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The authors studied Pi polymorphism using the Separator isofocusing method with slight modification. A new Pi allele was observed. Family pedigrees confirmed co-dominant inheritance with other Pi alleles. According to the electrophoretic mobility of its isoprotein bands, and to its frequency (0.04) this new allele is considered as a fourth Pi M subtype: Pi M4.
It is shown that a simple preferential transmission of the PiZ allele by PiZ-heterozygous males for alpha 1-antitrypsin deficiency cannot maintain the observed polymorphism at the locus without invoking any viability or fertility selection against the PiZ gene carriers (heterozygotes or homozygotes). From the data on frequencies of PiZ alleles in Europe, the estimates of such selection coefficients are shown to be of the order of 5-20%, which seems too large for natural populations. Furthermore, an analysis of 26 nuclear families, each ascertained through a heterozygous PiZ or homozygous ZZ child, does not provide statistical evidence for such a hypothesis.
This paper describes an original in vivo device to investigate and quantify cutaneous resorption of sebum. Such a phenomenon was explored using a photometric determination of residual skin surface lipids at different times following initial deposits of known amounts of artificial sebum on demarcated areas. The technique was carried out on seven healthy subjects. The chosen area was the anterior aspect of the forearm, owing to the very low sebum production of this site, less than the sensitivity of the measuring instrument. The kinetics of absorption of applied sebum turned out to be hyperbolic-like and well correlated with experimental results (r = 0.992), allowing a mathematical determination of the initial velocity of penetration of sebum into the skin, reaching 20 micrograms/cm2.min for a standard program including a mean initial deposit of 116 micrograms/cm2. This kinetics actually does not fit with a true percutaneous absorption of lipids but is compatible with that of absorption into the stratum corneum. It conveys the faster absorption of the latter for sebum, a well-known but not so far quantified property of stratum corneum. The model here described is not at once transposable to skin areas with high sebum production since, quite obviously in such zones, the stratum corneum is permanently saturated with skin surface lipids. Therefore, the conclusions of this work cannot be correlated with the regreasing parameters studied so far on the forehead, but they provide interesting data about the evolution of sebum following its output onto the skin surface and therefore a better understanding of sebaceous physiology.
Proinsulin-like components (PLC) and insulin have been measured in 24 hr urine samples from 8 healthy subjects. The mean excretion of PLC was 45.8 ng and that of insulin 314 ng; the PLC: insulin ratio was 0.14. Urinary PLC was increased 3.5 fold in a patient with a pancreatic islet cell tumor and the PLC: insulin ratio was 0.35. The urinary PLC: insulin ratio is lower than that of serum, presumably because of the relatively lower urinary clearance of the larger molecular weight PLC.
White matter signal hyperintensities (WMSH) are commonly seen on MRI of elderly subjects. The purpose of this study was to characterize metabolic changes in the white matter of elderly subjects with extensive WMSH. We used water-suppressed proton (1H) magnetic resonance spectroscopic imaging (MRSI) to compare six subjects with extensive WMSH with eight age-matched elderly subjects with minimal or absent WMSH, and phosphorus (31P) MRSI to compare nine subjects with extensive WMSH and seven age-matched elderly subjects without extensive WMSH. Relative to region-matched tissue in elderly controls, extensive WMSH were associated with increased signal from choline-containing metabolites, no significant change of signal from N-acetylaspartate, and a trend to a decreased phosphomonoester (PME) resonance. These findings suggest that WMSH may be associated with an alteration of brain myclin phospholipids in the absence of axonal damage. There were no differences in energy phosphates, consistent with lack of ongoing brain ischemia. Within the group with extensive WMSH, PME resonance measures were significantly lower in WMSH than in contralateral normal-appearing white matter. These results provide information on pathophysiology of WMSH and a basis for comparison with WMSH in Alzheimer's disease, vascular dementia, multiple sclerosis, and other diseases.
