Viral infections, immune responses and cognitive performance.
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Cognition↗
Biomedical subjects
A Smith
Publications and source records attributed to A Smith.
Hemopexin joins transferrin as representative members of a distinct class of receptor-mediated endocytic transport systems.
Receptor-mediated transport of heme by hemopexin in vivo and in vitro results in catabolism of heme but not the protein, suggesting that intact apohemopexin recycles from cells. However, until now, the intracellular transport of hemopexin by receptor-mediated endocytosis remained to be established. Biochemical studies on cultured human HepG2 and mouse Hepa hepatoma cells demonstrate that hemopexin is transported to an intracellular location and, after endocytosis, is subsequently returned intact to the medium. During incubation at 37 degrees C, hemopexin accumulated intracellularly for ca. 15 min before reaching a plateau while surface binding was saturated by 5 min. No internalization of ligand took place during incubation at 4 degrees C. These and other data suggest that hemopexin receptors recycle, and furthermore, incubation with monensin significantly inhibits the amount of cell associated of heme-[125I]hemopexin during short-term incubation at 37 degrees C, consistent with a block in receptor recycling. Ammonium chloride and methylamine were less inhibitory. Electron microscopic autoradiography of heme-[125I]hemopexin showed the presence of hemopexin in vesicles of the classical pathway of endocytosis in human HepG2 hepatoma cells, confirming the internalization of hemopexin. Colloidal gold-conjugated hemopexin and electron microscopy showed that hemopexin bound to receptors at 4 degrees C is distributed initially over the entire cell surface, including microvilli and coated pits. After incubation at 37 degrees C, hemopexin-gold is located intracellularly in coated vesicles and then in small endosomes and multivesicular bodies. Colocalization of hemopexin and transferrin intracellularly was shown in two ways. Radioiodinated hemopexin was observed in the same subcellular compartment as horseradish peroxidase conjugates of transferrin using the diaminobenzidine-induced density shift assay. In addition, colloidal gold derivatives of heme-hemopexin and diferric transferrin were found together in coated pits, coated vesicles, endosomes and multivesicular bodies. Therefore, hemopexin and transferrin act by a similar receptor-mediated mechanism in which the transport protein recycles after endocytosis from the cell to undergo further rounds of intracellular transport.
Animals↗
The Minnesota project: a focused approach to ambulatory quality assessment.
With national HMO quality assurance requirements pending for Medicare risk contracts, three HMOs in Minnesota established a working group with the state Department of Health to develop and test a new methodology proposed for quality of care review. A two-tiered system was developed for ambulatory chart review based on 15 hospitalization diagnoses having a potential for inadequate prehospital care. This system was applied to 796 cases from the HMOs (2% of admissions). Technical problems limited actual review to 673 of these cases. Although 304 (45%) of reviewed cases failed initial screening, physician review found only 22% of such failures (10% of reviewed cases) to represent probable quality of care problems. The approach appears to be feasible and unusually efficient. Although there is considerable variability that limits its potential use for interhealth plan comparison, the approach holds promise for quality assurance within an individual health plan.
Ambulatory Care↗
The site of origin of nonconfluent pulmonary arteries from a common arterial trunk or from the ascending aorta: its morphological significance.
There are three possible embryological derivatives for nonconfluent pulmonary arteries which arise from a common arterial trunk or from the ascending aorta. We considered the feasibility of identifying these derivatives on the basis of the site of origin. We examined 15 specimens, in which both pulmonary arteries arose by separate orifices from a common arterial trunk (persistent truncus arteriosus), and 3 specimens, in which one pulmonary artery arose from the ascending aorta, the other being connected to the morphologically right ventricle (hemitruncus). Measurements were made for both the upper and lower margins of the orifices of the pulmonary arteries and then expressed as a percentage of the length of the ascending common trunk or aorta. The position of origin ranged from 39 to 100% for the upper margin and from 17 to 90% for the lower margin, without significant difference between left and right arteries. Since the range varied so widely, we contend that it is not possible to make a morphological identification of the pulmonary artery under consideration simply on the basis of the location of the site of origin.
Aorta↗
[Attempts at analyzing the initiation of the initial processes of carcinogenesis based on the Xiphophorus melanoma model].
