[Evaluation of occlusal function according to Helkimo and Eismann].
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Biomedical subjects
Publications and source records attributed to C Neumann.
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Biopsies from 9 different oral papillomatous proliferations were analysed for human papilloma viral (HPV) sequences of types 1 to 19 and 21 to 26 by Southern blot analysis with 32p-labelled cellular DNA. HPV sequences were detected in 7 out of 9 biopsies obtained from individual patients. Of three cases with the clinical diagnosis focal hyperplasia Heck, two contained HPV-6 related sequences and one HPV 13. In addition, one tongue base papilloma contained HPV 11. A papilloma of the palate revealed HPV 11 sequences. HPV 6 could be demonstrated twice in the remaining 4 oral papillomatous proliferations. Two biopsies remained negative. The data shows that HPV DNA can be regularly demonstrated in oral papillomas.
The analysis of a total of 654 benign and malignant lesions of the skin, genitalia, lungs and bronchi, intestine, kidneys, bladder, mammae, and of the head and neck region, resulted in the identification of human papilloma virus 7 (HPV 7) infections in 3 individuals. One of these was an ordinary "butcher's wart," whereas the other 2 patients have never been involved in meat-handling or farming. One of the latter revealed extensive verrucosis of hands, feet, axilla, neck, and face, persisting for about 27 years, with new lesions arising in the neck region. Particularly the new lesions showed filiform morphology. The second patient has, for a period of more than 2 years, been showing filiform papillomas in the face which recurred after surgical removal. These 2 patients appear to represent the first cases of HPV 7 infections in non-butchers or non-meathandlers.
A total of 113 benign and malignant tumours of the mouth and upper respiratory tract have been analysed for the presence of papilloma virus DNA. Thirty-four (63%) of 54 papillomatous lesions were found to contain such DNA. Seventy-two percent of the laryngeal papillomas contained HPV 6 or HPV 11 DNA, whereas the oral papillomatoses harboured HPV 6 (15.6%), HPV 11 (9.4%), HPV 7 (9.4%), HPV 13 (12.5%) and HPV 32 (9.4%) DNAs. The high number of HPV 7 DNA-positive lesions was unexpected. In most of the malignant tumours no papilloma-viral DNA was found, with the exception of 3 tongue-base carcinomas, and in a metastasis from one of the tumours, which contained HPV 16 (3 biopsies) and HPV 2 related sequences (1 biopsy).
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It has been described before that only certain types of macrophages are capable to respond to lymphokines and that only certain macrophage phenotypes were able to migrate and to respond to migration inhibitory factors (MIF). With respect to the dissociation of MIF activities from a series of other biological activities, and with regard to the phenotype-associated response of macrophages to MIF it was asked: What are the characteristics of the MIF-responsive macrophage phenotype and what are the functional changes induced by MIF on macrophages in addition to inhibition of random migration? Bone marrow-derived macrophages on day 6 of culture were separated by hypotonic Percoll density gradient centrifugation into three distinct bands and analyzed for a variety of functions. It was found that migrating and MIF-responsive macrophages accumulate at a certain density. These macrophages were further characterized by monoclonal antibodies generated against murine macrophage phenotypes. One marker was found to be preferentially expressed by MIF-responsive macrophages. In order to study the inducibility of MIF responsiveness, bone marrow-derived macrophages on day 16 of culture which were poorly migrating and did not respond to MIF were induced to proliferate by the addition of L cell-conditioned medium. After proliferation had subsided, MIF sensitivity was restored. The effects of MIFs other than migration inhibition, on a number of functions which had been mapped within the cell cycle, were investigated. It was found that MIF acts anti-proliferative on "young", cycling macrophages. Non-cycling, mature macrophages were shifted to a state characterized by a decreased expression of transglutaminase and plasminogen activator and an increase of certain phenotypic surface markers. It is concluded that MIFs are differentiation-inducing signals, acting on the generation of macrophages from precursors but also in the recruitment of terminally differentiated macrophages to "inflammatory" type of macrophages which are functional in the induction of immune responses.
