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Biomedical subjects

G Lee

Publications and source records attributed to G Lee.

At least 199 records · Page 11Linked to original sources

Apparent pKa of the fatty acids within ordered mixtures of model human stratum corneum lipids.

PURPOSE: The apparent pKa of the fatty acids within hydrated (30% w/w) model human stratum corneum (SC) lipid mixtures should be measured. METHODS: The degree of ionisation of the fatty acids was calculated as a function of pH using Fourier transform infra-red spectroscopy. The relative intensity of the stretching bands of the unionized and ionized carboxylic groups was determined and fitted to the relevant expression for ionic equilibrium of a monoprotic acid. The pKa was then calculated for increasing proportion of unsaturated fatty acid in the lipid mixture. RESULTS: Values for pKa in the range 6.2-7.3 were found, increasing with greater proportion of oleic acid. These are some 1.5-3 pH units higher than the pKas of fatty acids in molecular solution. CONCLUSIONS: As there exists a pH-gradient across the SC, the degree of ionisation will also vary. In the innermost SC layers, a pH of 7 will produce 90% ionization of the fatty acids and head-group repulsion will be great. At the SC surface, the pH of 5 will cause almost minimal head-group repulsion, tending to increase crystallinity and promote a bilayer structure.

Ceramides↗

Pseudologia fantastica and gender identity disturbance in a Chinese male.

A Chinese patient with pathological lying (pseudologia fantastica) and gender identity disturbance is described. The stories "save face" and lack a truly self-aggrandising quality. The importance of keeping "face" and maintaining modest behaviour in the Chinese culture is central to the psychopathology.

Adult↗

Interaction of tau with the neural plasma membrane mediated by tau's amino-terminal projection domain.

The neuronal microtubule-associated protein tau is required for the development of cell polarity in cultured neurons. Using PC12 cells that stably express tau and tau amino-terminal fragments, we report that tau interacts with the neural plasma membrane through its amino-terminal projection domain. In differentiated PC12 transfectants, tau is found in growth cone-like structures in a nonmicrotubule-dependent manner. In hippocampal neurons, tau is differentially extracted by detergent and enriched in the growth cone and the distal axon when membrane is left intact. In PC12 transfectants, overexpression of tau's amino-terminal fragment, but not of full-length tau, suppresses NGF-induced process formation. Our data suggest that tau's amino-terminal projection domain has an important role in neuritic development and establishes tau as a mediator of microtubule-plasma membrane interactions.

Amino Acid Sequence↗

Origin of estradiol fatty acid esters in human ovarian follicular fluid.

The estradiol fatty acid esters are the most potent of the naturally occurring steroidal estrogens. These esters are present predominantly in fat, where they are sequestered until they are hydrolyzed by esterases. Thus they act as a preformed reservoir of estradiol. We have previously shown that ovarian follicular fluid from patients undergoing gonadotropin stimulation contains very high amounts of estradiol fatty acid esters (approximately 10(-7) M). The source of these esters is unknown. They can be formed by esterification of estradiol in the follicular fluid by lecithin:cholesterol acyltransferase (LCAT), or in the ovary by an acyl coenzyme A:acyltransferase. In order to determine which of these enzymatic processes is the source of the estradiol esters in the follicular fluid, we incubated [3H]estradiol with follicular fluid and cells isolated from human ovarian follicular fluid and characterized the fatty acid composition of the [3H]estradiol esters biosynthesized in each. In addition, we characterized the endogenous estradiol fatty acid esters in the follicular fluid and compared them to the biosynthetic esters. The fatty acid composition of the endogenous esters was different than those synthesized by the cellular acyl coenzyme A:acyltransferase, and the same as the esters synthesized by LCAT, demonstrating that the esters are produced in situ in the follicular fluid. Although the role of these estradiol esters in the ovary is not known, given their remarkable estrogenic potency it is highly probable that they have an important physiological role.

Chromatography, Thin Layer↗

Free colon transfer for resurfacing large oral cavity defects.