In an attempt to improve the primary treatment of malignant gliomas we used a concomitant 6-week course of chemoradiotherapy with 5 fluorouracil (5 FU) and hydroxyurea (HU) in 24 adults with anaplastic astrocytoma (AA) (7 cases) or glioblastomas (GLB) (17 cases). This patient population was characterised by a poor prognostic profile; 50% of cases had biopsic or subtotal surgery and 70% had GLB. Patients received 2 Gy/day 18 MV photons with 300 mg/m2 of 5 FU in continuous infusion and 500 mg x 4/day per os of HU, five days per week during 6 weeks. Treatment was poorly tolerated in terms of toxicity and implied heavy logistics (hospitalization, central venous access) worsening the quality of life which is already bad in malignant gliomas. Unfortunately we did not improve median survival which does not exceed 26 weeks with 7 long survivors (> 49 weeks). This pilot study does not offer any benefits over current standard approaches. Aggressive locoregional approaches such as this should perhaps be attempted in patients with a better profile.
Iron overload occurs frequently in thalassemia as a consequence of regular blood transfusions, and iron has been found to accumulate in bone, but skeletal toxicity of iron is not clearly established. In this study, bone biopsies of thalassemic patients were investigated by light (n = 6) and electron microscopy (n = 8) in order to analyze iron distribution and possible iron-associated cellular lesions. Sections (5 microns thick) were used for histomorphometry and iron histochemistry. Ultrathin sections were examined with an energy filtering transmission electron microscope. Iron was identified by electron energy loss spectroscopy (EELS), and iron distribution was visualized by electron spectroscopic imaging (ESI) associated with computer-assisted treatment (two-window method). This study shows that EELS allows the detection of 4500-9000 iron atoms, and that computer-assisted image processing is essential to eliminate background and to obtain the net distribution of an element by ESI. This study shows also that stainable iron was present along trabecular surfaces, mineralizing surfaces, and on cement lines in the biopsies of all patients. Moreover, iron was detected by EELS in small granules (diffusely distributed or condensed in large clusters), in osteoid tissue, and in the cytoplasm of bone cells, but not in the mineralized matrix. The shape and size (9-13 nm) of these granules were similar to those reported for ferritin. As for iron toxicity, all patients had osteoid volume and thickness and osteoblast surface in the normal range. Stainable iron surfaces did not correlate with osteoblast surfaces, plasma ferritin concentrations, or the duration of transfusion therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors have been using CO2-laser radiation routinely for more than 2 years. After having recalled the basic thermal properties of this beam, they present their experience. The goal of this work is to point out the particular benefit of CO2-laser cautery to perform tumoral haemostasis. The technical data of this CO2-laser haemostasis are detailed for 3 main indications: In cases of a precise origin of the haemorrhage, the coagulation of small intratumoural vessel necessitates a low output power: 2-4 watts in continued emission; 10-15 watts in the pulsed mode. The beam must be defocussed so as to be as large as the aimed vessel. A micro-manipulatotor is necessary for deeply located tumours. Basal meningiomas, neurinomas, giant adenomas are the best indications. If a diffuse bleeding is encountered in the operative cavity the output must be a little higher: 3-8 watts in continuous mode or 15-30 watts in the pulsed mode; first the cavity is swept with a defocussed CO2-laser ray; then the few larger vessels which have not been cauterized are coagulated one by one either by laser or by bipolar coagulation. The insertion zone of a meningioma can be efficiently coagulated by CO2-laser: a 150-200 watts output in the pulsed mode is necessary if the attachment is dural, a 300-400 watts pulsed output in the case of bony infiltration.
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The objectives of the study were: 1) to evaluate mortality in elderly patients requiring ventilatory support in Intensive Care Unit (ICU) and at 6, 12 and 18 months after discharge from ICU; 2) (main objective) to determine predictors of mortality in ICU and after discharge; and 3) to assess the life-style of survivors. One hundred and ten consecutive hospitalized patients > or = 70 years were included in this retrospective study. Follow-up evaluation was conducted by telephone interview. Mortality in ICU and after discharge was the outcome variable. Fifteen parameters were recorded at admission and during hospitalization. Residence, health status, and self-sufficiency were evaluated after discharge. 1) Mortality in ICU and at 6, 12 and 18 months after discharge was 38%, 60%, 63% and 67% respectively. 2) The predictors of mortality in ICU were admission in shock, and use of major therapeutic interventions. Predictors of mortality at 6 months were admission in shock, previous impaired health status and marital status. 3) Eighteen months after discharge 92% of the surviving patients (N = 33) had the same residence, 75% had the same health status, and 78% had the same autonomy compared with pre-admission status. We concluded that shock and previous health status but not age are predictors of short- and long-term prognoses in elderly patients hospitalized in ICU for mechanical ventilation.
