Hemoglobin oxygen affinity in patients suffering from arterial occlusive disease of the legs

Summary Parameters characterizing the hemoglobin oxygen affinity were determined in blood of 12 male patients suffering from arterial occlusive disease (AOD) of the legs and compared with data obtained earlier from healthy human subjects (controls). Due to a COHb content of 4.8%±2.2% in the cigarette-smoking AOD patients, the standard oxygen dissociation curve (ODC) was left-shifted, the half-saturation pressure (P₅₀) amounted to 24.8±1.7 mmHg (3.30±0.23 kPa), although the 2,3-diphosphoglycerate concentration was increased to 15.3±1.7 µmol/g Hb. Correcting the effects of elevated COHb shifts the P₅₀ to 26.3 mmHg (3.5 kPa) and increases the steepness of the ODC (Hill's n) from 2.79±0.27 to about 2.99, which is significantly different from controls. The Bohr coefficients after acidification of blood with lactic acid (BC_Lac) show high values at low oxygen saturations of hemoglobin (–0.50±0.04 in AOD patients, –0.32±0.04 in controls;P<0.05 at 10% S_O2). The cause of the alterations in hemoglobin oxygen affinity may be a reduced mean erythrocyte age, but also the influence of unknown factors generated, e.g., from anaerobic muscle metabolism in AOD.Abbreviations AOD Arterial occlusive disease of the legs - BC Bohr coefficient - BC_CO2 Bohr coefficient after acidification of blood with CO₂ - BC_Lac Bohr coefficient after acidification of blood with lactic acid - DPG 2,3-Diphosphoglycerate - ODC Oxygen dissociation curve - P₅₀ Oxygen pressure when hemoglobin is half-saturated     

Effects of Crowding on the Thermal Stability of Heterogeneous Protein Solutions

Crowding can substantially affect the transition of a protein between its native (N) and unfolded (U) states via volume exclusion effects. Also, it influences considerably the aggregation (A) of unfolded proteins. To examine the details, we developed an approach for computing the kinetic rates of the process N ↔ U → A in which the concentration of the protein is explicitly taken into account. We then compute the relative change with temperature of the protein denaturation for various fractional volume occupancies and partition of proteins in solution. The analysis indicates that, in protein solutions in which the average distance between proteins is comparable with the radius of gyration of an unfolded protein, steric effects increase the stability of the proteins which are in compact, native states. In heterogeneous protein solutions containing various types of proteins with different thermal stabilities, the unfolding of the most thermolabile proteins will increase the stability of the other proteins. The results shed light on the way proteins change the thermal stability of a cell as they unfold and aggregate. This study may be valuable in questions related to the dynamics of thermal injuries.     

Fertilization and early embryology: Effects of persistent chlorinated hydrocarbons on fertility and embryonic development in the rabbit

The commercial polychlorinated biphenyl (PCB) formulation Aroclor1260 (4 mg/kg body weight), technical grade dichlorodiphenyltrichloroethane(DDT; 3 mg) and Lindane (-hexachlorocyclohexane; 0.8 mg) wereadministered orally, either separately or in combination, tosexually mature female rabbits three times per week for 12–15weeks. Oviductal and uterine luminal fluid, cleavage stage embryos(day 1 post coitum), blastocysts (day 6), fetuses, exocoelicfluid and placentae (day 11) were analysed, firstly for chlorinatedhydrocarbon residues, and secondly for embryonic and fetal development.The doses applied were well tolerated by the treated animals.PCB and DDT accumulated in uterine secretions (day 6) but notin oviductal luminal fluid (day 1). Both chlorinated hydrocarbonswere found in preimplantation blastocysts. Residues in day 11fetuses were 16- (DDT) or 18-fold (PCB) higher than in day 6blastocysts. Significant amounts were also detected in placentaltissue and in exocoelic fluid. A specific accumulation of thehighly chlorinated biphenyl congener no. 180 was noted in fetuses,placentae and exocoelic fluid. The clear accumulation of thechlorinated hydrocarbon compounds in luminal fluid and embryonictissue is contrasted by rather weak effects on fertility. Nostatistically significant differences between treated animalsand controls were observed for fertilization rate and pre- andpost-implantation (up to day 11 post coitum) losses. However,in females exposed to PCB, a 20% higher loss of blastocystswas noticed, as compared with controls (P > 0.05). This effectwas shown on day 6 of embryonic development and may be due tothe embryotoxic activities of PCB.     

Psychological and social effects of orthodontic treatment

Adolescents with commonly occurring forms of malocclusion often are presumed to be at risk for negative self-esteem and social maladjustment. A randomized control group design was used to assess the psychosocial effects of orthodontic treatment for esthetic impairment. Ninety-three participants, 11 to 14 years old, with mild to moderate malocclusions, were randomly assigned to receive orthodontic treatment immediately or after serving as delayed controls. A battery of psychological and social measures was administered before treatment, during treatment, and three times after completion of treatment, the last occurring one year after termination. Repeated measures analyses of variance assessed group differences at the five time points. Parent-, peer-, and self-evaluations of dental-facial attractiveness significantly improved after treatment, but treatment did not affect parent- and self-reported social competency or social goals, nor subjects' self-esteem. In summary, dental-specific evaluations appear to be influenced by treatment, while more general psychosocial responses are not.This research was supported by Grant NIH-NIDR-R01-DE06154 from the National Institute of Dental Research.     

