Search PubMed⌕ Search

Biomedical subjects

A M Schwartz

Publications and source records attributed to A M Schwartz.

At least 19 recordsLinked to original sources
PubMed2006

New viral vector for efficient production of target proteins in plants.

A new potato virus X (PVX)-based viral vector for superproduction of target proteins in plants has been constructed. The triple gene block and coat protein gene of PVX were substituted by green fluorescent protein. This reduced viral vector was delivered into plant cells by agroinjection (injection of Agrobacterium tumefaciens cells, carrying viral vector cDNA within T-DNA, into plant leaves), and this approach allowed to dramatically reduce the size of the vector genome. The novel vector can be used for production of different proteins including pharmaceuticals in plants.

Agrobacterium tumefaciens↗
PubMed2006

Stability of plant mRNAs depends on the length of the 3'-untranslated region.

Eukaryotic mRNAs that prematurely terminate translation are recognized and degraded by nonsense mediated decay (NMD). This degradation pathway is well studied in animal and yeast cells. The data available imply that NMD also takes place in plants. However, the molecular mechanism of recognition and degradation of plant RNAs containing premature terminator codon (PTC) is not known. Here we report that in plant cells this mechanism involves the recognition of the sizes of the 3'-untranslated regions (3'UTR). Plant 3'UTRs longer than 300 nucleotides induce mRNA instability. Contrary to mammalian and yeast cells, this destabilization does not depend on the presence of any specific sequences downstream of the terminator codon. Unlike nuclear-produced mRNAs, plant virus vector long 3'UTR-containing RNAs, which are synthesized directly in the cytoplasm, are stable and translated efficiently. This shows that RNAs produced in the cytoplasm by viral RNA-dependent RNA polymerase are able to avoid the proposed mechanism.

3' Untranslated Regions↗
PubMed2000

Overexpression of the glucose-regulated stress gene GRP78 in malignant but not benign human breast lesions.

The 78 kDa glucose-regulated stress protein GRP78 is induced by physiological stress conditions such as hypoxia, low pH, and glucose deprivation which often exist in the microenvironments of solid tumors. Activation of this stress pathway occurs in response to several pro-apoptotic stimuli. In vitro studies have demonstrated a correlation between induced expression of GRP78 and resistance to apoptotic death induced by topoisomerase II-directed drugs. We were interested in characterizing this protein in human breast lesions for potential implications in chemotherapeutic intervention. Surgical specimens of human breast lesions and paired normal tissues from the same patients were flash frozen for these studies. Total RNA and/or protein were extracted from these tissues and used in northern and/or western blot analyses, respectively, to quantify the relative expression of GRP78. Northern blot analysis indicated that 0/5 benign breast lesions, 3/5 estrogen receptor positive (ER+) breast tumors, and 6/9 estrogen receptor negative (ER-) breast tumors exhibited overexpression of GRP78 mRNA compared to paired normal tissues, with fold overexpressions ranging from 1.8 to 20. Western blot analyses correlated with these findings since 0/5 benign breast lesions, 4/6 ER+ breast tumors, and 3/3 ER- breast tumors overexpressed GRP78 protein with fold overexpressions ranging from 1.8 to 19. Immunohistochemical analysis of these tissues demonstrated that the expression of GRP78 was heterogeneous among the cells comprising different normal and malignant glands, but confirmed the overexpression of GRP78 in most of the more aggressive ER- tumors. These results suggest that some breast tumors exhibit adverse microenvironment conditions that induce the overexpression of specific stress genes that may play a role in resistance to apoptosis and decreased chemotherapeutic efficacy.

Adult↗
PubMed1999

Hemorrhoids: what the dermatologist should know.

Anorectal disorders are common and more than one half of the population will experience one at some time during their lives. It is important for the clinician to recognize the differences between internal and external hemorrhoids and other anorectal problems such as fissures, abscesses, fistulas, skin tags, and a variety of dermatologic conditions because the treatment is often different. This article will discuss the anatomy, pathophysiology, diagnosis, and treatment of internal and external hemorrhoids.

Anal Canal↗
PubMed1999

Chronic hypertension with subsequent congestive heart failure in a western lowland gorilla (Gorilla gorilla gorilla).

