Biomedical subjects
J Frank
Publications and source records attributed to J Frank.
The role of pyrrolo-quinoline semiquinone forms in the mechanism of action of methanol dehydrogenase.
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Immunological studies of male homosexuals with the prodrome of the acquired immunodeficiency syndrome (AIDS).
Homosexual patients who mainly had the prodrome of the syndrome of opportunistic infection and Kaposi's sarcoma were studied immunologically. Patients showed diminished delayed hypersensitivity to recall antigens, diminished lymphocyte blastogenic responses, a suppressor cell for lymphocyte proliferative responses, low helper cells and an inverted helper:suppressor ratio. The patients had low levels of adherent monocytes. NK cell activity and antibody dependent cellular cytotoxicity were normal. Virtually all patients showed elevated serum thymosin alpha 1 levels and elevated serum lysozyme levels. The most consistent findings were the low helper cells, inverted helper:suppressor ratio and elevated serum thymosin alpha 1 and lysozyme. The patients with the prodrome should be subjected to therapeutic research with immunorestorative drugs.
Randomized comparisons of radiotherapy and CCNU versus radiotherapy, CCNU plus procarbazine for the treatment of malignant gliomas following surgery. A Southwest Oncology Group Report.
One hundred and fifteen eligible patients with histologically verified malignant gliomas (astrocytoma grade III-IV) were randomized to receive either radiotherapy 6 000 rads/7 week plus CCNU 130 mg/M2 every 6 weeks (treatment 1) or radiotherapy 6 000 rads/7 weeks plus CCNU 75 mg/M2 day 1 plus procarbazine 100 Mg/m2 days 1-14 every 6 weeks (treatment 2) within 4 weeks following surgical resection. The response rates showed no statistically significant differences between treatment 1 CR/PR - 24/17% and treatment 2 CR/PR - 14/14% (P-value = 0.31). The median survival was also not significantly different: 55 and 50 weeks for treatments 1 and 2, respectively. The most important prognostic parameter identified was age with younger patients showing higher response rates and longer survival. Patients' performance status was also a useful prognostic parameter for response and survival. Neither the extent of surgical resection nor the tumor grade correlated significantly with the outcome. Further studies are needed to identify active chemotherapeutic agents for the treatment of brain tumors.
Detection and determination of pyrroloquinoline quinone, the coenzyme of quinoproteins.
A convenient determination of pyrroloquinoline quinone (PQQ) in extracts of purified enzymes is possible with ion-pair chromatography on a HPLC reverse-phase column and with uv detection. However, when culture supernatants have to be analyzed, a fluorescence detection system is more appropriate. Proof for the presence of PQQ can be obtained by treating such a sample with butyraldehyde, which converts the coenzyme into a stable adduct having a suitable retention time in the system. The sensitivity and selectivity of the analysis can be further enhanced by reducing the sample with NaBH4, which produces the dihydrodiol form of the coenzyme (PQQH4) and oxidizing PQQH4 with NaIO4 to a strongly fluorescing compound. A procedure is described for the easy preparation of an apoenzyme from the quinoprotein glucose dehydrogenase of Pseudomonas aeruginosa strains. With this biological test system, very low amounts of PQQ can be detected. However, when PQQ is present in the form of adducts, the analysis has to be performed via reduction to PQQH4, oxidation with NaIO4, and HPLC.
The Southwest Oncology Group experience: adjuvant therapy for stage IB and II non-seminomatous testicular cancer.
During a two year period, 65 patients with Stage II non-seminomatous testis cancer were randomized to receive adjuvant chemotherapy and radiation. Of the 52 evaluable patients, 23 received radiation followed by chemotherapy (sequential), and 29 received the same chemotherapy as initial treatment, but had drug treatment temporarily interrupted for radiation (sandwich). The combined treatment was well tolerated, but did not eliminate recurrence. With regard to duration of survival and disease-free survival, no statistically significant difference could be found between the sequential and sandwich approaches.
Structural and functional evidence for multiple channel complexes in the outer membrane of Neurospora crassa mitochondria.
The outer membrane of mitochondria contains proteins that form channels called VDAC (voltage-dependent anion-selective channels). Two independent lines of evidence suggest that these channels occur in specific complexes in the outer membrane of Neurospora mitochondria. Electron microscopic images of these outer membranes reveal polymorphic crystalline arrays of putative pores. These arrays can be shown to be interrelated by movement in the membrane plane of a particular rigid channel triplet or of regular aggregates of this triplet. Detergent extracts of the same outer membranes induce single- and multiple-step conductances in planar phospholipid membranes, with a marked preference for the insertion of triplets and multiples of triplets. The tendency of the mitochondrial channels to occur as extended arrays, apparently built up from triplets, may have important functional and evolutionary implications.