Certain backcross hybrids (BC8-22) of a spotted X. maculatus (platyfish) and a non-spotted X. helleri (swordtail; recurrent parent) are highly sensitive to mutagenic carcinogens and, after a latent period of 8 to 12 months, develop melanoma of unicellular origin that is genealogically related to the spots of the platyfish. Sensitivity to the carcinogen or susceptibility to melanoma, respectively, are inherited in a Mendelian fashion and can be assigned to a "tumor gene-complex" (Tu-complex) consisting probably of almost 20 genes. The Tu-complex is located at the end of an autosome or sex chromosome, and is largely deregulated by crossing conditioned replacement of platyfish chromosome carrying regulatory genes (tumor suppressor genes, oncostatic genes, antioncogenes) for the Tu-complex by swordtail chromosomes lacking them. The melanoma-free condition of these BC-hybrids depends upon the skin-specific regulatory gene Bs (body side) that requires impairment in a pigment cell precursor for the outgrowth of melanoma. Structural mutations involving different breakpoints indicate that the signal for melanoma formation comes from a particular region of the Tu-complex where an accessory v-erb B related oncogene (x-erb B*a; 85% homology to the human EGF receptor gene) is located. Northern blot analyses of the melanoma cell line showed an about 20-fold overexpression of x-erbB*a. Both the inositol lipid turnover [(3H)inositol incorporated into phosphoinositides], and the xiphophorine pp60x-src kinase activity that are assumed to be causally involved in tumor formation showed a remarkable elevation in the melanoma as compared to the normal tissue (brain) of the tumorous and non-tumourous (with or without the Tu-complex) segregants. Other BC hybrids carrying the Tu-complex but lacking the linked regulatory gene develop melanoma "spontaneously". This kind of melanoma occurs early in the course of life, is of multicellular origin, and is inherited as a Mendelian character. In contrast to the BC hybrids requiring somatic mutation for melanoma formation, both inositol, lipid turnover and x-src activity are remarkable enhanced in both melanoma and normal tissues. A mutant of the laller BC hybrids carrying in addition of the Tu-complex the homozygous oncostatic gene g (g/g, "golden") that arrests pigment cell differentiation in the stem cell stage is incapable to develop melanoma spontaneously. Nevertheless it shows the elevation of inositol lipid turnover and x-src activity in its always healthy tissues. Following treatment with tumor promoters such as TPA and steroid hormones pigment cell differentiation recovers and melanoma of multicellular origin develops within 4 to 8 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Occupational carbamate pesticide intoxication in three farm workers. Implications and significance for occupational health in Jamaica.
The importance of occupational health practice principles in the delivery of health care to the working population is stressed by the authors' management of an incident of occupational pesticide poisoning. The clinical management of the patients involved, as well as the occupational and environmental health management of that incident, is discussed. An illustrative case report is used to describe an occurrence of carbofuran pesticide poisoning in three female farm workers in Jamaica. This report highlights the implications and significance of this incident in terms of the sensitivity of the medical profession to similar occupational health problems.
Adult↗
Receptor-mediated transport of heme by hemopexin regulates gene expression in mammalian cells.
Hemopexin (HPX) transports heme to liver parenchymal cells, undergoes receptor-mediated endocytosis, and recycles intact. Incubation of mouse hepatoma (Hepa) cells with heme-HPX causes a rapid dose- and time-dependent increase in the steady-state level of heme oxygenase (HO) mRNA. A maximum induction of 20-25-fold is achieved within 3 h after incubation with 10 microM heme-HPX. This accumulation of HO mRNA results primarily from increased transcription of the HO gene as judged by in vitro nuclear run-on assays. In addition, receptor-mediated transport of heme into Hepa cells significantly decreases the steady-state level of transferrin receptor (TfR) mRNA. While a 25-30-fold decrease in the amount of TfR mRNA is observed within 3 h of incubation of Hepa cells with 10 microM heme-HPX, no significant change in the rate of TfR gene transcription was detected. These regulatory effects of heme-HPX are not restricted to hepatic cells but are also observed in human promyelocytic HL-60 cells. This is the first direct demonstration of receptor-mediated transport of heme by hemopexin regulating gene expression in mammalian cells.
Animals↗
Outcome of elective prostatectomy.