Chronic severe subclinical systemic hypertension was diagnosed in a 28-yr-old male western lowland gorilla (Gorilla gorilla gorilla). Thoracic radiography, electrocardiography, and echocardiography revealed an enlarged heart with a hypertrophied left ventricle, mitral regurgitation, and a persistent left bundle branch block. Enalapril, later combined with nifedipine, was of some value in reducing the hypertension, with partial reversal of cardiac enlargement and resolution of the bundle branch block. Two years after initiation of treatment, the gorilla developed lethargy and dyspnea. The diagnosis of heart failure was confirmed under anesthesia; the gorilla did not recover and was euthanized. Postmortem examination confirmed congestive heart failure with chronic, fibrosing cardiomyopathy similar to that in other gorillas.

Animals↗
PubMed1998

Treatment of subungual myxoma preserving the nail matrix: a case report.

Subungual myxomas are uncommon, benign, expansile lesions that club the fingertip. Traditionally the nail matrix is incised, which results in permanent nail deformity. This report describes a midlateral approach that not only spares the nail apparatus but demonstrates that the nail can remodel even if a void is left under the nail matrix after excision of the tumor. The histologic examination of the tumor is described.

Female↗
PubMed1998

The lethal effects of Cyperus iria on Aedes aegypti.

The sedge Cyperus iria, a common weed in rice, contains large amounts of the insect hormone (10R) juvenile hormone III (JH III). Given its widespread distribution in Asia and Africa, we examined the possibility that C. iria could be used as a safe, inexpensive, and readily available mosquito larvicide. Plants of varying ages were harvested and leaves tested for lethal effects on larvae of the yellow fever mosquito, Aedes aegypti. The median lethal doses (LD50s) for frozen leaves from 1- and 2-month-old plants were 267 and 427 mg/100 ml of water, respectively. Leaves from 1-month-old C. iria contained 193 micrograms JH III/g fresh weight, whereas leaves from 2-month-old plants contained 143 micrograms JH III/g fresh weight. Larval sensitivity to the plant differed with age; 4-day-old larvae displayed the greatest mortality followed in decreasing sensitivity by larvae 5, 6, 3, and 2 days old. Six Cyperus species (C. albostriatus, C. alternifolius, C. esculentus, C. iria, C. miliifolius, and C. papyrus) of similar developmental stage were assayed for JH III content. Only C. iria was found to contain significant levels of JH III.

Aedes↗
PubMed1998

Growth inhibitory effects of 1,25-dihydroxyvitamin D3 and its synthetic analogue, 1alpha,25-dihydroxy-16-ene-23yne-26,27-hexafluoro-19-nor-cholecalcifero l (Ro 25-6760), on a human colon cancer xenograft.

The effect of 1,25-dihydroxyvitamin D3 and its synthetic analogue, 1alpha,25-dihydroxy-16-ene-23yne-26,27-hexafluoro-19-n or-cholecalciferol (Ro 25-6760), have been evaluated both in vitro and in vivo in human colorectal cancer cell lines expressing high (HT-29) and low (SW-620) levels of vitamin D receptor. 1,25-Dihydroxyvitamin D3 caused significant dose-dependent growth inhibition of HT-29 cells at concentrations ranging from 10(-11) to 10(-6). The antiproliferative effect of Ro 25-6760 on HT-29 cells was also dose-dependent with cell counts on day 6, ranging from 98% of control at 10(-11) M to 14% of control at 10(-6) M. However, 1,25-dihydroxyvitamin D3 and Ro 25-6760 did not have any growth inhibitory effect on SW-620 at all concentrations. In mice with HT-29 tumor xenografts, administration of vitamin D at 0.1 and 0.2 microg/injection i.p. three times/week did not cause any significant tumor growth delay, whereas synthetic analogue Ro 25-6760, at both concentrations, caused a significant tumor growth inhibition in comparison with the control arm. In 30% of mice treated by R0 25-6760 the tumors disappeared on average after the second injection, and tumor growth did not resume after drug withdrawal. However, both 1,25-dihydroxyvitamin D3 or Ro 25-6760 had no growth inhibitory effect at all applied concentrations in mice with the SW-620 tumor xenografts. The mechanism for this impressive growth inhibition is not yet elucidated and warrants further investigation.

Animals↗
PubMed1996

Mast cell counts are not useful in the diagnosis of nonulcerative interstitial cystitis.

