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Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 235 records · Page 13Linked to original sources

Quantitative junctional permeability measurements using the confocal microscope.

This paper describes the use of a photobleach method and confocal microscopy to compare the cell-to-cell transfer rate of 5,6 carboxyfluorescein in dissociated embryonic chick lens cells with those in the anterior epithelium of the whole embryonic chick lens. The average cell-to-cell transfer rates obtained were 7.9 x 10(-3) sec-1 in the dissociated cells and 2.6 x 10(-3) sec-1 in the anterior epithelium in an intact lens.

Animals↗

Type I collagen packing, conformation of the triclinic unit cell.

The X-ray diffraction pattern of tendon collagen can contain a number of sharp Bragg peaks indicating three-dimensional crystallinity of the sample. Optimal diffraction images have been obtained with a high flux synchrotron X-ray source and a carefully maintained sample environment and staining techniques. The Bragg peaks are always superimposed on a diffuse background. This makes interpretation of data difficult and a number of conflicting models of collagen packing have been proposed. The removal of the diffuse scatter from the images allows the Bragg peaks to be seen on a relatively flat background. This was conducted by modelling the background points as a series of two-dimensional polynomial functions. The resultant set of observed Bragg reflections serves as an excellent basis to test the validity of two contradictory packing modes; (1) the triclinic model, Fraser et al., (2) the microfibril model, Kajava. From this it can easily be seen that the model proposed by Kajava is inappropriate, since there is limited agreement between predicted positions of reflections and the positions of observable reflections on film. The packing of collagen molecules on a triclinic lattice is favoured by this criterion.

Animals↗

Improved survival of patients with chronic myelogenous leukemia undergoing allogeneic bone marrow transplantation.

A total of 28 patients with chronic myelogenous leukemia (CML) in chronic phase (CP) received bone marrow allografts from HLA-matched siblings at the University of Florida between August 1984-July 1992. The present study compares the disease-free survival (DFS) for those patients who were transplanted before or after August 1988 using the same conditioning regimen. The analysis shows significant difference in 3-year DFS for those patients transplanted post- vs. pre-August 1988 (69.6% vs. 20%, respectively; P = 0.006). A decrease in pneumonitis due to different etiologies from pre-August 1988 (6/13, 46%) to post-August 1988 (1/15, 7%) was statistically significant (P = 0.029). A decrease, although statistically insignificant, in the overall incidence and severity of acute and chronic graft vs. host disease (GVHD) after August 1988 was also noticed. This study indicates significantly improved outcome for patients with CML in CP who have been treated in the University of Florida after August 1988. Better supportive care and prophylaxis for GVHD most likely contributed to such improvement.

Adult↗

Initiation of anterior head-specific gene expression in uncommitted ectoderm of Xenopus laevis by ammonium chloride.

The role of homeobox-containing genes in the regional specification of the vertebrate embryo has been an area of intense research over the last decade. Whereas it appears that the homeobox genes of the Hox gene family play an important role in the specification of the trunk, the genes and processes involved in the specification of the head are less well understood. We have isolated a new head-specific homeobox gene, XANF-2, that appears to be involved in the regional specification of the anterior head of Xenopus embryos. This gene is initially expressed in the anterior dorsal region of early embryos and later exclusively in the primordium of the anterior pituitary gland. XANF-2 represents the earliest marker for the anterior pituitary lineage. Ammonium chloride is able to induce the expression of XANF-2 in uncommitted ectoderm. These and other data indicate that ammonium chloride is capable of inducing a large portion of the anterior dorsal region of the embryo which includes, but is not limited to, the anterior pituitary gland and cement gland anlagen. This implies that changes in intracellular ionic conditions play an important role in the formation of the anterior head region. In addition to NH4Cl, injection of follistatin RNA can induce transcription of XANF-2, suggesting that these two unrelated compounds can activate a chain of events leading to the formation of the amphibian head. Furthermore, we demonstrate that planar induction in Keller sandwiches can induce XANF-2 expression as well as the expression of the cement gland-specific gene, XCG 13, indicating that planar signaling can account for induction of even the most anterior regions of the embryo.