Ideal reconstruction of the oral cavity includes a durable lining that is thin, supple, and innervated, and that provides a lubricated surface that facilitates deglutition and speech. This paper describes the use of free colon transfer for relining the oral cavity. In three patients, segments of transverse colon, split along the antimesenteric border, were transferred as free flaps on the middle colic vessels for large defects involving the alveolar ridge, buccal mucosa, floor of the mouth, tongue, and pharyngeal walls. All flaps were transferred successfully without adverse vascular events, abdominal complications, or oro-cutaneous fistulas. One flap was re-elevated 2 weeks postoperatively for additional mandibulectomy. Two patients received postoperative radiation therapy and another patient received planned preoperative radiotherapy. The mucosal surface of the colon flattens to provide a thin, smooth, supple oral lining that produces moderate mucus, coapts well to the convoluted surfaces of the defects, and is durable to mastication and denture wear. Mucosal biopsy 2 years postoperatively in the nonradiated flap reveals normal colon mucosa with abundant mucin-producing cells. Free colon transfer is a "functional" reconstruction of the oral lining. The donor tissue is abundant and capable of resurfacing large, convoluted oral cavity surfaces with a thin, supple, mucus-secreting tissue that allows unimpaired tongue mobility, swallowing, speech, and denture wear. Furthermore, the presence of nonirradiated, mucus-secreting cells provides an avenue to further augment mucin production by topical and systemic agents.

Alveoloplasty↗

Characterization of feline Helicobacter pylori strains and associated gastritis in a colony of domestic cats.

Twenty-four young adult domestic cats from a commercial vendor were found to be infected with Helicobacter pylori. Histopathologic analyses, selected electron microscopy, and urease mapping were performed on mucosal samples collected from the cardias and fundi, bodies, and antra of these cats' stomachs. H. pylori organisms were abundant in all areas of the stomach on the basis of histologic evaluation and urease mapping. H. pylori infection was associated with a moderate to severe lymphofollicular gastritis in 21 of 24 cats (88%). The gastritis was most pronounced in the antral region and consisted mainly of multifocal lymphoplasmacytic follicular infiltrates in the deep mucosa. The severity of gastritis in the antrum corresponded to high numbers of H. pylori there on the basis of the use of the urease assay as an indicator of H. pylori colonization. Ten of 24 cats (42%) also had small to moderate numbers of eosinophils in the gastric mucosa. All 24 cats had gastric lymphoid follicles, with follicles being most prevalent in the antrum. Electron microscopy of gastric tissue revealed numerous H. pylori organisms, some of which were closely adhered to the mucosal epithelium. Human H. pylori gene-specific primers to ureA and ureB amplified products of similar sizes from H. pylori cat isolates. Digestion of the products with restriction enzymes resulted in fragments characteristic of the restriction fragment length polymorphism patterns of H. pylori isolates from humans. In the domestic cat, H. pylori infection is associated with a lymphofollicular gastritis, consisting of lymphocytic and plasmacytic infiltration into the lamina propria, and the organism appears to provide chronic antigenic stimulation resulting in the formation of gastric lymphoid follicles.

Animals↗

Temporal headaches and associated symptoms relating to the styloid process and its attachments.

The styloid process is a slender spike-like bony process that is attached to the base of the skull that has been of interest to physicians for centuries. From this process is the attachment for five structures--three muscles and two ligaments are attached to it. Any of these soft tissues of the styloid process are prone to be torn due to trauma by way of detachment of the periosteum from the bone. These lesions may occur from auto accidents, falls, sports injuries, to prolonged medical or dental procedures requiring excessive mouth opening. The detachment of Sharpey's fibres results in the release of noxious chemicals such as kinins, histamines, prostaglandins, etc, which can produce a withdrawal reflex, causing muscle tension, ischaemia, spasm and pain. Pain transmission via C fibres may induce a host of autonomic responses as well. We have observed 11 common pains and symptoms that are associated with soft tissue lesions of the styloid process and stylomandibular ligament. They are (1) headaches localised in the anterior temporal fossa, (2) sore throat and difficulty swallowing in the absence of inflammation, (3) pain radiating to the temporomandibular joint and ear, (4) voice alteration, (5) dry, non-productive cough, (6) pain in the masseter muscle, (7) restricted mandibular opening or the "closed lock", (8) development of the "open lock", (9) sinusitis, congested stuffy nose or post nasal drip, (10) tinnitus, and (11) excessive lacrimation and bloodshot eyes. A few drops of local anesthetic into the styloid process and stylomandibular ligament attachment can temporarily relieve the pain and symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Headache↗

