An immunological determination of specific activities of enzymes: its use in quantification of cross reactivity between enzymes of different origins.

An immunological method is presented which enables the determination of the specific activity of a pure enzyme without its extensive purification. The method consists essentially in the specific fixation of immunologically related enzymes to an immunoadsorbent containing specific antibodies raised against the wild-type form of the enzyme. We applied this method to determine the specific activity of plasmid-coded beta-galactosidases and to quantify the extent of cross-reaction between these enzymes and Escherichia coli beta-galactosidase.


[Carbonic anhydrases of bovine erythrocytes: comparative study of the anhydrase and esterase activity of different forms].

Comparative study of esterase activities (p- and o-nitrophenylacetate) allowed to characterize three groups of bovine erythrocyte carbonic anhydrases:--the first one includes CI, CII (isozyme of CI) and CIr ("artificial" product of CI).--the second one includes native CIv1 and "artificial" CIv1, first conformational variants of CI,--finally CIv2, second "artificial" conformational variant of CI. Possible modifications of the enzyme site between the first and the other enzyme groups are discussed. Except CIv2 of lower activity, all the products have identical carbonic anhydrase activity. The catalytic constants Km ap and kcat ap for hydrolysis of p-nitrophenylacetate have been determined for all enzymes; this study confirms the lower activity of CIv2.


[Picosecond energy transfer between the spectral forms of pigments from the reaction center of Rhodospirillum rubrum].

Absorption changes of reaction centers from Rhodospirillum rubrum at 748, 796 and 870 nm induced by 532 and 870 nm picosecond light pulses were investigated with a picosecond spectrometer. Kinetics of absorption changes at 748 and 796 had an additional bleaching when induced by the 532 nm pulse, in comparison with those at 870 nm. The additional bleaching was interpreted as a result of the excitation energy transfer via spectral forms of pigments of reaction centers. The experimental results fit the mathematical simulation of the additional bleaching for the following set of rate constant values: intrinsic conversion to the lowest excited singlet state in bacteriopheophytine molecule--10(13) s-1, energy transfer from bacteriopheophytine to P800 3.10(12) s-1, from P800 to P870--2.10(12) s-1.


[Redox processes in allergic reactions of the delayed type to microbial antigens].

The influence of common allergic response of delayed type to brucellosis antigen on the processes of glycolysis and dehydrogenase activity of Krebs' cycle in guinea pigs' blood and organs was studied. Along with inhibitory activity of four dehydrogenases investigated there was a depression of the glucolysis processes connected with reduction of the lactate, pyruvate content, and with depression of the LDH activity. An increase of the anaerobic fractions and lowering of aerobic fractions content and of the spectrum excess was seen in the isoenzyme LDH spectrum.


Linkage and gene localization of hereditary spherocytosis (HS).

Fifteen kindreds with dominant hereditary spherocytosis (HS) were studied. Expansion of the data from a family with an 8/12 translocation provided further evidence that at least one locus for HS is located near the breakpoint of the translocation. Linkage analysis of all families showed a lack of linkage with all marker loci studied except for Gm (IgG). Linkage between Gm and HS was shown to be significant with a maximum lod score of 3.42 at a recombination fraction of 22%. No heterogeneity of the recombination fraction was observed either between sexes or between families. These results are compatible with the hypothesis that HS is not a heterogeneous disorder.


Purine nucleoside phosphorylase in chronic lymphocytic leukemia (CLL).

Purine nucleoside phosphorylase (PNP), the enzyme schematically next to adenosine deaminase in the purine salvage pathway, has been demonstrated cytochemically in peripheral blood lymphocytes of healthy subjects and chronic lymphocytic leukemia (CLL) patients. The enzyme activity is confined to the cytosol. In healthy subjects the majority of lymphocytes are strongly reactive for PNP, whereas the rest are devoid of cytochemically demonstrable activity. The percentage of PNP-positive cells largely corresponds to the number of E rosette-forming cells and is inversely proportional to the number of Ig-bearing cells. In six of seven CLL patients studied only a minor percentage of the lymphocytes showed strong PNP activity, whereas the large majority (88%--98%) possessed trace activity. Such patients have a high number of Ig-bearing cells and a low number of E rosette-forming cells. A different pattern of markers was found in the lymphocytes of the seventh CLL patient: 66% were strongly reactive for PNP, an important number formed E rosettes, and a minor percentage were Ig bearing. These data indicate that PNP can be useful as a "nonmembrane" marker in the differentiation of the B and T cell origin in CLL and deserves to be studied in other lymphoproliferative disorders.


[Solitary secreting plasmocytoma in a femoral localization in a young man (author's transl)].

A pathological fracture in 20-year-old man led to the discovery of a right femoral plasmocytoma. Immunoelectrophoresis revealed the existence of a monoclonal Kappa IgG. After tumour reduction by radiotherapy and chemotherapy, surgical excision was possible with the insertion of a reconstructive prosthesus. Functional recovery was complete. The dysglobulinaemia completely disappeared and, with a two year follow-up, no dissemination of the plasmocytoma has been found.


Control of cell multiplication: preparation and immunological comparison of inhibitory factors in the homogenate and perfusate of the adult rat liver.

The control of organ cell multiplication by a negative feed-back mechanism implies that factors of the inhibitory mechanism are present in the blood and are produced by the target organ itself. We have examined the inhibitors which are present in the cytosol of adult rat liver as well as in efferent fluid from an isolated perfused organ. These two materials yielded predominantly protein molecules having in common a molecular weight of approximately 80 000 daltons and an isoelectric point between pH 8 and 9. They inhibit both the multiplication of LF hepatoma cells in vitro and the DNA synthesis in the remnant liver following partial hepatectomy in rats. The inhibitors were compared immunologically. When antibodies against the cytosol inhibitor were tested with the Ouchterlong technique against either the original antigen or the inhibitory fraction isolated from the perfusion effluent, a common precipitation line appeared. The inhibitory activity of both the cytosol and the perfusate was neutralized by prior incubation with anti-cytosol antibodies. These results, which strongly suggest a common inhibitor in the cytosol and the perfusate, strongly support the hypothesis of a feed-back mechanism for the control of liver cell proliferation.


Influence of dietary calcium selenium and methylmercury on eggshell thickness in Japanese quail.

A high Ca, semi-purified diet promoted greater egg production with thicker shells in Japanese quail hens. 7 ppm of dietary Se depressed egg weights with no effect on eggshell thickness. The addition of 20 ppm of MHg to either a low or high Ca diet containing Se depressed both egg production and eggshell thickness. Se residues of liver, kidney, and brain in Se-MHg fed quail were significantly higher than in Se treated quail, probably reflecting the ability of Se to bind with Hg. CA, an enzyme required for the formation of the carbonate radical of Ca carbonate in eggshells, was not reduced in the Se-MHg treated Japanese quail hens' blood or oviducts.


Histopathology and histochemistry of the insects treated with chemosterilants VI: brain damage including reduced neurosecretion caused by chemosterilants in Periplaneta americana (L).

The brain is damaged and neurosecretion is reduced in the P. americana treated with chemosterilants thio-tepa and bis (dimethylamino) dithiazolium chloride. The damage includes, separation of neurolemma, vacuolisation and chromatolysis in the nuclei of neurons and extensive damage to fibres. Reduced neurosecretion, vacuolisation in the cytoplasm and karyolysis in the nucleus of neurosecretory cells, are also observed. These changes in the brain are of considerable importance to understand the mode of action of the chemosterilants.


An apparent outbreak of rickettsial illness in Costa Rica, 1974.

A focal outbreak of highly fatal disease occurred in eastern Costa Rica in 1974. No rickettsial spotted fevers have previously been reported in Costa Rica. Nevertheless, the available evidence points to an unidentified rickettsial pathogen, probably of the spotted fever group, as the agent responsible for this outbreak.


Domestic triatomines (Reduviidae) and insect trypanosome infections in El Salvador, C.A.

Twenty-five Salvadoran communities have been surveyed to learn more about the distribution of Chagas' disease vectors and trypanosome parasites in that country. The results indicate that each of several factors--local variations in housing construction, insecticide applications, geographic elevation, and the vector species involved--can have a critical effect on transmission of the disease agent.


Evaluating cost-effectiveness of diagnostic equipment: the brain scanner case.

An approach to evaluating the cost-effectiveness of high-technology diagnostic equipment has been devised, using the introduction of computerised axial tomography (CAT) as a model. With the advent of CAT scanning, angiography and air encephalography have a reduced, though important, role in investigating intracranial disease, and the efficient use of conventional equipment requires the centralisation of neuroradiological services, which would result in major cash savings. In contrast, the pattern of demand for CAT scanning, in addition to the acknowledged clinical efficiency of the scanner and its unique role in the head-injured patient, ephasies the need for improved access to scanners. In the interest of the patients the pattern of service must change.


Aggression and flight behaviour of the marmoset monkey Callithrix jacchus: an ethogram for brain stimulation studies.

