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J Roe

Publications and source records attributed to J Roe.

16 recordsLinked to original sources
PubMed2000

Agrin fragments differentially induce ectopic aggregation of acetylcholine receptors in myotomal muscles of Xenopus embryos.

Agrin is an extracellular synaptic protein that organizes the postsynaptic apparatus, including acetylcholine receptors (AChRs), of the neuromuscular junction. The COOH-terminal portion of agrin has full AChR-aggregating activity in culture, and includes three globular domains, G1, G2, and G3. Portions of the agrin protein containing these domains bind to different cell surface proteins of muscle cells, including alpha-dystroglycan (G1-G2) and heparan sulfate proteoglycans (G2), whereas the G3 domain is sufficient to aggregate AChRs. We sought to determine whether the G1 and G2 domains of agrin potentiate agrin activity in vivo, as they do in culture. Fragments from the COOH-terminal of a neuronal agrin isoform (4,8) containing G3, both G2 and G3, or all three G domains were overexpressed in Xenopus embryos during neuromuscular synapse formation in myotomal muscles. RNA encoding these fragments of rat agrin was injected into one-cell embryos. All three fragments increased the ectopic aggregation of AChRs in noninnervated regions near the center of myotomes. Surprisingly, ectopic aggregation was more pronounced after overexpression of the smallest fragment, which lacks the heparin- and alpha-dystroglycan-binding domains. Synaptic AChR aggregation was decreased in embryos overexpressing the fragments, suggesting a competition between endogenous agrin secreted by nerve terminals and exogenous agrin fragments secreted by muscle cells. These results suggest that binding of the larger agrin fragments to alpha-dystroglycan and/or heparan sulfate proteoglycans may sequester the fragments and inhibit their activity in embryonic muscle. These intermolecular interactions may regulate agrin activity and differentiation of the neuromuscular junction in vivo.

Agrin↗
PubMed2000

Response to immunization with recall and neoantigens after prolonged administration of an HIV-1 protease inhibitor-containing regimen. ACTG 375 team. AIDS Clinical Trials Group.

OBJECTIVES: To ascertain if immunization results in the restoration of responses to recall antigens, in the development of responses to presumed neoantigens, and to identify the virologic and immunologic correlates of these responses in persons with HIV-1 infection. DESIGN AND SETTING: Open-label study carried out at three university-affiliated AIDS Clinical Trials Units in the United States. SUBJECTS AND METHODS: Thirty-one subjects participating in AIDS Clinical Trials Group Protocol 375 who had received zidovudine, lamivudine, and ritonavir for at least 48 weeks. Subjects were immunized with tetanus toxoid (TT) at entry and with inactivated hepatitis A vaccine (hep A) and keyhole limpet hemocyanin (KLH) at entry and 6 weeks. The development of antibody, lymphocyte proliferative assay (LPA), and delayed-type hypersensitivity (DTH) responses after immunization were monitored. RESULTS: The LPA and DTH responses to TT improved in 57 and 68% of participants, respectively; 73 and 65% developed enhanced LPA and DTH responses to KLH. Forty-eight percent of patients developed a four-fold increase in antibody concentration to tetanus. Seventy-three percent of patients without detectable hepatitis A antibodies at baseline developed antibodies after immunization. Eighty-three percent of patients experienced at least a four-fold rise in KLH antibody concentration. Immune activation and viral load predicted poor recall responses and the number of memory CD4+ T-cells predicted good responses to recall antigens. Naïve CD4+ T-cell numbers, decrease in viral load, increases in CD4+ and CD28+ cells, and decreases in immune activation were associated with responses to presumed neoantigens. CONCLUSIONS: Most HIV-infected patients treated with potent combination antiretrovirals develop responses to recall and presumed neoantigens after immunization. Functional immune restoration in response to immunization is related to control of viral replication, decreased immune activation as well as to both quantitative and qualitative restoration of circulating T- lymphocyte subpopulations.

AIDS-Related Opportunistic Infections↗
PubMed1999

Overexpression of agrin isoforms in Xenopus embryos alters the distribution of synaptic acetylcholine receptors during development of the neuromuscular junction.