Amino Acid Sequence↗

Forced midexpiratory time: reference values and the effect of cigarette smoking.

BACKGROUND: Forced midexpiratory time (FET25-75%), the time required to exhale from 25 to 75% of forced vital capacity (FVC), has been advocated as a relatively volume-independent measure of obstruction. Previous estimates of normal FET25-75% have not systematically studied the effect of age, height, sex, and smoking history. METHODS: We analyzed flow-volume loops from 369 normal lifetime nonsmokers and smokers, a random sample of the population of Michigan. Linear models including age and/or height were considered, with and without logarithmic transformation. RESULTS: The best models used age, or age and height, and no transformation. Age and height contributed much less to the variability of FET25-75% than to spirometric flows previously investigated. The largest r2 was found in the male smokers, with the largest contribution from age, suggesting a smoking effect. CONCLUSIONS: As age was the major contributor to the value of FET25-75% and that contribution was small, we suggest the use of simplified age-stratified reference values derived from our data.

Adult↗

Acute pouchitis and deficiencies of fuel.

PURPOSE: Acute pouchitis is a troublesome complication after restorative proctocolectomy. Deficiency of fuel, especially short chain fatty acids (SCFA), produced by anaerobic bacterial fermentation of saccharides, is implicated in ulcerative and diversion colitis. Our hypothesis was that SCFA deficiency occurs in acute pouchitis, and correction of the deficiency is associated with resolution of pouchitis. METHODS: Thirty-two patients were studied, 10 with histologically confirmed acute pouchitis and 22 with healthy pouches. Stool concentrations of SCFA (acetic, propionic, butyric, and valeric acids) were determined by gas-liquid chromatography. Quantitative bacteriologic studies of stool were carried out, and four-quadrant pouch biopsies were assessed by a pathologist who was unaware of the clinical state. Patients with pouchitis were treated for six weeks with metronidazole and given dietary advice to increase their intake of fermentable saccharides. RESULTS: Stool concentrations of SCFA were significantly less in pouchitis patients compared with patients with healthy pouches (340 mumol/g (range, 124-492) vs. 93 (range, 44-136) P < 0.01). No differences in anaerobic or aerobic counts were seen. Resolution of pouchitis was associated with a significant increase in SCFA, but anaerobic counts fell. CONCLUSION: Deficiency of SCFA is implicated in acute pouchitis.

Acetates↗

Recurrence patterns and complications in endometrial adenocarcinoma with cervical involvement.

BACKGROUND: Cervical involvement in endometrial carcinoma is a diverse entity, and the optimal management of these patients is not well understood. METHODS: Recurrence patterns and complications in 202 patients with histologically confirmed endometrial carcinoma with cervical involvement were retrospectively studied. RESULTS: The 5-year actuarial survival rate for all patients was 65%. Recurrences were documented in 80 (40%) of the patients, and the overall long-term survival rate in this group was 4%. Patients treated with radical hysterectomy (n = 33) had a 6% isolated pelvic recurrence rate and the lowest serious complication rate among the five treatment groups despite having the highest frequency of risk factors for recurrence among any of the groups studied. Patients treated with extrafascial hysterectomy alone (n = 37) had a 14% pelvic recurrence rate and very few complications. When radiotherapy preceded extrafascial hysterectomy (n = 37), the frequency of pelvic recurrences was 30%, and 19% experienced serious gastrointestinal or genitourinary tract complications. When radiotherapy followed extrafascial hysterectomy (n = 68), the pelvic recurrence rate was 24%, and 13% experienced serious complications. Overall, 24% of patients (49 of 202) had isolated pelvic recurrences, whereas 10% (21 of 202) had isolated distant recurrences and 5% (10 of 202) were simultaneously diagnosed with both pelvic and distant recurrences. CONCLUSIONS: This large data base suggests that older conventional forms of therapy, particularly those using preoperative radiotherapy, subject the patient to significant morbidity over a 5- to 10-year period and, in terms of local control, are not necessarily superior to therapeutic modalities using primary surgical evaluation, such as radical hysterectomy. Consideration of primary surgery should be given in the appropriate situation, and radical hysterectomy should be considered when gross cervical involvement is encountered and intraoperative exploration does not show obvious extrauterine disease.

