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Biomedical subjects

J Reed

Publications and source records attributed to J Reed.

At least 109 records · Page 6Linked to original sources

Placental cryptococcosis in a mother with systemic lupus erythematosus.

There are many pregnant mothers who have acquired immunodeficiency syndrome or who require immunosuppressive therapy for sundry reasons. Despite this, we have been able to find only one English-language report of placental cryptococcosis. We have had an opportunity to treat a pregnant mother who suffered from cryptococcal meningitis that complicated steroid treatment for lupus erythematosus. At 31 weeks' gestation, fetal distress necessitated delivery by cesarean section. The placenta had focally abundant intervillous and perivillous cryptococcal yeast cells, but there was no chorioamnionitis or villitis. Although there were no clinical or placental signs of transplacental infection, immunohistochemical labeling of villous stromal cells showed a conspicuously increased number of fetal macrophages.

Adult↗

Laparoscopic versus conventional appendectomy.

BACKGROUND: The results of recent series suggest remarkable advantages of laparoscopic appendectomy over the conventional open appendectomy. To determine if clear advantages could be established, the charts of all patients admitted to our institution with a presumptive diagnosis of acute appendicitis and subsequent appendectomy were retrospectively reviewed. STUDY DESIGN: From January 1990 through June 1992, there were 300 conventional open appendectomies and 66 laparoscopic appendectomies performed. Data from both groups were compared with respect to anesthesia time, operative time, postoperative morbidity, postoperative pain, time to regular diet, hospitalization period, cost, and return to normal activities. RESULTS: There were no significant differences between the laparoscopic and open appendectomy groups with respect to operative complications, postoperative morbidity, pain medication requirements, and time to regular diet. There were significantly longer anesthesia times, operative times, and operating room costs in the laparoscopic group. For complicated appendicitis, the laparoscopic technique resulted in infectious complications that required readmission in 45.5 percent of the patients. CONCLUSIONS: Laparoscopic appendectomy is a safe alternative to conventional open appendectomy for simple acute appendicitis. However, laparoscopic appendectomy is not superior to the conventional method with regard to operative time, postoperative morbidity, pain medication requirements, time to regular diet, length of stay, cost, or return to normal activity. Laparoscopic appendectomy may be contraindicated in complicated appendicitis (gangrene, perforated with abscess, or peritonitis) due to an increased rate of infectious complications requiring readmission.

Acute Disease↗

Primary structure elements responsible for the conformational switch in the envelope glycoprotein gp120 from human immunodeficiency virus type 1: LPCR is a motif governing folding.

The ability to undergo a particular conformational switch on moving from a polar to a less polar environment has been shown to be conserved at the CD4-binding domain of the envelope glycoprotein gp120 from human immunodeficiency virus type 1 despite considerable variability in primary structure and is essential for the process of binding to the T-cell receptor CD4. The elements necessary to the expression of this behavior have been examined in synthetic peptides using circular dichroism and have been found to include a tetrad, LPCR, plus a tryptophan at a position 8 residues C-terminal to it. In the absence of the tryptophan the conformational change from beta-sheet to alpha-helix as medium polarity decreases does not occur abruptly but, rather, in a linear fashion. In the absence of the LPCR tetrad, no transition to alpha-helix occurs even at 100% trifluoroethanol. These two domains interact to control not only the beta-->alpha transition but also both its cooperativity and the critical point on the polar-->apolar gradient at which it occurs. Sequence similarity searches of the protein data banks suggest that an LPCR tetrad, governing the folding behavior of subsequent residues, may occur as a conserved motif in proteins in general. Synthetic peptides with the sequence of non-gp120 proteins that contain the tetrad do in fact display a similar pattern of folding response to decreasing polarity, with a sharp, cooperative transition from beta-sheet to alpha-helix. The LPCR tetrad appears to be a motif that controls secondary structure in a manner supplementary to that predicted by folding algorithms.

Amino Acid Sequence↗

Total quality management system: its application in a community hospital research department.

Lehigh Valley Hospital initiated a program of total quality management using the model taught by Philip Crosby Associates. When the training began in the Research Department, we used the application of this model to identify, define and chart the various processes that a research project or study moves through from conception to publication. The resulting charts and process outlines enabled the Research Department personnel to recognize problem areas in the processes, and to chart the progress of a study at any given time. This provided us with both a better understanding of input and output in the research processes, and an opportunity to improve efficiency by correcting problem areas.

Biometry↗

Nosocomial herpes simplex virus infection associated with oral endotracheal intubation.