The aggressive and flight behaviour of the common marmoset monkey (Callithrix jacchus) is described and split into behavioural units, allowing analysis of agonistic behaviour evoked by electrical stimulation of the hypothalamus. The social context of the described units is also considered. C. jacchus shows clearly recognizable behavioural patterns. Free-born animals are very timid and show typical flight reactions. Within aggressive behaviour, two types of aggression can be distinguished: very violent attacks causing severe injuries, often accompanied by particular threat displays and observed during dominance and territorial encounters, and, on the other hand, relatively harmless short attacks, together with a noisy vocalization, for defensive purposes or keeping group members at a distance.


Threat, attack and flight elicited by electrical stimulation of the ventromedial hypothalamus of the marmoset monkey Callithrix jacchus.

In order to elucidate whether relatively primitive primates show a similar topological organization of substrates mediating defense and flight within the ventromedial hypothalamus as has been found in other mammals, 15 marmosets (Callithrix jacchus) were chronically implanted with a total of 57 electrodes for electrical stimulation. Experiments took place in a familiar environment and under systematically altered conditions. All anatomical sites yielding vocal threat and short attacks were found to be situated in the n. ventromedialis. Flight was elicited from a region immediately lateral to this nucleus and from sites in the posterior hypothalamus. Thus, it appears that the topological organization of defense and flight behavior in cat, oppossum and marmoset are essentially similar.


Functional properties of neurons in the monkey superior colliculus: coupling of neuronal activity and saccade onset.

One class of superior colliculus neuron was isolated which meets two criteria for participation in the initiation of visually elicited saccades. First, the pulse of spike activity recorded from these neurons was tightly coupled to saccade onset, preceding the onset of eye movements by approximately 20 msec. Secondly, if a visual stimulus sometimes elicited a saccade and sometimes failed to elicit a saccade, the occurrence of the spike pulse was highly correlated with saccade occurrence. For these neurons, there was a clear distinction between the most vigorous neuronal activity occurring in the absence of a saccade and the least vigorous activity accompanying appropriate saccades. These findings are consistent with views which attribute to the superior colliculus a role in the initiation of visually elicited saccades.


Localization and detection of visual stimuli following superior colliculus lesions in rhesus monkeys.

Rhesus monkeys were trained to fixate a central stimulus and to detect and localize a 50 msec light flash presented 6-80 degrees on either side of the central stimulus. Following large lesions of the superior colliculus, they showed persistent deficits in localizing flashes presented 43-80 degrees from the fixation stimulus. However, they were not consistently impaired when the flashes were presented more centrally, and their performance with peripheral stimuli improved when the stimulus duration was 1 sec. Thus, the superior colliculus appears to be necessary for the localization of brief visual stimuli in the far periphery.


Gene regulation in adaptive evolution.

It has been suggested that gene regulation may play a critical role in adaptive evolution. However, gene regulation has proved to be most refractory to experimental investigation in multicellular organisms. Using specially constructed stocks of Drosophila melanogaster, we have demonstrated the following. (1) The existence in natural populations of ample variation in regulatory genes that modify the activity of alcohol dehydrogenase (ADH), an enzyme coded by a structural gene locus, Adh, located on the second chromosome; the regulatory genes are located on the third chromosome, and thus are not adjacent to the structural locus. (2) The regulatory genes act not by means of post-transcriptional or post-translational modification of the gene product, but rather by controlling the number of ADH molecules; this is consistent with the hypothesis of gene regulation by means of macromolecules specifically binding at control sites adjacent to the structural gene locus. (3) The variation in regulatory genes is adaptively significant; adaptation to higher levels of environmental alcohol takes place not by changes in the Adh structural locus, but by changes in regulatory genes that control the number of ADH molecules in the organisms. Our results provide direct evidence of the importance of gene regulation in eucaryotic evolution.


ERG responses of rods and cones during dark adaptation.

We demonstrate the main electrophysiological events during dark adaptation. We correlate simultaneously the separate rod and cone responses, the ERC sensitivity curves, their timing and the biphasic dark adaptation curve.


In vitro and in vivo effect of PC 904, a new broad-spectrum penicillin, on ocular strains of Pseudomonas aeruginosa.

The in vitro and in vivo activities of PC 904 were tested against Pseudomonas aeruginosa isolated from infected eyes and were compared with carbenicillin and gentamicin. By the microtiter plate method, we tested 30 strains of P. aeruginosa in vitro; PC 904 was very active against 29, but one strain was resistant. In a comparative study, PC 904 was more active than carbenicillin but less active than gentamicin. In vivo tests were conducted on rabbit corneas infected with a strain of P aeruginosa isolated in El Salvador. At moderate and high dosage levels, PC 904'S efficacy was comparable to carbenicillin's but much less than gentamicin's. When tested for ocular toxicity, the subconjunctival administration of PC 904 was well tolerated. The drug's greater activity in vitro than in vivo was probably due to its high serum-binding capacity.


Transient paralytic attacks of obscure nature: the question of non-convulsive seizure paralysis.

Eleven patients with transient paralytic attacks of obscure nature are described. Paralysis could involve face or leg alone, face and hand, or face, arm and leg. The duration varied from two minutes to one day. Four patients had brain tumors, six probably had brain infarcts, and one a degenerative process. The differential diagnosis included TIAs, migraine accompaniments, and seizures. In the absence of good evidence for the first two, the cases are discussed from the standpoint of possibly representing nonconvulsive seizure paralysis (ictal paralysis, inhibitory seizure paralysis or somatic inhibitory seizure). Because of the difficulty in defining seizures as well as TIAs and migraine in their atypical variations, a firm conclusion concerning the mechanisms of the spells  was not attained. Two cases of the hypertensive amaurosis-seizure syndrome have been added as further examples of ictal deficits.


Hodgkin's disease: radiotherapeutic management at a cancer oriented community hospital.

Seventy-eight patients with Hodgkin's disease were treated with radiation therapy between July 1966 and July 1976 (30 Stage I, 28 Stage II, 20 Stage III). The mean follow-up period is greater than 5 years. 90% of Stage I, 86% of Stage II, 65% of Stage III, and 82% (64/78) of all patients are NED after radiotherapy alone. Since laparotomy option (1970) 89% (50/56) of patients are NED. Fourteen patients were failures. Chemotherapy "rescued" 6 of 14. Seven have died, 1 is alive with disease, and 1 died of leukemia. Absolute survival is 90% (70/78). Failures were more frequent in patients with unfavorable histological types (9/14), and Stage III disease, primarily IIIS+ or B category (7/14). Sites of failures were mainly extranodal, primarily lung (10/14) and bone (2/14), and are consistent with hematogenous dissemination. Laparotomy performed in 41 patients identified unsuspected splenic involvement in 9 cases (22%), but was a distinct failure in confirming most "small node" positive lymphangiograms. Two patients developed acute myelocytic leukemia, both while NED 5 years posttherapy. One patient had also received adjunctive MOPP. There has been no impairment in the quality of survival that could be directly attributed to radiotherapy.


Bone marrow regeneration following large field radiation: influence of volume, age, dose, and time.

Regeneration of bone marrow following radiation only was investigated using 111Indium as a bone scanning agent. Factors which influence local marrow regeneration are dose, age of the patient, and the total amount of the marrow which was irradiated. Time effects are not demonstrated in this study, except to the extent that most regeneration did occur within the first 12 months following irradiation. The most striking finding is the effect of the irradiation volume. Apparent inconsistencies in earlier reports concerning the dose effect could be explained by this effect alone.


The value of computerized tomography in delineating suprasellar extension of pituitary adenoma for radiotherapeutic management.

Radiotherapy plays a major role in the management of pituitary adenomas, either as a surgical adjunct or as the primary form of treatment. Small field precision techniques are utilized. The ability to employ limited field therapy and produce local control rates of 80--90% demands precise tumor localization. The extrasellar extension of pituitary adenomas has classically been demonstrated on angiographic and pneumoencephalographic examinations. Direct superior extension is accurately delineated by these examinations; lateral extension, however, is not and the total anterior-posterior extent of the tumor may be underestimated. The addition of computerized tomography significantly increases the information available in the assessment of tumor extension and the subsequent accuracy of treatment planning for radiotherapeutic purposes.


Preoperative irradiation of primarily unresectable colorectal carcinoma.

A series of 44 patients with colorectal carcinomas considered unresectable on presentation received preoperative irradiation to a dose of 4500--5000 rad (175--200 rad/day). After a waiting period averaging 6.5 weeks, 38 patients underwent exploration. Complete resection was possible in 27 patients. Of these, 22 patients remained disease-free with a median follow-up of 27 months. While longer follow-up periods are needed, the results indicate that the large percentage of unresectable and therefore surgically incurable colorectal carcinomas can be made resectable by preoperative irradiation, and a significant number of these may have been cured.


Preoperative radiotherapy in operable breast cancer: results in the Stockholm Breast Cancer Trial.

