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L Strauss

Publications and source records attributed to L Strauss.

At least 19 recordsLinked to original sources
PubMed2005

[Antiangiogenic and anti-immunosuppressive therapeutic strategies in human head and neck squamous cell carcinoma (HNSCC)].

BACKGROUND: Angiogenesis and tumor-associated immunosuppression are two of the hallmarks of carcinogenesis. In previous studies we demonstrated in vitro that HNSCC tumor cells attract monocytes via monocyte chemotactic protein-1 (MCP-1) and activate them via transforming growth factor-beta 1(TGF-beta1) to secrete interleukin (IL)-1alpha, which in turn stimulates tumor cells to secrete increased levels of the angiogenic and immunosuppressive vascular endothelial growth factor (VEGF). These findings suggest that interaction between the immune system and VEGF-mediated angiogenesis is important for progression of HNSCC. Recent studies in vitro show that retinoic acid (RA) downregulates the release of MCP-1 and TGF-beta1 by tumor cells. Therefore, we investigated the ability of RA to modulate the ability of tumor cells to recruit and activate monocytes for participation in VEGF-mediated angiogenesis and immunosuppression in vivo. MATERIAL AND METHODS: Mice (ten/group) were injected daily with RA (160 microg/kg) for 3 weeks. After that time mice were sacrificed, and paraffin sections of tumors were obtained and stained for VEGF-A, CD68, and PECAM (CD31) by immunohistochemistry. The lungs, liver, and myocardium were analyzed for macro- and micrometastases. The plasma protein levels of VEGF-A and MCP-1 were determined by ELISA. RESULTS: In RA-treated mice tumors regressed completely and RA prevented metastases (p=0.00) and macrophage infiltration (p=0.007). Treated mice downregulated VEGF-A (0 pg/ml) and MCP-1 (12 pg/ml) in peripheral blood (p=0.001). CONCLUSION: Our findings suggest a new therapeutic possibility: the development of treatment protocols that can block each of the ways in which tumors induce new blood vessel growth and immunosuppression of the host.

Angiogenesis Inhibitors↗
PubMed2001

Microkeratome-assisted posterior keratoplasty.

Microkeratome-assisted posterior keratoplasty is a new surgical technique that may be valuable in treating patients with corneal decompensation secondary to endothelial dysfunction. A hinged anterior stromal flap is fashioned in the host cornea using a microkeratome, and the diseased posterior stroma and endothelium are resected. A complementary donor stromal button is prepared using a microkeratome and an artificial anterior chamber. The donor button is transplanted and secured with sutures, and the flap is repositioned. The flap can be lifted later to remove the sutures or to correct residual refractive errors using an excimer laser. This technique may allow the use of infant corneal donor tissue and may improve the outcomes of posterior keratoplasty.

Aged↗
PubMed2001

Outsourcing manufacturing.

In addition to increasing their technical ability, some contract manufacturers are expanding the capacity of their operations by 20% per year. This article outlines how to capitalise on this trend and successfully move a manufacturing operation to a contract manufacturer.

Biotechnology↗
PubMed2000

Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract.

Estrogens induce pronounced structural and functional changes in male accessory sex glands and the lower urinary tract in both sexes, but the exact mechanisms of estrogen action are not fully understood. This study was undertaken to localise the tissue cell types that express estrogen receptor in adult rats, and to determine the receptor subtype (ERalpha and ERbeta) in order to identify sites that may respond directly to estrogens. In the male accessory sex glands (seminal vesicles, prostatic lobes and ampullary glands), ERbeta mRNA and protein were strongly expressed in the epithelium but not in the stroma, while ERalpha mRNA was present only in the fibromuscular tissue surrounding the prostatic collecting ducts in the posterior periurethral region and in ampullary gland stroma. In the epithelium of the urinary bladder and urethra of both sexes, high level of ERbeta mRNA and protein, but no ERalpha mRNA, was detected. The connective tissue in urinary bladder of both males and females, as well as that in prostatic urethra in males expressed ERalpha mRNA. The neural cells in the autonomic ganglia of the prostatic plexus were strongly positive for ERbeta mRNA, but were completely devoid of ERalpha. We conclude that ERbeta is the predominant ER subtype in the epithelium of adult male rat accessory sex glands and the lower urinary tract of both males and females, as well as in the prostatic neural plexus regulating the function of the lower urinary tract in males, while ERalpha is present only in the stromal compartment of distinct sites. These results indicate that in these tissues in intact adults there are multiple targets for direct estrogen action. Furthermore, the differential or complementary expression of the two ER subtypes suggests that they may have specific functions, and may explain the complex structural and functional changes induced by estrogens.

