Showing papers by "Jewish Hospital published in 1985"

The small-subunit ribosomal RNA gene sequences from the hypotrichous ciliates Oxytricha nova and Stylonychia pustulata.

Abstract: We have determined the complete nucleotide sequence of the small-subunit ribosomal RNA genes for the ciliate protozoans Stylonychia pustulata and Oxytricha nova. The sequences are homologous and sufficiently similar that these organisms must be closely related. In a phylogeny inferred from comparisons of several eukaryotic small-subunit ribosomal RNAs, the divergence of the ciliates from the eukaryotic line of descent is seen to coincide with the radiation of the plants, the animals, and the fungi. This radiation is preceded by the divergence of the slime mold, Dictyostelium discoideum.

Steroid myopathy: incidence and detection in a population with asthma.

Abstract: Sixty steroid-treated patients with asthma were evaluated for the presence of muscle weakness by use of both manual muscle testing and the Cybex II isokinetic dynamometer. The patients were compared to age and sex-matched sedentary control subjects. Forty-eight percent of the patients (12/25) taking greater than or equal to 40 mg per day of prednisone had hip flexor strength greater than or equal to 2 SD below the mean of age and sex-matched control subjects by Cybex testing (CT). Sixty-four percent of the patients (16/25) taking greater than or equal to 40 mg per day of prednisone were found on manual muscle testing to have hip flexor weakness. Only one patient taking less than 30 mg per day of prednisone was found to have muscle weakness. Biochemical parameters, including CPK, aldolase, SGOT, LDH, and LDH isoenzymes were measured to assess the degree of steroid-induced muscle damage. They neither correlated with the degree of hip flexor weakness as measured by CT, nor did they discriminate between patients receiving small doses and large doses of steroids. Changes in urinary excretion of creatine did not help to confirm the diagnosis of steroid myopathy. Although CT provides an objective means of assessing muscle strength in these patients, at this time no definitive chemical test is available for the diagnosis of steroid myopathy.

Pituitary-gonadal function in Klinefelter syndrome before and during puberty.

Abstract: Serum concentrations of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol were determined at intervals before and during puberty in 40 individuals with Klinefelter syndrome (47,XXY karyotype), of whom 27 had been detected in neonatal cytogenetic screening programs. Prior to the appearance of secondary sexual changes, basal serum hormone concentrations and acute responses to stimulation with gonadotropin-releasing hormone and human chorionic gonadotropin were normal. The timing of the onset of clinical puberty was normal. Early pubertal boys showed initial testicular growth and normal serum testosterone levels, while serum follicle-stimulating hormone and estradiol concentrations were significantly elevated. By midpuberty, the Klinefelter subjects were uniformly hypergonadotropic and their testicular growth had ceased. Serum testosterone concentrations after age 15 remained in the low-normal adult range. Serum estradiol levels remained high, irrespective of the presence or absence of gynecomastia. Exaggerated responses to gonadotropin-releasing hormone are seen in pubertal subjects with elevated basal gonadotropin values.

Elevation of RNA coding for tyrosine hydroxylase in rat adrenal gland by reserpine treatment and exposure to cold.

Abstract: When rats are treated daily with reserpine or maintained at 4 degrees C, the level of a specific RNA coding for tyrosine hydroxylase is elevated in the adrenal gland. The increase in this specific RNA temporally precedes and is quantitatively equal to the increase in adrenal tyrosine hydroxylase enzyme activity elicited by these treatments. These results suggest that prolonged stress may lead to changes in the levels of specific RNA species in the adrenal gland.

