Search PubMed⌕ Search

Biomedical subjects

L Martin

Publications and source records attributed to L Martin.

At least 235 records · Page 13Linked to original sources

The Sycp1 loci of the mouse genome: successive retropositions of a meiotic gene during the recent evolution of the genus.

The murine Sycp1 gene is expressed at the early stages of meiosis. We show that it is composed of a number of small exons and localized on mouse chromosome 3. In the laboratory strains, two retrogenes were also identified. The first one (Sycp1-ps1), on chromosome 7, has accumulated point mutations and deletions and is not transcribed. A second retrogene (Sycp1-ps2), on chromosome 8, is inserted within the continuity of a moderately repeated element, in an intron of another gene (Cad11). The two retroposition events can be dated to distinct periods in the evolution of the Muridae. Sycp1-ps2 has kept features indicative of a relatively recent origin, namely a nearly intact coding region, a poly(A) tail, and 14-bp terminal repeats. Its recent origin was confirmed by the fact that it is found in all the laboratory strains of mice, but neither in a recent isolate from Mus musculus domesticus wild stocks nor in the closely related subspecies M. musculus musculus, M. m. molossinus, M. m. castaneus, and M. m. bactrianus. Appearance of the more ancient Sycp1-ps1 retrogene is concomitant with the radiation of the genus. It is present in various Mus species (M. spretus, M. spicilegus, M. macedonicus, and M. cookii), but neither in the rat nor in the more closely related Pyromis genus. Transposition of retrotranscripts during meiosis and their hereditary establishment thus appear to occur relatively frequently. They may, therefore, play a significant role in the evolutionary process.

Animals↗

Purification, crystallization and preliminary X-ray analysis of Bacteroides fragilis Zn2+ beta-lactamase.

The Zn(2+) beta-lactamase from Bacteroides fragilis (E.C. 3.5.2.6) was overexpressed in Escherichia coli using an isopropylthiogalactoside-inducible T7 RNA polymerase expression system. Crystallization trials by the hanging-drop vapour-diffusion method have yielded two different crystal forms from two slightly different conditions. Crystals of form I belong to the monoclinic space group C2 with unit-cell dimensions a = 56.03, b = 43.98, c = 105.32 A, beta = 112 degrees and diffracted only up to 4.0 A. Crystals of form II are orthorhombic, space group P2(1)2(1)2(1) with unit-cell dimensions a = 48.10, b = 98.05, c = 111.76 A, diffract to at least 2.0 A and are suitable for high-resolution structural analysis.

Journal Article↗

Crystal structure of UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase from Escherichia coli.

UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD) is a cytoplasmic enzyme involved in the biosynthesis of peptidoglycan which catalyzes the addition of D-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA). The crystal structure of MurD in the presence of its substrate UMA has been solved to 1.9 A resolution. Phase information was obtained from multiple anomalous dispersion using the K-shell edge of selenium in combination with multiple isomorphous replacement. The structure comprises three domains of topology each reminiscent of nucleotide-binding folds: the N- and C-terminal domains are consistent with the dinucleotide-binding fold called the Rossmann fold, and the central domain with the mononucleotide-binding fold also observed in the GTPase family. The structure reveals the binding site of the substrate UMA, and comparison with known NTP complexes allows the identification of residues interacting with ATP. The study describes the first structure of the UDP-N-acetylmuramoyl-peptide ligase family.

Adenosine Triphosphate↗

In vitro and in vivo studies of a polyester arterial prosthesis with a warp-knitted sharkskin structure.

