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Biomedical subjects

R Weil

Publications and source records attributed to R Weil.

At least 91 records · Page 5Linked to original sources
PubMed1984

Nature and origin of the RNA associated with simian virus 40 large tumor antigen.

Simian virus 40 (SV40) large tumor (T) antigen isolated from mammalian cells undergoing lytic or transforming infection is associated with small RNA fragments ("T-antigen RNA") that are protected from nuclease digestion. The rather high complexity of the ribonuclease T1 fingerprints of T-antigen RNA suggested that it is mainly derived from cellular heterogeneous nuclear RNAs. In the present study, 5'-32P-labeled T-antigen RNA was hybridized to monkey, mouse, and human Alu and SV40 DNA, and the nucleotide sequence of 37 T1 oligonucleotides was determined. The results suggest that the bulk of T-antigen RNA is derived from noncoding, double-stranded, ordered regions of cellular heterogeneous nuclear RNAs that exhibit sequence homologies with interspersed repetitive elements of the cellular genome. The possible biological implications of these results are discussed.

Animals↗
PubMed1984

Clinical evaluation of Tc-99m N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate as a replacement for I-131 hippurate: concise communication.

A clinical comparison of Tc-99m N,N'-bis( mercaptoacetyl )-2,3- diaminopropanoate (Component A) (Tc-99m CO2-DADS-A) and I-131 hippurate was conducted in a series of five normal volunteers and 18 patients. Each subject was studied in one session with Tc-99m CO2-DADS-A and I-131-hippurate; digital and analog images were recorded for 30 min and after voiding. In the normal volunteers, digital images with Tc-99m CO2-DADS-A gave a kidney-to-background ratio at 3 min that was greater relative to I-131 hippurate, a leading-edge parenchymal transit time that was similar to I-131 hippurate, and a percent injected dose in the urine at 30 min that was slightly less than I-131 hippurate (p less than 0.05). In patients (serum creatinine 1.0 to 14.3 mg/dl), decreasing renal function impaired excretion of Tc-99m CO2-DADS-A more than that of I-131 hippurate (p less than 0.01). In analog images, Tc-99m CO2-DADS-A always gave superior spatial resolution. No evidence of hepatobiliary excretion was detected with either radiopharmaceutical. We conclude that Tc-99m CO2-DADS-A and similar compounds should be pursued as possible replacements for I-131 hippurate.

Alanine↗
PubMed1984

The anatomy of parathyroid hyperplasia.

Parathyroid hyperplasia aids the surgeon in studying parathyroid anatomy for several reasons: (a) Nature magnifies the glands in hyperplasia; (b) there is a strong clinical imperative to find all glands; (c) histologic controls help guide the dissections; and (d) postoperative clinical and laboratory responses help determine the presence of supernumerary glands. In this study of parathyroid hyperplasia we found four glands in each of 34 patients (136 glands total--37 operations). Six patients (18%) had parathyroid glands totally covered by thyroid tissue, five patients (15%) had mediastinal glands, one patient (3%) had a retroesophageal gland, and one (3%) had a "kissing pair." In addition, after four-gland parathyroidectomy, three patients gave evidence of functioning supernumerary glands (9%). Abnormalities in parathyroid anatomy occurred in almost half (47%) of these patients with parathyroid hyperplasia.

Adolescent↗
PubMed1983

Cardiothoracic emergencies associated with subclavian hemodialysis catheters.

Three adults have had life-threatening perforations of the vena cava or right atrium associated with the use of subclavian hemodialysis catheters. Subclavian hemodialysis catheters should be meticulously positioned in the superior vena-caval lumen so the tip does not tent the vena-caval wall. If a patient with a subclavian hemodialysis catheter experiences unexplained and refractory hypotension, especially during hemodialysis, cardiac or vena-caval perforation should be suspected.

Adolescent↗
PubMed1983

Sequential stimulation of cellular RNA synthesis in polyoma-infected mouse kidney cell cultures.

Lytic infection with polyoma virus leads in Go-arrested primary mouse kidney cell cultures to a mitotic host response. In the present work we focused our attention on cellular RNA synthesis shortly after onset of polyoma T-antigen synthesis. Onset of polyoma-induced stimulation of 45S pre-rRNA synthesis was determined by hybridization of total cellular RNA with a plasmid (pMrSalB) containing the 5'-end of the mouse ribosomal gene and of the other cellular RNA species by standard biochemical analysis of cellular fractions. The results showed that polyoma-induced stimulation of cellular hnRNA (hnRNP) synthesis, the earliest presently known host cell reaction, preceded onset of stimulated 45S pre-rRNA synthesis and that the latter was paralleled by polyoma-induced stimulation of 5S RNA, tRNA and overall protein synthesis. The polyoma-induced mitotic response is similar to that triggered by simian virus 40 and by certain nonviral mitogens.

