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Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 91 records · Page 5Linked to original sources
PubMed2000

The in situ conformation and axial location of the intermolecular cross-linked non-helical telopeptides of type I collagen.

BACKGROUND: Type I collagen contains specific lysine and hydroxylysine residues that are critical in the formation of intermolecular cross-links crucial for the normal configuration and stability of the 67 nm axial repeat of collagen fibrils in the extracellular matrix. The major cross-linkage sites are believed to occur between the non-helical terminal regions (telopeptides) and helical segments of adjacent collagen molecules. In this X-ray fibre diffraction study the tissue has been maintained in the hydrated fibrillar state, whilst detailed structural information was obtained using highly collimated synchrotron radiation. RESULTS: The axial component of the X-ray diffraction patterns extends more than twice as far in reciprocal space than that of any already published. The structure-factor phases were calculated using the multiple isomorphous addition method, avoiding model-based approaches, and produced an electron-density profile of the molecular arrangement projected on to the fibre axis to 0.54 nm resolution. This corresponds to the phasing of 124 orders of the meridional diffraction pattern. CONCLUSIONS: The axially projected electron-density profile and the electron-density difference maps showed that both the N- and C-terminal telopeptides are contracted structures. This profile puts narrow constraints on the possible conformations of the C-terminal telopeptide; the best fit to the electron-density profile is when the alpha1 chains adopt a folded conformation with a sharp hairpin turn around residues 13 and 14 of the 25-residue telopeptide. Our results reveal for the first time the location, parallel to the fibril axis, of the intermolecular cross-links in normal hydrated tissue. These cross-links are essential for the biological function of the tissue.

Binding Sites↗
PubMed2000

Melatonin suppression by light in euthymic bipolar and unipolar patients.

BACKGROUND: Previous studies have suggested that bipolar patients are supersensitive to light suppression of melatonin and that this may be a trait marker for genetic vulnerability. The present study was an attempt to replicate and extend this observation. Propranolol hydrochloride effects were compared with light effects because of the documented influence of beta-adrenergic receptors on melatonin production. Nighttime levels of corticotropin and cortisol were also examined as potential trait vulnerability markers. METHODS: Melatonin levels in euthymic bipolar patients (n= 29) were tested before and after 500-lux light was administered between 2 and 4 AM and on a separate night in the dark. Results were compared with those of a group of patients with unipolar depression (n= 24) and with those of a group of non-psychiatrically ill control subjects (n= 50). Lithium effects and propranolol effects were tested in subgroups. RESULTS: No group differences were seen in light suppression among bipolar patients, unipolar patients, and controls; an analysis of the whole group did not reveal differences in propranolol effect, differences in corticotropin or cortisol levels, or evidence for a lithium effect. However, patients with bipolar I affective disorder showed the following: (1) significantly lower melatonin levels on the light night, at baseline and following light exposure; and (2) a later peak time for melatonin on the dark night. CONCLUSIONS: The general hypothesis of increased light sensitivity in bipolar patients was not supported. However, melatonin secretion abnormalities were confirmed in the subgroup with bipolar I disorder. Further assessments of circadian rhythm disruption as a vulnerability marker in bipolar illness are indicated.

Adrenocorticotropic Hormone↗
PubMed2000

Malignant pleural mesothelioma presenting as spontaneous pneumothorax: a case series and review.

BACKGROUND: Malignant pleural mesothelioma (MPM) is thought to arise from the mesothelial cells that line the pleural cavities. Most patients initially experience the insidious onset of chest pain or shortness of breath, and it rarely presents as spontaneous pneumothorax. CASE REPORTS: We report four patients who presented in this manner. Three of the patients were exposed to asbestos directly or indirectly at shipyards during World War II; the fourth was exposed as an insulator's wife. Two of our cases were not recognized to have MPM on histologic examination at first thoracotomy and remained asymptomatic for 12 and 22 months, respectively. In none of the patients described herein, was spontaneous pneumothorax the cause of death. CONCLUSIONS: Since many people were exposed to asbestos during and after World War II, spontaneous pneumothorax in a patient with the possibility of such exposure should raise the suspicion of malignant pleural mesothelioma.

Aged↗
PubMed2000

[Acral necroses after therapy with quinine sulfate for calf cramps].

