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Biomedical subjects

L Simon

Publications and source records attributed to L Simon.

At least 73 records · Page 4Linked to original sources
PubMed1997

Progression into the first meiotic division is sensitive to histone H2A-H2B dimer concentration in Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae contains two genes for histone H2A and two for histone H2B located in two divergently transcribed gene pairs: HTA1-HTB1 and HTA2-HTB2. Diploid strains lacking HTA1-HTB1 (hta1-htb1 delta/hta1-htb1 delta, HTA2-HTB2/HTA2-HTB2) grow vegetatively, but will not sporulate. This sporulation phenotype results from a partial depletion of H2A-H2B dimers. Since the expression patterns of HTA1-HTB1 and HTA2-HTB2 are similar in mitosis and meiosis, the sporulation pathway is therefore more sensitive than the mitotic cycle to depletion of H2A-H2B dimers. After completing premeiotic DNA replication, commitment to meiotic recombination, and chiasma resolution, the hta1-htb1 delta/hta1-htb1 delta, HTA2-HTB2/HTA2-HTB2 mutant arrests before the first meiotic division. The arrest is not due to any obvious disruptions in spindle pole bodies or microtubules. The meiotic block is not bypassed in backgrounds homozygous for spo13, rad50 delta, or rad9 delta mutations, but is bypassed in the presence of hydroxyurea, a drug known to inhibit DNA chain elongation. We hypothesize that the deposition of H2A-H2B dimers in the mutant is unable to keep pace with the replication fork, thereby leading to a disruption in chromosome structure that interferes with the meiotic divisions.

Histones↗
PubMed1997

Pathogen-induced programmed cell death in tobacco.

Sacrificing an infected cell or cells in order to prevent systemic spread of a pathogen appears to be a conserved strategy in both plants and animals. We studied some of the morphological and biochemical events that accompany programmed cell death during the hypersensitive response of tobacco plants infected with tobacco mosaic virus. Certain aspects of this cell death process appeared to be similar to those that take place during apoptosis in animal cells. These included condensation and vacuolization of the cytoplasm and cleavage of nuclear DNA to 50 kb fragments. In contrast, internucleosomal fragmentation, condensation of chromatin at the nuclear periphery and apoptotic bodies were not observed in tobacco plants during tobacco mosaic virus-induced hypersensitive response. A unique aspect of programmed cell death during the hypersensitive response of tobacco to tobacco mosaic virus involved an increase in the amount of monomeric chloroplast DNA. Morphological changes to the chloroplast and cytosol of tobacco cells and increase in monomeric chloroplast DNA occurred prior to gross changes in nuclear morphology and significant chromatin cleavage. Our findings suggest that certain aspects of programmed cell death may have been conserved during the evolution of plants and animals.

Apoptosis↗
PubMed1997

Incidence of childhood-onset IDDM in black African-heritage populations in the Caribbean. The Caribbean African Heritage IDDM Study (CAHIS) Group.

OBJECTIVE: To compare incidence rates of childhood-onset IDDM among black African-heritage populations age 0-19 years in the Caribbean region. RESEARCH DESIGN AND METHODS: Population-based registries for IDDM were established on the eastern Caribbean islands of Antigua, Barbados, Dominica, St. Croix, St. Kitts, St. Thomas, and Tortola using standardized criteria from the World Health Organization (WHO) Multinational Project for Childhood Diabetes (DiaMond). Average annual incidence rates (IR) with 95% CI for 0-19 years olds were computed using the DiaMond Registry program for the 5-year period from 1989 to 1993. Poisson regression analysis was used to determine differences in incidence rates. RESULTS: The highest incidence rate for 0-19 year olds was for the black African-heritage population of St. Croix (IR 10.09 per 100,000; 95% CI 4.35-19.89), one of the U.S. Caribbean islands. A significant (P < 0.05) 3.9 variation in IDDM incidence across the registries was found when the IR for St. Croix was compared to the IR for Barbados (IR 2.57 per 100,000; 95% CI 0.90-4.64). CONCLUSIONS: The variation in childhood-onset IDDM incidence rates among the black populations of the eastern Caribbean islands is consistent with the geographic variation in IDDM incidence seen among African Americans in the U.S. Variation in incidence rates of childhood diabetes in black populations may reflect differences in level of white genetic admixture or exposure to environmental diabetogenic agents.