A randomized trial of preoperative radiotherapy in operable breast cancer was conducted from 1971 to 1976. The diagnosis was established by fine-needle aspiration biopsy. A dose of 4500 rad over five weeks was given to the chest wall, the breast and the lymph nodes of the axilla, the supraclavicular fossa and the internal mammary chain. Modified radical mastectomy was performed six weeks or more after completed radiotherapy. In control patients the same operation was performed without prior radiotherapy. By random allocation, one control group received no further treatment and postoperative irradiation was given to the other controls. Preoperative radiotherapy reduced the incidence of local and regional recurrence and of distant metastases, and also the mortality, as compared with the surgery only group. Postoperative radiotherapy as given in this trial gave almost equal reduction of local and regional recurrence but did not diminish the frequency of distant metastases or the mortality.


Postoperative radiation therapy for "early" carcinoma of the breast.

Two hundred and twenty-five cases of "early" carcinoma of the breast, showing no evidence of axillary lymph node metastasis, are presented. One hundred and thirty-six of these patients were treated by radical mastectomy only, and 89 received postoperative radiation therapy to the ipsilateral internal mammary and supraclavicular regions. The routine use of postoperative radiation therapy of all patients in this group is not warranted. Patients with inner quadrant and central or subareolar primary lesions benefit from postoperative radiation therapy with a 10 to 21% increase in the disease-free survival at ten years. Deep-seated tumors, irrespective of size and location, should also be considered for postoperative radiation therapy to the regional lymphatic chain and the ipsilateral chest wall.


Treatment of advanced Hodgkin's disease in pediatric patients.

From 1970 to 1976, twenty patients with stage II E or II B to IV B Hodgkin's disease were treated at Children's Hospital of Philadelphia. Initially, four of the stage II or III patients received planned total nodal irradiation (TNI) alone; three patients developed progressive disease during irradiation, and one relapsed after 18 months. These results with TNI led to the use of combined modality therapy. Sixteen patients (4, stage II E or B; 8, stage III; 4, stage IV) were treated with COPP (cyclophosphamide, Oncovin, prednisone, and procarbazine) and radiation therapy. In 14 patients treatment was started with COPP. Patients with disease below L2 received TNI; the rest received involved field (IF) or extended field (EF) irradiation. No patient treated with combination therapy encountered life-threatening toxicity. Relapse-free survival in 12 stage II or III patients is 100% with a median follow-up of 28 months (range, 24 to 91 months). Only one of four stage IV patients is alive. Combined modality therapy is effective, tolerable therapy for children with stage II B--III Hodgkin's disease. No relapses occurred in 10 patients given less that potentially curative radiation. Smaller radiation fields and lower doses are planned for the future.


Combined irradiation and surgery in the treatment of stage II carcinoma of the endometrium.

Between January 1969, and August 1975, 40 patients with pathologic Stage II carcinoma of the endometrium were treated at the Joint Center for Radiation Therapy. The treatment policy included external and intracavitary irradiation combined with surgery. The majority of patients received 4000 mg/hours of radium exposure using a Fletcher-Suit applicator and 4000 rad whole pelvis external irradiation, followed by hysterectomy and bilateral salpingooophorectomy. Median age of the patients was 61 years (39--88) and the median follow-up of the patients still alive was 69 months (29--102). Relapse-free 5-year survival corrected for intercurrent disease was 83% and uncorrected, 78%. Overall survival was 80%. Five patients had relapsing disease, three patients failed at distant sites only, one patient died of treatment related complications, and two failed locally and distantly. There were no failures in the pelvis alone. Although the relationshop between histologic grade and failure is not statistically significant, there were four failures among the 12 Grade III patients compared to two failures in 27 with Grades I and II. Similarly, 4 of 12 patients with gross cervical involvement developed relapsing disease, but only 2 of 28 failed with microscopic cervical involvement. This treatment policy yields excellent survival and continues to be our treatment recommendation.


Total skin electron beam therapy in mycosis fungoides.

Thirty-nine patients with mycosis fungoides were treated with total skin electron beam irradiation from 1971 to 1976, and all received minimum follow-up of 12 months. Details of treatment technique and dosimetry are given. Sixteen patients cleared completely. Seven patients are in long-term remission (1 1/2 to 4 1/2 years). Eleven patients died. Those who failed are now being treated with topical therapy with varying degrees of control. Some have been retreated with local irradiation. Most of the patients had extensive disease; for this group, total skin electron beam therapy was especially useful, as many of those who failed developed only minimal disease that was well controlled by topical measures.


Second neoplasms following megavoltage radiation in a pediatric population.

Previous reports of radiation-related neoplasia have relied primarily upon patients treated by orthovoltage to low doses for benign disease. This survey is believed to be the first to assess the incidence of second neoplasms following megavoltage therapy. The source was the records of all long-term pediatric survivors (88 patients) who were treated with megavoltage radiation (cobalt 60) at the University of Minnesota. There was an average follow-up period of 14 years during which 7 second neoplasms were discovered (8%). Five were not associated with prior radiation. Both radiation-related neoplasms were associated with low doses and one was without significant morbidity. Two of the seven neoplasms were malignant; one was not associated with radiation while the other was associated with prolonged chemotherapy and low dose radiation (1%). The only fatal second neoplasm was not associated with radiation but developed 5 years after prolonged chlorambucil treatment. This review reveals the tendency of childhood cancer victims to develop other neoplasms regardless of radiation. The finding of neoplasia induction only at low radiation doses supports the Gray hypothesis of decreased tumor induction at high doses through increased cell killing.


The role of radiation therapy in the treatment of soft tissue sarcomas of childhood.

The treatment of soft tissue sarcomas in children at the Joint Center for Radiation Therapy, Children's Hospital Medical Center, and the Sidney Farber Cancer Institute from 1970 to 1976 has been reviewed. Twenty-seven patients were diagnosed with rhabdomyosarcoma, and twenty patients were diagnosed with soft tissue sarcomas of other histologies. An aggressive, combined modality therapeutic approach was applied in the treatment of all patients with emphasis placed on conservation of function. Of irradiated patients, local control was achieved in 96% of those with rhabdomyosarcoma and 85% in other sarcomas. Cumulative relapse-free survival (actuarial) at 5 years is projected at 65% for the rhabdomyosarcoma patients and at 63% for the other sarcoma patients. Although there were differences in chemotherapy regimens (vincristine, actinomycin-D and cyclophosphamide for rhabdomyosarcoma and adriamycin and DTIC for other soft tissue sarcomas), the surgical and radiation therapeutic approaches are similar for both groups. The high probability of local control using function-conserving surgery and high dose radiation therapy supports this emerging approach. Improvements in survival will require better control of metastatic disease.


Natural history of papillary lesions of the urinary bladder in schistosomiasis.

Variable epithelial hyperplasia was observed in urinary bladder of nine capuchin monkeys (Cebus apella) when examined at cystotomy 94 to 164 weeks after infection with Schistosoma haematobium. These hosts were followed for 24 to 136 weeks postcystotomy to determine the status of bladder lesions in relation to duration of infection and to ascertain whether lesion samples removed at cystotomy reestablished themselves in autologous and heterologous transfers. There was involution of urothelial hyperplasia in eight of nine animals and no evidence for establishment of transplanted bladder lesions.


Carcinogenicity of triethanolamine in mice and its mutagenicity after reaction with sodium nitrite in bacteria.

Mice fed a diet containing 0.3 or 0.03% triethanolamine developed malignant tumors. Females showed a high incidence of tumors in lymphoid tissues, while this type was absent in males. Tumors in other tissues were produced at a considerable rate in both sexes, but no hepatoma was found. Triethanolamine was not mutagenic to Bacillus subtilis by itself, but it became mutagenic after reacting with sodium nitrite under acidic conditions or when the mixture was heated. Although N-nitrosodiethanolamine, a known carcinogen and mutagen, was detected in the reaction mixture by thin-layer chromatography, it may not be the main mutagenic product, because the product was a stable and direct mutagen and its mutagenic activity was destroyed by liver enzymes, unlike N-nitrosodiethanolamine. The lethal and mutagenic DNA damages produced by this unidentified product were susceptible to some extent to the repair functions of the bacteria.


Difference between mammary epithelial cells from mature virgin and primiparous mice.

Mammary epithelial cells from mature virgin mice are similar to those from primiparous mice in several respects. However, there is one known difference. The cells from the mature virgin must traverse the cell cycle in order to become competent to make casein and enzymatically active alpha-lactalbumin in vitro; those from the primiparous animal can make these proteins without first traversing the cycle. In this regard, cells from human placental lactogen- and prolactin-treated mature virgins are, after involution, similar to those from primiparous mice. The developemental block in the cells from the mature virgin, imposed by preventing cell cycle traversal, has been partially delineated. It does not appear to reside at the levels of ultrastructural maturation or the formation of casein messenger RNA. Rather, the lesion is postranscriptional and may be at the level of translation, or posttranslational modification, or both.


Isolation and purification of rat mammary tumor peroxidase.

7,12-Dimethylbenz(a)anthracene-induced rat mammary tumors often contain high levels of the enzyme perioxidase, a putative marker of estrogen dependence. This enzyme can be effectively extracted with 0.5 M CaCl2, giving rise to a soluble peroxidase with a molecular weight of about 50,000 as determined by gel filtration. This is the same size as the estrogen-induced peroxidase of rat uterus but smaller than other mammalian peroxidases. Further purification of the rat mammary tumor peroxidase by concanavalin A-Sepharose chromatography and hydrophobic interaction chromatography on phenyl Sepharose provides a 640-fold purification of the enzyme.