Carbon tetrachloride (CCl4) lethality in Sprague-Dawley rats is greatly amplified by pretreatment of Kepone (decachlorooctahydro-1,3,2-metheno-2H-cyclobuta[cd] pentalen-2-one). The increase in lethality was attributed to the obstruction of liver regenerative processes. These processes are essential for restoring the liver to its full functional capacity following injury by CCl4. Based on the available mechanistic information on Kepone/CCl4 interaction, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was constructed where the following effects of Kepone on CCl4 toxicity are incorporated: (1) inhibition of mitosis; (2) reduction of repair mechanism of hepatocellular injury; (3) suppression of phagocytosis. The PBPK/PD model provided computer simulation consistent with previously published time-course results of hepatotoxicity (i.e., pyknotic, injured and mitotic cells) of CCl4 with or without Kepone. As a further verification of this model, the computer simulations were also consistent with exhalation kinetic data for rats injected with different intraperitoneal (i.p.) doses of CCl4 in our laboratory. Subsequently, the PBPK/PD model, coupled with Monte Carlo simulation, was used to predict lethalities of rats treated with CCl4 alone and CCl4 in combination with Kepone. The experimental lethality studies performed in our laboratories were as follows: Sprague-Dawley rats were given either control diet or diet containing 10 ppm Kepone for 15 days. On day 16, rats in the Kepone treated group were given i.p. doses of 0, 10, 50, and 100 microliters/kg CCl4 (n = 9) while control rats were exposed to 0, 100, 1000, 3000, and 6000 microliters/kg CCl4 (n = 9). Lethality was observed at the 1000 (1/9), 3000 (4/9), and 6000 (8/9) microliters/kg doses for the control group and at the 50 (4/9) and 100 (8/9) microliters/kg for the treated group. Based on Monte Carlo simulation, which was used to run electronically 1000 lethality experiments for each dosing situation, the LD50 estimates for CCl4 toxicity with and without Kepone pretreatment were 47 and 2890 microliters/kg, respectively. Monte Carlo simulation coupled with the PBPK/PD model produced lethality rates which were not significantly different from the observed mortality, with the exception of CCl4 at very high doses (e.g., 6000 microliters/kg, p = 0.014). Deviation at very high doses of the predicted mortality from the observed may be attributed to extrahepatic systemic toxicities of CCl4, or solvent effects on tissues at high concentrations, which were not presently included in the model. Our modeling and experimental results verified the earlier findings of Mehendale (1990) for the 67-fold amplification of CCl4 lethality in the presence of Kepone. However, much of this amplification of CCl4 lethality with Kepone pretreatment was probably due to pharmacokinetic factors, because when target tissue dose (i.e., model estimated amount of CCl4 metabolites) was used to evaluate lethality, this amplification was reduced to 4-fold.
Stereotaxic brain lesioning is widely used to develop experimental models of human brain disease in the nonhuman primate. To avoid intraoperative vascular complications such as intracranial hemorrhage, we developed a methodology that is easy to implement. This method combines T1-weighted magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). This technique is applied to produce bilateral neurotoxic lesions of the rhinal cortex, a structure located medially in the temporal lobe, in eight baboons (including five sham-operated animals with needle descents but no ibotenic acid injection). Two other baboons were lesioned before the MRA technology was available. The MRA sequence (two-dimensional time-of-flight, axial acquisition) was used to localize the blood vessels in the needle trajectories, i.e., the highly vascularized sylvian fissure and temporal gyri. The vessel coordinates were transposed onto the coronal MRI-TI images, onto which the injection sites were determined and the planned needle tracks drawn. In the eight baboons that had MRA, 26.8% of these needle tracks had to be slightly displaced because of the presence of blood vessels. The stereotaxic coordinates of the final target sites were then calculated with respect to six skull landmarks that also served as a reference during surgery. No intracranial hemorrhage occurred in any of the eight baboons in which MRA was performed, in contrast to one of the two baboons not studied with MRA. The histological analysis showed a good extent of the rhinal lesions in all lesioned animals, with minimal damage to areas other than those that were targeted. Thus, combined use of MRI-TI and MRA proved to be reliable in reducing vascular complications, affording new advances for stereotaxic surgery in nonhuman primates.
