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Biomedical subjects

E Schuler

Publications and source records attributed to E Schuler.

11 recordsLinked to original sources
PubMed2001

Synthesis and biological activity of 7-oxo substituted analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid (5-DATHF) and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF).

We recently described the syntheses of 12a-c, 4-amino-7-oxo substituted analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid (5-DATHF), and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), in six steps from commercially available p-substituted methyl benzoates in 20-27% overall yields. Such analogues were tested in vitro against CCRF-CEM leukemia cells and showed that they are completely devoid of any activity, the IC(50) being higher than 20 microg/mL for all cases. To clarify if the presence of the carbonyl group in position C7, the distinctive feature of our synthetic methodology, is the reason for this lack of activity, we have now obtained the 7-oxo substituted analogues of 5-DATHF and DDATHF, 18a-c, in 10-30% overall yield. Testing of 18a-c in vitro against CCRF-CEM leukemia cells revealed that these compounds are totally inactive. A molecular modeling study of 18b inside the active site of the complex E. coliGARTFase-5-DATHF-GAR pointed to an electronic repulsion between the atoms of the 7-oxo group and the carbonyl group of Arg90 as a possible explanation for the inactivity of 18a-c.

Antineoplastic Agents↗
PubMed1999

Nonsurgical management of binocular diplopia induced by macular pathology.

OBJECTIVE: To treat binocular diplopia secondary to macular pathology. METHODS: Seven patients underwent evaluation and treatment. All had constant vertical diplopia caused by various maculopathies, including subretinal neovascularization, epiretinal membrane, and central serous retinopathy. Visual acuity ranged from 20/20 to 20/30 in the affected eye. All except 1 patient had a small-angle, comitant hyperdeviation with no muscle paresis. Sensory evaluation demonstrated peripheral fusion and reduced stereoacuity. Neither prism correction nor manipulation of the refractive errors corrected the diplopia. A partially occlusive foil (Bangerter) of density ranging from 0.4 to 1.0 was placed in front of the affected eye to restore stable, single vision. RESULTS: The Bangerter foil eliminated the diplopia in all patients. Two patients elected not to wear the foil; 1 patient was afraid of becoming dependent, and the other was bothered by the visual blur. Visual acuity in the affected eye was reduced on average by 3 lines. All patients maintained the same level of sensory fusion, with only 2 having reduced stereoacuity. Symptoms returned when the foil was removed or its density was reduced. CONCLUSION: Low-density Bangerter foils provide an effective, inexpensive, and aesthetically acceptable management for refractory binocular diplopia induced by macular pathology, allowing peripheral fusion to be maintained.

Adult↗
PubMed1999

Decompensated strabismus after laser in situ keratomileusis.

We present a case of decompensated nerve IV palsy with vertical diplopia afer bilateral laser in situ keratomileusis. As the patient was given monovision, we believe diplopia occurred with a decrease in vision in 1 eye and interruption of fusion. Although corrective spectacles to restore equal vision at distance were prescribes, the patient needed a prism to eliminate her double vision. We suggest a careful cover/uncover test and versions assessment in all candidates for refractive surgery who want monovision correction and a full ocular motility evaluation if there is any doubt about binocular issues.

Adaptation, Ocular↗
PubMed1994

Characterization of the human gene encoding LBR, an integral protein of the nuclear envelope inner membrane.

We have characterized the human gene encoding LBR, an integral protein of the nuclear envelope inner membrane. Restriction mapping shows that the transcription unit spans approximately 35 kilobases. A transcription start site is located approximately 4 kilobases 5' to the translation initiation codon, and an RNA splice of 3863 bases occurs in the 5'-untranslated region to generate mature HeLa cell mRNA. 5' to the identified transcription start site are two CCAAT sequences and potential recognition sites for several transcription factors including Sp1, AP-1, AP-2, and NF-kB. There are 13 protein coding exons in the LBR gene. LBR's nucleoplasmic domain is encoded by exons 1-4, and its hydrophobic domain, with eight putative transmembrane segments, is encoded by exons 5-13. The hydrophobic domain is homologous to three yeast polypeptides, suggesting that this higher eukaryotic gene could have evolved from recombination between a gene that encoded a soluble nuclear protein and a membrane protein gene similar to those in yeast. These results are the first to demonstrate the structural organization of a vertebrate gene encoding an integral membrane protein of the nuclear envelope that may be a member of a family of polypeptides conserved in evolution.