Animals↗
PubMed2000

Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract.

Estrogens induce pronounced structural and functional changes in male accessory sex glands and the lower urinary tract in both sexes, but the exact mechanisms of estrogen action are not fully understood. This study was undertaken to localise the tissue cell types that express estrogen receptor in adult rats, and to determine the receptor subtype (ER alpha and ER beta) in order to identify sites that may respond directly to estrogens. In the male accessory sex glands (seminal vesicles, prostatic lobes and ampullary glands), ER beta mRNA and protein were strongly expressed in the epithelium but not in the stroma, while ER alpha mRNA was present only in the fibromuscular tissue surrounding the prostatic collecting ducts in the posterior periurethral region and in ampullary gland stroma. In the epithelium of the urinary bladder and urethra of both sexes, high level of ER beta mRNA and protein, but no ER alpha mRNA, was detected. The connective tissue in urinary bladder of both males and females, as well as that in prostatic urethra in males expressed ER alpha mRNA. The neural cells in the autonomic ganglia of the prostatic plexus were strongly positive for ER beta mRNA, but were completely devoid of ER alpha. We conclude that ER beta is the predominant ER subtype in the epithelium of adult male rat accessory sex glands and the lower urinary tract of both males and females, as well as in the prostatic neural plexus regulating the function of the lower urinary tract in males, while ER alpha is present only in the stromal compartment of distinct sites. These results indicate that in these tissues in intact adults there are multiple targets for direct estrogen action. Furthermore, the differential or complementary expression of the two ER subtypes suggests that they may have specific functions, and may explain the complex structural and functional changes induced by estrogens.

Adolescent↗
PubMed2000

Distribution of collagen XII and XIV in the bladder wall of the male rat with outlet obstruction.

PURPOSE: Our previous studies indicate that neonatal estrogenization with diethylstilbestrol (neoDES) of male mice and rats causes partial outlet obstruction. In the present study, type XII and XIV collagens were localized in the bladder to study their role in the development of obstruction. MATERIALS AND METHODS: The bladder sections immunostained with smooth muscle specific a-actin antibody were double labeled either with collagen type XII or type XIV antibodies. The specimens were then analyzed with conventional and confocal fluorescence microscope. RESULTS: Type XII and XIV collagens were not evenly distributed in the bladder. Further, in neonatally estrogenized rats collagen XIV appeared inside smooth muscle fascicles. CONCLUSIONS: Non-overlapping distributions of collagen XII and XIV suggest their different roles in the urinary bladder. Penetration of collagen XIV inside smooth muscle fascicles may have a role in the development of DES-induced partial outlet obstruction.

Animals↗
PubMed1999

Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding affinities to estrogen receptors alpha and beta.

Estrogen-based drug therapy in cardiovascular diseases has been difficult because it has not been possible to separate the wanted vasculoprotective effect from the unwanted effects of the hormone to the reproductive system. Here, we demonstrate that, after endothelial denudation of rat carotid artery, the mRNA of the classical estrogen receptor (ERalpha) is constitutively expressed at a low level whereas the expression of the novel ERbeta mRNA increases >40-fold. Under in situ hybridization and immunohistochemistry, ERbeta mRNA and protein colocalize with the smooth muscle cells in the media and neointima. Treatment of ovariectomized female rats with the isoflavone phytoestrogen genistein, which shows 20-fold higher binding affinity to ERbeta than to ERalpha, or with 17beta-estradiol, which does not differentiate between the two receptors, provides similar dose-dependent vasculoprotective effect in rat carotid injury model. In addition in concentrations <10 microM, both ligands are equally inhibitory to the replication and migration of smooth muscle cells in vitro. However, only treatment with 17beta-estradiol, but not with genistein, is accompanied with a dose-dependent uterotrophic effect. The results suggest that preferential targeting to ERbeta will provide vasculoprotective estrogen analogs devoid of effects to the reproductive system.

