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Biomedical subjects

M Benson

Publications and source records attributed to M Benson.

At least 91 records · Page 5Linked to original sources

Interleukin 6 response to urinary tract infection in childhood.

This study analyzed the interleukin 6 (IL-6) response in 114 children with suspected urinary tract infection (UTI). Urine and serum samples were obtained at the time of enrollment. There were 90 children with UTI, 41 with and 49 without a temperature > or = 38.5 degrees C. The remaining 24 children did not have bacteriuria; 11 were febrile and 13 were not. The urinary IL-6 concentrations were higher in the children with UTI (mean, 129 units/ml) than in the children without bacteriuria (mean, 7 units/ml, P < 0.01). In contrast the serum IL-6 did not differ between children with or without UTI or between children with or without a temperature > or = 38.5 degrees C. The urinary IL-6 response was higher in children who were infected with P fimbriated Escherichia coli than in other children with UTI (P < 0.05). There was a correlation of urinary IL-6 with the degree of proteinuria, hematuria and urinary leukocyte counts (P < 0.001, P < 0.05, P < 0.05, respectively) but not with serum IL-6, CRP or temperature, and of serum IL-6 to C-reactive protein (P = 0.053) and renal concentrating capacity (P < 0.05). The results demonstrate that infections of the urinary tract activate an IL-6 response in children and that the magnitude of the IL-6 response is influenced by the properties of the infecting strain.

Adolescent↗

Clinical characteristics in a kindred with early-onset Alzheimer's disease and their linkage to a G-->T change at position 2149 of the amyloid precursor protein gene.

Patients from five generations of a family developed presenile Alzheimer's disease (AD) early in the fifth decade. Recent memory, information-processing speed, sequential tracking, and conceptual reasoning were the earliest cognitive functions affected. Language and visuoperceptual skills were largely spared early in the course of the disease. Later, there were progressive cognitive deficits and inability to perform the activities of daily living. Death occurred, on average, 6 years after onset. Three autopsies in affected members revealed cerebral amyloid deposits and neurofibrillary tangles. Clinical and pathologic features were typical for familial AD. Direct DNA sequencing revealed a G-->T change at position 2149 of the amyloid precursor protein (APP) gene that resulted in the substitution of phenylalanine for valine in the transmembrane domain of the mature protein. This mutation was present in DNA from all four examined affected individuals and linked to the disease with a lod score of 3.25, and was the most probable cause of AD in this family.

Adult↗

Effect of melanocyte stimulating hormone on human cultured choroidal melanocytes, uveal melanoma cells, and retinal epithelial cells.

PURPOSE: To establish methodology for the culture of human choroidal melanocytes to compare their responsiveness to melanocyte stimulating hormone (MSH) with that of their transformed melanoma counterparts and with that of the retinal epithelial cell. METHODS: Choroidal melanocytes from the choroid of eyes enucleated for the presence of malignant melanoma were cultured in MCDB 153 medium supplemented with insulin, transferrin, hydrocortisone, glutamine, nystatin, vitamin E, phorbol myristate acetate, bovine hypothalamic extract, cholera toxin, and chelexed fetal calf serum. RESULTS: High yields of pure spindle-shaped bipolar melanocytes were obtained with a doubling time of 3 to 4 days in nine consecutive eyes. Cells continued to divide after 4 months in culture. In contrast, uveal malignant melanoma cells grew rapidly in a relatively simple medium of Ham's F12:DMEM (1:1) supplemented with fetal calf serum, insulin, transferrin and glutamine. This medium was unable to support choroidal melanocytes. Choroidal melanocytes were DOPA-positive with appreciable tyrosinase activity that significantly increased with treatment with MSH. MSH also significantly altered the size, local density, and distribution of primary and mature melanosomes of ocular melanocytes. In contrast, uveal melanoma cells had a low level of tyrosinase activity and failed to respond to MSH with either an increase in enzyme activity or melanosome size. Retinal epithelial cells failed to show significant tyrosinase activity under the conditions studied or any increase in melanosome size in response to MSH. CONCLUSION: Ocular melanocytes show evidence of regulation by MSH and a range of mitogenic stimuli unlike the transformed melanoma cells, implying a loss of regulatory control in the latter.

Animals↗

Does platelet size correlate with function in patients undergoing cardiac surgery?