Successful management of female office workers with "repetitive stress injury" or "carpal tunnel syndrome" by a new treatment modality--application of low level laser.

Female office workers with desk jobs who are incapacitated by pain and tingling in the hands and fingers are often diagnosed by physicians as "repetitive stress injury" (RSI) or "carpal tunnel syndrome" (CTS). These patients usually have poor posture with their head and neck stooped forward and shoulders rounded; upon palpation, they have pain and tenderness at the spinous processes C5-T1 and the medial angle of the scapula. In 35 such patients we focused the treatment primarily at the posterior neck area and not the wrists and hands. A low level laser (100 mW) was used and directed at the tips of the spinous processes C5-T1. The laser rapidly alleviated the pain and tingling in the arms, hands and fingers, and diminished tenderness at the involved spinous processes. Thereby, it has become apparent that many patients labelled as having RSI or CTS have predominantly cervical radicular dysfunction resulting in pain to the upper extremities which can be managed by low level laser. Successful long-term management involves treating the soft tissue lesions in the neck combined with correcting the abnormal head, neck and shoulder posture by taping, cervical collars, and clavicle harnesses as well as improved work ergonomics.

Adult↗

A prospective comparison of laparoscopy and imaging in the staging of esophagogastric cancer before surgery.

OBJECTIVE: To carry out a prospective comparison of laparoscopy and combined imaging (CT and ultrasound) in the preoperative staging of distal esophageal and gastric cancer in patients who were selected for surgery. METHODS: Patients with clinically overt metastases or a contraindication to major surgery were excluded. One hundred and forty-five patients underwent chest radiography, CT of mediastinum and abdomen, and ultrasonography of abdomen and laparoscopy. The primary diagnoses were adenocarcinoma of the esophagogastric region in 110 cases, squamous cell carcinoma of the distal esophagus in 30 patients, and five miscellaneous. RESULTS: Thirty nine (27%) patients had metastatic disease outside the potential field of resection. Metastases were detected preoperatively by laparoscopy in 30 patients (sensitivity 77%) and by combined imaging in 15 (sensitivity 38%) (p < 0.01). Twenty four patients with adenocarcinoma had metastases to the peritoneal cavity, which were detected preoperatively by laparoscopy in 23 (sensitivity 96%) and by combined imaging in five (sensitivity 21%) (p < 0.01). Peritoneal metastases were not seen in patients with squamous cell carcinoma. Fifteen patients had hepatic metastases, which were detected preoperatively by laparoscopy in nine (sensitivity 60%) and by combined imaging in seven (sensitivity 47%). Laparoscopy was more sensitive than combined imaging in detecting metastases in patients with adenocarcinoma [laparoscopy 28, combined imaging 10 (p < 0.01)]. CONCLUSION: Addition of laparoscopy to the staging protocol prevented unbeneficial thoraco-abdominal exploration in 20 patients with adenocarcinoma. Thus, laparoscopy should be used in the assessment of patients with adenocarcinoma of the esophagogastric region before performing excisional surgery.

Adult↗

Urinary kallikrein in the rat: stimulation with angiotensin infusion but depression with increasing sodium concentration.

