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V Lewis

Publications and source records attributed to V Lewis.

At least 55 records · Page 3Linked to original sources

Restriction fragment length polymorphism analysis of HLA haplotypes in families with type I diabetes mellitus.

HLA Class II polymorphisms were analysed in 27 families with at least one Type I diabetic proband using Southern blotting technique according to 10th Histocompatibility Workshop Standards. The probes used were DRB, DQA1, DQB1 and DOB. We have studied 108 haplotypes and performed segregation analysis with HLA serology and restriction fragment length polymorphism (RFLP) data and compared "affected" with "non-affected" haplotypes (not inherited by IDDM patients). RFLPs correlated well with DR and DQ serology and detected additional polymorphisms. In particular, DQB polymorphism analysis showed segregation of the DQw3 splits with 88.5% of the DR4 affected haplotypes bearing the DQw3.2 split (now DQw8) and 11.5% the DQw3.1 split (now DQw7) while in the non-affected DR4 haplotypes 33.3% were DQw3.2 and 66.6% were DQw3.1. Haplotype analysis showed that DR4-DQw3.2 was in strong linkage with the U fragment (2.1 kb Taq I) of DQA2 (DX alpha) and with the L fragment (5.4 kb BamH I) of DOB. This study confirms previous observations of DQB polymorphisms in heterozygous IDDM patients, supports the protective effect of DQw3.1 (DQw7) against the development of the disease and demonstrates the importance of DQw3.2 (DQw8) for susceptibility to Type I diabetes.

Diabetes Mellitus, Type 1↗

Hand dominance of parents and other relatives of autistic children.

Hand preferences of 219 mothers and 186 fathers of autistic children were assessed using the Annett Handedness questionnaire. Subgroups of 54 mothers and 57 fathers with a family history of language-related developmental disorders were identified. Parents also reported the handedness of other relatives. Mothers (but not fathers) in the main group were significantly more likely to be consistently right-handed than females in the general population, but this was not specifically associated with a family history of language problems. There was no evidence of an increased incidence of consistent left-handedness in either the whole group of parents or the subgroups. Reported handedness of other relatives showed no abnormal distribution in relation to a comparison group. The findings are discussed in relation to theories about genetic factors in language-related developmental disorders in general, and autism in particular.

Adult↗

Retention of intrauterine fetal bone increases menstrual prostaglandins.

Intrauterine retention of fetal bone is a rare complication of abortion that can cause secondary infertility by an unknown mechanism. We report such a case in which menstrual fluid prostanoids were measured to elucidate the possible pathophysiology. The pattern of prostanoid increases was similar to that seen in intrauterine device users.

6-Ketoprostaglandin F1 alpha↗

The t complex polypeptide 1 (TCP-1) is associated with the cytoplasmic aspect of Golgi membranes.

The t complex polypeptide 1 (TCP-1) is a protein of unknown function expressed in large amounts during spermatogenesis. Rat monoclonal antibodies recognizing TCP-1 have been prepared and used to immunoprecipitate and Western blot a 57 kd protein from germ cell and tissue culture cell extracts. In tissue culture cells, indirect immunofluorescent localization of antigen indicated a perinuclear distribution similar to that of the Golgi apparatus. Analysis of the TCP-1 distribution in tissue culture cells showed that the polypeptide was associated with the cytoplasmic aspect of membranes of the trans-Golgi network (TGN). The distribution in spermatids suggested that TCP-1 was localized to structures often associated with the developing acrosome. The TCP-1 antigenic epitopes are highly conserved, allowing the protein to be identified in cells across a wide variety of vertebrate species and tissues. These experiments suggest that TCP-1 may be essential for transport of proteins through the exocytic pathway in all cells and required in large amounts for acrosome formation in developing spermatids.

Acrosome↗

TNF-alpha gene polymorphisms in type 1 (insulin-dependent) diabetes mellitus.