The present study was undertaken to assess the performance of a new knitted and gelatin-sealed polyester vascular graft that is believed to have greater dimensional stability than current commercial devices. Samples of the uncrimped, crimped, and sealed prosthesis were submitted to a series of in vitro and in vivo trials. Four commercial polyester knitted devices were included as controls for the in vitro tests, which included measurements of the textile and yarn structure and physical, chemical, and thermal properties of the graft, such as water permeability, dilatation, suture retention strength, melting point, and crystallinity index. The in vivo evaluation involved implanting the prototype device as a canine thoraco-abdominal bypass for periods ranging from 4 h to 1 year and assessing the biocompatibility, biofunctionality, and biostability of the explanted specimens. The warp-knitted structure of the prototype device has a unique sharkskin stitch that confers a superior dilatation resistance and suture retention strength to the prosthesis. The animal trial demonstrated that the gelatin ensures initial hemostasis without preclotting. The gelatin is bioresorbed during the first 2 weeks of implantation, which generates a temporary, moderate, acute inflammatory response. An external capsule of granulomatous tissue and an internal collagen capsule are formed between the first and third month. Analysis of the textile and physical properties of the explanted prostheses confirmed there was neither dilatation nor significant changes in structure or mechanical performance during implantation, thus confirming the biostability of this new prototype device and opening the way for clinical trials.

Anastomosis, Surgical↗

Effects at two years of a low-fat, high-carbohydrate diet on radiologic features of the breast: results from a randomized trial. Canadian Diet and Breast Cancer Prevention Study Group.

BACKGROUND: The appearance of breast tissue on mammography varies according to its composition. Fat is radiolucent and appears dark on mammography, while stromal and epithelial tissue has greater optical density and appears light. Extensive areas of radiologically dense breast tissue seen on mammography are associated with an increased risk of breast cancer. PURPOSE: The purpose of the present study was to determine whether the adoption of a low-fat, high-carbohydrate diet for 2 years would reduce breast density. METHODS: Women with radiologic densities in more than 50% of the breast area on mammography were recruited and randomly allocated to an intervention group taught to reduce intake of dietary fat (mean, 21% of calories) and increase complex carbohydrate (mean, 61% of calories) or to a control group (mean, 32% of calories from fat and 50% of calories from carbohydrates). Mammographic images from 817 subjects were taken at baseline and compared with those taken 2 years after random allocation by use of a quantitative image analysis system, without knowledge of the dietary group of the subjects or of the sequence in which pairs of images had been taken. The effects of the intervention on the mammographic features of breast area, area of dense tissues in the breast, and the percent of the breast occupied by dense tissue were examined using t tests. Multiple regression was used to examine these effects while accounting for age at trial entry, weight change, and menopausal status. RESULTS: After 2 years, the total area of the breast was reduced by an average of 233.7 mm2 (2.4%) (95% confidence interval [CI] = 106.9-360.6) in the intervention group compared with an average increase of 26.3 mm2 (0.3%) (95% CI = -108.0-160.5) in the control group (P = .01). The area of density was reduced by 374.4 mm2 (6.1%) (95% CI = 235.1-513.8) in the intervention group compared with an average of 127.7 mm2 (2.1%) (95% CI = 8.6-246.7) in the control group (P = .01). Weight loss was associated with a reduction in breast area. The effect of the intervention on breast area was only marginally statistically significant after weight change, menopausal status, and age at trial entry were taken into account (P = .06). Greater weight loss and becoming postmenopausal were associated with statistically significant reductions in the area of density on the mammographic image at 2 years (P = .04 and P<.001, respectively). Age at entry into the trial was marginally significant in the same direction (P = .06). The effect of the intervention on area of density remained statistically significant after controlling for weight loss, age at entry, and menopausal status (P = .03). The change in the percentage of dense tissue in the mammographic image was not significantly different between the two groups (P = .71). CONCLUSIONS AND IMPLICATIONS: These results show that after 2 years, a low-fat, high-carbohydrate diet reduced the area of mammographic density, a radiographic feature of the breast that is a risk factor for breast cancer. Longer observation of a larger number of subjects will be required to determine whether these effects are associated with changes in risk of breast cancer.

Adult↗

Cooperative exosite-dependent cleavage of synaptobrevin by tetanus toxin light chain.

