Apoptosis in the failing human heart

BACKGROUND: Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure. METHODS: Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined. RESULTS: Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonstration of DNA-strand breaks in myocyte nuclei was coupled with the documentation of chromatin condensation and fragmentation by confocal microscopy. All these findings reflect apoptosis of myocytes. The percentage of myocytes labeled with BCL2 (which protects cells against apoptosis) was 1.8 times as high in the hearts of patients with cardiac failure as in the normal hearts, whereas labeling with BAX (which promotes apoptosis) remained constant. The near doubling of the expression of BCL2 in the cardiac tissue of patients with heart failure was confirmed by Western blotting. CONCLUSIONS: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.     

Impact of local-negative-feedback on the MRS avalanchephotodetector operation

Metal-Resistance-Semiconductor (MRS) photodetectors are characterized by a resistive layer placed in series to an avalanching region. In this paper, we report the characterization of such devices, we define a parameter extraction procedure, and we derive a quantitative model of the MRS operation. Due to the presence of the ohmic layer, the detector works as an ensemble of pixels with separately stabilized operating bias. In this way, compared to avalanche photodiodes (APDs), MRS achieve superior gain uniformity with the same sensitive area. However, there are still aspects of the fabrication technology and of the detector structure which have to be improved     

Analogue micropowered log-domain tone controller for auditoryprostheses

A micropower tone-control circuit comprising two first-order log-domain filters and a subtractor built with MOS transistors in weak inversion is described. The tone-controller is capable of providing bass cut/boost and treble cut operations. This circuit is being used in new designs of a conventional (acoustic) hearing-aid and cochlear implant     

Noninvasive assessment of hepatobiliary and renal elimination of cysteinyl leukotrienes by positron emission tomography

N-Acetyl-leukotriene E4 has been identified as an endogenous, biologically less active cysteinyl leukotriene metabolite in rodents and humans. To evaluate the ratio of hepatobiliary to renal elimination of leukotrienes noninvasively by positron emission tomography (PET), we synthesized N-[11C]acetyl-leukotriene E4 by chemical N-acetylation of leukotriene E4. After the intravenous injection of N-[11C]acetyl-leukotriene E4 in normal rats and monkey, uptake by the liver and subsequent excretion into bile were largely responsible for its rapid elimination from blood. In the Cynomolgus monkey, renal excretion of the leukotriene into urine was of additional quantitative importance. Kinetic modeling indicated a mean transit time through the liver of 17 minutes and 34 minutes in rat and monkey, respectively; the corresponding hepatic excretion half-times amounted to 8.5 minutes and 16 minutes. In a mutant rat strain deficient in the hepatobiliary excretion of cysteinyl leukotrienes across the canalicular membrane, the apparent mean liver transit time was 54 minutes, and the hepatic excretion half-time was 29 minutes, indicating prolonged organ storage and metabolism. After transport from the liver back into the circulating blood of omega-oxidized and beta-oxidized metabolites of N-[11C]acetyl-leukotriene E4, renal excretion compensated for the impairment of hepatobiliary elimination in the transport mutant. Metabolite analyses in urine after intravenous injection of N-[3H]acetyl-leukotriene E4 indicated the extensive inactivation of N-acetyl-leukotriene E4 by beta-oxidation from the omega-end in the mutants. A similar shift from hepatobiliary to renal cysteinyl leukotriene elimination was monitored in rats with cholestasis due to bile duct obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distance of pneumotransport of granular materials by retarded dense bed

Translated from Khimiya i Tekhnologiya Topliv i Masel, No. 12, pp. 8–10, December, 1993.     

Fifteen years of cutaneous and mucocutaneous leishmaniasis in Bolivia: a retrospective study

The photosensitizing properties of p-nitroacetophenone (PNAP), a well-known radiosensitizer, have been studied in near UV region. The mechanism of PNAP photosensitization has been investigated by testing the efficiency of singlet oxygen production using photooxidation of 2,2,6,6-tetramethylpiperidine (TEMP) and photodegradation of guanosine. In both the cases, the enhancement effect of deuterated solvents has been observed. Results of these experiments suggest the significant role of type II mechanisms in PNAP photosensitization.     

Comparative influence of a single allergen exposure on the different components of airway response to methacholine

We compared the effects of an allergen challenge on airway responsiveness to methacholine, the slope of the dose-response curve (DRC) and post-methacholine fall in forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1)/FVC, and determined whether any changes in these parameters were related to the presence and magnitude of the late asthmatic response (LAR) in mild stable asthma. Twenty-three allergic asthmatic subjects had an allergen challenge, preceded and followed 24 (n = 12) and/or 48 (n = 22) h later by a methacholine challenge. Sixteen subjects had a dual asthmatic response to the allergen. On the post-allergen methacholine challenge, as compared with the pre-allergen test, differences in mean fall in FVC or FEV1/FVC at 20% fall in FEV1 and the slope of the DRC did not achieve statistical significance, even in the group with LAR, which showed a significant increase in airway responsiveness at 24 h. There was, however, a correlation between allergen-induced changes in PC20 and (1) the change in post-methacholine FVC fall in the LAR group at 48 h, and (2) the change in the slope of the DRC in the early-asthmatic-response group at 24 h. In conclusion, allergen-challenge-induced changes in airway response to methacholine are heterogeneous among asthmatic subjects and although it may increase airway responsiveness (PC20), particularly in late responders, it minimally affects the other aspects of airway response to methacholine, suggesting that a more powerful or sustained allergic stimulus is required to modify the latter.     

Polymerase chain reaction versus culture for detection of Ureaplasma urealyticum and Mycoplasma hominis in the urogenital tract of adults and the respiratory tract of newborns

The efficiency of the polymerase chain reaction (PCR) was compared with that of culture for detection of Ureaplasma urealyticum and Mycoplasma hominis in 726 clinical specimens comprising 189 gynecological samples, 362 urological samples, and 175 samples from newborn infants. The sensitivity of PCR versus culture was 95% for both organisms, while the sensitivity of culture versus PCR was 91% for Ureaplasma urealyticum and 84% for Mycoplasma hominis. Furthermore, PCR tests were faster than culture tests, allowing the time to diagnosis to be reduced from two to five days to 24 h.     

Motor learning by field approximation

We investigated how human subjects adapt to forces perturbing the motion of their ams. We found that this kind of learning is based on the capacity of the central nervous system (CNS) to predict and therefore to cancel externally applied perturbing forces. Our experimental results indicate: (i) that the ability of the CNS to compensate for the perturbing forces is restricted to those spatial locations where the perturbations have been experienced by the moving arm. The subjects also are able to compensate for forces experienced at neighboring workspace locations. However, adaptation decays smoothly and quickly with distance from the locations where disturbances had been sensed by the moving limb. (ii) Our experiments also how that the CNS builds an internal model of the external perturbing forces in intrinsic (muscles and / or joints) coordinates.