Tissue-specific inhibitor of lymphocyte proliferation extracted and purified from calf spleen. Biological and chemical properties.

A partly purified calf spleen extract which inhibits lymphocyte proliferation in a tissue-specific, species-nonspecific, nontoxic, and reversible way, and may thus contain a chalone-like activity, has been further characterized. Our results show that the inhibitor works in G1-phase. The activity is resistant to heat, trypsin- and ribonuclease-treatment. It appears to be an acidic molecule and it does not appear to contain ribonucleic acid. These properties are compared to the characteristics which have been described for tissue-specific inhibitors of lymphocyte proliferation by other authors.


[Effect of diphenylhydantoin administered during gestation and lactation on the motor development and cerebellar histology of the young rat].

Rattus norvegicus females were treated by diphenylhydantoin (D.P.H.), all along pregnancy and lactation. 4 groups were constituted: a 100 mg DPH/kg/day group, a 50 mg DPH/kg/day group; a placebo group (treated with pure water), and control group. D.P.H. was given twice a day by a gastric tube. The cerebellar Purkinje cells studied through light microscopy and transmission electron microscopy in young rats (25 days old) showed no visible alteration. 2 motorcoordination tests were applied to the young rats, during their 2nd and 3rd weeks of post-natal life. Young rats of DPH 100, DPH 50 and placebo groups showed a backwardness relatively to control. This backwardness may be attributed to the maternal forced feeding stress, but not to a specific action of the DPH.


[Demonstration of multiple innervation of skeletal muscle fibers in the rat following localized repetitive freezing of the sciatic nerve].

The medial head of the gastrocnemius muscle of the rat was denervated by three successive freezings of the sciatic nerve at the same focal localization. After the third denervation, the compound potentials obtained during a transient period of time indicated that some muscle fibres are innervated by two or several axonal terminals. It can be concluded from the electrophysiological, histological and cytoenzymological results that this multiple innervation is polyneural and located within a single end-plate.


[Molecular forms of acetylcholinesterase in the slow muscle and the fast muscle of the chicken].

Five molecular forms of AChE are present in the slow (ALD) and twitch (PLD) muscles of the chick. These forms have 4 S, 7 S, 11 S, 15 S and 20 S sedimentation coefficient in sucrose gradient. The heaviest forms, the 20 S and 15 S of AChE are absent in uninnervated muscles and present in innervated muscles. In innervated muscles, the 20 S and 15 S AChE are present in both nerve-free segments and end-plates zones. The 20 S and 15 S which are not specifically associated with the end-plate zones in the chick could be considered as a biochemical "marker" of neuromuscular interactions.


[In vitro expression of the thyroid gland genome. Difference between chromatin and DNA].

In vitro, transcription by thyroid chromatin has been compared to that carried out by deproteinized DNA prepared from the same tissue. The chromatin-primed transcripts are represented by 4S and 10S RNAs, whereas the DNA-primed transcript is heterogenous and polydisperse. The sequences expressed in vitro have been analyzed by hydridization of 4S and 10S RNA to the total native thyroid DNA. Most of the sequences transcribed are represented by intermediate repetitive-associated an unique sequence. Furthermore, they are expressed only by chromatin and not by DNA. Thus, thyroid chromatin very likely holds in vitro the same fonctional restriction exhibited in vivo, whereas the transcriptional behaviour of thyroid DNA is totally aspecific.


[Effect of glycolysis inhibitors on the uptake of metronidazole by the protozoa Tritrichomonas foetus and Entamoeba invadens].

Uptake of metronidazole by the anaerobic protozoa, Tritichomonas foetus and Entamoeba invadens is dependent on the energy metabolism of these organisms. The inhibitors of glycolysis, iodoacetamide and sodium fluoride, inhibit the uptake. An atmosphere of hydrogen eliminates this inhibition in the hydrogenase-containing T. foetus but not in E. invadens which lacks the enzyme.


[Effect of urethane on the granulopexic activity of the reticuloendothelial system and the production of virus inhibiting factor or interferon].

Urethane (ethyl carbamate) did not affect the rate of the clearance of carbon from the blood in splenectomized mice, while this compound slowed down the carbon clearance in intact mice. Production of virus-inhibiting factor (IF) or interferon, especially early IF induced by virus was impaired by urethane in splenctomized mice as well as intact ones. The role of reticulo-endothelial system in IF formation was discussed.


[Effect of long-term phenytoin treatment on the levels of calcium and magnesium in rat femurs].

In young male rats, long-term treatment with phenytoïn reduces the amount of calcium and magnesium in the femurs and provokes a stimulation of the parathyroiïds witnessed by the hypertrophy and hyperplasy of the parathyroid cells. Neither plasma calcium nor plasma and erythrocyte magnesium are modified.


[Histo-autoradiographic study of a testosterone target organ, the epididymis of the lizard (Lacerta vivipara), after administration of 3H-17 beta-estradiol].

[6,7 3H] oestradiol-17 beta was injected into castrated male viviparous lizards in order to compare retention of this steroid to that of testosterone during the period of sexual activity. Retention of the isotope in epididymis was greater than in blood, lung and stomach. Radioautographs of epididymis indicated that oestradiol or a metabolite was concentrated in cell nuclei and over discharged secretory granules as was observed with testosterone. Reason of such binding is not yet known.


[Effect of various 2-methyl-(4'-chlorobenzoyl)-4-phenoxy)-2 propionic acid (LF 153) analogs on the respiratory activity of rat liver mitochondria].

Seven analogs of methyl-2 [chloro-4' benzoyl)-4 phenoxy]-2 propionic acid, (LF 153) have been tested for their effects on respiration and phosphorylation of rat liver mitochondria suspensions. They differ from one another by the sort of binding between both aromatic cycle as well as by the nature and position of the halogenated substitutions and alpha methylation in the propionic chain. All the compounds which have been tested acted as inhibitors of the electron transport chain and uncouplers of phosphorylations.


[Kinetics of Mn2+ ion metabolism in rat hepatic tissue].

Intravenous injection of MnSO4 with 54Mn (0,33 mg/100 g) into rats showed that Mn2+ ions are transferred into intracellular organites and specially into mitochondria. The mitochondrial clearance curve of 54Mn has been analyzed. It is appeared that three compartments participate in the distribution of Mn2+. The third compartment is the most important.


[Intestinal and renal excretion of phosphorus and calcium in rats receiving potassium metabisulfite, tannic acid and ethanol, alone or in combination].

In the young rat, the addition of potassium metabisulfite or tannic acid in the diet decreases the fecal excretion of phosphorus, but increases its urinary excretion, whereas the addition of ethanol induces opposite results. These different effects are additive. On the other hand, the ethanol increases the urinary excretion of calcium, but only in the animals which receive neither metabisulfite nor tannic acid.


[Lactate dehydrogenase and its isoenzymes in human umbilical cord tissue].

Study on umbilical cord tissue, completely bloodless, for determination of lactate deshydrogenase activity and its distribution among the five iso-enzymes. Comparison with placenta, amniotic fluid, serums of blood of cord and of mother. Cord tissue is very active (about 360 muKatals, in average) and it is a similar result in placenta (as it is possibly bloodless). Blood serum of cord is more active than amniotic fluid, which is more active than maternal serum, but they are 80 to 200 times less active than cord tissue. After electrophoresis, a very large predominance of the slow iso-enzymes L.D.H. 4--5 is found in cord tissue (72%), amniotic fluid (67%) and placenta (56%), whereas the fast iso-enzymes L.D.H. 1--2 are predominant in the serums of cord blood and of mother. These data indicate an intense metabolic activity in the cord tissue, which has also an high level of lactate, and this seems related to the foetal metabolism for anaerobic glycolysis in oxygen weakly provided tissues.


[Histological study of the development of Fasciola hepatics in Lymnaea truncatula, L. glabra and L. palustris infested at hatching].

The development of Fasciola hepatica is histologically analysed in Limnaea truncatula, L. glabra and L. palustris infested at hatching with a single miracidium. The development of the redial generations of Fasciola is not affected by the species of snail host but depends on growth of the snail. In snails of size within 2 mm (considered at the day 49 of infestation to 20 degrees C), the rediae show a delay of maturity compared with rediae observed in snails of higher sizes. The distribution of redia 1 of generation 1 should have an influence on growth of the snail host.


[Hormonal regulation of 5 alpha-reductase activity in anterior pituitary gland microsomes of the male rat].

It was previously shown that the microsomal 5 alpha-reductase activity in the male rat pituitary was increased by castration. Subcutaneous administration of androgens to castrated rats prevented the rise in 5 alpha-reductase activity. Their relative efficiency was as follows: 5 alpha-dihydrotestosterone greater than 5 alpha-androstane-3 alpha, 17 beta-diol greater than testosterone. Under our experimental conditions 5 alpha-androstane-3 beta, 17 beta-diol and estrogens were inefficient. The rise in 5 alpha-reductase activity following castration is exclusively located in hypophysis and it is probably due to an increased of the enzyme biosynthesis.


[Effect of L-eburnamonine on bronchial respiratory resistance in the anesthetized guinea pig. Comparison with vincamine].

In anesthetized guinea pigs, i.v. injection of l-eburnamonine (l-E) induced a moderate constriction of bronchia. This bronchoconstriction was partially antagonized by atropine and brompheniramine and nearly completely inhibited by papaverine; methysergide was devoid of antagonistic activity. It was suggested that the contractive activity of l-E is complex and not specific. Similar results were obtained with vincamine (Vi) but vincamine's bronchoconstriction was not completely inhibited by papaverine. Furthermore, the bronchoconstrictor activity of Vi was more important and more durable than that of l-E.


[Intestinal motility after intraduodenal and intrajejunal feeding].

Post-prandial intestinal motility, analysed through two electromyographic parameters, duration of inhibition of myoelectric complex (DIMC) and percentage of spike potentials (PSP), was studied after ingestion of glucids, proteins and lipids. Post-prandial intestinal motility depends on both chemical nature and caloric load of nutriments: DICM depends on those two factors but PSP only depends on nature of nutriments. Post-prandial intestinal motility also depends on route of administration of nutriments. Intra-jejunal administration versus intra-duodenal administration increases DIMC observed for glucids and proteins, diminishes DIMC observed for lipids and diminishes PSP observed for glucids and proteins. These results indicate a specificity of intestinal post-prandial motility with characteristics of nutriments. Intestinal digestion and absorption of nutriments, just as hormonal secretion in response to intestinal passage of nutriments could explain such a specificity.


[Effect of protein deprivation on ammonia metabolism in the rat].

