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Biomedical subjects

B Hamilton

Publications and source records attributed to B Hamilton.

At least 37 records · Page 2Linked to original sources

Sequence analysis of pre-ferredoxin-NADP(+)-reductase cDNA from Cyanophora paradoxa specifying a precursor for a nucleus-encoded cyanelle polypeptide.

A cDNA clone for pre-ferredoxin-NADP+ reductase (FNR) was obtained by screening a Cyanophora paradoxa expression library with antibodies specific for cyanelle FNR. The 1.4 kb transcript was derived from a single-copy gene. The precursor (41 kDa) and mature forms (34 kDa) of FNR were identified by western blotting of in vitro translation products and cyanelle extracts, respectively. The derived amino acid sequence of the mature form was corroborated by data from N-terminal protein sequencing and yielded identity scores from 58% to 62% upon comparison with cyanobacterial FNRs. Sequence conservation seemed to be even more pronounced in comparison with enzymes from higher plants, but using the neighbor joining method the C. paradoxa sequence was clearly positioned between the prokaryotic and eukaryotic sequences. The transit peptide of 65 or 66 amino acids appeared to be totally unrelated to those from spinach, pea and ice plant but showed overall characteristics of stroma-targeting peptides.

Amino Acid Sequence

Pathology of congenital syphilis in rabbits.

We have developed a model for congenital syphilis in the rabbit. This report provides additional information on newborn tissue pathology in animals that were infected in utero. A total of 35 pregnancies were evaluated, each containing 6 to 12 newborns. In the infected group, the mortality was approximately 50%; of the live newborns, half appeared normal and half were hyperreflexic, weak, and runty. Gross pathology in the sickly newborns was quite prevalent and involved enlarged spleens with isolated spots of necrosis; enlarged livers that were overtly congested and hemorrhagic and had numerous granular, white spots; and brains with hemorrhage in the occipital area. Histopathology was apparent in different tissues. Lymphocytes, plasma cells, and vacuolated macrophages were prominent in livers, spleens, brains, and bones. A few actively motile treponemes were visualized by dark-field microscopy within extracts of spleen and within cerebrospinal fluid. Low numbers of treponemes were also demonstrated in sections of brain and liver by using the Warthin-Starry silver stain technique. Blood hematocrits were decreased, and extramedullary hematopoiesis was prominent within spleens and livers; this is consistent with anemia. This rabbit model exhibits many of the same pathologic features commonly found in human congenital syphilis.

Animals

Effects of monomeric acrylic embedding media on the antigenicity of two epitopes of the MIC2-encoded Ewing's sarcoma cell membrane antigen.

Comparative electron microscopic studies of pre- and postembedding immunolabeling experiments have shown that the antigenicity of some epitopes is lost during acrylic resin embedding of the respective tissues. In the present investigation we have tested the sensitivities of two embedding-labile epitopes (HBA-71 and HBA-45) of the Ewing's sarcoma-associated MIC2-encoded E2 antigen to the effects of the different treatment steps, which are necessary for the preparation of ultrathin sections. The extent of antigenic retention was quantitated using flow cytometry and enzyme-linked immunosorbent assays (ELISA) of tumor cell lines, thymocytes and cell membrane extracts. Fixation, dehydration and high temperature treatment of MIC2-positive cells showed only minor effects on the reactivity with the HBA-71 and HBA-45 antibodies. However, exposure of the cells to the monomeric acrylic resins LR White (LRW), LR Gold (LRG) and Lowicryl K4M at 4 degrees C for 2-18 h resulted in a significant reduction of the HBA-71 and HBA-45 reactivities. In contrast, the antigenicity of both epitopes was maintained during treatment with the apolar Lowicryl HM20 embedding medium under these non-polymerizing conditions. The resins have no direct effect on the HBA-71/HBA-45 antigen, since it could be extracted in intact form from membranes of native, but not of fixed, tumour cells using LRW for membrane solubilization. These data indicate that the HBA-71/HBA-45 antigen remains in the cell membrane and is indirectly influenced by the extraction/modification of adjacent membrane constituents. The adverse effects of the polymerization process, in the case of embedding at low temperature in Lowicryl HM20, destroyed MIC2-antigenicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins

Endotoxin, TNF-alpha, interleukin-6 and parameters of the cellular immune system in patients with intraabdominal sepsis.