The light chain (L chain) of tetanus neurotoxin (TeNT) has been shown to have been endowed with zinc endopeptidase activity, selectively directed toward the Gln76-Phe77 bond of synaptobrevin, a vesicle-associated membrane protein (VAMP) critically involved in neuroexocytosis. In previous reports, truncations at the NH2 and COOH terminus of synaptobrevin have shown that the sequence 39-88 of synaptobrevin is the minimum substrate of TeNT, suggesting either the requirement of a well defined three-dimensional structure of synaptobrevin or a role in the mechanism of substrate hydrolysis for residues distal from the cleavage site. In this study, the addition of NH2- and COOH-terminal peptides of synaptobrevin, S 27-55 (S1) and S 82-93 (S2), to the synaptobrevin fragment S 56-81 allowed the cleavage of this latter peptide by TeNT to occur. This appears to result from an activation process mediated by the simultaneous binding of S1 and S2 with complementary sites present on TeNT as shown by surface plasmon resonance experiments and the determination of kinetic constants. All these results favor an exosite-controlled hydrolysis of synaptobrevin by TeNT, probably involving a conformational change of the toxin. This could account for the high degree of substrate specificity of TeNT and, probably, botulinum neurotoxins.

Amino Acid Sequence↗

Group B streptococcus bacteremia in nonpregnant adults.

BACKGROUND: We report the largest series of group B streptococcal (GBS) bacteremia cases reported at a single institution. METHODS: During a 10-year period (1985-1994), 90 GBS bacteremia cases (0.95% of significant bacteremic episodes) were detected. We describe the 51 episodes that occurred in nonpregnant adults for which enough clinical and microbiological information is available. RESULTS: Incidence of GBS has significantly increased during the study period (from 0.08 per 1000 admissions in 1985 to 0.3 per 1000 in 1994). Mean age of patients was 63.3 years (range, 21-88 years) and 53% were men. The most common underlying conditions were liver diseases (35.3%), malignancies (33.3%), and diabetes mellitus (27.5%). Only 2 patients did not have any underlying condition and no patient with the human immunodeficiency virus had GBS bacteremia in our series. The origins of the episodes of bacteremia were as follows: primary bacteremia (39.2%), skin and soft tissue infections (15.7%), urinary tract infections (11.8%), pneumonia (9.8%), peritonitis (9.8%), catheter infection (5.9%), postendoscopic bacteremia (5.9%), and endocarditis (2%). All isolates were susceptible to penicillin G potassium, ampicillin sodium, cephalothin sodium, cefotaxime sodium, and vancomycin hydrochloride. One ciprofloxacin hydrochloride-resistant strain was discovered and resistance to erythromycin stearate increased from 8% in 1992 to 18% in 1994. The overall mortality rate was 33.3% and deaths were considered related to the GBS bacteremia in 25.5% of the cases. Factors for poor prognosis were central nervous system diseases, alcoholism, shock, renal failure, and consciousness impairment. CONCLUSIONS: Group B streptococcus is a rising cause of bacteremia in elderly patients with severe underlying conditions. It conveys high morbidity and mortality rates. Macrolides should not be used empirically for treatment of patients with penicillin allergies.

Adult↗

30-day oral toxicity study of domoic acid in cynomolgus monkeys: lack of overt toxicity at doses approaching the acute toxic dose.

Domoic acid was orally administered to 3 cynomolgus monkeys at doses of 0.5 mg/kg for 15 days and then at 0.75 mg/kg for another 15 days. After the 30-day dosing period, the treated monkeys were killed. Parameters monitored as markers for toxicity included body weight, food and water consumption, clinical observations, hematology, serum chemistry, light microscopy of all major organs (including brain and retina), and glial fibrillary acid protein immunohistochemistry. Domoic acid in serum and 24-hour urine samples was measured at several time points. All parameters measured remained unremarkable. Domoic acid concentrations measured in the 24-hour urine samples indicated that gastrointestinal absorption in the monkey was approximately 4-7 percent of the administered dose, which is at least twice that previously reported for the rat.

