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Biomedical subjects

J Humphrey

Publications and source records attributed to J Humphrey.

At least 19 recordsLinked to original sources
PubMed1995

An acidic sequence within the cytoplasmic domain of furin functions as a determinant of trans-Golgi network localization and internalization from the cell surface.

The mammalian endopeptidase, furin, is predominantly localized to the trans-Golgi network (TGN) at steady state. The localization of furin to this compartment seems to be the result of a dynamic process in which the protein undergoes cycling between the TGN and the plasma membrane. Both TGN localization and internalization from the plasma membrane are mediated by targeting information contained within the cytoplasmic domain of furin. Here, we report the results of a mutagenesis analysis aimed at identifying the source(s) of targeting information within the furin cytoplasmic domain. Our studies show that there are at least two cytoplasmic determinants that contribute to the steady-state localization and trafficking of furin. The first determinant corresponds to a canonical tyrosine-based motif, YKGL (residues 758-761), that functions mainly as an internalization signal. The second determinant consists of a strongly hydrophilic sequence (residues 766-783) that contains a large cluster of acidic residues (E and D) and is devoid of any tyrosine-based or di-leucine-based motifs. This second determinant is capable of conferring localization to the TGN as well as mediating internalization from the plasma membrane. Thus, these observations establish the existence of a novel, autonomous determinant distinct from sorting signals described previously.

Amino Acid Sequence↗
PubMed1995

Characterization of recombinant soluble human transforming growth factor-beta receptor type II (rhTGF-beta sRII).

Recombinant human transforming growth factor soluble receptor Type II (rhTGF-beta sRII) corresponding to the 159 amino acid extracellular domain of hTGF-beta RII has been expressed in insect cells using the baculovirus expression system or in a mouse myeloma cell line. N-terminal sequence analysis of the purified protein revealed the removal of the 23 amino acid signal peptide. In SDS-PAGE, the rhTGF-beta sRII resolves into multiple bands due to N-linked glycosylation. Recombinant hTGF-beta sRII is a TGF-beta antagonist and will inhibit the biological activities of TGF-beta 1, TGF-beta 3, and TGF-beta 5 on TGF-beta-responsive cell lines, such as murine HT-2 or human TF-1 with an ED50 of approximately 0.3 micrograms/mL. However, hTGF-beta sRII does not inhibit TGF-beta 2 bioactivities in these cell lines, suggesting that hTGF-beta RII has low affinity for TGF-beta 2. Polyclonal antibodies to hTGF-beta sRII have been produced in goats and purified on Protein-G affinity columns. This antibody can inhibit TGF-beta 1,2,3,5-dependent bioactivities on human cell lines such as TF-1. Additionally, this antibody has species cross-reactivity and will also inhibit TGF-beta-dependent bioactivities on murine cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Pupillary and visual thresholds in young children as an index of population vitamin A status.

A prototype scotopic sensitivity machine was used to evaluate pupillary and visual thresholds for 295 Indonesian children aged 1-5 y, most of whom were initially vitamin A-deficient. Subjects were tested 6 and 9 mo after receiving a high dose of vitamin A. A group of 136 older children was tested at 6 mo after dosing; all subjects underwent testing at 9 mo. After testing at 9 mo, children randomly received either a second high dose of vitamin A or placebo and were tested a final time 2 wk later. Children with abnormal pupillary thresholds had significantly higher relative dose responses (RDRs) (P < 0.01) and significantly lower serum retinol values (P = 0.05) than did normal children. The mean pupillary threshold rose (eg, retinal sensitivity fell) as vitamin A status deteriorated between 6 and 9 mo after initial dosing, and was significantly different from a group of normal American children tested previously (P < 0.001). After placebo-controlled dosing, the decline in pupillary and visual thresholds (rise in retinal sensitivity) was significant for children receiving vitamin A but not for children receiving placebo.

Aging↗
PubMed1994

Acute renal toxicity associated with suramin in the treatment of prostate cancer.

The use of suramin, a polysulfonated naphthylurea, in the treatment of advanced prostate cancer currently is being investigated. A 52-year-old man developed acute renal dysfunction after receiving nine doses of suramin. His suramin therapy was discontinued, but his serum creatinine level continued to rise to 10.8 mg/dl during the next 6 days. The patient was not rechallenged with suramin, and his renal function returned to baseline within the next 3 weeks. Future investigators of this drug should be aware of the possibility of such a reaction with parenteral administration.

Acute Kidney Injury↗
PubMed1994

Physician management preferences and barriers to care for rural patients with depression.

