Search PubMed⌕ Search

Biomedical subjects

D M Stewart

Publications and source records attributed to D M Stewart.

At least 37 records · Page 2Linked to original sources
PubMed1997

Butenafine 1% cream in the treatment of tinea cruris: a multicenter, vehicle-controlled, double-blind trial.

BACKGROUND: Butenafine hydrochloride, a potent antifungal agent related to the allylamines, has been used in Japan for treating various cutaneous mycoses including tinea cruris. OBJECTIVE: We compared the safety and efficacy of butenafine hydrochloride and its vehicle when used once daily for 2 weeks to treat tinea cruris. METHODS: Patients (n = 93) with tinea cruris and a positive potassium hydroxide examination and mycologic culture were enrolled. Of the 76 patients assessed for efficacy, 37 applied butenafine and 39 applied vehicle once daily for 2 weeks. Assessments were made at the end of the 2-week treatment period and 4 weeks after the end of treatment. RESULTS: Patients in the butenafine group had a higher mycologic cure rate by day 7 (66% vs 13%, p < 0.0001), with marked improvement 4 weeks after the end of treatment (81% vs 13%, p < 0.0001). They also had a higher rate of effective treatment at day 7 (29% vs 5%, p < 0.01) and at 4 weeks after treatment (73% vs 5%, p < 0.0001). Adverse events definitely related to butenafine treatment were limited to one case of burning sensation after application. CONCLUSION: Butenafine applied once daily for 2 weeks is effective in treating tinea cruris. The proportion of patients cured increased between the end of treatment and 4 weeks after treatment.

Administration, Topical↗
PubMed1997

Clobetasol propionate emollient 0.05 percent: hypothalamic-pituitary-adrenal-axis safety and four-week clinical efficacy results in plaque-type psoriasis.

Two clinical trials were conducted to evaluate the safety and antipsoriatic efficacy of a new 0.05 percent emollient formulation of clobetasol propionate (CP). In a crossover study of hypothalamic-pituitary-adrenal (HPA)-axis effects in 12 patients with psoriasis or eczema, 1.5 gm of CP emollient, applied to lesions twice daily for seven consecutive days, resulted in fewer patients with serum cortisol concentrations < 10 micrograms/100 mL than CP cream 0.05 percent (1vs 4); such concentrations were seen in two other patients during both treatment phases. A double-blind, randomized, parallel-group clinical trial in patients with moderate to severe plaque-type psoriasis showed that four weeks' treatment with CP emollient 0.43 to 0.5 gm twice daily (n = 35) was significantly more effective than emollient vehicle (n = 39) in reducing total signs/symptoms and scaling by Day 4, erythema and skin thickening by Day 8, and pruritus by Day 15. CP emollient was rated superior to vehicle by Day 4 in physician's gross assessment ratings and by Day 15 in patient's self-assessment ratings. In all assessments, CP emollient continued to be superior to vehicle during the remainder of the treatment period and two-week posttreatment period. No significant differences were observed in tolerability or serum cortisol effects during the course of the study.

Adult↗
PubMed1996

Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains.

Src homology 3 (SH3) domains have been shown to mediate selected interactions between signaling molecules and are essential for the activation of a number of receptor-driven pathways. The Wiskott-Aldrich syndrome protein was identified as a protein that associated selectively with the SH3 domains derived from c-Src, p85alpha, phospholipase Cgamma1, and c-Fgr. Significantly reduced association was detected to the N-terminal SH3 domain and the tandem SH3 domains of p47(phox), and no binding was detected to the SH3 domain of n-Src, the C-terminal SH3 domain of p47(phox), or either of the SH3 domains of p67(phox). Three peptides corresponding to potential Wiskott-Aldrich syndrome protein SH3 domain binding motifs were found to inhibit its association with c-Src, Fgr, and phospholipase Cgamma1 SH3 domains, but not the p85alpha SH3 domain. These peptides have the sequences MRRQEPLPPPPPPSRG, TGRSGPLPPPPPGA, and KGRSGPLPPVPLGI and show homology with other SH3 domain binding motifs. It is possible that the intracellular association of Wiskott-Aldrich syndrome protein with other signaling proteins is mediated by its SH3 domain-binding regions, and this may play a role in its putative function as a regulatory molecule in immune cells.

