Involution and regeneration of the thymus in mice,induced by bacterial endotoxin and studied by quantitative histology and electron microscopy

Lipopolysaccharide from S. typhosa, injected intraperitoneally into Swiss albino mice, produced acute thymic involution—maximal at 48 hours after injection, followed by regeneration that was complete within 5 to 7 days. Using tissues fixed and embedded for electron microscopy, cell counts were made with the light microscope and cytological details were examined in electron micrographs. The cellular events of involution and regeneration were similar to those produced by injection of adrenal glucocorticoids, but it remains to be determined whether or not endotoxin acts on the thymus by inciting adrenal cortical secretion. Involution appeared to be the result of both the death of small lymphocytes and reduced lymphopoiesis in the thymus. Within 48 hours, macrophages had cleared away the cellular debris and medullary epithelial cells showed signs of hypertrophy and increased putative secretory activity. Subsequently, large lymphocytes proliferated at an accelerated rate in the subcapsular cortex, the cortex grew in width by the accumulation of small lymphocytes, and regeneration ceased when the thymus had reached its former size. These observations provide circumstantial evidence for the hypothesis that in regeneration, medullary epithelial cells increase their production of a lymphopoietic hormone which stimulates mitotic proliferaton of cortical lymphocytes.     

Comparative study of the Jordan left-right reversal test, the reversals frequency test, and teachers' observations

The intertest pass/fail reliability of the Jordan left-right reversal test (JRT) and reversals frequency test (RFT) was compared on 510 "regular classroom" and 126 "learning handicapped" children. Children were divided into two age groups, 5 to 8 years and 9 to 13 years. Teachers completed a questionnaire assessing whether they felt a reversal problem existed. Statistical analysis showed low to moderate agreement between the pass/fail rate of the two tests (p less than 0.001) for both age groups of normal children; however, no statistical agreement was found for either age group of learning handicapped children. There was only very low agreement between the teacher's assessment of reversals and the pass/fail rates for both age groups of normals and the 9- to 13-year-old learning handicapped group. No agreement was found for the 5- to 8-year-old learning handicapped group. The effect of test design and recommendations for the clinical investigation of reversals are discussed.     

What do Irish women know about cervical screening?

In anticipation of the launch of the national cervical screening programme, a questionnaire was distributed amongst 200 women on the maternity wards of the Coombe Women's Hospital. The questionnaires revealed that 24% of the women surveyed never had a smear test and 50% of these did not know how the test was performed. The majority of all women did not know what a smear test showed and 26% did not know the meaning of an abnormal smear. Irish women's knowledge of cervical screening is limited, and the success of the proposed programme will depend on an improvement in public information and education.     

Accumulation of exogenous polyamines in gerbil brain after ischemia

Regionally selective delayed neuronal degeneration is a characteristic sequel of cerebral ischemia. Recent evidence indicates that changes in brain polyamine metabolism may be critical for nerve cell survival after ischemia. Within hours after ischemia, intracellular putrescine levels are greatly increased and remain elevated for days, whereas only minor changes are noted in the levels of the polyamines spermine and spermidine. In contrast, the extracellular levels of all polyamines are low after ischemia. Injections of polyamines following ischemia, however, can protect neurons in the gerbil brain from delayed cell death, with spermine being the most potent of the polyamines. In the present study, therefore, we sought to determine if increased polyamine uptake occurs in the brain after ischemia. In the hippocampal slice preparation, temperature-dependent uptake was unique for spermine, but not for spermidine or putrescine. Uptake of [¹⁴C]spermine was transiently increased after ischemia, peaking at 150% of control by 12–13 h and subsiding by 24 h. Intravenous injections of [³H]spermidine resulted in a postischemic accumulation of this polyamine throughout the forebrain parenchyma. We conclude that:

1. Active cellular uptake of spermine is transiently increased early after ischemia;
2. A nonspecific accumulation of exogenous polyamines occurs early after ischemia probably owing to a compromised blood-brain barrier, and
3. The findings indicate that exogenous polyamines can exert their effect directly in the brain after ischemia.

     

Phase I/II investigation of paclitaxel, ifosfamide and carboplatin for advanced non-small-cell lung cancer.

