An immunoperoxidase study on herpes simplex virus encephalitis.

Using formalin-fixed, paraffin-embedded sections, indirect immunoperoxidase studies were performed on 3 autopsied and 1 biopsied cases of herpes simplex virus (HSV) encephalitis. Specific reaction was observed in all 4 cases. Distinct stain was observed both in neurons and in glial cells. Electron microscopic studies performed on the same material revealed HSV particles stained with electron-dense reaction products. The advantages and disadvantages of the use of formalin-fixed, paraffin-embedded material in immunoperoxidase studies of viral disease are discussed.


Scanning electron microscopy of retinoblastoma.

Two cases of the so-called undifferentiated retinoblastoma are demonstrated where typical rosettes were absent. However, cell groups resembling rosettes existed. Scanning electron microscopy revealed a tendency of the cells to arrange in circles or in garland-like formations. In one of the cases lymphocytes were found and in the other photoreceptor elements and tubuloreticular inclusions within the endothelial cells were seen.


Effects of local anesthesia on gingival cAMP levels.

The basal levels of cAMP in the attached gingiva of Rhesus monkeys and the changes in tissue cAMP levels produced by infiltration anesthesia with lidocaine and lidocaine containing 1:100,000 epinephrine were studied. The basal level of cAMP in uninjected monkey gingiva ranged from 12 to 20 picomoles of cAMP per mg of gingival protein. This level was 75 times greater than the cAMP content of monkey blood plasma. Infiltration of the attached gingiva with saline or plain lidocaine for 5 minutes did not produce any significant changes in tissue cAMP levels. Infiltration of the gingiva with lidocaine containing 1:100,000 epinephrine, on the other hand, caused a very marked increase in tissue cAMP levels. Thirty seconds after infiltration with lidocaine with 1:100,000 epinephrine there was a 250% increase in cAMP content of the anesthetized tissue versus the uninjected control tissues. The maximal increase in tissue cAMP levels was observed 5 minutes after infiltration when the cAMP content of the gingiva was 1000 to 1100% above the control level. It is proposed that regulation of tissue cAMP levels by epinephrine or other agents may prove of therapeutic usefulness in regulating inflammation and healing of tissues after surgery or other trauma.


Systemic and topical use of poly I.C. in treatment of generalized neonatal herpes simplex infection with severe ocular involvement.

A case of Neonatal Herpes Simlex Virus (RSV) Encephalitis with severe ocular manifestation treated by topical systemic and intrathecal Interferon inducer, Poly IC (Polyriboinosinic acid-Polyribocytidylic acid) is reported. Prior to the administration of Poly IC, no Interferon could be detected neither in blood nor in CSF and vesicular fluid from conjunctiva. Intravenous administration of the drug initiated measurable levels in blood and tears, but not in CSF. However, intrathecal injection induced persistent high levels of Interferon in CSF. Virus clearance from conjunctiva tears and vesicular fluid occurred after three days of topical application of Poly IC. The mechanism of action of Poly IC, the laboratory results and the therapeutic conclusions are discussed in detail. This is the first report of intrathecal administration of Poly IC in a case of HSV Encephalitis.


Cerebral gigantism (Sotos' syndrome) and cataracts.

A five-year-old girl with cerebral gigantism (Sotos' syndrome) and cataracts is described. Sotos' syndrome, characterized by generalized gigantism with normal endocrine studies has rarely been reported with ocular abnormalities and never with cataracts. It is important to study any child with cataracts for systemic disease.


The role of sulfhydryl groups in contraction of vascular smooth muscle.

While high concentrations (50 micronmol/l) of merurial sulfhydryl (SH) reagents p-chloromercuribenzoate (PCMB) and p-chloromercuriphenyl sulfate (PCMPS) caused a nonspecific inhibition of constrictor responses in isolated rabbit ear arteries, lower concentrations had selective effects. At a concentration of 10 micronmol/l both agents abolished responses to epinephrine and reduced responses to barium and calcium, but responses to caffeine were unaffected by PCMB and potentiated by PCMPS. Responses to histamine were little affected by PCMPS, but with PCMB, histamine responses were first reduced but later potentiated. In contrast, ethacrynic acid, a nonmercurial SH inhibitor which gains access to the intracellular space, failed to show any specificity of action and inhibited contractile responses to all these agonists. The results suggest that SH inhibitors whose actions are limited to the cell membrane exert both specific and nonspecific effects. The specific effect may be at SH groups associated with the alpha adrenoceptor while nonspecific effects may involve changes in membrane permeability.


[Electrotonic transmission in the mammalian central nervous system (author's transl].

The aim of this review is to present the electrophysiological data, obtained in the mammalian central nervous system, which show that depolarisations recorded intracellularly, under certain experimental conditions can be interpreted in terms of electrotonic coupling. The results were obtained from very different structures: primary sensory nuclei, sensori-motor integration centres and motor nuclei. The association of the phenomenon of electrotonic transmission with a known ultrastructural substrate--the "gap junction"--has been defined by the term electrotonic coupling. In the cases where it has not been possible to link depolarisations with the presence of gap junctions, other possible morphological correlates have been envisaged. The functional significance of electrotonic interactions are discussed on the basis of information obtained from different experimental approaches.


Effect of silver nitrate application on the conjunctival flora of the newborn: and the occurrence of clostridial conjunctivitis.

Newborn conjunctival cultures were obtained from 35 babies prior to silver nitrate application and 48 hours later. On initial culture, 46 facultative bacteria and 27 anaerobes were recovered; 48 facultative and 18 anaerobes were recovered after 48 hours. Haemophilus vaginalis, Bacteroides species and anaerobic cocci decreased in numbers, whereas S. epidermidis, Micrococcus and Propionibacterium acnes increased during this time interval. Clostridial species were isolated from two cases who developed conjunctivitis, along with Peptostreptococcus in one of the cases. In vitro experiments demonstrated lack of killing of C. perfringens in silver nitrate concentrations of 0.1 percent, even after 24 hours exposure.


Clonal growth of Entamoeba histolytica and other species of Entamoeba in agar.

This is the first description of a method for growing axenized Entamoeba histolytica as colonies from single cells in agar suspension. Factors affecting the efficiency of colony formation included unknown characteristics of the amebal strain, age of cells used, and the type and concentration of agar employed. Colony formation was dependent upon filling deep vessels (culture tubes or tissue culture flasks) with agar, probably to maintain reduced oxygen tension, and upon solidifying the agar rapidly at 0 C. It was demonstrated in a study with the drug metronidazole that the agar colony method was useful for quantifying cell viability in drug testing. Eleven of 12 E. histolytica strains tested, as well as one Entamoeba terrapinae, one Entamoeba barreti, and 3 Entamoeba invadens strains formed colonies in agar suspension. E. histolytica-like amebae (Laredo type) and E. moshkovskii formed only tiny colonies in agar.


Pyridoxine kinase in Plasmodium lophurae and duckling erythrocytes.

Pyridoxine kinase enzyme activity was greatly increased in duckling erythrocytes infected with Plasmodium lophurae. Pyridoxine kinase activity in parasites freed from erythrocytes was much greater than that of uninfected erythrocytes. The apparent Km for pyridoxine of the parasite enzyme was 6.6 times 10(-5) M whereas the host red cell enzyme Km was 1.9 times 10(-6) M. Deoxypyridoxine inhibited host and parasite pyridoxine kinase activity with an apparent Ki of 1.5 times 10(-6) and 8.6 times 10(-6) M, respectively. These results suggest that the vitamin B6 metabolism of the malaria parasites is distinct and separate from that of the host erythrocytes.


Calcium pyrophosphate crystal deposition disease and hyperparathyroidism: a controlled, prospective study.

A prospective, controlled study of patients with primary hyperparathyroidism has been carried out to establish the relation of this endocrinopathy to calcium pyrophosphate dihydrate crystal deposition disease. Eight of 26 patients with documented hyperparathyroidism were found to have chondrocalcinosis compared to four of 104 individuals in the control group (p less than 0.01). Two of these eight patients had confirmed pseudogout attacks shortly after parathyroidectomy. Four other patients, including two without chondrocalcinosis, gave a history of typical pseudogout. Patients with hyperparathyroidism and chondrocalcinosis were significantly older than those without the articular lesion (p = 0.006). We could not delineate specific metabolic abnormalities of hyperparathyroidism which contributed to the development of chondrocalcinosis.


Calcium pyrophosphate dihydrate crystal formation in model hydrogels.

Using powder x-ray diffraction analysis, we studied calcium pyrophosphate crystal formation in silica and gelatin gels was well as in comparable aqueous solutions. We demonstrated that the physiological salts, monoclinic and triclinic calcium pyrophosphate dihydrate can be formed in gels and that gels do affect the type of crystals formed from ions in solution. These observations support our hypothesis that calcium pyrophosphate dihydrate crystal deposition in joints is regulated by the physical chemical gel state of the connective tissue matrix.


A new form of Niemann-Pick disease characterised by temperature-labile sphingomyelinase.

A new type (F) of Niemann-Pick disease characterised by childhood onset of splenomegaly, lack of neurological involvement, and diminished sphingomyelinase activity is described. The clinical presentation and heat-labile sphingomyelinase activity of this type F Niemann-Pick disease distinguishes it from other types of Niemann-Pick disease.


Pyridine nucleotide oxidation-reduction state of the cerebral cortex in the awake gerbil.

A new approach to study the effect of ischemia on the brain of the awake gerbil is described. The measurement of NADH fluorescence from the surface of the cortex is done by a time-sharing fluorometer/reflectometer connected to the brain via a flexible light guide and an implanted cannula. The response of the gerbil brain to anoxia and spreading depression is described. By unilateral occlusion of the carotid artery an increase in NADH was measured in the ipsilateral hemisphere.


Intracortical horizontal connections of neurons in cat and monkey motor cortex.

The present paper deals with the study of the structure of horizontal neuron chains, one of the aspects of intracortical intraneuronal relationships. The motor cortex (field 4) of cats and lower monkeys (Papio hamadryas and Macacus rhesus s. M. mullata) was treated by the impregnating method of Golgi--Kopsh. The drawings of neurons from 90-micrometer sections were made by means of a camera lucida. Three possible pathways of impulse transmission along neuron chains in a horizontal direction were revealed. These were: a pyramido-pyramidal system of connections which may possibly spread excitatory influence among several columns; a basket-pyramidal connection system; and connections which arise from successive switchings between neighboring neurons of one layer.


An x-ray microanalysis study of differences in concentration of elements in brain cells due to opiates, cell type, and subcellular location.