Animals↗
PubMed1983

Causes of death after kidney transplantation.

During the five-year period September 1974 through August 1979, two hundred nine consecutive patients received their first kidney transplant in Denver. During 2.5 to 7.5 years of follow-up, 54 patients (26%) died. Infection was the leading cause of death during all intervals and was responsible for 22 (41%) of the 54 deaths. Pneumonia was primarily responsible for 14 of the 22 deaths from infection. The other causes of death were cardiovascular problems in 11 patients (20%), suicide in eight patients (15%), gastrointestinal (GI) tract problems in seven patients (13%), malignant neoplasms in two patients (4%), and miscellaneous problems in four patients (7%). Twenty-six (48%) of the 54 deaths occurred more than one year after primary transplantation; 12 of these 26 patients had already returned to chronic hemodialysis. To minimize mortality after transplantation, patients and their physicians must remain alert to the ongoing risks to which these patients are exposed, including the risks of sudden death from infection, myocardial infarction, pulmonary embolus, suicide, or GI tract perforation.

Adult↗
PubMed1983

Characterization of the surface proteins of SV40-transformed mouse and human cells: absence of SV40-specific proteins.

The proteins of a number of SV40- and spontaneously transformed mouse and human cell lines were compared in an effort to identify a surface protein which would correspond to the SV40 tumor-specific transplantation antigen (TSTA). Analysis of the one- and two-dimensional electrophoretic patterns of 35S-methionine-labelled total proteins and 125I-labelled surface proteins of several of these cell lines failed to reveal the presence of proteins specific to transformation by SV40. Antisera were prepared against SV40- and spontaneously transformed mouse cells in syngeneic mice. In serological assays, these antisera reacted with surface antigens common to both SV40- and spontaneously transformed mouse cell lines. Electrophoretic analysis of the 125I-surface-labelled proteins which these antisera immunoprecipitated from extracts of SV40- and spontaneously transformed mouse and human cells identified a set of common surface proteins with apparent molecular weights of 15, 46, 50, 72, 77, 105, 150 and 230kdal. No SV40-specific surface proteins were detected. Two of the transformed cell surface proteins (105 and 150kdal) were present as well in membrane fractions of 35S-methionine-labelled primary mouse kidney cultures. The proteins of the primary cultures could not be iodinated by lactoperoxidase suggesting that these proteins were present at a "cryptic" location at the surface of normal cells. We were not able to obtain serological or immunochemical evidence for the presence of SV40 large T-antigen at the surface of any of the SV40-transformed cell lines tested using either hamster anti-SV40 tumor sera, a rabbit antiserum against SDS-denatured gel-purified large T-antigen or antisera against SV40-transformed mouse cells. In conjunction with the report that large T-antigen released from disrupted SV40-transformed cells will bind to cell surfaces (Lange-Mutschler and Henning, 1982), we consider the possibility that the specific rejection of SV40-induced tumors by sensitized animals is the result of immunological reactions against both common transformation-related surface antigens and SV40 T-antigen from disrupted cells that has bound to the surface of other tumor cells.

Animals↗
PubMed1983

Serum-induced stimulation of nucleoplasmic and nucleolar transcription in mouse 3T3 fibroblasts revisited.

Transition of 3T3 mouse fibroblasts from a quiescent to a growing state was induced by the addition of 10% fresh bovine serum to the culture medium. The number of DNA-synthesizing cells began to increase 10-11 h after the addition of serum and reached a maximum of 70-80% around 24 h. In quiescent cells, maintained in 0.5% serum, residual RNA synthesis represented mainly nucleoplasmic transcription (hnRNA, 5-S RNA and tRNA). Synthesis of tRNA was 2-3-fold increased by 1-2 h after addition of serum; however, a significant stimulation of hnRNA, 5-S RNA and 45-S pre-rRNA synthesis could only be observed around 4h. The experimental data also revealed a close temporal relationship between the onset of serum-stimulated hnRNA and overall protein synthesis. Determined colorimetrically, the cellular RNA and protein content began to increase by 4-5 h and had doubled by 24 h. Virtually the same results on RNA and protein synthesis were obtained when the experiments were performed in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. From our results we concluded that serum-stimulated overall RNA and protein synthesis preceded by several hours serum-induced S phase and was independent of DNA replication.