Type 1 (insulin-dependent) diabetes mellitus, like some other autoimmune diseases, is linked to certain alleles coded by genes in the HLA-D region. Sequence analysis of DQ beta chains indicates that aspartic acid at codon 57 confers resistance to the development of Type 1 diabetes. However, a full explanation for the HLA-association of Type 1 diabetes, particularly the increased susceptibility of DR3/4 heterozygotes is still awaited. The localisation of tumour necrosis factor genes on the short arm of chromosome 6 between HLA-B and the complement genes (Class III) prompted us to investigate a possible polymorphism of TNF-alpha at the genomic level in relation to Type 1 diabetes susceptibility. A dialleleic TNF-alpha restriction fragment length polymorphism was found with Ncol and its segregation with HLA-haplotypes analysed in diabetic families. We describe here a strong linkage of TNF-alpha alleles with certain DR haplotypes. For example, the common extended haplotype HLA A1-B8-DR3 was almost exclusively associated with the 5.5 kb TNF-alpha allele whereas Bw62-DR4 with the 10.5 kb allele. Thus both alleles segregate to diabetic patients. DR matched haplotypes of affected family members differed significantly from those of the non-affected at the TNF alpha locus. All affected sibling pairs in 11 multiplex affected families were identical for TNF-alpha alleles, even if they were only haploidentical for HLA-B-DR haplotypes. In addition, heterozygosity for the TNF-alpha alleles was significantly more frequent in the patients. This tight linkage of TNF-alpha alleles with some extended haplotypes could help to explain the HLA-association of Type 1 diabetes as well as some other autoimmune diseases.

Diabetes Mellitus↗

Cortical and trabecular bone mineral content in women with endometriosis: effect of gonadotropin-releasing hormone agonist and danazol.

Cortical bone (distal radius and ulna) and trabecular bone mineral content of the thoracolumbar vertebrae (T-12 to L-4) were measured with single-photon absorptiometry and quantitative computed tomography, respectively, in 55 women with laparoscopically staged endometriosis before, during, and after treatment with a gonadotropin-releasing hormone agonist (GnRH-a) or danazol. Mean pretreatment potassium phosphate mineral contents of T-12 to L-4 were 174 to 201 mg/ml in stage I to IV endometriosis and were within the 100 to 115th percentile of normal women. Similarly, cortical bone mineral contents were normal and were not significantly affected by either medication. Trabecular bone decreased significantly to 92.6 +/- 1.7% (n = 11, P less than 0.001) and 92.3 +/- 2.5% (n = 7, P less than 0.01) of baseline year after 6 months and 9 months of GnRH-a treatment and remained significantly depressed at 95.8 +/- 1.9% (P less than 0.0025) and 94.8 +/- 2.5% (P less than 0.005) 6 months after stopping treatment. Thus, cortical and trabecular bone mineral contents of women with endometriosis are normal, but treatment with GnRH-a induced significant loss of trabecular bone.

Adult↗

Memory impairments and communication in relatively able autistic children.

Autistic people have specific memory difficulties. The effects of these difficulties on communication in relatively able autistic children and learning impaired controls were assessed in three experiments. The experiments tested the ability to: (1) carry out instructions; (2) ask questions without repetition; and (3) answer questions about past activities. When specific memory skills were required autistic children's communication was impaired relative to controls. When the need to use these skills was eliminated from the tasks the autistic children performed as well as controls. Some practical and theoretical implications of the findings are discussed.

Adult↗

Ultrasound detection of axillary lymph node metastases in breast cancer.

Presence or absence of lymph node metastases is the most accurate prognostic indicator in breast cancer. Clinical examination is unreliable in detecting involved nodes. Preoperative ultrasound scan of the axilla has been performed in 140 consecutive women with breast cancer. The sensitivity for involved nodes was 66% which was significantly higher than clinical examination (42%) (P = less than 0.01). However ultrasound gave more false positives than clinical examination and thus no overall improvement in prognostic information was achieved.

Adult↗

Axillary lymph node status in carcinoma of the breast.