The correlation of endotoxin (ET), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and cellular immune parameters with multiple organ failure and lethal outcome in intraabdominal infections was studied in a group of 18 patients with peritonitis, abscess or pancreatitis. Of these patients, 7 developed respiratory failure and 5 died due to multiple septic organ failure. The peak levels of ET (2.7 +/- 1.3 ng/ml) in the course of the disease were followed by moderate increases of TNF-alpha (mean 147 +/- 41 pg/ml) and IL-6 (170 +/- 61 pg/ml) within 2 days. Analysis of the parameters for the last 12 days prior to death or discharge showed, that the patient group with lethal outcome was characterized by significant lower mean plasma levels of TNF-alpha (less than 75 pg/ml versus greater than 160 pg/ml) and IL-6 (less than 130 pg/ml versus greater than 270 pg/ml), as well as high rates of unstimulated thymidine uptake into peripheral mononuclear blood cells (greater than 44000 cpm/8 x 10(6) PMBC/18 h versus less than 24000 cmp), T-lymphocyte depression (CD3; approximately greater than 40% reduction) with lower T-helper/inducer subset cell numbers (mean CD:CD8 ratio 1.0 +/- 0.55 versus 1.8 +/- 0.2) and lower lectin (PHA) stimulation values (1.9 +/- 1.4 versus 4.1 +/- 1.0). These data demonstrate an anergic immune status with low mediator levels and depressed T-lymphocyte function in patients with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen

Socio-economic factors associated with HIV infection in pregnant women.

The HIV epidemic in women in Edinburgh has characteristics which enable a total population study. We studied retrospectively all women with a known history of injection drug use or with a seropositive drug-using partner in a five year period from 1985-1990. We sought to quantitate lifestyle and environmental factors associated with HIV infection in pregnant women and to test two hypotheses: that infected women would have more adverse socio-economic features, and that there would be a change in these factors with time. There were 244 pregnant women in the study. They were slightly younger than all Edinburgh City women and much less likely to be married. They were much more likely to live in areas of multiple housing deprivation. Only 16% of women, and 28% of partners, were in paid employment; 90% of women smoked and 76% had a history of injection drug use. Some 28% of previous children were in the care of another, often a relative, 8% of women had a recent prison admission, and 58% of those tested had antibodies to Hepatitis B. Univariate analysis showed that none of these factors was significantly different in HIV seropositive women except for prison admission, previous infection with Hepatitis B, which probably all related to type of drug use. Linear logistic regression suggested two other variables which distinguished between groups, but because these are composite, and dependent on incomplete data, this must be interpreted with caution. The same overall associations were found when only women with a history of injection drug use were considered. There was no statistically significant change in these factors with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Estimation and characterization of the potential renal organ donor pool in Pennsylvania. Report of the Pennsylvania Statewide Donor Study.

The Pennsylvania Statewide Donor Study evaluated deaths under the age of 66 occurring in 149 participating hospitals in 1987. After elimination of 6146 patients from 11,983 based upon ICD-9 code criteria, an on-site medical record review was performed on 5603 patients. Each patient was assessed for organ donor suitability based upon brain death and medical suitability criteria--and, after a series of eliminations, 453 patients were found to have a moderate or higher potential as acceptable organ donors. An estimation of the organ donor rate was placed between 38.3 and 55.2 donors per million population per year, depending upon the stringency of organ donor criteria. Educational efforts targeted at physicians, patient's families and transplant surgeons will be necessary, however, to attain this maximal rate.

Adult

Meiotic chromosome behaviour reflects levels of sequence divergence in Sus scrofa domestica satellite DNA.

We present a general model for the evolution of chromosome-specific satellite DNA subfamilies. Sus scrofa domestica has a bimodal karyotype with two autosomal subsets of 12 meta-/submetacentric (Mc) and 6 acrocentric (Ac) chromosome types (Mc and Ac "subgenomes"). We show that the centromeric heterochromatin is characterised by two distinct satellite DNA families designed Mc1 and Ac2. Mc1 is a diverse satellite family of the Mc subgenome of which certain members with a 100 bp repeat unit are found to occur at the pericentromeric regions of each Mc autosome, while others are chromosome-specific, e.g. clone Mc pAv1.5, a higher order repeat variant, which hybridises specifically to chromosome 1. Ac2 is a homogeneous satellite occurring at the subterminal pericentromeric regions of all Ac autosomes. DNA sequence analyses showed that all clones investigated are built up from a 14 bp repeat unit which is highly conserved. In situ hybridisation to meiotic pachytene nuclei revealed a distinct spatial arrangement of the Ac2 centromeric satellite.

Animals

Multicenter comparison of once- and twice-daily isradipine to hydrochlorothiazide for the treatment of hypertension in elderly patients.

After 8 weeks of isradipine, a twice-a-day dihydropyridine calcium channel blocker, 49% of elderly patients showed a complete response (sitting diastolic blood pressure less than or equal to 85 mm Hg) and 36% showed a partial response (sitting diastolic blood pressure decrease greater than or equal to 10 mm Hg) for an 85% total response rate. Hydrochlorothiazide gave a complete response in 36% of the patients and a partial response in 33%, for a 69% total response rate (p less than 0.0046). Because elderly subjects have reduced clearance for many drugs, we determined how those who responded to twice-a-day administration would respond to once-a-day administration. After 4 weeks of isradipine administered once a day, 54% of the patients showed a complete or partial response, whereas 38% of the patients who were changed to placebo showed a response. In contrast, 82% of patients receiving hydrochlorothiazide once a day showed a response, whereas 60% of patients who were changed to placebo showed a response. These data indicate that the standard formulation of isradipine was not effective when administered once a day.