Actuarial Analysis↗

Rapid differentiation of closely related isolates of two plant viruses by polymerase chain reaction and restriction fragment length polymorphism analysis.

Immunocapture reverse transcriptase-polymerase chain reaction (RT-PCR) followed by restriction fragment length polymorphism (RFLP) analysis of the product has been shown to be an effective procedure for discriminating serologically indistinguishable isolates of two plant viruses, raspberry bushy dwarf (RBDV) and zucchini yellow mosaic (ZYMV). For both viruses, only limited sequence information was available at the time of primer design, but most of the isolates which were tested could be amplified (the one exception being a serologically quite distinct isolate of ZYMV). Restriction endonucleases revealing diagnostic RFLPs were readily identified. Each of two isolates of ZYMV could be detected in the presence of the other and the relative proportions approximately quantified by visual estimation of the relative intensity of the appropriate bands. A range of isolates of different RBDV pathotypes were compared; isolates were grouped in ways that accorded with their known history. Computer analysis of the published sequence from which the primers had been derived showed the sequenced isolate to be identical with an isolate imported from the USSR. The PCR/RFLP procedure is rapid (it can be completed in less than 2 days), effective and will probably be generally applicable to distinguishing closely related virus isolates, even where little sequence information is available.

Base Sequence↗

Vibrational neutron spectroscopy of collagen and model polypeptides.

A pulsed source neutron spectrometer has been used to measure vibrational spectra (20-4000 cm-1) of dry and hydrated type I collagen fibers, and of two model polypeptides, polyproline II and (prolyl-prolyl-glycine)10, at temperatures of 30 and 120 K. the collagen spectra provide the first high resolution neutron views of the proton-dominated modes of a protein over a wide energy range from the low frequency phonon region to the rich spectrum of localized high frequency modes. Several bands show a level of fine structure approaching that of optical data. The principal features of the spectra are assigned. A difference spectrum is obtained for protein associated water, which displays an acoustic peak similar to pure ice and a librational band shifted to lower frequency by the influence of the protein. Hydrogen-weighted densities of states are extracted for collagen and the model polypeptides, and compared with published calculations. Proton mean-square displacements are calculated from Debye-Waller factors measured in parallel quasi-elastic neutron-scattering experiments. Combined with the collagen density of states function, these yield an effective mass of 14.5 a.m.u. for the low frequency harmonic oscillators, indicating that the extended atom approximation, which simplifies analyses of low frequency protein dynamics, is appropriate.

Amino Acid Sequence↗

The upper arm basilic-cephalic loop for distal bypass grafting: technical considerations and follow-up.

PURPOSE: The performance of a graft created from the upper arm basilic and cephalic veins in continuity was investigated. METHODS: Retrospective analysis of 50 patients, who underwent 54 distal reconstructions with an upper arm vein loop graft between February 1989 and October 1993 (male-to-female ratio of 30/20; mean age of 69.2 years, range 39 to 87; 74% had diabetes) was undertaken. Vein grafts were harvested through a near continuous incision, leaving a skin bridge in the cubita. Intraoperative angioscopy was used to exclude endoluminal disease and to directly observe valvulotomy of the nonreversed part of the graft. RESULTS: Operations were performed for limb salvage in 98.2% of 17 primary and 37 reoperative procedures. Eleven femoropopliteal, 33 femorotibial-pedal, seven popliteal-distal, and two outflow jump grafts were performed. The ipsilateral saphenous vein was unavailable because of previous infrainguinal bypass in 35, coronary artery bypass grafting in 14, and unsuitable quality in 5 cases. Thirty-eight grafts were used in continuity, and 16 grafts required repair or splicing with additional vein segments. Primary 30-day patency rate was 92.6% (n = 4 occlusions). No operative deaths occurred. The cumulative patency rate at 1 year was 74.4%, the limb salvage rate 90.7%. CONCLUSIONS: The upper arm vein loop is a durable graft with excellent short-term and midterm patency rates. Sufficient vein length can be obtained to reach the below-knee and midtibial levels. Angioscopic quality assessment is a valuable adjunct to exclude endoluminal disease most commonly occurring in the median cubital vein. Straightening the curve of the median cubital vein and valvulotomy do not influence patency rates. This is a valuable technique for vascular surgeons that enables rescue of ischemic limbs under otherwise difficult circumstances.