Synapse formation involves a large number of macromolecules found in both presynaptic nerve terminals and postsynaptic cells. Many of the molecules involved in synaptogenesis of the neuromuscular junction have been discovered through morphological localization to the synapse and functional cell culture assays, but their role in embryonic development has been more difficult to study. One of the best understood of these molecules is agrin, a synaptic extracellular matrix protein secreted by both motor neurons and muscle cells, that organizes the postsynaptic apparatus, including high-density aggregates of acetylcholine receptors (AChRs), at the neuromuscular junction. We tested the specific hypothesis that different agrin isoforms made by neurons and muscle cells contribute to agrin's synapse organizing activity in the embryo. Agrin isoforms were overexpressed by injecting synthetic RNA into Xenopus laevis embryos at the one- or two-cell stage. To mark cells containing agrin RNA, green fluorescent protein (GFP) RNA was coinjected. The relative area of muscle AChR aggregates was measured by confocal microscopy and image analysis in GFP-positive segments of injected embryos. Innervated regions of myotomal muscles were compared in animals injected with a mixture of agrin and GFP RNAs or with GFP RNA alone. Overexpression of COOH-terminal 95-kDa fragments of a rat agrin isoform made only by neurons (4,8) and the major isoform (0,0) made by muscle cells both increased AChR cluster area by 100-200%. Rat agrin protein was colocalized with AChR aggregates in innervated regions of muscles in injected embryos. These results show that agrin derived from both the nerve terminal and the muscle cell could contribute to synaptic differentiation at the embryonic neuromuscular junction. They further demonstrate the usefulness of overexpression by RNA injection as an assay for molecular function in embryonic synapse formation.

Agrin↗
PubMed1999

Capillary blood sampling for self-monitoring of blood glucose.

New and emerging capillary blood sampling technologies for self-monitoring of blood glucose (SMBG) are reviewed for their impact on factors pertaining to users such as pain, and from the standpoint of skin physiology and technical feasibility. Innovative blood sampling techniques based on lancets for skin penetration on nonfinger (alternate) sites such as the forearm seem to be virtually painless, convenient and cost effective as compared to other methods such as laser-based perforation of fingertips. Alternate site blood sampling with new lancet devices appears not only medically sound but also technically practical and user-friendly. It is anticipated that alternate site blood sampling techniques would improve compliance rate and, consequently, outcome of treatment for patients with diabetes.

Blood Glucose↗
PubMed1993

Parathyroid hormone increases cytosolic calcium concentration in adult rat cardiac myocytes.

The heart is a target organ for parathyroid hormone (PTH), and the action of this hormone on the myocardium may be mediated through the ability of PTH to increase cytosolic calcium ([Ca2+]i) in the myocardial cells. However, direct evidence for such an effect of PTH is lacking, and the mechanism(s) through which the hormone can potentially exert such an effect have not been elucidated. In the present study these questions were examined using cardiac myocytes isolated from adult rats. Both PTH-(1-34) and PTH-(1-84) produced a dose-dependent increase in [Ca2+]i of myocytes, but the effect of the latter was significantly (P < 0.01) greater than the former. This action of PTH was abolished by the inactivation of the hormone, the use of a PTH antagonist, or by verapamil. The G protein activator, guanosine 5'-O-(3-thiothriphosphate) (GTP gamma S), mimicked the effect of PTH, whereas pertussis toxin, the G protein inhibitor, guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), or ryanodine significantly reduced the PTH-induced rise in [Ca2+]i. Dibutyryl- and 8-bromoadenosine-3',5'-cyclic monophosphate, forskolin, 12-O-tetradecanoylphorbol 13-acetate, and staurosporine did not increase [Ca2+]i in myocytes, and staurosporine did not alter the PTH-induced rise in [Ca2+]i. BAY K 8644 augmented the effect of PTH on [Ca2+]i. These data demonstrate that 1) PTH increases [Ca2+]i of cardiac myocytes, 2) this action is receptor mediated and is produced by activation of the L-type calcium channels following stimulation of G protein(s), and 3) the rise in [Ca2+]i is due to both augmented entry of calcium into the myocytes and mobilization of calcium from sarcoplasmic reticulum by a calcium-induced calcium release mechanism.

Animals↗
PubMed1983

Prevention of unexpected infant death. Evaluation of the first seven years of the Sheffield Intervention Programme.