PURPOSE: Mast cell counts have been advocated as useful in the pathological diagnosis of interstitial cystitis. To determine the clinical significance of mucosal and detrusor muscle mast cells we quantified mast cells within the lamina propria and detrusor muscle in nonulcerative interstitial cystitis, and various inflammatory and neoplastic bladder diseases. MATERIALS AND METHODS: Mast cells from Giemsa stained sections were enumerated from 8 cases of clinically diagnosed nonulcerated interstitial cystitis and 32 control cases having inflammatory or neoplastic bladder disease. Cystectomy specimens from controls also included sections from normal (5) and inflamed transitional mucosa (4) distant from the invasive tumor. RESULTS: There was no significant difference in mast cell counts when considered absolutely or relative to the muscle-to-mucosa ratio in cases of nonulcerative interstitial cystitis and controls. CONCLUSIONS: Our findings indicate that mast cell counts are not useful in the evaluation of nonulcerative interstitial cystitis and do not represent a diagnostic criterion for inclusion or exclusion of the disease.

Adult↗
PubMed1994

Indolic compounds affect tryptophan binding to rat hepatic nuclei.

This study evaluates the effects of indolic or indole-related compounds on binding of L-tryptophan (saturable, stereospecific and of high affinity) to rat hepatic nuclei or nuclear envelopes. Addition of any one of many indolic or indole-related compounds, and particularly of 3-methylindole, does not inhibit in vitro binding of [3H]tryptophan to hepatic nuclear envelopes. However, when 3-methylindole (10(-10) to 10(-4) mol/L) is added in combination with unlabeled L-tryptophan (10(-4) mol/L), it diminishes the inhibitory effect of unlabeled L-tryptophan alone. Scatchard analysis of the binding affinities of in vitro [3H]tryptophan binding to hepatic nuclear envelopes using L-tryptophan in the absence or presence of 3-methylindole reveals similar dissociation constants (KD) under the two conditions, but the binding concentrations (Bmax) were greater in the combined group compared with that in the L-tryptophan alone group. Addition of 3-methylindole to liver before homogenization decreases specific [3H]tryptophan binding to nuclei compared with controls (without addition). L-Tryptophan tube-fed to rats with or without 3-methylindole administration increases in vitro hepatic protein synthesis compared with that of saline tube-fed controls. 3-Methylindole itself does not affect protein synthesis. Our report describes the effects of 3-methylindole on specific tryptophan binding to hepatic nuclear envelope receptor and discusses the possible implications thereof.

Animals↗
PubMed1993

Use of monoclonal antibodies MSN-1 and B72.3 in the prediction of the natural history of endometrial hyperplasia.

Forty patients, originally diagnosed as endometrial hyperplasia, were reviewed histopathologically and evaluated for immunohistochemical staining with antibodies directed against TAG-72 and MSN-1 antigens. All patients had follow-up endometrial biospies or hysterectomies from 1 to 13 years later. The extent of regression to normal of nonhyperplastic endometrium, persistence as any type of endometrial hyperplasia, or progression to endometrial adenocarcinoma was correlated with the histologic hyperplastic subtype and immunohistochemical staining. As expected, cases of complex or atypical hyperplasia more often progressed to carcinoma than cases of simple or no hyperplasia. Interestingly, MSN-1 positivity was more prevalent in cases of higher grades than lower grades of hyperplasia and was associated with the tendency to show persistent hyperplasia or progression to carcinoma. B72.3 positivity was uncommon in the hyperplastic endometrium and was not correlated with clinical regression or progression. Although the tendency for progression of endometrial hyperplasia to endometrial carcinoma is best judged histologically, MSN-1 may add prognostic information in subgroups of hyperplasia.

Adenocarcinoma↗
PubMed1992

Tryptophan binding to nuclei of rat brain.

Nuclei purified from whole rat brain specifically bind [3H]tryptophan ([3H]Trp) under in vitro conditions. Excess unlabeled Trp (10(-4) M) is an effective inhibitor of in vitro [3H]Trp binding to brain nuclei. Rats tube-fed L-tryptophan (Trp) (30 mg/100 g body wt) 30 min to 4 hr before killing revealed decreased specific binding of [3H]Trp to purified brain nuclei in vitro. By Scatchard analysis, the nuclei from whole brain appear to contain one binding site for [3H]Trp, and the KD is 263 nM. A number of Trp-related compounds, Trp metabolites, or other amino acids and their analogues were observed to compete for in vitro [3H]Trp binding to brain nuclei. The ability of Trp analogues, metabolites, and other cognate compounds to inhibit in vitro [3H]Trp binding to brain nuclei was evaluated and utilized to map the active site of Trp binding.