Administration, Oral↗

An evaluation of the use of dried blood spots from newborn screening for monitoring the prevalence of cocaine use among childbearing women.

A collaborative March of Dimes study was designed to examine the utility of dried blood spot (DBS) materials routinely collected from newborns as a source for monitoring cocaine exposure and to assess the prevalence of cocaine use among childbearing women in Georgia. We used a modified urinary radioimmunoassay (RIA) to anonymously detect the cocaine metabolite benzoylecgonine (BE) in DBSs. Extensive efforts were undertaken to assure absolute nonlinkage of BE data to any individual. The positive results found by RIA were confirmed by a mass spectrometry (MS) method specifically developed to detect BE in DBSs. BE was measured in 23,141 DBSs collected during 2 months of routine newborn screening in Georgia. A good correlation was observed for RIA results versus MS results (r2 = 0.97). The estimated minimal statewide BE prevalence was 4.8 per 1000 childbearing women. We demonstrated that immunoassay testing for cocaine without confirmatory testing can yield falsely elevated prevalence rates. When proper confirmatory testing is done, DBSs are a valuable source for population-based monitoring of substance abuse among childbearing women.

Blood Specimen Collection↗

Cystic rectal duplication: a rare cause of neonatal intestinal obstruction.

A case of cystic rectal duplication revealed on day 2 of life by a low intestinal occluding syndrome is reported. Radiologic imaging (ultrasonography, cystography, rectography) showed a large, retrorectal liquid formation in the pelvis and abdomen, with pelvic compression of the terminal alimentary canal and lower urinary tract. Magnetic resonance imaging demonstrated a liquid formation with clearly defined edges and no medullary involvement, thus ruling out the possibility of a previous meningeal hernia. Biological markers were within normal limits. On day 4, a 9 x 6-cm cystic rectal duplication was removed, followed by a temporary colostomy. Pathologic examination demonstrated typical rectal architecture with ciliated cells. Radiologic and clinical findings at 2-month follow-up were reassuring. This case report is exceptional for the following reasons: (1) As a rule, rectal duplications are relatively rare (70 cases reported in the literature); (2) The means of disclosing a neonatal rectal duplication is unusual (4 cases reported in the literature); (3) The volume of the malformation was considerable; and (4) Heterotopic ciliated epithelium was present.

Cysts↗

Acute chest syndrome of sickle cell disease: radiographic and clinical analysis of 70 cases.

BACKGROUND: Acute chest syndrome (ACS) is a pulmonary illness with fever, chest pain, leukocytosis and new pulmonary opacity in a patient with sickle cell disease. It is a common reason for hospitalization in sickle cell patients, and a significant cause of mortality. The etiology of ACS is unclear. Lung or bone infarction and infection, among other possible causes, have been proposed. OBJECTIVE: We reviewed the chest radiographs and medical records of 41 patients with 70 episodes of ACS and correlated the clinical and radiographic courses in an attempt to better characterize and understand the syndrome. RESULTS: In 87 % of episodes, no identifiable etiology of ACS was found. This group of patients had a median age of 14 years and showed dramatic clinical and radiographic improvement within 24 h of therapy. In the remainder of episodes (13 %), an identifiable etiology was found, usually bacterial pneumonia. These patients were younger than the group without an identifiable etiology (median age 2 years) and had a prolonged radiographic course of illness. CONCLUSION: The chest radiographs of children with ACS without an identifiable etiology have an extremely typical appearance and evolution. Only in cases which do not have this typical pattern should infection be suspected as the underlying cause.

Acute Disease↗

The Dialine II graft: a new collagen-impregnated warp-knitted polyester arterial prosthesis.