Adult female Sprague Dawley rats were divided into three groups and given two daily doses of: 1) morphine (25 mg/kg at each injection), or 2) methadone (5 mg/kg), or 3) saline for nine days. Two hours before the rats were killed on day 10, they were given a double dose of the drugs. Fifteen minutes before being killed, some of the morphine-treated rats were given the opiate antagonist naloxone (2.5 mg/kg), which caused a sudden arousal in these rats. At the time of killing, the preoptic-hypothalamic region was repidly removed and frozen in liquid propane to prevent translocation of elements in cells. Frozen 4-micrometer sections were cut, freeze-dried, and electron-probed in a scanning electron microscope, and energy-dispersive x-ray spectra were collected. The characteristic peak-to-continuum ratio for all detectable elements was determined in both the nucleus and the cytoplasm of ependymal cells and neurons. The data from nine cells of each type in each rat brain were then subjected to one- and three-way analysis of variance. The results show significant differences in the distribution of elements (sodium, magnesium, phosphorus, sulfur, chlorine, potassium, and calcium) which are dependent upon: 1) subcellular localization, 2) cell type, and particularly, 3) opiate treatment. The behavioral state produced by the opiates is correlated with the effects they have on intracellular concentration of several elements, most notably, sodium.


Activation of brain tryptophan hydroxylase by a phosphorylating system.

A significant activation of tryptophan hydroxylase (TPH) was achieved by the addition of 1 mM ATP and 10 mM MgCl2 to 100,000g supernatant prepared from mouse midbrain. The activation produced an increase of enzyme activity by 50-70% above control. Cyclic AMP was not a necessary component in the activation as initially suspected; neither was the involvement of a cyclic AMP-dependent protein kinase detected. The enzyme activation by Mg+2-ATP was totally retained after dialysis, thus excluding the possibility of an allosteric effect. In contrast to the activation, TPH was found to be sensitive to inactivation by acid phosphatase, a dephosphorylating enzyme. These findings are consistent with the proposal that the enzyme activation may involve a phosphorylation process. Furthermore, the activation by Mg+2-ATP in the brain preparations was only minimally observed from neonatal mice and could be abolished from adult mice by administration of hydrocortisone. It appears that the phosphorylation process, as postulated here, may be under developmental and hormonal influences.


On potassium functional feedback in neuromuscular junction.

The dependence of the reversal potential (Erev) of intracellular end-plate potentials (epp) on activity patterns was studied in frog neuromuscular preparations. A shift of Erev to the positive side was found with change in frequency of stimulation from 1/sec to 50/sec. This shift corresponds to the increase of potassium concentration in the synaptic cleft to 7.0 mM. The effect of potassium concentration [K+]0 in the bath solution on quantal content (m) of epp was studied. The quantity m increased when [K+]0 was varied within the range 4.7-8.7 mM; m decreased when [K+]0 was greater than 8.7 mM. Such a relationship between m and [K+]0 is accounted for by the combined effect of potassium on transmitter secretion and electrogenic processes in motor nerve terminals. The correlation between the change of m with [K+]0 and initial epp amplitudes was found and was attributed to potassium efflux from post-synaptic region in varying quantity depending on the initial epp amplitudes. A scheme of synaptic self-regulation by means of potassium feedback is suggested.


A possible mechanism of infertility by acute cadmium intoxication.

A possible mechanism of infertility by Cd was investigated from the standpoint of influence of Cd on the contractile responses of isolated seminal vesicle from guinea pigs to K, acetylcholine, noradrenaline, Ba and Ca by using the Magnus method. Cd inhibited the contractile responses to the contractile agents tested in a dose-dependent manner. Cd showed the preferential inhibition against the contractile responses to K and Ca. The inhibitory effect of Cd on the contractile responses to noradrenaline and acetylcholine was hardly removed. The effect of Cd was inhibited by the thiol compounds, glutathione and thiola. The active mechanism of Cd was discussed in relation to Ca mobilization.


Lithium prophylaxis of corticotropin-induced psychosis.

Corticotropin is one of the few accepted treatments for acute exacerbations of multiple sclerosis and retrobulbar neuritis. Psychosis is a serious side effect usually necessitating discontinuation of the drug therapy. Because mood disorders preponderated in most patients previously described with this psychosis, 27 patients were empirically treated with lithium carbonate concurrently with corticotropin. In none of the patients treated with lithium did a psychotic reaction occur, although in a comparable group of 44 patients previously treated identically with corticotropin but without lithium, six (14%) became psychotic.


Quality and duration of survival in glioblastoma multiforme. Combined surgical, radiation, and lomustine therapy.

A retrospective evaluation of the quality and length of survival of 74 patients nonrandomly receiving lomustine, 100 to 110 mg/sq m, following craniotomy and irradiation for glioblastoma multiforme was performed. After surgery all patients were capable of at least partial self-care. Patients receiving postoperative irradiation and lomustine had a median survival of 11.5 months. While receiving chemotherapy, 40% of these patients were capable of at least partial employment; 75% were able to care for themselves. These levels of function were stable for 70% of the average postoperative course (8.0 months), following which a decline ensued.


Metyrapone test with adrenocorticotrophic levels. Separating primary from secondary adrenal insufficiency.

Basal plasma adrenocorticotrophic hormone (ACTH) and cortisol concentrations as well as plasma ACTH and 11-deoxycortisol responses to the administration of a single dose of metyrapone were evaluated in 104 patients with intact pituitary-adrenal axis, in 20 patients with secondary adrenal insufficiency, and in seven patients with primary adrenal insufficiency. In patients with primary adrenal insufficiency, baseline ACTH levels were high. Following metyrapone administration, 11-deoxycortisol concentrations were low and ACTH levels did not change. In patients with secondary adrenal insufficiency, baseline plasma ACTH levels were normal, but neither 11-deoxycortisol nor ACTH levels increased in response to metyrapone. The metyrapone test is not only useful to screen for adrenal insufficiency, it is also useful to differentiate a primary from a secondary cause.


Epstein-Barr virus antibodies in Sudanese patients with nasopharyngeal carcinoma: a preliminary report.

With the use of an immunofluorescence technique Epstein-Barr viral capsid antigen antibody titers were determined in the sera from 226 Sudanese: 41 with nasopharyngeal carcinoma (NPC), 77 with other head and neck cancers, 21 with malignant lymphomas, 63 with other cancers, 6 with specific granulomas, and 18 normal controls. Of the NPC patients, 87.8% had titers of 320 or greater and 43.9% had titers of 2,560 or more, whereas none had titers of less than 40. Their geometric mean titer (GMT) level was 1,855. However, compared to the NPC patients, the other patients and normal controls showed significantly higher percentages of sera with low titers and lower percentages of sera with high titers and they had a GMT that was 4--16 times lower. The high NPC titers were independent of age, sex, tribe, or locality of patients. The preliminary results indicated the importance of future immunovirologic and immunogenetic field investigations on the natural history of the Epstein-Barr virus and on the genetics of the host.


Surface glycopeptide change triggered by contact between normal cells from rat liver and their simian virus 40-transformed cells from the same virus.

Surface glycopeptide changes triggered by mixed culture of normal cells from rat liver cell line WIRL-3 and simian virus 40-transformed cells from the same line were studied. In addition, biologic responses of the normal cells and the transformed cells to three kinds of surface glycopeptides derived from the normal cells, the transformed cells, and these cells in mixed culture were investigated. Surface glycopeptide derived from the mixed culture showed a quantitative increase and a qualitative change in the glycopeptide structure, not detected in the surface glycopeptide of normal cells and transformed cells cultured separately. The surface glycopeptide changes observed in the mixed culture were mainly ascribable to normal cells responding to transformed cells, and a surface glycopeptide change in normal cells induced a qualitative surface glycopeptide change in transformed cells. Differences in biologic response of normal cells and transformed cells to the above three surface glycopeptides were investigated with the use of inhibition of [3H]thymidine uptake of the cells by the three different surface glycopeptide preparations. The inhibition rates of uptake in normal cells were 30% by all three surface glycopeptides (200 microgram/ml culture medium); inhibition rates in transformed cells were 65% by mixed-culture surface glycopeptide, 50% by normal cell-surface glycopeptide, and 35% by transformed cell-surface glycopeptide.


Enhanced oncornavirus expression in Marek's disease tumors from specific-pathogen-free chickens.

An oncornavirus was recovered from cell cultures of kidney tumors from specific-pathogen-free chickens inoculated with Marek's disease herpesvirus (MDHV). The MDHV inoculum was free of infectious avian leukosis virus (ALV). Direct examination of a variety of tissues from MDHV-inoculated chickens demonstrated increased levels of ALV-specific RNA compared to tissues from diluent-inoculated (control) chickens. DNA from cultured kidney tumor cells annealed to an ALV complementary DNA probe at the same rate and exhibited the same extent of homology as DNA from cultured control kidney cells. This finding indicated the absence of exogenous ALV proviral sequences. As with vertically transmitted endogenous ALV of subgroup E, the oncornavirus recovered from kidney tumor cell cultures failed to replicate in chicken embryo fibroblast (CEF) cultures of the C/E phenotype, but did replicate in turkey embryo fibroblasts (TEF), which are permissive for replication of endogenous ALV of subgroup E. These oncornavirus particles served as a helper virus to form Rous sarcoma virus pseudotypes, which produced foci in TEF cultures but not in CEF cultures of the C/E phenotype. Whether enhanced expression of endogenous oncornavirus contributes to MDHV-induced tumorigenesis is not known.


Radiation induction of endogenous type C virus from mouse cells transformed in vitro by murine sarcoma virus.

Cell lines from AKR and BALB/c mouse embryos were compared for their sensitivity to X-ray induction of endogenous type C virus. K-Balb cells, a Balb/3T3 cell line nonproductively transformed by Kirsten murine sarcoma virus, were found to be sensitive to X-irradiation. At a dose as low as 50 R, X-rays induced virus expression in K-Balb cells, and the induction frequency increased with increasing dose of X-rays up to 400 R. Among two classes of inducible endogenous viruses carried by K-Balb cells, only Balb:virus-2 was activated by X-irradiation, whereas both Balb:virus-1 and Balb:virus-2 were activated after the cells were treated with 5-iodo-2'-deoxyuridine. UV light and 4-nitroquinoline 1-oxide were also shown to induce virus expression in K-Balb cells. The virus-induction frequency for these physical and chemical carcinogens was much lower (approximately 3 times 10(-4)) than that for 5-bromo-2'-deoxyuridine (approximately 1 times 10(-1)).


Phenotypically distinct target cells for murine sarcoma virus and murine leukemia virus marrow transformation in vitro.