In order to investigate the mechanisms of the hyperammonemia previously described in protein deprivation, the effects of sucrose and fasting on the ammonia metabolism were studied in control, streptozotocine-induced diabetics and colectomized rats. Hyperammonemia, hyperglutaminemia, hypouremia and intolerance to an ammonium load were observed in the control group after a 5 days sucrose-feeding. Any of these abnormalities were found in the diabetic animals whereas hyperglutaminemia did not occur in colectomized animals. It is concluded that protein deprivation obtained by sucrose feeding involves an hyperammonemia by a reduction of ureogenesis (which seemed to be related to an elevation of the ratio insulin/glucagon) and an hyperglutamininemia of colic origin.


[A and C particles in mouse embryos].

Electron microscopic examination of embryos of the BALB/c and AKR strains of mice from the 1-cell stage to 14 days of age revealed 2 types of intracisternal A particles, one type of C particle budding into the extracellular space and an endoplasmic reticulum-association "dense-cored veiscle". The occurrence of the particles showed a marked dependence on the developmental stage of the embryo. A small percentage of 1 blastomere embryos in both strains showed the presence of a small number of A particles. Embryos of 1 to 16 blastomeres of the AKR strain with A particles were on average more frequent than in the BALB/c strain. The percentage of 7 and 14 day embryos with C particles was much greater in AKR than in Balb/c mice.


[Cytological and cytochemical effects of a liver extract from an adult rat on chick embryo hepatocytes and fibroblasts cultivated in vitro].

The effects of an extract from adult liver on chick embryo hepatocytes and fibroblasts cultivated in vitro are studied with cytological and quantitative cytochemical methods. This substance inhibits the multiplication of hepatocytes adn prevents these cells from entering into the S phase of the cycle. No effect is observed on the chick embryo fibroblasts. Not any morphological alterations are observed in the two cell types.


[Arachidonic acid activation of the rat cardiovascular system].

The hypotensive activity of arachidonic acid is more important by intraaortic than by intravenous injection, in the rat. The evisceration of the animal abolishes this difference and reduces the activity of arachidonic acid. This action is not accompanied by thrombopenia and is only observed with high doses of arachidonic acid in this species. The hypotensive activity is inhibited by indomethacin but not by tranylcypromine.


Treatment of unilateral iliac artery disease by femorofemoral bypass grafting.

Between Jan. 1, 1970 and June 30, 1977, 50 men and 23 women underwent femorofemoral bypass grafting. The average age of the group was 64.7 years. The procedure was performed for disabling claudication in 50 patients and for limb threatening ischemia in 23. Knitted Dacron grafts were used in all but two patients. The operative mortality was 4.1% and the late mortality 21.9%. There were six complications related to the prostheses, three infected grafts and three false aneurysms. Thrombosis of the graft occurred in 15 patients; the graft was successfully revised in 2. The cumulative 5-year patency rate determined by life-table methods was 73.4%. The causes of failure appeared to be well defined and unilateral iliac artery disease. The donor iliac artery, poor runoff through a diseases deep femoral artery on the recipient side and infection of the graft. This study indicates that femoro-femoral bypass has a definite place in the management of patients with unilateral iliac artery disease. The procedure can be performed on selected patients with a low operative mortality and an acceptable patency rate.


Knitted Dacron ultra-lightweight grafts--a warning.

A 61-year-old man presented with gross femoral and abdominal pulsation secondary to severe ectasia of an ultra-lightweight Dacron graft. All patients who have received this particular graft should be followed up closely and probably the graft should be replaced if progressive enlargement occurs.


Neocarzinostatin: a phase I clinical trial with five-day intermittent and continuous infusions.

Neocarzinostatin, a polypeptide antibiotic, was administered by both continuous and intermittent intravenous infusion to 76 patients with a variety of malignant diseases. Doses ranged from 500 to 6500 units/m2 X 5 days. With levels greater than or equal to 1800 units/m2, bone marrow suppression (particularly thrombocytopenia) was the dose-limiting toxicity. Delayed bone marrow recovery was less dose-dependent and occurred in 58% of initial treatment courses in solid tumor patients. Allergic reactions were more frequent with intermittent than with continuous infusions (20% vs. 2% of courses). No complete or partial remissions were observed among solid tumor patients although clinical improvement was noted in one patient with mycosis fungoides and one patient with multiple myeloma. One complete and two partial remissions were noted among 21 patients with acute leukemia. There was one complete remission in a patient with chronic leukemia. Leukemic patients on intermittent therapy evidenced greater change in bone marrow cellularity than those treated by continuous infusion. Although neocarzinostatin has some activity in the treatment of acute leukemia, continuous infusion offers no advantage over intermittent therapy.


A rational approach to dementia.

Dementia is a common problem facing all medical practitioners and it frequently results in hospitalization and death. This review provides a framework for dealing with dementia in clinical practice that is based on both traditional concepts and recent advances in the understanding of the problem. Distinguishing at the bedside between dementia and other disorders of intellect is emphasized. The main causes of dementia and their clinical characteristics are reviewed and a rational approach to definitive diagnosis is developed. Simple, effective symptomatic forms of therapy are described.


Studies of mixed lymphocyte reactions, surface B cell antigens, and intracytoplasmic immunoglobulins in "null cell" acute lymphocytic leukemia.

Lymphoblasts from "null cell" acute lymphocytic leukemia (ALL) were analyzed for the pattern of proliferation displayed in a mixed lymphocyte reaction (MLR), the presence of a B cell surface antigen, and for the presence of intracytoplasmic immunoglobulin (ICIg). "Null cell" ALL was defined by cytologic and cytochemical criteria and by the absence of spontaneous rosette formation and surface membrane immunoglobulin in cell suspensions of the malignant lymphocytes. In eleven of fourteen patients the proliferative characteristics of lymphoblasts in the MLR were similar to those observed with normal B enriched lymphocytes. In eleven cases studied, anti-B cell serum reacted with a majority of the lymphoblasts. None of the ten cases examined displayed ICIg in the lymphoblasts. We conclude that the "null" lymphoblast from most cases of ALL is a B cell in an early stage of development.


T-cell chronic lymphocytic leukemia: report of a case and review of the literature.

We recently observed a unique case of T-cell type chronic lymphocytic leukemia, documented by cell surface marker analyses. Immunologic tests at the time of diagnosis were as follows: 1) skin tests were negative; 2) in vitro lymphocyte responses to antigens or pokeweed mitogen were absent; 3) in vitro lymphocyte responses to phytohemagglutinin, concanavalin-A or allogeneic cells were low but significant; and 4) stimulating capacity of leukemic T cells were absent. Chromosomal analysis of bone marrow showed a pattern of 45 chromosomes with a marker chromosome. Terminal deoxynucleotidyl transferase activity was very low. Patient responded extremely well to COP (cyclophosphamide-oncovin-prednisone) therapy. Patient died of recurrent transitional cell carcinoma while his leukemia was in complete remission, approximately 20 months after the diagnosis of T-cell CLL.


Concanavalin A-inducible suppressor cells in regional lymph nodes of cancer patients.

Regional tumor-draining lymph nodes of 11 of 14 patients with urological tumors and one of four controls studied contained suppressor cell precursors that could be activated by concanavalin A (Con A) to suppress the proliferative response of autologous lymphocytes to Con A. In contrast, no suppression of lymphocyte proliferation by lymph node cells that were not activated with Con A was observed in four patients tested. The suppressive effect was not due to decreased viability or increased release of cold thymidine by Con A-activated cells nor to alteration in the time course of the proliferative response of Con A-activated cells. Mitomycin C treatment of lymph node cells 24 hr after activation did not abrogate their suppressive activity. Peak suppression was observed after 72 hr in culture. The amount of suppression measured could be maximized by treatment of suppressor cells with mitomycin C 24 hr after activation and by washing the cells immediately before pulse labeling with tritiated thymidine. The concentration of Con A required to produce peak suppression varied from patient to patient with optimal doses ranging from 5 to 25 microgram/ml.


Interaction of int protein with specific sites on lambda att DNA.

We have studied the interaction of highly purified Int protein with DNA restriction fragments from the lambda phage attachment site (attP) region. Two different DNA sequences are protected by bound Int protein against partial digestion by either pancreatic DNAase or neocarzinostatin. One Int binding site includes the 15 bp common core sequence (the crossover region for site-specific recombination) plus several bases of sequence adjoining the core in both the P and P' arms. The second Int-protected site occurs 70 bp to the right of the common core in the P' arm, just at the distal end of the sequence encoding Int protein. The two Int binding sites are of comparable size, 30-35 bp, but do not share any extensive sequence homology. The interaction of Int with the two sites is distinctly different, as defined by the observation that only the site in the P' arm and not the site at the common core region is protected by Int in the face of challenge by the polyanion heparin. Restriction fragments containing DNA from the bacterial attachment site (attB) region exhibit a different pattern of interaction with Int. In the absence of heparin, a smaller (15 bp) sequence, which includes the left half of the common core region and the common core-B arm juncture, is protected against nuclease digestion by Int protein. No sequences from this region are protected by Int in the presence of heparin.


Platinate toxicity: past, present, and prospects.

Using traditional toxicologic methods, four species were studied for their qualitative and quantitative predictiveness of the toxic effects of cis-dichlorodiammineplatinum(II) in man. Of the four species studied, mouse, monkey, rat, and dog, the latter two gave the best overall results. Using an in vivo rat model, it was found that except for chloroplatinic acid, eight of the tested analogs were less nephrotoxic than the parent drug, cis-dichlorodiammineplatinum(II). The in vitro renal toxicity screen using flounder tubules showed that of the 26 compounds studied, about half were less toxic than the parent compound. This in vitro mini-tox system can be performed about 30 times faster and at one fiftieth the cost of the in vivo model. The in vitro studies also provided evidence that the biochemical site of toxicity of platihates is on ATPases. The latter studies suggested a basis for unifying the mechanistic interpretation of the toxic actions on such disparate target organs as the kidney, nerve, stomach, and inner ear.


[Demonstration of a soluble factor capable of inhibiting allogenic lymphocyte proliferation in man].

During the secondary mixed lymphocyte reaction (MLR), i.e. after the double in vitro allogenic sensitization between responding and stimulating cells bearing at least one HLA-DR incompatibility, suppressor cells are developed [1]. They are able to inhibit a primary MLR provided that the stimulating cells possess the same DR incompatibility as the immunizing cells. We report here that this inhibition is due to the production by these cells of a soluble suppressor factor which acts on responding cells provided that they share at least one gene product of the HLA-D region with the cells producing the factor. This a feedback process of auto-inhibition occurring after hyperimmunization. The action of this suppressor factor seems to be genetically restricted to an as yet unknown locus in linkage disequilibrium with HLA-DR.


