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M Frexes-Steed

Publications and source records attributed to M Frexes-Steed.

15 recordsLinked to original sources
PubMed2001

Evidence for mitogen-associated protein kinase activation and transduction of mitogenic signals by platelet-derived growth factor in human meningioma cells.

OBJECT: Coexpression of platelet-derived growth factor (PDGF)-BB and activated PDGF-beta receptor in meningioma cells indicates that this cytokine may act as an autocrine or paracrine stimulant of meningioma growth. The intracellular events transducing signals from PDGF-beta receptor tyrosine kinases are unknown. In this study the authors evaluated whether or not mitogen-activated protein kinases (MAPKs) are expressed in meningiomas, regulate their growth, and transduce mitogenic signals of PDGF-BB. METHODS: Ten human meningioma tumors as well as cells cultured from two normal leptomeninges and 10 additional human meningiomas were evaluated using Western blot analysis to determine the presence of MAPK and phosphorylated (activated) MAPK. The effects of PD098059, a selective inhibitor of MAPK phosphorylation/activation, on proliferation of meningioma cells stimulated with 10% fetal bovine serum was also evaluated. Last, the authors evaluated whether PDGF-BB stimulation of meningioma cells was associated with activation of MAPK. Western blots of lysates from meningiomas and from cultured leptomeningeal and meningioma cells demonstrated MAPK and phosphorylated MAPK. Treatment with PD098059 produced a 52 to 84% (x = 69.8) loss in [3H]thymidine incorporation, which was associated with a partial or complete loss of phosphorylated MAPK after 3 days of treatment. The PDGF-BB produced a significant increase in [3H]thymidine incorporation and phosphorylation of MAPK at 1 and 3 days. Coadministration of PD098059 completely blocked PDGF-BB's stimulation of [3H]thymidine incorporation and cell proliferation concomitant with reduced MAPK phosphorylation. CONCLUSIONS: The findings indicate that MAPK is constitutively expressed in leptomeningeal and meningioma cells and transduces mitogenic signals of PDGF, contributing to the growth of human meningiomas.

Adolescent↗
PubMed2000

A pilot study of neoadjuvant paclitaxel and radiation with correlative molecular studies in stage II/III breast cancer.

A commonly used approach to the management of locally advanced breast cancer currently involves neoadjuvant chemotherapy, followed by surgery and radiation. Earlier neoadjuvant regimens had utilized doxorubicin, making concurrent treatment with radiation less desirable given dose-limiting normal tissue toxicities. With the development of paclitaxel, we can now reconsider the use of concurrent chemoradiation in the treatment of breast cancer. Although paclitaxel is a known radiation sensitizer, its precise mechanism of action is still unclear. One of its proposed mechanisms is that it binds tubulin and induces an M-phase arrest. As cells in M-phase are very sensitive to radiation, it thereby increases radiation sensitivity. The ability to predict tumor response for individual patients would allow us to tailor subsequent therapy for the individual patient. This study is designed to evaluate if paclitaxel's effects on the cell cycle of an individual patient can predict the responsiveness of that patient's tumor to paclitaxel and radiation. Patients will be treated with 3 cycles of paclitaxel followed by concurrent paclitaxel and radiation prior to definitive surgery.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Occult breast carcinoma presenting as an axillary mass.