Unsaturated fatty acid requirements for growth and survival of a rat mammary tumor cell line.

A cell line, the growth and survival of which is markedly affected by linoleic acid, has been established from a carcinogen-induced rat mammary tumor. The cells have been continuously passaged in 5% rat serum plus 10% fetal calf serum-supplemented medium. The rat serum component was found to be indispensalbe, for when it was omitted the growth rate rapidly declined and the cells died by 5 to 7 days. Removal of the rat serum from the growth medium also resulted in a dramatic loss of Oil Red O-positive droplets in the cells, suggesting that the lipid component of rat serum might be a major growth-promoting principle in rat serum. This is likely since the total lipid fraction, but not the delipidized protein fraction, could largely supplant requirement of the cells for rat serum. Pure linoleic acid was found to be effective in maintaining the cell growth in delipidized serum or in whole fetal calf serum-supplemented medium. Fatty acid analysis revealed a 19-fold higher amount of linoleic acid in rat serum than in fetal calf serum.


Vasopressin stimulation of acetate incorporation into lipids in a dimethylbenz(a)anthracene-induced rat mammary tumor cell line.

In a preliminary report we described the effects of rat prolactin on the incorporation of [14C]acetate into lipids by a cell line from a dimethylbenz(a)anthracene-induced rat mammary tumor. The characteristics of the response to prolactin were very similar to those described for the normal rat mammary gland; namely, insulin was required for full expression of the response, maximal activity was not seen until 36 hr after the addition of the hormones, and growth hormone was able to elicit the same response. However, we were unable to detect binding of 125I-labeled prolactin to these cells, and furthermore, other more purified prolactin preparations were inactive. Upon further investigation we discovered that the activity resided in a low-molecular-weight fraction of the rat prolactin B-1 preparation and was probably either vasopressin or oxytocin or both. These data suggest the possibility that vasopressin may play a role in rodent mammary tumorigenesis.


Use of nitroglycerin ointment in congestive heart failure. Results of acute and chronic therapy.

7 consecutive patients with congestive heart failure refractory to standard therapy were treated with nitroglycerin ointment (GTNO). The pulmonary wedge pressure decreased from a control value of 30+/-1 to 15+/-1 mm Hg (mean +/-SEM), and the arteriovenous oxygen difference narrowed from 6.8+/-0.5 to 5.5+/-0.3 ml%, after GTNO therapy. The heart rate decreased in 5 patients and the systolic blood pressure was either unchanged or decreased slightly. A reduction in the echocardiographic end diastolic dimension was noted in all patients. The transmyocardial gradient (systemic artery diastolic pressure - pulmonary artery wedge pressure) increased in all except 1 subject. The double product decreased in 5 of the 7 patients. Hemodynamic improvement was maintained for 4.5-7 h. All patients were symptomatically improved on chronic GTNO treatment. Our results indicate that GTNO is a useful agent in the management of heart failure which is unresponsive to standard therapy.


Stress testing and working capacity in Chagas' cardiomyopathy.

The EKG response to exercise and the working capacity in a group of 70 patients with positive serology for Chagas' disease has been determined by stress testing on a bicycle-ergometer, in order to establish the usefulness of such a test in the early diagnosis of Chagas' cardiomyopathy. The exercise EKG provides information which cannot be obtained by other diagnostic procedures, since the stress test can induce or increase ventricular arrhythmia, and is particularly indicated in patients with Chagas' infection and the incipient forms of Chagas' cardiomyopathy. Measuring the working capacity is useful in order to establish the degree of functional impairment of each individual patient. After the application of oral digoxin, no significant increase of ventricular extrasystoles following exercise has been observed and the working capacity has improved in the majority of the studied cases with Chagas' cardiomyopathy.


Immunofluorescence study of the hypothalamo-infundibular LRH tract and serum gonadotropin levels in the female squirrel monkey during the estrous cycle.

The study of LRH reactive neurons of the medial basal hypothalamic group was made with rabbit antisera to unconjugated synthetic LRH, in normally cycling female squirrel monkeys. The specifically immunoreactive material present along the hypothalamo-infundibular LRH tract shows significant modifications that are particularly distinct in the lateral, posterior and anterior labia of median eminence, with a maximum concentration during the early and middle follicular phases, a sudden fall to a minimum concentration during the late follicular and ovulatory phases and with a progressive increase during the luteal and early follicular phases. Serum FSH and LH levels show a progressive decrease from the luteal phase to the late follicular phase, with differential modifications suggesting that a double regulation might take place in cycling squirrel monkeys. A parallel is suggested between the specifically reactive material along the hypothalamo-infundibular tract, serum gonadotropin levels and variations in the medial basal hypothalamic and infundibular LRH concentrations during the estrous cycle in the squirrel monkey.


Histochemical and ultrastructural effects of enovid E on the endometrium of the baboon.

Endometrium from a group of baboons treated with the oral contraceptive, Enovid E, was studied histologically, histochemically and ultrastructurally, and compared to endometrium from normally cycling animals. All endometria were obtained by transcervical uterine biopsy between 10 and 14 days of the treatment cycle or the normal menstrual cycle. Histologically, no discernible differences between the control and experimental endometria were apparent. While observable differences were not evident between the endometrial alkaline phosphatase and succinate dehydrogenase activities of control and experimental animals, there was an increased acid phosphatase activity in the Enovid E-treated baboon endometrium. Ultrastructurally, the glandular cells of treated animals appeared to be more physiologically advanced than did those from the control endometria. These advances were evident from the prominent Golgi complex, increased development of the endoplasmic reticulum and increases in the size, number and complexity of mitochondria. The functional correlates of these morphological and histochemical observations are discussed and compared to human endometrial studies.


Ultrastructural and morphometric aspects of the juxtaglomerular apparatus in the monkey kidney.

The authors describe the ultrastructure of the juxtaglomerular apparatus in five adult male Cebus apella monkeys and communicate morphometric data of the macula densa. In comparison with several species of rodents examined before, the macula cells of the monkey contain many more mitochondria and possess a particularly thick basal membrane. The relative volume of the nuclei is slightly smaller than in rodents. The Goormaghtigh cells of the monkey resemble those of the other animals investigated. The epithelioid (or juxtaglomerular) cells do not contain secretory granules. This observation reminds one of the behavior of the epithelioid cells of guinea pigs.


A complete immunoglobulin gene is created by somatic recombination.

Using a pCRI plasmid containing an enzymatically synthesized, full-length DNA transcript of immunoglobulin lambda chain mRNA as the hybridization probe in the Southern gel blotting experiments (Southern, 1975), we identified three DNA fragments of 8.6, 4.8 and 3.5 kb in Eco RI-digested total DNA from BALB/c mouse embryos. A fourth fragment of 7.4 kb was found in addition to these three fragments in similarly digested total DNA from a lambda chain-secreting myeloma (HOPC 2020). We have cloned the four DNA fragments in an EK-2 phage vector, lambdaWES, and characterized them with respect to size, type of lambda gene sequences contained and position of these sequences in the fragments, using agarose gel electrophoresis, the gel blotting technique and electron microscopic R loop mapping. The embryonic DNA clones Ig 99 lambda, Ig 25lambda and Ig 13lambda contain one copy each of V lambdaI, C lambdaI and V lambdaII sequences, respectively, while the myeloma DNA clone Ig 303lambda contains one copy each of V lambdaI and C lambdaI sequences that are separated by a 1.2 kb nontranslated DNA segment. Ig 25lambda was also shown to contain a DNA segment of approximately 40 base pairs (bp) (J sequence) that lies 1.2 kb away from the C lambdaI sequence and is homologous to the V-C junction region of a lambdaI mRNA. Heteroduplex analysis of the three lambdaI DNA clones revealed that Ig 303lambda DNA is composed of two parts, one of which is entirely homologous to one end of Ig 99lambda, and the other to one end of Ig 25lambda DNA. The sequence arrangement observed in the cloned DNA is the same as that in the corresponding cellular DNA. This was shown by identifying certain restriction enzyme cleavage sites on the cloned DNAs and demonstrating the presence of these sites in the total cellular DNA by the gel blotting technique. The site of the homology switch is at the boundary of the V sequence and the 1.2 kb nontranslated DNA segment, and corresponds to the position of the J sequence on the Ig 25lambda DNA. We consider the above experimental results the most direct evidence for somatic rearrangement in immunoglobulin genes. We discuss the significance of these findings for the origin of genes in the evolution of higher organisms and in cell differentiation.


Molecular cloning and expression in E. coli of a yeast gene coding for beta-galactosidase.