One hundred twenty-one patients with newly diagnosed, previously untreated Hodgkin disease underwent abdominal and pelvic computed tomographic (CT) scanning and bipedal lymphography. These studies were followed by staging laparotomy, which included biopsy of the liver, retroperitoneal and mesenteric lymph nodes, and splenectomy. Correlation of the results of the imaging studies with the histopathologic diagnoses revealed a small--but significant--increased accuracy of lymphography compared with CT in assessing the retroperitoneal lymph nodes. The theoretical advantages of CT scanning in detecting lymphomatous deposits in lymph nodes about the celiac axis and the mesentery, or in the liver and spleen, were not confirmed. In part this was due to the relative incidence and the small size of individual lesions at these sites in patients with Hodgkin disease at the time of initial diagnosis and staging.
The purpose of this work was to study the interrelationship of proliferation and secretion of plasminogen activator (PA) and interferon (IFN) by murine macrophages. For induction of macrophage proliferation and secretion of PA, concanavalin A (Con A) was used. Secretion of IFN was induced by polyinosinic polycytidylic acid complex. The glucocorticoid dexamethasone acetate (DA) (10(-6)-10(9) M) inhibited Con A-stimulated secretion of PA and synthesis of DNA as evaluated by incorporation of [3H]thymidine. DA did not inhibit IFN induction. Preincubating macrophages with DA for 45 h reduced basal proliferation and secretion of PA but did not reduce responsiveness to Con A. Also retinoic acid, a modulator of carcinogenesis was used in inhibition studies because of its known antagonistic effects on lymphocyte mitogenesis. In macrophages a biphasic effect of retinoic acid (1 X 10(-5) - 5 X 10(-5)M) was found: (a) inhibition of DNA synthesis and secretion of PA during the first 45 h of incubation, and (b) enhancement of DNA synthesis (but not PA secretion) after 72 h. Secretion of IFN was not affected. It is suggested that secretion of PA but not IFN is linked to cell cycle traverse of macrophages.
Vitamin cofactor saturations of placental enzymes were assayed in 54 Kenyan women. In addition, studies were conducted to determine whether placental vitamin deficiencies were associated with deficiencies in maternal or cord blood and to determine whether neonatal birthweights were influenced by vitamin nutriture. All samples were analyzed by vitamin cofactor saturation tests of glutathione reductase, transketolase, and glutamic-pyruvic transaminase. Standard indices were used to determine vitamin deficiencies. The activity of placental diamine oxidase, a pyridoxal phosphate-requiring enzyme was also measured and examined in relation to pyridoxine nutriture. No placental riboflavin deficiencies were found although 73% of maternal red blood cells (RBC) and 35% of cord RBC were deficient. Thiamine deficiencies were found in 15% of placentas, 59% of maternal RBC and 41% of cord RBC. Pyridoxine deficiencies occurred in 24% of placentas, 35% of maternal RBC, and 15% of cord RBC. Low birth weights were found to be associated with maternal riboflavin deficiencies. Maternal RBC riboflavin and thiamine deficiencies correlated with deficiencies in cord blood, and pyridoxine deficiencies in maternal RBC were associated with deficiencies in the placenta. A trend of lower placental diamine oxidase activity was noted in pyridoxine-deficient placentas and pyridoxine-deficient mothers.
We used a laser Doppler velocimeter for measurement of skin blood flow in 63 healthy control subjects and in patients with dysautonomias. We measured vasoconstrictor responses to inspiratory gasp, standing, Valsalva maneuver, and cold stimulus. An abnormal profile was defined in terms of the percentage of abnormal test results, the results of individual tests, and the alterations in the shape of the recorded response. These measurements of vasomotor function may permit the diagnosis of focal abnormalities of peripheral nerve sympathetic failure.
