Are we rescuers... or victims?
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Biomedical subjects
Publications and source records attributed to I Lee.
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In the growing chick a marked stimulation in soluble and mature arterial elastin synthesis occurs 2 and 5 weeks after hatching. Measurement of [3H]valine and [3H]proline incorporation into arterial soluble protein during this period indicated that most of the label is found in a 70 000 dalton protein subunit. The labeled soluble subunit had the characteristics of native soluble elastin or tropoelastin. During the period in which the greatest percentage increase in mature elastin occurs, the highest specific activities of soluble [3H]valine-labeled protein were observed. These changes were striking and suggest a developmental period for the growing chick in which factors related to elastin metabolism may be more easily studied.
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A patient with syphilitic glomerulonephritis had a renal biopsy and was treated for secondary syphilis. Light, electron, and immunofluorescence microscopic studies revealed an acute proliferative glomerulonephritis with subepithelial, intramembranous, and subendothelial immune complex deposits containing IgG, IgA, IgM, C4, and C3. Similar local deposits containing predominantly IgM were noted in areas of mesangial proliferation. Indirect fluorescent antibody studies employing rabbit treponemal antibody and sheep antirabbit globulin conjugate revealed the presence of treponemal antigen in the glomerular deposits. This finding provides strong evidence for the immunopathogenesis of the glomerular lesion as well as a causal link with Treponema pallidum.
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Thirty-five pulmonary carcinomas were studied retrospectively with monoclonal antibody (MCA) 44-3A6 raised against a human adenocarcinoma cell line. The antibody was applied to cytologic smears of bronchial brushings originally stained with the Papanicolau method, and to conventional tissue sections. Ten of 12 adenocarcinomas (ADC) immunostained strongly in sections and smears, as did five of seven large-cell "undifferentiated" carcinomas (LCUC). Eight neuroendocrine carcinomas (NEC) and eight squamous-cell carcinomas (SCC) were negative, except for rare weakly positive foci. We conclude that MCA 44-3A6 can be effectively applied on cytologic smears, and that it could be valuable in the precise classification of pulmonary carcinomas. The immunoreactivity of the ADC and SCC was predictable. Positive immunostaining in some LCUC confirms that these constitute a heterogeneus tumor class that includes cases that are phenotypically ADC despite the absence of obvious glands. Occasional immunostaining in NEC suggests focal exocrine differentiation as previously noted by electron microscopy.
Positron emission tomography, single photon emission computed tomography and planar projection imaging of radioactive tracers have long been in use for detecting and diagnosing disease in human subjects. More recently, advanced versions of these same technologies have begun to be used across the breadth of modern biomedical research to study non-invasively small laboratory animals in a myriad of experimental settings. In this report, we describe some of the new instruments and techniques that make these measurements possible and illustrate, with a few examples, the potential power of these methods in modern biomedical research.
Provision of wartime medical services is influenced by the psychological as well as the immediate physical injuries caused by war. But the psychological trauma of war is much less clearly understood than direct physical injury. The Second International Conference on Wartime Medical Services concentrated on these broader, less tangible effects of war, particularly in children. UNICEF estimates that 80% of the direct and indirect victims of military action are children and women. Other papers at the conference included reports on Israeli parents' fears for their children, combat stress reactions in Israeli soldiers, the physical and psychological responses of 35 Iranian-held American hostages and of Finnish veterans of the Finnish/Soviet war (1941-44), the nature of injuries to Palestinians in the Occupied Territories, and injuries from chemical attack in Iran and medical responses to these.