The yeast Kluyveromyces lactis synthesizes a beta-galactosidase (EC 3.2.1.32) which is inducible by lactose. We have isolated the gene that codes for this enzyme using recombinant DNA techniques. K. lactis DNA was partially digested with the restriction endonuclease Eco R1 and joined to Eco R1-digested pBR322 plasmid DNA using DNA ligase. ligase. A lac-mutant of Escherichia coli lacking the structural gene for beta-galactosidase was transformed with ligated DNA. Three lac+ transformants containing recombinant plasmids were selected. Two of the plasmids (pK15 and pK17) contain four Eco R1-K. lactis DNA fragments having molecular weights of 2.2, 1.4, 0.55 and 0.5 x 10(6) daltons. The other plasmid (pK16) lacks the smallest fragment. E. coli carrying any of these plasmids produce beta-galactosidase activity that has a sedimentation coefficient and immunological determinants that are nearly identical to K. lactis beta-galactosidase and distinctly different from E. coli beta-galactosidase. DNA-DNA hybridization studies show that the four Eco R1 fragments in pK15 hybridize to K. lactis but not to E. coli DNA.


Changes of enzyme activity in larval salivary glands following the induction of respiration dependent puffs in giant chromosomes of Drosophila melanogaster.

Changes in the activity of 3 enzymes--lactate dehydrogenase (LDH), soluble malate dehydrogenase (sMDH), and pyruvate kinase (PK)--in homogenates of larval salivary glands of Drosophila melanogaster were studied before and after the induction of heat sensitive puffs with trinactin. The activities of 2 enzymes (LDH and sMDH) were enhanced after puff induction, an effect that was abolished in the presence of cycloheximide. Pyruvate kinase activity did not change after puff induction. The results indicate a relation between the increase of LDH and sMDH activity due to de novo synthesis and the induction of heat sensitive puffs.


The differential response of isolated intestinal crypt and tip cells to the inductive actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The cell specific induction of uridine diphosphate(UDP)-glucuronyltransferase by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in intestinal epithelium was studied by administering [14C] TCDD (8 microgram/kg to adult female rats). Intact epithelial cells from the tip and crypt regions were isolated by differential vibration of rat duodenum. Cell separation was monitored by electron microscopy and marker enzymes. UDP-glucuronyltransferase and radioactivity were assayed in both cell types 0 h, 3 h, 10 h, 1 day, 3 days and 5 days after treatment. UDP-glucuronyltransferase activities were not significantly changed in either cell type isolated from TCDD-treated rats until 24 hr after treatment when a three-fold increase in crypt cell activity was evident. No significant changes in UDP-glucuronyltransferase activity were observed in the differentiated tip cells until 3 days after TCDD treatment. UDP-glucuronyltransferase was increased approximately two-fold in both cell types from 3 and 5 days following TCDD treatment. There was a negative correlation between the time-course of UDP-glucuronyltransferase induction and the [14C]TCDD concentrations measured in these cells. These studies suggest that the undifferentiated cells of the intestinal crypt region are more sensitive to TCDD inductive actions than are the absorptive tip cells.


Factors affecting the binding of polycyclic aromatic hydrocarbons to human embryo cells, and transformable and non-transformable hamster embryo cells.

The effects of various factors, including population doubling number, percent of confluence, serum concentration and storage in liquid nitrogen on the binding of several polycyclic aromatic hydrocarbons to human and hamster embryo cells were studied. The binding of 7,12-dimethylbenz[a]-anthracene (DMBA) to hamster embryo cells DNA, RNA and protein was maximal after 22 h of treatment. In contrast, binding to human embryo cell macromolecules increased for at least 55 h. Treatment of hamster embryo cells at 100% confluence resulted in much less binding than treatment at 70% confluence, whereas with human embryo cells the binding increased, or remained constant, following treatment at the greater confluence. The transforming frequency of hamster embryo cells decreases with increasing population doubling number. Accordingly, we found that the binding of DMBA to hamster embryo DNA, RNA and protein decreased approximately 100-fold between population doubling numbers 8 and 20. In transformable cell cultures, DMBA was bound to hamster embryo cell DNA to a greater extent than to RNA or protein. The binding of DMBA to nucleic acids was much greater than binding by either dibenz[a,h]anthracene (DB[a,h]A) or dibenz-[a,c]anthracene (DB[a,c]A), both of which had low binding values at all population doubling numbers tested. Therefore, the best correlation of binding with carcinogenicity and transforming activity was observed with DMBA. Storage of hamster embryo cells in liquid nitrogen did not alter their binding characteristics. Binding of all three hydrocarbons to human embryo cell nucleic acids was low during all population doubling numbers studied, while binding to cellular protein increased until population doubling number 70 and then decreased sharply.


The formation of dihydrodiols by chemical or enzymic oxidation of 3-methylcholanthrene.

The chemical oxidation of 3-methylcholanthrene in an ascorbic acid-ferrous sulphate-EDTA reaction mixture gave all five possible dihydrodiols. The structures and stereochemistry of the dihydrodiols were shown by UV, mass and NMR spectral studies and by chemical examination to be cis-2a,3-dihydroxy-3-methylcholanthrene, trans-4,5-dihydro-4,5-dihydroxy-3-methylcholanthrene, trans-7,8-dihydro-7,8-dihydroxy-3-methylcholanthrene, trans-9,10-dihydro-9,10-dihydroxy-3-methylcholanthrene, cis-11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene and trans-11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene. An examination by HPLC of the dihydrodiols formed in the metabolism of 3-methylcholanthrene by rat-liver microsomal preparations showed the presence of trans-4,5-dihydro-4,5-dihydoxy-3-methylcholanthrene, trans-7,8-dihydro-7,8-dihydroxy-3-methylcholanthrene, trans-9,10-dihydro-9,10-dihydroxy-3-methylcholanthrene and trans-11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene, identified by comparison of their UV and chromatographic characteristics with those of authentic standards. Tentative identification of cis- and trans-1,2-dihydroxy-3-methylcholanthrene, cis-2a,3-dihydroxy-3-methylcholanthrene and cis-11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene as metabolites were made from their mobilities using HPLC. A quantitative comparison of the dihydrodiols formed from 3H-labelled 3-methylcholanthrene by microsomal preparations from the livers of normal and 3-methylcholanthrene-treated rats was carried out. trans-9,10-Dihydro-9,10-dihydroxy-3-methylcholanthrene and cis- and trans-1,2-dihydroxy-3-methylcholanthrene were formed when 3-methylcholanthrene was incubated with mouse skin in organ culture.


[Primary visual centers in the frog (Rana esculenta L.) and the problem of ipsilateral projections. Radioautographic study].

The topographic organization of the frog's primary visual system has been reexamined in Rana esculenta using autoradiographic technique. 10 to 24 hrs following an intraocular injection of tritiated proline, an intense labelling was observed contralaterally in the various retinal projection centres (preoptic area); neuropils of Bellonci; corpus geniculatum of the thalamus; posterior thalamus; posterodorsal preoptic area; magnocellular pretectal nucleus and basal optic nucleus; tectal laminae A to G of Potter), as already described. Furthermore, the presence of a ipsilateral projection within the hypothalamus (preoptic area), the thalamus (neuropils of Bellonci and corpus geniculatum) and the pretectium (posterior thalami neuropil, pretectal optic area) is confirmed. On the other hand, the existence of ipsilateral retinotectal (to Potter's lamina F) and retino-tegmentomescencephalic projections (to the basal optic nucleus), which were thusfar questioned, has been demonstrated.


[Structural diversity of communicating intercellular junctions (gap junctions) in the posterior cecal epithelium of the crustacean Orchestis].

Two types of gap junction are described, they are different in the size, the spacing and the polarity of their intramembrane particles. The dense type shows two kinds of particles which rather remain joined to the P fracture face. The loose type shows larger and more spaced out particles which rather are held by the E fracture face. These observations demonstrate that one needs to shade the distinction between P-type gap (Vertebrate) and E-type gap (Arthropoda).


[Lack of participation of cytoplasmic choline in the synthesis of acetylcholine in the striatal synaptosomes of the rat].

Synaptosomes prepared from Rat striatum were loaded with (14C) choline at 0 degrees C in the course of a 60 min. preincubation. After the removal, by washing, of the extracellular molecules, synaptosomes were incubated 5 min. at 37 degrees C in the presence of (3H) choline. The measurement of the amounts of (3H) ACh and of (14C) ACh formed allowed us to conclude that the acetylation of the molecules of choline was directly coupled to their passage through the synaptosomal membrane.


[Kinetics of the pulmonary clearance of inhaled cadmium and its accumulation in rat liver and kidneys].

Pulmonary clearance rate of cadmium (Cd), inhaled in the form of an aerosol of Cd acetate, is very slow (half-life 53 days). However, results demonstrate that an important part of Cd cleared from the lung is recovered in liver and kidney. Liver binds this metal rapidly but to a limited extent, whereas renal accumulation is slow but continuous throughout the three months following exposure.


[The effect of anesthetics on the basal secretion of immunoreactive growth hormone in rats].