The effect of attentional cueing on conscious awareness of stimulus and response

Attending to a cued location in space leads to faster reaction times when a stimulus is presented there. The reasons for this attentional effect, and its specific locus in the information-processing chain between stimulus and response, remain unclear. One suggestion is that attention speeds the conscious detection of stimuli. Surprisingly, this possibility appears not to have been tested directly. To resolve this question, we asked subjects to make simple responses to lateralised targets that followed either a valid, invalid or neutral cue, and to judge the perceived time of the target onset, or of their response, by delayed report of the position of a clock hand. Our results showed that only a small and non-significant part of the attentional effect is due to delayed conscious awareness of the stimulus. The greater part of the attentional effect is localised either subsequent to conscious detection of stimuli or occurs in a separate, parallel processing stream from that which generates the motor response. Electronic Publication     

De novo 13q partial duplication identified by cytogenetic, biochemical and molecular approaches

A 3.5-month-old female infant manifesting dysmorphic facies, developmental delay and failure to thrive was referred for cytogenetic evaluation. Peripheral lymphocytes revealed three chromosomally distinct cell lines: 46,XX/46,XX,10p+/47,XX,10p+,+mar. Dermal fibroblasts revealed only the 46,XX,10p+cell line. High resolution G-, R-, and Q-banding suggested that the extra chromosomal material (10p+) represented a duplication of the segment 13q14----13qter. Parental karyotypes were normal. As absolute identification of de novo chromosomal abnormalities, based solely on cytogenetic studies, is sometimes difficult, both biochemical and molecular approaches were undertaken to elucidate this abnormality in more detail. Dosage effects were examined using esterase D (localized to 13q14.1) and the DNA probes p1E8 and p9A7 (localized to 13q22 and 13q31/32, respectively). These studies suggested the presence of only 2 copies of esterase D, but 3 copies of both DNA probes, allowing identification of the breakpoint at 13q14.2.     

Thermoregulatory responses to cold during a 7-week acclimatisation process in rabbits

A group of six rabbits reared at +20°C ambient temperature was adapted to moderate cold by housing for seven weeks at +10°C. Rectal and skin temperatures, metabolic heat production and respiratory evaporative heat loss were recorded continuously over 1 h for each animal on 3 days per week in the climatic chamber.There was no significant change either of rectal or of ear skin temperature during the acclimatisation process. On the other hand, metabolic heat production was progressively reduced (20% in the 7th week). Slight changes of mean skin temperature and respiratory evaporative heat loss could not account for compensation. Therefore it must be concluded that both adaptive improvement of peripheral insulation and reduction of heat production were achieved during the acclimatisation process. Both processes together ensure that deviations of core temperature are minimal. The possible origin of the functional adaptive effects is discussed. The results are in full agreement both with former neurophysiological results and with system-theoretical considerations of adaptive processes.Dedicated to the 60th birthday of Professor Dr. Kurt Brück     

A controlled study of a specific MAO A reversible inhibitor (R011-1163) and amitriptyline in depressive illness

A double blind comparative study of amitriptyline and a new reversible MAO A inhibitor R011-1163 was conducted in 25 depressed inpatients over 4 weeks. Response to treatment was assessed with the Hamilton depression rating scale, the Carroll depression self rating scale and the Visual analogue scale. Both drugs produced significant changes in depressive symptomatology (P less than 0.01, MANOVA) and there were no statistically significant differences between drugs (P greater than 0.05 MANOVA). Side effects were of mild to moderate severity with dry mouth the most commonly reported side effect of amitriptyline and vague, generalised headache in patients, treated with R011-1163.     

An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and common carotid atherosclerosis

Plasma homocysteine (Hcy) concentration has been shown to be influenced by a mutation in the gene coding methylenetetrahydrofolate reductase (MTHFR). Although plasma Hcy is related to atherosclerotic disorders, conflicting results have been reported about the association between MTHFR gene polymorphism and sclerotic lesions of the common carotid arteries. The effect of age–gene interaction on carotid arterial remodeling was investigated in elderly subjects with several risk factors for atherosclerosis. We evaluated sclerotic lesions of the common carotid arteries by ultrasonography in 326 patients (mean age ± standard deviation, 73 ± 12 years) and studied relations among the known risk factors for atherosclerosis, including MTHFR gene polymorphism and its interactions with age and sex. Of the 326 subjects studied, 136 had MTHFR genotype CC, 136 genotype CT, and 54 genotype TT. The three groups did not differ with respect to background factors such as age, history of cigarette smoking, blood pressure, lipids or uric acid, or in the incidence of atherosclerotic diseases. Spearman's rank correlation revealed a significant relationship between gender, age, Brinkman index, systolic blood pressure, triglycerides, HDL-cholesterol (HDL-C), uric acid, and MTHFR gene polymorphism. Multiple regression analysis using intima-media complex thickness (IMT) as a criterion variable and risk factors, including MTHFR gene polymorphism as explanatory variables showed that MTHFR gene polymorphism (P = 0.039) was a significant independent explanatory variable for IMT, along with gender (male) (P < 0.001), age (P < 0.001), systolic blood pressure (SBP) (P = 0.047), total cholesterol (T-C) (P < 0.001), and HDL-C (P < 0.001). Furthermore, a general linear model analysis revealed that interaction between age and MTHFR gene polymorphism was significantly associated with IMT, independently of age, SBP, T-C, and HDL-C in male subjects. However, age–gene interaction was not observed in female subjects. The findings of the present study confirm an association between MTHFR gene polymorphism and common carotid atherosclerosis in the Japanese population and further support the role of risk factor–gene interaction in common carotid atherosclerosis. Received: May 14, 2001 / Accepted: June 8, 2001