1. The kallikrein response to angiotensin II infusion in the conscious rat was studied to compare it with the response in the dog. 2. Active kallikrein was measured by the aprotinin-suppressible esterase technique in 20 min periods. Angiotensin (5 x 10(-9) to 5 x 10(-2) micrograms min-1) was infused in 10 mM saline in period 10 (group A), or in 90 mM saline in periods 10-12 (group B). 3. In group A, no dose of angiotensin was antinatriuretic. Natriuresis and urinary sodium concentration were dose dependent. 4. Kallikrein excretion was dose dependent with angiotensin (P < 0.0001) and inversely correlated with urinary sodium concentration (P = 0.011). In natriuretic and non-natriuretic rats, kallikrein excretion after angiotensin was inversely correlated with urinary sodium concentration in the preceding period. 5. In group B, natriuresis and urinary sodium concentration were dose dependent. Kallikrein excretion in periods 10-13 was inversely correlated with urinary sodium concentration in the preceding period (P = 0.0001) and inversely correlated with urinary osmolality in periods 9-13. 6. Infusion of angiotensin II at 5 x 10(-6) micrograms min-1 led to antinatriuresis. 7. Formulae were derived which enabled the opposing effects of angiotensin and urinary sodium concentration on kallikrein excretion to be separated. In group A both these effects were statistically significant only in the natriuretic rats (natriuresis > 20 mumols per period). In group B the formulae showed a dose-dependent rise in kallikrein excretion, which was counteracted by the decrease in kallikrein excretion associated with the increasing urinary sodium concentration. 8. With infusions of 0.9% saline, kallikrein excretion in periods 10-13 was inversely correlated with urinary sodium concentration in the preceding period (P = 0.001). 9. The overall effect in the rat differs from that in the dog, where kallikrein increases with angiotensin natriuresis and dilution of the urine occurs.

Angiotensin II↗

Beta-structure in human amylin and two designer beta-peptides: CD and NMR spectroscopic comparisons suggest soluble beta-oligomers and the absence of significant populations of beta-strand dimers.

Intensity variation for the positive far UV CD band was observed for three 'beta-sheet' peptides. In 6% HFIP, an amyloidogenic species (human pancreatic amylin) displays, on standing, an extremely intense 192-nm band which diminishes upon physical agitation. A concurrently formed Tyr sidechain band at 274 nm disappears completely with agitation, linking the enhancement of the 192-nm band to the highly ordered stacking of beta-sheets. NMR studies indicate that the beta-states of the three peptides are oligomeric, not beta dimers. A membrane-forming EAK peptide displays NMR peaks due to the low concentration of 'random coil' monomers present in slow equilibrium with beta-oligomers; solutions of a more hydrophobic ELKA peptide, which displays an intense 195-nm band, contain only oligomeric species. NMR studies at 25% HFIP revealed the structural requirements for inhibition of beta-oligomer formation.

Amino Acid Sequence↗

Differential effect of phosphorylation and substrate modulation on tau's ability to promote microtubule growth and nucleation.

The neuronal microtubule-associated protein tau promotes microtubule assembly and has been implicated in the development of axonal morphology. To study the effect of phosphorylation and substrate modulation on tau's distinct activities to promote growth of existing microtubules and nucleation of new ones, we phosphorylated bacterially expressed human tau by cAMP-dependent protein kinase in the absence or presence of heparin, an acidic substrate modulator. We found that heparin increased phosphorylation of tau by a factor of more than 2 and produced tau bands with decreased electrophoretic mobility. We demonstrate that phosphorylation of tau in the absence or presence of heparin similarly reduced tau's activity to promote microtubule growth, whereas tau's activity to promote microtubules was suppressed much more after phosphorylation in the presence of heparin. Using recombinant tau fragments we showed that heparin-induced phosphorylation caused a specific shift in electrophoretic mobility indicative of a change in tau's conformation. By aminoterminal sequencing of a tau fragment starting at residue 154 we provide evidence that phosphorylation of serine 156 is responsible for this mobility shift and for the effect on tau's nucleation activity. We conclude that tau's activities to promote growth of existing microtubules and nucleation of new ones are differentially affected by the phosphorylation of specific tau residues. Regulation of the phosphorylation state by substrate modulation may play an important role in regulating tau's function.

