Shigella Infection of Henle Intestinal Epithelial Cells: Role of the Host Cell

The process of Henle 407 embryonic intestinal epithelial cell infection by Shigella flexneri 2a M42-43 was studied in an in vitro model system. The role of the Henle cell was assessed. It was established that entry of S. flexneri into cells was suppressed by reagents which inhibit uptake of particles by phagocytic cells. The compounds tested included cytochalasin B, dibutyryl-cyclic adenosine monophosphate, choleragen (Vibrio cholera enterotoxin), iodoacetate, and dinitrophenol. Cytochalasin B inhibited infection at concentrations of 1.0 mug/ml or greater. Dibutyryl-cyclic adenosine monophosphate at concentrations of 1 mM and choleragen at 0.1 mug/ml caused significant suppression of infection. Iodoacetate or dinitrophenol, at 0.1 mM concentrations, inhibited internalization of virulent shigellae, and a combination of these compounds inhibited infection at 0.01 mM concentrations. Preincubation of Henle cell monolayers with the combination of iodoacetate and dinitrophenol (0.05 mM) also inhibited infection markedly. The data suggest that infection of epithelial cells by S. flexneri in vitro is accomplished by an endocytic process induced by virulent bacteria. The process appears to be similar to uptake of particles by phagocytic cells. Ultrastructural analysis by transmission electron microscopy provided corroborative evidence of phagocytosis of shigellae by Henle cells in that intracellular bacteria were often observed within membrane-limiting vacuoles resembling phagosomes.     

Examination of the Factor Structure and Correlates of the Perceived Military Healthcare Stressors Scale

The current study evaluated the factor structure, reliability estimates, correlates, and predictive utility of the Perceived Military Healthcare Stressor Scale (PMHSS) in a sample of active duty military medical personnel (N = 1,131) deployed to Joint Base Balad in Iraq. The sample was composed of an approximately even split of male (51.2%) and female (48.8%) participants who ranged in age from 18 to 60 years. The PMHSS is a 21‐item measure that was designed to assess the impact of specific medical stressors that military healthcare providers may encounter while deployed. An exploratory factor analysis of the PMHSS revealed the presence of two distinct factors: trainable and futility stressors. Confirmatory factor analysis showed that a bifactor model best represented the data, with all items loading higher on the general factor relative to their specific subscale factors. Evidence of partial scalar invariance by gender was found. The PMHSS was significantly correlated with several convergent measures, including assessments of posttraumatic stress disorder (PTSD), depression severity, distress due to both combat exposure and general deployment‐related concerns, and positive affect, rs = .30–.59. PMHSS scores were more strongly correlated with PTSD and depression in women than in men, and they provided incremental validity in predicting convergent measures over and above other related constructs. Healthcare–specific stressors are an understudied area, and this study provides new insights into how deployment‐related caregiving stress may impact deployed military medical personnel independently of the impact of combat experiences.     

Antenatal differentiation of the human intervertebral disc

Summary To study the antenatal differentiation of the human intervertebral disc, the columns of forty eight embryos and fetuses were examined histologically. The primitive disc is composed of two structures: the notochord which shows a progressive expansion into the disc, and the fibrocartilaginous perinotochordal disc. No histological sign of interaction between notochordal and perinotochordal cells, which may explain the notochordal expansion into the discs, was seen. On the other hand, the notochordal intervention in the cartilaginous differentiation of the inner zone is probable.

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Différenciation anténatale du disque intervertébral humain

Résumé Cette étude de la différenciation anténatale du disque intervertébral humain repose sur l'examen de coupes histologiques de quarante huit colonnes vertébrales d'embryons et de foetus. Le disque primitif est composé de deux structures : la notochorde, qui présente une expansion progressive de son diamètre au sein du disque, et le disque périnotochordal, d'abord mésenchymateux puis fibrocartilagineux. Il n'a pas été mis en évidence de signe histologique témoignant d'une interaction entre les cellules notochordales et les cellules périnotochordales qui puisse expliquer l'expansion de la notochorde au sein des disques. Le rôle de la notochorde dans la différenciation cartilagineuse de la zone centrale est par contre probable.