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A refined model has been developed for the folding of 16S rRNA in the 30S subunit, based on additional constraints obtained from new experimental approaches. One set of constraints comes from hydroxyl radical footprinting of each of the individual 30S ribosomal proteins, using free Fe(2+)-EDTA complex. A second approach uses localized hydroxyl radical cleavage from a single Fe2+ tethered to unique positions on the surface of single proteins in the 30S subunit. This has been carried out for one position on the surface of protein S4, two on S17, and three on S5. Nucleotides in 16S rRNA that are essential for P-site tRNA binding were identified by a modification interference strategy. Ribosomal subunits were partially inactivated by chemical modification at a low level. Active, partially modified subunits were separated from inactive ones by binding 3'-biotinderivatized tRNA to the 30S subunits and captured with streptavidin beads. Essential bases are those that are unmodified in the active population but modified in the total population. The four essential bases, G926, 2mG966, G1338, and G1401 are a subset of those that are protected from modification by P-site tRNA. They are all located in the cleft of our 30S subunit model. The rRNA neighborhood of the acceptor end of tRNA was probed by hydroxyl radical probing from Fe2+ tethered to the 5' end of tRNA via an EDTA linker. Cleavage was detected in domains IV, V, and VI of 23S rRNA, but not in 5S or 16S rRNA. The sites were all found to be near bases that were protected from modification by the CCA end of tRNA in earlier experiments, except for a set of E-site cleavages in domain IV and a set of A-site cleavages in the alpha-sarcin loop of domain VI. In vitro genetics was used to demonstrate a base-pairing interaction between tRNA and 23S rRNA. Mutations were introduced at positions C74 and C75 of tRNA and positions 2252 and 2253 of 23S rRNA. Interaction of the CCA end of tRNA with mutant ribosomes was tested using chemical probing in conjunction with allele-specific primer extension. The interaction occurred only when there was a Watson-Crick pairing relationship between positions 74 of tRNA and 2252 of 23S rRNA. Using a novel chimeric in vitro reconstitution method, it was shown that the peptidyl transferase reaction depends on this same Watson-Crick base pair.
Eighteen paragangliomas of the head and neck (11 carotid body tumors, four glomus tympanicum tumors, three glomus jugulare tumors) were studied retrospectively. Tissue from each of these tumors was immunostained for the presence of serotonin, a variety of neuropeptide hormones, and the enzyme neuron-specific enolase (NSE). Seven tumors were studied by electron microscopy. The clinical and laboratory records were reviewed for evidence of endocrine activity or metabolic imbalance. All tumors displayed diffuse and intense immunostaining for NSE. In addition, a wide variety of hormonal substances could be identified. Those most frequently demonstrated were serotonin and leu-enkephalin. Ten of the 11 carotid body tumors demonstrated immunoreactivity for multiple hormones. By electron microscopy all tumors contained a heterogeneous population of membrane-bound neurosecretory granules. None of these tumors was associated with a clinically apparent endocrine syndrome. We conclude that paragangliomas of the head and neck are neuroendocrine tumors that are capable of synthesizing a variety of hormonal substances. These hormonal substances rarely elicit a clinically apparent endocrine or metabolic imbalance. All of the tumors demonstrated immunostaining for NSE. Future studies on serum levels of NSE may provide useful diagnostic and follow-up data.
Fifty-five cases representing a spectrum of disease states of the human liver and 10 normal liver controls were examined for the presence of the ras oncogene product p21. Conventional formalin-fixed, paraffin-embedded sections were immunostained by the avidin-biotin complex method with the broadly reactive ras p21 monoclonal antibody (Mab) RAP-5. The specificity of the reactions was confirmed by immunostaining selected samples with Mab Y13-259. In the normal liver, virtually no hepatocytic immunostaining was noted. Variable, often extensive, and convincing immunoreactions were noted in diverse forms of hepatitis, cirrhosis, and allograft rejection; the strongest immunostaining was found in samples of focal nodular hyperplasia. Hepatic adenomas and hepatocellular carcinomas showed unevenly distributed, moderate to weak reactions or no reaction at all; cholangiocarcinomas did not immunostain. In reactive but non-transformed liver cell populations, enhanced p21 ras reactions seemed to correlate with the severity of the injury and the intensity of the proliferative response. The uneven and comparatively weak ras p21 reactions noted in adenomas and carcinomas suggest that this oncogene product may be involved only transitorily in their transformation processes and possibly may not be involved in certain variants thereof.