Visual problems in the handicapped child.

The importance of carrying out a preliminary examination of vision and eye movements in all handicapped is stressed. In any case of doubt a full ophthalmological and orthoptic examination is essential and is best carried out in the congenial environs of a District Handicap Centre. Eight hundred and ninety-three children with a wide variety of handicaps were seen at the Leeds Regional Child Assessment Centre between 1972 and 1977, and 324 were found to have a visual or visuomotor defect. The types of defects are discussed under headings which describe the main handicap.


Assessing and facilitating play in handicapped children.

The importance of using the play period in an educational curriculum to promote social and cognitive growth is discussed, especially as it pertains to handicapped children. Facilitation and stimulation of play at the child's current level of functioning is advocated. A sample play programme is discussed as an illustration of how problems in planning can be handled. A list of decision points and important factors to consider in planning for play is then provided.


Profile: the voluntary council for handicapped children.

The Voluntary Council for Handicapped Children is an independently elected Council, established under the aegis of the National Children's Bureau in 1975. The Council arose from a recommendation in the Eileen Younghusband Working Party's report, Living with Handicap, in 1970. This major report draws attention to the gaps, overlaps and general lack of co-ordination and information about services for handicapped children. It recommended the creation of a genuinely multidisciplinary council to provide a forum for joint discussion and action, to offer a comprehensive advisory and information service covering all aspects of childhood disability. The Voluntary Council for Handicapped Children is unique in providing a comprehensive service for all categories of handicap, and for statutory and voluntary agencies. Parents and professionals can use the Council as a resource centre on an individual basis, although casework cannot be provided. The role of the Council is essentially that of a signpost to existing resources. It is, in effect, an advisory body collecting, evaluating and disseminating information, promoting study and discussion by organizations and individuals and seeking to identify gaps in present services.


T cell-mediated immune responses of lupus-prone BXSB mice and other murine strains.

Cellular-mediated immunity in the newly described BXSB strain of mice, which is prone to autoimmune disease, has been compared with that of two other strains, C57Bl/6 and 129/J. Quantificaiton of cytotoxic T cell responses to alloantigens and viruses (lymphocytic choriomeningitis and vaccinia virus) showed no difference in the kinetics of appearance and relative activity of cytotoxic T cells per spleen between the young and old BXSB and the control mice. The T cell-dependent primary footpad swelling after local injection with lymphocytic choriomeningitis virus was within the same range for all strains tested with respect to kinetics, but the size was greater by two-fold in C57Bl/6 mice. The susceptibility to systemic infection and subsequent induction of lymphocytes immune to Listeria monocytogenes were about equivalent in all strains. However, clearance of Listeria by the reticuloendothelial system and early non-immune bactericidal activity of the young and old BXSB were significantly lower than in the control strains. The results indicate that the cellular-mediated immunity (CMI) of BXSB mice compared favourably with that of other strains and that there is no apparent differences between CMI of BXSB mice before the onset of disease and during the course of disease. The role of the reduced reticuloendothelial function of BXSB mice in their autoimmune disease or in their high susceptibility to infection remains to be determined.


Depressed primary in vitro antibody response in rheumatoid arthritis.

We have studied the primary in vitro antibody response toward a hapten in cultures of peripheral blood lymphocytes from twenty-two patients suffering from regular rheumatoid arthritis (RA). These patients were not receiving immunosuppressive drugs or corticosteroids and had not taken Aspirin or non-steroidal anti-inflammatory agents for at least 72 hr. The control groups included thirty-two healthy subjects and twenty-seven control patients. The mean anti-TNP response of the RA patients was significantly lower than that of both control groups. No pre-existing anti-TNP or IgG response could be detected. A search for suppressor cells in co-cultures of RA and normal lymphocytes was negative. On the contrary, the extent of allogeneic enhancement in such co-cultures was comparable to that observed when control lymphocytes were co-cultured. RA serum added to normal lymphocytes cultures showed a dramatic inhibitory effect in only two out of nine cases. A follow-up study has strongly suggested that RA lymphocytes could increase their in vitro antibody response upon treatment.


The immunopathology of Hodgkin's disease.

Answers are beginning to emerge to the questions posed in the introduction to the preceding section. In vitro techniques that allow characterization of malignant cells have particular relevance when, as in Hodgkin's disease, the precise identity of the cells remains in doubt. Monolayer tissue cultures derived from Hodgkin's disease tumours and maintained as established cell lines have proven amenable to a variety of cytogenetic, immunological, enzymatic, and ultrastructural studies. Tissue culture experiemnts, in conjunction with meticulous immunological studies of individual Reed-Sternberg cells from non-cultured tumours, suggest that neoplastic cells of Hodgkin's disease are related to, and possibly derived from, cells of the monocyte-macrophage system. The lymphocytes that comprise an integral part of the cellular proliferation and form the basis for histological subclassification of the tumour could be a manifestation of cell-mediated immunity against this non-lymphoid malignant cell. The immunodeficiency of patients with untreated Hodgkin's disease of limited anatomical extent is not the primary event of the disorder and probably not related to the site at which the aetiological agent acts. The deficit does not result solely from impaired T-cell function and appears to arise as a consequence of excessive suppressor cell activity. Inhibitory monocyte-lymphocyte interactions may be one of the causes of defective cell-mediated immunity in Hodgkin's disease. The possible significance of elevated levels of circulating immune complexes in the serum of patients with Hodgkin's disease is indicated by the finding that such complexes react with cells of long-term monolayer tissue cultures derived from the tumour. Circulating immune complexes may be one source for intracellular immunoglobulin in non-cultured Hodgkin's disease cells. The presence of polyclonal immunoglobulin G on the membrane and within the cytoplasm of Reed-Sternberg cells could be due to in vivo binding and ingestion of immune complexes by such cells. The specificity of the interaction between soluble complement-containing immune complexes and neoplastic cells of Hodgkin's disease depends on the nature of the complexed antigen. The complexes could non-specifically attach via an Fc receptor or, if the complexed antigen is identical to a tumour cell antigen, the binding could be specific. If the immune complexes are tumour specific they could provide a source for isolation and identification of tumour-associated antigens. However, the aetiological significance of antigens and putative oncogenic viruses thus far identified in association with Hodgkin's disease remains to be clarified.


Propanil-chloracne and methomyl toxicity in workers of a pesticide manufacturing plant.

In a survey of occupationally acquired disease in workers at a pesticide plant, we found that 11 (11%) of 102 workers had been hospitalized for illness related to chemical exposures; highest hospitalization rates occurred in packaging (27%), production (22%), and maintenance (9%) workers. Commonest causes of hospitalization were intoxication by the carbamate pesticide methomyl [1-(methylthio)ethylideneamino methyl carbamate], a reversible cholinesterase inhibitor, and methemoglobinemia following exposure to 3,4-dichloroaniline. On clinical evaluation, five (46%) of 11 packaging workers, the group with the highest exposure to methomyl, had experienced blurred vision or pupillary constriction. Seventeen (61%) of 28 production workers with exposure to dichloroaniline and propanil (3'4'-dichloropropionanilide) had chloracne, an acne-form dermatosis caused by the contaminant tetrachlorazobenzene in propanil and dichloroaniline. The chloracnegenic potentials of propanil and dichloroaniline were verified by rabbit ear tests. These findings reemphasize the hazards inherent in the the manufacture and formulation of pesticides and herbicides.


Detection of environmental depigmenting substances.

We systematically screened the depigmenting capacity of several phenols, catechols and organic antioxidants. Clear-cut depigmentation was achieved with monomethyl ether of hydroquinone (MMH) and tertiary butyl catechol (TBC) using black guinea pigs and black mice as animal models. A goal was to establish a reliable in vivo method to demonstrate or to predict the depigmenting action of chemicals on mammalian melanocytes. There was no universal solvent or optimal body site, although all tested areas could be depigmented. Irritation induced by some vehicles and test materials produced false positive responses. False negative responses with known depigmenting chemicals were observed. Utilizing these observations, we propose a model for screening medicinal and industrial chemicals for depigmenting capacity.


Interdigital clavus: predisposition is the key factor of soft corns.

The soft corn is defined as an interdigital hyperkeratosis. Footwear contributes to interdigital corns when there is a congenital or acquired predisposing factor. These predisposing factors cause apposition of particular bony prominences between adjacent toes. The congenital factors include a short first metatarsal, a short fifth metatarsal, or third and fourth metatarsals of equal length. The acquired predisposing factors are hallux valgus and associated abduction, hammer deformity, burrowing and curling of the lesser toes. Sixty-five per cent of the 1,063 interdigital corns studied occurred in the fourth interspace. Seventy per cent of the fourth interspace corns occurred between the proximal interphalangeal joint of the fourth toe and distal interphalangeal joint of the fifth toe. Conservative treatment is recommended for most cases.


Pathology of spastic muscle in cerebral palsy.

The histopathology of muscle in cerebral palsy has not been elucidated because correlated morphologic and biochemical data on normal pediatric muscles are insufficient to allow adequate correlation of pathologic findings. One hundred and eight muscle biopsies were taken during reconstructive operations on 85 patients. Normal values for pediatric muscles were obtained from a literature review and supplemented with our data on normal patients. Fiber sizes are normally different for children of different ages. Histochemical staining of enzyme systems demonstrate that adenosine triphosphatase staining, pre-incubated at pH 9.4, 4.6, AND 4.3 WAS USED FOR FIBer typing and fiber size. Depending on the muscle biopsied and the clinical status of the patient, there is a variety of patterns of type I and type II fiber atrophy, hypertrophy, and myopathy. In some cases, denervation changes are present to suggest nerve entrapment. Correlated clinical observations suggest type I fiber predominant muscles do not re-educate well when surgically transferred to perform a specified function.


The enzymatic replication of DNA.

Enzymatic mechanisms of DNA replication have been investigated using small bacteriophages as probes to illuminate the cellular systems upon which they must rely during infection. Conversion of the circular, single-stranded DNAs of phages M13, G4, and phi X174 to their duplex forms has revealed the participation of diverse ways to start a new chain and a complex DNA polymerase III holoenzyme upon which all these systems depend for chain elongation. The phi X174 system, which is the most exacting and revealing of the host chromosomal replication pattern, includes at least twenty polypeptides for making the viral DNA into a duplex and multiplying the duplex. Resolution and purification of these numerous proteins is in train and their reconstitution into a "replisome"-like structure is envisioned.


Determination of left ventricular wall thickening in patients with chronic systemic hypertension. Correlation of electrocardiography and echocardiography.

