Donor cell leukemia: a critical review

Approximately 40 cases of DCL have been reported in the literature; cases have been reported after allografts from bone marrow, peripheral blood and cord blood. The study of these cases may provide new insights into the mechanisms of leukemogenesis. Some data suggest that the prevalence of this complication has been under-estimated. Most cases of DCL have occurred following transplantation for leukemia, but there have also been cases reported after transplantation for non-malignant conditions. Various mechanisms have been proposed to explain how DCL arise and are briefly discussed. Additional studies are needed to define with more detail both the true prevalence of this complication and its precise pathogenetic mechanism.     

Hyphenation of Raman spectroscopy with gravimetric analysis to interrogate water-solid interactions in pharmaceutical systems

A moisture sorption gravimetric analyzer has been combined with a Raman spectrometer to better understand the various modes of water-solid interactions relevant to pharmaceutical systems. A commercial automated moisture sorption balance was modified to allow non-contact monitoring of the sample properties by interfacing a Raman probe with the sample holder. This hybrid instrument allows for gravimetric and spectroscopic changes to be monitored simultaneously. The utility of this instrument was demonstrated by investigating different types of water-solid interactions including stoichiometric and non-stoichiometric hydrate formation, deliquescence, amorphous-crystalline transformation, and capillary condensation. In each of the model systems, sulfaguanidine, cromolyn sodium, ranitidine HCl, amorphous sucrose and silica gel, spectroscopic changes were observed during the time course of the moisture sorption profile. Analysis of spectroscopic data provided information about the origin of the observed changes in moisture content as a function of relative humidity. Furthermore, multivariate data analysis techniques were employed as a means of processing the spectroscopic data. Principle components analysis was found to be useful to aid in data processing, handling and interpretation of the spectral changes that occurred during the time course of the moisture sorption profile.     

Early malignant change in a solitary neurofibroma not associated with neurofibromatosis: a case report

A 31-year old woman presented with a mass on the posterolateral aspect of the lower third of the right leg. The mass had undergone fine needle aspiration biopsy previously at another center and was diagnosed as neurofibroma. The patient was evaluated to determine the existence of neurofibromatosis but no positive findings were obtained, thus the mass appeared to be a solitary, local neurofibroma. The mass was totally excised with the involved nerve fascicles. The histopathological evaluation showed foci of malignant transformation of the solitary neurofibroma. The patient was reoperated on, and the surrounding tissues were widely excised together with the tibial nerve; the defect was grafted with the sural nerve. Clear margins were achieved. No complications ocurred and the patient was satisfied. She survived and had neither recurrence nor metastasis during 2 years follow-up. This patient is presented as a case report of a malignant peripheral nerve sheath tumor, specifically the focal malignant degeneration of a solitary neurofibroma.     

Subcutaneous endoscopically assisted ligation (SEAL) of the internal ring for repair of inguinal hernias in children: a novel technique

Subcutaneous endoscopically assisted ligation (SEAL) is a technique for high ligation of the patent processus at the internal ring without a groin incision or dissection of the vas and vessels. Under endoscopic visualization through a single umbilical port, a suture is guided extraperitoneally around the internal ring, avoiding the vas and vessels. The safety, efficacy (recurrence risk), and cost-effectiveness of this unproven procedure must be tested against standard open repair in a trial.     

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs

BACKGROUND: Amino-penicillins are a major cause of delayed-type reactions to penicillins. OBJECTIVES: The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. METHODS: We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. RESULTS: A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. CONCLUSIONS: These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.     

Characterization of Drosophila fruitless-gal4 transgenes reveals expression in male-specific fruitless neurons and innervation of male reproductive structures

The fruitless (fru) gene acts in the central nervous system (CNS) of Drosophila melanogaster to establish male sexual behavior. Genetic dissection of the locus has shown that one of the fru gene's promoter, P1, controls the spatial and temporal expression of male-specific FruM proteins critical to determining stereotypical male sexual behavior. By using the Gal4-expression system, we show that a 16-kb fragment of the fru P1 promoter's 5' regulatory region drives the expression of Gal4 in a subset of FruM-expressing neurons within both the pupal and adult CNS. Colocalization of FruM and a Gal4-responsive reporter shows that the fru(P1)-gal4 fusion construct generates expression in both previously characterized FruM-expressing neurons as well as within cells of both the CNS and the peripheral nervous system that have not been demonstrated as FruM-expressing. Gal4-expressing neurons are shown to innervate abdominal organs directly relevant to fru function; specifically, the muscle of Lawrence (MOL) and the male internal reproductive organs. Innervations of the latter are shown to originate from identified FruM-serotonergic neurons. Furthermore, we show that the MOL neuromuscular junction is sexually dimorphic. Finally, we describe Gal4 expression in neurites innervating male reproductive structures that are hypothesized to be targets of fru function. Isolation of the regulatory sequences controlling the expression of fru in the CNS, therefore, provides a potent tool for the manipulation of FruM-expressing neurons and for understanding the cellular basis of Drosophila reproductive behavior.     