BACKGROUND: The aim of this study was to evaluate feasibility and tolerability of the three-drug combination of paclitaxel, ifosfamide and carboplatin (TIC) in patients with advanced non-small-cell lung cancer. The specific objectives of the study were: (i) to define the dose-limiting toxicities (DLTs) and the maximum-tolerated dose of ifosfamide administered as part of the combination; and (ii) to determine the overall response rate and overall survival of patients treated with this regimen. PATIENTS AND METHODS: Patients with untreated, stage IIIB (pleural effusion) or stage IV non-small-cell lung cancer were enrolled in one of three cohorts. Patients received paclitaxel 200 mg/m(2) as a 1-h infusion on day 1 with carboplatin at an area under the concentration-time curve (AUC) of 6 mg.min/ml on day 2. For dose level I, ifosfamide was administered at a dose of 2 g/m(2) on days 1 and 2. For dose levels II and III, the dose of ifosfamide was decreased to 1.5 g/m(2) on days 1 and 2 and the dose of carboplatin was decreased to AUC 5 mg.ml/min. Therapy for dose levels I and III included filgrastim support (5 micro g/kg/day), which was initiated on day 3 and continued until after day 11 or until an absolute neutrophil count >10 000/ micro l. Treatment cycles were repeated every 21 days. Once the phase II dose was established, a full cohort of patients received therapy at this dose level to examine further the regimen's activity and tolerability. RESULTS: Neutropenia was the DLT encountered for dose levels I and II. No DLT was encountered in the initial six patients treated at dose level III, and therefore this dose level was declared the recommended phase II dose. A total of 49 patients were treated at the recommended phase II dose. The predominant non-hematological toxicity encountered with this triplet regimen was cumulative peripheral neuropathy. Of the 65 eligible patients enrolled in this study, 17 (26%) responded. There were 15 patients with partial responses (23%), two with regression, and 26 with stabilization of disease (40%). Median progression-free and overall survival were 4.8 and 9.4 months, respectively. CONCLUSIONS: The combination TIC is well-tolerated. This triplet regimen produced response and survival rates in advanced non-small-cell lung cancer similar to those of other current combination chemotherapy regimens.     

Synthesis,SAR studies,and insecticidal activities of certain N-heterocycles derived from 3-((2-chloroquinolin-3-yl)methylene)-5-phenylfuran-2(3H)-one against Culex pipiens L. larvae

An acid hydrazide derivative was synthesized and transformed into a variety of valuable N-heterocycles such as pyridazinone, oxadiazole, triazolopyridazinone, and triazole derivatives via reactions with certain carbon electrophiles such as 4-methoxybenzaldehyde, indole-3-carbaldehyde, pentan-2,4-dione, and carbon disulfide. The chemical structures of all prepared compounds were verified via their analytical and spectroscopic data. The insecticidal activity of the N-heterocycles was evaluated against field and lab strains of the third larval instar of Culex pipiens. All tested compounds exhibited higher larvicidal activity against the lab strains compared to the field strains, with dissimilar ratios. The obtained results demonstrate that the high toxicity achieved by oxadiazole followed the order of furanone, pyridazinone and hydrazide, with lower LC₅₀ values of the hydrazone and N-acetylpyridazinone derivatives compared to that of imidacloprid. Interestingly, these compounds are promising agents for insect pest control, especially since they are insoluble in water and can overcome the disadvantages of neonicotinoid applications in pest management programs.

A new series of N-heterocycles including pyridazinone, oxadiazole, triazolopyridazinone, and triazole derivatives were synthesized from the acid hydrazide via its reaction with certain carbon electrophiles.     

Antibodies to certain arboviruses in humans from a flooded village in Egypt

A study was carried out on 180 sera collected from inhabitants of a seepage flooded village (Begiram) in a Nile Delta governorate in Egypt. The aim of the study was to monitor the prevalence of certain arboviruses; some of them are known to be endemic in Egypt. Sera were screened by ELISA except for the HTN by IF, and the results indicated that WN and SFS exhibited the highest prevalence 45.5% followed by SFN (21%). These 3 viruses are known to be endemic in Egypt. The high prevalence of W.N. and S.F.S viruses in Begiram village in comparison to lower rates detected in sera from nearby Sharkqiya governorate collected almost at the same time may reflect the adverse effect of the environmental change in the flooded village. RNF virus which caused a major epidemic in Egypt in 1977 and continued to be circulating until 1980, its antibodies were detected only in those above 20 years of age with a prevalence rate of 5%. Antibodies against two tick borne viruses viz QRF and CCHF were also detected with low prevalence rate 2.75% and 1.1% respectively; also antibodies to the rodent-borne HTN virus were detected with prevalence rate 1.1%. Antibodies to mosquito borne SIN and BAT viruses were not detected in the tested sera.     

The counterbend phenomenon in flagellar axonemes and cross-linked filament bundles

Recent observations of flagellar counterbend in sea urchin sperm show that the mechanical induction of curvature in one part of a passive flagellum induces a compensatory countercurvature elsewhere. This apparent paradoxical effect cannot be explained using the standard elastic rod theory of Euler and Bernoulli, or even the more general Cosserat theory of rods. Here, we develop a geometrically exact mechanical model to describe the statics of microtubule bundles that is capable of predicting the curvature reversal events observed in eukaryotic flagella. This is achieved by allowing the interaction of deformations in different material directions, by accounting not only for structural bending, but also for the elastic forces originating from the internal cross-linking mechanics. Large-amplitude static configurations can be described analytically, and an excellent match between the model and the observed counterbend deformation was found. This allowed a simultaneous estimation of multiple sperm flagellum material parameters, namely the cross-linking sliding resistance, the bending stiffness, and the sperm head junction compliance ratio. We further show that small variations on the empirical conditions may induce discrepancies for the evaluation of the flagellar material quantities, so that caution is required when interpreting experiments. Finally, our analysis demonstrates that the counterbend emerges as a fundamental property of sliding resistance in cross-linked filamentous polymer bundles, which also suggests that cross-linking proteins may contribute to the regulation of the flagellar waveform in swimming sperm via counterbend mechanics.