The Dialine graft, a new prototype of knitted vascular prosthesis that uses a different brand of polyester fibers as an alternative to Dacron fibers, has been shown to offer excellent in vitro physical performance and in vivo healing. Although it still requires preclotting, the Dialine prosthesis was made impervious by impregnation of bovine type I collagen cross-linked with vapors of formalin. The purpose of the present investigation was to compare the in vitro physical characteristics of the Dialine II graft with those of the collagen-impregnated Hemashield graft. In addition, we studied the healing performance as a thoracoabdominal bypass in dogs for prescheduled periods of implantation ranging from 4 hours to 6 months. In vitro, the bursting strength, resistance to dilatation, and suture retention strength properties of the Dialine II prosthesis were all shown to exceed those of the Hemashield control graft. In the first weeks after implantation, the Dialine II grafts induced a discrete inflammatory response, as shown by the constant leukocyte counts observed both before implantation and when the animals were killed, as well as by the histologic observation of a few inflammatory cells in contact with the collagen. Consequently, the Dialine II grafts showed a slow rate of bioresorption of cross-linked collagen. At 1 month, a thin internal collagenous capsule was present at both anastomoses, laying over the original collagen coating. At 3 and 6 months, areas of thrombotic deposits and endothelialized areas were observed on the luminal surface. Because results of early clinical trials have been highly satisfactory, this prosthesis may be recommended for use without restriction as a medium- and large-diameter blood conduit.

Animals↗

Renal echinococcosis: clinical study of 34 cases.

PURPOSE: Hydatid disease, a cyclo-zoonotic parasitic infestation caused by the larval stage of the cestode Echinococcus granulosus, is prevalent worldwide. We reviewed the clinical findings of a large series of renal hydatidosis treated in an endemic area with special emphasis on diagnostic pitfalls. MATERIALS AND METHODS: A retrospective 15-year review in a rural area of central Spain (600,000 population), with a global incidence of hydatidosis of 10 new cases per 100,000 population per year, revealed 34 with renal echinococcosis treated surgically (3 to 4% of officially confirmed cases of hydatidosis). Clinical, radiological and laboratory data were analyzed. RESULTS: Renal hydatid disease mimicked other diseases. The combination of clinical history, imaging studies, and serological and urine investigation yielded a reliable pretreatment diagnosis in only 50% of cases and a presumptive diagnosis in 71%. Among imaging studies computerized tomography was the most valuable diagnostic examination. Moderate eosinophilia was found in half of the cases, while a third had scoleces in the urine. A diagnostic and therapeutic algorithm is presented. CONCLUSIONS: Preoperative diagnosis of renal hydatid disease is difficult even in an endemic zone. Imaging studies are suggestive but usually inconclusive, and the differential diagnosis with a renal tumor or complicated cyst may not be made without surgery. Renal sparing surgery is possible in a significant proportion of cases, particularly when preoperative diagnosis has been considered. Significant surgical morbidity can be expected, and the risk of anaphylaxis and hydatid seeding, although low, should not be overlooked.

Adolescent↗

[Tracheal intubation in prehospital resuscitation: importance of rapid-sequence induction anesthesia].

OBJECTIVE: To investigate complications of emergency endotracheal intubation (EEI), possibly facilitated by rapid-sequence induction, in the prehospital critical care setting: 1) the difficulty of intubation; 2) the cardiorespiratory consequences of intubation; 3) the relationship between the occurrence of complications and prognosis. STUDY DESIGN: Prospective non randomized, open study. PATIENTS: All patients treated over a 5-month period by a physician-manned ambulance service and requiring EEI. METHODS: Patients were allocated either in with cardiac arrest (CA) group or a group with maintained spontaneous circulation (SC). Difficulty of intubation was assessed by the number of attempts. RESULTS: Two hundred and twenty-four consecutive EEI were carried out by physicians (46%) and residents (38%) not trained in anaesthesia, anaesthetists (8%), or nurse anaesthetists (7%). Trachea was intubated after a maximum of three attempts in all patients. Success rate at the first attempt was 91%. It was 92% in CA patients (n = 76) and 90% in SC patients (P = 0.59). Anaesthetic induction, with (n = 112) or without (n = 12) succinylcholine, was used to facilitate 84% of intubations in SC patients. Complications occurred in 30 patients (20%). There was no relationship between the latter and hospital mortality, duration of ventilatory support, duration of stay in the intensive care unit. CONCLUSION: In this study, EEI in SC patients was frequently facilitated by rapid sequence induction and was associated with a high success rate at the first attempt, as in CA patients. Morbidity was low. All physicians involved in emergency airway management should be skilled in this technique.