In the years 1973-79, 39452 infants born to parents resident in Sheffield were scored at birth for risk of unexpected infant death. Before 1973 post-perinatal mortality in Sheffield was on average 11.5% above the rate for England and Wales. Since 1973 it has only once exceeded the rate for England and Wales. "Possibly preventable" deaths have fallen from 5.2 to 1.9 per 1000. 12% of this decline is associated with a rise in the average age of the mother and a fall in the number of pregnancies, 9% with a reduction in precipitate deliveries, 24% with an increase in breastfeeding, 18% with extra care given by health visitors to high-risk infants, and 36% with other factors. The reduction in mortality attributed directly to the effect of increased visiting of high-risk infants is numerically similar to the number of lives saved by treating cancers of children. This suggests that home visiting by health visitors is highly cost-effective.

Clinical Trials as Topic↗
PubMed1982

Hormone dependency in N-nitrosomethylurea-induced rat mammary tumors.

The majority (87%) of N-nitrosomethylurea-induced rat mammary tumors regressed within 1 week after hypophysectomy (hypox). After a hypox-induced tumor regression, ovine PRL (oPRL), and 17 beta-estradiol (E2) were administered separately or in combination in order to define the individual role of these hormones in regulating tumor growth and influencing estrogen (E), progesterone (Pg), and PRL receptor (R) levels. Administration of E2 (2.5 micrograms twice daily) or oPRL (20 IU daily, started 5 days after hypox and continued for 10 days, resulted in stabilization of tumor growth. Simultaneous administration of E2 and oPRL resulted in a synergistic effect and reactivation of tumor growth. ER levels in mammary tumors were significantly lower than those in the control 15 days after hypox (P less than 0.01). Treatment with E2, oPRL, or both simultaneously had no significant effect on ER levels. A significant decline in PgR levels was noted at both 5 and 15 days after hypox. Whereas treatment with oPRL had no significant effect on PgR levels, E2 administration either alone or in combination with oPRL restored PgR levels to control values. PRLR levels were unchanged from control values at 5 days, but significantly declined (P less than 0.005) 15 days after hypox. Treatment with E2, oPRL, or both hormones simultaneously partially maintained PRLR and prevented the decline to the extremely low level noted in the untreated group. We conclude that the growth of nitrosomethylurea-induced rat mammary tumors is dependent on both E2 and PRL. There was a synergistic effect between E2 and PRL on tumor growth but not on ER, PgR, or PRLR. Neither E2 nor PRL had any significant effect on ER after hypox. PgR is under E2 control. Either E2 or PRL or both hormones were able to maintain PRLR in mammary tumors after hypox.

Adenocarcinoma↗
PubMed1976

Post-traumatic intestinal obstruction.

The roentgenographic and pathologic findings in three patients with delayed post-traumatic intestinal obstruction are described. The pertinent literature also is reviewed to delineate the variable pathophysiology of the clinical phenomenon. As a result of the increasing incidence of blunt trauma in our society, the problem of occult intra-abdominal injury resulting in subsequent clinical disease always should be considered in the differential diagnosis of patients presenting later with intestinal complaints. Once considered, routine roentgenologic evaluation usually is diagnostic, and arteriographic evaluation should be considered if the diagnosis is strongly suspected in the face of normal contrast studies. If intestinal obstruction is diagnosed, operative treatment is indicated, simple, and effective.

Abdominal Injuries↗
PubMed1975

The occurrence of a phosphorylated glycosphingolipid in Aspergillus niger.

A novel type of water-soluble phosphorylated glycosphingolipid was isolated from Aspergillus niger by a simple procedure involving precipitation, DEAE-cellulose chromatography and preparative t.l.c. Besides ceramide and phosphorus it contains inositol, galactose, mannose and small amounts of glucosamine.

Aspergillus↗
PubMedDate not supplied

Hypokalemia, hypophosphatemia, and compartment syndrome of the leg after downhill skiing on moguls.

Any process that increases intracompartmental pressure may precipitate compartment syndrome. We report the case of a patient with hypokalemia and hypophosphatemia who presented with compartment syndrome of the legs after a day of downhill skiing on moguls. The presentation is followed by a review of the pathophysiology, etiology, clinical presentation, and management of compartment syndrome, as well as the relationship between hypokalemia, hypophosphatemia, and the development of muscle injury.

Adult↗