BACKGROUND: To determine by culture the frequency of herpes simplex virus reactivation complicating oral endotracheal intubation. Additionally, clinical appearance and recognition of patient infection by attendant health care workers were studied. Last, evidence of any occupational acquisition of herpes simplex virus infection was sought. METHODS: In a prospective, non-randomized study, three serial viral cultures were taken of oro-facial or mucosal sites on the day of oral endotracheal intubation and in the subsequent 3rd and 5th or 7th days from 51 consecutive adults undergoing oral endotracheal intubation in a suburban community hospital. Clinical variables including appearances of lesions and therapeutic interventions were noted during serial assessments by study authors. Employee health records were reviewed for evidence of health care worker occupational herpes simplex virus infection associated with these cases. RESULTS: Of 51 patients, 4 were culture positive on the day of oral endotracheal intubation. Of the remaining 47 patients, serial cultures during the first week post intubation revealed herpes simplex virus in 25 (53.2%) patients. Of cohort variables studied, a history of prior oral herpes simplex virus was significantly associated with a subsequent positive viral culture for herpes simplex virus (relative risk, 2.29; 95% confidence interval, 1.48 to 3.56). Typical or atypical lesions were visible in only 52% of the herpes simplex virus culture-positive cases. No occupational transmission of herpes simplex virus was detected. Tape-securing practices appeared to contribute to the morbidity of herpes simplex virus eruptions. CONCLUSIONS: Nosocomial reactivation of herpes simplex virus infection complicated oral endotracheal intubation in our patient population in approximately one half of the patients who were intubated for more than 48 hours during the first week after the procedure. Clinically, the infection was recognizable in only one half of the virus culture-positive cases. Increased awareness of this infection is needed by health care workers, patients, and families. More information is needed on optimal therapy and prevention.

Aged↗

Amplitude of the ocular pneumoplethysmography waveform is correlated with cardiac output.

BACKGROUND AND PURPOSE: Ocular pulse amplitude, the amplitude of the ocular pneumoplethysmographic waveform, is altered in several ophthalmologic diseases that disturb ocular blood flow, implying that ocular pulse amplitude may provide an estimate of ocular blood flow. Because ocular blood flow currently cannot be quantified in humans, two experiments were undertaken to evaluate the association of ocular pulse amplitude with total body blood flow. METHODS: In experiment 1, cardiac output was determined by cardiac catheterization in 181 patients who underwent OPG-Gee testing during the same hospitalization. In experiment 2, 110 instances of atrial arrhythmia captured on ocular pneumoplethysmographic tracings were evaluated for transient changes in heart rate (R-R ratio) associated with transient changes in ocular pulse amplitude (ocular pulse amplitude ratio). RESULTS: In experiment 1, average ocular pulse amplitude in the two eyes (OPAAV) was significantly correlated with cardiac output/heart rate (r = 0.53; p < 0.0001) and cardiac index/heart rate (r = 0.43; p < 0.0001). In experiment 2, R-R ratio was significantly correlated with ocular pulse amplitude ratio (r = 0.85; p < 0.001). CONCLUSIONS: These results show that ocular pulse amplitude, a physiological measurement obtained from the globe, is correlated with cardiac output. They imply that ocular pulse amplitude may provide a clinically useful estimate of at least the pulsatile component of ocular blood flow.

Aged↗

Conformational properties of the beta(400-436) and beta(400-445) C-terminal peptides of porcine brain tubulin.

Two peptides from the C-terminal region of the major beta-tubulin isotype (400-436 and 400-445) that include the critical areas for interaction with MAP2 and tau were examined to determine their conformations in aqueous solution. Despite a high theoretical potential for alpha-helix formation, CD spectroscopy showed that these peptides consisted primarily of random coil with some reverse turn. This was unaffected by the presence of counterions to the negatively charged side chains (Ca2+, Mg2+), but did change when the side-chain charges were neutralized by lowering the pH; under these conditions, the alpha-helix content of the longer peptide rose to 25% and the C-terminal truncated peptide to 15%. The peptides also adopt alpha-helical structure in the presence of trifluoroethanol, the truncated peptide again attaining a lower maximum percentage. The beta(400-445) peptide was also studied by 1-D and 2-D NMR techniques. The results indicate that at pH 5.6 or 7 in an aqueous solution the peptide is extremely flexible and lacks regular secondary structure, consistent with the CD results. Both peptides inhibited microtubule-associated protein-stimulated tubulin assembly, with the longer peptide being about 4 times as inhibitory as the smaller peptide. Neither was inhibitory in the absence of microtubule-associated proteins, indicating that interaction with this species was necessary for inhibition. The greater activity of the longer peptide could be due to the extra negative charges in this peptide and/or the greater tendency of this peptide to form an alpha-helical structure under the appropriate conditions.