The authors investigated basal levels of plasma immunoreactive growth-hormone in the rat (R-GH) after administration of 3 different anesthetic drugs: urethan, chloral hydrate and gamma-hdroxy-butyrate (GHB). Lowest R-GH concentrations (5 +/- 3 ng/ml) are observed after urethan; they are significantly higher (15 +/- 4 ng/ml) after chloral hydrate but this anesthetic also causes hyperglycemia (210 +/- 30 mg/100 ml). Normal blood glucose levels are observed under GHB narco-analgesia which elicits a clear-cut R-GH secretory episode (70 +/- 5 ng/ml); basal values (12 +/- 3 ng/ml) are maintained for several hours thereafter.


[Analysis of the tissue interactions responsible for the mesonephogenic determination in amphibians, by the in vitro culture technic].

The cultivation of mesonephric lateral mesoblast, in combination with the dorso-caudal endoblast, with or without cordomesoderm, leads to the differentiation of mesonephric tubules in Bufo bufo and Pleurodeles waltlii. Then, the nephric duct does not seem to be necessary to nephric differentiation under in vitro cultivation conditions.


[Rapid recording of the fluorescence spectrum emitted by an isolated living cell].

In order to use the selectivity of fluorescence emission for biomedical purposes, a microspectrofluorimeter has been built around an inverted microscope. The excitation is supplied by a 450 W Xenon lamp coupled with a monochromator allowing excitation from 230 to 600 nm. The fluorescence is analysed by a Grism (association prism-grating) and the spectrum focused on the 500 channels of the target of an Optical Multichannel Analyser. Related to good resolution and dispersion (0.44 nm/channel), improvement of signal to noise ratio (dark current suppression, and accumulation of spectra), this microspectrofluorimeter with high sensitivity is well adapted to the study of biological mechanism in single living cells (macrophages, monocytes, lumphocytes).


[Development and evaluation of a method of high pressure liquid chromatography for the determination of the level of degradation of thyroliberin (TRH) in blood].

The degradation of the TRH by plasma was studied using a sensitive method for the separation of TRH and products formed by high-pressure liquid chromatographic analysis (HPLC). The detected products are TRH-3H or synthetic TRH. The HPLC analysis is performed on a microparticulate (10 mu) silica gel chromatographic column with CH3CN/0,01 M NH4OAc, at pH 6 (30/70) (V/V). This technique provides a good separation of TRH and the other products of degradation. In our experimental conditions, the human plasma degrades 62.5 +/- 5% of of TRH in 60 mn; very similar results are obtained with thin layer chromatography.


[Cartilaginous tissue and nalidixic acid].

1. Medication with nalidixic acid never produced articular lesions in adult animals. 2. In the species of immature animals, if sensitive to nalidixic acid, the articular lesions were macroscopically and microscopically identical. 3. The lesions regressed spontaneously as the basal germinative layer was never affected.


[Simple technic for culture of locus coeruleus nucleus in the newborn mouse].

The dissecting procedure and tissue culture technique on collagen coated coverslips in Leighton tubes, of newborn Mouse nucleus locus coeruleus and the regular histofluorescence demonstration of catecholaminergic fibers in the outgrowth zone are described. This simple method allows 10 day--long experiments .


[Application of the ion-thinning methods to the high-resolution study of human dental enamel crystals].

Ion thinning technique applied to high resolution T.E.M. study of human dental enamel crystallites makes it possible to visualize a great number of dislocations. Dislocations proved not to be due to artifacts induced by the ultramicrotome diamond knife. They are related to the crystal apartite structure.


[Origin of a mitogrenic factor for cultivated macrophages (IMF: Inflammatory Mitogenic Factor) found in exudates of non-specific acute inflammation].

The mitogenic activity of inflammatory exudate obtained from irradiated Rats is reduced. After transfer of bone marrow syngeneic cells into irradiated Rats this mitogenic activity is further decreased, while after transfer of thymic cells it is increased. It is postulated that the mitogenic activity of inflammatory exudate could be related to thymic cells and that T lymphocytes may be involved in non specific-inflammatory reactions.


[Regional variations and particle binding of free amino acids in the rat brain: effects of amphetamine and methaqualone].

Amphetamine and methaqualone affected aspartate level in various regions of Rat brain. Increased aspartate level in cerebral cortex of methaqualone treated Rats was produced in the aspartate fraction whose binding to subcellular particules was Na+ dependant. This work suggest that aspartate level was altered only in brain fraction implicated in the pharmacological effects of the drugs.


[Trials of mixed grafts of 5 cell lines from human brain tumors in athymic nude mice].

Five established lines derived from human brain tumors were mixed in pairs and injected into athymic nude Mice. The observation of mixed tumors and patterns of rejection obtained after inoculation enabled us to classify these five lines according to their aggressiveness in a heterologous host. In addition, the SA 52 line induced an inhibitory effect on graft growth (or a facilitation of rejection).


[Demonstration by stereological methods of pre-prophase doubling of the number of ribosomes in Ehrlich tumor cells].

Homogeneous populations of G1, S or G2 Ehrlich tumor cells are analysed by stereological methods at the ultrastructural level. This analysis demonstrates that the number of cytoplasmic ribosomes is doubled before the prophase.


[Early effect of estradiol on ultrastructure of chromatin in the endometrium and hormone-dependent mammary tumors].

After in vivo and in vitro administration of aestradiol, the chromatin of lamb endometrium and of hormone-dependent 7,12-dimethylbenzanthracene Rat mammary tumors is rapidly transformed from a condensed into a diffuse chromatin. A stimulation of 3H leucine incorporation into protein was also observed. These modifications were specific for estrogen receptor ligands and for estrogen responsive tissues. In vitro tamoxifen induced pycnosis. These changes could be used to improve the prediction of hormone dependency of human breast and uterine cancers.


[Demonstration of a 2d LH-RH neurosecretory system in the duck hypothalamus].

Using immunocytochemical techniques with an anti-LH-RH immuneserum, evidence of two neuronal systems secreting LH-RH has been shown in the Duck hypothalamus. In addition to the previously described system, located in the preoptic nucleus, a second system could be demonstrated in the infundibular nucleus. The perikarya of the infundibular LH-RH producing neurons were significantly smaller than those of the preoptic neurons. On the other hand, under the experimental conditions used, the infundibular system had approximately five times less LH-RH secreting neurons than the preoptic system, and its perikarya appeared less heavily loaded in IR LH-RH. The LH-RH containing axons from both neuronal populations ran down to the external layer of the median eminence, where they ended in close contact with the capillaries of the hypophysial portal system.


[Persistence of orientation-selective cells of the primary visual cortex in kittens enucleated unilaterally at birth and reared in darkness].

In kittens dark reared (6 weeks old) orientation selective cells are no longer recorded in the primary visual cortex, while in kittens of same age, enucleated at birth unilaterally and reared in identical conditions, 30% of visual cortical cells are shown to be orientation selective and in addition respond preferentially to horizontal and vertical orientations.


[Adaptation of the deoxyglucose method to the cellular level: histologic preparation of the central nervous system for high resolution radioautography].

Vascular perfusion of all products required for primary fixation, postfixation, dehydration and embedding of nervous tissue in Epon permits radio-autographic detection of radioactivity accumulated in the central nervous system after intravenous injection of [3H]deoxyglucose. This histological technique should allow application of the deoxyglucose method at cellular if not subcellular level, since a high proportion of the tracer appears to be retained in situ in specimens adequately preserved for light and electron microscope radio-autography.


[Electron microscopy of mitochondrial DNA in Podospora anserina and the presence of a multimeric range of circular DNA molecules from senescent cultures].

Mitochondrial DNA from young cultures of race s of Podospora anserina was isolated. Its density in Cesium chloride density equilibrium gradients was 1.694 g/cc. Examination by the electron microscope revealed that ca 1% of this DNA consisted of circles, 31 micrometer in contour length; the remaining DNA was composed of linear molecules ranging in length from 2 to 33 micrometer. In DNA of similar density obtained from senescent cultures of the same race s, about 11% of the molecules consisted of a multimeric set of circles ranging in size from 0.9 to 15 micrometer, with most being in the 1.8 and 2.7 micrometer classes. The similarity of these DNA molecules with the mitochondrial DNA from rho(-) yeast mutants is discussed.


[A malignant tumour in the female genital tract of Pachygnatha clercki Sundevall, 1823 (Arachnida, Araneae, Tetragnathidae)].

A first case of genuine neoplasm is reported in the order Araneida. This epithelial tumor, proceeding from oviduct ends, invades uterus; malignancy is strongly supported by cell structure and extensive local behavior.


[A model of enzymatic kinetics].

In this Note, we study a system of differential equations representing the kinetics of an enzymatic reaction. For a closed system, and in the domain where it has a biological significance, it is shown that: (i) there exists a unique equilibrium point, which is an asymptotically stable point; (ii) if several enzymes act on the same substrates, the equilibrium values of the substrates concentrations take their values within the range of the equilibrium values achieved with each of these enzymes, (iii) the kinetics of the reaction can be approached by a single first-order differential equation, which may be seen as a generalization of the Michaelis equation.


[Differentiation of human megakaryocytes in culture starting from the primordial circulating cells in the newborn].