OBJECTIVE: Platelet dysfunction secondary to cardiopulmonary bypass (CPB) is one of the major reasons for nonsurgical post-operative bleeding in cardiac surgery. Whether platelet size is an indicator for platelet function was investigated in patients undergoing coronary artery bypass grafting. DESIGN: Prospective study. SETTING: Intra-operative, cardiac surgery operations. PATIENTS: 80 consecutive patients undergoing coronary artery bypass grafting. Excluding criteria were pre-operative coagulation disorders and medication with anticoagulants within the last 10 days before the operation day. MEASUREMENTS AND RESULTS: Platelet function was assessed by aggregometry using a turbidimetric method (inductors: ADP 2.0 mumol/l, collagen 4 micrograms/l, epinephrine 25 mumol/l). Mean platelet volume (MPV) was measured by an electrical conductivity method. Measurements were carried out before, during, and after CPB until the 1st post-operative day on intensive care unit (ICU). Platelet size decreased significantly during CPB (max. -25% after weaning from bypass) and returned to baseline values on the 1st post-operative day. Platelet count (ranging from 93 - 304 x 10(9)/l) did not correlate significantly with MPV or aggregation variables. Maximum aggregation and maximum gradient of aggregation induced by ADP and collagen were significantly decreased by CPB with the most pronounced reduction at the end of CPB (ranging from -25% to -45%). Analyses of co-variance revealed a significant correlation between changes in MPV and changes in aggregation variables (ADP, collagen). CONCLUSIONS: Platelet volume is easy to measure even in the operation room or in ICU and may indicate abnormalities in platelet function in the post-bypass period of cardiac surgery patients.

Adult↗

Myofibroblasts in hollow visceral myopathy: the origin of gastrointestinal fibrosis?

A patient with hollow visceral myopathy is reported in whom light microscopical studies of the small and large intestine showed typical features of degeneration, thinning, and fibrous replacement of smooth muscle of the gastrointestinal tract. Electron microscopy showed a striking increase in collagen with minimal fibroblast proliferation. Smooth muscle fibres had a range of ultrastructural abnormalities including myofilament disarray, electron lucency of the cytoplasm, and proliferation of the endoplasmic reticulum. Some fibres seemed to have typical ultrastructural characteristics of myofibroblasts, and others to be transition forms between typical smooth muscle cells and typical myofibroblasts. It seems likely that the fibrosis typical of this disorder has its origin in the transformation of smooth muscle fibres from a purely contractile to a myofibroblast collagen synthetic phenotype.

Adolescent↗

Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers.

The oncoprotein encoded by bc1-2 is unique because of its intracellular location (a mitochondrial membrane protein) and apparent mode of action (suppression of apoptosis). To date, this oncogene has been associated only with the development of certain forms of human B-cell lymphoma. In this report, we describe our experience with a monoclonal antibody made against a synthetic peptide for bc1-2 that can recognize the bc1-2 protein and identify cells in human prostate glands expressing this proto-oncogene with in situ immunohistochemical procedures. These procedures were utilized to survey a series of 62 human tissues to evaluate whether bc1-2 might have a role in the developing prostate gland or in prostate oncogenesis. While all primordial epithelial cells in a fetal prostate gland immunostain for bc1-2, normal and hypertrophic prostate glands of the adult show bc1-2 expression restricted to the basal cells. All epithelial cells in areas of prostatic intraepithelial neoplasia were stained by this antibody, as were most (62%) localized invasive prostatic carcinomas. In contrast, all primary prostatic carcinomas and metastases obtained from metastatic prostate cancer patients after hormone treatment (hormone-refractory tumors) stained positive for bc1-2. This study demonstrates that the oncoprotein encoded by bc1-2 can be detected at sequential stages in the natural history of human prostate cancer. Since the bc1-2 oncoprotein is known to suppress the cellular response to apoptotic stimuli, it will be important to determine whether bc1-2 expression is a factor in the development of prostate cancers and in the survival of hormone-refractory prostate cancer cells.

Antibodies, Monoclonal↗

Imaging of mediastinal masses in children.

Conventional radiographs show the mediastinum to be the most frequent location of thoracic masses in children. The compartmental approach to evaluation of pediatric mediastinal masses is advised. Compartmental localization and lesion internal characteristics are best determined by cross-sectional imaging techniques. These techniques as well as the causes and significance of the common pediatric mediastinal masses are discussed. Imaging of the thymus is emphasized because normal thymic tissue can mimic pathologic conditions and the thymus is a common thoracic location for neoplasms in children.

Child↗

Characterization of an isoelectric focusing variant of SAA1 (ASP-72) in a family of Turkish origin.

