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Biomedical subjects

M Sanders

Publications and source records attributed to M Sanders.

At least 91 records · Page 5Linked to original sources
PubMed1993

Insulin-like growth factors stimulate erythropoiesis in serum-substituted umbilical cord blood cultures.

The stimulatory effects of the insulin-like growth factors (IGFs) on erythroid colony formation by hematopoietic progenitor cells derived from adult bone marrow and peripheral blood have been well demonstrated. To enhance our understanding of the potential role of IGFs in human newborn erythropoiesis, we studied the effects of IGF-I and IGF-II on neonatal erythropoiesis in vitro. Erythroid progenitor cells were recovered from umbilical cord blood collected at scheduled Cesarean sections from women with term, uncomplicated pregnancies. Light-density cord blood mononuclear cells were cultured for 7 days in a serum-substituted culture system supplemented with and without purified human recombinant erythropoietin (0.5 to 2.0 U/mL) and recombinant human IGFs. Addition of IGF-I (1 to 100 ng/mL) resulted in up to a 4-fold increase over baseline erythropoietin-dependent colony formation at 7 days with a maximal effect at 10 ng/mL. While subphysiologic doses of IGF-II caused a modest stimulation of erythropoiesis, addition of a physiologic concentration (100 ng/mL) resulted in up to a 4-fold enhancement in erythroid colony formation. This stimulatory effect persisted in cultures of mononuclear cells that were depleted of monocytes, myeloid cells, T cells and B cells prior to culture, suggesting that enhancement is the result of a direct IGF effect on progenitor cells. Addition of IGFs in the absence of erythropoietin resulted in erythroid colony formation in some but not all experiments. Whereas IGF-I was the primary regulator of erythropoietin-independent erythroid colony formation by adult erythroid progenitors, IGF-II was the predominant regulator of erythropoietin-independent erythroid colony formation by neonatal progenitor cells. We conclude that IGFs in physiologic doses directly stimulate neonatal cord blood erythroid progenitor cells and may play a role in developmental control of human erythropoiesis.

Blood↗
PubMed1992

Antibody affinity to retinal S-antigen in patients with retinal vasculitis.

Using a modified enzyme-linked immunosorbent antibody method that included dissociation of antigen antibody complexes with sodium thiocyanate, we examined the functional affinity of antibody to retinal S-antigen in 48 patients with retinal vasculitis and 46 age-matched healthy control subjects. Antibody affinity was markedly lower in patients with retinal vasculitis than in healthy subjects. Low-affinity antibody was more prevalent in acute retinal vasculitis and in patients with normal levels of circulating immune complexes. We found distinct differences between the antiretinal antibodies found in patients with retinal vasculitis and those in control subjects. The association of low-affinity antibody with normal levels of circulating immune complexes may suggest defective regulation of antiretinal autoimmunity and have important pathogenic implications.

Antibody Affinity↗
PubMed1992

A vasopressin analog that binds but does not activate V1 or V2 vasopressin receptors is not internalized into cells that express V1 or V2 receptors.

To assess whether receptor binding is sufficient to initiate vasopressin receptor endocytosis in cells expressing the vasopressin V1 or V2 receptors, we synthesized a novel fluorescent-labeled vasopressin analog, [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid), 2-(O-ethyl)-D-tyrosine, 4-valine, 8-lysine-N6-carboxytetramethylrhodamine] vasopressin (R-CLVP), that binds to vasopressin receptors but does not activate intracellular events such as the mobilization of intracellular calcium or the activation of adenylate cyclase. We compared the manner in which this analog was endocytosed in cells expressing V1 (A-10, rat smooth muscle cells) or V2 (LLC-PK1, porcine kidney cells) receptors with that of a full agonist, [1-(beta-mercaptopropionic acid), 8-lysine-N6-carboxytetramethylrhodamine] vasopressin (R-MLVP) [Lutz et al. (1990) J. Biol. Chem. 265, 4657-4663; Lutz et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87,6507-6511]. We showed that R-CLVP bound to both types of receptors with good affinity. It failed to increase cyclic AMP concentrations in LLC-PK1 cells and did not increase the mobilization of intracellular calcium in A-10 cells. It bound to the surface of both these cell types in a diffuse manner and it did not undergo receptor endocytosis in either cell type. In contrast, R-MLVP, an agonist that bound to both receptor subtypes and elicited changes in intracellular cyclic AMP and calcium, bound to the surface of these cells in a diffuse manner at early times after exposure, and rapidly underwent endocytosis. We conclude that binding of vasopressin to its receptors alone is insufficient to cause receptor endocytosis, and other events distal to the receptor are required to initiate endocytosis. R-CLVP should be a useful analog in determining the factors responsible for initiating receptor endocytosis.