Human neonatal blood mononuclear cells were seeded in plasma clot containing high dose of a crude erythropietin. Pure megakaryocyte colonies were observed rarely and most of the colonies were mixed, megakaryocytes being located between subcolonies of erythrocytic bursts. The megakaryocytic nature of large cells could be clearly confirmed by the presence of platelet peroxidase, demarcation membranes, and alpha granules detected by electron microscopy; in addition mature micromegakaryocytes were recognized, shedding platelets.


Effect of sublingual nitroglycerin on regional flow in patients with and without coronary disease.

We evaluated the effects of sublingual nitroglycerin on indices of regional coronary flow and coronary resistance (CR) in 12 selected patients with coronary artery disease (CAD) and eight with normal coronary arteries (NCA), using continuous thermodilution. Resting total left ventricular flow, reflected by coronary sinus flow (CSF), and anterior regional flow, reflected by great cardiac vein flow (GCVF), in NCA and CAD patient groups, were similar. However, in a subgroup of six patients, with CAD limited to the anterior descending artery, GCVF was lower and anterior regional CR (CRANT) higher than the NCA subjects. Nitroglycerin reduced the systolic pressure-heart rate product similarly in both patient groups. CSF and GCVF in NCA subjects declined 15% and 17%, respectively, as total CR (CRT) and CRANT increased. In the CAD subgroup, consisting of patients with CAD limited to the anterior descending, GCVF increased 48% as CRANT declined 50%, and CSF was unchanged. In the other CAD subgroup of patients with CAD in the right and/or circumflex arteries, GCVF declined 32% and CRANT increased 46% as CSF was minimally increased. These data imply that sublingual nitroglycerin reduces both CSF and GCVF in NCA patients as oxygen demands decrease. In certain CAD patients, however, nitroglycerin alters regional coronary venous blood flow, suggesting a redistribution of flow from normally perfused to hypoperfused regions.


Chemical and immunochemical measurement of total iron-binding capacity compared.

Radiometric, colorimetric, and two immunochemical methods for measuring total iron-binding capacity are compared. We evaluated the procedures on the basis of precision, applicability to a pediatric population, and accuracy as assessed by analytical recovery of purified transferrin. The immunoephelometric assay for transferrin provides significant advantages over the other methods examined.


An automated turbidimetric rate method for immunoglobulin assays.

A turbidimetric rate method for the determination of immunoglobulins IgG, IgA, and IgM has been adapted to an automatic kinetic rate analyzer. The procedure can be run on mildly lipemic sera without correction for sample light scatter. We report correlations with results by an immunodiffusion method and a manual laser nephelometric technique. The automated rate procedure described provides a rapid, accurate, precise and sensitive way to measure immunoglobulins.


Thyroid function in early sub-acute thyroiditis.

A 53-year-old woman with an early form of de Quervain's disease involving both thyroid lobes was found to have her thyroid uptake of iodine suppressed, although the serum thyroid hormone concentrations were normal while the administration of TRH resulted in significant increase in the serum TSH concentrations. After administration of TSH the thyroid reserve was found to below. The diagnosis of sub-acute thyroiditis was confirmed on biopsy. The above data seem to indicate that the suppression of the thyroid uptake in the early stage of de Quervain's disease may be directly caused by the inflammatory condition of the gland, rather than, as is usually the case, by the excess of thyroid hormones and, consequently, by the suppression of pituitary TSH secretion.


Bromocriptine suppression of the thyrotrophin response to thyrotrophin releasing hormone.

A single oral dose of 5 mg of bromocriptine significantly lowered the TSH response to 200 microgram TRH intravenously in eight healthy men compared with control experiments in the same subjects. This finding may be relevant in chronic bromocriptine therapy.


225 skateboard injuries in children.

Among 225 skateboard accidents treated at the Children's Hospital, Sheffield, in 8 months from August 1977, there were 92 fractures (40.9 per cent), of which 19 required manipulation under general anesthetic. Most involved the upper limb. Next most frequent were lacerations, bruises, abrasions, and injuries of joints and soft tissues. Four children had concussions (one with a fractured skull), 8 others had minor head injury, and 23 had soft tissue injuries of the head and neck. As for the reasons for the accidents, 20 per cent were due to hitting a stone, 10 per cent to a hole or bump in the pavement, 8 per cent to collisions, and three accidents to faults in the skateboards. Sixteen of the children were injured on the first day of their skateboarding. The role of protective clothing was uncertain. The city has no skateboard parks. Injuries due to skateboards were compared to injuries due to playground equipment.


Critical study of the value of renal clearances measured by the single shot technic.

A critical approach to the problem of establishing new methods of measurement of kidney function is presented. Variability of the reference clearances inulin and PAH is large, thus reference method ratios close to 1 are not sufficient to ascertain the value of the method under investigation. EDTA 51Cr and hippuran 125I, single shot technics illustrate the need for more accurate criteria required for validating a new technic.


The contraction induced by calcium ions in isolated guinea-pig vas deferens.

1. When isolated guinea-pig vas deferens was pretreated with 0.01% sodium edetate in an isotonic sucrose medium and then transferred to an edetate-free sucrose medium, the addition of CaCl2 (1.1 to 35.2 mmol/l) induced a contraction. 2. The contraction was greatest when the CaCl2 was added soon after pretreatment with edetate, and decreased with increasing time, almost disappearing after 1 h. 3. When KCl (1.4 to 22.4 mmol/l) was added in place of CaCl2, the contraction was lowest soon after pretreatment with edetate, and increased with time; after 1 h, the effect, was 80.7% of that observed in a preparation that had not been pretreaated with edetate.


In vitro activity of carbenicillin, ticarcillin, sisomicin and netilmicin alone and in combination against Pseudomonas aeruginosa.

The in vitro activity of carbenicillin, ticarcillin, sisomicin and netilmicin alone and in combination against 35 strains of Pseudomonas aeruginosa was investigated. Ticarcillin was more active than carbenicillin and sisomicin was more active than netilmicin. There was enhanced killing of many strains of P. aeruginosa by the combination of carbenicillin or ticarcillin with sisomicin or netilmicin.


The relation of radiation sensitivity to pronuclear chromosome structure. I. Different radiation sensitivities between Drosophila melanogaster and Phryne cincta.

After treatment of mature spermatozoa of Phryne cincta egg mortality rates were determined and chromosomal mutation rates by examination of the polytene chromosomes of the F1 progeny.--A comparison of the results with similar studies made on Drosophila melanogaster yielded a two- to threefold higher sensitivity in Phryne cincta. Evaluation of data concerning DNA amounts, heterochromatin contents, distribution of breaks, repair capacities in two-break sites and oxygen concentrations in mature spermatozoa revealed no contradiction to the hypothesis that the greater sensitivity of Phryne cincta is mainly due to a high degree of spiralization of the paternal pronucleus chromosomes.


Oral administration of thyrotropin-releasing hormone (TRH) in the diagnosis of thyreopathies.

The authors summarize their experience with a simple test for the diagnosis of hyper--and hypothyroidism after oral administration of thyrotropin-releasing hormone (TRH). The practical advantage of this test is the absence of unpleasant side-effects described after the intravenous administration and elimination of stress of the patients and health workers associated with injection.


The use of autologous and allogeneic venous grafts for arteriovenous fistulas in chronic haemodialysis.

The development of haemodialysis treatment and kidney transplantation has brought forth effective therapy and long-term survival in patients with irreversible renal failure. One of the factors limiting successful long-term treatment is the difficulty involved in the patients repeatedly on to the artificial kidney. Once all the routine techniques of creating subcutaneous arteriovenous have been exploited, the use of venous grafts provides further opportunities for vascular access for regular haemodialysis. Evaluation of the immediate results and of long-term average cumulative patency in 24 autologous and 24 stored allogeneic venous grafts revealed fewer complications and better long-term usability in venous allografts. Allogeneic venous grafts appear to offer a suitable replacement for venous autografts in the surgical technique of arteriovenous fistulas. Their advantages include easy availability, low cost, and long-term usability in chronic dialysis.


[Toxoplasmosis transmission by blood transfusion? (author's transl)].

T-cells of the chicken tumour HPRS-1, mouse mastocytoma cells, Friend virus-transformed erythroleukaemia cells as well as normal human, mouse and chick erythrocytes were tested for their receptivity to toxoplasma infection. The studies indicate that T-cells and mastocytoma cells, which may be counted as part of the white blood cell series, have the highest invasion rate after incubation with toxoplasma. Friend-erythroleukaemia cells were less often affected; mature human, mouse and chick erythrocytes were refractory. The results suggest that cells of the white blood cell series are receptive to toxoplasma infection but that nucleated precursors of the red series may also be so, while mature erythrocytes cannot be infected. The possibility of transmission of toxoplasmosis by blood transfusion can no longer be doubted.


[Potassium metabolism in combined administration of pindolol and clopamide in long-term treatment of hypertension (author's transl)].

Potassium metabolism was studied in a multicentre trial of 174 out-patients with arterial hypertension of mild or moderate degree who were receiving both beta-adenergic blockers and a diuretic (1 tablet Viskaldix, containing 10 mg pindolol and 5 mg clopamide). The antihypertensive effect, heart rate and drug tolerance were also analysed. During the 15-week treatment there were no significant changes in potassium metabolism. Systolic and diastolic blood pressure, both on standing and lying, were significantly decreased, while heart rate remained within normal limits. In no instance was it necessary to discontinue the drug because it was not well tolerated.


