Identification of a 'genuine' mammalian homolog of nematodal CED-4: is the hunt over or do we need better guns?
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Biomedical subjects
Publications and source records attributed to K Schrader.
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The properties of casein micelles in milk concentrates are of interest for the use of ultrafiltered (UF) skim milk concentrates in dairy products, and for the general understanding of colloidal stability and behavior of the casein micelle. The rheological behavior of UF skim milk concentrate with a casein concentration of 19.5% (wt/wt) was investigated at different pH and NaCl concentrations by analyzing flow viscometry and small amplitude oscillatory shear measurements. Viscometric flow curves were fitted to the Carreau-Yasuda model with the aim of determining values for the viscosity at infinite high shear rates and thereby estimate the voluminosity of the casein micelles (nu(casein)) in the UF concentrate. The voluminosity of the casein micelles increased with addition of NaCl and decreased when pH was decreased from 6.5 to 5.5. At pH 5.2, nu(casein) increased because of acid-induced aggregation of the casein micelles. The changes in nu(casein) could be interpreted from transmission electron microscopy of freeze-fractured samples of the UF concentrate and partly from dynamic light scattering measurements. Altered interactions between casein micelles due to different pH and NaCl concentrations are proposed to occur due to collapse of the kappa-casein layer, changed ionic strength, and altered distance between casein micelles.
Aspartoacylase deficiency is a neurodegenerative disease which typically starts in the first months of life with muscular hypotonia and developmental standstill. One of the first diagnostic procedures in this situation is an ultrasound of the brain. There is little information available about sonographic changes in Canavan disease. We present for the first time an ultrasound follow-up in a proven case of aspartoacylase deficiency from 3 weeks to 22 months. High echogenicity of the white matter was present in the neonatal period. Additional sonographic phenomena resulting in a characteristic pattern were shown in further investigations. The distinctive sonomorphology is compared to a few other cases in the literature. The correlation to the neuropathological course of the white matter changes is discussed. Recognition of the sonographic features in addition to the clinical presentation may contribute to an effective biochemical work-up.
The chemical components of tarbush (Flourensia cernua) leaves were fractionated by extracting successively with hexanes, diethyl ether, and ethanol. Volatile profiles of each fraction were identified by using GC-MS. The hexanes fraction contained mostly monoterpenoids, while the ethanol fraction volatiles were primarily sesquiterpenoids. Crude fractions were tested for activity against fungi, algae, and termites. Application of as little as 1 microg of the essential oil from the hexanes fraction was sufficient to provide visible antifungal activity in bioautography assays. The diethyl ether fraction showed selective activity against the cyanobacterium responsible for the 2-methylisoborneol-induced off-flavor sometimes associated with catfish farming operations. All three fractions exhibited a high degree of antitermite activity.
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The recurring translocation t(10;11)(p13;q14) which is found in acute myeloid leukemia (AML) and in acute lymphoblastic leukemia (ALL) results in the fusion of the putative transcription factor AF10 to CALM encoding a clathrin assembly protein. Previous studies using mainly fluorescence in situ hybridization (FISH) analysis have shown that the CALM/AF10 rearrangement is found in immature acute myeloid leukemia (AML) of subtype M0 and M1 and in T cell ALL. In this study we analyzed the CALM/AF10 and AF10/CALM fusion mRNAs in a series of three patients with AML, one patient with T-ALL and two patients with precusor T lymphoblastic lymphoma. In all six patients the breakpoint in CALM is at the 3' end of the coding region (nt1926/1927 or nt 2091/2092). Three breakpoints could be identified in AF10 (nt 588/589, nt 882/883 and nt 978/979). These data demonstrate that the CALM/AF10 fusions found in patients differ only slightly with respect to the portion of AF10 present and that there is no obvious difference between the fusions found in AML patients compared to those found in patients with lymphoid malignancies. Leukemia (2000) 14, 93-99.