Amino Acid Sequence↗
PubMed1994

Rhythmic oscillations with a wavelength of 0.5-2 min in transcranial Doppler recordings.

We have studied intracranial pressure (ICP) B-waves and their association with rhythmic changes in blood flow velocity (B-wave equivalents) by transcranial Doppler sonography (TCD) monitoring. In overnight TCD recordings in 10 normal young adults, these rhythmic changes in blood flow velocity were higher and more frequent during REM sleep and sleep stage 1 than during other sleep stages. B-wave equivalents also had a longer wavelength during REM sleep. Their relative frequency in these normal subjects over one night ranged from 35 to 73%. Peripheral resistance (assessed by the Pourcelot index) was lower and heart rate was higher at the peak of these oscillations. These results support the hypothesis that ICP B-waves are caused by vasodilation. A non-linear relationship between ICP and blood flow velocity was found during B-waves in 9 of 11 patients with suspected NPH. Our results throw doubt on the suggestion that a relative frequency of less than 80% B-wave activity can be a valid indicator for shunt responsiveness in patients with suspected normal pressure hydrocephalus (NPH). ICP recordings in suspected NPH should be accompanied by polysomnography to avoid misleading results due to variability of B-wave appearance dependent on sleep pattern.

Adult↗
PubMed1993

Middle cerebral artery blood flow velocity in healthy persons during wakefulness and sleep: a transcranial Doppler study.

In 10 normal young adults, middle cerebral artery blood flow velocity was measured continuously over one night by transcranial Doppler sonography. Polysomnography was used to assess the different sleep stages and waking state. During rapid eye movement (REM) sleep, middle cerebral artery blood flow velocity was higher than in any other sleep stage and wakefulness. During the waking state the velocity was higher than in sleep stage 2. Spontaneous rhythmic oscillations of cerebral blood flow velocity were found related to different stages of sleep. A fast Fourier's transformation of the Doppler wave forms revealed a periodicity of 20-75 seconds, which was most prominent during REM sleep and to a lesser degree during sleep stages 1, 2 and 3 and the waking state. These waves may correspond to intracranial pressure changes referred to as B-waves.

Adult↗
PubMed1993

Liver carcinogenesis associated with feeding of ethionine in a choline-free diet: evidence against a role of oval cells in the emergence of hepatocellular carcinoma.

In an attempt to clarify the role of oval cells in the emergence of hepatocellular carcinoma, we fed rats a choline-free diet containing 0%, 0.05% or 0.1% ethionine. The incidence and nature of premalignant and malignant hepatic lesions were then related to the degree of oval cell proliferation. Intake of choline-free diet alone for up to 12 mo was associated with minimal oval cell proliferation; cholangiofibrosis, hepatocellular nodules and hepatocellular carcinoma were observed in 55%, 23% and 14% of the animals, respectively. When rats were given the choline-free diet with 0.05% ethionine, proliferation of oval cells was more pronounced; after a 6- to 12 mo feeding period, cholangiofibrosis (57%) was again observed. However, hepatocellular nodules (91%) and hepatocellular carcinoma (74%) were the most common lesions seen with this feeding regimen. Finally, rats fed the choline-free diet with 0.1% ethionine had massive oval cell proliferation and progressive loss of parenchymal liver tissue. Most of these animals died before they had consumed the choline-free diet with 0.1% ethionine for 12 mo. Rats in this group (96%) exhibited large and numerous cholangiofibrotic lesions, but hepatocellular nodules and carcinoma were not detected. In all animals of each experimental group, hyperplastic bile duct cells in areas of cholangiofibrosis and oval cells were positive for cytokeratin 19, an intermediate filament protein present only in bile duct cells in normal liver. Hepatocellular nodules and hepatocellular carcinoma were invariably negative for cytokeratin 19. We interpret these findings to suggest that oval cells are not involved in the histogenesis of hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

[Malate dehydrogenase isoenzymes in myocardial infarction].

Plasma CPK activity and the activity of isoenzymes MDH, AST and LDH were assessed in 60 patients with myocardial infarction of different severity, with reference to the time since the onset of the attack. The peaks of CPK and MDH-C activity were reached sooner than those of LDH-M and AST-C, while the CPK and MDH-C curves were similar. The severity of the disease showed correlation to later onset of enzyme peaks and markedly delayed decrease in the respective values. Increased activity of mitochondrial isoenzymes and blood LDH-M provided additional information on the severity of the disease. Delayed normalization of these activities was associated with a poor diagnosis.

Aged↗