     

Variable-ratio schedules of timeout from avoidance: effects of anxiolytic drugs

Concurrent performances in rats were studied under conditions where responses on one lever postponed shock on an unsignaled avoidance schedule, and responses on another level produced periods of signaled timeout from avoidance on a variable-ratio schedule. This procedure resulted in relatively high rates of responding on the timeout lever, and provided a baseline which permitted simultaneous evaluation of drug effects on two different types of negative reinforcement (shock postponement vs timeout). Chlordiazepoxide and ethanol selectively increased responding on the timeout lever at low doses, while higher doses decreased responding on both levers. Two 5-HT(1A) agonists, buspirone and 8-OH-DPAT, had different effects. Buspirone decreased responding across all effective doses, but 8-OH-DPAT increased responding on both the timeout and avoidance levers, with greater increases noted in responding maintained by timeout. These results replicate and extend previous findings, and support the notion that traditional anxiolytic drugs like chlordiazepoxide and ethanol may increase the reinforcing properties of escape from an avoidance schedule. Differences between the behavioral effects of buspirone and 8-OH-DPAT may reflect differential activity at the 5-HT(1A) receptor or the dopaminergic properties of buspirone.     

Find your department's rung on the ladder of sophistication

How highly evolved is your materials management department? Those on the lower rungs of the evolutionary ladder have passive, non-strategic roles and simply react to input from other departments; those that have evolved to higher levels are more active and involved in the organization's strategic decisions.     

温血心停跳液与冷晶体心停跳液对狗心率变异性的影响

为探讨体外循环（ＣＰＢ）导致心脏植物神经系统（ＣＡＳ）损伤的机理,了解温血心停跳液能否防止ＣＰＢ后心率变异性（ＨＲＶ）的降低,采用对照方法观察了温血心停跳液与冷晶体心停跳液对狗ＨＲＶ的影响。结果显示：ＣＰＢ后温血心停跳液组（ＷＢ组）和冷晶体心停跳液组（ＣＣ组）的全频谱（ＴＰ）、低频（ＬＦ）和高频（ＨＦ）均较术前明显降低（Ｐ＜０．０５）,而且ＣＣ组比ＷＢ组降低更明显（Ｐ＜０．０５）,但ＬＦ／ＨＦ在组内及组间均无明显变化（Ｐ＞０．０５）。ＣＰＢ后２４小时平均心率（ＭＨＲ）明显增加（Ｐ＜０．０５）,且ＣＣ组高于ＷＢ组（Ｐ＜０．０５）。本研究表明：采用温血心停跳液或冷晶体心停跳液的ＣＰＢ不会干扰ＣＡＳ平衡,但均能使ＨＲＶ降低,温血心停跳液不能防止ＨＲＶ损害。     

Phase I study of an engineered aglycosylated humanized CD3 antibody in renal transplant rejection

BACKGROUND: The potential therapeutic benefits of CD3 monoclonal antibodies, such as OKT3, have been limited by their immunogenicity and their propensity to activate a severe cytokine release syndrome. This has constrained the clinical use of OKT3 to the treatment of acute rejection episodes of organ allografts. METHODS: We have humanized a rat CD3 antibody and created a single amino acid substitution in position 297 of the IgG1 heavy chain to prevent glycosylation and, consequently, binding of the therapeutic antibody to Fc receptors and to complement. This antibody has been given as first line antirejection therapy in nine kidney transplant recipients with biopsy-proven acute rejection episodes. RESULTS: None of the patients demonstrated any antiglobulin response nor any significant cytokine release syndrome. Seven of the nine showed evidence of resolution of their rejection, although some patients experienced re-rejection. CONCLUSIONS: These findings suggest that CD3 antibodies can be engineered to lose their toxicity while retaining their potency as immunosuppressants. Nonactivating humanized CD3 monoclonal antibodies now merit further investigation in the management of transplant patients and in therapy of autoimmune diseases.     

Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients

BACKGROUND: Campath 1H is a depleting, humanized anti-CD52 monoclonal antibody that has now been used in 31 renal allograft recipients. The results have been very encouraging and are presented herein. METHODS: Campath 1H was administered, intravenously, in a dose of 20 mg, on day 0 and day 1 after renal transplant. Low-dose cyclosporine (Neoral) was then initiated at 72 hr after transplant. These patients were maintained on low-dose monotherapy with cyclosporine. RESULTS: At present, the mean follow-up is 21 months (range: 15-28 months). All but one patient are alive and 29 have intact functioning grafts. There have been six separate episodes of steroid-responsive rejection. One patient has had a recurrence of her original disease. Two patients have suffered from opportunistic infections, which responded to therapy. One patient has died secondary to ischemic cardiac failure. CONCLUSIONS: Campath 1H has resulted in acceptable outcomes in this group of renal allograft recipients. This novel therapy is of equal efficacy compared to conventional triple therapy, but allows the patient to be steroid-free and to be maintained on very-low-dose immunosuppressive monotherapy.