Amino Acid Sequence↗
PubMed1996

Studies of the expression of the Wiskott-Aldrich syndrome protein.

The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by thrombocytopenia, eczema, disorders in cell-mediated and humoral immunity, and a proclivity to lymphoproliferative disease. The gene responsible encodes a 53-kD proline-rich protein of unknown function (WASP). We produced a FLAG-WASP fusion protein that was used to immunize mice and produce mAbs against WASP. Using monoclonal anti-WASP in Western immunoblots, we have determined that WASP is present in the cytoplasmic but not nuclear fraction of normal human peripheral blood mononuclear cells, in normal human platelets, in T lymphocytes, non-T lymphocytes, and monocytes. The protein is produced in the B cell immunoblastic cell line DS-1, in normal EBV-transformed B cell lines, and in HEL92.1.7, but is barely detectable in MOLT-4 and not detectable in K562. WASP was present in two of four EBV-transformed cell lines from WAS patients. Splenic tissue immunostaining was performed in two patients, and the results correlated with the results of the Western blots. Sequence analysis of WASP cDNA from two patients who produce WASP show mutations causing amino acid substitutions. These studies establish a foundation for further studies aimed at understanding the function of WASP.

Amino Acid Sequence↗
PubMed1996

IL-15 induces the release of soluble IL-2Ralpha from human peripheral blood mononuclear cells.

The recently identified and cloned cytokine IL-15 shares many of the T-cell and B-cell stimulatory activities of IL-2 and utilizes the beta and gamma chains of the IL-2R for binding and signaling. The present report shows that, like IL-2, IL-15 in a concentration and time-dependent manner causes the release of sIL-2Ralpha from PHA-activated human peripheral blood mononuclear cells. This effect of IL-15 is largely direct and independent of IL-2. Blocking of the IL-2Rbeta chain with the antibody Mik-beta1 prevented the release of sIL-2Ralpha by IL-15 but not by IL-2. IL-7, another cytokine utilizing the gamma chain of the IL-2R, drove the release of sIL-2Ralpha as well. Several clinical conditions are associated with abnormal serum sIL-2Ralpha levels and are also monitored by the measurement of sIL-2Ralpha. The reason for sIL-2Ralpha release is not fully understood. In this study, IL-15, like IL-2 was shown to be a potent inducer of sIL-2Ralpha release in vitro.

Antibodies, Monoclonal↗
PubMed1996

Release of sIL-2R alpha from and activation of native human peripheral blood mononuclear cells by recombinant IL-15.

The cytokine interleukin (IL)-15 shares several activities with IL-2. Both cytokines induced expression of cell-surface IL-2R alpha (CD25) on freshly isolated human peripheral blood mononuclear cells (PBMC) in the absence of other exogenous stimuli. They also stimulated the release of soluble IL-2R alpha and induced proliferation of these cells in 1-week cultures in a time- and dose-dependent manner. Recombinant IL-7 could also induce the expression of CD25, although sIL-2R alpha was released at only low levels. In monocyte-depleted PBMC the sIL-2R alpha release was minimal. When isolated T cells or non-T cells were stimulated by rIL-15 or rIL-2, cell surface CD25 was expressed, but released sIL-2R alpha was undetectable. On stimulation with rIL-15, more than 80% of all natural killer cells expressed CD25 and more CD8br+ lymphocytes were positive for CD25 compared to stimulation by rIL-2. These results may be clinically relevant because several diseases are associated with high serum levels of sIL-2R alpha which may he not only due to IL-2 but also due to IL-15 stimulation.

Cell Division↗
PubMed1995

Molecular genetic analysis of X-linked hypogammaglobulinemia and isolated growth hormone deficiency.

In 1980 the clinical syndrome of X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA/GHD) was described. XLA/GHD patients have reduced serum levels of Ig and normal cell-mediated immunity, and thus resemble patients with Bruton's X-linked agammaglobulinemia (XLA). However, XLA/GHD patients also have isolated GHD. Mutations and deletions in the Bruton's tyrosine kinase gene (BTK) are responsible for Bruton's XLA. We investigated BTK gene expression in an XLA/GHD patient from the family originally described by Northern analysis, cDNA sequencing, and Western analysis of protein production using mAb to BTK. BTK mRNA was normal in size and abundance, and the mRNA sequence was normal over the coding region, except for a single silent mutation. BTK protein was present in normal amounts in PBMC of this patient. Thus, at the molecular level, XLA/GHD is a different disease entity from Bruton's XLA. These results suggest that undescribed genes critical for B cell development and growth hormone production exist on the X chromosome.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1995

Production of monoclonal antibodies to Bruton's tyrosine kinase.