Adult↗

Return to well-being and function after infrainguinal revascularization.

PURPOSE: The purpose of this study was to assess functional status, well-being, and symptom relief of patients after infrainguinal revascularization for severe peripheral vascular disease. METHODS: Two questionnaires were used to assess symptoms, functional status, and well-being before operation and 6 months after operation. Sociodemographics, comorbidities, indications for surgery, graft location, and morbidity, mortality, patency, and limb salvage rates were obtained via vascular registry. RESULTS: Of 318 patients who underwent revascularization over a 1-year period, 276 patients were asked to complete the questionnaires. Of the 156 patients who completed both questionnaires, mean age was 66 years, 67% were men, 84% had diabetes mellitus, and 83% had various heart-related conditions. Mean length of stay was 15.3 days. Distal graft sites were popliteal (29%), tibial/peroneal (40%), and pedal/plantar (31%). The operative morbidity rate was 21%, the cumulative primary graft patency rate was 93%, the cumulative secondary graft patency rate was 95%, and the limb salvage rate was 97% at 6 months. At follow-up, improved functioning of instrumental activities of daily living, mental well-being, and vitality were reported. Symptoms of calf cramping and toe or foot pain when walking and at rest were also improved. Sores or ulcers improved, but leg swelling did not. The only independent predictor of improved function and well-being was the patients' perception of their status at baseline: those patients who functioned better before operation reported improved function and well-being at 6 months. Only 45% of patients reported feeling "back to normal" at 6 months. CONCLUSION: Reported health status at baseline was a predictor of improved function, mental well-being, and resolution of symptoms after infrainguinal revascularization. Expected return to "normal" may take longer than 6 months.

Activities of Daily Living↗

Dorsalis pedis arterial bypass: durable limb salvage for foot ischemia in patients with diabetes mellitus.

PURPOSE: Although the technical feasibility of pedal artery bypass for limb salvage is now well established, questions remain about its most appropriate use and its long-term durability. METHODS: We reviewed our experience over an 8-year period in 367 consecutive patients undergoing 384 vein bypass grafts to the dorsalis pedis for limb salvage. RESULTS: Ninety-five percent of the patients had diabetes mellitus. Infection complicated ischemia at initial presentation in 55.2% of patients. The preoperative arteriogram demonstrated a patent dorsalis pedis in 362 extremities (92.8%). Four hundred two patients underwent exploration for bypass, including 29 patients without demonstrated arteries on the arteriogram but audible pedal Doppler signals. Successful bypasses were carried out in 357 of 362 cases, where preoperative arteriography demonstrated a patent dorsalis pedis artery (98.6%), 16 of 28 cases explored on the basis of a Doppler signal alone (57%), and 11 of 12 patients where angiographic status was unknown. All procedures were performed with vein: in situ 38.5%, reversed 29%, nonreversed 18%, arm vein 7%, and composite vein 8%. Inflow was taken from the common femoral artery in 34%, superficial femoral or popliteal arteries in 60%, a previously placed graft in 5%, and a tibial artery in 1%. There were seven perioperative deaths (1.8%) and 21 myocardial infarctions (5.4%). Twenty-nine grafts failed within 30 days (7.5%), but 19 were successfully revised. Eight of the 10 failed grafts resulted in major amputation (80%). Over the remaining study period, there were 39 additional graft failures, of which 17 were successfully revised, and 17 additional major amputations. Actuarial primary and secondary patency and limb salvage rates were 68%, 82%, and 87%, respectively, at 5 years' followup. The actuarial patients survival rate was 57% at 5 years. Patency rates were similar for in situ and translocated saphenous vein grafts. CONCLUSIONS: Dorsalis pedis arterial bypass is an effective limb salvage procedure with long-term durability comparable to distal vein grafts placed into more proximal arteries.