Breast carcinoma presents rarely (<5% of cases) as an axillary mass without an obvious primary tumor. The value of mammography in detecting an occult breast carcinoma is low, with a sensitivity of 29 per cent and specificity of 73 per cent. MRI and positron emission tomography (PET) are potentially more sensitive in this setting. We present a case recently seen at the Vanderbilt University Hospital, a 63-year-old woman with a 2-cm painless mass in the right axilla. Mammography was negative, and fine needle aspiration revealed atypical cells suspicious for malignancy. An excisional biopsy of the right axillary lymph node revealed metastatic adenocarcinoma, most likely breast primary. A PET showed increased uptake of 18-fluorodeoxyglucose and 99m Technetium in the right axilla and the right lateral breast. The patient underwent right modified radical mastectomy. The final pathological report revealed a 0.9-cm primary tumor in the upper inner quadrant of the breast and 1 of 41 nodes positive for tumor. This case confirms that mammography has low sensitivity in identifying the primary tumor in occult breast carcinoma and illustrates the usefulness of PET in identifying the primary tumor. We advocate an aggressive approach to evaluation of the breast in women presenting with metastatic adenocarcinoma in the axillary nodes. This evaluation should include clinical examination and mammography in all cases, and PET and MRI in selected cases. PET and MRI may be particularly useful when considering a breast-conserving surgical procedure.

Adenocarcinoma↗
PubMed1994

An alternative technique for laparoscopic cholangiography.

The current methods utilized for laparoscopic cholangiography involve cystic duct cannulation and present practical difficulties and potential hazards. An alternative method for intraoperative cholangiography is described which is easy, quick, and safe. The Kumar clamp (a gift from Sabi Kumar, M.D.) is placed across the infundibulum. A 23-gauge sclerotherapy needle is introduced through a side port in the clamp and directed into the infundibulum. The cholangiogram is obtained prior to any dissection in the triangle of Calot, thereby avoiding iatrogenic common bile duct injuries due to misidentification of the cystic duct or anomalous anatomy. To date no pathology has been missed and no complications have resulted from this technique.

Acute Disease↗
PubMed1993

A review of the results of laparoscopic versus open appendectomy.

Proponents of laparoscopic appendectomy emphasize the advantages of laparoscopic operation--decreased hospitalization, paralytic ileus, postoperative pain and wound complications, including infection. This study compared open laparoscopic appendectomy with laparoscopic appendectomy. To compare the two techniques, patients undergoing laparoscopic appendectomy at four hospitals were compared with patients undergoing open appendectomy during a six month period. Excluded were incidental appendectomies and patients with perforated appendicitis. An equal number of pediatric patients undergoing laparoscopic and open procedures were included in the analysis to avoid bias, because most of the laparoscopic appendectomies were performed in the adult patient population (age of more than 16 years). A University Medical Center, a Veterans Administration and two community hospitals were the settings. Patients undergoing laparoscopic appendectomy (n = 54) had an average age of 25.7 +/- 1.5 (range of six to 59 years). These patients were compared with 121 patients undergoing open appendectomy whose average age was 23.7 +/- 1.8 (range of three to 83 years). The race and gender distribution were similar in the two groups. Traditional open appendectomy was compared with a group of patients undergoing laparoscopic appendectomy. Variables evaluated were operating room time, number of patients who reported nausea, days until patient tolerated a regular diet, days of hospitalization, postoperative pain medication and wound infection rate. Results are expressed as the mean plus or minus standard error of the mean. Analysis of variance was used to compute continuous variables and Fischer's exact test was used for discrete variables. The laparoscopic approach was attempted in 61 patients and completed in 54 patients. Open appendectomy was performed upon 121 patients. Nineteen patients (18 who underwent open operation and one patient who underwent laparoscopic operation) were excluded from further analysis because of perforated appendicitis. The open procedure took less time (p < 0.05). However, there were more wound infections than in the laparoscopic group (seven of 103 versus zero of 53; p = 0.09). Patients with acute appendicitis recuperated more quickly from the laparoscopic procedure, as evidenced by the time until eating regular diet, period of hospitalization, incidence of nausea and pain medications on postoperative day one (p < 0.05). The absence of wound infections after laparoscopic appendectomy can be attributed to the practice of placing the appendix in a sterile bag or into the trocar sleeve before removal from the abdomen. Laparoscopic appendectomy reduces the period of hospitalization, postoperative ileus, nausea and postoperative pain in patients with acute appendicitis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

The 'fading' Meckel's diverticulum. An unusual scintigraphic presentation.