The most common cause of acral cyanosis is vascular spasm which can be induced by several drugs. An 87-year-old woman developed red and livid skin lesions on the fingers of both hands and several toes one month after beginning treatment with quinine sulfate 200 mg daily. The skin lesions progressed to necrosis in some areas. Quinine sulfate is a widely prescribed drug for nocturnal cramps. The following side effects may develop, particularly in the elderly: exanthems, pruritus, urticaria, erythema multiforme, purpura and photosensitivity. Our case points to the possibility of acral necrosis and demonstrates the efficacy of vasodilator treatment.

Acrodermatitis↗
PubMed2000

Hyperhomocyst(e)inemia induces multiorgan damage.

Hyperhomocyst(e)inemia has been associated with the development of hypertension, stroke, and cardiovascular, cerebral/neuronal, renal, and liver diseases. To test the hypothesis that homocyst(e)ine plays an integrated role in multiorgan injury in hypertension, we employed: (1) spontaneously hypertensive rats (SHR) in which endogenous homocyst(e)ine levels are moderately high (18.1 +/- ().5 microM); (2) control age- and sex-matched Wistar Kyoto (WKY) rats in which homocyst(e)ine levels are normal (3.7 +/- 0.3 microM). To create the pathophysiological condition of hyperhomocyst(e)inemia, 20 mg/day homocyst(e)ine was administered for 12 weeks in (3) SHR (SHR-H) and in (4) WKY (WKY-H) rats. (5) Endogenous homocyst(e)ine levels were reduced slightly but not significantly from 18.1 +/- 0.5 microM to 12.5 +/- 0.7 microM in SHR by folic acid administration (SHR-F). Plasma and tissue levels of homocyst(e)ine were determined by HPLC and spectrophotometric methods. Plasma and sympathetic ganglion (neuronal) matrix metalloproteinase (MMP) activity was measured by zymography. Activity of neuronal MMP was increased in hyperhomocyst(e)inemic rats as compared with controls. Mean arterial pressure (mmHg) was 95 +/- 5, 126 +/- 8,157 +/- 10, 188 +/- 5, and 165 +/- 12 in WKY, WKY-H, SHR, SHR-H, and SHR-F, respectively. Urinary protein (mg/day) was 0.11 +/- 0.03, 0.88 +/- 0.22, 0.47 +/- 0.10, 0.89 +/- 0.21, and 0.81 +/- 0.21 in WKY, WKY-H. SHR, SHR-H, and SHR-F, respectively, as measured by the Bio-Rad dye binding assay. The relationships between increased arterial pressure, plasma homocyst(e)ine, and urinary protein were delineated. Plasma and neuronal creatinine phosphokinase (CK) isoenzymes were measured by agarose gel electrophoresis. All three CK isoenzymes, i.e., MM, MB, and BB, specific for skeletal, cardiac, and nerve tissue, respectively, were induced following 12 weeks' hyperhomocyst(e)inemia, suggesting multiorgan injury by homocyst(e)ine. Homocyst(e)ine induces endocardial endothelial cell (capillary) apoptosis and may reduce capillary cell density. Structural damage to aorta, myocardium, kidney, and renalureter was analyzed by histology. Results suggested an integrated physiological role of homocyst(e)ine in injury to the endothelial/epithelial cell lining in the respective organs.

Animals↗
PubMed2000

The major tegumental antigen of Fasciola hepatica contains repeated elements.

In order to provide a better understanding of the interaction between the liver fluke (Fasciola hepatica) and the immune system of its mammalian host immunoreactive lambda bacteriophage clones containing F. hepatica cDNA have been isolated. Plasmids from these clones were sequenced and found to encode a family of proteins containing certain common elementst. All the clones contained a coding repeating sequence (RRRXCA) which is conserved at the nucleic acid level followed by a non-repeating element coding for the C terminal used by the proteins which shows conservation of amino acids at certain positions. Antisera raised against a beta-galactosidase fusion protein with one of these sequences as a terminal extension was used to localize the immunoreactive antigens. Binding was predominantly in the tegument of the juvenile fluke but was reduced in the adult tegument. The wall of the uterus showed strong reactivity in the adult. Rats immunized with the beta-galactosidase fusion protein showed enhanced resistance to challenge infections. The role of these antigens in the host response to infection by F. hepatica is discussed.

Amino Acid Sequence↗
PubMed2000

Carbohydrate regulation of leaf development: Prolongation of leaf senescence in Rubisco antisense mutants of tobacco.