M-mode echocardiography was performed in 81 patients with chronic arterial hypertension in order to determine the specificity and sensitivity of the various ECG criteria used for diagnosing left ventricular hypertrophy (LVH) in the determination of left ventricular wall thickening (LVWT). Fifteen popular ECG criteria were studied and showed to be highly specific for LVWT (90 percent to 100 percent). TV1 greater than TV6, RV8 greater than 20 mm and SV1 + Rmax V5 or V6 greater than 35 mm were the most sensitive criteria (69 percent, 54 percent, and 52 percent respectively). The popular limb lead criteria for LVH were less sensitive than the precordial lead criteria in the determination of LVWT. The Estes point system, although less sensitive than some of the other voltage criteria, showed an absolute specificity for LVWT. The ST segment deviation with strain pattern was found in 46 percent of patients with LVWT. An isolated ST segment deviation without any other voltage criterion reflected at most only mild wall thickening. Six patients with LVWT had normal ECG; all of them were categorized in the mild LVWT group. Left axis deviation was found to be a poor indicator of wall thickening in uncomplicated hypertensive patients.


An unusual cause for mitral valve fluttering.

A 23-year-old patient with patent ductus arteriosus had coarse diastolic fluttering of the mitral valve leaflets on the echocardiogram in the absence of usual causes.


Pneumopericardium following laparoscopy.

There have been no published reports of pneumopericardium complicating laparoscopy. Following an apparently uncomplicated laparoscopy, a 35-year-old woman developed pneumopericardium associated with subcutaneous emphysema of the neck. This resolved without specific therapy and without sequelae.


[Electrocardiographic and histomorphological changes in the myocardium of rats with Selye's experimental hypertension].

The authors described electrocardiographic and histomorphological changes in white rats with coarctation hypertention, induced by the method of Selye. The electrocardiographic changes were manifested as prologation of preauricular-ventricular conduction time, dislocation of the intermediate part ST to the isoelectrical line, low, negative or biphasic T-wave at the initial stages of the experiment, but after the thirthieth day there was a pathologic Q-wave, a reduced voltage of the steap curves and manifested left type of ECG in the majority of the experimental animals. Histomorphological and histochemical study on thmyocardium revealed in the beginning of the experiment mainly lesion changes, but sign of myocardial hypertrophy and manifested difuse and/or focal myocardial fibrosis on the 30th to the 90th day of the experiment.


[Organ cultures of human embryonic and fetal cartilage tissue (histological and histochemical studies)].

The author examined histologically and histochemically the peculiarities of tendon tissue of human embryos and fetuses. Inferences were made that under the conditions of organ culture for 7 days in the explanted tendon pieces there were histological peculiarities, characteristic of the reactions of the embryonal tendon tissue in the preparation and of the ossification with formation of "a zone of cellular columns". Processes of ossification were not observed which is explained by the lack of vascular in the explants. He found a reduced amount of acid glycosaminoglycans, an increase of the amount of neutral mucopolysaccharides and topographic redistribution of lipids and glycogen contrary to the data, observed in the control tissues.


Evidence for divergent glucose effects on calcium metabolism in pancreatic beta- and alpha 2-cells.

Elucidation of the role of Ca2+ in the secretion of insulin and glucagon is complicated by the presence of different types of cells in the pancreatic islets. Visualization of calcium in sections of guinea pig pancreas with the histochemical reagent glyoxal bis-2-hydroxyanil revealed the most intense staining in the endocrine part but no differences between various islet cell types. A procedure for eliminating the majority of the beta-cells by streptozotocin injection in the guinea pig enabled a comparison of collagenase-isolated islets rich in alpha 2-cells with islets from untreated animals rich in beta-cells. The latter islets contained 24.6 +/- 2.4 mmol calcium/kg dry wt, as estimated by flameless atomic absorption spectrophotometry. This is twice as much as noted for the exocrine pancreas or the islets rich in alpha 2-cells. After storage for 3 days in culture medium, the two types of islets contained similar amounts of calcium. The cultured islets displayed differences related to cellular composition when measuring the incorporation of 45Ca into a lanthanum-nondisplaceable (intracellular) pool. In the presence of 3 mM glucose, more 45Ca was incorporated into the islets rich in alpha 2-cells. Increasing the glucose concentration to 20 mM with or without further addition of 30 U/liter bovine insulin was without effect on the 45Ca uptake into the islets rich in alpha 2-cells but stimulated that into islets rich in beta-cells. The different calcium dependence on glucose in the two types of islets may indicate that increased uptake of Ca2+ is a component of the mechanism for the secretion of both insulin and glucagon.


Plasma levels of 16 alpha-hydroxypregnenolone, 16 alpha-hydroxyprogesterone and 16 alpha-hydroxydehydroepiandrosterone in the fetus and neonates.

Simultaneous determination of unconjugated 16 alpha-hydroxypregnenolone (16 alphaOH-Preg), 16 alpha-hydroxyprogesterone (16 alphaOH-Prog) and 16 alpha-hydroxydehydroepiandrosterone (16 alphaOH-DHEA) in fetal and neonatal plasma was performed utilizing a newly developed radioimmunoassay. In all neonates, the three 16 alpha-hydroxysteroid levels were consistently higher in umbilical cord plasma than in the maternal peripheral circulation. 16 alpha-OH-Preg in the umbilical arterial plasma increased from 11.2 +/- 3.1 at 24 weeks to 29.7 +/- 12.0 ng/ml at term, 16 alphaOH-Prog from 15.5 +/- 3.2 to 34.3 +/- 11.0 ng/ml and 16 alphaOH-DHEA from 5.1 +/- 1.2 to 5.9 +/- 1.0 ng/ml. In the anencephalic neonates, only 16 alphaOH-Preg showed an increase pattern under ACTH priming. 16 alpha-OH-Preg levels for normal full term neonates remain relatively constant at the first 24 hr and show a slight decrease at 3 days post partum. In small full term neonates, 16 alphaOH-Preg levels in umbilical arterial plasma are considerably higher than in normal neonates and remain at roughly equivalent levels for the first 5 days post partum. 16 alphaOH-Prog and 16 alphaOH-DHEA levels in umbilical arterial plasma in normal and small full term neonates are almost equal and both groups show a rapid decrease during the first 24 hr. Comparison with findings of the three 16 alpha-hydroxysteroids in fetal and neonatal plasma is discussed.


Clustering of chromosomal aneuploidy and tracing of nondisjunction in man.

Chromosomal aneuploidy is the most frequent genetic damage observed in newborn children and originates as a rule from nondisjunction during maternal or paternal germ cell development. The error of chromosome segregation could be allocated in the past--at least in cases of 47,XXY--to maternal meiosis I (50%) or meiosis II (10%) and to paternal meiosis I (40%). Recent cytological improvements with various banding techniques enabled a further study on the origin of nondisjunction. Summarizing the published data one can argue that errors in Downs' syndrome are most often due to cleavage errors during maternal meiosis I. Approximately 70% of errors occur in oogenesis and only 30% in spermatogenesis. Maternal meiosis I seems also to be involved in most cases of fetal trisomy 16. Such a preferential missegregation of chromosomes offers the possibility of studying more closely the very mechanisms of nondisjunction in mammalian meiosis and early cleavages.


Down's syndrome and maternal age in British Columbia, 1972--75.

The occurrence of Down's syndrome in British Columbia during the period 1972-75 is analyzed with respect to maternal age distribution. This period is compared with previously studied periods. No marked trends are evident in the various age group-specific rates studied. The significance of these findings is discussed in connection with a possible role of environmental nutagens in induction of Down's syndrome and the maternal age effect.


Cell-free synthesis of the mitochondrial ADP/ATP carrier protein of Neurospora crassa.

ADP/ATP carrier protein was synthesized in heterologous cell-free systems programmed with Neurospora poly(A)-containing RNA and homologous cell-free systems from Neurospora. The apparent molecular weight of the product obtained in vitro was the same as that of the authentic mitochondrial protein. The primary translation product obtained in reticulocyte lysates starts with formylmethionine when formylated initiator methionyl-tRNA (fMet-tRNAfMet) was present. The product synthesized in vitro was released from the ribosomes into the postribosomal supernatant. The evidence presented indicates that the ADP/ATP carrier is synthesized as a polypeptide with the same molecular weight as the mature monomeric protein and does not carry an additional sequence.


An electrophoretic study of native myosin isozymes and of their subunit content.

Myosin polymorphism in muscles has been studied by a variety of electrophoretic techniques, in non-dissociating and in dissociating conditions. The analysis of myosin isozymes in the native state was achieved in pyrophosphate buffer and required only minute amounts of protein; identical results were obtained with purified or crudely extracted myosin. The determination of the subunit content of each isozyme was done in the presence of sodium dodecyl sulphate or urea for light chain, and in a phenol, acetic acid and urea system for heavy chain screening. Electrophoresis in non-dissociating conditions has led to the separation of up to a dozen of myosin isozymes, differing in mobilities by as much as 30%. Muscle specificity of myosin was clearly established. Apart from a few exceptions, all the muscles tested were shown to contain more than one myosin species; fast-twitch muscles for instance all contained the same three isozymes, but in variable ratios. Class specificity of myosin appeared related to the relative proportions of isozymes in a given muscle. A second electrophoresis in dissociating solvents of the myosin bands first resolved in pyrophosphate buffer has then allowed a further characterization of the various isozymes. The differences in mobilities observed in the native state were shown to come either from the light chains, or from the heavy chains, or from both. The first case was illustrated by the three species present in fast muscles, which were shown to correspond to three alkali light-chain isozymes, the heterodimer representing in some instances up to 40% of the total. Next to light-chain muscle type specificity, electrophoresis in the phenol, acetic acid, urea system has led to the detection of differences in the heavy chains of fast, slow and cardiac myosins. The application of these various electrophoretic techniques to the analysis of the modification of myosin isozymes during development or in pathology studies can be considered.


Heart muscle disease among adult Nigerians: role of nutritional factors in its aetiology.

A study of 44 Nigerians with heart muscle disease defined as congestive cardiac failure and cardiac enlargement of unknown cause with a presenting diastolic blood pressure of not more than 100 mm Hg has shown 20 were alcoholics. 12 of these belonged to the high socioeconomic class. 17 were thiamine deficient; 11 of these consumed alcohol excessively and 8 of the 11 belonged to the high socioeconomic class. Only 3 alcoholics were identified in 52 controls. None of the 3 patients was thiamine deficient but 10 others were. Only 1 patient with heart muscle disease had a reversible high output cardiac failure. The mean serum albumin of the patients with heart muscle disease was significantly lower than controls. There was no significant difference between the mean levels of serum potassium in the study group and controls. It is concluded that chronic alcoholism is not rare among Nigerians with heart muscle disease. Although there is no convincing evidence to show that malnutrition or thiamine deficiency could in themselves cause the chronic myocardial failure seen in heart muscle disease, they could be conditioning factors which increase the susceptibility of the heart to other injurious agents.