Animals↗
PubMed1998

Dietary phytoestrogens and their role in hormonally dependent disease.

Epidemiological studies suggest that diets rich in phytoestrogens (plant estrogens), particularly soy and unrefined grain products, may be associated with low risk of breast and prostate cancer. It has also been proposed that dietary phytoestrogens could play a role in the prevention of other estrogen-related conditions, namely cardiovascular disease, menopausal symptoms and post-menopausal osteoporosis. However, there is no direct evidence for the beneficial effects of phytoestrogens in humans. All information is based on consumption of phytoestrogen-rich diets, and the causal relationship and the mechanisms of phytoestrogen action in humans still remain to be demonstrated. In addition, the possible adverse effects of phytoestrogens have not been evaluated. It is plausible that phytoestrogens, as any exogenous hormonally active agent, might also cause adverse effects in the endocrine system, i.e. act as endocrine disrupters.

Animals↗
PubMed1998

Genistein exerts estrogen-like effects in male mouse reproductive tract.

The aim of this study was to evaluate the estrogenicity of genistein in the neonatal and adult male mouse reproductive tract. In intact adults, genistein (2.5 mg s.c./kg of body weight/day for 9 days) reduced testicular and serum testosterone concentrations, pituitary LH-content and prostate weight. In castrated adults, genistein (0.025-2.5 mg s.c./kg of body weight) increased expression of c-fos gene in prostatic urethra. In adult, neonatally estrogenized mice showing an increased estrogen sensitivity, a 10-day treatment with genistein (2.5 mg s.c./kg of body weight) induced development of squamous epithelial metaplasia in prostatic collecting ducts. Neonatally, only a very high dose of genistein (1 mg/pup per day; i.e. approximately 500 mg/kg of body weight) induced persistent structural changes, similar to those seen in mice treated neonatally with diethylstilbestrol, in the urethroprostatic complex. These results suggest that in adult males, genistein induces the typical estrogenic effects in doses comparable to those present in soy-based diets, while in neonatal animals, considerably higher doses are required to show estrogen-like activity.

Aging↗
PubMed1998

Effect of long-term salmeterol treatment on exercise-induced asthma.

BACKGROUND: With long-term administration of salmeterol, the extent of protection afforded by the drug against experimental precipitants of asthma such as methacholine and adenosine may decrease. Whether this effect extends to a clinically relevant stimulus such as exercise is unknown. METHODS: We performed a random-order, double-blind, crossover trial in 20 patients with exercise-induced asthma. Each patient received inhaled salmeterol or placebo twice daily for a month, with a one-week washout period between treatments. The patients performed cycle ergometry while breathing frigid air 30 minutes after the morning dose and 9 hours later on the 1st, 14th, and 29th study days. The primary end point was the extent of the decrease in forced expiratory volume in 1 second (FEV1) 10 minutes after exertion. RESULTS: With placebo, significant airway narrowing developed at all times (mean [+/-SE] decrease from base line in FEV1, 19+/-2 percent in the morning and 18+/-2 percent in the evening). The morning dose of salmeterol attenuated the degree of bronchoconstriction at all times (decrease in FEV1 on day 1, 5+/-2 percent; on day 14, 10+/-3 percent; and on day 29, 9+/-3 percent; P=0.10). Its ability to act throughout the day, however, decreased with long-term administration (decrease in FEV1 from morning to evening on day 1, 6+/-2 percent; on day 14, 15+/-3 percent; and on day 29, 14+/-3 percent; P=0.003). CONCLUSIONS: Protection against exercise-induced asthma is maintained with long-term administration of salmeterol, but the length of time that the drug remains active after a single dose decreases.

Adrenergic beta-Agonists↗
PubMed1998

Comparison of two dosage regimens of albuterol in acute asthma.