OBJECTIVE: To describe rural primary care physicians' current preferences in treating depression and the barriers they face in providing effective care for this condition. DESIGN: Cross-sectional survey of randomly selected practicing primary care physicians registered in Arkansas. SETTING: Primary care practices in nonmetropolitan counties. PARTICIPANTS: Forty of 50 eligible physicians completed a face-to-face interview; one physician, an interview by telephone; and two physicians, an interview in questionnaire form. Total response rate was 86%. MAIN OUTCOME MEASURES: Physician preferences for and barriers to the effective management of depression. RESULTS: An estimated 44% of rural physicians consider medication alone to be the best initial approach to treating depression; 30% prefer to prescribe medication and refer patients to mental health care professionals for counseling; and 26% prefer to prescribe medication and conduct counseling themselves. The greatest barriers to treatment were the physician's lack of time and the patient's failure to recognize depression. Most physicians had recently referred one or more depressed patients to specialty care and had encountered few referral sources, long waiting lists, and inadequate follow-up. CONCLUSIONS: The majority of rural primary care physicians prefer to treat depressed patients in their practices themselves. Except for the limited availability of specialty services, most of the barriers to the provision of effective care for depression perceived by rural physicians do not appear to be unique to rural practices.

Adult↗
PubMed1994

The cytoplasmic domain mediates localization of furin to the trans-Golgi network en route to the endosomal/lysosomal system.

To investigate the mechanisms of membrane protein localization to the Golgi complex, we have examined the intracellular trafficking of epitope-tagged forms of the mammalian endopeptidase, furin, in stably transformed rat basophilic leukemia cells. Our studies show that furin is predominantly localized to the trans-Golgi network (TGN) at steady state, with smaller amounts present in intracellular vesicles. Biochemical and morphological analyses reveal that furin is progressively delivered to a lysosomal compartment, where it is degraded. Analyses of furin deletion mutants and chimeric proteins show that the cytoplasmic domain is both necessary and sufficient for localization to the TGN in various cell types. Interestingly, deletion of most of the cytoplasmic domain of furin results in a molecule that is predominantly localized to intracellular vesicles, some of which display characteristics of lysosomes. To a lesser extent, the cytoplasmically deleted molecule is also localized to the plasma membrane. These observations suggest the existence of an additional determinant for targeting to the endosomal/lysosomal system within the lumenal and/or transmembrane domains of furin. Thus, the overall pattern of trafficking and steady state localization of furin are determined by targeting information contained within more than one region of the molecule.

Amino Acid Sequence↗
PubMed1990

An improved video-based computer tracking system for soft biomaterials testing.

We present an improved video-based computer system for on-line tracking of small markers moving in a plane. The system consists of a CCD camera, a video monitor, a dedicated 80386/20 microcomputer, a video frame grabber, and custom software. Up to four markers can be tracked at the 30-Hz video frame rate using a two-step, correlation-based search procedure. We discuss the requisite hardware and software requirements and illustrate how this tracking system can be used to collect strain data during biaxial stretching tests on planar soft tissues. Operating at 30 Hz, this system is an improvement over those previously reported, which are either slower or yield less information.

Algorithms↗
PubMed1984

Oculoskeletal myopathy with abnormal mitochondria.

A clinical, electrophysiological and pathological review of 14 patients having oculoskeletal myopathy with abnormal mitochondria was undertaken. These patients present with ophthalmoplegia, and mild skeletal muscle weakness. The clinical course is slowly progressive. Electromyographic examination shows myopathic changes. Serum enzymes are normal. The diagnosis is confirmed by skeletal muscle biopsy which shows abnormal mitochondria, including crystalloid inclusions on electron microscopy. These patients form a distinct clinical group in which the risk of sudden cardiac death is much less than it is in the Kearns-Sayre syndrome.

Adult↗
PubMed1982

Carbamylcholine modulation of E-rosette formation. Effect of plasmapheresis in myasthenia gravis.

Myasthenia gravis may result from a reduction of available acetylcholine receptors at the neuromuscular junction, likely secondary to the presence of anti-acetylcholine receptor antibodies. Since T lymphocytes appear to carry a similar nicotinic acetylcholine receptor, we investigated the capacity of T cells from patients with myasthenia gravis to bind sheep erythrocytes. In addition we determined the effect of carbachol, a cholinergic agonist, on E-rosette formation, and the role of myasthenic serum in modulating these responses. Two groups of patients were identified; one with normal numbers of E-rosettes forming cells (E-RFC) and the other with significantly reduced numbers. The majority of patients with myasthenia had a reduced number of carbachol-sensitive T cells. Incubation of their serum (or the IgG fraction) with normal T cells led to a reduction in numbers of E-RFC, particularly of the carbachol-sensitive subset. These effects were blocked by d-tubocurarine and not by atropine. Following plasmapheresis, normal numbers of E-RFC were detected in the patients and the serum inhibitory activity was no longer detected. The data suggest that in parallel to the achievement of some degree of clinical improvement, plasmapheresis may restore some aspects of lymphocyte function.

Adolescent↗