Evaluation of left ventricular performance in aortic stenosis, aortic regurgitation and mitral regurgitation from the stroke work/left ventricular mass ratio. Europ. J. Cardiol., 10/4, 279--294. 132 patients with a pure valvular dysfunction affecting a single orifice, namely aortic stenosis, aortic or mitral regurgitation, were studied. All patients, including 20 control subjects, underwent hemodynamic examination of both right and left heart chambers including left cineangiography. Using the stroke work index/myocardial mass ratio (SWI/MLV), for which the limits in normal subjects are narrow (0.81 +/- 0.03 . g-1) it was possible to divide these patients into three groups: Group I (SWI/MLV greater than 0.87 gm . g-1) characterized by a proportionately greater increase in stroke work index than myocardial mass (hyperfunctioning ventricle). Group II (0.87 gm . g-1 greater than or equal to SWI/MLV greater than or equal to 0.75 gm . g-1) characterized by a parallel increase in stroke work index and myocardial mass (normally functioning ventricle). Group III (SWI/MLV less than 0.75 gm . g-1) for which the increase in myocardial mass was proportionately greater than that of the stroke work index (hypofunctioning ventricle). As one progresses from group I to III, there is a concomitant fall in ventricular function with decreased mean velocity of circumferential fiber shortening (VCF), ejection fraction (EF) and increased enddiastolic volume (EDV) together with the hypertrophy of the left ventricle during the last stage. We conclude that the SWI/MLV ratio is an easy to calculate index, independent of the unerlying dysfunction, which evaluates left ventricular function by taking into account the myocardial mass.


Assessment of a combination of doses of fenoterol and ipratropium suitable for a single metered-dose aerosol.

This paper reports a study of the bronchodilator effects of doses of the beta 2 agonist fenoterol and the muscarinic blocker ipratropium suitable for administering in combination as a standard dose of two discharges from a single metered-dose pressurised aerosol. In 12 middle-aged bronchitics who had already been shown to respond to both types of drug the combination was almost always a little (6% on average) more effective than either drug singly. It is possible that an equal or better effect could have been obtained if fenoterol or perhaps ipratropium had been given alone in an individually determined maximally effective dose.


Suppressor cells and immunodeficiency in (NZB x NZW)F1 hybrid mice.

Old (15-20 month) male (NZB x NZW)F1 (B/W) mice have severely impaired spleen cell reactivity to phytohemagglutinin (PHA), a mitogen which stimulates mainly T lymphocytes. Spleen cells from old mice markedly suppressed the PHA response of splenocytes from young (3-4 month) B/W males. Similar suppressor activity was not present in the spleens of old mice of four nonautoimmune strains. The suppressor activity of old B/W spleen cells was mediated by a nonphagocytic, radioresistant, mononuclear leukocyte. Although this cell was eluted in the "T lymphocyte" fraction of nylon wool colums, it was not sensitive to treatment with anti-Thy-1 antiserum and complement. Suppressor activity was lost after 18 h incubation at 37 degrees C in tissue culture medium. Supernatants of these overnight cultures had no suppressive effect on fresh young B/W spleen cells. Old B/W spleen cells suppressed PHA reactivity more than concanavalin A or lipopolysaccharide reactivity. Kinetic studies demonstrated an increasing suppression with time over 72 h of culture. This study demonstrate that the severely impaired PHA reactivity of old B/W mice is mediated, at least in part, by active suppression.


Ontogeny of cells involved in the suppressor circuit of the immune response.

Some macrophage (M phi) cell surface structures which bind T cell-derived factors remain intact after the M phi are killed by heating at 56 degrees C (but not 72 degrees C) for 45 min. As a result, appropriately killed M phi (HK M phi) can act as competitive antagonists for those M phi functions which are involved in binding and active presentation of T cell-derived regulatory signals. By blocking the transmission of these signals with HK M phi, we have found that the spleens of newborn mice contain considerable numbers of "latent" helper cells whose activity is not ordinarily seen because it is overridden by suppressor mechanisms. Similarities between these neonatal helper cells and a subset of adult T helper "inducer" cells (cell surface phenotype Ly-1+; Ly-2-, 3-; IJ+; Qa 1+), whose activity appears in significant numbers only after immunization, are described.


Studies on T lymphocyte activation II. The target cells for concanavalin A-induced growth factors.

Growth factors contained in Con A(concanavalin A)-conditioned media (CM) maintain exponential growth in T cell blasts derived from mitogen stimulation of spleen cells with Con A, phytohemagglutinin, lentil lectin and pokeweed mitogen (PWM), as well as from mixed lymphocyte reactions to H-2D or I-C-encoded determinants and from non-H-2 Mls locus-controlled reactions. Such growth factors are strictly T cell blast-specific, inasmuch as they do not stimulate resting, small T or B lymphocytes nor B cell blasts generated by lipopolysaccharide or lipoprotein activation. The responsiveness of T cell blasts to CM appears to be the result of the availability on the cell surface of an acceptor site for growth factors which is not expressed in resting cells, because T cell blasts, but not small spleen cells, absorb out the growth-promoting activity contained in CM. Furthermore, lectins such as Con A and PWM interfere with the blast surface membrane in such a way that they inhibit the response to growth factors. Finally, there is no detectable allotypic or isotypic restriction in the activity of Con A-CM on a variety of target T cell blasts.


Mg2+-ATPase defective mutant of Escherichia coli and thiamine transport.

Mg2+-ATPase deficient mutant of Escherichia coli showed an evident dependency of thiamine uptake on the oxidative metabolism of glucose, whereas the parent strain did not. In both cells, this uptake was completely inhibited by H+ conductors.


Combined laparoscopy and minilaparotomy in the management of unruptured tubal pregnancy: a preliminary report.

Following laparoscopic diagnosis of unruptured tubal pregnancy, six patients underwent partial salpingectomy using a minilaprotomy technique. None of the patients had any complications resulting from the surgery. Four were discharged within 48 hours of surgery and the others on the 3rd postoperative day. When an ectopic pregnancy has been diagnosed before rupture the technique seems preferable, as it entails a less extensive hospital stay than does conventional laparotomy. The smaller incision is more comfortable and is cosmetically acceptable. The technique is relatively easy to use, and it is hoped that the minimal invasion of the peritoneal cavity will have a less deleterious effect on future fertility.


Induction of suppressor cell mechanism in antilymphocyte serum-induced skin allograft tolerance in mice.

In the B10.D2 leads to B10.D2(M504) strain combination (H-2D incompatibility), 20--40% of skin allografts survive for more than 100 days in ALS-treated recipients. Allograft tolerance in ALS-treated recipients could not be abolished by adoptively transferred normal or immune syngeneic spleen cells, but it could be adoptively transferred by spleen or lymph node cells to sublethally irradiated syngeneic mice. The suppressive activity of transferred cell population markedly declined after treatment with anti Thy-1.2 serum and complement. Cells with suppressor activity could be demonstrated by adoptive transfers as early as 5 days after skin grafting and ALS treatment. The results showed that the long-term allograft-promoting effect of ALS was caused not only by a decrease in the graft-rejection cell potential of the recipients (as demonstrated by other authors earlier) but also by the activation of a T cell-mediated suppressor mechanism.


[In vitro stimulation of peripheral blood lymphocytes with allogeneic lymphocytes or phytomitogens in patients with insulin-dependent diabetes mellitus (author's transl)].

The lymphocyte transformation response to the allogeneic lymphocytes (mixed lymphocyte culture, MLC) was determined in nineteen well-controlled insulin-dependent diabetics (IDD) and nineteen matched normal subjects. All possible combinations between lymphocytes from the patients and controls were mixed in both one-way and two-way MLC. From the results of one-way MLC, the stimulatory capacity (SC) and responding capacity (RC) of IDD lymphocytes were compared with those of normal lymphocytes as follows: (1) Nm leads to N: 10,538 +/- 3,937 N; normal lymphocytes (2) Nm leads to D: 8;466 +/- 5,387 D; IDD lymphocytes (3) Dm leads to N: 7,562 +/- 3,088 m; mitomycin-treated stimulating lymphocytes (4) Dm leads to D: 7,102 +/- 4,873 (leads to; stimulatory direction, results; M +/- SD cpm) IDD lymphocytes showed a marked depressive function as stimulators (SC, (1) -- (3)), but the RC of IDD lymphocytes was unchanged ((1) -- (2)). Phytomitogen-response was studied simultaneously for the same responding lymphocytes (N, D) of MLC. IDD lymphocytes exhibited significantly decreased responses to phytohemagglutinin P, pokeweed mitogen and concanavalin A.


The intercellular distribution of mutations induced in oocytes of Drosophila melanogaster by chemical and physical mutagens.

When females of Drosophila melanogaster are treated with chemical or physical mutagens, not only in one but also in both of the two homologous X chromosomes of a given oocyte, a recessive sex-linked lethal mutation may be induced. A method is described that discriminates between such "single" and "double mutations". A theory is developed to show how a comparison between the expected and the observed frequency of double mutations yields an indication of the intercellular distribution (random or nonrandom) of recessive lethal mutations induced by mutagenic agents in oocytes and, consequently, of the distribution (homogeneous or nonhomogeneous) of those agents.--Three agents were tested: FUdR (12.5, 50.5 and 81.0 micrograms/ml), mitomycin C (130.0 micrograms/ml) and X rays (2000 R, 150 kV). After FUdR feeding, no increase in the mutation frequency usually observed in D. melanogaster without mutagenic treatment was obtained (u = 0.13%, namely three single mutations among 2332 chromosomes tested). After mitomycin C feeding, 104 single and three double mutations were obtained. All of the 50 mutations observed after X irradiation were single mutations. The results obtained in the mitomycin C and radiation experiments favor the assumption of a random intercellular distribution of recessive lethal mutations induced by these two agents in oocytes of D. melanogaster. Reasons are discussed why for other types of mutagenic agents nonrandom distributions may be observed with our technique.


Organization of the qa gene cluster in Neurospora crassa: direction of transcription of the qa-3 gene.