OBJECTIVES: To determine the symptomatic and urodynamic outcome of elective prostatectomy and to establish whether the outcome is influenced or can be predicted by preoperative urodynamic measurements. DESIGN: Prospective non-randomised study with follow up at a mean of 11 months after operation. Most men were assessed jointly by a urologist and a general practitioner. SETTING: Department of urology in a teaching hospital serving a large district population. PATIENTS: 253 Men listed for elective prostatectomy because of symptoms and low urinary flow rates (less than 15 ml/s) and excluding those already on a waiting list or with acute urinary retention, clinically apparent prostatic cancer, and neurological or cerebrovascular disease; 217 (86%) were followed up. INTERVENTION: Elective prostatectomy. MAIN OUTCOME MEASURE: Classification on the basis of relief of symptoms assessed by patients and urologist and general practitioner and of symptom scores obtained by questionnaire. RESULTS: Of the 217 men followed up, 171 (79%) had a satisfactory subjective review and 155 (72%) had a satisfactory review and also low symptom scores. An unsatisfactory outcome was associated with preoperative symptoms of urge incontinence, small prostatic size and resected weight, low voiding pressures, and low urethral resistance. Preoperative maximum urinary flow rates did not predict outcome. Men with poor outcome could be classified into two groups: those with irritative symptoms who were more likely before operation to have had urge incontinence and detrusor instability and men with symptoms of poor urinary flow who were more likely before operation to have had a small prostate, low voiding pressures, and low urethral resistance. In patients in the second group flow rates or voiding pressures improved little after operation. Men with stable detrusors and either low urethral resistance or low voiding pressures were less likely to do well after prostatectomy, but despite these associations preoperative urodynamic measurements were unable to predict outcome accurately. CONCLUSIONS: Prostatectomy was satisfactory in relieving symptoms and improving urodynamic measurements in most men, but even in those with classic symptoms and low urinary flow rates a substantial minority experienced little improvement afterwards and urodynamic measurements did not accurately predict outcome in individual patients.
Follow-Up Studies↗
A cross-reactive idiotype on anti-DNA antibodies defines a H chain determinant present almost exclusively on IgG antibodies.
We have previously reported two anti-idiotypic antibodies, 3I and 8.12, that recognize L chain determinants on anti-DNA antibodies. We have generated a new anti-idiotypic antibody, F4, that recognizes a H chain determinant on cationic anti-DNA antibodies. F4 reactivity is present in high titer in serum of approximately 60% of SLE patients and on 84 of 706 myeloma proteins. It is preferentially associated with 3I reactive L chains. Furthermore, antibodies bearing both the F4 and 3I idiotypic determinants preferentially bind DNA. Amino acid sequencing of H chains isolated from four F4-reactive myeloma proteins suggests that they derive from two currently identified VH gene families. F4 reactivity is restricted almost exclusively to Ig of the IgG isotype suggesting that F4 may recognize either a somatically mutated hypervariable region or a variable region used late in the immune response. F4, therefore, represents a new idiotypic family preferentially associated with auto-Ag specificity and having features of an Ag-driven immune response.
Amino Acid Sequence↗
Making cervical screening work.
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Computer Systems↗
Tests to hit the target.
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Communication↗
Cross sensitivity to antithyroid drugs.
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Aged↗
Transcriptional activation of the heme oxygenase gene by heme and cadmium in mouse hepatoma cells.
Treatment of mouse hepatoma (Hepa) cells with heme or cadmium chloride in serum-free medium causes a rapid increase in the steady-state level of heme oxygenase (HO) messenger RNA. This increase is both dose- and time-dependent. Maximum accumulation of HO mRNA is observed 3 h after addition of either agent. Treatment of Hepa cells with heme or CdCl2 also stimulates the transcription of the HO gene, as judged by in vitro nuclear transcription run-on assays. The maximum rate of HO gene transcription occurs 2 h after treatment with either agent. Comparison of the relative increase in the rate of HO gene transcription with the relative increase in the level of HO mRNA demonstrates that transcriptional activation is the primary mechanism by which heme and cadmium produce the accumulation of HO mRNA in Hepa cells. Cadmium may also influence other processes involved in the expression of HO, since the time course of mRNA accumulation diverges from that of gene transcription. However, neither heme nor cadmium alters the rate of HO mRNA degradation. Cobalt chloride and heat shock, which are potent inducers of HO mRNA in rat liver and rat C6 glioma cells, respectively, have only a small effect on the level of HO mRNA in mouse hepatoma cells.