Three-dimensional reconstruction of chromatin fibers.
We have obtained tilt series of thin sections of chromatin fibers embedded in araldite-epon and stained with uranyl acetate. The tilt series contain between 12 and 18 micrographs, spanning tilt ranges between 84 and 117 degrees. Reconstructions in three dimensions have been obtained by filtered back-projection from each tilt series. The reconstructions have been low-pass filtered in order to reduce the amount of noise. In the reconstructions it is possible to approximately localize the nucleosomes. In several regions they show a clear zigzag arrangement, but in other regions it is difficult to determine the sequence of the nucleosomes. In any case there is no clear indication of a solenoidal arrangement. We discuss the rules which may give rise to a 3-D arrangement of the nucleosomal zigzag.
Suppressor cell activity among the peripheral blood leukocytes of selected homosexual subjects.
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Nine years of experience with a piston-type pneumatic TAH-driver--reliability and consequences.
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Automatic control and regulation of two rollerpumps for biventricular bypass.
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Effect of reconstructive surgery on the blood flow in the extremities. Early and late results.
The effect of vascular reconstruction on limb blood flow was studied in 20 patients with arterial disease in the lower extremity. Blood flow was determined with isotope dilution technique, ankle systolic pressure was estimated with the aid of Doppler ultrasounds. Circulation was studied prior to the operation (i); immediately afterwards (ii); 2-4 months later (iii); and 12-20 months later (iv). In obliterative limb arterial disease blood flow had remarkably slowed down with high vascular resistance in the limb. After surgery blood flow reached almost normal level and vascular resistance in the extremity also decreased to normal. Both the O2 uptake by the extremital tissues and systolic perfusion pressure in the ankle increased after the operation. At a later phase of the postoperative period blood flow in the limb slightly decreased but even after a year it was greatly improved and vascular resistance was much less as compared to the state before reconstructive vascular surgery.
Phase II evaluation of anguidine in central nervous system tumors: a southwest Oncology Group study.
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Combination chemotherapy for advanced sarcomas of bone and mesothelioma utilizing rubidazone and DTIC: a Southwest Oncology Group Study.
Twenty-three patients with disseminated bony sarcoma and 23 patients with malignant mesothelioma were evaluable in a Southwest Oncology Group (SWOG) clinical trial utilizing rubidazone and DTIC. One partial remission (PR) was observed in a previously untreated patient with metastatic Ewing's sarcoma. One patient with giant cell tumor of bone had an improvement, short of PR. Thirteen patients with osteogenic sarcoma and 23 with malignant mesothelioma had no response to this combination of drugs. The major toxic effects of therapy included nausea, vomiting, and myelosuppression, especially leukopenia; no cardiac toxicity was noted. We conclude that the combination of rubidazone and DTIC is inactive in bony sarcoma and mesothelioma.
Architecture of Limulus polyphemus hemocyanin.
The architecture of the 48-meric hemocyanin of the horseshoe crab Limulus polyphemus has been determined from electron micrographs of whole (48-mer) molecules and half- (24-mer) molecules. The assembly of hexamers of kidney-shaped subunits can produce two dodecameric enantiomorphs, designated as right and left. The assembly of 24-mers can again result in two enantiomorphs. By taking into account the rocking effect described by Van Heel and Frank [Van Heel, M., & Frank, J. (1981) Ultramicroscopy 6, 187-194], we deduced that the 24-meric half-molecule is made up of two copies of the left dodecameric enantiomorph. In addition, the two constituent dodecamers of the half-molecule are shifted with respect to a symmetric head-to-tail arrangement, which makes it possible to distinguish two different faces of the 24-mer, termed flip and flop. A model of the whole molecule was built from two copies of the 24-meric half-molecule. This model presents the four distinct views observed in the electron microscope (pentagon, ring, cross, and bowtie). In addition, the model shows the pentagonal view to exist in two varieties: symmetric and asymmetric. An analysis of electron micrographs presenting the pentagonal view by image processing using the statistical technique of correspondence analysis confirmed the existence of two types of pentagonal view, representing projections of a molecule built from two copies of the left 24-meric enantiomorph. In addition, the best fit between the averaged molecule images and the possible models was observed with a flop-flop inter 24-mer contact. The final model is shown in a series of stereo views produced by computer graphical techniques.
Multivariate statistical analysis of ribosome electron micrographs. L and R lateral views of the 40 S subunit from HeLa cells.
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Correspondence analysis of aligned images of biological particles.
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Direct structural localization of two toxin-recognition sites on an ACh receptor protein.
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