Animals↗
PubMed1983

Polyoma-induced stimulation of nucleoplasmic transcription is paralleled by development of resistance against actinomycin D.

Polyoma virus induced in quiescent, Go-arrested mouse kidney cells a lytic infection. Synthesis of the polyoma T-antigens began 7-8 h after infection and was followed by a mitotic reaction of the host cell comprising stimulated synthesis and accumulation of cellular (mainly ribosomal) RNA and protein and duplication of the host cell chromatin (S-phase). In the present work we focused attention on nucleoplasmic transcription, i.e. synthesis of hnRNA, 5S RNA and tRNA. To inhibit selectively nucleolar transcription we used low concentrations of actinomycin D (act. D). Synthesis of 45S precursor- ribosomal RNA in mock- and polyoma-infected mouse kidney cells was completely blocked by 0.05 micrograms/ml act.D within 2 h. In mock-infected cells also nucleoplasmic transcription was rather sensitive against 0.05 micrograms/ml act.D. Polyoma- induced stimulation of nucleoplasmic transcription began around 12 h and was paralleled by the development of resistance against act.D. Resistance of nucleoplasmic transcription in virus-infected cells was thus similar to that observed by others in uninfected, proliferating mammalian cells. The possible biological implications of these results are discussed.

Animals↗
PubMed1982

The relation between polyoma T-antigen and increased 5S RNA synthesis in cell-free extracts from polyoma-infected mouse kidney cell cultures.

In polyoma-infected mouse kidney cell cultures 5S RNA synthesis began to increase around 16 h, i.e. 7-9 h after the onset of polyoma T-antigen synthesis. The rate of polyoma-induced 5S RNA synthesis reached a maximum plateau around 25 h when it was 1.8-2.0 times higher than in mock-infected parallel cultures. Stimulation of 5S RNA synthesis in vivo thus coincided in time with the increase in total cellular RNA and protein. Cell-free extracts (S100) prepared at 15 h from mock-(S100-M) or polyoma-infected (S100-Py) mouse kidney cell cultures were indistinguishable with respect to protein concentration and 5S RNA synthesis, using a cloned somatic Xenopus borealis 5S gene as template. S100-Py extracted 25 h after infection contained 30% more protein and synthesized 1.5-2.0 times more 5S RNA than S100-M. Complete removal of the polyoma T-antigens from S100-Py by 3 cycles of immunoprecipitation with hamster anti-T serum remained without effect on stimulated 5S RNA synthesis. However, a linear relationship between 5S RNA synthesis and protein concentration of S100-M and S100-Py was observed.

Animals↗
PubMed1982

Inactivation of interferons: halomethyl ketone derivatives of phenylalanine as affinity labels.

Antiviral activity of rabbit and mouse fibroblast interferons was irreversibly destroyed by treatment with halomethyl ketone derivatives of phenylalanine but not by treatment with a halomethyl ketone derivative of lysine. The inactivation reaction was pH dependent, suggesting the involvement of an amino acid residue ionizing in the region of pH 7. Tryptophan and phenylalanine, known ligands of interferons, protected rabbit interferon substantially against inactivation by the chloromethyl ketone derivative of N-tosylphenylalanine. Mixed bovine brain gangliosides protected rabbit and mouse interferons against inactivation by this reagent. Although halomethyl ketone derivatives of phenylalanine were originally designed and used for affinity labeling of the active site of chymotrypsin and similar enzymes, no evidence was found for a chymotrypsin-like activity of interferons. It is proposed that halomethyl ketone derivatives of phenylalanine inactivate interferon by an affinity labeling mechanism, first binding to a hydrophobic binding site and then reacting irreversibly with a nearby nucleophilic amino acid residue, which appears to be a histidine. This conclusion implies that a hydrophobic site on interferons is necessary for their antiviral activity.

Affinity Labels↗
PubMed1982

Simian virus 40 large tumor antigen: a "RNA binding protein"?

Simian virus 40 large tumor antigen was isolated by immunoaffinity chromatography from monkey or mouse cell cultures undergoing lytic or transforming infection. RNase-treated gel-purified large tumor antigen, on hydrolysis with alkali, gave about equimolar amounts of AMP, GMP, CMP, and UMP. Furthermore, RNA fragments of approximately 45 nucleotides could be isolated from large tumor antigen purified by the same procedure. Mapping of the T1 oligonucleotides showed a high complexity, as indicated by the presence of unique sequences of 15-30 nucleotides and of poly(A). This is compatible with the hypothesis that these RNA fragments are derived from cellular pre-mRNAs or mRNAs. Our results suggest that Simian virus 40 large tumor antigen is a RNA-binding protein and might possibly be involved in regulation of synthesis, maturation, or translation of cellular mRNAs.