Na channels in skeletal muscle concentrated near the neuromuscular junction

Abstract: Neuronal function depends crucially on the spatial segregation of specific membrane proteins, particularly the segregation associated with sites of synaptic contact. Understanding the factors governing this localization of proteins is a major goal of cellular neurobiology. A conspicuous example of synaptic specialization is the almost exclusive localization of vertebrate skeletal muscle acetylcholine (ACh) receptors to the subsynaptic membrane of the neuromuscular junction (for example, refs 1,2). The localization of other membrane proteins in skeletal muscle has been much less studied, but a knowledge of their distribution is crucial for understanding the factors governing regional specialization. We have explored the distribution in muscle of the voltage-gated Na channel responsible for the action potential using the loose patch-clamp technique, and have measured Na currents in 5-10 micron-diameter membrane patches as a function of distance from the end plate region of snake and rat muscle fibres. Here we report that the Na current density immediately adjacent to the endplate is 5-10-fold higher than at regions away from the endplate. The increased Na current density falls off rapidly with distance, reaching the background level 100-200 micron from the endplate. Although one might expect ACh receptors to be concentrated near the region of ACh release, such a concentration for Na channels, which propagate the impulse throughout the length of the cell, is surprising and suggests that factors similar to those responsible for concentrating ACh receptors at the endplate also operate to concentrate Na channels.

Immune function in chronic active Epstein-Barr virus infection

Abstract: The spectrum of illness attributed to Epstein-Barr virus (EBV) includes patients with symptoms persisting for more than 1 year without any other obvious underlying disease. High titers of antibodies to EBV, either IgG antiviral capsid antigen or anti-early antigen, can be demonstrated. In this study, 13 patients diagnosed as having chronic active EBV infection were examined to determine aspects of their immunologic status. Morphological examination and fluorescent antibody analysis revealed no abnormalities in the phenotypes of peripheral blood white cells present in these patients. Compared to those from healthy control individuals, mononuclear cells from the patients showed a markedly depressed ability to produce both interleukin-2 and interferon after stimulation with mitogen and a phorbol ester. Studies of natural killer (NK) cell activity revealed that unfractionated mononuclear cells from patients with chronic active EBV infection were significantly lower in killing activity compared to the control group. Fractionation procedures to enrich for large granular lymphocytes resulted in an increase in NK activity for all individuals, but killing activity still remained slightly lower in the patients than in the control group. The dysfunctions which were found in patients with chronic active EBV infection may reflect a primary defect in natural immune functions of the patients predisposing them to a chronic or intermittent clinical disease rather than a self-limiting illness. Alternatively, the abnormalities detected in these experiments may be a result of the viral infection itself.

31P spin-lattice relaxation times and resonance linewidths of rat tissue in vivo: dependence upon the static magnetic field strength.

Abstract: Phosphorus-31 NMR spin-lattice relaxation times and resonance linewidths of rat leg muscle, brain, and liver metabolites in vivo have been examined at 1.9-, 4.7-, and 8.5-T static magnetic field strengths. The resonance linewidths expressed in ppm that have been measured are independent of field strength. The spin-lattice relaxation times of muscle and brain phosphorus metabolites decrease linearly with increasing field strength while those of liver are constant over the range of static fields examined.

Adenocarcinoma of the rectum: Results of radiotherapy and resection, endocavitary irradiation, local excision, and preoperative clinical staging

Abstract: The management of rectal cancer in 102 patients at the Jewish Hospital of St. Louis is reviewed. Therapy combining external irradiation, endocavitary irradiation, local excision, and excisional operation has been used in the treatment of adenocarcinoma of the rectum. Pretreatment evaluation for tumor fixation, ulceration, palpable presacral lymph nodes, distance of tumor from dentate line, size of tumor, and histologic grades was used to assign patients to treatment groups. Local recurrence is <2 percent, and two-year tumor-free survival is approximately 87 percent in patients receiving 2000 R or 4500 R preoperatively. Pathologic downstaging of tumors was noted more frequently with 4500 R preoperative irradiation. Endocavitary irradiation appears adequate to treat only favorable lesions. Only tumor fixation and histologic grade of the tumor notably affected survival. A logical plan for choosing the appropriate method of treatment using combined modalities is proposed.

Regulation of macrophage lysosomal secretion by adenosine, adenosine phosphate esters, and related structural analogues of adenosine.