An acidic variant of serum amyloid A (SAA) identified previously by isoelectrofocusing in a family of Turkish origin has been characterized at the genomic level. DNA sequence analysis revealed that individuals expressing the variant pI6.1/pI5.7 isoforms (the mother and three of four children) were heterozygous at the SAA1 gene locus. Their SAA1 gene sequences contained an adenine, as well as the usual guanine, at the position corresponding to the second base of codon 72. The presence of both bases predicts two SAA1 protein sequences, one having aspartic acid and the other glycine at position 72. While the Gly-72 SAA1 (+/- Arg-1) sequence represents the normal pI6.5/pI6.0 isoforms, the Asp-72 SAA1 (+/- Arg-1) sequence corresponds to the variant pI6.1/pI5.7 isoforms.

Adult↗

6,7-Diepicastanospermine, a tetrahydroxyindolizidine alkaloid inhibitor of amyloglucosidase.

A tetrahydroxyindolizidine alkaloid, 6,7-diepicastanospermine, was isolated from the seeds of Castanospermum australe by extraction with methanol and purified to homogeneity using ion-exchange, preparative thin-layer, and radial chromatography. A very low yield of a pyrrolidine alkaloid, N-(hydroxyethyl)-2-(hydroxymethyl)-3-hydroxypyrrolidine, was also obtained by analogous methods. The purity of both alkaloids was established by gas chromatography of their trimethylsilyl (TMS) derivatives as better than 99%. The molecular weight of each alkaloid was established as 189 and 161, respectively, by mass spectrometry, and the structure of each was deduced from their 1H and 13C NMR spectra. The structure of the pyrrolidine alkaloid is suggestive of a possible biosynthetic route to the polyhydroxyindolizidine and polyhydroxypyrrolizidine alkaloids which co-occur in C. australe. 6,7-Diepicastanospermine was found to be a moderately good inhibitor of the fungal alpha-glucosidase, amyloglucosidase (Ki = 8.4 x 10(-5) M) and a relatively weak inhibitor of beta-glucosidase. It failed to inhibit alpha- or beta-galactosidase, alpha- or beta-mannosidase, or alpha-L-fucosidase. Comparison of its inhibitory activity toward amyloglucosidase with those of its isomers, castanospermine and 6-epicastanospermine, demonstrated that epimerization of a single hydroxyl group can produce significant alteration of such inhibitory properties.

Chromatography, Gas↗

Prenatal diagnosis of hereditary amyloidosis in a Portuguese family.

Portuguese-type amyloidosis is an autosomal dominant condition caused by a point mutation of the prealbumin (transthyretin) gene. The mutation can be detected directly by the presence of a restriction site for Nsil. We report the first prenatal diagnosis for this condition, performed in the first trimester by chorionic villus sampling, polymerase chain reaction, and restriction enzyme digestion.

Amyloidosis↗

Effect of an incontinence training program on nursing home staff's knowledge, attitudes, and behavior.

To test a behavioral approach for urinary incontinence (UI), 166 staff in four nursing homes participated in a quasi-experimental study that measured knowledge and attitudes about UI and compliance with toileting protocols. The intervention group (N = 96) showed a slight increase in knowledge; their attitudes remained positive over the four testing times. Compliance with the more critical component of the toileting protocol was only 72%, although evidence existed that the protocol reduced UI. Results are discussed in terms of the sociocultural environment of nursing homes.

Female↗

Haemangioma of the optic disc.

Isolated capillary haemangiomata of the optic disc are uncommon; they may be associated with the von Hippel-Lindau syndrome. Renal carcinoma occurs in almost one-third of patients with this condition, and it may go unnoticed until metastases occur. Early nephrectomy offers a cure. It is important, therefore, that all patients with optic disc capillary haemangiomata as well as their relatives are referred for screening for the stigmata of this disease.

Adult↗

Effects of tamoxifen and somatostatin analogue on growth of human medullary, follicular, and papillary thyroid carcinoma cell lines: tissue culture and nude mouse xenograft studies.