In this prospective study, axillary clearance specimens from consecutive routine mastectomies and wide excisions for carcinoma were divided into three segments by sutures in the theatre: apical (furthest from the tumour), mid and basal (nearest to the tumour) segments. Each specimen was then randomized to either formalin or Carnoy's fixation. Following fixation, lymph nodes were dissected from each of the three segments, sectioned once through the hilum, and examined microscopically. There was a significant (P less than 0.05) difference in the total number and number of reactive lymph nodes harvested from Carnoy's compared with formalin-fixed material. The number of nodes containing metastatic carcinoma was not significantly different (P = 0.64). In several cases, involved apical segment lymph nodes were found with no involvement of the proximal groups; this observation may have serious implications for the procedure of proximal lymph node sampling in the surgical management of breast cancer. It is suggested that clearing of axillary contents with Carnoy's fixative does not provide any additional information of clinical significance, although it may allow the pathologist to identify lymph nodes rapidly.

Acetates↗

Structure and function of Fc receptors on macrophages and lymphocytes.

Cell surface receptors for the Fc portion of immunoglobulin confer on most cells of the immune system the ability to communicate with the humoral antibody response. These Fc receptors are known to be particularly important for the function of various effector cells, such as macrophages, since they are involved in mediating a variety of activities including endocytosis, antibody-dependent cellular cytotoxicity, and triggering the release of potent inflammatory agents. Over the past few years, a considerable amount has been learned about the structure and functions of the Fc receptors expressed by murine and human cells, due to the availability of specific anti-receptor antibodies and the isolation of Fc receptor cDNA clones. In general, these receptors are transmembrane proteins whose extracellular domains contain two immunoglobulin-like regions and are thus members of the immunoglobulin gene family. Their domain structure consists of a glycosylated extracellular domain, a single membrane-spanning segment, and a relatively long cytoplasmic domain. The cytoplasmic tails exhibit a surprising degree of variation in length and amino acid sequence. This review summarizes some recent information concerning the structure and expression of the Fc receptors found on murine and human macrophages and lymphocytes. Particular attention is paid to the functional activities of these receptors, and the possible relationship between receptor function and receptor structure.

Animals↗

Effect of growth temperature on the lipids, outer membrane proteins, and lipopolysaccharides of Pseudomonas aeruginosa PAO.

Growth of Pseudomonas aeruginosa PAO1 at 15 to 45 degrees C in tryptic soy broth resulted in changes in the lipids, lipopolysaccharides (LPSs), and outer membrane proteins of the cells. Cells grown at 15 degrees C contained, relative to those cultivated at 45 degrees C, increased levels of the phospholipid fatty acids hexadecenoate and octadecenoate and reduced levels of the corresponding saturated fatty acids. Furthermore, the lipid A fatty acids also showed thermoadaptation with decreases in dodecanoic and hexadecanoic acids and increases in the level of 3-hydroxydecanoate and 2-hydroxdodecanoate as the growth temperature decreased. In addition, LPS extracted from cells cultivated at the lower temperatures contained a higher content of long-chain S-form molecules than that isolated from cells grown at higher temperatures. On the other hand, the percentage of LPS cores substituted with side-chain material decreased from 37.6 mol% at 45 degrees C to 19.3 mol% at 15 degrees C. The outer membrane protein profiles indicated that at low growth temperatures there was an increase in a polypeptide with an apparent molecular weight of 43,000 and decreases in the content of 21,000 (protein H1)- and 27,500-molecular-weight proteins.

Adaptation, Physiological↗

Transport of macrophage Fc receptors and Fc receptor-bound ligands to lysosomes.