An in vitro hematopoietic microenvironment was established from explained fragments of bone marrow from adult noninbred NIH Swiss mice with the use of corticosteroid-reconstituted horse serum. Infection with Kirsten murine sarcoma virus (Ki-MuSV) with either a Rauscher murine leukemia virus (R-MuLV) or Balb:virus-1 helper virus coat reduced proliferation of granulocytic and pluripotent hematopoietic stem cells and produced neoplastic transformation of both macrophages and preadipocytes in the adherent cell population within a 4-week period. Ki-MuSV-transformed, virus-releasing macrophages formed clusters of 4-49 cells in 0.8% methylcellulose-containing medium in the absence of added colony-stimulating factor (CSF), synthesized lysozyme, ASD-chloroacetate substrate-specific esterase-M, and CSF, and produced tumors following inoculation iv into adult NIH Swiss mice or ip into newborn NIH Swiss mice. In cultures infected with helper leukemia viruses R-MuLV or Balb:virus-1, gradual transformation of a distinct cell phenotype was observed over a 9-week period with generation of increasing numbers of atypical myeloblasts and promyelocytes which showed dyssynchronous nuclear-cytoplasmic maturation, basophilic granulation, cytoplasmic vacuolation, and formation of incompletely maturing CSF-dependent granulocyte-macrophage colonies in vitro and small spleen colonies in vivo. These data demonstrated that rapid biologic expression of the murine sarcoma virus genome in specific adherent "stromal" marrow cells prevents detection of a more subtle helper-virus-induced dysmyelopoiesis in a distinct nonadherent cell population.


Avian oncovirus Mill Hill No. 2: pathogenicity in chickens.

Mill Hill No. 2 (MH2), an avian tumor virus, was studied for its transforming and oncogenic effects. In tissue culture it induced transformation of chicken fibroblasts and yolk sac macrophages. When injected into the chicken, the main feature of this virus was its ability to cause liver and kidney carcinoma, in addition to sarcoma. MH2-associated viruses did not transform cell cultures but were able to cause only lymphoma in the birds. Light and electron microscopy were used in a detailed histologic study of the tumors induced by MH2 virus. An unclassified round cell sarcoma was produced in soft tissues at sites of injection; there was no evidence of origin from endothelium. In the kidney, carcinomas mixed with a malignant stroma were found. Hepatocarcinomas were the dominant tumors found in the liver. The lymphomas produced by the associated virus were poorly differentiated and highly malignant. The study illustrated the highly oncogenic potential of this virus and offered a model for the analysis of the carcinogenic events in a more specific way.


Infectivity tests of secretions and excretions from cattle infected with bovine leukemia virus.

Secretions and excretions from cattle with persistent bovine leukemia virus (BLV) infections were tested for BLV by inoculation into sheep. Development of antibody to the BLV glycoprotein antigen and reisolation of virus from peripheral blood leukocytes were the two criteria used to confirm infection in test sheep. The virus was detected in milk from 4 of 6 cows examined and in colostrum from 1 of 4 cows examined. The virus was not detected in semen from 8 bulls or in nasal secretions, saliva, and urine from 2 cows.


Human brain tumor transplantation into nude mice.

Seven human brain tumors were transplanted into the brains (6/7 takes) and subcutaneous tissues (7/7 takes) of athymic nude mice. Compared to experimental animal brain tumors, these tumors, taken directly from patients in the operating room and transplanted, grew more slowly in the mice; their growth rates following explant generally paralleled those in the patients. A rough correlation was seen between the degree of the tumor's malignancy and both successful take and rate of growth following explant. The tumors' growth rates increased during serial transplantation after explant. Two tumors developed into long-term serial lines; both came from gliosarcomas. Preliminary chemotherapy experiments with these two lines demonstrated different chemosensitivities. One line was very sensitive to the nitrosoureas and resistant to procarbazine; the other line was more sensitive to procarbazine than to the nitrosoureas. This model permits study of the biologic behavior of human brain tumors growing intracerebrally and subcutaneously in nude mice.


GFA and S 100 protein levels as an index for malignancy in human gliomas and neurinomas.

Human glia-specific proteins S 100 and GFA were quantitated by use of a rocket immunoelectrophoresis technique with monospecific antisera. No relation was found between the S 100 protein content of an astrocytoma and its degree of neoplasia. However, the lower the GFA protein content of the astrocytoma, the more malignant it was. Similarly, the more malignant a neurinoma was, the lower was its S 100 protein content. Therefore, the levels of these proteins might be used as indexes of neoplastic dedifferentiation.


Immunohistologic evaluation of the lymphoreticular infiltrate of human central nervous system tumors.

Forty-five nervous system tumors (9 glioblastomas, 9 meningiomas, 15 assorted primary neural tumors including 3 medulloblastomas, and 12 brain tumors metastatic to the brain were analyzed for their content of lymphocytes, granulocytes, and macrophages. Cell suspensions were prepared by enzymatic digestion; lymphocytes and granulocytes were quantitated by morphology following cytocentrifugation, and macrophages were quantitated by IgG EAC (erythrocyte-antibody-complement) rosette formation. EA (erythrocyte-antibody) adsorption to sections of tumor was employed to determine the distribution of the IgG Fc receptor-positive cells within the tumors and to serve as quality control for selective release of Fc receptor-positive cells by enzyme digestion. The 9 glioblastomas had a mean macrophage content of 41% (range: 5-78%); the 9 meningiomas, 42% (range: 5-80%); the 3 medulloblastomas, 6% (range: 2-15%); and the metastatic tumors, 21% (range: 2-50%). Lymphocyte contents were variable but generally less than 10%. Most tumors contained less than 10% granulocytes. EA adsorption demonstrated that Fc receptor-positive cells were distributed throughout the tumor mass, although different types of patterns were observed. There was an excellent correlation between the percent EAC rosette-positive cells in suspensions and the extent of EA adsorption to the tumor sections. The significance of the study primarily rests in the demonstration that most nervous system tumors contain high numbers of infiltrating host cells, primarily macrophages.


Effects of subcutaneous administration of chemical carcinogens on leukemia in C58 mice.

The effects of sc administration of 3-methylcholanthrene (MCA), 7,12-dimethylbenz[a]anthracene (DMBA), and benzo[a]pyrene (BP) on spontaneous viral leukemia and subcutaneous sarcoma induction have been studied in weanling C58/J mice. MCA produced significantly more sarcomas at the inoculation site than did DMBA or BP; moreover, it interfered with leukemia development. DMBA produced fewer sarcomas, and the incidence of leukemia was comparable to that found in the controls. BP accelerated the incidence of leukemia, although no sarcomas were produced. When the effect of the age of the mice at the time of MCA treatment on the incidence of leukemia and sarcomas was studied, newborn and weanling mice were found to develop primarily sarcomas, whereas no sarcomas were produced in the 16-week-old mice, and 52-64% of the 16-week-old mice developed leukemia. The reason no sarcomas were found in the C58 mice was apparently different from the reason no sarcomas were found in AKR mice, inasmuch as the AKR mice did not live long enough for sarcomas to develop. Immunologic surveillance may have played a part in the sarcoma suppression in the C58 mouse.


Trisomy no. 15 in murine thymomas induced by chemical carcinogens, X-irradiation, and an endogenous murine leukemia virus.

Chromosome banding techniques were used to examine the karyotype of tumor cells from thymic lymphomas induced by three different carcinogens (X-irradiation, polycyclic aromatic hydrocarbons, and an endogenous leukemogenic virus) after injection into neonatal mice of 2 different inbred mouse strains (CFW/D and C57BL/Ka). A total of 89 tumors were studied, and of these 85.4% were characterized by a modal chromosome number of 41. The additional chromosome was the result of a specific abnormality identified as trisomy of chromosome no. 15. The results obtained were independent of the carcinogenic agents and the strain of mouse used. Of the 13 tumors found to have a normal chromosome complement, 4 were induced by X-irradiation and the remaining 9 by the chemical carcinogens. All 15 virus-induced tumors analyzed had a modal chromosome number of 41.


Lipoprotein X and alkaline phosphatase as indicators of cholestasis.

Lipoprotein X is considered to be an indicator of cholestasis, but its clinical usefulness is unclear owing to different methods of measurement in use and varying definitions of cholestasis. We investigated the reliability of the qualitative determination of lipoprotein X in predicting cholestasis, defined here as the presence of stainable bile in tissue sections. Liver tissue and serum were collected from 42 patients. Patients were divided into those who did and those who did not have stainable bile in tissue sections. Lipoprotein X was demonstrated by electrophoresis and polyanion precipitation. Lipoprotein X in serum correlated with the presence of stainable bile (p = 0.0006). A normal range of alkaline phosphatase values correlated with the absence (p = 0.04), but elevated values did not correlate with the presence of stainable bile. In patients known to have elevated alkaline phosphatase, the presence of lipoprotein X still correlated with the presence of bile (p = 0.008). We conclude that lipoprotein X is a reliable indicator of cholestasis and that it is more useful than alkaline phosphatase in this application.


[Tangier-disease (author's transl)].

Tangier disease is a rare autosomal recessive lipid transport disease characterized by the absence of the usual high density lipoproteins from plasma and cholesteryl ester storage in many organs. 25 cases of Tangier disease have been described so long. The predominant clinical symptoms include tonsilar hypertrophy, splenomegaly and peripheral neuropathy. The cholesteryl ester storage is limited to macrophages, Schwann's cells and intestinal smooth muscle cells. Hypocholest erolemia (less than 80mg/dl), hypertriglyceridemia (greater than 200 mg/dl), and the absence of high density lipoproteins in agarose electrophoresis are the major plasma abnormalities. The protein moiety of normal high density lipoprotein consists of apoprotein A-I and apoprotein A-II. In Tangier disease, serum concentrations of these apoproteins are reduced to less than 1% and 5-10%, respectively. Theories concerning the pathogenesis of Tangier disease are only incomplete and unproved up to now; however, a structural abnormality of apoprotein A-I causing an inability to  bind to lipid or other proteins (apoprotein A-II) is consistent with several of the recent biochemical findings. The imbalance of cellular cholesterol metabolism caused by the absence of high density lipoproteins as well as the presumed role of these lipoproteins in cholesterol removal from cells are discussed in this article.


Intracellular collagen fibrils in human sarcomas.

Intracellular collagen was detected by electron microscopy in 14 sarcomas including six osteogenic sarcomas, three liposarcomas, three malignant fibrous histiocytomas, one pleomorphic rhabdomyosarcoma, and one childhood rhabdomyosarcoma. It was contained in not only the fibroblastic cells, but also in the osteoblastic, lipoblastic, myofibroblastic, and primitive cells of the various tumors. The banded intracellular collagen fibrils were observed in large phagocytic vesicles and in smaller membrane-bound vesicles which also appeared to fuse with lysosomes. Residual banding could be seen as well in many such phagolysosomes. Banded collagen was also noted in a primary explant in tissue culture. These findings suggest that the configurations of intracellular collagen seen, are parts of a continuum of a secondary pathway of collagen degradation in mesenchymal tissue and that pathway is one factor indicating a close interrelationship between these sarcomas.