In Neurospora crassa, the enzyme quinate (shikimate) dehydrogenase catalyzes the first reaction in the inducible quinic acid catabolic pathway and is encoded in the qa-3 gene of the qa cluster. In this cluster, the order of genes has been established as qa-1 qa-3 qa-4 qa-2. Amino-terminal sequences have been determined for purified quinate dehydrogenase from wild type and from UV-induced revertants in two different qa-3 mutants. These two mutants (M16 and M45) map at opposite ends of the qa-3 locus. In addition, mapping data (Caseet al. 1978) indicate that the end of the qa-3 gene specified by M45 is closer to the adjacent qa-1 gene than is the end specified by the M16 mutant site. In one of the revertants (R45 from qa-3 mutant M45), the aminoterminal sequence for the first ten amino acids is identical to that of wild type. The other revertant (R1 from qa-3 mutant M16) differs from wild type at the amino-terminal end by a single altered residue at position three in the sequence. The observed change involves the substitution of an isoleucine in M16-R1 for a proline in wild type. This substitution requires a two-nucleotide change in the corresponding wild-type codon.--The combined genetic and biochemical data indicate that the qa-3 mutants M16 and M45 carry amino acid substitutions near the amino-terminal and carboxyl-terminal ends of the quinate dehydrogenase enzyme, respectively. On this basis we conclude that transcription of the qa-3 gene proceeds from the end specified by the M16 mutant site in the direction of the qa-1 gene. It appears probable that transcription is initiated from a promoter site within the qa cluster, possibly immediately adjacent to the qa-3 gene.


[Characteristics of bacteriophage lambda and P1 modification-restriction in Escherichia coli strains controlled by factor R124].

The specifities of restriction of bacteriophages P1 and lambda controlled by R plasmids in Escherichia coli have been investigated. The isogenic strains harbouring the plasmids pAS26 coding for restriction endonuclease R.EcoRI, R245 coding for restriction endonuclease R.EcoRII and and R124 have been investigated in the present work. Modification-restriction controlled by R124 has been found to differ in specificity from those controlled by R245 and pAS26. Frequencies of restriction of bacteriophages P1vir and lambdavir specified by R124 pasmid differ from the frequencies in the strains harbouring pAS26 and R245 plasmids as well. The difference is due to the specifity of restriction-modification controlled by R124 plasmid. The data obtained are consistent with the determination of R124 specified restriction-modification activity as a novel one designated R.EcoRIII.


Escherichia coli RNA polymerase binding and initiation of transcription on fragments of lambda rifd 18 DNA containing promoters for lambda genes and for rrnB, tufB, rplC,A, rplJ,L, and rpoB,C genes.

Promoters of genes for bacteriophage lambda and for Escherichia coli ribosomal RNA (rrnB), elongation factor Tu (tufB), ribosomal proteins L11 (rplK), L1 (rplA), L10 (rplJ), and L7/L12 (rplL), and RNA polymerase subunits beta (rpoB) and beta' (rpoC) were studied by use of two types of filter binding assays which measured E. coli RNA polymerase binding and initiation of transcription on restriction fragments of lambda rifd 18 DNA. The DNA fragments selectively retained on filters were eluted, concentrated, and analyzed by gel electrophoresis. The binding characteristics of these promotor fragments were qualitatively determined by varying the RNA polymerase, salt, and glycerol concentrations in the polymerase binding assay with HaeIII fragments of lambda rifd 18 DNA. The approximate map locations of these small HaeIII fragments were determined by HaeIII digestion of the larger, previously mapped EcoRI, HindIII, and SmaI restriction fragments of the phage DNA. The base compositions proximal to the 5' ends of mRNA's from promoters on these DNA fragments were elucidated by the polymerase initiation assay, in which the addition of various combinations of nucleoside triphosphates to the reaction allowed RNA polymerase to form high-salt-resistant initiation complexes with some of the known SmaI + EcoRI, EcoRI + HindIII, or HaeIII restriction fragments of lambda rifd 18 DNA. The data obtained by this technique are consistent with the map positions and 5' mRNA base sequences of the known lambda promotors p'R, po, pR and pL. In the main focus of this work, we have determined the approximate map locations and 5' mRNA base compositions of several promoters for known E. coli genes including rrnB, tufB, rplK,A, and rplJ,L. No promoter was detected between rplL and the rpoB,C genes. Thus our data are consistent with the conclusion of Yamamoto and Nomura (1978) that the beta and beta' mRNA is probably cotranscribed from the promoter for rplJ,L. Finally, the approximate map positions and the NTP combinations which initiated transcription of several unknown lambda and E. coli in vitro promoters are reported. The methods reported should prove useful for studying the characteristics of promoters on other cloned DNA regions.


Transfer of genome fragments in double infection of E. coli with T5 and phi X174 bacteriophages.

Double infection of Escherichia coli by two DNA phages (phi X174 and T5) resulted in encapsidation into T5 particles of T5 DNA containing linked fragments of phi X174 DNA. The phi X474 sequences in T5 "hybrid" DNA were detected by RNA-DNA hybridization.


Plasmid pKC7: a vector containing ten restriction endonuclease sites suitable for cloning DNA segments.

Plasmid pKC7, a derivative of pBR322, specifies resistance to both ampicillin and kanamycin. The DNA of this small plasmid (5.8 kb) contains unique sites for insertion of DNA cleaved with ten different restriction endonucleases. A detailed restriction endonuclease cleavage map is presented. The utility of this plasmid for cloning is discussed.


[Clinical experience with mammography using grids (author's transl)].

Duplicate examinations were carried out on 122 patients in order to compare the results of mammography using a grid technique (Diagnost U. Müller) with a film-screen systemadn also a conventional set without screens (Mamma-Diagnost, Müller). The results were compared with reference to film quality and dose. The new technique was superior to the conventional method in all respects, independent of the size of the gland. Another advantage of the grid technique was the larger available film size. Dose requirements for grid mammography with a film-screen system was less than for conventional techniques by a factor of about 1.8. The results speak for increased use of the grid technique in clinical practice.


[Quantitative analysis as part of computer tomography of the skull (author's transl)].

The possibilities of quantitative evaluation of skull computer tomograms were explored in a group of 22 normals and compared with a group of 26 patients with cerebral tumours. Quantitative measurements of normal cerebral tissue and of tumours have revealed mean values for these groups which permit certain fundamental conclusions.


[A comparison of cerebral angiography and computer tomography in patients with strokes (author's transl].

The computer tomographic findings in 230 patients with a clinical diagnosis of strokes or cerebral infarcts are described. In 185 of these patients cerebral angiography was performed in addition. The size and localisation of infarcts as shown on the computer tomogram were compared with the changes found in the carotid angiogram and were also related to the localisation of occlusion or stenosis of the corresponding extra- and intracranial vessels. In the presence of a normal carotid angiogram, CT may show infarcts of varying localisation and size; with stenoses or occlusion of the extracranial portion of the internal carotid artery, the infarcts tend to be smaller and that, in the presence of occulsions of the intracranial cerebral vessels, infarcts tend to be more extensive and to correspond to the territory supplied by the occluded vessels. Twenty-eight intracerebral haematomas and nine cerebral tumours were found amongst patients who presented as cerebral infarcts, with little evidence of massive cerebral bleeding; these are discussed separately.


[The value of cranial computed tomography in posterior fossa epidermoids and dermoids (author's transl)].

Report on posterior fossa epidermoids and dermoids (3 in the cerebellopontine angle, 1 in the region of the fourth ventricle). Computed tomographic aspects are related with other neuroradiological findings. Differential diagnosis of these mass lesions is discussed in detail, especially of low density and (rarely occuring) high density epidermoids.


[Computed tomography of soft tissue sarcomas (author's transl)].

CT findings in 50 patients with histologically verified soft tissue sarcomas are presented. In nearly all the cases the cross-sectional view and the higher resolution of density make it possible to determine exactly location of the tumors, their size and relationship to adjacent structures. Thus CT opens a new dimension, which is of great value for staging and therapy treatment planning. The high rank of CT in the follow-up after therapy and the detection of recurrent tumor is demonstrated. The contribution of CT, however, to the anatomic characteristics and its prospective value with the regard to soft tissue tumor is less important. Further limits of the method are discussed.


[Ultrasound diagnosis of renal stones (author's transl)].

Infusion urography and ultrasound examinations were performed in 54 patients in order to diagnose renal stones. The patients were examined because of upper abdominal pain, suspected renal calculi or for follow-up of known calculi. In 20 patients, stones could be demonstrated by both methods. In four patients, radiological suspicion of the presence of stones was not confirmed by ultrasound. In two patients ultrasound produced false positives and in seven patients renal stones were demonstrated only by sonography. These results were obtained with a mechanical sector scanner. The advantages and disadvantages of compound and of real-time-scanners and their place in the diagnosis of kidney stones are discussed.


[Sonography and angiography in the investigation of space-occupying lesions of the kidney (author's transl)].

The results of angiography and sonography in 132 patients suspected of having a space-occuping lesion in a kidney were compared; they were examined by excretion urography, ultrasound and renal angiography. All lesions demonstrated angiographically had already been seen by ultrasound. Difficulties were experienced with cysts of less than 3 cm. Diameter situated in the region of the hilum, which did not always produce echo-free images. Infected renal cysts appeared as avascular space-occupying lesions on angiography, but showed echoes on sonography.


[Acute renal vein thrombosis in infancy (author's transl)].

Two cases of acute renal vein thrombosis are presented. Instead of angiography, sonography was used to perform the diagnosis. After short discription of the etiology, clinic and roentgensymptomatology, the sonographic semiology is emphasized. In the discussion the sonographic differentialdiagnosis is reviewed and the possible therapeutic proceedings are mentioned. The value of sonography as non-invasive method, especially in newborn is therefore established.


[Sonography and pharmacoangiography of the pancreas (author's transl)].

Real-Time-Sonography and pharmacoangiography with vasodilating drugs was performed in 63 patients with suspected pancreatic disease. Confirmation of the pancreatic lesion could be obtained in 41 cases by the symptomatology, pancreatic function test, autopsy, operation, laparoscopy with fine-needle-biopsy and by the roentgenologic visualization of pancreatic calcifications. Considering the relatively advanced disease of pancreatic carcinoma in our six patients the sonographic diagnosis was correct in all of them and with pharmacoangiography we failed on one case. In chronic pancreatitis correct diagnostic results with pharmacoangiography could be obtained in 8 of 18 cases and with sonography in 14 of 18 patients. In this study sonography showed certain advantages in comparison with angiography, but both methods were complementary and a better result in the differential diagnosis between chronic pancreatitis and pancreatic carcinoma could be achieved.


[Hemorrhage through the pancreatic duct -- endoscopic-radiological diagnosis (author's transl)].

Hemobilia and pancreatic hemorrhage must be considered in the differential diagnosis of bleeding fromthe papilla Vateri. Retrograde pancreaticography and angiography are the essentials of the further diagnostic workup. Both methods together can reveal the origin and localization of the bleeding.


