies have been made of the impulse response and noise characteristics of a tomographic system using a gamma camera. Fourier transform, deconvolution and iterative methods have been used with a CDC 6600 computer to reconstruct images from data obtained for various experimental arrangements of sources in a cylindrical phantom. It is shown that with an appropriate attenuation correction the impulse response in the reconstruction is substantially constant, independent of the position of the source in the phantom and that the reconstruction technique used is of secondary importance.The resolution obtained for the impulse response and the relative noise level throughout the non image part of the reconstructions is shown for different experimental situations.The measured variance in the reconstruction of an extended uniform activity source was found to be somewhat below the theoretical value except at high count densities (above 1,000 counts per image element) where the limit of accuracy of the reconstruction is shown to be imposed by the variation in the camera sensitivity over the field of view.     

The extracellular matrix molecule tenascin-R and its HNK-1 carbohydrate modulate perisomatic inhibition and long-term potentiation in the CA1 region of the hippocampus

Perisomatic inhibition of pyramidal cells regulates efferent signalling from the hippocampus. The striking presence of HNK-1, a carbohydrate expressed by neural adhesion molecules, on perisomatic interneurons and around somata of CA1 pyramidal neurons led us to apply monoclonal HNK-1 antibodies to acute murine hippocampal slices. Injection of these antibodies decreased GABAA receptor-mediated perisomatic inhibitory postsynaptic currents (pIPSCs) but did not affect dendritic IPSCs or excitatory postsynaptic currents. The decrease in the mean amplitude of evoked pIPSCs by HNK-1 antibodies was accompanied by an increase in the coefficient of variation of pIPSC amplitude, number of failures and changes in frequency but not amplitude of miniature IPSCs, suggesting that HNK-1 antibodies reduced efficacy of evoked GABA release. HNK-1 antibodies did not affect pIPSCs in knock-out mice deficient in the extracellular matrix molecule tenascin-R which carries the HNK-1 carbohydrate as analysed by immunoblotting in synaptosomal fractions prepared from the CA1 region of the hippocampus. For control, HNK-1 antibody was applied to acute sections of mice deficient in the neural cell adhesion molecule NCAM, another potential carrier of HNK-1, and resulted in decrease of pIPSCs as observed in wild-type mice. Reduction in perisomatic inhibition is expected to promote induction of long-term potentiation (LTP) by increasing the level of depolarization during theta-burst stimulation. Indeed, LTP was increased by HNK-1 antibody applied before stimulation. Moreover, LTP was reduced by an HNK-1 peptide mimic, but not control peptide. These results provide first evidence that tenascin-R and its associated HNK-1 carbohydrate modulate perisomatic inhibition and synaptic plasticity in the hippocampus.     

电针对去势大鼠外周血淋巴细胞雌激素受体影响的研究

目的　从生殖内分泌 -免疫网络角度探讨电针治疗围绝经期综合征的作用机制。方法　以去势大鼠为实验对象 ,取双侧三阴交、太溪、后三里穴 ,采用放射免疫法和流式细胞分析技术 ,观察电针治疗对去势大鼠血清雌激素 (E2 )、促黄体生成素 (LH)、促卵泡生成素(FSH)及外周血淋巴细胞内雌激素受体 (ER)水平的影响。结果　电针可使去势大鼠血清E2 明显升高 ,LH及FSH明显下降 ,外周血淋巴细胞内ER明显升高 ,与造模组比较有显著性差异。结论　电针可明显改善去势大鼠的生殖内分泌功能 ,并能调节免疫细胞的雌激素受体表达。