Amino Acid Sequence↗
PubMed1992

The identification of the Bs breakpoint and of two possible Bar genes.

Two coding regions were identified within a 110 kb region which includes all mapped Bar breakpoints. Both lie proximal to the identified Bar breakpoints. The first coding region, designated BarA, is 5 kb from the most proximal Bar mutation, B581, and 66 kb from the Bs breakpoint. It encodes a 1.3 kb transcript, which is found in late third instar larvae but is absent in 1-3-day-old pupae. Bi, R(B)hd3, B85c15, and Bs result in overproduction of this transcript in late third instar larvae. A second coding region, which was previously identified as BarH1, maps 18 kb from B581 and 79 kb from the Bs breakpoint. In third instar larvae, the abundance of the BarH1 transcript is very low in both wild type and various Bar mutatants, with the exception of R(B)hd3. In 1-3-day-old pupae, the level of the BarH1 transcript is higher. BarH1 was previously identified as the Bar gene. However, this report raises the possibility that BarA rather than BarH1 is the Bar gene or that more than one gene may be involved in Bar position effects.

Animals↗
PubMed1992

Otitis media due to blastomycosis: report of two cases.

Blastomycosis as a causative agent in cases of otitis media has not previously been reported. Two patients recently presented with otitis media and head and neck masses due to Blastomyces dermatitidis. Initial evaluation suggested neoplastic disease, but biopsy confirmed a fungal etiology for the masses in both patients. Relapse after administration of ketoconazole was noted in one patient, who was an adult; the other patient was a child. Otitis media and masses of the head and neck are unusual features of blastomycosis. Blastomycosis should be considered in the differential diagnosis for patients with such mass lesions and for patients with otitis media.

Adult↗
PubMed1992

Results of selective percutaneous controlled radiofrequency lesion for treatment of trigeminal neuralgia in 240 patients.

Trigeminal neuralgia may be treated in several ways. In the present study, the efficacy of a selective percutaneous radiofrequency (RF) neurolysis in the gasserian ganglion was evaluated in 240 patients. The recurrence rate after a single treatment was 28.3% within 2 years. After multiple treatments (n = 68), the recurrence rate had decreased to 8.3% (n = 20). Thus, the overall success rate at the end of the follow-up period was 91.7%. The mean follow-up period was 50 months (range 12-96 months). Except for corneal anesthesia in 3.7% of the patients, no serious complications occurred.

Adult↗
PubMed1991

Lysis of autologous melanoma cells by tumor-infiltrating lymphocytes: association with clinical response.

Tumor-infiltrating lymphocytes (TILs) can be grown in vitro in medium containing interleukin-2 (IL-2). In clinical trials at the Surgery Branch of the National Cancer Institute, patients with metastatic malignant melanomas were treated with IL-2 plus the adoptive transfer of autologous TILs. At the time of treatment, TILs were assayed for in vitro lysis of fresh autologous and allogeneic melanoma cells and Daudi cells. Patients were evaluated for clinical response 4-8 weeks later. Lysis of autologous tumor cells by TILs was significantly higher for responding than for nonresponding patients. Tumor cells from responding and nonresponding patients were equally sensitive to lysis by allogeneic lymphokine-activated killer (LAK) cells. There was no difference between TILs from responding and nonresponding patients for lysis of LAK-sensitive Daudi cells, which was low in most cases and demonstrated that TIL lysis of autologous tumor cells was not due to LAK cells. The observed association of autologous tumor cell lysis by TILs with clinical response suggests that the development of culture methods to optimize lysis of autologous tumors may lead to increased response rates using this TIL treatment regimen.