BACKGROUND: The standard therapy for acute episodes of asthma in the United States consists of three 2.5-mg doses of aerosolized albuterol given every 20 minutes. Whether this approach represents optimum therapy has never been tested. METHODS: This study employed a prospective, sequential design in which the effects of two doses of 5.0 mg of aerosolized albuterol administered during 40 minutes (high dose) were contrasted with the standard dose (three 2.5-mg doses). Improvements in pulmonary function, clinical resolution of the asthma attacks, and admission rates were used as primary endpoints. Both regimens were part of an overall care plan that involved objective, pretested decision algorithms. RESULTS: In an emergency department, 160 patients who presented with acute exacerbations of asthma received either standard (n = 80) or high-dose (n = 80) albuterol treatment. There were no significant baseline differences in gender, racial composition, clinical signs and symptoms, medication use, or peak expiratory flow (PEF) between the groups. Both treatment schedules were effective, but the high-dose regimen increased lung function more rapidly and to a greater extent than standard-dose therapy. It also resulted in lower charges to third party payers. More subjects attained the discharge criteria quicker and left the emergency department with peak expiratory flows closer to normal. Fewer patients in the high-dose group were admitted, but this trend did not quite reach statistical significance. CONCLUSIONS: Two 5.0-mg treatments of aerosolized albuterol at a 40-minute interval provide effective therapy for acute exacerbations of asthma. This combination of dose and frequency promotes maximum bronchodilatation, increases efficiency, and reduces the risks of undertreatment.

Acute Disease↗
PubMed1998

Inhibition of 17beta-hydroxysteroid oxidoreductase by flavonoids in breast and prostate cancer cells.

Several flavonoids and isoflavonoids were found to inhibit 17beta-oxidoreduction of estrogens by the purified 17beta-HSOR type 1, or in cell lines expressing 17beta-HSOR type 1 enzyme (T-47D breast cancer cells) or type 2 (PC-3 prostate cancer cells). The structural demands for the inhibition of estrone (E1) reduction and estradiol (E2) oxidation catalyzed by 17beta-HSOR types 1 and 2, respectively, were not identical. Flavones, flavanones, and isoflavones hydroxylated at both the double ring (positions 5 and 7) and ring B (position 4') were the most potent inhibitors of E1 reduction in T-47D cells, and by the purified type 1 enzyme whereas flavones hydroxylated at positions 3, 5, and 7 of rings A and C, with or without a hydroxyl group in ring B, were capable of inhibiting E2 oxidation in PC-3 cells. Change to flavanone structure, or hydroxylation at position 3 of ring C of flavones, or methylation of the hydroxyl group at position 4' of ring B of flavones and isoflavones reduced or abolished their inhibitory activity on E1 reduction in T-47D cells. On the contrary, hydroxyl group at position 3 of flavones (flavonol structure) markedly increased the inhibition of E2 oxidation in PC-3 cells. Thus, changes in the number and location of hydroxyl groups may discriminate inhibition of E1 reduction and E2 oxidation. Some of the differences may be due to differences in pharmacokinetics of these compounds in T-47D and PC-3 cells. Inhibition of 17beta-HSORs could lead to an alteration in the availability of the highly active endogenous estrogen, but the effects of these compounds in vivo cannot be predicted on the basis of these results alone. Some of these compounds (isoflavones) are estrogenic per se, and they may replace endogenous estrogens, whereas flavones are only very weakly estrogenic or nonestrogenic. Regarding prevention or treatment of estrogen-related diseases, apigenin, coumestrol, and genistein raise special interest.

17-Hydroxysteroid Dehydrogenases↗
PubMed1997

The influence of parasympatholytics on the resolution of acute attacks of asthma.