[Phlebography for pre- and posttherapeutic control of fibrinolysis and thrombectomy (author's transl)].

The indications for fibrinolysis or thrombectomy when there is suspected fresh ilio-femoral venous thrombosis should be based on accurate phlebography at the earliest possible moment. Early posttherapeutic phlebography under standardised conditions should be used to control further treatment. Later examinations document the final outcome. Early phlebography, when treatment has been discontinued and has been unsuccessful, shows the so-called "Rischhalte phenomenon", which may be an indication for further thrombectomy. Seven cases are reported in which primary fibrinolysis with streptokinase was followed by thrombectomy with a Fogarty catheter. 3-Step-phlebography provides the essential information which governs treatment and demonstrates its results.


[Isotope methods in the radiological diagnosis of venous disease. II. Indications and accuracy (author's transl)].

Radiological diagnostic methods for the diagnosis of abnormalities of veins were discussed in the light of 1,683 contrast venograms and isotope examinations in 650 patients with acute and chronic diseases of veins. For patients with increased thrombotic risks, the 125 I-fibrinogen test is recommended as a sensitive and simple method. Where there are symptoms of venous thrombosis, radionuclide venography, together with other noninvasive methods, may be used for establishing whether there are indications for contrast venography. These may also provide evidence of previous pulmonary emboli. These methods should also be used where there is clinical suspicion of previous pulmonary emboli. Non-invasive isotope methods have proved to be sensitive techniques for preliminary examinations and for follow-up. Contrast venography is necessary if definitive treatment is planned.


[Radio-nuclide phlebography: methods, indications and clinical value (author's transl)].

Radionuclide venography (RNV) is an easily performed, rapid and non-invasive diagnostic examination for the detection of deep-vein thrombosis. Provided the procedure is followed out in a standardized order, the results are highly reliable and accurate, especially in the iliac and femoral veins. Therefore, because of this advantage and the possibility of simultaneous lung perfusion scanning and the lack of serious complications this method fills a gap between contrast phlebography and fibrinogen test. 122 limbs of 69 patients were investigated by RNS. 65% showed pathologic results. In 48% thrombotic venous occlusions could be demonstrated. Pulmonary embolic perfusion defects were found in 46% of patients presenting deep vein thrombosis but only in 15% of patients without pathologic findings in RNV. In correlation with contrast phlebography in 11 patients there was no discrepancy neither in recognition nor in localization of the thrombotic occlusion. The essential findings in RNV and the resulting diagnostic conclusions are demonstrated.


[Changes in the cervical spine in juvenile rheumatoid arthritis (author's transl)].

Changes in the cervical spine in juvenile rheumatoid arthritis can be shown by A.P., lateral and functional views with maximal flexion and extension, and particularly by tomography. The latter is essential for proper evaluation of the atlanto-occipital and atlanto-axial joints and of the odontoid. Atlanto-axial subluxation was found in eight out of eighty-four patients. Destruction of the odontoid was found in twelve out of fifty-three patients examined by tomography. The earliest tomographic changes at the atlanto-occipital joint consists of isolated joint narrowing, erosions and fusion and were observed in sixty-four out of sixty-six patients examined. Similar findings at the atlanto-axial joint were observed in thirty-seven out of sixty-six cases. The severity of the changes correlated with seropositivity and duration of the disease. The most marked changes were found with a prolonged history and a positive Rose-Waaler reaction.


[The radiological appearances of the normal joint spaces in the hand (author's transl)].

The radio-carpal joints in 120 normal persons were examined by arthrography. It was shown that this joint communicates with the carpal joints, carpo-metacarpal joints and with the distal radio-ulnar joint. Three types, with various accessory pouches, could be defined. A study of the normal radiological anatomy of the radio-carpal joint is necessary before a diagnosis of pathological changes in the joint can be made.


[Antiepileptic therapy with valproinic acid. Correlations of side effects and serum levels of valproinic acid].

The side effects and possible side effects of the therapy with valproic acid were documented in 66 outpatients with epilepsy over a period of one year. The serum levels of valproic acid were measured gaschromatographically over the same period. The majority of the patients received a combined medication. The occurrence of side effects or possible side effects of valproic acid led to a dosage reduction of discontinuation of the compound in 25% of the patients. Patients complaining of tiredness showed significantly higher serum valproic acid levels than patients without clinical side effects. The other comparisons between the serum valproic acid levels in the case of clinical side effects and changes in laboratory findings and the serum levels of patients without side effects or changes in laboratory findings did not indicate a definite difference.


[Plastic surgery in mongoloid children].

The aim of plastic surgery in children with Down-syndrome is the improvement of speech as well as improvement of cosmetic appearance. Altering the typical mongoloid physiognomy facilitates the integration of these children into the community. In our Department during the past 6 months plastic surgery was performed in 27 children for the correction of macroglossia, saddle nose deformity, epicanthic folds, receding chin, fatty neck and deformity of the ears. Macroglossia was present in every case, the extent of further surgery varies according to the clinical deformity. It is essential to discuss the implications of surgery in these children with the parents in order to avoid later disappointment.


[Sodium fluoride in the therapy of osteoporosis].

Every form of osteoporosis--except the physiological involution osteoporosis--requires treatment. Osteoporosis is no disease by itself but a result or a concomitant phenomenon of various diseases. Therefore the primary disease has to be treated also. Only for the so-called idiopathic osteoporosis hitherto no cause is known. Today sodium fluoride is the only substance with an influence upon the bone which may induce re-ossification and re-stabilization. In the described series of investigations this compound, with which treatment by gradual dosage is possible, has proved its effectiveness. Osteoporosis is more than bone porosity, therefore additionally afflicted organic or functional system like the muscular apparatus, bone marrow, or the intraosseous blood supply, must be treated too. Psychological guidance of the patient is necessary as he must be motivated for activity.


Nicotinamide modulation of rat pancreatic islet cell responsiveness in vitro.

The influence of nicotinamide (NA), a highly suitable precursor substrate for NAD synthesis in various tissues, on islet cell responsiveness was determined. After a 30 minute perifusion with this compound, nicotinamide, in a dose-dependent manner, potentiated glucose-induced insulin secretion. Maximal potentiation (approximately 250%) was observed at 20 mM NA and the threshold for potentiation was 3 mM. In the absence of glucose, NA did not affect basal secretion rates. Mannoheptulose blocked the primary stimulant action of glucose and the potentiating effects of NA. NA did not alter the rate of glucose usage by isolated islets. These results further underscore the possible importance of pyridine nucleotides in stimulated secretion.


Substrate specificity of a heparan sulfate-degrading endoglucuronidase from human placenta.

A heparan sulfate-degrading endoglucuronidase was isolated from human placenta and partially purified by affinity chromatography on heparan sulfate-Sepharose 4B. The endoglucuronidase has a molecular weight of approximately 100 000 estimated by gel chromatography and a broad pH optimum between pH4 and pH6. Carboxyl reduced heparan sulfate is not split by partially purified endoglucuronidase, but inhibits the action of that enzyme towards non-modified heparan sulfate. Low molecular weight heparan sulfate (Mr approximately 3 000) is not attacked by the endoglucuronidase. N-Desulfated heparan sulfate and heparin are only weak substrates. The amino sugar adjacent to the glucuronic acid residue appearing at the reducing terminal of heparan sulfate fragments liberated by the endoglucuronidase appears to be exclusively N-acetylated glucosamine.


The cells involved in cell-mediated and transplantation immunity in the normal outbred rabbit. XIII. The identity of the responder cells and the role of phagocytic cells in the mixed leucocyte culture reaction.

The ability of rabbit spleen cells depleted of thymus, bone marrow or appendix-derived cells to respond in the one-way mixed leucocyte reaction (MLR) has been investigated. The specific subpopulations of lymphoid cells were eliminated by lysis of these cells in the presence of specific antisera and complement. Phagocytic cells (monocytes and heterophils) were removed with a strong magnet after incubation with carbonyl iron particles. The results indicate that the MLR-responding cells are thymus-derived and that neither bone marrow-derived cells nor appendix-derived cells are essential for the blastogenic response following stimulation with allogeneic cells. A minimum number of phagocytic cells is required for a significant response. These cells, however, exhibit a non-specific (accessory) role and can be supplied by either the responding or the stimulating cell population.


The Papillon-Lefèvre syndrome: keratosis palmoplantaris with periodontopathy. Report of a case and review of the cases in the literature.

The Papillon-Lefévre syndrome (PLS) is an autosomal recessive trait characterized by diffuse transgredient palmar-plantar keratosis (PPK) and premature loss of both the deciduous and permanent teeth. In most cases, the PPK is noted within the first 3 years of life. The periodontal lesions begin shortly after the start of both the primary and the permanent dentitions. The teeth are affected in the order of their eruption, exhibiting inflammation of the periodontal tissue, bleeding of the gums, pocket formation, loosening, and finally spontaneous exfoliation without showing definite signs of root resorption. After an edentulous interval, the same process begins anew shortly after the second dentition. Ectopic intracranial calcifications, mental retardation, and increased susceptibility to infections have often been seen in PLS patients and may thus be regarded as facultative signs.


Comparative patterns of serum immunoglobulin levels in specific-pathogen-free congenitally athymic (nude), hereditarily asplenic (Dh/+), congenitally athymic-asplenic (lasat) and splenectomized athymic mice.

Serial determinations of serum immunoglobulin levels were assessed in congenitally athymic (nude), hereditarily asplenic (Dh/+) and congenitally athymic-asplenic (lasat) mice and the results compared to normal intact littermate controls (nu/+), neonatally splenectomized nu/+ and neonatally splenectomized nude mice. Quantification of Ig levels was accomplished by radial immunodiffusion, for IgM, IgG1, IgG2a, IgG2b and IgA antibody isotypes. Intact spleen and/or thymus function was shown to have marked effects on the age-dependent development of serum IgM, IgG2b and IgA production. Furthermore, because of higher levels of IgA in congenitally athymic-asplenic mice and neonatally splenectomized nude mice v. sham splenectomized nude mice, it is suggested that an IgA-specific suppressor population resides in the spleen. Finally, because of frequent problems in the literature in interpretation of immunoglobulin values, the criteria for the statistical evaluation of such data in establishing normal serum Ig values and ascertaining real differences between treatment groups are emphasized.


Effect of visceral leishmaniasis on congenitally athymic mice.

Congenitally athymic mice were more susceptible to challenge with amastigotes of Leishmania donovani than were their thymus-intact littermates. This increased susceptibility correlated with a lack of Arthus and delayed-type responses when animals were skin tested with leishmanial antigen.