Animals↗
PubMed1992

Inhibitory effect of demoxepam on tryptophan binding to rat hepatic nuclei.

Since some patients with eosinophilia-myalgia syndrome ingested tryptophan along with benzodiazepines, we investigated whether demoxepam, the N-desalkylated compound of chlordiazepoxide, would influence the binding of tryptophan to hepatic nuclei. L-Tryptophan has been shown to bind (saturable, stereospecific, and of high affinity) to rat hepatic nuclei and nuclear envelopes. We report that demoxepam has an inhibitory effect on in vitro [3H]tryptophan binding to rat hepatic nuclei and has an apparent KD approximately 22 microM.

Algorithms↗
PubMed1992

Studies with compounds that compete with tryptophan binding to rat hepatic nuclei.

Tryptophan has been demonstrated to affect hepatic RNA and protein metabolism. Binding of tryptophan to nuclear envelope proteins has been demonstrated to be saturable, stereospecific, and of high affinity. The hepatic nuclear envelope tryptophan binding protein (glycoprotein) has been purified to apparent homogeneity using either concanavalin A-agarose or tryptophan-agarose. The receptor has an Mr of approximately 34,000, which is the same as that observed when [3H]tryptophan has been crosslinked to nuclear proteins. In this study, we investigated whether analogs, metabolites or related compounds of tryptophan as well as other amino acids may bind to rat hepatic nuclei using in vitro [3H]tryptophan binding assays. Our results indicate that compounds that compete with [3H]tryptophan binding to hepatic nuclei or nuclear envelopes contain the alpha-amino-propionic acid structure. Such compounds were 5-fluoro tryptophan, 7-aza tryptophan, 5-hydroxy tryptophan, alanine, phenylalanine, tyrosine, cysteine and cystine. It was of interest that, whereas tryptophan-methyl ester and tryptophan-ethyl ester competed, alpha-methyl tryptophan, N-formyl tryptophan, N-acetyl tryptophan, and N-methyl tryptophan did not compete with [3H]tryptophan binding to hepatic nuclei or nuclear envelopes. Nonetheless, only the in vivo administration of L-tryptophan was able to stimulate nucleocytoplasmic efflux of hepatic RNA and protein synthesis.

Amino Acids↗
PubMed1992

Effect of benzodiazepines on tryptophan binding to rat hepatic nuclei.

This study evaluates whether or not some of the benzodiazepines would influence the binding of L-tryptophan to rat hepatic nuclei or nuclear envelopes. Previous publications have indicated that binding of L-tryptophan to hepatic nuclear envelope proteins was saturable, stereospecific, and of high affinity. In this study, we investigated whether some of the benzodiazepines would influence L-tryptophan binding to rat hepatic nuclei or nuclear envelopes as assayed by in vitro L-(5-3H) tryptophan binding. Our results indicate that the addition of chlordiazepoxide, diazepam, prazepam, flurazepam, nordazepam, N-desalkylflurazepam, temazepam, oxazepam, lorazepam, or 4-chlorodiazepam has little influence on the L-(5-3H) tryptophan binding to hepatic nuclei in vitro. However, the addition of demoxepam, the N-desalkylated compound of chlordiazepoxide, caused marked competition with 3H-tryptophan binding to hepatic nuclei in vitro. When chlordiazepoxide (1 mg/100 g body weight) is administered intraperitoneally 20 min before killing, the isolated hepatic nuclei reveal decreased specific L-tryptophan binding compared to controls. Also, rats pretreated with chlordiazepoxide intraperitoneally before tube-feeding L-tryptophan revealed diminished tryptophan-induced hepatic nuclear RNA efflux and protein synthesis. Our results suggest that chlordiazepoxide, possibly by itself or through a metabolite, can act to affect hepatic nuclear binding of L-tryptophan and to inhibit the stimulatory effect of L-tryptophan on hepatic protein synthesis.

Animals↗