Amino Acid Sequence↗

Orientation, assembly, and stability of microtubule bundles induced by a fragment of tau protein.

The neuronal microtubule-associated protein tau has been implicated in the development of axonal morphology including the organization of microtubules into a uniformly oriented array of microtubules commonly referred to as "bundle." Determination of the functional organization of tau has revealed that regions of tau protein which flank the microtubule-binding domain affect the bundling of microtubules in vitro with a microtubule-binding fragment of tau being most effective [Brandt and Lee, 1993: J. Biol. Chem. 268:3414-3419]. In order to study the relation of microtubule bundles that form in vitro to those observed in the axon, we determined the orientation of individual microtubules in bundles and the effects of bundling on microtubule assembly and stability in cell-free assembly reactions. Here we report that bundles induced by a microtubule-binding fragment of tau contain randomly oriented microtubules as determined by using the difference in growth rates at microtubule plus and minus ends. We demonstrate that in vitro bundling increases microtubule growth (about 30%), stabilizes microtubules against dilution- and cold-induced disassembly, and allows microtubule nucleation despite the absence of a tau region which has previously been shown to be required for tau-dependent microtubule nucleation. We conclude that conditions that stabilize microtubules can lead to bundle formation and allow microtubule assembly by a mechanism different from that employed by microtubule-associated proteins. The data also support the view that additional mechanisms besides the action of tau and tubulin exist in order to organize microtubules in the axon.

Cell-Free System↗

Somatically mutated member of the human V lambda VIII gene family encodes anti-myelin-associated glycoprotein (MAG) activity.

A highly conserved small family of human V lambda genes was identified by DNA homology to a V lambda gene isolated from a patient with demyelinating peripheral neuropathy, and which encodes an autoantibody with anti-MAG activity. Comparison of the genes indicates that the patient V lambda gene was derived from one of the germline genes. Together with published analyses of other anti-MAG IgM antibodies, which also appear to be mutated in comparison to known germline V genes, these results suggest that development of these pathogenic antibodies may reflect an antigen-driven, T cell-dependent process.

Autoantibodies↗

Intraneural topography of the ulnar nerve in the cubital tunnel facilitates anterior transposition.

The surgical management of cubital tunnel syndrome includes anterior transposition of the ulnar nerve. The success of all transposition procedures is dependent on placement of the nerve anterior to the medial epicondyle without tension. Fifteen cadaveric upper extremities underwent anterior transposition followed by anterior transposition with separation of the most proximal motor branches from the main ulnar nerve for a distance of 1, 2, and 3 cm. Proximal dissection of these motor branches achieved an average gain in distance from the epicondyle of 71%, with an average distance from the epicondyle of 3.6 cm. The intraneural topography of the ulnar nerve was studied in five additional cases. Cross-section analysis of the fascicular anatomy at 333 microns intervals along the length of the nerve with longitudinal reconstructions confirmed a safe dissection plane without interfascicular plexus formation. The most proximal motor branch in the forearm could be traced proximally an average of 6.7. cm within the nerve before interfascicular mingling occurred (range 6.0 to 7.5 cm). Thus, 6.0 cm represented the upper limit of safe proximal dissection in these nerves. Proximal separation may be performed without disruption of interfascicular plexus connections and will facilitate anterior transposition.

Cadaver↗

Aberrant estradiol flare despite gonadotropin-releasing hormone-agonist-induced suppression is associated with impaired implantation.

Our results confirm the previous report that rapid suppression by GnRH-a is favorable relative to delayed suppression (1). They further indicate that the pattern of E2 production during GnRH-a-induced ovarian suppression may be predictive of cycle outcome. We suggest that imperfect pituitary suppression of bioactive LH as indicated by an aberrant rise in E2 during GnRH-a down-regulation may compromise oocyte quality and ultimately impair implantation. Further study of follicular phase E2 response to GnRH-a suppression may provide a prognostic marker for implantation.

Embryo Implantation↗