The translocation t(10;11)(p13;q14) has been observed in acute lymphoblastic leukemia (ALL) as well as acute myeloid leukemia (AML). A recent study showed a MLL/AF10 fusion in all cases of AML with t(10;11) and various breakpoints on chromosome 11 ranging from q13 to q23. We recently cloned CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene), the fusion partner of AF10 at 11q14 in the monocytic cell line U937. To further define the role of these genes in acute leukemias, 10 cases (9 AML and 1 ALL) with cytogenetically proven t(10;11)(p12-14;q13-21) and well-characterized morphology, immunophenotype, and clinical course were analyzed. Interphase fluorescence in situ hybridization (FISH) was performed with 2 YACs flanking the CALM region, a YAC contig of the MLL region, and a YAC spanning the AF10 breakpoint. Rearrangement of at least one of these genes was detected in all cases with balanced t(10;11). In 4 cases, including 3 AML with immature morphology (1 AML-M0 and 2 AML-M1) and 1 ALL, the signals of the CALM YACS were separated in interphase cells, indicating a translocation breakpoint within the CALM region. MLL was rearranged in 3 AML with myelomonocytic differentiation (2 AML-M2 and 1 AML-M5), including 1 secondary AML. In all 3 cases, a characteristic immunophenotype was identified (CD4+, CD13-, CD33+, CD65s+). AF-10 was involved in 5 of 6 evaluable cases, including 1 case without detectable CALM or MLL rearrangement. In 2 complex translocations, none of the three genes was rearranged. All cases had a remarkably poor prognosis, with a mean survival of 9.6 +/- 6.6 months. For the 7 AML cases that were uniformly treated according to the AMLCG86/92 protocols, disease-free and overall survival was significantly worse than for the overall study group (P = .03 and P = .01, respectively). We conclude that the t(10;11)(p13;q14) indicates CALM and MLL rearrangements in morphologically distinct subsets of acute leukemia and may be associated with a poor prognosis.
Field potential recording was used to investigate properties of synaptic transmission and long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in both hippocampal slices of mutant mice in which the alpha-subunit of the olfactory cyclic nucleotide-gated channel (alpha3/OCNC)1 was rendered null and also in slices prepared from their wild-type (Wt) littermates. Several measures of basal synaptic transmission were unaltered in the OCNC1 knockout (KO), including maximum field excitatory postsynaptic potential (fEPSP) slope, maximum fEPSP and fiber volley amplitude, and the function relating fiber volley amplitude to fEPSP slope and paired-pulse facilitation. When a high-frequency stimulation protocol was used to induce LTP, similar responses were seen in both groups [KO: 1 min, 299 +/- 50% (mean +/- SE), 60 min, 123 +/- 10%; Wt: 1 min, 287 +/- 63%; 60 min, 132 +/- 19%). However, on theta-burst stimulation, the initial amplitude of LTP was smaller (1 min after induction, 147 +/- 16% of baseline) and the response decayed faster in the OCNC1 KO (60 min, 127 +/- 18%) than in Wt (1 min, 200 +/- 14%; 60 min, 169 +/- 19%). Analysis of waveforms evoked by LTP-inducing tetanic stimuli revealed a similar difference between groups. The development of potentiation throughout the tetanic stimulus was similar in OCNC1 KO and Wt mice when high-frequency stimulation was used, but OCNC1 KO mice showed a significant decrease when compared with Wt mice receiving theta-burst stimulation. These results suggest that activation of cyclic nucleotide-gated channels may contribute to the induction of LTP by weaker, more physiological stimuli, possibly via Ca2+ influx.
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The expression of specialized signal transduction components in mammalian olfactory neurons is thought to be regulated by the O/E (Olf-1/EBF) family of transcription factors. The O/E proteins are expressed in cells of the olfactory neuronal lineage throughout development and are also expressed transiently in neurons in the developing nervous system during embryogenesis. We have identified a C. elegans homologue of the mammalian O/E proteins, which displays greater than 80% similarity over 350 amino acids. Like its mammalian homologues, CeO/E is expressed in certain chemosensory neurons (ASI amphid neurons) throughout development and is also expressed transiently in developing motor neurons when these cells undergo axonal outgrowth. We demonstrate that CeO/E is the product of the unc-3 gene, mutations in which cause defects in the axonal outgrowth of motor neurons, as well as defects in dauer formation, a process requiring chemosensory inputs. These observations suggest that the O/E family of transcription factors play a central and evolutionarily conserved role in the expression of proteins essential for axonal pathfinding and/or neuronal differentiation in both sensory and motor neurons.
Results of this study confirm that high temperature (118 degrees C/15 min) and high pressure (400 MPa/5 min) processing of skim milk, skim milk ultrafiltration and ultracentrifugation fractions, and model milk salt solutions cause dramatic shifts in their colloidal and soluble Ca phosphate equilibrium that affect their pH, dissolved Ca content, turbidity, and casein micelle microstructure. The relations between high temperature and high pressure processing-induced changes in the colloidal and soluble Ca phosphate equilibrium were evaluated in raw, pasteurized, and high temperature treated skim milk, ultrafiltration retentate and permeate of pasteurized skim milk, clear ultracentrifugation infranatant of pasteurized skim milk, and synthetic milk ultrafiltrates with and without lactose or Ca. The magnitude of the pH and dissolved Ca shifts caused by high temperature and high pressure processing was a function of casein micelle concentration. Ultrafiltration permeate exhibited the most drastic shits in pH and dissolved Ca contents due to high temperature and high pressure processing. Although high temperature processing reduced the pH of ultrafiltration permeate from 6.59 to 6.03 and the dissolved Ca from 100% to 58%, high pressure processing reversed both of these changes. These changes in high temperature and high pressure processed milk, milk fractions, and model milk salt solutions were related to microstructural changes in the casein micelles as revealed by electron microscopy.