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Using a contact hypersensitivity model in BALB/c mice we have previously been able to show that Corynebacterium parvum or C. parvum serum (C.p.s.) of mice treated 24 hr before with C. parvum inhibited the suppressor T-lymphocyte (Ts-cell) response induced by epicutaneous antigen overload with 2,4-dinitrofluorobenzene (DNFB) or by i.v. injection of 2,4-dinitrobenzene sulfonic acid (DNBSO3) without inhibition of the T effector cell response (TDH-cell). In the present investigation we further analyzed the factor responsible for Ts-cell inhibition. Treatment of the C.p.s. with sheep-antimouse interferon (IFN) globulin neutralized its Ts-cell inhibitory effect. Intravenous (i.v.) injection of a crude mouse fibroblast IFN (340 U per mouse) 2 hr after i.v. application of a dose of DNBSO3 inducing tolerance had a similar Ts-cell inhibitory effect as observed with C.p.s. Injection of an electrophoretically pure alpha- and beta-IFN preparation (1000 U per mouse) increased contact sensitivity in mice sensitized with an antigen overload and inhibited the induction of Ts-cells by DNBSO3 i.v. This result is highly suggestive that the Ts-cell inhibitory factor in serum of C. parvum-treated mice is IFN and it shows that Ts-cells as compared to TDH-cells are susceptible to the inhibitory effect of highly purified IFN. This finding suggests that IFN may be an important immunoregulatory factor of delayed hypersensitivity not only in contact allergy but also in bacterial and viral defense.
Transglutaminase was detected either at the single cell level by fluorescent staining with dansylcadaverine or in cell homogenates by incorporation of [14C] putrescine into alpha-casein. In the mouse it was found that erythrocytes, granulocytes, thymocytes or lymphocytes with or without concanavalin A stimulation were negative in the fluorescence test. Normal peritoneal washout macrophages and peritoneal exudate cells stained positive to varying degrees (induced with mineral oil 64%, with thioglycollate 50%, with proteose peptone 22%, normal washout 1%). Macrophages from bone marrow liquid cultures were 20% positive at day 3 and 100% at day 17. Promonocytes and monocytes were negative. Positively stained cells also phagocytosed opsonized sheep erythrocytes. The degree of staining varied considerably in the macrophage-like cell lines IC21 (100%), J774.2 (75%), P388-D1 (50%). This result and those from autoradiography studies indicate that expression of transglutaminase is not associated with the S-phase of the cell cycle. The fluorescence test correlates quantitatively with the [14C] putrescine incorporation test. The enzyme is Ca2+-dependent and appears neither to be on the outer cell surface nor being released into the culture medium. Circumstantial evidence indicates that it is also not compartmentalized in cytoplasmic vesicles. While the induction and modulation of enzyme expression is still under study, it is concluded that transglutaminase is a new marker for macrophages of a certain differentiation or activation state.
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Macrophages were obtained from seven-day-old bone marrow liquid cultures to which a colony-stimulating factor from L-cell-conditioned medium had been added. It was found that the yield of macrophages from the bone marrow liquid culture was dependent on the type and brand of culture dishes. Highest yields were obtained in teflon membrane bag cultures. The cumulative yield after serial passage of macrophages was 700-fold of the cell input after two months. After mechanical detachment from plastic culture dishes, the survival rate of cells was related to the brand of the plastic dish. Viability also varied greatly after pretreatment of cells with scandicain (28%), proteinase K (78%), or pronase (99%). After mechanical detachment of macrophages or pretreatment with scandicain, adherence to plastic, latex phagocytosis and chemotaxis was not or only slightly impaired, whereas the same functions after protease treatment were greatly reduced or even abolished and were only recovered after another culture period. Scandicain, proteinase K, and pronase treatment was mitogenic to macrophages in contrast to mechanical detachment. Pronase treatment also induced release of plasminogen activator activity. The results demonstrate that macrophages respond extremely sensitive to environmental conditions and to various insults by changing their functional state.