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Biomedical subjects

J Roth

Publications and source records attributed to J Roth.

At least 505 records · Page 28Linked to original sources

The evolutionary origins of intercellular communication and the Maginot Lines of the mind.

By extending the evolutionary age of the vertebrate hormones from the vertebrates to include the metazoans, we expand their phyletic distribution about 30-fold. By tracing these molecules into the unicellular range including both eukaryotes and prokaryotes, the distribution of these molecules becomes very wide indeed. While "universal" or "ubiquitous" is probably not yet warranted, their recognition as "cosmic" molecules rather than "parochial" molecules does seem appropriate. Interestingly, the breakdown of the barriers for the hormonal molecules between the vertebrates and the rest of the metazoans, between the metazoans and the unicellular organisms, between the eukaryotes and prokaryotes, or the eubacteria and archebacteria is concordant with findings in multiple other systems. For example, hemoglobin or myoglobin is present in higher plants, Protozoa, and insects. The photosynthetic proteins of higher plants have their homologues in the photosynthetic bacteria, and the heat shock proteins of eukaryotes have their equivalents in the prokaryotes as well.

Animals↗

Isolation and characterization of lon mutants in Salmonella typhimurium.

In this paper we report the isolation and characterization of lon mutants in Salmonella typhimurium. The mutants were isolated by using positive selection by chlorpromazine resistance. The physiological and biochemical properties of the lon mutants in S. typhimurium are very similar to those of Escherichia coli lon mutants. Mutants altered at this locus contain little or no activity of the ATP-dependent protease La and show a number of pleiotropic phenotypes, including increased production of capsular polysaccharides, increased sensitivity to UV light and other DNA-damaging agents, and a decreased ability to degrade abnormal proteins.

ATP-Dependent Proteases↗

Cationic colloidal gold--a new probe for the detection of anionic cell surface sites by electron microscopy.

Particles of colloidal gold were coated with poly-L-lysine to prepare cationic colloidal gold. Monodispersed colloidal gold with a particle diameter of 5, 8, or 15 nm and poly-L-lysine with a molecular weight of 350,000 or 1500-8000 were used. The resulting complexes were used to label red blood cell membranes. The labeling was sensitive to neuraminidase treatment or acid hydrolysis, demonstrating that cationic colloidal gold binds preferentially to anionic cell surface constituents. Cationic colloidal gold can be used at physiological pH values and ionic strength, as well as at low pH values, making it a flexible probe for detection of anionic cellular components.

Erythrocyte Membrane↗

Pattern of DNA increase in macronuclear anlagen of Tetrahymena.

By combining cytophotometry with autoradiography, five stages of macronuclear anlagen can be discriminated by their DNA content until the end of the first cell cycle after conjugation in Tetrahymena. DNA increases from 2C to about 32C. Each S-phase is followed by a non-synthetic period. Comparing the mean nuclear DNA content after and before each S-phase revealed that 16C anlagen contain significantly less DNA than twice the amount of 8C anlagen. This is unlike the situation in other S-phases during which the amount of DNA is precisely doubled. In the second cell cycle after conjugation some of the cells increase their macronuclear G2 DNA content beyond the 64C stage, while the majority show a mean G2 content of about 64C.

Animals↗

Glycocalyx heterogeneity of rat kidney urinary tubule: demonstration with a lectin-gold technique specific for sialic acid.

The distribution of sialic acid residues in rat kidney urinary tubule was investigated by light and electron microscopy with a lectin-gold technique. The application of the sialic acid specific Limax flavus lectin resulted in intense plasma membrane labeling of the epithelium of the entire proximal tubule and thin limbs of loop of Henle. In contrast, the plasma membrane of the epithelium lining the medullary portion of the thick ascending limb of Henle was not labeled. In the cortical portion, however, microvilli-bearing positive and smooth-surfaced negative cells were present. Moreover, all cells of the convoluted distal tubules were labeled along their plasma membrane. These data demonstrate the existence of a gross difference in glycocalyx composition between proximal tubules and thin limbs of loop of Henle on one hand and thick ascending limbs on the other. In addition, fine heterogeneity in glycocalyx composition between medullary and cortical portion of thick ascending limb exists. It is concluded that the differences in sialic acid content of the glycocalyx may be related to the functional diversity exhibited by these tubular regions.