Cell Division↗
PubMed1991

Gestational age assessment in preterm neonates weighing less than 1500 grams.

Postnatal assessment of gestational age in preterm neonates traditionally has been performed using the methods of Dubowitz and Ballard. This study was designed to determine the accuracy of these methods in a sample of very low birth weight preterm neonates. Dubowitz and Ballard examinations were done on 110 preterm neonates within the first 72 hours of life by a neonatologist masked to the gestational age assessed antenatally. Mean birth weight was 1066 +/- 256 g (SD). These data were compared with gestational age assessments using last menstrual period and best obstetric estimate calculated by an obstetrician unaware of the neonatal examination. Mean gestational age using last menstrual period was 28.3 +/- 2.9 weeks. Mean differences between last menstrual period and Dubowitz/Ballard were -2.8 +/- 2.1 weeks and -2.6 +/- 2.2 weeks, respectively. Results using best obstetric estimate were similar. An ophthalmologist examined lens vessels of 89 neonates. A similar pattern toward overestimation of gestational age interval by Dubowitz/Ballard was seen at each lens vessel grade. The Dubowitz and Ballard examinations are inaccurate methods of assessing gestational age in preterm neonates with birth weights less than 1500 g.

Birth Weight↗
PubMed1991

Induction of circulating neonatal stem cell populations.

Hematopoietic cell differentiation and growth are regulated by paracrine molecules that include insulin and insulin-like growth factors (IGFs). IGF-I and -II stimulation of erythropoiesis in cultures of adult bone marrow and peripheral blood cells and murine fetal liver cells has been previously reported. In order to investigate whether these paracrines also influence differentiation and proliferation of human neonatal progenitor cells, we assessed their effects in cultures of umbilical cord blood and adult blood and marrow cells, using a serum-substituted system. IGF-I stimulated colony-forming unit-erythroid (CFU-E)-derived colony formation by adult cells by up to 265%, while IGF-II augmented colony formation by up to 100% in the presence of erythropoietin. Stimulation occurred in a saturable fashion over concentrations of 0 to 200 ng/ml. Similar results were obtained in subcultures of adult-circulating progenitors. Moreover, a subpopulation of erythropoietin-independent adult CFU-E was stimulated to proliferate by IGF-I but not by IGF-II. In contrast to these effects in adult marrow culture, IGF-II exerted a greater stimulatory effect on neonatal CFU-E proliferation than did IGF-I in erythropoietin-containing cultures. Additionally, IGF-II stimulated proliferation of erythropoietin-independent neonatal CFU-Es in a concentration-dependent fashion. Together, the data are consistent with the hypothesis that somatomedins are involved in developmental regulation of erythropoiesis.

Adult↗
PubMed1990

[Effective treatment of essential trigeminal neuralgia using percutaneous selective heat coagulation of Gasser's ganglion].

Trigeminal neuralgia may be treated in several ways. In the present study the efficacy of a selective percutaneous radiofrequency neurolysis in the gasserian ganglion was evaluated in 172 patients. A complete result was seen in 96.5% of the patients. The recurrence rate within 2 years amounted to 28.3%. Forty-seven patients underwent several treatments with a maximum of four within this period of time. The recurrence rate in the entire study population after 2 years was 8.1%. The mean follow-up period was 50 months (range 9-90 months). Except for the occurrence of corneal anaesthesia in 4% of the patients no serious complications were encountered.

Adult↗
PubMed1990

P2-purinergic receptors activate a guanine nucleotide-dependent phospholipase C in membranes from HL-60 cells.