The usual scintigraphic presentation of a Meckel's diverticulum is progressive accumulation of Tc-99m pertechnetate within the ectopic gastric mucosa that parallels uptake in the stomach. The authors present a case of an adult with acute gastrointestinal bleeding, negative endoscopic and radiologic evaluation, and atypical scintigraphy. An abnormal focus of uptake appeared at the same time as the stomach but faded away in the 15-minute image before reappearing while the stomach was still progressively accumulating the radioisotope. Meckel's diverticulum was confirmed by surgery. This case emphasizes the importance of scintigraphy in the evaluation of gastrointestinal bleeding, and it further emphasizes that any uptake that cannot be physiologically related is suspicious, even in a young adult.

Adult↗
PubMed1992

Role of leucine and other amino acids in regulating protein metabolism in vivo.

The present study examines the independent effects of amino acids and leucine in modulating insulin's effect on leucine kinetics in 24-h fasted conscious dogs during an experimental period where insulin was infused at 600 mU.kg-1.h-1. Group I (n = 7) received saline, group II (n = 10) received sequential infusions of L-leucine at 0, 1, 3, and 1 mumol.kg-1.min-1 each lasting for 90 min, and group III (n = 6) received L-amino acids with doses of L-leucine matching those of group II. Plasma leucine (mumol/l) was 120 +/- 5 basally and 135 +/- 23 and 129 +/- 12 during the infusion of 3.0 mumol.kg-1.min-1 in groups II and III compared with 40 +/- 3 in group I. Leucine rate of appearance (mumol.kg-1.min-1) was 3.5 +/- 0.3 during the basal period and was suppressed 80% in both groups II and III as compared with 40% in group I (P less than 0.01). Leucine oxidation (basal = 0.7 +/- 0.15 mumol.kg-1.min-1) dropped 20% in group I but increased to threefold basal in group II and twofold in group III (P less than 0.05). Nonoxidative rate of disposal (basal = 2.6 +/- 0.2 mumol.kg-1.min-1) dropped 25% in group I and 55% in group II but did not change in group III. These data show that, in addition to insulin, amino acids and particularly leucine cause a marked suppression of proteolysis. Availability of all amino acids to prevent hypoaminoacidemia is necessary to sustain basal rates of protein synthesis. The infusion of leucine alone resulted in significant stimulation of leucine oxidation.

Amino Acids↗
PubMed1990

Role of insulin and branched-chain amino acids in regulating protein metabolism during fasting.

This study examines the independent effects of insulin and amino acids on protein metabolism after a 12-h and 4-day fast in healthy volunteers. Leucine (Leu) kinetics were examined during sequential insulin infusions of 0 (group I) or 0.0125 (groups II and III), 1.2, and 10 mU.kg-1.min-1. Plasma Leu was maintained at 12-h fasted levels in groups I and II and at 84-h fasted levels in group III. Four-day fast (vs. 1 day, P less than 0.01) was associated with a 79% drop in plasma insulin and elevations in plasma Leu (122%), Leu rates of appearance (Ra) (21%), and Leu oxidation (56%), and no change in nonoxidative rates of disappearance (Rd). Insulin resulted in a dose-dependent suppression of endogenous Leu Ra with group III = I greater than II. Leu oxidation rose 1.7-fold in group III at the highest insulin dose but remained stable in the two other groups. In conclusion, 4-day fasting is associated with enhanced proteolysis and Leu oxidation with no change in nonoxidative Rd (protein synthesis). Elevated branched-chain (and other) amino acids were required to restore tissue sensitivity and specificity to the effects of insulin on protein metabolism after 4 days of fasting.

Adult↗
PubMed1989

Amino acids augment insulin's suppression of whole body proteolysis.