Benzaldehyde was administered by inhalation to female and male Sprague-Dawley rats for 14 consecutive days (low level: 500 ppm; medium level: 750 ppm; high level: 1000 ppm). Effects of this chemical were investigated during and at the end of the exposure period. Throughout the experiment, significant hypothermia and a reduction of motor activity were observed in all rats exposed to benzaldehyde and were accompanied in high-level rats by a severe impairment of the central nervous system, as evidenced by abnormal gait, tremors, and a positive Straub sign. Histopathologic examination of tissues from exposed rats showed a goblet cell metaplasia that was largely confined to the respiratory epithelium lining the nasal septum in male rats. No other abnormal microscopic changes were observed. A no effect level was not observed in these studies.
After explaining the idea and purpose of cosmetic products, we report on the course of development these products usually take: marketing briefing, selection of the raw materials, serial experiments and stability tests, and finally, dermatophysiological efficacy tests. In particular, we deal with the application of adenosine triphosphate (ATP) and its moisturing and smoothing effect on human skin. Our results are discussed in detail.
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The combined effects of ethinyl estradiol (EE) (0.5 micrograms/g s.c. once daily for 4 days) and tetracycline (TC) or doxycycline (DC) (50 micrograms/g i.v.) on liver weight and water content, serum transaminases, alkaline phosphatase, urea, triglycerides, and cholesterol as parameters of various liver functions were investigated in mice. It became apparent that depending on the parameter tested synergistic and antagonistic effects may occur, e.g., synergistic effects were observed with the serum transaminases and liver cholesterol; antagonistic effects were seen with the serum urea and serum cholesterol.
The response of the peripheral nervous system to various dose levels of tributoxyethyl phosphate (TBOP) was investigated in Sprague-Dawley rats. Groups of randomized female and male rats (10 rats/gender/dose level) were administered a single oral dose of TBOP (1.0 to 3.2 g/kg for females; 1.0 to 9.0 g/kg for males). Physiological parameters were measured in surviving rats three weeks following TBOP administration. A significant reduction (p less than 0.05) in caudal nerve conduction velocity (NCV) was observed in both female and male rats. Light and electron microscopic examination of sciatic nerve sections showed degenerative changes in both myelinated and unmyelinated fibers of female (2.0 g/kg) and male (6.8 g/kg) groups. Advanced degeneration was observed only in the highest dose level of both genders (3.2 g/kg for females; 8.0 and 9.0 g/kg for males). Although similar morphological changes were observed in both genders, females were more susceptible than males to the toxic effects of this compound.
The effects of a widely used trialkyl phosphate (TP), tributoxyethyl phosphate (TBOP), on the peripheral nervous system of Sprague-dawley (SD) rats were investigated. Male and female SD rats were administered this chemical by gavage over a period of 18 weeks (low dose: 0.25 ml kg-1; high dose: 0.50 ml kg-1). Electrophysiological changes observed at 18 weeks in all test animals included a significant reduction (P less than 0.001) in nerve conduction velocity and an important increase (P less than 0.001) of both relative (RRP) and absolute refractory period (ARP). Light and electron microscopic examination of sciatic nerve from all test animals showed the presence of degenerating myelin sheaths accompanied by axonal swelling. An advanced stage of degeneration was indicated by the presence of lamellated electron dense inclusions in unmyelinated nerve fibres.
Biological effects of a single exposure to moderate or high concentrations of 2-propanol were investigated in Sprague-Dawley rats. Acute toxicity (LC50, t:8 hours) of this widely used solvent was determined and found to be 19000 ppm (17380-20760 ppm) for females and 22500 ppm (19200-26400 ppm) for males. Determination of blood levels of 2-propanol and its metabolite, acetone, was carried out during and after a single 4-hour exposure (Concentration range: 500 to 8000 ppm). The amount of acetone and 2-propanol was directly related to the various air concentrations of alcohol inhaled. Increase of exposure time to 8 hours enhanced considerably the amount of blood acetone which could be determined even 20 hours after exposure. These findings indicate a slow conversion of this alcohol to acetone which can be used as biochemical indicator to exposure. Histopathological examination of rats exposed to high levels of 2-propanol shows typical lesions of chemical pneumonitis and pulmonary edema accompanied by foamy vacuolization of liver cells and severe focal cytoplasmic degradation.