Impact of aftercare in the treatment of alcoholics: a cross-lagged panel analysis.

Participation in aftercare activities during the first 3 months following discharge from inpatient treatment had a positive effect on outcome at 3 months and 6 months, but participation decreased between 3 and 6 months as patients who were doing best began to drop out of the aftercare system.


Selective surgical resection in small cell carcinoma of the lung.

Surgical resection has failed notably as definitive treatment for small cell carcinoma of the lung. Newer treatment programs combining intensive chemotherapy with radiation therapy achieve a significant response in about 85 percent of cases, with about 50 percent of patients showing clinically complete remission. Long-term survival without recurrence has been the outcome in a small minority of cases. A frequent mode of failure after treatment of limited disease is recurrence within the chest. The course of one patient treated early in this series suggests that exclusion of initial surgical resection from programs of combined treatment may be a serious omission. Since that time, four patients have undergone initial resection, apparently with uniformly favorable courses to date. Selection criteria based on staging factors are proposed. Admittedly, only a minority of patients will be suitable for this treatment at the time of first diagnosis. Much opportunity exists for improvement in survival rates of patients, even those with limited disease.


Evaluation of sternal bone marrow aspiration for detection of tumor cells in patients with bronchogenic carcinoma.

We evaluated sternal bone marrow aspiration as a routine pretreatment procedure in patients with bronchogenic carcinoma. The overall rate of identification of tumor cells by this technique was found to be low. When oat cell bronchogenic carcinoma was considered as a separate entity, the positive rate was higher. However, in no instance did the bone marrow aspiration result in a change in clinical staging.


Vascular relaxation, aging and thyroid hormones.

Previous work indicates vascular can be studied in vitro and that there is a marked age-associated decrease in the ability of rat aortic strips to relax in response to beta-adrenergic agonists. The present studies were aimed at better understanding the role of thyroid hormones in vascular relaxation and aging. Removal of the thyroid gland from young rats resulted in a decrease in the ability of isoproterenol to relax the aorta. Relaxation caused by nitroglycerin, a non-specific relaxant, was not impaired by thyroidectomy. In 22-month-old rats, isoproterenol caused no relaxation unless exogenous thyroid hormones were administered. Hypophysectomy seven months prior to testing improved the ability of thyroid hormones to restore isoproterenol relaxation of the aorta. The loss of relaxation with age could be due in part to a pituitary mediated loss of responsiveness of aortic tissue to thyroid hormones. The data provide new evidence for the importance of thyroid hormones in beta-adrenergic receptor mediated vascular relaxation and demonstrate that the loss of aortic relaxation with aging can be reversed.


[Skin manifestations in renal transplants].

The authors studied the skin disorders in 50 patients who have undergone renal transplantation. They observed: -- Viral infections (herpes simplex, herpes Zoster, warts) in 56% of the patients. -- Bacterial infections in 36%, resulting in septicemia in 8% of the cases. -- Fungal infections in 26% of the patients. These infections appeared more severe than usual and recurred frequently. The occurence of several infections processes in the same patient was not uncommon. The clinical aspect and high incidence of various infections is related to immunosuppresive therapy. However, there is no clear-cut correlation between the type of infection and the type of treatment used. -- Squamous cell carcinoma occured in one patient. A high incidence of malignancies is known to occur in immunosuppressed patients. -- Skin signs related to hemodialysis (pruritus, hypermelanosis, skin dryness, vascular disturbances) regressed. -- The incidence of adverse reactions to drugs was high. -- 4 cases of ulcerations of the oral mucosa probably related to Azathioprine were observed.


[Aspects to the malignoma of the parotid gland and extratemporal facial nerve surgery (author's transl)].

Malignomas of the great salivary glands are--after own examinations--localized to ca. 90% in the parotid gland and ca. 10% in the sublingual gland. The frequency of different malignomas of the parotid gland, their age and sex incidence, pareses of the facial nerve before therapy, methods of therapy, relapses, letality and survival time are discussed. On own cases the method of extra-temporal reconstructive plastic surgery of the facial nerve is demonstrated.


[Islet cell carcinoma causing Verner-Morrison syndrome (author's transl)].

Predominant symptoms of the Verner-Morrison syndrome are diarrhea and hypokalemia; further symptoms can be impaired carbohydrate tolerance, hypercalcemia distension of the intestine and skin alterations. Diagnosis can be confirmed by computer tomography, angiography and demonstration of increased plasma levels of VIP and GIP. This syndrome is due to islet cell carcinoma of the pancreas in about one third of all cases observed. Total duodeno-pancreatectomy has to be performed, if surgery is possible at all. Patients who cannot be operated upon may receive combined cytostatic therapy.


Gastroenteritis: etiology, pathophysiology and clinical manifestations.

The infectious etiologic agents of gastroenteritis are manifold and have only recently been studied in greater depth. Part of the problem in studies pertaining to diarrhea is the difficulty in identifying fecal "pathogens" among an enormous number of indigenous fecal microorganisms. Finally, the recognition of the pathogenicity of enterotoxins has created an awareness of the complexity of gastrointestinal physiology with host-parasite interactions.


[Dynamics of changes in rat osseous system in chronic cadmium poisoning].

The rats were given subcutaneously CdSO4 in doses 0.7 mg/kg of body weight once a week during one year. After the lapse of 6, 9 and 12 months, the animals were sacrificed and their blood was used to determine the preselected biochemical indices (erythrocytes, hemoglobin, hematocrit, levels of protein, albumins, globulins GOT, GPT, AP and its isoenzymes, calcium, inorganic phosphorus, urea and creatinines). Simultaneously radiological examinations were performed on prepared and dehydrated long bones being estimated. Changes were revealed in morphological parameters of long bones with a marked demineralisation of epiphyses after 9 months of investigations. The above changes were found to correlate with those referring to biochemical indices levels, intensifying with the increase of the exposure period.


[Concentration of serum iron and transferrin saturation with iron as indices of changes resulting from chronic exposure to chemicals in industry].

An attempt was undertaken to use the following indices of systemic changes resulting from longlasting occupational exposure to some chemicals: -- ferrum concentration in blood serum, the level of latent capacity to bind ferrum, and the degree of transferrin saturation with ferrum. The examination involved 177 clinically healthy men, aged 18--60. The control group consisted of 40 healthy men, aged 22--60. In 30.5% of persons, deviations were found, which might be induced by disturbances in general immunity of the organism, whereas in 16,4% the deviations might indicate chronic systemic changes.


Normocholesterolemic dysbetalipoproteinemia with xanthomatosis.

A patient is described who has marked palmar xanthomatosis associated with a normal concentration of plasma cholesterol. Analysis of xanthomas revealed them to contain large quantities of cholesterol with both intra- and extracellular lipids. Examination of plasma lipoproteins showed them to be consistent with a pattern of dysbetalipoproteinemia (Type III hyperlipoproteinemia). VLDL had beta-mobility on electrophoresis, a high cholesterol/triglyceride ratio, and increased apoprotein B. However, arginine-rich apoprotein was not increased in VLDL, in contrast to hypercholesterolemic patients with the Type III pattern. Nevertheless, the E3 subfraction of the arginine-rich apoprotein was virtually absent, which is characteristic of dysbetalipoproteinemia. Cholesterol and bile acid synthesis were in the normal range. Thus, of particular interest was the development of severe xanthomatosis without hypercholesterolemia in this patient. Therefore, tissue accumulation of cholesterol was apparently the result of a qualitative abnormality in lipoproteins and not due to an excess of plasma cholesterol.


Relationship between lipolysis, cyclic AMP, and fat-cell size in human adipose tissue during fasting and in diabetes mellitus.

The in vitro relationship between fat-cell size, glycerol release, and peak concentration of cyclic AMP was investigated in human adipose tissue obtained from 25 obese nondiabetic patients before and after a 7-day fast and from 23 patients with untreated diabetes mellitus. In the obese nondiabetic patients there was a linear correlation between fat-cell size and cyclic AMP concentration, and fat-cell size and the rate of lipolysis. This was found both in nonfasting and fasting nondiabetic patients. However, in diabetes mellitus, there was only a relationship between cell size and cyclic AMP concentration. The alpha-adrenergic and beta-adrenergic activity in human adipose tissue was assessed by comparing the effect of isoprenaline and noradrenaline on the cyclic AMP concentration. The activity of both receptors was found to be increased in fasting obese patients and in diabetics. In both conditions the alpha-adrenergic response to catecholamines predominated in small fat cells, whereas in large ones the beta response predominated. The results suggest that during fasting and in diabetes mellitus there is a correlation between fat-cell size and the responsiveness of the adrenergic receptors. Thus, catecholamines may be involved in regulating the fat-cell volume. The view is expressed that the abnormal catecholamine-induced lipolysis is solely due to changes at the level of the adrenergic receptors during fasting, whereas in diabetes mellitus the sequentional activation of lipolysis is disturbed at deeper sites as well.


Insulin release in response to calcium in the diagnosis of insulinoma.

A calcium infusion (4 mg Ca++/kg/hr) significantly increased plasma insulin levels and reduced blood glucose in 4 patients with insulin-secreting pancreatic islet cell tumors. These parameters were not altered by a similar infusion of calcium in normal volunteers, 2 patients with alimentary hypoglycemia, and 2 with functional hypoglycemia. No difference in response was observed between patients with benign and malignant beta-cell tumors. Infusion of diazoxide (600 mg) with calcium blocked the stimulation of the latter on insulin secretion. The results indicate the usefulness of calcium infusion in the diagnosis of insulin-secreting tumor.


The syndromes of primary hormone resistance.

The clinical features, genetics, pathophysiology, and management of endocrine diseases in which primary hormone resistance is the fundamental defect have been reviewed. Primary hormone resistance has been documented for nearly all hormones--vasopressin, parathyroid hormone, growth hormone, adrenocroticotropin, thyrotropin, gonadotropins, insulin, androgens, cortisol, aldosterone, progesterone, thyroid hormones, and vitamin D. A striking exception is estradiol, a steroid that may be vital for early embryonic development. Most of the hormone unresponsiveness syndromes represent only partial defects, and it is likely that most such patients go unrecognized. Therefore, hormone resistance should be suspected not only when a patient presents with hypofunction of particular endocrine system combined with high endogenous hormone levels but also whenever apparently normal function of an endocrine system is associated with inappropriately elevated levels of the corresponding hormone. The value of these defects in hormone responsiveness as a natural laboratory for the study of the normal mechanisms of hormone action is discussed.


Metabolic basis of endotoxicosis.