PURPOSE: To evaluate the role of parasympatholytics in the resolution of acute attacks of asthma. METHODS: This study employed a prospective sequential design in which the influence of 0.5 and 1.0 mg of ipratropium bromide on peak expiratory flow rates (PEFR), hospital admissions, and length of stay (LOS) in the emergency department (ED) was evaluated. The parasympatholytic was added to a well-investigated standard therapeutic regimen that was anchored by the use of repetitive doses of albuterol, and employed pretested decision algorithms. RESULTS: One hundred and thirty-one patients received ipratropium (l) and 123 who did not (NI) served as controls. There were no significant pretreatment between group differences in gender, racial composition clinical signs and symptoms, or PEFR. The presence of ipratropium in the regimen did not influence discharge/admission patterns, LOS, the rate of improvement of the patients, or the level of PEFR achieved. CONCLUSION: Anticholinergic agents such as ipratropium are not first-line treatments for acute asthma. They do not add any therapeutic benefit to the effects of albuterol given in divided doses over 1 hour, nor do they facilitate recovery in patients whose immediate response to sympathomimetics is impaired.

Acute Disease↗
PubMed1997

Observations on the effects of aerosolized albuterol in acute asthma.

To determine the dose of albuterol required to terminate acute episodes of asthma, 92 acutely ill subjects received three doses of 2.5 mg each by nebulization every 20 min. Peak expiratory flow rates (PEFR) and signs and symptoms were serially monitored. A dose-response increase in pulmonary function was found, but only 66% of the subjects improved sufficiently to be sent home. Of these, 56% required < or = 5.0 mg of drug to reach the discharge threshold, whereas the remainder needed 7.5 mg. In 34% of participants, albuterol was ineffectual. These individuals were characterized by more severe obstruction at presentation, and after three doses of medication their PEFR still did not exceed 40% of the expected value. Further treatment in the emergency department (ED) or hospital was not immediately helpful, and these patients ultimately required 3.8 +/- 0.4 d of inpatient care to become asymptomatic. There were no discernible differences between responders and nonresponders in the type or quantity of medications used. However, the nonresponders had more severe disease as measured by recurrent hospitalizations and ED visits. This study demonstrates that, in emergency situations, albuterol does not relieve acute airway obstruction in all asthmatic individuals with equal efficacy. Two-thirds of patients are sensitive, and in these patients 5 to 7.5 mg of albuterol provides optimal treatment. In the remainder, albuterol, even in high doses, has little effect for days.

Acute Disease↗
PubMed1996

Hyperfractionated craniospinal radiation in medulloblastoma.

From 1986 to 1991, 13 patients at Northwestern Memorial Hospital were entered onto a pilot study designed to test the feasibility of treating children with medulloblastoma (11 patients) or primitive neuroectodermal tumors of the cerebral hemispheres (2 patients) with hyperfractionated craniospinal radiotherapy (HFxRT). Follow-up times ranged from 10 to 96 months with a median of 53 months. The patients were prospectively divided among three treatment arms depending on prior treatment history, if any, and degree of surgical resection. The 3 patients in group I had undergone gross total resection of the primary site, receiving 64.8 Gy to the primary site and 31.2 Gy directed to the craniospinal axis (CSA). Of these 3 patients, patient 1 had residual disease in the thoracic spine at T-10. The 8 patients in group II, who had gross residual disease remaining at the primary site, received 72 Gy to the primary site and 34 Gy to the CSA. Five of these eight patients in group II also received 8-in-1 chemotherapy. The 2 patients in group III had already failed chemotherapy and were then treated with 60 Gy to the primary site and 26 Gy to the CSA. Of the 11 patients in groups I and II, 7 of the 11 (64%) have never recurred. Two of the three group-I patients have not recurred, and 5 of the 7 group-II patients have not recurred. In addition, patient 7 (group II) remains alive after salvage with bone marrow transplant, following a local failure bordering the tentorium. Unfortunately, neither of the group-III patients could be salvaged with HFxRT. Acute/subacute toxicities included 7 cases of external auditory canal or skin desquamation, 2 cases of postradiation somnolence, and 1 case each of poor wound healing and neutropenia. Chronic toxicities included hypothyroidism in 2 patients and growth problems in 2 patients. Neuropsychologic complications affected only the 3 youngest patients in the study. Three patients developed neurologic sequelae attributed to radiation, including 1 with progressive urinary incontinence, 1 who developed a transient ischemic attack, and 1 who became progressively ataxic. Our research, although based on a small number of patients, suggests that hyperfractionated radiation therapy to craniospinal access is feasible and that the survival results are favorable. This treatment strategy should be further explored in a phase-III randomized trial.