We have previously determined that human neutrophils and monocytes, as well as neutrophil/monocyte progenitor cells, express a subtype of P2-purinergic receptors (for ATP) which activate the inositol phospholipid signalling system. In the present study, membranes prepared from HL-60 promyelocytic leukemia cells were used to examine the mechanism by which these ATP receptors activate phosphatidylinositol-specific phospholipase C (PI-PLC) under defined in vitro conditions. Micromolar concentrations of the receptor agonists ATP, UTP, and ATP gamma S stimulated the GTP-dependent formation of inositol bisphosphate (IP2) and inositol trisphosphate (IP3) in washed membranes prepared from undifferentiated HL-60 cells prelabeled with [3H]inositol. The stimulatory effects of these nucleotides on PI-PLC appeared to be mediated through a GTP binding protein since minimal inositol polyphosphate accumulation was observed in the absence of guanine nucleotides. The increased inositol polyphosphate formation triggered by these nucleotide receptor agonists did not result from inhibition of GTP breakdown. Neither was it a consequence of increased [3H]polyphosphatidylinositol levels resulting from enhanced activity of membrane-associated PI- or PIP-kinases. Instead, the stimulated phospholipase activity was apparently receptor-mediated. The rank order of potency observed in these in vitro membrane assays (ATP = UTP greater than ATP gamma S much greater than TTP greater than CTP much greater than beta, gamma-CH-ATP) was similar to that observed with intact HL-60 cells. This order of potency appears to distinguish the P2-purinergic receptors expressed by human phagocytic leukocytes from the P2 gamma-purinergic receptors which activate PI-PLC in turkey erythrocyte membranes.

Animals↗
PubMed1990

Internalization of vasopressin analogs in kidney and smooth muscle cells: evidence for receptor-mediated endocytosis in cells with V2 or V1 receptors.

To determine whether receptor-mediated endocytosis occurs in vasopressin-responsive cells, we developed a model system using synthetic fluorescent-labeled vasopressin analogs and A10 (smooth muscle) and LLC-PK1 (kidney epithelial) cells in culture; these cell lines express V1 and V2 vasopressin cell surface receptor types, respectively. We used epifluorescence microscopy to examine the binding, internalization, and intracellular destination of [1-(2-mercapto)propionic acid,8-lysine-N6-carboxytetramethylrhodamine] vasopressin (R-MLVP) and [1-(2-mercapto)propionic acid,8-lysine-N6-carboxyfluorescein]vasopressin (F-MLVP) in these cells. The rhodamine-labeled fluorescent vasopressin analog, R-MLVP, initially bound in a diffuse manner at the cell surface of both A10 and LLC-PK1 cells and could be displaced by excess unlabeled [8-arginine]vasopressin. After incubation at 37 degrees C, bound ligand rapidly aggregated into small clusters or patches, which were internalized in a manner consistent with receptor-mediated endocytosis. Subsequent processing of internalized ligand-receptor complexes appeared to differ between A10 and LLC-PK1 cells. In the case of LLC-PK1 cells, ligand was delivered to a tightly focused lysosome compartment in the perinuclear region of the cell, and receptor molecules were replenished at the cell surface. The lysosomal location of ligand was supported by the quenching of fluorescence in the internalized vesicles when F-MLVP was used as a fluorescent tracer. In the case of A10 cells, ligand became localized to a vesicular compartment and reappearance of receptor at the cell surface was limited. Our data are consistent with the occurrence of receptor-mediated endocytosis of vasopressin in cells with V1 and V2 receptors.

Animals↗
PubMed1990

Correction of hallux valgus with metatarsocuneiform stabilization.

51 feet in 30 patients were evaluated clinically and radiographically an average of 27.6 months after undergoing a modified McBride bunionectomy with a metatarsocuneiform stabilization. An inlay block of bone was used after achieving corrected position of the first metatarsal. The retrospective review included an anteroposterior x-ray, in which definite trabecular bridging was present in only 25.5% of the cases. The metatarsocuneiform joint was asymptomatic regardless of its x-ray appearance. The average intermetatarsal angle was reduced from 14.6 degrees to 8.7 degrees. This procedure attempts to restore near-normal anatomy, thereby preventing transfer metatarsalgia from shortening or elevation of the first metatarsal. Acceptable correction is possible in both moderate and severe deformities.

Adult↗