Whereas as specific immunological responses are elicited only after a delay of some days, alteration in various biochemical parameters is observed within 1-2 h of endotoxin administration in a number of animal species. Generally the level of several hepatic enzymes (tryptophan pyrrolase, phophoenol pyruvate carboxykinase) metabolites (glycogen, NAD) and intermediates in the energetic homeostasis is lowered by the toxin, increased by the glucocorticoid hormones and maintained at the normal level when the toxic effects of endotoxin are annulled by the counter effects of the protective agent (such as cortisone). Antagonism is also noted on the synthesis of cellular RNA, DNA and protein. However, no unitary process has as yet been singled out to possessing a cause and effect relationship between toxicity and survival. In the intact animal, it is not possible to affirm whether the toxin exerts a direct effect on the organ, the cell or the process in question, especially since endotoxin is phagocytized by the cells of the reticuloendothelial system (RES) in the liver and elsewhere and since the biochemical parameters are a property of the organ specific epithelial cells. Experiments with tissue slices suffer from the problem of permeability and uptake in vitro and are not readily reproducible. Isolated cells in culture are theoretically ideal but exhibit loss of functions and undergo neoplastic type of transformation that renders them unsuitable for relevant biochemical studies. Primary explants of the hepatocytes and the RE cells, as well as hybrids between these two cellular types appear more promising. However, at the moment, isolated liver preparations perfused in vitro offer the best solution by exhibiting intact function, morphology and excellent reproducibility. Collectively, it is tempting to speculate that the extent of subsequent immunological response is a reflection of the preceding biochemical processing, that both sorts of events are in some way mediated by the RE cells, and that the latter may most easily be studied in the intact liver in vitro.


Concanavalin A-mediated agglutination of 3T3 cells after exposure to UV-irradiated herpes simplex virus.

Studies were made to determine the effect of UV-irradiation of herpes simplex virus (HSV) on Concanavalin A (Con-A)-mediated agglutination of 3T3 cells. There were three different phases of agglutination by Con-A of cells infected with HSV. The agglutinability began to increase from 3 or 4 hr, or 72 hr after exposure of cells to HSV. The early-appearing agglutinability was further divided into two phases, based on its sensitivity to metabolic inhibitors. These were tentatively called "Early 1 or inhibitor sensitive", "Early 2 or inhibitor insensitive" and "Late" agglutinability. "Early 1" agglutination, detected from 3 hr post infection (pi), was induced by treating cells with HSV, either active or UV-irradiated for less than 5 min and was inhibited when actinomycin D (1 microgram/ml) or cycloheximide (50 microgram/ml) was added to the cultures. "Early 2" agglutination began to increase from 4 hr pi when cells were inoculated with HSV irradiated for 7 to 20 min and was not affected by either inhibitor. HSV irradiated for 6 min failed to induce either agglutinability. "Late" agglutination, observed 72 hr pi, was detected in cultures which had been treated with HSV irradiated for 4 to 15 min. Among those, virus irradiated for 6 to 8 min was most efficient. HSV-transformed cells were also agglutinated without exception by low concentrations of Con-A.


[Influence of "prudent" diet and clofibrate upon apolipoprotein B in hyperlipoproteinemia type IIa (author's transl)].

If patients with hyperlipoproteinemia type IIa are treated with diet and additionally over a period of two weeks with 2 grams of Clofibrate daily, the cholesterol-level in the serum decreases. This decrease is caused mainly by a reduction of the apolipoprotein B and the LDL-cholesterol in serum. If elevated cholesterol-levels in the serum are reduced through a "prudent" diet, the concentration of apolipoprotein B in serum remains the same. It is not fully understood which influence a diet, which is rich in poly-unsaturated fatty acids and has a low content of saturated fatty acids and carbohydrates, has upon the lipoproteins in the serum. The mode of action of this diet and its significance for the concentration of HDL need further investigation.


Evaluation of a bovine virus diarrhea vaccine.

Singer Strain bovine virus diarrhea (BVD) modified live-virus vaccine, produced in a continuous bovine cell line using equine serum in the growth medium, evoked a high level of serum antibodies and protected against virulent challenge in vaccinated calves. Transmission of vaccinal virus from vaccinated cattle to susceptible controls did not occur when vaccinated and nonvaccinated cattle were kept in constant contact for 23 days. Postvaccinal reactions to the viral vaccine were not observed in vaccinated cattle from 10 feedlots or in cattle vaccinated with multiple doses of the experimental vaccine.


A regulatory system controlling the production of cytochrome aa3 in Neurospora crassa.

The mitochondria of the cyt-2-1, cya-3-16, cya-4-23 and 299-1 nuclear mutants and the [mi-3] and [exn-5] cytoplasmic mutants of Neurospora crassa are deficient in cytochrome aa3, while the cyb-1-1 and cyb-2-1 mutants have mitochondrial b-cytochrome deficiencies. However, the mitochondria from cyb-1-1 cyt-2-1, cyb-1-1 [mi-3] and cyb-2-1 [mi-3] double mutants contain 30% to 50% of the amount of cytochrome aa3 that is present in mitochondria from wild-type; i.e. cyb-1-1 and cyb-2-2 act as suppressors of the cytochrome aa3 deficiency phenotypes that are associated with cyt-2-1 and [mi-3] mutations. The production of cytochrome aa3 can be induced in cyt-2-1 and [mi-3] by growing cells in medium containing antimycin A, an inhibitor of electron transport in the cytochrome bc1 segment of the mitochondrial electrontransport chain. Moreover, the growth of the [mi-3] mutant is strongly stimulated by low concentrations of antimycin A. The induction of cytochrome aa3 by antimycin treatments does not occur in [exn-5], cya-4-23 and 299-1 cells; but does take place in cya-3-16 cells. Although some of the seven constituent polypeptides of cytochrome aa3 are present in mitochondria of [mi-3], the holoenzyme complex is not formed in the mutant. In contrast, the mitochondria of cyb-1-1 [mi-3] and cyb-2-2 [mi-3] double mutants contain a fully assembled cytochrome oxidase complex as well as some unassembled subunit polypeptides. The observations are indicative of the existence of at least two regulatory systems controlling the production of cytochrome aa3. One of the circuits appears to control the basal or "constitutive" production of cytochrome oxidase, the other seems to coordinate the level of cytochrome aa3 with some function of the mitochondrial cytochrome bc1 complex, possibly electron transport.


Eukaryotic ribosomal proteins stimulate Escherichia coli stringent factor to synthesize guanosine 5'-diphosphate, 3'-diphosphate (ppGpp) and guanosine 5'-triphosphate, 3'-diphosphate (ppGpp).

When supplemented with Escherichia coli stringent factor, 80S ribosomes from various sources failed to support guanosine tetra- and pentaphosphate ((p)ppGpp) synthesis. In contrast, ribosomal proteins from 80S, 60S or 40S particles (mouse embryos, rabbit reticulocytes) crossreacted with the E. coli stringent factor. Significant stimulation of (p)ppGpp synthesis was achieved with a concentration as low as 5 micrograms of ribosomal proteins/ml. These observations may provide additional crtieria to detect homologies between eukaryotic and prokaryotic ribosomal proteins.


Nuclear mutants of Neurospora crassa temperature-sensitive for the synthesis of cytochrome aa3. I. Isolation and preliminary characterization.

Three nuclear mutants of Neurospora crassa, temperature-sensitive for the synthesis of cytochrome aa3 have been isolated. When grown at 41 degrees C the mutants have large amounts of KCN-insensitive respiration, reduced amounts of cytochrome aa3 and cytochrome c oxidase activity, and grow more slowly than wild-type cultures grown at the same temperature. When the mutants are grown at 23 degrees C, they are virtually indistinguishable from wild-type strains. The mutants were selected on the basis of their slow growth at 41 degrees C in medium containing salicylhydroxamic acid, and by their inability to reduce 2,3,5-triphenyltetrazolium chloride at 41 degrees c. The selecttion technique was designed to eliminate mutants that did not carry thermolabile electron transport chain components. However, studies on the thermolability of the cytochrome oxidase activity in isolated mitochondria indicate that the enzyme of the mutants is no more susceptible to heat denaturation than is the enzyme in wild-type mitochondria. This suggests that the synthesis or assembly of cytochrome aa3 may be altered in the mutants at the restrictive temperature.


Petite deletion map of the mitochondrial oxi3 region in Saccharomyces cerevisiae.

Fifty eight mitochondrial mutants (p + mit- mutants), all deficient in cytochrome oxidase activity and previously assigned to the genetic region oxi3 on the mitochondrial DNA, were mapped by the method of "petite deletion mapping". This procedure resulted in the identification of at least twenty one different classes of oxi3 mutants, which could be arranged in a linear order. Moreover, it provided a set of twenty three p- petite mutants, each containing a differentially deleted mit DNA segment included in the oxi3 region. The two sets of mutants, p+ oxi3- and p- oxi3+, will be of interest for a further genetic and physical analysis of this mitochondrial DNA segment which spans over about ten thousand base pairs and controls the subunit I of cytochrome oxidase.


Dephosphorylation of histone H1 after mengovirus infection of Ehrlich ascites tumor cells.

The effect of mengovirus infection on the extent of phosphorylation of histone H1 was studied in Ehrlich ascites tumor cells. After prelabeling of the nuclear protein with [32P] orthophosphate, the excorporation of radioactivity was followed as a function of time postinfection. Employing high-resolution polyacrylamide gradient slab gel electrophoresis and autoradiography, it was found that, compared to a relatively slow turnover of phosphate groups in histone H1 in mock-infected cells, in mengovirus-infected cells the excorporation of radiolabel from histone H1 was significantly enhanced. In the latter case, the decrease of histone-bound radioactivity was paralleled by a reduction of the band multiplicity in the histone H1 region of the electrophoresis profile. It was also shown that the microheterogeneity in the histone H1 complements isolated at various times postinfection was reduced to the same basal 3-band level by incubation of the nuclear protein fractions in the presence of alkaline phosphatase. After this treatment, the band multiplicity equaled that found in histone H1 from stationary cells.


30S ribosomal proteins cross-linked to 16S RNA by periodate oxidation followed by borohydride reduction.

Gel electrophoretic techniques have been used to reexamine the RNA-protein cross-linking reaction induced by periodate oxidation and borohydride reduction of 30S ribosomal subunits. The results show that a number of 30S ribosomal proteins become attached to intact 16S RNA by this method, in addition to those already published. It follows that this cross-linking technique as it stands is of little value as a topographical probe of the environment of the 3'-terminus of the 16S RNA.


[Indication for and evaluation of plasmaprotein determinations (author's transl)].