Arteries↗

Soluble tumor necrosis factor receptors reduce bowel ischemia-induced lung permeability and neutrophil sequestration.

OBJECTIVES: To evaluate the possible role of tumor necrosis factor (TNF) in the development of lung injury after bowel ischemia, and the ability of TNF-soluble receptors to negate TNF toxicity, using a rat small bowel ischemia and reperfusion model. DESIGN: Prospective, randomized, controlled laboratory study. SETTING: Research laboratory. SUBJECTS: Forty adult male Sprague-Dawley rats weighing approximately 300 g. INTERVENTIONS: The rats were divided equally into four groups: a) ischemia and reperfusion alone; b) those animals receiving TNF antibodies (1 mL) before reperfusion; and c) those animals receiving 200 micrograms of human recombinant TNF soluble receptors. These 30 anesthetized rats underwent 60 mins of superior mesenteric artery occlusion per 4 hrs of reperfusion. The remaining ten animals were sham operated (laparotomy), serving as controls. Lung permeability was measured using bovine serum albumin labeled with 125I, and organ injury was assessed histologically. MEASUREMENTS AND MAIN RESULTS: Thirty and 60 mins after declamping and reperfusion, plasma TNF concentrations increased to 830 +/- 66 and 173 +/- 56 pg/mL, respectively, compared with 10 pg/mL before ischemia (p < .001). In sham-operated control rats, TNF concentrations did not increase from baseline concentrations. Four hours after reperfusion, sequestration of neutrophils in the pulmonary microcirculation was noted (319 +/- 60 vs. 84 +/- 13 neutrophils/10 high-power fields in sham-operated rats [p < .04]). Pulmonary microvascular leak also occurred, as measured by translocation of radiolabeled albumin into the bronchoalveolar space and expressed as the ratio of bronchoalveolar lavage to blood concentrations. This ratio was 5.3 +/- 0.8 in ischemic control animals compared with 1.1 +/- 0.3 in sham animals (p < .03). Treatment with antibodies to TNF before reperfusion attenuated the pulmonary injury (75 +/- 6 neutrophils/10 high-power fields, permeability index 1.6 +/- 0.1) less than in ischemic controls (p < .005). A similar protection was achieved with soluble TNF receptors, which prevented bowel ischemia-induced lung neutrophil sequestration (117 +/- 35 neutrophils/10 high-power fields, pulmonary vascular leak ratio of 2.3 +/- 0.1, p < .05). CONCLUSIONS: The results of this study show that ischemia and subsequent reperfusion of the intestine in rats produce lung injury. This injury is mediated, at least in part, by TNF. Soluble TNF receptors are an effective tool in preventing lung TNF injury after intestinal ischemia.

Animals↗

Rapid diagnosis of pulmonary tuberculosis by using Roche AMPLICOR Mycobacterium tuberculosis PCR test.

A rapid PCR-based test for the diagnosis of pulmonary tuberculosis, the Roche AMPLICOR Mycobacterium tuberculosis test (AMPLICOR MTB), was evaluated. Results from AMPLICOR MTB were compared with culture results and the final clinical diagnosis for each patient. A total of 985 specimens from 372 patients were tested. When AMPLICOR MTB results were compared with resolved results, i.e., a specimen grew M. tuberculosis or was obtained from a patient with a clinical diagnosis of tuberculosis, the sensitivity, specificity, positive predictive value, and negative predictive value for the AMPLICOR MTB test were 66.7, 99.6, 91.7, and 97.7%, respectively. These results were comparable to those obtained from culture. Test results were available approximately 6.5 h after specimen receipt in the laboratory. Our data demonstrate that AMPLICOR MTB will provide rapid, valuable information for the diagnosis and control of tuberculosis.