Animals↗

The trans-tubular network of the hepatocyte Golgi apparatus is part of the secretory pathway.

We have recently demonstrated the presence of sialyltransferase and sialic acid in a trans-tubular network (TTN) continuous with trans Golgi apparatus cisternae of rat liver hepatocytes. Based on these findings, we concluded that this structure, which also exhibited thiamine pyrophosphatase and acid phosphatase activity, is an integral part of the Golgi apparatus and functions in sialylation. In the present study, by comparing the distribution of a major hepatocyte secretory product with that of sialyltransferase, we sought to determine whether the TTN is also part of the secretory pathway. Examination of adjacent serial thin sections labeled for albumin showed its presence throughout the TTN and simultaneously provided new details about the structural complexity of the TTN. Double-immunolabeling with protein A-gold allowed the direct demonstration of albumin throughout the sialyltransferase containing TTN. Additional double staining protocols (combination of preembedding enzyme cytochemistry with postembedding immunolabeling) revealed the presence of albumin in both the thiamine pyrophosphatase and acid phosphatase positive regions of the TTN. These data show that albumin, a nonglycosylated secretory protein, reaches the TTN where terminal glycosylation of glycoproteins occurs. Therefore, it appears that the TTN of rat hepatocytes which functions in terminal glycosylation is also part of the constitutive secretory pathway.

Albumins↗

Parametric imaging of experimentally simulated Wolff-Parkinson-White syndrome conduction abnormalities in dogs: a concise communication.

In order to test the diagnostic potential of phase analysis of radionuclide ventriculography (RNV) for localizing accessory bundles in Wolff-Parkinson-White (WPW) syndrome, 24 experimental runs were performed in three open chest instrumented dogs. After a baseline study, WPW syndrome was simulated by stimulation at seven different sites around the base of the ventricles, and RNV's were obtained. Subsequent data processing including Fourier transformation allowed the localization of the site of the first inward motion of the ventricles by an isophasic wave display. In sinus rhythm, the septum contracted first. During ectopic premature ventricular stimulation by triggering the atrial signal, the phase scan was altered only when the stimulus was applied earlier than 20 ms before the expected QRS complex during sinus rhythm. During stimulation with fixed frequency, only the left lateral positions of the premature stimulation were detected by phase analysis with a sensitivity of 86%. Neither the antero- or posteroseptal nor the right ventricular premature contraction pattern could be exactly localized.

Animals↗

Physical aspects of total body irradiation in Basel.

Total body irradiations have been performed on 112 patients at the University Hospital in Basel since 1979. Total body irradiations are effected in order to prepare patients with leukemia for bone marrow transplantation. The irradiation technique with 4 MV X-rays is described. The patients are treated without lung-shieldings. The dose-measurements show an acceptable homogeneity. The applied technique is very easy in comparison with other centers. A main point is making the patient's position as comfortable as possible. The accuracy of dose-application and dose-distribution is considered clinically acceptable.

Humans↗

Physical treatment planning of total body irradiation.

The treatment planning of total body irradiations shows partially other problems than conventional treatments. The data refer to long source-skin-distance and large fields, which are even larger than the patient. In most centres, it is aspired to a homogeneous dose distribution. But its importance is not known, at present. The radiobiology has to yield further answers to a lot of questions. This and the clinical results must help to decide, which technique is the best to eliminate leukemic cells and to avoid side effects as interstitial pneumonia.

Aging↗

Right ventricular function in patients with chronic obstructive pulmonary disease.

Simultaneous right heart catheterization and radionuclide ventriculography were performed in 27 patients with a wide range of chronic obstructive pulmonary disease. Central hemodynamics and radionuclide studies were done at rest and during exercise. In the resting state the right ventricular ejection fraction (RVEF) was in the normal range (43.3 +/- 6%). During exercise a significant (p less than 0.001) decrease of RVEF to 38.8 +/- 6.7% occurred. The pulmonary artery mean pressures were 19.9 +/- 3.8 at rest. During exercise a significant (p less than 0.001) increase to 41 +/- 9.8 mm Hg occurred. There was a linear relationship between pulmonary pressures and RVEF during exercise in patients with pulmonary artery pressures not exceeding 35 mm Hg. In patients with right ventricular end-diastolic wall thickness greater than or equal to 6 mm a curvilinear relationship between these parameters could be observed with a flattening of the curve at higher pressures (greater than 35 mm Hg) and lower ejection fractions (less than 35% RVEF). Radionuclide ventriculography cannot substitute for right heart catheterization. Echocardiography is useful for interpretation of right ventricular ejection fractions in advanced chronic obstructive pulmonary disease.