All components of the "fluid tissue" blood should be considered as functional units. This seems familiar to physicians for the blood cells. For the dissolved plasmaproteins most doctors are, however, not yet used to think in functional terms. We propose a functional classification of well-characterized plasmaproteins, and a list of correlations between clinical conditions and protein changes. The clinician and the director of the laboratory have special knowledge and accordingly different tasks. An outline of the possible distribution of their duties and for their collaboration is given. We propose the stepwise evaluation of laboratory tests requested which in its details is obviously quite subjective and debatable. Accordingly, tests are categorized for routine, for special questions, and for scientific investigation. Finally, the clinician ought to know possible sources of error and mistake. For detailed advice, he may ask the director of the laboratory. If these principles--details may be modified--are respected, doctors should be able to obtain the laboratory data they need for diagnosis and treatment with minimal inconvenience to the patient and lowest cost to the community.


[Chemical modification of ferricytochrome c by N-(2,2',5,5'-tetramethyl-3-carboxypyrroline-1-oxyl)-imidazole].

Chemical modification of pig heart ferricytochrome C by the paramagentic analog of N-acetylimidazole-N-(2,2',5,5'-tetramethyl-3-carboxypyrroline-1-oxyl)-imidazole has been studied. Two main modified preparations, both with the single spin label per molecule, have been isolated by means of chromatography on CM-Sephadex C-25. The study of UV-difference spectra of the SL-preparations versus native Cyt C, the spectrophotometric titration of the tyrosine residues in modified proteins and the study of their reaction with hydroxylamine allow to conclude that one of these preparations (fraction II) is lysine modified Cyt C-SL(Lys)-Cyt C and the other (fraction III) is tyrosine modified protein-SL(Tyr)-Cyt C. From the present results and the data available in literature the most probable location of the modification sites in the three-dimentional structure of Cyt C is Tyr-74 in SL (Tyr)-Cyt C and one of the neighbouring lysil residues Lys 72 or Lys 73 in SL (Lys)-Cyt C on the molecular surface. From the absorbtion and CD-spectra of the modified and native Cyt C in the spectral interval 190--450 nm and from the high resolution PMR data the conclusion has been made that  the chemical modification does not alter the immediate vicinity of the heme group and the molecular structure of Cyt C as a whole. Therefore both SL-modified preparations might be useful for the conformational and functional investigations of Cyt C.


Chemical and radiation induced late dominant lethal effects in mice.

Although theoretically expected, experimental data to date have not shown dominant lethal expression to occur throughout the developmental period. Specifically, late post-implantation effects have not been demonstrated. We routinely use an experimental technique in which parental females mated to mutagenically treated males are allowed to give birth and wean their litter, and their uterine horns are then inspected for uterine scars indicative of live and dead embryos. In a number of experiments in which males were mutagenically treated with either chemicals or X-irradiation, a discrepancy was observed between the number of live embryos as determined by the scar technique and the number of live observed at birth, suggesting the possibility of embryonic losses at a late stage in development. Initial analyses showed that mutagenic treatment increased the percentage of these late losses. These differences were statistically significant in 2 of 3 analyses. Factors affecting statistical significance and an understanding of dominant lethal mutations are discussed.


Sleep apnea, hypopnea and oxygen desaturation in normal subjects. A strong male predominance.

Thirty asymptomatic men and 19 asymptomatic women were monitored during one night's sleep to determine the incidence of breathing abnormalities and oxygen desaturation in normal subjects. Twenty men accounted for 264 episodes of nocturnal oxygen desaturation or abnormal breathing. Women never experienced oxygen desaturation, and only three had a total of nine episodes of apnea. These sex differences were highly significant (P less than 0.003). In men, increasing age and obesity correlated positively with the incidence of nocturnal oxygen desaturation and abnormal breathing. Four asymptomatic men weighing more than 90 kg dropped their saturation to very low levels (68 to 72 per cent). Abnormal breathing and oxygen desaturation during sleep in subjects with chronic obstructive lung disease of the syndrome of hypersomnolence with periodic breathing may represent the superimposition of smoking or obesity on a normal tendency to snoring and oxygen desaturation in men.


Alpha-adrenergic hyper-responsiveness in asthma.

Because alpha-adrenergic stimulation causes bronchoconstriction, the alpha-adrenergic responsiveness of 21 subjects with allergic asthma was compared with that of 16 subjects with allergic rhinitis and 38 normal control subjects. None of the patients had taken medications for at least 30 days before study. Alpha-adrenergic responsiveness was measured by the capacity of phenylephrine to constrict the cutaneous vascular bed and to dilate the pupillary sphincter muscle. Asthmatic subjects required 4.0 +/- 0.6 ng to reduce their cutaneous blood flow by 50 per cent, whereas normal controls required 32.0 +/- 7.5 ng (P less than 0.005) and subjects with allergic rhinitis required 23.7 +/- 9.4 ng (P less than 0.02). The pupils of asthmatic subjects dilated by greater than 0.5 mm in response to 1.8 +/- 0.14 per cent phenylephrine, patients with allergic rhinitis required 2.4 +/- 0.16 (P less than 0.01), and normal controls needed 2.7 +/- 0.07 (P less than 0.00001). Therefore, the patients with allergic asthma had significantly enhanced alpha-adrenergic responses when compared both to normal subjects and patients with allergic rhinitis; the possibility that increased alpha-adrenergic activity contributes to the asthmatic diathesis warrants further exploration.


Bovine virus diarrhea-mucosal disease. II. Isolation and characterization of a cytopathogenic virus and experimental production of the disease.

A disease broke out in calves in the Tokachi district of Hokkaido. It induced pyrexia, respiratory symptoms, diarrhea, bloody feces, leukopenia, and sometimes erosion of the oral mucous membrane and muzzle. Its morbidity rate was 90% and its fatality rate 50%. Bovine virus diarrhea (BVD) virus was isolated from organs of dead calves and blood and feces of affected calves. It exhibited a cytopathic effect on calf kidney cell culture. Antisera against the Nose and the Oregon C24V strains of BVD virus showed an antibody titer of the same order against the homologous virus and the isolated strain. Antiserum against the isolated strain, however, showed much lower antibody titers against the Nose and the Oregon C24V strains than against the homologous virus. When inoculated with the isolated virus, two calves manifested acute symptoms, but recovered at any rate. One of them, however, suffered again from clinical infection and died eventually 37 days after inoculation. It presented pathological changes closely resembling those of the case of spontaneous infection. Virus was recovered from its principal organs, intestinal canal, and lymph nodes of various regions of the body.


Inactivated-concentrated virus antigen for indirect complement fixation test of foot-and-mouth disease.

To the culture fluids of BHK-21 cells infected with each of types O, A, and Asia 1 of foot-and-mouth disease virus was added acetylethyleneimine to 0.05% (v/v). The mixtures were incubated at 37 degrees C for 24 hours. To them were then added polyethylene glycol 6000 to 10% (w/v), and the mixtures concentrated to one-tenth of the initial volume. The resulting inactivated-concentrated virus antigens showed a complement fixation (CF) titer ranging from 12 to 24. The recovery rate of CF activity was 40 approximately 60%. This activity of each antigen was maintained at 4 degrees C or -70 degrees C for 6 months at least. Experimentally infected cattle were examined for the development of antibody by the aid of the indirect complement fixation (ICF) test with those antigens. As a result, ICF antibody began to be detected 3 approximately 5 days after inoculation. Its titer reached a maximum 10 approximately 14 days after inoculation and decreased gradually thereafter. It was detected even 232 days after inoculation. There was a tendency for the development of ICF antibody to be parallel with that of neutralizing antibody. It was suggested that ICF antibody might be type-specific. In conclusion, the antigens prepared had such high activity that they could be used for the determination of antibody by ICF. In addition, they were of great practical value because of their sufficient keeping quality and safety.


Field trials on transmissible gastroenteritis live virus vaccine in newborn piglets.

Field trials were conducted on attenuated live virus vaccine of transmissible gastroenteritis to confer active immunity to newborn piglets. To examine innocuity and efficacy of the vaccine, a total of 714 newborn piglets were subjected to these trials. Of them, 357 piglets were administered orally with 10(7.0) TCID50 within 3 days after birth, and the other 357 piglets served as nonvaccinated controls. No undesirable postvaccinal reaction was observed in any vaccinated piglet. Suckling piglets born from nonimmune sows showed a good antibody response after vaccination. They were different, however, in antibody titer from one experimental place to another. Antibody levels were high in piglets raised in the northern experimental places. On the contrary, the antibody response of suckling piglets born from immune sows was influenced by vaccination. In most of these piglets, antibody titers declined markedly and disappeared finally 3 months after vaccination. About 25% of the non-vaccinated piglets showed an antibody response by pen contact with vaccinated ones.


Computer simulation of Gumboro disease outbreak. II. Results obtained with models G-1 and G-2.

The authors conducted a computer simulation with their Models G-1 and G-2 for Gumboro disease ten times in each of the following initial conditions: (1) size of population, 50, 100, and 1,000 chickens; (2) age of housing, 1, 7, 14, and 21 days; (3) nine levels of parentally conferred immunity in one-day-old chicks; (4) four levels of virus contamination; and (5) three steps of coefficient for aggravating morbid status. Every simulation was operated up to the age when all the birds of a flock turned to be insusceptible so as to yield the daily numbers of chickens (1) susceptible, (2) diseased, (3) immunized, and (4) removed, and (5) the accumulation of diseased chickens. The innate resistance, parentally conferred immunity, virus contamination, and morbid status were expressed in such values that they could be compared with one another. As a result, Model G-2 produced a more realistic epizootic pattern than Model G-1, but both models concealed the effect of differences in size of population and in age of housing. Notwithstanding the incompleteness of the models, the computer simulation gave valuable information for a further advancement in this series of studies.


Solubilization of a mammalian beta-adrenergic receptor.

Binding sites for iodohydroxybenzylpindolol with characteristics of a beta2-adrenergic receptor have been identified in a crude membrane fraction from guinea-pig lung. The binding sites could be solubilized by treatment of the membrane fraction with digitonin. Upon solubilization receptors retain their beta2-adrenergic type as indicated by the rank order of potencies of agonists in binding-inhibition experiments. The solubilized receptors demonstrate a marked increase in affinity for agonists compared with particulate receptors whereas antagonist affinity remains unchanged. Solubilized receptors are insensitive to divalent cations (Mg2+, Mn2+, Ca 2+) which increase the potency of agonists for particulate receptors. The effects of Mg2+ can be reversed by Gpp(NH)p in particulate preparations; Gpp(NH)p is ineffective for the solubilized preparation. These experiments establish that beta-adrenergic receptors can be solubilized even from crude mammalian membrane preparations. They also show that the mammalian beta-adrenergic receptor in situ is under constraints with respect to agonist affinity and is modulated by divalent cations and guanyl nucleotides in the intact membrane.


Correlation between the effects of salbutamol on contractions and cyclic AMP content of isolated fast-and slow-contracting muscles of the guinea pig.