Animals↗
Human immunodeficiency viruses in patients attending a sexually transmitted disease clinic in London, 1982-7.
OBJECTIVE: To determine the prevalence of infection with the human immunodeficiency virus (HIV) in all patients attending a London sexually transmitted disease clinic over four weeks at the end of 1987 and to see how it varied from that in similar samples studied between 1982 and 1986. DESIGN: Anonymous testing of serum samples from consecutive heterosexual and homosexual patients having routine serological investigations for syphilis. Testing was for anti-HIV-I, anti-HIV-II, and hepatitis B core antibody (anti-HBc) and P24 antigen. Age, nationality, sexual orientation, and past sexually transmitted diseases were recorded for each patient. Gonorrhoea rates by quarters were analysed among homosexual and bisexual men and heterosexual men and women from 1981 to 1987. SETTING: Outpatient department of genitourinary medicine. PATIENTS: A total of 1074 patients attending consecutively for syphilis serology. Thirty five homosexual and bisexual men were excluded (these were regular attenders as part of a prospective study of the natural course of HIV infection). MEASUREMENTS AND MAIN RESULTS: The prevalence of anti-HIV-I in homosexual and bisexual men in 1987 was 25.6% (64/250). Results in the same clinic population between 1982 and 1984 had shown a rise in prevalence, which flattened out in 1985-6 and continued at that level. Among heterosexual attenders in 1987 the prevalence of anti-HIV-I was 1% (women 4/412; men 4/377), which contrasted with a prevalence of 0.5% (women 2/395; men 3/757) in January 1986. One homosexual man was seropositive for anti-HIV-II and seronegative for anti-HIV-I. Among homosexual and bisexual men the rate of gonorrhoea had declined by an average of 2.7% a year since 1981, such that by 1987--and for the first time in the clinic--there was no significant difference in the rates between these men and heterosexual men and women. CONCLUSIONS: The appearance of HIV-I infection among heterosexuals indicates a need for more aggressive education programmes and intervention strategies along the lines adopted for homosexual men. Surveillance for HIV-II infection is needed to provide information for future policy in national screening programmes.
Acquired Immunodeficiency Syndrome↗
Trisomy 18 at age 21 years.
Here we report on a woman with non-mosaic trisomy 18, who is now 21 years old. She has the characteristic face of older trisomy 18 survivors, marked kyphoscoliosis, spastic quadriplegia with contractures, and profound mental retardation. She has pyorrhea with loss of three canine teeth. At 20.5 years, she had her first menstrual cycle with development of secondary sexual characteristics.
Abnormalities, Multiple↗
Chorionic villus sampling--short-term versus long-term culture in a subtle 2; 18 translocation.
Prenatal diagnosis on chorionic villous tissue was performed for a woman with the karyotype 46,XX,t(2;18)(q32;q12)--a subtle 'difficult' translocation. The case illustrates the necessity of good quality cytogenetics for accurate prenatal diagnosis. For chorionic villi this can be obtained only with long-term culture.
Chorionic Villi Sampling↗
Use of three-dimensional computerized tomography in the diagnosis of an obstructed coronoid process.
The principles of three-dimensional computerized tomography are discussed. An unusual case of an iatrogenically induced coronoid obstruction is presented with the three-dimensional computerized tomograph as an integral tool in its diagnosis.
Adult↗
Sequential cytogenetic studies in an ovarian cancer cell line.
Cytogenetic analysis of a human ovarian carcinoma cell line JoN was performed at passages 6, 43, and 89. At passage 6 there were pseudodiploid and pseudotetraploid cells containing up to 22 markers. Pseudodiploid cells predominated. Significant differences were seen in the later analyses. At passages 43 and 89, cells had a modal number of 44 and 88 chromosomes with four new reciprocal translocations and loss of all unidentified markers. There was retention of one identified marker throughout plus one that gradually disappeared. Karyotypes at passages 43 and 89 were identical, suggesting stability of rearrangements. These changes indicate continuing chromosomal rearrangements in culture, not necessarily creating more complexity.
Chromosome Aberrations↗