Many studies of white matter high signal (WMHS) on T2-weighted MRI have disclosed that it is related to cerebral ischaemia and to brain atrophy. Atrophy of the corpus callosum (CC) has also been studied in relation to ischaemia. Our objective was to test the hypothesis that CC atrophy could be due to ischaemia. We therefore assessed CC, WMHS and brain atrophy in patients with risk factors without strokes (the risk factor group) and in those with infarcts (the infarct group), to investigate the relationships between these factors. We studied 30 patients in the infarct group, 14 in the risk factor group, and 29 normal subjects. Using axial T1-weighted MRI, cortical atrophy and ventricular enlargement (brain atrophy) were visually rated. Using axial T2-weighted MRI, WMHS was assessed in three categories: periventricular symmetrical, periventricular asymmetrical and subcortical. Using the mid-sagittal T1-weighted image, the CC was measured in its anterior, posterior, mid-anterior and mid-posterior portions. In the normal group, no correlations were noted between parameters. In the infarct group, there were significant correlations between CC and brain atrophy, and between CC atrophy and WMHS. After removing the effects of age, gender and brain atrophy, significant correlations were noted between some CC measures and subcortical WMHS. In the risk factor group, there were significant correlations between CC and brain atrophy and between CC atrophy and WMHS. After allowance for age, gender and brain atrophy, significant correlations between some CC measures and periventricular WMHS remained. The hypothesis that CC atrophy could be due to cerebral ischaemia was supported by other analyses. Namely, for correlations between the extent of infarcts and partial CC atrophy in patients with anterior middle cerebral artery (MCA) and with posterior MCA infarcts, there were significant correlations between the extent of infarct and mid-anterior CC atrophy in the former, and posterior CC atrophy in the latter. Our findings could indicate that CC atrophy is associated with cerebral ischaemia.
We report the fourth case of combined D-and L-2-hydroxyglutaric aciduria presenting with neonatal encephalopathy and subependymal cysts.
The availability of the Arabidopsis genome revealed the complexity of the gene families implicated in dithiol disulfide exchanges. Most non-green organisms present less dithiol oxidoreductase genes. The availability of the almost complete genome sequence of rice now allows a systematic search for thioredoxins, glutaredoxins and their reducers. This shows that all redoxin families previously defined for Arabidopsis have members in the rice genome and that all the deduced rice redoxins fall within these families. This establishes that the redoxin classification applies both to dicots and monocots. Nevertheless, within each redoxin type the number of members is not the same in these two higher plants and it is not always possible to define orthologues between rice and Arabidopsis. The sequencing of two unicellular algae (Chlamydomonas and Ostreococcus) genomes are almost finished. This allowed us to follow the origin of the different gene families in the green lineage. It appears that most thioredoxin and glutaredoxin types, their chloroplastic, mitochondrial and cytosolic reducers are always present in these unicellular organisms. Nevertheless, striking differences appear in comparison to higher plant redoxins. Some thioredoxin types are not present in these algal genomes including thioredoxins o, clot and glutaredoxins CCxC. Numerous redoxins, including the cytosolic thioredoxins, do not fit with the corresponding higher plant classification. In addition both algae present a NADPH-dependent thioredoxin reductase with a selenocysteine which is highly similar to the animal thioredoxin reductases, a type of thioredoxin reductase not present in higher plants.
Dried seeds and nuts are widely consumed by indigenous populations of the western Sahel, especially those who inhabit rural areas. In light of the need for quantitative information regarding the content of particular nutrients in these plant foods, we collected dried pumpkin (Cucurbita spp) seeds and nuts of Cyperus esculentus in the Republic of Niger and analyzed them for their content of essential amino acids, minerals and trace elements, and fatty acids. On a dry weight basis, pumpkin seed contained 58.8% protein and 29.8% fat. However, the lysine score of the protein was only 65% relative to the FAO/WHO protein standard. The pumpkin seed contained useful amounts of linoleic (92 microg/g dry weight) and the following elements (on a microg per g dry weight basis): potassium (5,790), magnesium (5,690), manganese (49.3), zinc (113), selenium (1.29), copper (15.4), chromium (2.84), and molybdenum (0.81), but low amounts of calcium and iron. Except for potassium (5,573 microg/g dry weight) and chromium (2.88 microg/g dry weight), the C. esculentis nuts contained much less of these same nutrients compared to pumpkin seeds. In conclusion, pumpkin seeds represent a useful source of many nutrients essential to humans. The data in this report should of practical value to public health officials in rural areas of sub-Saharan Africa.
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