The effects of isoprenaline and salbutamol on incomplete tetanic contractions of the isolated soleus (slow contracting) and extensor digitorum longus (EDL-fast-contracting) muscles of the guinea pig were studied and an attempt made to correlate these effects on contractility with changes in cyclic AMP concentrations. Salbutamol was 10-12 times less potent than (+/-)isoprenaline in decreasing the force of subtetanic contractions in the soleus and between 5-6 times less potent in increasing the force of subtetanic contractions in the EDL. This observation plus the lack of activity of both the selective beta1-adrenoceptor antagonist (atenolol) and the selective beta1 agonist (H 133/22) in the EDL implies involvement of beta2-adrenoceptors in these responses of the muscles to isoprenaline and salbutamol. The soleus muscle was about 6-12 times more sensitive to effects of beta-adrenoceptor agonists than the EDL. In concentrations which produced effects on muscle contractility, salbutamol significantly elevated cyclic AMP concentrations in both types of muscle. These effects were antagonised by propranolol. It seems clear that the contrasting effects of sympathomimetic amines on slow-and fast contracting muscle are mediated through a common mechanism-elevation of cyclic AMP. Possible explanations of this apparent paradox are discussed.


Alterations in surface proteins of rat cells transformed by avian sarcoma virus B77.

Cell membrane proteins of avian sarcoma virus B77V--transformed cells LWF B55 and LWF B77 and uninfected rat embryo fibroblasts were analyzed by SDS acrylamide gel electrophoresis. Following alterations in cell surface proteins of LWF B55 and LWF B77 cells were found: one, a slight decrease of two high molecular weight proteins the larger of which corresponds presumably to "LETS" protein and a decrease of a protein with approximative molecular weight 50 000; two, increase in content of proteins with molecular weight of about 90--95 000 and 70--75 000 as well as a marked increase of a protein with molecular weight of 30--35 000.


Collagenolytic activity in leukocytes isolated from patients with leukemias and Hodgkin's disease.

Collagenolytic activity in leukocytes and plasma concentration of hydroxyproline were estimated in 80 patients with leukemias and Hodgkin's disease and in 20 healthy individuals. An increase of both studied parameters was found in chronic myelocytic leukemia and Hodgkin's disease, and a decrease was shown in acute myelocytic leukemia and acute lymphatic leukemia. The results obtained imply that metabolic changes occur in leukemia leukocytes, and indicate the presence of disturbances in the metabolism of connective tissue in the studied disorders.


Peripheral motor nerve conduction velocities in children undergoing chronic hemodialysis.

Peroneal motor nerve conduction velocities (MNCVs) were performed on 58 children aged 20 months to 12 years undergoing chronic hemodialysis. No patient had any clinical manifestations of uremic polyneuropathy. The mean MNCV in 21 children at the onset of dialysis was 42.0 m/sec; significantly slower than the control group of 51.4 +/- 5.3 m/sec (p less than 0.001). 16 studied performed between the 1st and 6th month had a mean MNCV of 43.2 +/- 5.7 m/sec, also slower than the normal controls (p less than 0.001). We conclude that peroneal MNCVs are reduced in most children at the initiation of chronic hemodialysis and do not change significantly during the next 6--12 months and that the routine practice of obtaining such studied is of no value in the clinical management of children undergoing chronic hemodialysis.


Exaggerated natriuresis in ACTH hypertension in sheep.

Adrenocorticotrophic hormone (ACTH) administration to sheep (100 IU/day) produces a sustained increase in arterial pressure within 24 h. The effect of ACTH on excretion of an intravenous saline load was tested in 8 adult cross-bred Merino ewes. A significant diuretic response to saline loading was found after 24 h but no increased natriuresis. On days 3 and 6, diuretic and natriuretic responses were both significantly increased. Steroid-induced sodium retention may have abolished the natriuretic effect on day 1.


Nephritogenic glycoprotein. VIII. Demonstration of the limited role of immune complex mechanism for the production of membranous glomerulonephritis.

Proliferative glomerulonephritis was induced in rats by a single injection in the hind footpads of the glycoprotein isolated from pronase digests of homologous renal cortex, in spite of the evidence that the glycoprotein no longer possessed the antigenic activity with respect to producing the nephrotoxic antibody. In rats given the glycoprotein (without trichloroacetic acid (TCA) treatment) prepared from pronase digests of homologous renal cortex, morphologic changes of proliferative glomerulonephritis were followed (3--4 months after injection) by those of typical membranous glomerulonephritis with an immunofluorescent 'granular' pattern, but in animals which received the glycoprotein (with TCA treatment), the morphologic changes of the kidney were those of proliferative glomerulonephritis with an immunofluorescent 'mesangial' pattern throughout the whole course. Morphologic changes of membranous glomerulonephritis induced in the group given the glycoprotein (without TCA treatment) can be explained by an immune-complex mechanism, superimposed on the basic pathogenesis (common to both groups) of proliferative glomerulonephritis with immunofluorescent 'mesangial' pattern.


Studies on ATP: thiamine diphosphate phosphotransferase activity in rat brain.

The experiments described in this paper serve as a contribution to the solution of the discrepancies which exist in the assay of ATP:thiamine diphosphate phosphotransferase activity (EC 2.7.4.15), presently in use as a tool for the diagnosis of Leigh's disease (SNE, subacute necrotizing encephalomyelopathy). The results obtained with this phosphotransferase assay can, in part, be explained by the presence of thiamine triphosphate (ThTP) in the preparation of thiamine diphosphate (ThDP) used as a substrate, by the inhibition by ATP of the ThTP phosphohydrolase activity, present in fractions of rat brain homogenates, and by the stimulation by ThDP of the ATPase activity. When [2(-14)C-thiazole]thiamine was used for the synthesis of [14C]ThTP in fractions of rat brain, it was found that after chromatographic separation of thiamine and its phosphates, 14C radioactivity could be demonstrated in the ThTP fractions, even in the absence of an enzyme source. Probably a complex is formed between [14C]thiamine and a phosphate ester which behaves chromatographically as ThTP. It is concluded that the assay system for the measurement of ThTP synthesis in its present form is, in our hands, not suitable for diagnostic purposes.


Regulation of (Na+, K+) adenosinetriphosphatase of nerve ending membranes: action of norepinephrine and a soluble factor.

Norepinephrine added in vitro to nerve ending membranes from rat cerebral cortex stimulates the activity of (Na+, K+) adenosinetriphosphatase (ATPase) only in the presence of the soluble brain fraction. In its absence norepinephrine inhibits the enzyme. (Mg2+)ATPase also showed stimulation by norepinephrine in the presence of the soluble fraction, but of lesser magnitude. The activation of (Na+, K+)ATPase by norepinephrine is not reproduced by cyclic AMP and is not antagonized by either alpha- or beta-adrenergic blocking agents. These results suggest that the stimulation caused by norepinephrine is a direct effect on the enzyme and is not mediated by cyclic AMP or adrenergic receptors.


Selective changes in the phosphorylation of endogenous proteins in subcellular fractions from cyclic AMP-induced differentiated neuroblastoma cells.

The endogenous phosphorylation of specific proteins was studied in subcellular fractions from proliferating and cAMP-induced differentiated neuroblastoma cells. Fractions containing nuclear, membrane-bound, and cytosolic proteins were incubated with [gamma-32P]ATP, in the presence and absence of added cyclic nucleotides. Phosphate incorporation into specific proteins was determined by slab-gel electrophoresis of sodium dodecyl sulfate-solubilized reaction products. Cytosol fractions from differentiated cells demonstrated a twofold increase in cAMP-dependent phosphorylation of a specific protein with apparent mol wt of 59,000 daltons and a comparable decrease in cAMP-independent phosphorylation of another protein (97,000). The nuclear fraction of differentiated cells showed an increase in the cAMP-independent phosphorylation of two nonhistone proteins (110,000 and 102,000). Membrane fractions from differentiated cells exhibited a differential decrease in endogenous phosphorylation of specific proteins. Selective alterations in the phosphorylation of specific proteins in various subcellular components may be important biochemical events associated with the increased levels of differentiated functions in neuroblastoma cells in culture.


The transcerebral arteries. A postmortem arteriographic study.

For precise interpretation of CT brain scan and magnification angiography, an in-depth knowledge of the arteries of the white substance is necessary. Postmortem arteriographic studies on a large series of brains provide us with significant information about morphologic as well as pathological changes, of which a few interesting aspects are elucidated.


Effect of experimentally induced generalized seizures on the wakefulness--sleep cycle.

The effect of experimentally induced generalized seizures on the relations between the various phases of sleep in the wakefulness--sleep cycle was studied in cats with chronically implanted electrodes. After generalized convulsions induced by electrical stimulation of the dorsal hippocampus, unlike those of amygdalar origin, clearly defined changes were observed in the structure of the wakefulness--sleep cycle. In the postseizure period, with increasing wakefulness sharp depression of paradoxical sleep takes place. However, in slow wave sleep only slight changes were observed. Instead of a rebound phenomenon, paradoxical sleep was sharply induced in cats after preliminary deprivation of paradoxical sleep as a result of generalized seizures induced by electrical stimulation of the neocortex. Nonspecific hyperactivation of the brain, in the form of epileptiform discharges, thus has a particularly marked effect on the structure of paradoxical sleep.


[Surgery of endocrine pancreatic tumors. Results of a survey in the German Federal Republic].

Within a ten-year scan (1967-1976) 207 insulinomas, 50 gastrinomas, 8 Verner-Morrison tumours, 5 glucagonomas and 12 endocrine pancreatic tumours with associated MEA syndrome (multiple endocrine adenomatosis) were treated surgically at  various university hospitals (information obtained by questionnaire). Half of the insulinomas were treated by enucleation, one third by resection of the tail of the pancreas. Total gastrectomy was the procedure of choice in 80% of patients with gastrinoma, but sometimes pancreatic resection to remove the tumour was added. An new therapeutic concept of using histamine-H2 receptor antagonists for treating patients with Zollinger-Ellison syndrome is discussed. In the eight patients with a Verner-Morrison syndrome removal of the tumour or distal pancreatic resection was the procedure of choice.


Germ cell malignancies of the ovary.

Historically, ovarian germ cell malignancies carry a very poor prognosis. The use of surgery alone or in combination with radiation therapy does not appreciably increase survival. The combination of surgery, chemotherapy, and, in some instances, radiation therapy has accounted for an 89% two-year survival in 26 patients with germ cell malignancies of the ovary exclusive of "pure" dysgerminoma. Short-term chemotherapy appears as effective as the long-term therapy advocated by other investigators.


Pelvic mass presenting as meralgia paresthetica.