Previous investigations have shown that increased source strength as a result of elevated CO(2) can alter the timing of the phases of change that occur in photosynthetic rates during dicot leaf ontogeny [Miller et al. (1997) Plant Physiol 115: 1195-1200]. To evaluate the converse situation of decreased source strength, we examined leaf development in rbcS antisense mutants of tobacco. These mutants have depressed Rubisco levels and decreased rates of carbohydrate production. We found that antisense leaves are longer-lived than wild type leaves and that this appeared to be due to a prolongation of the senescence phase of development, as monitored by photosynthetic rates, chlorophyll content, and the abundance and activity of Rubisco. Declines in these parameters during leaf ontogeny in both the wild type and mutant plants were generally accompanied by coordinate reductions in the levels of rbcS mRNA and rbcL mRNA, as well as by reductions in chloroplast rRNA, chloroplast DNA and total protein. We suggest that the prolongation of senescence in the antisense leaves is due to an impact of source strength on leaf developmental programming that occurs, at least in part, at the level of transcript abundance of nuclear and chloroplast genes for chloroplast rRNAs and proteins. We hypothesize that plants are capable of sensing a range of source strength conditions to initiate and modulate leaf developmental programming.

Journal Article↗
PubMed2000

Use of PEG-rHuMGDF in platelet engraftment after autologous stem cell transplantation.

This paper summarizes a pilot, sequential dose-escalation study of PEG-rHuMGDF in patients with advanced malignancies who had delayed platelet recovery after autologous stem cell transplantation (ASCT). Patients were randomized to receive either placebo (n = 11) or PEG-rHuMGDF at 5 (n = 9), 10 (n = 6), or 25 (n = 7) microg/kg/day by subcutaneous injection for 14 days and were monitored for 5 weeks. Across all treatment groups, eight patients had platelet recovery to > or = 20 x 10(9)/l by day 21. The proportion of patients achieving platelet recovery, the median number of days and units of platelet transfusions were similar for the placebo and the PEG-rHuMGDF groups. PEG-rHuMGDF was well tolerated at all dosages. The incidence rates of adverse events in all groups were similar. No deaths on study, no drug-related serious adverse events, and no development of neutralizing antibodies to MGDF occurred.

Adult↗
PubMed2000

Risk factor clustering in hypertensive patients: impact of the reports of NCEP-II and second joint task force on coronary prevention on JNC-VI guidelines.

INTRODUCTION: Although the association of hypertension with established risk factors has been noted in several population studies, the recent redefinition of dyslipidaemia, hypertension and diabetes calls for reassessment of the prevalence and pattern of risk factor clusters in essential hypertension. OBJECTIVE: To analyse the risk factor profile of Israeli patients with essential hypertension seen by primary care physicians and in hypertension specialty clinics, based on current definitions of dyslipidaemia hypertension and diabetes and JNC-VI guidelines for the assessment of risk factors. DESIGN AND SETTING: We analysed the risk profile of 324 Israeli hypertensive subjects using the JNC-VI risk table and risk grouping. A total of 122 consecutive patients were recruited from primary care clinics and 212 consecutive patients were recruited from a hospital based hypertension clinic. RESULTS: Amongst hypertensive individuals with no known target organ damage, only 1.5% had no risk factors other than hypertension, whereas all hypertensives with coronary artery disease had additional risk factors. Of the six listed major JNC-VI risk factors (smoking, dyslipidaemia, diabetes, age, sex, family history of cardiovascular disease), hypertensive subjects without coronary artery disease (coronary artery disease-negative) had 3.02 +/- 0.10 risk factors, whereas hypertensive subjects with coronary artery disease (coronary artery disease positive) had 3.6 +/- 0.07 risk factors other than hypertension (P < 0.01). Dyslipidaemia defined by NCEP-II criteria was the most common associated risk factor identified in 93% of coronary artery disease-positive and 77% of the coronary artery disease-negative hypertensive subjects. The most common dyslipidaemic abnormality was an increased LDL cholesterol (79.2% of the cohort), followed by hypertriglyceridaemia (31.7%) and low HDL cholesterol (22.3%). Nevertheless, in nearly half of the coronary artery disease-negative patients, LDL cholesterol concentrations were within 30 mg dL-1 of the target levels. The most common dyslipidaemic variant was isolated hypercholesterolaemia (42%), whereas the syndrome X dyslipidaemic combination of hypertriglyceridaemia and low HDL was strikingly uncommon, observed in 2.8% of the coronary artery disease-positive and 0.8% of the coronary artery disease-negative patients. CONCLUSIONS: (i) JNC-VI group risk A patients (no risk factors) comprise a very small minority in this cohort (< 5%); (ii) dyslipidaemia is exceedingly common with mild hypercholesterolaemia being the most prevalent variant and hypertriglyceridaemia with low HDL the least common form.