Aged

Nursing research.

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Clinical Competence

Functional outcome following spinal cord injury. A comparison of specialized spinal cord injury center vs general hospital short-term care.

The functional outcomes of 185 patients with spinal cord injuries undergoing rehabilitation who were initially treated in a specialized short-term care unit (center patients) were compared with those of 153 patients initially treated in general hospitals (noncenter patients). After stabilization, all patients were admitted to the Rehabilitation Institute of Chicago (Ill) and received the same rehabilitation program. The groups were comparable in terms of demographic, injury, and medical characteristics at the time of rehabilitation center admission, but the duration from injury to rehabilitation was more than twice as long for noncenter patients. While center patients were discharged from the rehabilitation center at equivalent functional skill levels, their daily rate of functional gains during the rehabilitation center stay was significantly greater than that of noncenter patients although the length of stay at the rehabilitation center was comparable for the two groups. These results support the practice of specialized short-term spinal cord injury care as a means of enhancing rehabilitation outcome.

Activities of Daily Living

Control of Saccharomyces cerevisiae catalase T gene (CTT1) expression by nutrient supply via the RAS-cyclic AMP pathway.

In Saccharomyces cerevisiae, lack of nutrients triggers a pleiotropic response characterized by accumulation of storage carbohydrates, early G1 arrest, and sporulation of a/alpha diploids. This response is thought to be mediated by RAS proteins, adenylate cyclase, and cyclic AMP (cAMP)-dependent protein kinases. This study shows that expression of the S. cerevisiae gene coding for a cytoplasmic catalase T (CTT1) is controlled by this pathway: it is regulated by the availability of nutrients. Lack of a nitrogen, sulfur, or phosphorus source causes a high-level expression of the gene. Studies with strains with mutations in the RAS-cAMP pathway and supplementation of a rca1 mutant with cAMP show that CTT1 expression is under negative control by a cAMP-dependent protein kinase and that nutrient control of CTT1 gene expression is mediated by this pathway. Strains containing a CTT1-Escherichia coli lacZ fusion gene have been used to isolate mutants with mutations in the pathway. Mutants characterized in this investigation fall into five complementation groups. Both cdc25 and ras2 alleles were identified among these mutants.

Adenylyl Cyclases

Endogenous inhibition of red blood cell Na,K-ATPase in essential and pregnancy-induced hypertension.

Digoxin-like inhibitors of Na,K-ATPase have been implicated in the pathophysiology of essential (EH) and pregnancy-induced hypertension (PIH). A technique that enhances dissociation of digoxin from red blood cells (RBC) was used to displace endogenous digoxin-like substances from RBCs. RBC membranes were preincubated in Na and ATP (Release) or Na,K,Mg and ATP (Retention) prior to measuring ATPase activity. Groups studied were: 39 men with EH and 34 controls plus 10 women with PIH and 17 normotensive controls. All displayed similar increases in Na,K-ATPase activity (24.0 +/- 7.9%) following Release. Plasma digoxin immunoreactivity (DI) was measured in pregnant women, m = 0.25 +/- 0.07 ng/ml. No DI was detected in nonpregnant women, but RBCs from these women demonstrated the same increase in Na,K-ATPase activity after Release. The 24% increase in activity achieved by Na and ATP preincubation can be reversed by adding K and Mg to the Release suspension. However, after RBC-bound digoxin is displaced by Release preincubation, addition of K and Mg cannot promote renewed binding and pump inhibition. Thus, the observed endogenous inhibition is not due to displacement of a digoxin-like substance but probably is related to alteration of the enzyme-membrane interaction. Furthermore, even though pregnant women demonstrate DI, an inhibitory substance with digoxin-like binding could not be recognized using this technique.

Adult

Efficacy and safety of isradipine in hypertension.

Of the calcium channel blocking drugs, only verapamil is approved in the United States for treatment of hypertension. Isradipine is a 1,4-dihydropyridine calcium blocker that may be given on a twice-daily basis. It causes peripheral vasodilation with minimal cardiodepressant activity. We undertook a double-blind, parallel group randomized, multicenter study of 203 hypertensive subjects to examine the efficacy and safety of isradipine in treatment of hypertension. Subjects were given 0, 2.5, 5, 7.5, or 10 mg isradipine twice daily for up to 5 weeks. There was a significant dose-response relationship between isradipine dose and decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Isradipine 15 mg/day reduced supine pressure by 16/15 mm Hg in patients with starting DBP less than 105 mm Hg and by 38/22 mm Hg in those with starting DBP greater than or equal to 105 mm Hg. There was no significant orthostatic fall in blood pressure at any dose. Heart rate (HR) increased on an average by only a maximum of four beats/min. The drug was slightly more effective in the elderly in the standing position than in the young in the standing position. Adverse effects were mild, and only six patients were discontinued from the study because of adverse effects. Isradipine appears to be a safe, effective drug in monotherapy of hypertension at a wide range of patient ages.

Adolescent