A 40-year-old woman presented to her gynecologist with an apparent unilateral neuropathy of the lateral cutaneous femoral nerve of the thigh (meralgia paresthetica). On examination, the sensory disturbance extended outside the usual distribution of the lateral femoral cutaneous nerve, suggesting a more proximal lumbar plexus involvement. She was subsequently found to have uterine fibroid disease. At the time of surgery a large posteriorly situated uterine mass was noted to compress the superior portion of the lumbar plexus. Following surgery, she has been symptom-free.


Dysplastic enamel in odontomas.

A series of odontomas was studied by light microscopy, with special emphasis on abnormal enamel in these lesions. The findings were compared to those in amelogenesis imperfecta and in other conditions in which abnormal enamel is found. It was concluded that dysplastic enamel exhibits a number of appearances which are described in this article. A strongly basophilic laminated material was also found, often covering prismatic enamel, but it did not itself appear to be a form of enamel; its identity is not clear. Odontomas, being readily available, offer a good opportunity to study dysplastic enamel.


Ultrastructure of mucoepidermoid carcinoma in minor salivary glands.

Three cases of mucoepidermoid carcinoma of minor salivary glands were studied by electron microscopy. Mucus-secreting cells contained numerous mucous globules and bundles of fine cytoplasmic filaments. Another cell type contained a large number of glycogen particles, akin to tumor cells in glycogen-rich adenocarcinoma, and it is postulated that these cells represent the intermediate cells observed by light microscopy. Epidermoid cells contained a moderate amount of tonofilaments and various numbers of organelles. Mucus-secreting and epidermoid cells that surrounded a cystic space exhibited many microvilli. Results of this study support the theory that mucoepidermoid carcinoma develops from salivary gland duct cells with different cellular differentiation potentials and, in general, agree with the conventional grading system of mucoepidermoid carcinoma.


Gingival metastasis from primary hepatocellular carcinoma. Report of a case.

A case of primary hepatocellular carcinoma metastatic to the gingiva is described. Hepatocellular carcinoma is an uncommon malignancy, generally occurring in a cirrhotic liver, which rarely metastasizes to the maxillofacial area. Of eight such cases in the English-language literature, the present case is the fourth involving metastasis to the gingiva. Hepatocellular carcinoma would seem to metastasize with equal frequency to the gingiva and to the mandibular bone. In the case described, histologic examination of the gingival lesion definitively established the diagnosis following somewhat equivocal results of needle biopsy of the liver.


[Diagnosis and therapy of Wilms' tumor based on a survey of 16 children with nephroblastoma].

On the second place in malignant diseases of children, after the leukemias, we could find the Wilms-Tumor. Of the 16 children we treated in the years from 1965 to 1977, 8 children died, 2 patients couldn't be any longer observed and 6 patients are still alive. 5 children of these have obtained now a relapse-free survival from 1 year and 2 months to 2 years and 7 months. We could see, that the prognosis depends only on the stage of the tumor and not on the age of patients. On 3 cases we will try to show, how difficult the diagnosis of the Wilms-Tumor is and how important it is, to treat resolutely pulmonary and liver metastases. As diagnostic methods were used i. v. P., the sonography and the selective renalangiography. Since 1976 our treatment consists of preoperative irradiation of tumors, nephrectomy, postoperative irradiation of tumor-bed and adjuvant chemotherapy (actinomycin D, vincristine and adriamycin). Pulmonary and liver metastases are a domain for chemotherapy, combined with irradiation (danger of pneumonitis and toxic hepatitis) and eventually a resection is necessary. Only the good cooperation of an oncologic team could achieve an improvement of the cure rate of this tumor, as we know from the American countries (survival 75%).


Evidence that raphe-spinal neurons mediate opiate and midbrain stimulation-produced analgesias.

The present experiments were undertaken to assess the role of neurons in the nucleus raphe magnus (NRM) in mediating opiate and stimulation-produced analgesias. A cannode for both electric stimulation and local opiate microinjection was placed in the midbrain preiaqueductal gray region of decerebrate or chloralose-urethane anesthetized cats. Microelectrodes recorded the responses of medullary NRM neurons. Raphe-spinal neurons were identified by antidromic activation from the cerevical spinal cord. Fifteen of 20 raphe-spinal cells tested were excited by electrical stimulation of the midbrain. Of 49 NRM neurons tested, 26 were excited by either systemic or midbrain injection of opiate agonist. Twelve of 33 NRM cells tested by midbrain microinjection were excited. In 10 the effect was reversed by naloxone. Seventeen raphe-spinal neurons were tested; 5 showed naloxone-reversible excitation to either midbrain or intravenous injection of opiates. NRM neurons respond to auditory and somatic stimuli; at least half respond maximally to somatic stimuli of noxious intensity. These findings are consistent with the hypothesis that the raphe-spinal projection mediates opiate and electrical stimulation-produced effects from midbrain sites. The properties of raphe-spinal neurons suggest that they are part of a negative feedback system which monitors and limits the output of spinal dorsal horn pain-transmission neurons.


Corynebacterium parvum as an adjuvant for Trypanosoma cruzi epimastigote vaccines: a comparison with saponin and Bordetella pertussis.

The effect was compared in CBA mice of adding Corynebacterium parvum, saponin, and Bordetella pertussis to living or killed Trypanosoma cruzi (Y strain) epimastigote vaccines on the induction of protective immunity against subcutaneous (s.c.) challenge with blood trypomastigotes. The addition of C. parvum to a low dose of T. cruzi vaccine, which alone was non-protective, generated a greater degree of protection than did saponin or B. pertussis. C. parvum alone increased resistance to infection to a variable and usually weak extent. The addition of C. parvum to larger doses of T. cruzi vaccine, which were themselves sufficient to elicit some degree of protection, improved resistance when the challenge was given 1 or 12 weeks after immunization, but lowered it at 3 weeks. It is concluded that the comparative efficacy of adjuvants for T. cruzi vaccines needs to be assessed on 3 parameters: (1) the dose of antigen, (2) the dose of adjuvant and (3) the time interval between immunization and challenge.


Suppression of malignancy in mouse-man hybrid cells.

Somatic cell hybrids were prepared by fusing malignant mouse melanoma cells with diploid human lymphocytes and fibroblasts in the presence of inactivated Sendai virus. Clones of hybrid cells differed from one another with respect to the number of chromosomes. In particular, human chromosomes were preferentially lost and mouse chromosomes retained. Hybrid clones containing a range of human chromosomes were selected and assayed for tumorigenicity in nude mice, and the presence or absence of specific human chromosomes was correlated with malignancy. Both human lymphocytes and human fibroblasts suppressed the malignancy of mouse melanoma cells. In most cases, suppression of malignancy was complete; in a few cases, tumours developed but the tumorigenicity of these hybrids was considerably less than that of the parent melanoma cells. Chromosome analyses failed to localize the suppressive effect to a specific chromosome.


Noncondylomatous wart virus infection of the postmenopausal cervix.

Noncondylomatous papilloma virus infection of the cervix is much more common than formerly realized. The majority of patients are young, but two cases are reported here in postmenopausal women.


REM sleep deprivation and pain thresholds in rats.

The relationship between REM sleep deprivation and pain threshold was measured using 36 Sprague-Dawley female rats. Relative to that of the controls, a significant lowering of threshold to painful electrical stimulation was observed during each of the post-treatment tests, i.e., immediate, and after 3- and 24-hr. recovery periods, for the animals which had been REM deprived.


Lack of alpha-adrenergic component in the chronotrophic action of serotonin on isolated atrium of hamster.

Effects of serotonin on alpha-adrenergic receptors of isolated hamsters' atria preparation were investigated. The positive chronotropic effect of serotonin on isolated atria of the hamster is not related with postsynaptic alpha-adrenergic receptors.


Effect of exogenous cAMP in the rabbit right auricle.

Isotonic solution of cAMP-Na was applied into spontaneously beating auricular fibres by a cut-end method. Cyclic AMP enhanced the spontaneous rate (mean 48%) and increased the contractile tension (mean 297%). These results provided direct evidence that cAMP is involved in the spontaneous activity and contraction in the heart muscle.


Atopic dermatitis: clinical and immunologic aspects and treatment.

Atopic dermatitis is a chronic disease marked by exacerbations and remissions. It begins in early infancy and may persist into late adulthood. Flares of dermatitis may be precipitated by emotional stess, extremes or sudden changes in humidity or temperature, and other factors. Treatment consists primarily of the use of mild topical agents to reduce inflammation and pruritus. Long-term systemic therapy with corticosteroid is not recommended. Topical preparations containing agents that increase the local levels of cyclic adenosine monophosphate (eg, caffeine) may be useful.


The study of the influence of DDT on the antirachitic activity of vitamin D in rats.

Rachitic Wistar strain rats were administered with a therapeutic dose of vitamin D3 or vitamin D3 with DDT or cod-liver oil containing the same and tenfold larger amount of DDT. No alterations in the activity of vitamin D were found.


The effect of drugs stimulating central dopaminergic system on transformation of exogenous adenine into c-AMP.

We tested the effect of dopamine (DA), apomorphine (APM), amantadine (AMD), dimethylaminoadamantane (DMAD) or haloperidol (HP) on the in vitro formation of c-AMP from ATP labelled intracellularly with exogenous 14C-adenine or from endogenous ATP in the slices of rat striatum. DA stimulated the synthesis of c-AMP from endogenous and 14C-adenine labelled ATP. Nonspecific stimulants of the dopaminergic system, APM, AMD and DMAD, stimulated the c-AMP synthesis much weaker than DA did. After application of APM, ADM or DMAD, the utilization of ATP formed from 14C/U/adenine for synthesis of c-AMP was lower than after DA. The effects of combined treatment with DA together with APM, AMD or DMAD was additive. HP, 1 X 10(-3) M did not change the amount of radioactive and total c-AMP, but inhibited the stimulatory action of DA and, to a lesser degree, of APM, AMD and DMAD. The synthesis of c-AMP from endogenous ATP stimulated with APM, AMD and DMAD in striate body slices was inhibited by HP more strongly than the synthesis of c-AMP from ATP labelled with exogenous 14C-adenine. The results indicate that ATP synthesized from intracellular adenyl nucleotides is more effectively utilized for the synthesis of c-AMP stimulated by APM, AMD or DMAD in striate body slices, than ATP labelled with 14C-adenine.


Biochemical studies on endometrium from postmenopausal women receiving hormone replacement therapy.

Nuclear oestrogen-receptor and soluble progesterone-receptor have been measured in postmenopausal endometria from women receiving either Premarin or Premarin plus norethisterone. Oestradiol dehydrogenase has been measured in some samples. It is concluded that the doses of Premarin currently in use have a potent oestrogenic effect on the endometrium. Norethisterone does not affect the amount of oestrogen entering the nucleus but it may temporarily suppress the biological activity of the oestrogen.