Amino Acid Sequence↗

Substitutions of hydrophobic amino acids reduce the amyloidogenicity of Alzheimer's disease beta A4 peptides.

The deposition of amyloid protein aggregates in brain is the main pathological feature of Alzheimer's disease. Their principal constituent is a peptide termed beta A4, which comprises up to 43 amino acid residues. It is highly insoluble under physiological conditions and aggregates into filaments that form very dense clusters in vivo and in vitro. Based on a beta A4 prototype sequence spanning residues 10 to 42 or 43, we have designed analogues in which hydrophobic amino acid residues in position 17 to 20 were substituted by more hydrophilic residues. Depending on the kind of newly introduced amino acids and their position within the sequence, the substitution of only two residues led to variants exhibiting a broad spectrum of different properties. Common to them was a reduced beta-sheet content after solubilization in water and in the solid state. Some of the variants showed significantly reduced amyloidogenicity: although still forming filaments, they did not aggregate into the highly condensed depositions that are typical for amyloid. In addition, they could be solubilized in 200 mM-NaCl and KCl. When mixed with beta A4 peptides bearing the natural sequence, two of the analogues could inhibit the formation of filaments in vitro. These results demonstrate that a well-preserved hydrophobic core around residues 17 to 20 of beta A4 is crucial for the formation of beta-sheet structure and the amyloid properties of beta A4. The introduction of structural alterations within this region may guide the development of reagents for the therapy of Alzheimer's disease.

Alzheimer Disease↗

Atrial natriuretic peptide is phosphorylated by intact cells through cAMP-dependent ecto-protein kinase.

Recently we demonstrated the presence of cell-surface-located cAMP-dependent protein kinase (ecto-PK A) activity in a number of different cell types [Kübler, D., Pyerin, W., Bill, O., Hotz, A., Sonka, J. and Kinzel, V. (1989) J. Biol. Chem. 264, 14549-14555]. The question of the physiological role of externally directed kinase activity prompted a search for potential natural substrates present in the intercellular fluid. In the present study we have investigated the phosphorylation by ecto-PK A of the human atrial natriuretic peptide ANP99-126, a hormone released by cardiac cells. This 28-amino-acid peptide carries the phosphorylation consensus sequence Arg-Arg-Ser-Ser for the PK A. Incubation of various cell lines (including epithelial, epidermal, myoblast and lymphoma cells) or freshly isolated blood cells (macrophages, erythrocytes and platelets) with ANP in the presence of low micromolar concentrations of ATP resulted in the phosphorylation of ANP at Ser residues. The ANP phosphorylation reaction proved strictly dependent on cAMP; cAMP could not be replaced by cGMP. The phosphorylation was inhibited by the PK A-specific inhibitory peptide and increased linearily for up to 15 min and with a Km value of 3-5 microM for ANP. At higher ATP concentrations (greater than 100 microM) the incorporation rates amounted to about 0.3 mmol P (mol ANP)-1 min-1. The rise of intracellular cAMP in HEL30 (an epidermal cell line) after application of the beta-adrenergic receptor agonist isoproterenol led to an approximately three-fold stimulation of ANP phosphorylation which appears to be brought about by an efflux of intracellular cAMP. Employing cell supernatant fluids and cell sonicates, it could be shown that the phosphorylation of ANP results from the ecto-PK A. Comparison of ANP with ANP phosphorylated in vitro using purified catalytic subunit of PK A showed that phosphorylation is accompanied by certain changes in the average solution conformation of the peptide, consistent with the changes known to occur in its biological activity. Our results demonstrate cAMP-dependent phosphorylation of the peptide hormone analogue ANP99-126 by intact cells through ecto-PK A, an intriguing mechanism for post-translational processing of ANP.

Adenosine Triphosphate↗

Physical performance of a positron tomograph for brain imaging with retractable septa.

Performance characteristics of a new design of positron tomograph with automatically retractable septa for brain imaging have been studied. The device, consisting of block BGO detectors (8 x 8 elements per block), has a ring diameter of 76 cm and an axial FOV of 106.5 mm. The in-plane resolution is on average 5.8 mm and 5.0 mm (FWHM) for stationary and wobble sampling, respectively, over the central 18 cm of the transaxial FOV. Its unique feature is the capability of data acquisition both in the 'conventional' 2D mode (with septa) or 3D mode (septa retracted) where coincidences between any of the 16 detector rings are acquired. When scattered events are subtracted, the efficiency for a 20 cm diameter uniform cylinder increases overall by a factor of 4.8 between 2D (septa extended) and 3D modes. For a 20 cm phantom the trues/singles ratio is higher for 3D than for 2D but for a given unscattered trues rate, the randoms rate in 3D is higher. At 380 keV the scatter fraction within a 20 cm cylinder is 10% (septa extended) and 36% (retracted). In spite of the increase in scatter when septa are retracted, the increased efficiency in the 3D mode of acquisition yields distinct advantages, particularly in the many studies where tracer concentration is low and consequently where dead time and random rates are less important.

