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Biomedical subjects

L Martin

Publications and source records attributed to L Martin.

At least 145 records · Page 8Linked to original sources

[Solid cell nests and thyroid pathologies. Retrospective study of 1,390 thyroids].

Solid Cell Nests (SCN) of the thyroid gland were considered as embryonic remnants or as squamous metaplasia of follicular epithelium. In a retrospective study of 1 390 thyroids, SCN were found in 9.7 % of thyroids (16 % men and 8 % women, chi(2) : p <0, 01). The number of SCN rises with increasing number of sections examined. No statistical differences were found with age or thyroid disorders and presence of SCN, excluding the metaplastic theory. SCN contained in 38 % of cases, neuroendocrine cells (calcitonin and/or calcitonin gene related peptide, chromogranin A) and thyroglobulin cells was observed in 78.3 % of SCN. The different cell types of SCN fitted with the ultimobranchial remnant theory. Thus, some rare carcinomas (like mixed medullary and vesicular carcinoma or mucoepidermoid carcinoma) might originate from SCN.

Adenoma↗

Immunoreactivity to cytokeratin 8/18 in patients with soluble liver antigen (SLA) positive autoimmune hepatitis (AIH type 3) is not sufficient for diagnostic use.

"Soluble liver antigen" (SLA) has been reported to be an infrequent but in certain cases a unique marker of autoimmune hepatitis, with cytokeratins 8 and 18 as major antigenic components. Using precharacterized sera, we could confirm trypsin sensitivity and a molecular weight of approximately 50 kD of the reactive protein. However, the reaction differed from that of cytokeratins 8 and 18 by molecular weight and a pI of 7.5. A significant reactivity to cytokeratin 8 and 18 preparations was seen in only 1/12 patients. Immunoscreening of a human liver expression gene bank yielded no clones with sequence homology to cytokeratins. We conclude that reactivity in SLA positive sera is not mainly directed against cytokeratins 8/18 and recommend native antigen preparations for diagnostic use until the exact molecular nature of the 52 kD SLA antigen has been elucidated.

Autoantibodies↗

Personality characteristics that increase vulnerability to sexual harassment among U.S. Army soldiers.

The study examines personality characteristics that may increase vulnerability to sexual harassment among active duty Army personnel. A survey was administered to 1,060 male soldiers and 305 female soldiers at three Army posts located in the United States. Sexual harassment was measured by the Sexual Experiences Questionnaire, which assesses unwanted sexual behaviors in the workplace. Two gender-related personality characteristics derived from the Extended Personal Attributes Questionnaire were hypothesized to increase vulnerability to sexual harassment. Negative Femininity, which reflects extreme passivity, and Negative Masculinity, which includes antisocial characteristics, were both found to be positively correlated with unwanted sexual experiences among male and female soldiers.

Adult↗

Protection against the mortality associated with disease models mediated by TNF and IFN-gamma in mice lacking IFN regulatory factor-1.

Mortality and cytokine production associated with disease models mediated by TNF- and IFN-gamma were studied in mice lacking IFN regulatory factor-1 (IRF-1). IRF-1 knockout (KO) mice showed no mortality after the injection of a dose of LPS lethal in intact control mice (LD95). KO mice showed lower circulating levels of TNF and IFN-gamma than controls. KO mice also showed lower TNF and IFN-gamma mRNA in the spleen or liver than controls. KO mice had smaller spleens than controls, which contained similar percentage but lower absolute count of macrophages and lower percentage and absolute count of NK cells. IRF-1 KO mice survived longer than controls after the coinjection of LPS and galactosamine. IRF-1 KO mice also showed less mortality than controls after the injection of Con A and in a model of cerebral malaria. After the injection of a lethal dose of TNF (LD88), mortality was similar between KO and intact mice. Mortality was also similar after the coinjection of two nonlethal doses of TNF and IFN-gamma, a lethal combination (LD100). This study shows that the lack of IRF-1 protects against the mortality associated with disease models mediated by TNF and IFN-gamma but has no effect on the mortality directly induced by TNF and IFN-gamma. The lack of IRF-1 appears to result in impaired production of TNF and IFN-gamma, reflecting a down-regulation of gene expression in the liver and spleen as well as a reduction in the number of splenic cells.

Animals↗

Rational engineering of a miniprotein that reproduces the core of the CD4 site interacting with HIV-1 envelope glycoprotein.

Protein-protein interacting surfaces are usually large and intricate, making the rational design of small mimetics of these interfaces a daunting problem. On the basis of a structural similarity between the CDR2-like loop of CD4 and the beta-hairpin region of a short scorpion toxin, scyllatoxin, we transferred the side chains of nine residues of CD4, central in the binding to HIV-1 envelope glycoprotein (gp120), to a structurally homologous region of the scorpion toxin scaffold. In competition experiments, the resulting 27-amino acid miniprotein inhibited binding of CD4 to gp120 with a 40 microM IC(50). Structural analysis by NMR showed that both the backbone of the chimeric beta-hairpin and the introduced side chains adopted conformations similar to those of the parent CD4. Systematic single mutations suggested that most CD4 residues from the CDR2-like loop were reproduced in the miniprotein, including the critical Phe-43. The structural and functional analysis performed suggested five additional mutations that, once incorporated in the miniprotein, increased its affinity for gp120 by 100-fold to an IC(50) of 0.1-1.0 microM, depending on viral strains. The resulting mini-CD4 inhibited infection of CD4(+) cells by different virus isolates. Thus, core regions of large protein-protein interfaces can be reproduced in miniprotein scaffolds, offering possibilities for the development of inhibitors of protein-protein interactions that may represent useful tools in biology and in drug discovery.