Bacteriological Techniques↗

Cross linking of collagen is increased in colonic diverticulosis.

Development of colonic diverticulosis is a function of age and declining colonic wall mechanical strength. The latter is partly a consequence of changes in the collagen structure. Collagen from unaffected human colons (n = 20, age range 20-80 years) and those with colonic diverticulosis (n = 5, age range 67-80 years) were obtained at necropsy. The total collagen content was measured as the hydroxyproline content and cross linkage by collagen solubility in weak acid was studied. The colonic total collagen content was constant with age (mean (SD) 15.8 (0.3) mg/100 mg wet weight of tissue). The acid solubility of the collagen, however, increased after the age of 40 years: at over 60 years, colonic diverticulosis was associated with an increased acid solubility ratio compared with values in unaffected colons (15.3 (0.2); compared with 9.2 (0.2), p < 0.001). The cross linking of colonic collagen increases with age. These changes seem to be a factor in the aetiology of colonic diverticulosis.

Adult↗

A molecular model of low-voltage-activated calcium conductance.

1. T-type or low-voltage-activated Ca2+ channels (IT) expressed in the mammalian thalamus play an important physiological role in the induction of membrane potential oscillations and in the regulation of the timing of synaptic signaling. On the basis of recent molecular studies on Ca2+, Na+, and K+ channels, a structure-kinetic model has been proposed for IT. 2. The model considers that the pore-opening process of IT is governed by three of the four protein domains that are arranged asymmetrically across the membrane plane. The three cytoplasmic linkers connecting individual channel domains serve as inactivation gates. On a membrane voltage change, each domain may engage independently into a sequential, thermodynamically coupled conformational change, thereby causing channel activation and inactivation. 3. A linear Marcov chain reaction with coupled channel activation and inactivation was adopted to test the kinetic feasibility of this trimeric model in a single-compartmental thalamic cell. The differential equations for voltage-dependent rate constants and transitional rates were solved to produce macroscopic T-type Ca2+ current. 4. Our simulation results indicate that this novel structure-kinetic model produces excellent predictions of the macroscopic behaviors of IT, and, more importantly, it provides some new insights into the microscopic mechanism underlying channel recovery.

Animals↗

Pulmonary function tests in HIV-infected patients without AIDS. Pulmonary Complications of HIV Infection Study Group.

To determine the prevalence, incidence, and types of lung diseases that occur in association with HIV infection, 1,353 subjects, including HIV-seropositive homosexual men, injection drug users, female sexual partners of HIV-positive men, and HIV-seronegative control subjects from the first two transmission categories were evaluated prospectively in a multicenter study. Patients with AIDS at the time of initial evaluation were excluded. One thousand two-hundred ninety-four subjects who had no AIDS-defining diagnosis within 3 mo of enrollment had measurements of FVC, FEV1 and DLCO at the time of enrollment. As a group, all subjects had mean values of FVC and FEV1 close to 100% predicted. Those with CD4 counts below 200/mm3 had slightly reduced DLCO compared with the others. Subjects with a history of HIV-associated symptoms (thrush, weight loss, herpes zoster) also had a reduced DLCO compared with those without symptoms. Injection drug users had reduced FVC, FEV1 and DLCO compared with homosexual men and female sexual partners of HIV-infected men, with DLCO more substantially reduced. Part of the reduction in DLCO in drug users was attributable to factors other than HIV infection, especially cigarette smoking and race. Using predicted values that take cigarette smoking into account, the prevalence of abnormality in DLCO was higher among injection drug users (33.3%) than among homosexual men (11.2%) and female sexual partners (12.7%). These results show that advanced HIV infection, characterized by CD4 count < 200/mm3 or HIV-associated symptoms, and factors unrelated to HIV infection, including race, cigarette smoking, and injection drug use, are all associated with reductions in DLCO measurements.

Bisexuality↗