Adolescent↗
PubMed1997

Ebrotidine versus ranitidine in the healing and prevention of relapse of duodenal ulcer. A multicentre, double-blind, parallel, randomized, controlled study.

Two hundred and fifty patients were included in a double-blind, parallel, randomized, controlled clinical trial. Duodenal ulcer treatment lasted up to 8 weeks. Forty-nine patients were followed up for prevention of ulcer relapse for up to one year. All patients received either ranitidine (300 mg/day in the healing phase and 150 mg/day in the follow-up phase) or ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4 -thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide , CAS 100981-43-9, FI-3542) (400 mg/day in both phases) as a single dose at bedtime. Both groups were matched in all demographic parameters, except for a significantly higher percentage of smokers in the ranitidine group. The percentage of total healing was almost the same with both products. Healing occurred in a higher percentage with ebrotidine at weeks 4 (75% versus 66.7%) and 6 (87% versus 79.7%). A higher effect of ebrotidine on the incidence of duodenitis was identified during the whole study, but only reached statistical significance at week 6. The relapse rate during the follow-up phase showed no differences between the two study treatments, relapse percentage figures being 25% for ebrotidine and 24% for ranitidine. There were no differences in the number of unscheduled visits between the two groups, although 57% of patients in the ranitidine group had to make a second follow-up visit, as compared with 33% in the ebrotidine group. Both drugs caused hardly any side effects, affecting only one patient from each group: one patient with ebrotidine suffered from diarrhoea and one patient with ranitidine developed a skin rash on the limbs. Administration of ebrotidine in a single dose (400 mg/d) was at least as effective and safe as ranitidine both for healing and relapse prevention in patients with duodenal ulcer.

Adult↗
PubMed1997

[Surgical approach on rabbit embryos. A model trial of bladder exstrophy].

We describe herein a new model of surgical approach of an early mammalian embryo. Indeed the developmental mechanisms of numerous congenital anomalies, such as bladder exstrophy, remain obscure, and progresses in their knowledge must be achieved to propose better treatments. But up to now all the successful reports in experimental models of early produced malformations concerned birds or batracians, whose development is very different from human. We used the rabbit. Twenty-five time matted does were operated at 12.5 days of gestation. Out of their 247 embryos, 99 underwent a surgical procedure. Forty-eight were injured in order to produce an exstrophy. In 18 cases, the embryo extruded from the uterine cavity and could not be reintegrated, and 2 sacs were found empty. The remaining 31 were only exteriorized. Nine additional does received intravenous teratogen at 12.5 days of gestation. In the group of operated embryos we obtained 6 full-term fetuses, one of whom had a cloacal exstrophy. No exstrophy was noted among the intact embryos, neither in the 87 fetuses submitted to the teratogen. We conclude that: it is possible to operate on an early mammalian embryo, and to obtain further growth until term and that the exstrophy we observed in one case resulted from the surgical specific procedure.

Animals↗
PubMed1996

Betidamino acids: versatile and constrained scaffolds for drug discovery.