Antigens, Neoplasm↗
PubMed1982

Clinical comparison of Tc-99m N,N'-bis(mercaptoacetamido)ethylenediamine and [131I]ortho-iodohippurate for evaluation of renal tubular function: concise communication.

Recent experiments in normal animals have shown that Tc-99m N,N'-bis(mercaptoacetamido)ethylenediamine (Tc-99m DADS) is a potential technetium-99m-labeled replacement for [131I]ortho-iodohippurate(I-131 Hipp). We compared the two agents in eleven patients with renal transplants (serum creatinine range: 0.9--5.7 mg/dl). Digital and analog images were recorded for 30 min and after voiding. The results indicate that the relative extraction efficiency index of Tc-99m DADS is 76% +/- 3 (mean +/- s.e.m.), that the leading-edge parenchymal transit time of Tc-99m DADS is 137% +/- 6, and that the percentage of injected Tc-99m DADS in the bladder at 30 min is 25% +/- 4 of that of I-131 Hipp (all p less than 0.05). Forty percent of patients showed some hepatobiliary excretion of Tc-99m DADS. We conclude that the biologic properties of Tc-99m DADS are inferior to those of I-131 Hipp and that analogs of Tc-99m DADS should be evaluated in an attempt to find a more suitable technetium-99m-labeled replacement for I-131 Hipp.

Animals↗
PubMed1981

[In vitro dentinogenesis of mice fetuses tooth germs in the presence of fluoride. Morphological nad historical observations].

Observations show that fluoride alters dentinogenesis in vitro. Morphological and cellular alterations are greater when the tooth germs are young and/or when the time of incubation is longer and the dose of fluoride higher. In the predentine, the stainability of proteoglycans is partially reduced. The persistence of alcianophilic zones far from the site of secretion indicates some delay of the process of matricial maturation.

Animals↗
PubMed1981

Calcification in end-stage kidneys.

This study was carried out to determine the frequency and to quantitate the severity calcium-phosphate deposits in end-stage kidneys. In 57 of 59 end-stage kidneys obtained from patients with a variety of different renal diseases, calcium levels were greater than 2 standard deviations (SD) above control values. The mean calcium concentration was 157 +/- 24 mmol/kg dry defatted tissue in the end-stage kidneys as compared to 17 +/- 1 mmol/kg in the control kidneys. Histologically, calcium was deposited in the cortical tubular cells, basement membranes and interstitium. It would appear that calcification occurred during the course of renal failure rather thant terminally in that the kidney calcium concentration bore no relationship to the calcium X phosphate product, and the calcium concentration in the kidneys of uremic patients undergoing dialysis (144 +/- 23 mmol/kg) was no greater than that found in uremic patients not undergoing dialysis (188 +/- 62 mmol/kg). It is suggested that calcification may damage the diseased kidney accelerating the rate of renal functional deterioration.

Adolescent↗
PubMed1981

99mTc-DTPA renal studies for acute tubular necrosis: specificity of dissociation between perfusion and clearance.

In order to evaluate the usefulness of radionuclide renal studies in differentiating acute tubular necrosis from other causes of decreased renal clearance (e.g., rejection) in renal transplant patients, we assumed that acute tubular necrosis would be common during the first 4 days after cadaveric transplantation (group 1) and uncommon 3 weeks or longer after transplantation (group 2). There were 38 renal studies in 34 patients in group 1 and 62 studies in 27 patients in group 2. Each renal study consisted of both a technetium-99m-DTPA and an iodine-131-hippuran study. Perfusion, clearance, and transit time in the 99mTc-DTPA study, and clearance and transit time in the 131I-hippuran study were visually graded on a 5 point scale without knowledge of the time of study or clinical diagnosis. There were 19 studies in group 1 and 25 studies in group 2 with clearance decreased two or more gradations. Eleven 99mTc-DTPA studies had perfusion 2 or more gradations better than clearance; all 11 were in group 1 (p less than 0.01). Other dissociations within the 99mTc-DTPA and 131I-hippuran studies, or between them, did not distinguish the two groups. Data support the hypothesis that decreased clearance with relatively well preserved perfusion in 99mTc-DTPA studies is common in acute tubular necrosis and uncommon in other causes of decreased renal clearance.

Acute Kidney Injury↗