Leucine (LEU) kinetics were assessed using a primed-continuous infusion of L-[1-14C]LEU in normal overnight-fasted male volunteers during a basal period and an experimental period where insulin (INS) was infused at either 0.6, 1.2, 2.5, 5.0, 10, or 20 mU.kg-1.min-1 with euglycemia maintained. Two protocols were used: 1) subjects were allowed to develop hypoaminoacidemia or 2) plasma essential amino acids (AA) were maintained near basal levels by frequently monitoring plasma LEU in conjunction with variable infusions of an AA solution (LEU infused = 0.41, 0.72, 0.93, 1.03, 1.31, and 1.35 mumol.kg-1.min-1 at escalating INS doses, respectively). Basal rates of LEU appearance (Ra), nonoxidative disappearance (NORd) and oxidative disappearance (OXRd) were similar in both protocols (means = 1.74, 1.40, and 0.36 mumol.kg-1.min-1, respectively). INS infusions without AA resulted in a progressive decrement in LEU Ra (14 to 45%), NORd (16-41%), and OXRd (3-56%) compared with basal values. The infusion of AA resulted in an additional reduction in endogenous Ra (P less than 0.01; approximately 100% suppression achieved at plasma INS greater than 1,000 microU/ml) and a blunting of NORd reduction (P less than 0.05) at each dose of INS. Observed differences in INS's suppression of LEU Ra between the two protocols suggests the existence of a component of whole body proteolysis that is highly dependent on circulating plasma AA. Therefore, hypoaminoacidemia associated with INS treatment would appear to blunt the responsiveness of INS's suppression of protein breakdown and in the presence of near basal plasma AA, proteolytic suppression by INS is enhanced.

Adult↗
PubMed1988

The role of leucine in hepatic ketogenesis.

Isolated hepatocyte studies demonstrated that leucine can be a precursor of ketone bodies. In this study we examine the relative contribution of leucine to hepatic ketogenesis in vivo. Three groups of conscious dogs with long-term indwelling catheters in the femoral artery, hepatic vein, and portal vein were studied. Group I (n = 3) animals were fasted overnight for 24 hours, and those in groups II and III (n = 4, each) were fasted for 62 to 68 hours (designated 3-day fast). Groups I and III received intravenous saline solution (0.9%) and served as controls. In group II selective acute insulin deficiency (SAID) was induced by a peripheral intravenous somatostatin (SRIF) infusion and intraportal glucagon (0.55 ng/body weight/min). Net hepatic production (NHP) of ketone bodies (kb) and leucine (leu) was measured by the arteriovenous difference technique. Hepatic conversion of leucine to ketone bodies was measured by continuous infusion of L-U-[14C]-leucine and by determination of the appearance of [14C]-ketone bodies across the liver. In the group fasted overnight NHPleu was 0.02 +/- 0.01 mumol/kg/min, a value not different from zero. NHPkb was 3.1 +/- 0.1 mumol/kg/min and hepatic conversion of leucine to ketone bodies accounted for 3.5% of NHPkb. Insulin deficiency after 3 day's fasting resulted in a near 70% increase in NHPleu (from basal values of 0.31 +/- 0.1 mumol/kg/min to 0.52 +/- 0.06 mumol/kg/min during SAID, p less than 0.01). NHPkb increased from 11.0 +/- 1.0 to 15.5 mumol/kg/min (p less than 0.05). The rate of leucine conversion to ketone bodies (L-C) increased from 1.1 +/- 0.25 to 2.4 +/- 0.3 mumol/kg/min (p less than 0.01) with SAID. We conclude that as the dog progresses to fasting, the contribution of leucine carbon to hepatic production of ketone bodies increases from 3.5% to 10% (p less than 0.01), and this value increases to 15% (p less than 0.01 versus groups I and II) after SAID. Furthermore, the amount of leucine carbon taken up by the liver was not sufficient to account for all [14C]-labeled leucine to ketone bodies. The data suggest that the leucine carbon converted to ketone bodies must have been derived from intrahepatic protein sources of possibly from the keto acids of leucine, which are derived by the breakdown of leucine at distant sites, such as skeletal muscle or adipose tissue.

Animals↗
PubMed1987

Experience with adrenocortical neoplasms in childhood.