Cardiovascular Diseases↗
PubMed2000

Fibrotic aortic stenosis in a patient with dwarfism.

In this report, we present an adult patient with dwarfism who had severe aortic stenosis with markedly thickened fibrotic valve leaflets without calcification. These findings were well demonstrated by both two- and three-dimensional transesophageal echocardiography and confirmed at surgery and by pathological examination.

Adult↗
PubMed2000

Early discharge with drain in situ following axillary lymphadenectomy for breast cancer.

One-hundred and two women had axillary lymphadenectomy for breast cancer and were randomised to early discharge with axillary drain in situ on the third postoperative day or standard duration 7 day hospital stay. The two groups did not differ with respect to seroma formation, wound infection or psychological profile as measured by the Hospital Anxiety and Depression Scale and Spielberger State Trait and Anxiety Inventory. Patient satisfaction levels were high in the early discharge group. The results confirm that early discharge after axillary lymphadenectomy is safe, practicable and satisfactory for patients. Such a policy offers considerable resource savings.

Clinical Trial↗
PubMed2000

PM10 dispersion modeling for Treasure Valley, Idaho.

The recorded exceedances of the 24-hr PM10 National Ambient Air Quality Standard (NAAQS) in Treasure Valley, Idaho, have been associated with prolonged stagnation periods during the winter. A comprehensive modeling study of PM10 impact in Treasure Valley was performed to support the State Implementation Plan (SIP). The study included base-year and short-term episodic conditions. The ISCST3 (Industrial Source Complex Short Term 3) model, using the base-year meteorology and gridded emissions of mobile sources, point sources, and wood burning as input, generally agreed well with measurements in both temporal patterns and annual averages. The WYNDvalley model was evaluated using monitoring data and was used to simulate the PM10 impact for episodic exceedances during stagnant winter conditions. An emission inventory was prepared for a base year (1995) and then extrapolated to the years 2000, 2005, 2010, and 2015 in order to determine air quality planning requirements. According to the simulations using base-year emissions and meteorology, exceedances are not expected. However, exceedances at some stations could be expected using projected emissions and episodic meteorology. Results from emission control strategies we developed indicate that mobile-source emissions have the most significant impact; reduction of 25% would be needed to eliminate the simulated exceedances in all projected years.

Air Pollution↗
PubMed2000

Decreased quality of peripheral blood progenitors collected after a peripheral blood progenitor transplant.

The purpose of this study was to determine the quality of peripheral blood progenitor cells (PBPC) collected after an initial autologous PBPC transplant. Tandem autologous transplants have been used in the treatment of several malignancies. Routinely, PBPC have been collected prior to the first transplant and used for both transplants. In the current study, PBPC harvested prior to the first high-dose therapy (HDT) were used as a source of progenitors for transplant 1, and a combination of bone marrow harvested prior to the first course of HDT and PBPC collected approximately 85 days after the first transplant were used to support the second HDT. We analyzed the quality of the PBPC collected 85-120 days after HDT and autologous PBPC transplant. CD34 and colony-forming units granulocyte-macrophage (CFU-GM) contents of those collections were poor, and hematopoietic recovery was more consistent with recovery from a bone marrow transplant than a PBPC transplant. Thirteen of 15 patients received both transplants. Days to absolute granulocyte count of 500 was 10 +/- 1.5 for the first transplant and 13.3 +/- 3.7 for the second (p < 0.01). The number of days to platelet count of 20,000 was 14.3 +/- 10.7 for the first transplant and 18 +/- 7 for the second transplant (p = 0.066). The number of days of total parenteral nutrition (TPN) and intravenous morphine used by patients for the first and second transplants was similar, whereas the length of hospitalization was 21.8 +/- 3.6 for the first transplant and 27.6 +/- 7.8 for the second transplant (NS). In conclusion, it appears that the quality of PBPC collected following a previous PBPC transplant may be compromised.

Adolescent↗