Betidamino acids (a contraction of "beta" position and "amide") are N'-monoacylated (optionally, N'-monoacylated and N-mono- or N,N'-dialkylated) aminoglycine derivatives in which each N'acyl/alkyl group may mimic naturally occurring amino acid side chains or introduce novel functionalities. Betidamino acids are most conveniently generated on solid supports used for the synthesis of peptides by selective acylation of one of the two amino functions of orthogonally protected aminoglycine(s) to generate the side chain either prior to or after the elongation of the main chain. We have used unresolved Nalpha-tert-butyloxycarbonyl-N'alpha-fluorenylmethoxycarbonyl++ + aminoglycine, and Nalpha-(Nalpha-methyl)-tert-butyloxycarbonyl-N'alpha-fluo renylmethoxycarbonyl aminoglycine as the templates for the introduction of betidamino acids in Acyline [Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph(Ac)-D4Aph(A c)-Leu-Ilys-Pro-DAla-NH2, where 2Nal is 2-naphthylalanine, 4Cpa is 4-chlorophenylalanine, 3Pal is 3-pyridylalanine, Aph is 4-aminophenylalanine, and Ilys is Nepsilon-isopropyllysine], a potent gonadotropin-releasing hormone antagonist, in order to test biocompatibility of these derivatives. Diasteremneric peptides could be separated in most cases by reverse-phase HPLC. Biological results indicated small differences in relative potencies (<5-fold) between the D and L nonalkylated betidamino acid-containing Acyline derivatives. Importantly, most betide diastereomers were equipotent with Acyline. In an attempt to correlate structure and observed potency, Ramachandran-type plots were calculated for a series of betidamino acids and their methylated homologs. According to these calculations, betidamino acids have access to a more limited and distinct number of conformational states (including those associated with alpha-helices, beta-sheets, or turn structures), with deeper minima than those observed for natural amino acids.

Amino Acid Sequence↗
PubMed1996

Amyloidosis-related cauda equina compression in long-term hemodialysis patients. Three case reports.

STUDY DESIGN: These case reports illustrate the neurologic manifestations due to beta 2 microglobulin amyloid deposition at the lumbar spine level in long-term hemodialysis patients. OBJECTIVE: Radiologic investigations suggested the amyloid origin of extradural soft tissue deposition, which was confirmed by histologic examination after surgical excision. SUMMARY OF BACKGROUND DATA: Although cervical myelopathy is a recently recognized complication of long-term dialysis-related beta 2 microglobulin amyloidosis, neurologic manifestations due to amyloid deposition at the lumbar spine level have rarely been reported. METHODS: Three case reports of cauda equina compression in long-term hemodialysis patients are presented. Follow-up radiography, computed tomography, and magnetic resonance imaging were performed and patients underwent surgical decompression of the thecal sac. RESULTS: In two patients, the compression resulted from the development of a destructive spondylarthropathy, and from the infiltration of extradural spaces and ligaments by an abnormal soft tissue. The third patient had lumbar spinal stenosis due to multiple disc protrusion and to hypertrophy of facet joints and ligamentum flavum. Multilevel laminectomies enabled excision of an abnormal fibrous tissue responsible for the thecal sac compression. Histologic examination of the excised fibrous tissues disclosed amyloid deposits in intervertebral discs, apophysial joints, and ligaments. CONCLUSIONS: In long-term hemodialysis patients, cauda equina compression may develop as the consequence of beta 2 microglobulin amyloid deposition in lumbar intervertebral discs, facet joints, and ligaments. Magnetic resonance imaging is well suited to show the extent of the compression and supports the argument for the amyloid origin of extradural soft tissue.

Adult↗
PubMed1996

[Epidural lipomatosis: complication of long-term corticotherapy. Apropos of 2 cases].

Spinal epidural lipomatosis (SEL) is defined as the deposition of loose fat tissue in the epidural space. Two cases are reported which illustrate the main features of this uncommon disease. Most frequently SEL is revealed by neurologic manifestations such as an acute chronic spinal cord compression. Corticosteroid therapy and obesity are the main factors able to induce the disease. The common location of the SEL at the thoracic spine is explained by the physiologic abundance of fat and by the relative narrowness of the spinal canal at this level. An osteoporotic vertebral crush fracture which reduces the diameter of the canal frequently reveals the SEL. MRI confirms the diagnosis of SEL and shows the extent in the spinal canal. The treatment of SEL is difficult. The decrease or the stop of corticosteroid therapy has allowed the recovery in a few cases with chronic neurologic symptoms. The risks of a surgical procedure are important in these patients and the medical or surgical treatment should be discussed taking into account the clinical symptoms of SEL, its location and extent, and the risks of recurrence if corticosteroid therapy must go on.