The experience with adrenocortical neoplasms in childhood is reviewed. During three decades, ten children with adrenocortical neoplasms were seen at the authors' institution. The literature was reviewed, and 209 patients 16.5 years or younger were found. All ten patients at Vanderbilt University Hospital (VUH) presented with endocrine manifestations of the tumor. Three patients had Cushing's, two patients had virilization, and five patients had features of both. In the literature, virilization, alone or with Cushing's, was the most common mode of presentation. Feminizing tumors were uncommon and nonfunctional tumors rare. The majority of patients were female. Features associated with malignancy included 17-KS levels greater than 40 mg/24 hr, diameter greater than 6 cm, weight greater than 500 g, and histologic evidence of diffuse growth pattern, vascular invasion, and tumor cell necrosis. Although uncommon, adrenocortical neoplasms should be suspected in children with Cushing's, virilization, feminization, or a combination of these. There has been an increased incidence reported in patients with hemihypertrophy, Beckwith-Wiedemann syndrome, hemangiomas, and nevi. Following endocrinologic evaluation, imaging studies should be performed. CT scan appears to be the most useful diagnostic tool. A posterior operative approach is recommended for suspected adenomas. An anterior thoracoabdominal approach is favored for suspected malignancies with uncompromised en bloc resection. There is no evidence that adjuvant therapy provides any additional benefit.

17-Hydroxycorticosteroids↗
PubMedDate not supplied

What getting sick means.

The concepts of health, disease and death have intrigued man since the beginning of time and are continually evolving. In the nonwestern societies the models which have been proposed for the etiology of disease have a dichotomous view of disease causation which is derived from either natural or supernatural forces. In the Western societies these concepts are well defined. The numerous advances in the fields of genetics and molecular biology have added a new dimension to the understanding of the various factors involved in the pathogenesis of disease processes. These advances have allowed a greater understanding of numerous disease processes including the inborn errors of metabolism, endocrine disorders and human neoplasia. Several recent advances in the areas of molecular biology and physiology allowing this increased understanding of human disease are presented.

Disease↗
PubMedDate not supplied

Amino acids enhance insulin resistance to exogenous glucose infusion in overnight-fasted humans.

The role that amino acids play in regulating exogenous glucose infusion during hyperinsulinemia was examined in overnight-fasted volunteers. Each study consisted of both a 30-minute basal period and a 4-hour experimental period during which insulin was infused at either 0.6, 1.2, 2.5, 5.0, 10, or 20 mU/kg/min with euglycemia maintained. Two protocols were used. In the first (I), subjects were allowed to develop hypoaminoacidemia, and in the second (II), plasma amino acid levels were maintained near basal by frequently monitoring plasma leucine levels in conjunction with exogenous infusion of an L-amino acid solution. The amount of amino acids infused were 0.85 +/- 0.11, 1.53 +/- 0.17, 1.97 +/- 0.13, 2.18 +/- 0.50, 2.78 +/- 0.61, and 2.83 +/- 0.44 mg/kg/min at escalating insulin doses, respectively. When amino acids were infused, the amount of glucose required to maintain euglycemia was lower at each insulin dose used (4.5 +/- 0.3 vs 3.6 +/- 0.4, 7.6 +/- 0.5 vs 6.9 +/- 0.3, 10.4 +/- 1.0 vs 8.7 +/- 0.5, 13.3 +/- 0.8 vs 10.2 +/- 0.4, 14.7 +/- 0.8 vs 11.7 +/- 0.6, and 14.9 +/- 0.6 vs 11.8 +/- 0.8 mg/kg/min at escalating insulin doses, respectively; p less than 0.05). The calculated maximal infusion rates were 15.8 +/- 0.6 vs 12.6 +/- 0.4 mg/kg/min (protocol I vs II, p less than 0.001), while the concentrations required to achieve half-maximal rates were 153 +/- 22 and 134 +/- 22 microU/ml (p = ns), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