Bruton's X-linked agammaglobulinemia is caused by mutations in a cytoplasmic protein tyrosine kinase termed Bruton's tyrosine kinase (BTK). The protein is expressed in all members of the B cell lineage and is critical for B cell development. The protein consists of several modules, including a pleckstrin homology domain and the Src homology domains SH1, SH2, and SH3. We report here the production of monoclonal antibodies against the pleckstrin homology domain of human BTK. The antibody was produced by immunizing mice with a FLAG-BTK fusion protein. Hybridoma supernatants were screened by ELISA using a GST-BTK fusion protein as the antigen. Selected monoclonal antibodies recognize denatured BTK on Western blots of peripheral blood mononuclear cell lysates. Mouse BTK protein is also detected. These antibodies should be useful in assessing patients with immune deficiency, as well as in studying normal B cell development.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1990

Kaposi's sarcoma of the lower extremity as the first sign of AIDS.

The authors review four cases of Kaposi's sarcoma that were presented to the Foot Clinics of New York and affiliated North General Hospital during a 1-year period from the fall of 1987 to the fall of 1988. The authors conclude that it is sometimes difficult to diagnose Kaposi's sarcoma and to differentiate between the acquired immunodeficiency (AIDS) form and the classic form. Guidelines for diagnosis and a profile of the AIDS-related and non-AIDS-related Kaposi's sarcoma patient are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Bizarre behavior following the ingestion of levo-desoxyephedrine.

This is the first reported case of transvestism in a heterosexual male that occurred only after ingestion of the contents of six to eight Vicks inhalers. The patient's gender cross-dressing was associated with sexual excitement and masturbatory behavior. This case is consistent with other cases of gender cross-dressing and sexual excitement following inhaler abuse, but in the previous cases reported the subjects were homosexual men. Levo-desoxyephedrine, also known as levo-methamphetamine, the main active ingredient in Vicks Inhalers, is known to have amphetamine-like properties. Stereotypic behavior is consistent with behavior that follows the use of amphetamine. Transvestism has traditionally been thought to be based on a psychodynamic model; however, the authors postulate several biochemical mechanisms whereby levo-desoxyephedrine may play a role in the bizarre behavior exhibited by this 32-year-old man. It is suggested that inhalers be placed in a new class of drugs that can be dispensed only by a pharmacist or physician.

Adult↗
PubMed1980

The release of vasoactive intestinal peptide during altered mid-gut blood flow.

In a series of 17 dogs of which 6 were controls experiments were undertaken to measure arterial and portal vasoactive intestinal peptide (VIP) levels during reduced cephalic mesenteric artery flow states and following reperfusion of the ischaemic mid gut. The flow states examined were basal flow, 50 per cent of basal flow and 25 per cent of basal flow. Zero flow was examined for 20 min and reperfusion of the ischaemic mid gut for 20 min. Peripheral and portal VIP levels were found to be massively elevated during all the flow states studied but particularly during reperfusion of the ischaemic mid gut.

Anesthesia↗
PubMed1979

Acetaminophen overdose: a growing health care hazard.

Clinical reports support acetylcysteine as an effective agent in the prevention of severe hepatic necrosis and mortality in acetaminophen toxicity [2, 8, 13]. The agent is safe and easily administered to the patient. Further studies are needed before acetylcysteine is considered the agent of choice in the management of acetaminophen overdosage in this country.

Acetaminophen↗
PubMed1978

Speckled lentiginous nevus.

Speckled lentiginous nevus is, we feel, a distinctive nevocytic disorder and a clinical variety of nevus-cell nevus. The speckled areas show varying histological patterns that range from nevus incipiens to junctional and compound nevi. The background shows histological features of lentigo simplex. It is our contention that speckled lentiginous nevus should be separated from nevus spilus and nevus spilus tardus (Becker's), which we consider to be variants of epidermal nevus.

Adolescent↗