Brain↗

The pre-operative anaesthetic visit. Its value to the patient and the anaesthetist.

One hundred and thirty-two patients staying in hospital more than 24 h were visited pre- and postoperatively. Patients were asked a standard set of questions, and 39% could not remember accurately what they were asked. This has important medicolegal implications. In 15% of patients, information that significantly altered subsequent anaesthetic management was discovered, but in less than 3% would ignorance of the patient's condition have required postponement of the surgery. We conclude that the major reason for a pre-operative visit by an anaesthetist is that patients appreciate it, rather than it being medically necessary.

Adolescent↗

Secondary data in nursing research.

Secondary data are increasingly incorporated into nursing research studies, as nurses seek to capture and address the complexity of patient care. There is, however, little discussion in methodological literature about this type of data; the meaning is taken for granted and the data are regarded as simple sources of information, which are convenient and cost-effective. This approach denies the social meaning of the data, and is likely to lead to misinterpretation of the content. This paper discusses these analytical issues with reference to a research study which used secondary data (nursing care plans) in an examination of the ways in which nurses assess their patients. Using this data led to an increased understanding of the social world in which assessment took place.

Data Interpretation, Statistical↗

Magnetic resonance imaging evaluation helps to delineate a recurrent skin cancer present under the skin flap.

A case of recurrent squamous cell carcinoma under a skin flap as confirmed and delineated by magnetic resonance imaging (MRI) is described. This report illustrates a potentially new indication for MRI in clinical dermatology, namely, to define skin cancer recurrences under skin flaps and grafts and to determine the extent of underlying tissue involvement. The cost-effectiveness of MRI and the use of gadolinium, an MRI contrast agent, in the evaluation of skin tumors are also addressed.

Aged↗

Expression of the normal p53 gene induces differentiation of K562 cells.

The multistep nature of human cancers is well illustrated by chronic myelogenous leukemia (CML), a clonal hematologic malignancy with two distinct phases: chronic and acute. Transition between these phases is characterized by unregulated growth and loss of differentiation of myeloid cells and their progenitors. We recently reported that loss of normal p53 expression correlates with transition from the chronic to acute phase in at least 25% of cases of CML. However, the precise relationship between this loss and biologic features of acute-phase CML is uncertain. To study this question, we artificially expressed normal p53 in K562, an erythroid acute-phase CML cell line lacking normal p53 expression. Biological effects were assessed by determining several growth parameters and by measuring synthesis of hemoglobin, a feature of mature erythroid cells. K562 cells expressing normal p53 had an increased proportion of cells in G1 versus S + G2, a longer doubling time and a lower growth saturation density than control K562 cells or K562 cells with antisense p53. Cells with normal p53 also expressed up to 50-fold more hemoglobin than controls. These data are consistent with the notion that loss of p53 expression may be responsible for many of the features of acute-phase CML cells. The data also demonstrate direct involvement of p53 in differentiation processes.

Cell Cycle↗

Establishment and characterization of monoclonal antibodies against an octahedral gallium chelate suitable for immunoscintigraphy with PET.

As a prerequisite for preparing bispecific antibody conjugates containing anti-tumor and anti-metal chelate binding sites that can be used for pretargeted immunoscintigraphy, monoclonal antibodies (Mabs) have been raised against an octahedral metal chelate synthetized from gallium (Ga) and the hexadentate ligand N,N'bis[2-hydroxy 5-(ethylene beta carboxy) benzyl] ethylenediamine N,N' diacetic acid (Ga-HBED-CC). With use of the Farr assay, binding studies with the 67Ga-labeled chelate and three clones of anti-chelate Mabs showed that none of the Mabs were able to precipitate more than 50% of the Ga-chelate, suggesting an enatiomerism of the Ga-chelate and a sensitivity of the Mabs to either one or the other chelate enantiomer. This could be confirmed by comparing the circular dichroism spectra of the Ga-chelate fractions that passed affinity columns containing the Mabs immobilized on sepharose without retention. With use of a Ga-HBED-CC enantiomer, whole-body retention in mice, preinjected with the corresponding anti-metal chelate Mab of ca. 70% ID, was measured compared to 2.1% retention in mice not preinjected with the Mab. Due to the high affinity of chelate-to-Mab binding in vivo, bispecific antibody conjugates prepared from the fragments of the anti-Ga-chelate Mab might be suitable for pretargeted immunoscintigraphy with the short-lived positron-emitter 68Ga.

Animals↗