Adolescent↗
PubMed1995

Optic pathway tumors in children: the effect of neurofibromatosis type 1 on clinical manifestations and natural history.

OBJECTIVE: To distinguish the clinical manifestations and natural history of optic pathway tumors (OPT) associated with neurofibromatosis type 1 (NF-1 OPT) from that of OPT not associated with NF-1 (non-NF-1 OPT). METHODS: Two groups of children with OPT were compared: (1) 17 children with NF-1 OPT who were followed prospectively, and (2) 19 children with non-NF-1 OPT who were identified retrospectively by a review of medical records. RESULTS: Precocious puberty was a common initial sign in the children with NF-1 OPT (5/17), and was not found in any patients without NF-1. In contrast, children with non-NF-1 OPT had symptoms attributable to increased intracranial pressure (12/19 and nystagmus (5/19); these symptoms were not found in any patient with NF-1. Decreased visual acuity at the time of diagnosis was common in both groups. There was no significant difference between the children with NF-1 OPT and those with non-NF-1 OPT as to age at diagnosis or sex distribution. Optic nerve involvement was more common in NF-1 (p < 0.001). Both isolated and bilateral optic nerve tumors were found exclusively in children with NF-1, whereas chiasmal (p = 0.016) and optic tract involvement (p = 0.001) were more common in those with non-NF-1 OPT. Radiographic evidence of hydrocephalus was found in none of the children with NF-1 OPT compared with 79% of the non-NF-1 OPT group. Progressive disease was seen in 12% of patients with NF-1 OPT compared with 63% of those with non-NF-1 OPT. CONCLUSIONS: Differences exist between NF-1 OPT and non-NF-1 OPT both at the time of diagnosis and during follow-up. Optic pathway tumors caused by NF-1 and non-NF-1 OPT have different biologic properties that distinguish both their initial clinical manifestations and their natural history.

Astrocytoma↗
PubMed1994

A pilot study of isotretinoin in the treatment of juvenile chronic myelogenous leukemia.

BACKGROUND: Juvenile chronic myelogenous leukemia (CML) is a rare myeloproliferative disease of infants and young children for which there is no effective therapy other than allogeneic bone marrow transplantation. In vitro, isotretinoin (13-cis-retinoic acid) attenuates both the spontaneous proliferation of leukemic peripheral-blood progenitor cells (granulocyte-macrophage colony-forming units) and their selective hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF). We conducted a pilot study to evaluate the clinical efficacy of isotretinoin in juvenile CML. METHODS: To be eligible the patients had to have newly diagnosed untreated disease, leukocytosis with monocytosis, marrow with less than 25 percent blasts, hepatosplenomegaly, no chromosomal abnormalities, and negative viral cultures and antibody titers. Isotretinoin was administered orally in single daily doses of 100 mg per square meter of body-surface area. When possible, patients subsequently underwent bone marrow transplantation. RESULTS: Ten children (median age, 10 months) were enrolled in the study. In all 10 there was spontaneous colony formation of leukemic progenitor cells in vitro. In the eight patients tested there was hypersensitivity to GM-CSF. The only toxic effect of isotretinoin therapy was cheilitis in two patients. Four children had disease progression. Two children had complete responses to isotretinoin (normalization of the white-cell count and disappearance of organomegaly), three had partial responses (more than a 50 percent reduction in the white-cell count and degree of organomegaly), and one had a minimal response (more than a 50 percent reduction in the white-cell count, but a 26 to 50 percent reduction in the degree of organomegaly). The median duration of response was 37 months (range, 6 to 83). Three of the four children who had a complete or partial response and who did not undergo bone marrow transplantation were alive 36 to 83 months after the diagnosis of juvenile CML. The spontaneous colony formation in vitro was reduced in samples from the five patients in whom this factor was reassessed during treatment. There was also a reduction in the hypersensitivity of leukemic progenitor cells to GM-CSF in the two patients retested. CONCLUSIONS: Isotretinoin can induce durable clinical and laboratory responses in patients with juvenile CML.

Child, Preschool↗