Mouse macrophage Fc receptors specific for IgG1/IgG2b mediate the binding and pinocytic uptake of soluble IgG-containing antibody-antigen complexes. Internalization of these multivalent IgG complexes is accompanied not only by the intracellular degradation of the ligand, but also by a net decrease in the number of plasma membrane Fc receptors and an accelerated rate of receptor turnover. In contrast, internalized receptors bound to a monovalent ligand, the high affinity Fab fragment of the antireceptor mAb 2.4G2, escape degradation by rapidly recycling to the cell surface. In this paper, we have characterized the intracellular pathway involved in the endocytosis and transport of Fc receptors in the J774 macrophage cell line. The results show that the uptake of multivalent ligands follows the normal pathway of receptor-mediated endocytosis: internalization in clathrin-coated pits and coated vesicles, delivery to endosomes, and finally to acid hydrolase-rich lysosomes. Immunoprecipitation of radiolabeled receptor from Percoll density gradients showed that endocytosis of the IgG complexes also results in the concomitant transport of the receptor to lysosomes. Although uptake of the monovalent Fab fragment had no detectable effect on intracellular receptor distribution, preparations of 2.4G2 Fab rendered multivalent by adsorption to colloidal gold were as effective as the IgG complexes at causing lysosomal accumulation of internalized receptors. Thus, it is likely that the down-regulation and degradation of Fc receptors which occurs during the endocytosis of antibody-antigen complexes is due to the transport of internalized receptors to lysosomes. Moreover, the ability of certain Fc receptor-bound ligands to interfere with receptor recycling and trigger lysosomal transport seems to depend on ligand valency rather than on the presence or absence of Fc domains on intact IgG molecules.

Animals↗

Human platelet alpha-adrenergic receptors and responses during pregnancy: no change except that with differing hematocrit.

The possibility that platelet aggregation is altered during pregnancy is controversial. We tested for alterations of alpha-adrenergic receptor-induced platelet function during pregnancy compared to that in the early phase of the menstrual cycle. We found no change in alpha-adrenergic receptor concentration or in affinity of the receptor for epinephrine. The potency and sensitivity of epinephrine to inhibit adenylate cyclase, a response mediated by alpha 2-adrenergic receptors, was not different in platelets from the two groups of subjects. The ability of epinephrine to potentiate aggregation by adenosine diphosphate was significantly increased during pregnancy; however, this was an artifact introduced by lower hematocrits during pregnancy that resulted in an increased citrate concentration in the preparations of platelet-rich plasma from these women. The difference was eliminated by normalization of citrate concentration. Thus effects of alpha-adrenergic receptors on platelet function are not different during pregnancy. It is mandatory to recognize artifactual effects of differing hematocrits on platelet aggregation studied in vitro.

Adenylyl Cyclase Inhibitors↗

Perioperative complications of elective tracheostomy in critically ill patients.

This study was designed to examine prospectively the incidence of perioperative complications associated with elective tracheostomy in critically ill patients. An experienced surgeon and anesthesiologist participated in every tracheostomy procedure. In 81 procedures, there was no loss of airway control for greater than 20 sec, no airway obstruction, no blood loss exceeding 50 ml, and no aspiration. One patient (1.2%) had cardiovascular instability. During the next 48 h, two patients (2.4%) required wound packing to control hemorrhage but did not require blood transfusion and two patients (2.4%) had evidence of supraclavicular subcutaneous emphysema that was physiologically inconsequential. There was no perioperative mortality or major morbidity associated with the tracheostomy procedure. We conclude that, under controlled conditions, elective tracheostomy can be performed safely in critically ill patients.

Adolescent↗

Marjolin's ulcer complicating a pressure ulcer: case report and literature review.

Fifteen years after spinal cord injury and 14 years after development of a sacral pressure ulcer in a paraplegic man, a squamous cell carcinoma was found on biopsy during surgical reconstruction of the pressure ulcer. The patient refused the extensive surgery necessary to remove the infiltrating tumor, and the wound was closed with a latissimus dorsi flap. Pressure ulcers remain a problem in spinal cord injured and other disabled patients. Malignant degeneration (Marjolin's ulcer) in chronic pressure ulcers and other chronic skin ulcerations may become more widespread as the life span of spinal cord injured patients increases.

Adult↗

Management of chronic sternal osteomyelitis.

The management of 2 patients in whom chronic sternal osteomyelitis developed after apparently uncomplicated coronary artery bypass operations is described. Each patient had become totally disabled because of chronic, draining sinus tracts. Eradication of the infection required total sternectomy and excision of all infected costal cartilage. Subsequent reconstruction was accomplished by using bilateral pectoralis major myocutaneous advancement flaps without any maneuvers to stabilize the anterior chest wall. Both patients have resumed full activity and have returned to work with only minimal residual compromise of pulmonary function.

Aged↗