Inhibition of translocation of viable Escherichia coli from the gastrointestinal tract of mice by bacterial antagonism.

The incidence of translocation of viable Escherichia coli C25 from the gastrointestinal tract to the mesenteric lymph nodes was compared in gnotobiotic mice colonized with only E. coli C25 and in gnotobiotic mice colonized with E. coli C25 plus the whole cecal flora from specific pathogen-free mice. The population levels of E. coli C25 in the ilea and ceca of these mice also were compared. E. coli C25 maintained high population levels in the gastrointestinal tracts of the monoassociated gnotobiotes, and the incidence of translocation to the mesenteric lymph nodes was 100%. The gastrointestinal population levels of E. coli C25 were reduced drastically in the gnotobiotes associated with both E. coli C25 and a cecal flora with concomitant reduction in the incidence of translocation of E. coli C25 from 100 to 0%. A decrease in the numbers of viable E. coli C25 per mesenteric lymph node also accompanied the decrease in C. coli C25 population levels in the gastrointestinal tracts of these mice. Thus, high population levels of E. coli C25 in the gastrointestinal tracts of monoassociated gnotobiotic mice appear to promote translocation of viable E. coli C25 to the mesenteric lymph nodes. Bacterial antagonism of E. coli population levels in conventional mice, therefore, could be one mechanism whereby viable E. coli are confined to the gastrointestinal tract.


Complement activation in acne vulgaris: consumption of complement by comedones.

Comedones, the contents of acne lesions, were shown to consume scomplement hemolytic activity in normal serum. This consumption was stimulated by the addition of serum from patients with inflammatory acne. Absorption of acne serum with Propionibacterium acnes cells removed all stimulating activity. Immunoelectrophoretic analysis of serum incubated with comedones revealed the conversion of C3 and factor B in normal serum. The addition of acne serum resulted in cleavage of C4. In serum treated with ethylene glycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, only C3 and factor B were converted. This indicates that comedones may activate complement by either the classical or the alternative pathway. It is suggested that P. acnes cells in comedonal material are responsible for the complement activation.


Depression of contact sensitivity by Pseudomonas aeruginosa-induced suppressor cells which affect the induction phase of immune response.

The cellular basis of depression of contact sensitivity to oxazolone in mice injected with Pseudomonas aeruginosa was studied. Cells from draining lymph nodes of mice sensitized with oxazolone 18 h previously were able to induce contact sensitivity to normal mice when administered in their footpads. In contrast, cells from draining lymph nodes of P. aeruginosa-injected and oxazolone-sensitized donors failed to induce contact sensitivity when injected in the footpad of normal mice and were capable of actively blocking the immunizing process brought about by lymph node cells from sensitized mice when injected together in the footpad of normal recipients. The P. aeruginosa-induced suppressor cells required antigenic stimulation, had precursors sensitive to cyclophosphamide, and did not affect the effector mechanisms of contact sensitivity. Thus, the results suggest that P. aeurginosa depresses contact sensitivity to oxazolone by enhancing the activity of suppressor cells which normally arise during the sensitization process and which affect the afferent limb of the immune response, probably by inhibiting the normal recruitment of T lymphocytes in the draining lymph nodes.


Role of environment in the development of "natural" hemagglutinins in Minnesota miniature swine.

"Natural" hemagglutinin titers against a panel of fixed erythrocyte antigens were determined for groups of Minnesota miniature swine reared conventionally, in a specific pathogen-free facility, and in germfree isolators. Sera were assayed for hemagglutination (HA) titers by the microtiter method against 12 species of erythrocytes stabilized by treatment with pyruvic aldehyde and formaldehyde. These erythrocytes were stable for up to 2 years and gave slightly enhanced HA titers as compared to fresh, unfixed erythrocytes. Of the sera from conventional swine tested, the highest "natural" HA titers were directed towards rabbit, cat, swine dog, and burro erythrocytes (greater than 1:1,000), intermediate titers were detected against human A, B, and O, and sheep, pig, and chicken erythrocytes (1:64 to 1:1,000), whereas the lowest titers were found against ox and goat erythrocytes (less than 1:8). Titers obtained with sera from specific pathogen-free swine were 2- to 16-fold lower than those of conventional swine, but were of a similar distribution with regard to the species of erythrocyte tested. Germfree swine sera uniformly exhibited HA titers less than 1:4 against all species of erythrocytes. The majority of these hemagglutinins were immunoglobulin M class but there were some agglutinins of immunoglobulin A class and a slight amount of immunoglobulin G class. Specificity of these agglutinins was examined by absorption tests. The results are consistent with the hypothesis that natural hemagglutinins develop due to dietary or microbial antigenic stimulation, or both.


Suppression of lymphocyte response to concanavalin A by mucopolysaccharide material from Treponema pallidum-infected rabbits.

The testicular fluid and serum from rabbits infected intratesticularly with Treponema pallidum inhibited the mitogenic response of normal rabbit peripheral blood lymphocytes to concanavalin A. Mucopolysaccharide material present in the testicular fluid and serum was associated with the lymphocyte-inhibitory activity. Degradation of the mucopolysaccharide material with hyaluronidase resulted in the loss of the inhibitory activity of testicular fluid and serum of T. pallidu-infected rabbits.


Augmentation of lymphocyte surface immunogenicity following treatment with dimethyl-sulphoxide.

A mixed leucocyte culture is an in vitro tool for assessing differences in cell surface antigenicity between two cell populations. The MLC technique has been used to assess alterations in immunogenicity of rat lymphocytes, when exposed to the agent dimethyl-sulphoxide. Using four different rat strains, DMSO has been shown to be a surface-active agent that significantly increases the immunogenicity of both splenic and peripheral blood rat lymphocytes, as assessed by an increase in MLC reactivity. No augmentation of MLC reactivity is seen when syngeneic lymphocytes are used in the culture system as both effector and stimulator lymphocytes, thus confirming the immunological nature of the enhancement seen in allogeneic cultures.


Alkali-labile sites and post-irradiation effects in gamma-irradiated biologically active double-stranded DNA in aqueous solution.

Gamma-irradiation of double-stranded RF-DNA of bacteriophage phi X174 in aqueous solution in the presence of oxygen produces at least one type of alkali-labile site. It is lethal and gives rise to breaks by alkali and is identical with the damage which becomes manifest by post-irradiation heat treatment. The effect of alkali is dependent on temperature. Furthermore, the excision repair system is not involved in eliminating lethal nucleotide damage in RFI-DNA.


Skin and bone lesions (dermato-osteolathyrism), possible side effects of D-penicillamine treatment, in a boy with cystinuria.

A 2 1/4 year-old boy was treated for cystinuria and urolithiasis with high fluid intake, sodium bicarbonate, and D-penicillamine, over a period of 5 3/4 years, unauthorized interruptions and prescribed pauses included. Therapy was partially sucessful but regrowth of calculi coincided with interruptions of D-penicillamine administration and also with the institution of a low-dose D-penicillamine regime. Flat feet, scoliosis, pectus carinatum, hypermobility of joints, molluscoid pseudotumors and atrophic scars were alarming side effects of D-penicillamine. However, the possibility was not excluded that a forme fruste of an Ehlers-Danlos syndrome preexisted in this boy and was effected by D-penicillamine. Only the molluscoid pseudotumors regressed when D-penicillamine was reduced or omitted temporarily. Osteolathyrism caused by D-penicillamine has hitherto not been reported in man.


Low temperature activation of post mortem glycogenolysis in bovine skeletal muscle fibres.

Trimmed strips of sternomandibularis muscles taken from freshly-slaughtered cattle were placed in an isotonic myograph and cooled to 1 degree C. Spontaneous activity due to neuromuscular irritability was minimized by keeping muscle surfaces moist and anaerobic and was monitored by electromyography. Muscle strips were removed and frozen for histochemical analysis after they had completed their initial phase of cold-induced shortening (several hours). Control strips maintained for an equal time at 24 degrees C rarely depleted the stainable glycogen in any of their muscle fibres so as to become PAS-negative. In chilled muscle strips, however, glycogenolysis was activated in some muscle fibres and they became PAS-negative. In serial sections, most of the PAS-negative fibres exhibited strong ATPase and weak succinate dehydrogenase activity. Fibres with weak ATPase and strong succinate dehydrogenase activity rarely became PAS-negative. These results are in agreement with biochemical reports of a cold-induced (less than 5 degrees C) activation of glycolysis in skeletal muscle post mortem. Investigations on untrimmed lengths of excised sternomandibularis muscle indicated that longitudinal muscle damage caused in cutting muscle strips for the myograph and/or their more rapid rate of initial cooling had facilitated the depletion of stainable glycogen.


Ultrastructural localization of adenosine triphosphatase in the stellate reticulum, stratum intermedium and ameloblasts of the mouse molar.

ATPase activity in the developing first mandibular molar of the mouse was demonstrated at the electron microscopic level with the method of Wachstein & Meisel (1957). It was localized along the cell surfaces of the ameloblast and stratum intermedium interface, the stratum intermedium and the stellate reticulum. The ATPase final reaction product was also present at the cell membranes of the proximal region of adjacent ameloblasts and extended to the level of the nuclei. The demonstration of ATPase mainly on the plasma membranes was similar to the observations by other investigators of various non-odontogenic cell types involved in the exchange of materials across plasma membranes.


A histoenzymatic study of rat intrafusal muscle fibres.

The histochemical activities of myofibrillar adenosine triphosphatase (ATPase), succinic dehydrogenase (SDH) and alpha glycerophosphate dehydrogenase (alpha-GPD) were studied in intrafusal muscle fibres of rat fast and slow muscles. The ATPase reaction was carried out after the three standard acid preincubations. The cold K2-EDTA preincubated ATPase reaction product was similar to that seen following the regular or alkali-preincubated ATPase reaction, except that the intermediate bag fibres exhibited much higher activity after cold K2-EDTA preincubation. Following either acetic acid solution or cold and room temperature K2-EDTA-preincubation, followed by the ATPase reaction, chain fibres of the fast muscles vastus lateralis and extensor digitorum longus exhibited a very low amount of reaction product as compared with those of the slow soleus. Veronal acetate and K2-EDTA preincubations (and equally preincubation in acetic acid solution) resulted in acid stable ATPase activity along the entire length of the typical bag fibres but only in the polar regions of the intermediate bag fibres. On the basis of differing alpha-GPD reaction, two sub populations of nuclear chain fibres were discovered in one spindle. It is a matter of conjecture, to what extent the histochemical differences of intrafusal fibres from fast and slow muscles reflects functional distinctions in the response to stretch of muscle spindles from fast and slow muscles.