Modulation of premotor mirror neuron activity during observation of unpredictable grasping movements

Using transcranial magnetic stimulation, we explored the properties of premotor mirror neurons during the passive observation of a reaching-grasping movement in human subjects. Two different experiments were run using video-clips as visual stimuli. Video-clips showed a normally performed (control stimulus) or an anomalous reaching-grasping movement executed by delaying the time of the appearance of the maximal finger aperture (experiment 1), or substituting it with an unpredictable closure (experiment 2). Motor evoked potentials were recorded at different time-points during the observation of the video-clips. Profiles of cortical excitability were drawn and compared with the kinematic profiles of the corresponding movement. Passive observation of the natural movement evoked a profile of cortical excitability that is in concordance with the timing of the kinematic profile of the shown finger movements. Observation of the uncommon movements did not exert any modulation (experiment 1) or evoked an activity that matched, at the beginning, the modulation obtained with observation of the natural movement (experiment 2). Results show that the resonant motor plan is loaded as whole at the beginning of observation and once started tends to proceed to its completion regardless of changes to the visual cues. The results exclude the possibility of a temporal fragmentation of the resonant plan, because activation of different populations of mirror neurons for each phase of the ongoing action. They further support the notion of the role of the mirror system as neural substrate for the observing-execution matching system and extend the current knowledge regarding mechanisms that trigger the internal representation of an action.     

Magnitude of right-to-left shunt as the only determinant of stroke in a pair of identical twins

Abstract. Right-to-left shunt due to patent foramen ovale is a well-established risk factor for stroke in the young. The magnitude of shunt seems to be correlated to the risk of stroke in individuals. We report the cases of two 51-year-old identical twins, with similar risk factors for ischemic stroke, in which the sibling with a large and permanent shunt suffered a left hemispheric stroke and the other, with a small and latent shunt, was asymptomatic. In a three-year follow-up, the siblings were both asymptomatic, and the dimensions of shunts were unchanged. Our cases stress the importance of quantifying right-to-left shunt in order to stratify the risk of stroke in individuals, and suggest a role of heredity in patency of foramen ovale.     

Is the use of laparoscopy to determine presence of contralateral patent processus vaginalis justified in children greater than 2 years of age?

Purpose

Contralateral inguinal hernia exploration in cases of unilateral inguinal hernia remains a controversial topic. The authors have been using the in-line laparoscopic technique of contralateral evaluation for unilateral inguinal hernia in children less than 2 years of age. Because of the case of the procedure and lack of morbidity, we decided to expand the use of this procedure up to age 8 years in January 2000. The purpose of this study is to evaluate if the incidence of contralateral hernia in children greater than 2 years justifies the procedure.

Methods

This is a retrospective study of all children who underwent contralateral exploration for unilateral inguinal exploration over a 20-month period. The procedure was offered routinely to all patients up to age 8 years. During the repair, the contralateral inguinal ring was examined laparoscopically using the in-line technique for the presence of a contralateral hernia. The incidence of contralateral hernia was determined, and the results were stratified by age. Patients who underwent unilateral inguinal hernia repair without laparoscopic contralateral exploration or bilateral inguinal hernia repair without laparoscopic contralateral explorations were excluded from the study.

Results

A total of 284 laparoscopic explorations were performed. Positive explorations were seen in 65 of 171 (38%) of children less than 2 years of age, 19 of 101 (20%) of children 2 to 8 years of age, and 1 of 12 children greater than 8 years of age (8%). There were no operative complications.

Conclusions

Laparoscopic contralateral exploration is safe and effective. Because of the low morbidity, the risk to benefit ratio warrants its use in children up to 8 years of age. This sample size is too small to make any meaningful statement in children older than 8 years.     

Down-regulation of mitotic checkpoint in transformed human embryo lung fibroblasts induced by N-methyl-N’-nitro-N-nitrosoguaridine

Background Mutations in mitotic checkpoint genes have been detected in several human cancers, which exhibit chromosome instability. We wanted to know whether mutation of hBubl could occur in transformed human embryo lung fibroblasts (HELF) cells induced by a chemical carcinogen. Methods HELF cells were transformed by N-methyI-N‘-nitro-N-nitrosoguaridine (MNNG), and three flasks of transformed HELF cells (named as T1, T2, and T3) were selected as amplifiers, and mutations of hBubl in these transformed cells were analyzed by PCR-SSCP and sequencing. Results It was found that any one of three transformed cell lines exhibited aneuploidy with a low mitotic checkpoint function. Subsequent PCR-SSCP and sequence analysis showed an AGT to CGTor ATT mutation at codon 80 in hBubl gene in T1 cells with a resultant change in amino acid sequence. Conclusion Our study demonstrated that the mitotic checkpoint genes could be targets of MNNG.