Amino Acid Motifs↗

Electronic temperature monitoring and feedback to correct adverse vaccine storage in general practice.

OBJECTIVE: To evaluate the effect of direct feedback of temperature conditions followed by a telephone educational questionnaire to correct adverse vaccine storage, and to determine the consistency of vaccine storage conditions at provider sites over six months. PARTICIPANTS: 32 general practitioner vaccine providers in metropolitan Adelaide. DESIGN: Temperatures were monitored for 14 days using electronic temperature monitors, with repeat monitoring at two and six months. Feedback was given to vaccine providers and an educational questionnaire was administered after initial monitoring. MAIN OUTCOME MEASURE: Number of sites with more than 20% of recordings < 2 degrees C or > 8 degrees C and/or more than 5% of recordings < 0 degree C or > 15 degrees C. RESULTS: 13 (41%) sites had initially suboptimal storage. Following the interventions, storage was corrected in all but three (23%) of these sites. Only 10 (52%) of the 19 initially optimal sites had consistent optimal storage at two and six months. CONCLUSION: Electronic monitoring with direct feedback of storage temperatures was effective in correcting adverse storage at most suboptimal sites. Vaccine storage at initially optimal sites was not consistent. Our findings have important implications for further research and public health measures aimed at correcting and maintaining optimal vaccine storage.

Bacterial Vaccines↗

Determination of the MurD mechanism through crystallographic analysis of enzyme complexes.

UDP -N- acetylmuramoyl- L -alanine: D -glutamate (MurD) ligase catalyses the addition of d -glutamate to the nucleotide precursor UDP -N- acetylmuramoyl- L -alanine (UMA). The crystal structures of three complexes of Escherichia coli MurD with a variety of substrates and products have been determined to high resolution. These include (1) the quaternary complex of MurD, the substrate UMA, the product ADP, and Mg2+, (2) the quaternary complex of MurD, the substrate UMA, the product ADP, and Mn2+, and (3) the binary complex of MurD with the product UDP - N- acetylmuramoyl- L -alanine- D -glutamate (UMAG). The reaction mechanism supported by these structures proceeds by the phosphorylation of the C-terminal carboxylate group of UMA by the gamma-phosphate group of ATP to form an acyl-phosphate intermediate, followed by the nucleophilic attack by the amino group of D-glutamate to produce UMAG. A key feature in the reaction intermediate is the presence of two magnesium ions bridging negatively charged groups.

Adenosine Diphosphate↗

Metallopeptidase inhibitors of tetanus toxin: A combinatorial approach.

The bacterial protein tetanus toxin (TeNt), which belongs to the family of zinc endopeptidases, cleaves synaptobrevin, an essential synaptic protein component of the neurotransmitter exocytosis apparatus, at a single peptide bond (Gln76-Phe77). This protease activity is a particularly attractive target for designing potent and selective synthetic inhibitors as a possible drug therapy for tetanus. beta-Aminothiols mimicking Gln76 of synaptobrevin have been previously shown to inhibit the tetanus neurotoxin enzymatic activity in the 35-250 microM range. These compounds have now been modified to interact with S' subsites of the TeNt active site, with the aim of increasing their inhibitory potencies. Combinatorial libraries of pseudotripeptides, containing an ethylene sulfonamide or an m-sulfonamidophenyl moiety as the P1 side chain and natural amino acids in P1' and P2' positions, were synthesized. The best inhibitory activity was observed with Tyr and His as P1' and P2' components, respectively. This led to new inhibitors of TeNt with Ki values in the 3-4 microM range. These molecules are the most potent inhibitors of TeNt described so far.

Amino Acid Sequence↗

Rectal duplication in an adult: unusual cause of a buttock mass. Report of a case.

PURPOSE: Duplications of the rectum are extremely rare embryologic events, with almost 70 cases reported in the world literature. We report on a 39-year-old female patient with a duplication of the rectum. METHODS: Physical examination showed a left buttock mass; rectal examination revealed the presence of a painless mass compressing the rectum posterolaterally, confirmed by computerized tomography. RESULTS: The patient was operated on with a abdominal then a sacrococcygeal approach. After a complete excision, the postoperative course was unremarkable. Histology revealed a rectal duplication lined with heterotopic cylindric ciliated epithelium. DISCUSSION: This case shows that the diagnosis of rectal duplication is difficult and can be confused with other types of anorectal pathology. The presence of heterotopic ciliated epithelium has rarely been described. Complete excision of the duplication should be possible in most cases using a transcoccygeal, transanal, or abdominoperineal approach, depending on anatomic considerations.