Adolescent↗

A code of ethics for the medical dosimetrist--the American Association of Medical Dosimetrists experience.

The Committee on Protocol and Ethics of the American Association of Medical Dosimetrists (AAMD) has developed a Code of Ethics for a radiation oncology society of medical dosimetrists. The purpose of the code of ethics is fourfold: (1) Establish an ideal of professional conduct specific to the medical dosimetry profession; (2) Develop a statement of the moral values and commitment of the AAMD; (3) Recognize professional relationships and obligations; and (4) Define goals to which the medical dosimetrist should aspire. The Code of Ethics was adopted as AAMD policy in October 1995.

Ethics, Professional↗

A code of ethics for the medical dosimetrist--the American Association of Medical Dosimetrists experience.

The Committee on Protocol and Ethics of the American Association of Medical Dosimetrists (AAMD) has developed a Code of Ethics for a radiation oncology society of medical dosimetrists. The purpose of the code of ethics is fourfold: (1) Establish an ideal of professional conduct specific to the medical dosimetry profession; (2) Develop a statement of the moral values and commitment of the AAMD; (3) Recognize professional relationships and obligations; and (4) Define goals to which the medical dosimetrist should aspire. The Code of Ethics was adopted as AAMD policy in October 1995.

Ethics, Medical↗

All-trans retinoic acid in relapsing malignant gliomas: clinical and radiological stabilization associated with the appearance of intratumoral calcifications.

PURPOSE: To evaluate the therapeutic effect of all-trans retinoic acid (ATRA) with and without cytosine arabinoside in relapsing malignant gliomas. PATIENTS AND METHODS: 9 patients (8 male, 1 female, age 53.9 +/- 11.2) with relapsing malignant gliomas (grade IV:6; grade III:3) were treated by ATRA 1 to 21 months after the end of their initial treatment. ATRA was given unceasingly during 2 to 17 months at 90 mg/d. In 6 patients it was associated to cytosine arabinoside (4 g/course, 1 to 9 courses every 4 weeks). RESULTS: 4 non-responder patients died 2.5 to 4 months after starting therapy. One patient who had been reoperated before receiving ATRA and cytosine arabinoside (5 course) had no sign of tumor recurrence after 17 months of treatment. In 4 responder patients (2 glioblastoma and 2 anaplastic astrocytoma) a clinical and radiological stabilization (time to progression) during 9 +/- 2.5 months was observed. This stabilization was associated in 3 of them with the appearance of intra tumoral calcifications visualized on repeated CT scans and confirmed in one patient by post-mortem examination. All of them had received cytosine arabinoside (1 to 9 courses) with ATRA; however small calcifications were also observed in one non-responder patient who did not receive aracytine. CONCLUSION: These results suggest: a) a therapeutic effect of ATRA in combination with cytosine arabinoside in patients with relapsing malignant gliomas b) that intratumoral calcifications are related to the effects of ATRA on differentiation and/or on endothelial t-PA production and that these effects explain the tumor progression arrest in responder patients. The transient efficiency is probably related to the pharmacokinetics of ATRA or to changes of cellular mechanisms that modulate the cell response to the drug and is a critical issue for this therapy.

Adult↗