Aged↗

A randomized, prospective trial of adjuvant chemotherapy in adults with soft tissue sarcomas of the head and neck, breast, and trunk.

Since 1977, 31 patients were entered in a randomized, prospective study testing the efficacy of adjuvant chemotherapy after aggressive local treatment of high-grade sarcomas of the head, neck, breast, and trunk (excluding retroperitoneal sarcomas). All patients had complete resection of gross tumor and underwent postoperative radiotherapy (6000-6300 rads over 7-8 weeks). Seventeen patients received adjuvant chemotherapy consisting of doxorubicin (less than or equal to 550 mg/m2), cyclophosphamide (less than or equal to 5500 mg/m2), and methotrexate (less than or equal to 1000 mg/kg). Three-year actuarial disease-free survival in the chemotherapy arm was 77%, compared to 49% in the no-chemotherapy arm (P = 0.075). Three-year overall actuarial survivals in the two treatment arms, however, were 68% and 58%, respectively (P = 0.38). Considering only patients with tumors of the trunk (22 patients), 3-year actuarial disease-free survival in the chemotherapy arm was 92%, compared to 47% in the no-chemotherapy arm (P = 0.006). Actuarial 3-year overall survival in the chemotherapy arm was 82%, compared to 61% in the no-chemotherapy arm (P = 0.18). An additional 26 patients were treated in an identical fashion, but were not part of the randomized trial because of contraindications to chemotherapy, refusal to enter the randomized trial, or because they were treated before 1977 in a trial in which all patients received chemotherapy. Considering the entire group of 57 patients, follow-up ranged from 10 to 86 months (median, 35 months). Local control was achieved in 46 patients (81%); 3-year actuarial disease-free and overall survivals were 67% and 77%, respectively. A tendency toward improved disease-free survival was apparent among patients treated with chemotherapy (P = 0.018), but there was no statistically significant improvement in overall actuarial survival (P = 0.46). The subgroup of patients with sarcomas of the trunk (39 patients) demonstrated the greatest benefit from chemotherapy, with regard to disease-free survival (P less than or equal to 0.001). The most significant toxicity associated with chemotherapy was doxorubicin-induced cardiomyopathy, which resulted in clinically apparent congestive heart failure in five patients. Thus, the use of chemotherapy when combined with aggressive local measures appears to improve disease-free survival, but additional patients and longer follow-up are necessary to determine if improved overall survival will result.

Actuarial Analysis↗

Immunoprecipitation of insulin receptors from cultured human lymphocytes (IM-9 cells) by antibodies to pp60src.

The family of tyrosine-specific protein kinases includes proteins encoded by retroviral oncogenes as well as receptors for insulin and several growth factors. Antibodies to pp60src, the protein encoded by the src oncogene of Rous sarcoma virus (RSV), can specifically immunoprecipitate affinity-labeled insulin receptors from cultured human lymphocytes (IM-9 cells). This precipitation is specifically inhibited by the src gene product purified from RSV-transformed rat cells. These observations provide evidence that there is structural homology between the insulin receptors and pp60src.

Cross Reactions↗

Mott cells are plasma cells defective in immunoglobulin secretion.

Plasma cells containing intracellular inclusions of immunoglobulin (Russell bodies) are known as Mott cells, and are found in large numbers in lymphoid organs in autoimmune mice. Hybridoma technique was used to produce cell lines of this phenotype by fusing spleen cells from a NZB mouse with a nonproducing hybridoma cell line (Sp2/0-Ag14), allowing us to carry out studies of this cell type at the biochemical level. Ultrastructurally the inclusions were distended cisternae of rough endoplasmic reticulum, suggesting a block in the secretory pathway of the cells. Biosynthetic labeling studies confirmed that these cell lines have either a complete or partial block of secretion of immunoglobulin, possibly due to an abnormal light chain.

Animals↗