The knowledge that (1) the normal thyroid contains somatostatin, (2) polypeptide growth factors influence thyroid cell function, and (3) thyroid cells contain steroid hormone receptors prompted us to add somatostatin analogue No. 201-995 (SMS) (5 ng/ml) and/or tamoxifen citrate (TAM) (5 mumol/L) to 7-day monolayer cultures (50,000 cells/well) of three separate human thyroid carcinoma cell lines: DR081 (medullary), WR082 (follicular), and NPA'87 (papillary). Results, tabulated as cell numbers/well (X10(5) on day 7, revealed that TAM inhibited growth of medullary and follicular cells and that TAM plus SMS inhibited growth of papillary cells. In vivo studies of subcutaneous tumor cell xenografts in nude mice have documented that TAM (5 mg subcutaneous pellet) significantly inhibits the growth of medullary implants. Flow cytometric DNA studies of medullary cell cultures demonstrated a reduced G2 + M phase with TAM treatment. For papillary cell implants, TAM plus SMS (5 micrograms subcutaneously, twice daily) did not suppress tumor growth. All three cell lines were negative for estrogen receptor; addition of estradiol (5 ng/ml) to medullary cell cultures neither stimulated replication nor reversed the inhibitory effects of TAM in vitro. We conclude that (1) TAM slowed the growth of a cell line of human medullary carcinoma, both in vitro and in vivo; (2) this effect was not reversed by estradiol; (3) TAM plus SMS inhibited replication of a papillary carcinoma cell line in vitro, but not in vivo; and (4) TAM alone and TAM plus SMS inhibited replication of cultures of a human follicular thyroid carcinoma cell line. TAM and SMS may be useful in treatment of some human thyroid carcinomas.

Adenocarcinoma↗

Foscarnet therapy of cytomegalovirus retinitis in AIDS.

Cytomegalovirus (CMV) retinitis is the most common cause of blindness in AIDS. Twenty patients were treated with a 21-day course of foscarnet therapy by continuous infusion. Response to therapy was good in eight (47%) of 17 evaluable patients; partial arrest of progression was observed in eight (47%); and no response was obtained in one (6%). Foscarnet therapy did not lead to suppression of urinary excretion of CMV in four of 12 patients who nonetheless had improvement in retinal lesions. Toxic effects, especially reversible renal failure, were common, with blood creatinine increase in 50% and dialysis in two patients. Renal toxicity occurred primarily during the third week of therapy. Anemia (hemoglobin less than 80 g/L) occurred in 10 patients after a mean of 14.5 +/- 5.1 days of therapy and required transfusion. Review of this study and of data from a previous case series, however, was inconclusive regarding the additional benefit of a third week of therapy. Maintenance therapy was given to seven patients. Four had recurrence of CMV retinitis at a mean interval of 62 +/- 52 days. Only one patient has maintained prolonged remission on maintenance (greater than 24 weeks). Toxicity on the maintenance protocol included anemia (two of seven patients) and increased creatinine blood levels (one of seven patients). Zidovudine therapy in six patients did not contribute to increased toxicity of induction or maintenance therapy. Drug levels during continuous infusion were stable for individual patients but showed wide inter-patient variability. Peak levels of post-maintenance infusion varied both within and between patients.

Acquired Immunodeficiency Syndrome↗

A monoclonal immunoglobulin A (kappa) factor VIII:C inhibitor associated with primary amyloidosis: identification and characterization.

Factor VIII:C inhibitors associated with primary amyloidosis have not been previously reported. A patient with autopsy-proved primary amyloidosis developed renal failure requiring peritoneal dialysis. Purpura and a prolonged partial thromboplastin time (PTT) were first observed 3 years later, after treatment was changed from peritoneal dialysis to hemodialysis. Plasma contained a time-dependent factor VIII:C inhibitor. The inhibitor on isoelectric focusing showed two peaks of activity, one with an isoelectric point (pl) of approximately 4 and the second larger, with a pl of approximately 8. Both were neutralized only by antisera to IgA and kappa light chain. A monoclonal antibody prepared in Balb/c mice against the variable region of the kappa light chain also blocked the inhibitor. The delayed onset of the coagulopathy could be explained by the change from peritoneal to hemodialysis, because in the former, significant amounts of the paraprotein, indicated by an "M-spike," were recovered in the dialysate. N-terminal amino acid sequencing of the first 20 amino acids of the variable region of the kappa light chain from the urinary protein and the splenic amyloid subunit showed identity.

Amino Acid Sequence↗

Rape law: a feminist legal analysis.

Rape law is analyzed from the feminist perspective. Feminism can be credited with making the first serious efforts to empower women in all aspects of life, including the right to be free from sexual assault. Part 1 describes feminist theory concerning rape, Part 2 discusses some of the misogynistic images that have influenced rape law while Part 3 surveys some of the changes that have occurred in the United States, England and Israel concerning rape law. Part 4 analyzes the effects of these changes.

England↗