Adult↗
PubMed1996

Impact of Medicaid managed care on child and adolescent emergency mental health screening in Massachusetts.

OBJECTIVE: The study evaluated the impact of Medicaid managed care on decision making during emergency mental health screening and the outcomes of such screening for children and adolescents. METHODS: Data on client attributes and on system characteristics (payer, referral source, and disposition) were available for 297 Medicaid and non-Medicaid episodes of emergency mental health screening that occurred one year before the implementation of a statewide managed Medicaid program in Massachusetts and 393 episodes that occurred one year after implementation. Outcomes included changes in the volume of service provided and in the pattern of dispositions, particularly inpatient admissions. RESULTS: Although the total volume of child and adolescent emergency screening episodes significantly increased after implementation of Medicaid managed care, inpatient admissions decreased significantly. Among episodes not covered by Medicaid, no significant changes were noted after implementation on any variables. In the Medicaid group, significant differences were found in client attributes and system characteristics. After implementation the volume of emergency screening episodes for Medicaid clients increased significantly, and inpatient admissions decreased significantly. The pattern of dispositions changed significantly, with increased use of newly available crisis stabilization services. CONCLUSIONS: Although implementation of Medicaid managed care achieved the short-term goal of a decrease in hospitalizations, and probably concomitant savings, issues of quality of care for children and adolescents, and savings over the longer term, remain to be addressed.

Adolescent↗
PubMed1996

Case mix in the "downsizing" state hospital.

OBJECTIVE: The study examined whether local variations in levels of community-based services affect the case mix of state hospitals undergoing census reduction. METHODS: Trends in case mix over a 14-year period were analyzed at two Massachusetts state hospitals, one of which underwent more rapid census reduction due to expanded community resources in the catchment area it served. Data on patients' hospital use and on sociodemographic and diagnostic characteristics obtained from 1977, 1986, and 1991 assessments of the hospitals' populations were compared. These time points represented the beginning, midpoint, and end of the census reduction period. Data from 1991 on patients' behavioral and functional status were also examined. RESULTS: Parallel trends on many dimensions were evident at the two hospitals as their censuses fell. By 1986 the hospital operating in the area with greater community services had fewer elderly and long-stay patients but a higher number of admissions per patient. In 1991 this hospital's population also had more patients with high-risk violent behaviors and lower levels of functioning. CONCLUSIONS: Although alternative treatment settings allow diversion of many types of patients from state hospitals, expanded community-based services and alternative inpatient beds have not diverted some patient subgroups, including recidivists and patients with behaviors that present risks in other settings. Plans for meeting the clinical needs and behavioral challenges posed by such patients must be part of any further deinstitutionalization or privatization efforts.

Adolescent↗
PubMed1996

[Saturated heterocyclic compounds. 216 (1). Synthesis, structure and ring opening of trans-perhydro-1,4-benzoxazepin-3-one derivatives].

trans-Perhydro-1,4-benzoxazepin-3-ones 2a-e were synthesized and transformed to condensed-skeleton perhydro-trans-1,4-benzoxazepines 3a,b, the thiones 4a,b, the urea derivatives 5a,b, and N-acylated compounds 6a-e. Compounds 6b,d were ring-opened by hydrochloride acid in ethanol to yield trans-2 (1-carbethoxyethoxy)-1-(acylaminomethyl)-cyclohexane derivatives 7b,d. The 1H- and 13C-nmr investigation and X-ray analysis of 5b and 6c,d proved that the expected N-acylated derivatives were formed and that both rings of the annolated compounds have a chair conformation.

Acetylation↗