Abstract: Zymosan particle-stimulated beta-galactosidase secretion by mouse peritoneal macrophages was found to be inhibited by micromolar concentrations of adenosine, AMP, ADP, and ATP. Inhibition by all four agents was increased to approximately 80% by adding erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; 10 microM) an adenosine deaminase inhibitor, to the incubation medium. The inhibition of lysosomal enzyme secretion by ATP, ADP, and AMP was reversed by adding alpha, beta -methylene ADP (100 microM), a 5'-nucleotidase inhibitor, to the incubation medium. Inhibition by adenosine, however, was unaffected by alpha, beta -methylene ADP indicating that the inhibition by AMP, ADP, and ATP only occurred after they had been converted to adenosine by cell surface phosphohydrolases, including 5'-nucleotidase. Theophylline, a competitive antagonist of the binding of adenosine to plasma membrane adenosine receptors, failed to reverse the inhibitory effect of adenosine indicating the probable site of adenosine action to be intracellular. Other purine nucleosides, e.g., guanosine, and several purine and ribosemodified structural analogues of adenosine also inhibited zymosan-stimulated beta-galactosidase secretion, while xanthosine and certain pyrimidine nucleosides, e.g., thymidine, were inactive in this respect.

The Incidence of Neuropathy Following Upper Extremity Nerve Blocks

Abstract: This study was undertaken to determine the incidence of neuropathy following upper extremity nerve blocks when these blocks were administered by a group of private-practicing and experienced anesthesiologists. The block history of 854 consecutive patients was recorded and an overall incidence of post-block neuropathy of 0.36% was found, (i.e., three patients out of 854). The numbers were felt to be too small to draw a valid conclusion as to etiology. We concluded that the incidence of post-block neuritis is relatively low and the severity of the neuropathy is not great. Studies purporting to demonstrate significant differences in incidence of neuropathy related to technique or drugs must be based on very large populations. No such studies are currently in the literature.

Regional differences in the inductive activity of the mesenchyme of the embryonic mouse urogenital sinus

Abstract: Embryonic urogenital sinuses (UGS) of 16-day-old mice were divided into two or three zones (cranial half and caudal half; or cranial third, intermediate, and caudal thirds). Following tryptic digestion, these zones were separated into their mesenchymal (UGM) and epithelial (UGE) components. The cranial and caudal zones of the UGM were recombined separately with the different zones of the UGE or with adult mouse urinary bladder epithelium (BLE). Following four weeks of growth in syngeneic male hosts, tissue recombinants of cranial UGM + caudal UGE contained numerous prostatic ducts and urethral glands. Conversely, recombinants composed of caudal UGM + cranial UGE developed into fibromuscular tissue covered with urethral epithelium and did not contain prostate, but occasionally contained urethral glands. Urethral glands were usually present in grafts of cranial UGM + cranial UGE or in grafts of the intact intermediate third of the UGS. In heterotypic recombinants of the UGM + adult BLE, prostatic glands were induced only when cranial UGM was utilized. Urethral glands were not observed in tissue recombinants prepared with adult BLE. These data suggest that regional differences in mesenchymal inductive ability and epithelial responsiveness play a role in the harmonious morphogenesis of the male lower genitourinary tract.

Primary and Secondary Transport of Cations in Bacteria

Abstract: Bacterial physiology makes sense in the chemiosmotic framework, but it does not encourage fundamentalism. It is now well established that bacteria transport many sugars, amino acids, and other nutrients with the aid of secondary porters; and that the electrochemical potential of protons across the plasma membrane provides the driving force, just as Mitchell envisaged (Reviews: Mitchellis2 and Harold3). But the activities of these porters are supplemented by a variety of primary transport systems energized by ATP and by other phosphoryl donors, and organisms differ from one another in their complement of transport systems. The movements of K+ and Na+ ions illustrate the interplay between the primary and secondary modes of energy-linked transport. This essay is concerned with the fermentative bacterium Streptococcus faecalis. Streptococci lack respiratory chains and anaerobic redox pathways, relying on glycolysis or arginine fermentation for the production of ATP. Like other bacteria (indeed, living cells in general), streptococci accumulate K+ ions and extrude both N a + and protons. The cytoplasmic K+ level is typically 500 m M or more though the external one may be as low as 50 p M , giving a concentration gradient of lo4. The usual growth media contain 100-200 m M Na+, but the cytoplasmic N a + level is 1 m M or less. The cytoplasmic pH, 7.5 to 8, is normally at least one unit more alkaline than that of the medium, and the membrane potential is of the order of -120 mV (interior negative). A little reflection will show that a t least two of the cations involved must be transported actively, and we seek to discover both how and why. We still do not fully understand how the free energy represented by the ATP/ADP couple is used for ion transport and have much to learn about the functional purposes of this energy expenditure. However, we think that we have now identified the main catalytic systems and characterized them in terms of their ion fluxes and energy inputs. With the players recognizable, the plot seems a little less obscure.