Adult↗

Fire!

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Adolescent↗

Antireflux surgery in children under 3 months of age.

PURPOSE: The aim of this study was to analyze the indications and results of fundoplication in 110 infants under 3 months of age. METHODS: A retrospective review was conducted on the charts of all infants operated on for gastroesophageal reflux disease (GERD) at the UCLA Medical Center from January 1980 to December 1997. There were 59 boys and 51 girls. Recurrent emesis was the indication for operation in 62 of 110 infants, and respiratory symptoms in 85 of 110, with 54 of 110 having both. Neurological impairment was present in 32%. Prematurity was present in 21%; 35% had associated anomalies. Overall, 81 of 110 infants (73.6%) had one or more associated major malformations or disorders. Reflux was confirmed by upper gastrointestinal series findings in 63 of 78, esophageal pH monitoring in 60 of 62, and endoscopy in five of seven. RESULTS: Mean age at operation was 1.8+/-0.1 months and mean weight was 3,686+/-90.2 g. A Nissen fundoplication was performed on 104 children, and six underwent a Thal procedure. Thirty-one had a gastric emptying procedure for delayed gastric emptying. Complications occurred in 7 infants. Emesis was controlled in 57 of 62 patients, aspiration in 38 of 48, and apneic spells in 54 of 57. Follow-up greater than 6 months was available for 73 patients. There were nine late deaths, all related to severe associated malformations. Seven patients required a redo fundoplication for recurrent reflux. CONCLUSIONS: Nissen fundoplication can be performed safely in symptomatic infants under 3 months of age with low mortality and morbidity rates and with resolution of the presenting symptoms in 79% of infants.

Female↗

Gastric emptying procedures decrease the risk of postoperative recurrent reflux in children with delayed gastric emptying.

PURPOSE: Although several centers often perform gastric emptying procedures (GEP) together with fundoplication for gastroesophageal reflux (GER) and delayed gastric emptying (DGE), the benefit of GEP is controversial. The present study addresses the question of whether adding a GEP in children with preoperatively diagnosed GER and DGE affects the recurrence rate of GER after Nissen fundoplication (NF). METHODS: A retrospective chart review was performed on all children under the age of 16 years, operated on for GER from 1980 to 1997, who had a preoperative diagnosis of DGE, and at least 6 months of follow-up. Gastric retention of more than 50% of a radiolabeled meal at 90 minutes was considered DGE. Recurrent reflux was defined as reappearance of GER symptoms, confirmed by postoperative esophagram or 24 hours of pH monitoring. RESULTS: Of the 183 patients with DGE, 92 were available for long-term follow-up. Of these, 20 had no gastric emptying procedure performed (no-GEP group) and 72 had a GEP performed together with an NF (GEP group). Groups were comparable as to age at operation, mean follow-up time, male to female ratio and prevalence of associated anomalies. A higher prevalence of neurological impairment (NI) was present in the GEP group (48.6% v20.0%). Mean preoperative gastric retention was significantly higher in the GEP group (69.9 +/- 1.3%) than in the no-GEP group (61.4 +/- 2.2%). No complications resulted from the GEP. Recurrent reflux rate was 18.1% in the GEP group (13 of 72) versus 35.0% (7 of 20) in the no-GEP group. Actuarial analysis disclosed a marginally significant difference in the rate of recurrent reflux between the groups (P = .057) and estimation of the relative risk showed a 1.94 increase of recurrent reflux risk in the no-GEP (0.89<RR<4.20). CONCLUSIONS: Children with DGE, who did not have GEP, had twice the frequency of recurrent reflux as those who had a GER Preoperative screening for DGE, as well as operative correction of DGE at the time of fundoplication, is therefore recommended.

Child, Preschool↗

Papular-purpuric "gloves and socks" syndrome: polymerase chain reaction demonstration of parvovirus B19 DNA in cutaneous lesions and sera.

We report a typical case of papular-purpuric "gloves and socks" syndrome (PPGSS) in which primary infection by parvovirus B19 was demonstrated by seroconversion to this virus; parvovirus B19 DNA was also identified by polymerase chain reaction (PCR) methods in the sera of the patient and in the cutaneous biopsy specimen, both taken 4 days after the onset of clinical manifestations. To our knowledge, this is the fourth published case in which parvovirus B19 DNA has been recovered from the skin by PCR. Serologic studies and PCR investigations in cutaneous biopsy for other viruses including herpes simplex virus types 1 and 2, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6, 7, and 8 were negative. Clinically, our case presented some additional features, which have not been previously described in cases of PPGSS, namely dysuria with vulvar edema and erythema, and unilateral petechial rash on the breast. The histopathologic findings of our case were nonspecific and consisted of an interface dermatitis with slight vacuolar degeneration at the dermoepidermal junction and a superficial perivascular inflammatory infiltrate mostly composed of lymphocytes, with numerous extravasated erythrocytes. We review the cases of PPGSS published in the literature with respect to the different viruses that have been proposed as etiologic agents and conclude that acute infection by parvovirus B19 is the only one that has been adequately proved.

Adult↗