Human keratinocytes that have not terminally differentiated synthesize laminin and fibronectin but deposit only fibronectin in the pericellular matrix.

Abstract: Fibronectin and laminin production by human keratinocytes cultured in serum-free, low-calcium medium without a fibroblast feeder layer were examined by several techniques. By indirect immunofluorescence, fibronectin but not laminin appeared as short radial fibrils between the cells and the substratum, and in the pericellular matrix. Synthesis of fibronectin and laminin by 7-day keratinocyte cultures was determined by 18 hr 35S-methionine metabolic labeling followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. Fibronectin accounted for 2.9% of total synthesized protein, 26.5% of fluid phase protein secretion, and 4.3% of deposited ECM protein. In contrast, only 0.1% of the total synthesized protein was laminin, little (6.3%) of this product was secreted, and none of this product was deposited in the ECM. Our results indicate that human keratinocytes under culture conditions that prevent terminal differentiation in vitro can synthesize, secrete, and deposit fibronectin in the extracellular matrix. Although these cells synthesize laminin, they secrete very little and deposit no detectable laminin in the matrix under these culture conditions. From these data we believe that fibronectin may play an important role in the interaction of epidermal cells with connective tissue matrix during wound healing or morphogenesis in in vivo situations in which the epidermis is not terminally differentiated.

Heterogeneity of breast carcinomas determined by flow cytometric analysis.

Abstract: Eight cases of primary breast carcinoma were studied for evidence of heterogeneity by flow cytometry using propidium iodide staining of DNA. Tumors ranged from 2.5 to 8.0 cm in greatest dimension, mean 4.2 cm. Five to 11 samples, determined by tumor size, were analyzed from each primary tumor in addition to 4 axillary lymph nodal metastases from 3 of the 8 cases. The presence of carcinoma was demonstrated histologically in each flow cytometric sample. Three of the carcinomas showed only diploid DNA content. Three showed the same single hyperdiploid population in each sample. Two carcinomas (2.5 and 3.5 cm) were heterogeneous and demonstrated 2 or 3 hyperdiploid populations. The 2 or 3 distinct hyperdiploid populations were present singly or sometimes in combination in one sample. Five of the 11 samples from 1 of the heterogeneous tumors and its axillary metastasis contained a single diploid population. Therefore, flow cytometric analysis of a single sample from a breast carcinoma may not be representative of the entire tumor. The study of multiple samples of breast carcinomas by flow cytometry is necessary for full characterization of the tumors.

Failure of sulfites to produce clinical responses in patients with systemic mastocytosis or recurrent anaphylaxis: results of a single-blind study.

Abstract: Although sulfite sensitivity can precipitate asthma in a subpopulation of subjects with asthma, its role in precipitating anaphylaxis or as a nonspecific mast cell degranulator in systemic mastocytosis has not been examined. To evaluate critically the importance of sulfites in these diseases, eight patients with systemic mastocytosis and 25 patients with unexplained, recurrent anaphylaxis were challenged in a single-blind fashion; sodium bisulfite in capsules was administered in increasing doses of 1, 5, 10, 25, 50, 100, and 200 mg every 30 minutes. On separate occasions a liquid suspension of 200 mg of sodium bisulfite was administered to one patient with systemic mastocytosis and nine patients with anaphylaxis. Vital signs, pulmonary function tests, plasma histamine levels, and clinical reactions were monitored. There were no observable responses in either the mastocytosis group or in 23 of 25 patients in the anaphylaxis group. Two patients in the anaphylaxis group with initial positive challenges had similar symptoms on subsequent placebo challenge. One subject with asthma and with a history suggestive of sulfite sensitivity responded to oral challenge with 5 mg of sodium bisulfite and 100 μg of sodium bisulfite intradermally with a dramatic reduction in FEV, requiring treatment with bronchodilators. A comparison of baseline plasma histamine levels with those obtained after the sulfite challenge procedure in each category demonstrated a significant rise ( p