[A new method for combined auto-alloplastic tooth reimplantation with a parallel A1203-ceramic root].

The operative procedure for partially replacing the root with A12O3 ceramic represents a good possibility for preserving teeth in which the pulpa is devitalized. The method used in connection with the well known autoplastic reimplantation not only presents an alternative to the traditional apicoectomy but also provides additional stabilization of the tooth by lengthing the root with cocotostabile and biocompatible A1203 ceramic. The method was tested in humans and monkeys. Argumentation was based on histological examination via light microscopy.


[Animal experimental tests of a new filling material (Isocap)].

An experimental investigation with animals (Rhesus monkeys) concerning pulp tolerance to two premeasured dosages of calcium hydroxide cement (Reocap and Reocap-E) as well as a pre-measured dosage of filling material (Isocap) in an injection capsule was carried out (78 class V cavities). As with the negative controls, a very slight reaction, or none at all, developed in response to the two calcium hydroxide cements and the new filling material, with and without application of capping material. When five other accidentally exposed pulpae were dissected, direct capping under the corresponding preconditions (punctate exposed pulpa, longer storage period for calcium hydroxide cement) showed the characteristic formation of reparative dentin.


[The mathematical rationale for the clinical EEG-frequency-bands. 1. Factor analysis with EEG-power estimations for determining frequency bands].

In order to determine whether the clinically used frequency bands of the EEG can also be obtained by a mathematical system we did a factor analysis with 480 EEG recordings, 5 minutes each, in 60 healthy male volunteers. A power spectrum analysis was done and 57 frequency bands between 1.5 and 30.0 Hz in a half Hz steps were calculated. The factor structure obtained made the following frequency bands (Hz) reasonable: deltaF = 1.5 - 6.0, thetaF = 6.0 - 8.5, alpha1F = 8.5 - 10.5, alpha2F = 10.5 - 12.5, beta1F = 12.5 - 18.5, beta2F = 18.2 - 21.0, beta3F = 21.0 - 30.0. Except for alpha1F all other 6 frequency bands were represented by one general factor with the complexity 1. The variance of the alpha1F band is explained by several of the 6 factors. The clinically known and the by factor analysis obtained frequency bands in the beta-range are similar. The clinically alpha-band is subdivided into two frequency bands alpha1F and alpha2F by the factor analysis. The clinically known border line between delta- and theta-band of 3.5 Hz cannot be found by factor analysis.


[Somatosensory evoked cortical potentials (SSEP) in regenerating nerves following suture (author's transl)].

In 37 patients with sutured median and ulnar nerves 106 SSEP were evaluated. Stimulation of the finger nerves was performed at a rate of 4-6/sec. In the early stage of reinnervation, just when the electrical stimulus was perceived, the second positive component (P2) of the SSEP could be recorded, but the primary part of the SEP (N1/P1) was highly reduced or absent. At this time no peripheral nerve action potential or muscle action potential could be obtained. In a follow-up study the sensory regenerating process expressed in a clinical sensibility index (S1-S4+), corresponded well with latency and amplitude of the primary potential of the SSEP: N1-latency decrease and N1/P1 and especially P2/N3-amplitude increase corresponded with improving sensibility. The abnormally high P2-wave is assumed to be an expression of central adaptation and reintegration. The method seems to be of diagnostic value as a test of peripheral nerve function especially in early and late stages of reinnervation, in verification of collateral reinnervation and in objectifying sensory defects in forensic cases.


[EMG-findings and nerve conduction velocity in herpes zoster disease (author's transl)].

We have performed a myography on three patients and an additional study of the nerve conduction velocity (CV) on two adult patients suffering from herpes zoster. It could be demonstrated that the affected muscles can suffer at the same time a neuropathy as well as a myopathy. We found fibrillations and CV-reduction also in clinically healthy nerves and muscles. The abnormal findings were most prominent in the clinically affected segments and often suggested an in portio lesion of the motor unit. The infiltration of the spinal ganglion appears to have no paramount significance for the understanding of this disease.


Purification of two dexamethasone-binding proteins from rat-liver cytosol.

Two dexamethasone-binding proteins have been purified from rat liver cytosol. The main purification steps are: precipitation by protamine sulphate, affinity chromatography on CH-Sepharose 4B to which 11-deoxycorticosterone is linked through a disulfide bond and DEAE-cellulose chromatography. Two binding components elute from the DEAE-cellulose column at 0.12 M and 0.2 M NaCl, respectively. By means of dodecylsulphate/polyacrylamide gel electrophoresis it was demonstrated that both components are composed predominantly of a single polypeptide with molecular weights of about 45 000 and 90 000. Antibodies to the two polypeptides have been elicited in rabbits. The antibodies to the 45 000-Mr polypeptide cross react with the 90 000-Mr component. Likewise the antibodies to the 90 000-Mr protein precipitate the 45 000-Mr polypeptide. Either of the two antibody preparations immunoprecipitates the major part (approximately 70%) of the dexamethasone-binding activity of the cytosol.


The detection of cysteine-homocysteine mixed disulphide in plasma of normal fasting man.

Cysteine-homocysteine mixed disulphide, formed in the degradation of methionine, is detected routinely in the plasma of fasting patients homozygous for homocystinuria and in some obligate heteroxygotes. It has not hitherto been identified in the plasma of normal fasting man. Using a highly cross-linked resin with lithium citrate buffers on a JEOL. Amino Acid Analyser, we have detected the mixed disulphide in every one of the plasma samples from twenty normal fasting subjects. The mean concentration was 3.25 mumol/l (SD 0.85, N = 20), with a range of from 1.68 to 4.85 mumol/l. The other neutral and acidic amino acids were within the accepted normal range. The study shows that circulating homocysteine is normally not immediately transformed to cystathionine or remethylated to methionine; some combines with cysteine to form measurable amounts of mixed disulphide. Since homocysteine may produce endothelial damage, the present findings could be relevant to an understanding of the pathogenesis of vascular disease.


Initial cholesterol esterification rate in hyperlipoproteinaemia: effects of triglyceride-rich lipoproteins.

The initial cholesterol esterification rate (LCAT activity) was determined in ninety-four hyperlipidaemic subjects. LCAT activity was elevated in hypertriglyceridaemia, whereas patients with hypercholesterolaemia had normal activities. In hypertriglyceridaemic subjects LCAT activity correlated with the concentrations of d less than 1.006 lipoproteins, plasma triglycerides, cholesterol and cholesterol esters and phospholipid levels. Addition of d less than 1.006 lipoprotein to normal plasma resulted in a dose dependent stimulation of enzyme activity with a sigmoidal response curve. When the d less than 1.006 lipoproteins were removed from hypertriglyceridaemic plasma by ultracentrifugation, the enzyme activity in the residual d greater than 1.006 fraction dropped, but still was higher than in normal plasma and correlated with the amount of d less than 1.006 lipoproteins originally present. Thus, high LCAT activity in hypertriglyceridaemia cannot be explained solely by the presence of an increased d less than 1.006 lipoprotein concentration. An increase of enzyme concentration or changes in concentration or composition of other lipoproteins (high density lipoproteins) may contribute to the high LCAT activity in hypertriglyceridaemia.


Skin polyamine levels in psoriasis: the effect of dithranol therapy.

Concentrations of putrescine, spermidine and spermine were determined in biopsies of skin of eight control subjects and of uninvolved skin and skin lesions of eight psoriatic patients before and after topical therapy with dithranol. Mean spermidine and spermine concentrations in uninvolved skin of psoriatic patients were normal, but putrescine concentration was elevated. In psoriatic skin lesions all three amines were significantly elevated. Chemotherapy effectively reduced polyamine concentrations in involved skin touards normal. This decrease in polyamine levels correlated with reduction of the proliferative activity of the epidermis and with clinical improvement of the patients.


Polymorphic acetylation and aminopyrine demethylation in Gilbert's syndrome.

Polymorphic acetylation was investigated in twenty-seven patients with Gilbert's syndrome using the sulphadimidine test. Whereas the finding of 51% slow acetylators in seventy-eight control persons agreed well with the expected frequency in a continental European population, the prevalence of slow acetylators in Gilbert's syndrome was increased to 78% (P less than 0.03, Woolf's G-test). After oral administration of 14C-aminopyrine there was no significant difference between seventeen patients with Gilbert's syndrome and twenty-seven normal controls in total plasma clearance of aminopyrine (280 +/- SD 100 and 270 +/- 60 ml/min) and in the disappearance curve of 14CO2 in breath (0.23 +/- 0.04 and 0.22 +/- 0.03 h-1, respectively). Thus, whereas aminopyrine metabolism appears unaffected in the examined patients, the data documents a new association between slow acetylator status and Gilbert's syndrome.


Intestinal and renal handling of calcium in human diabetes mellitus: influence of acute oral glucose loading and diabetic control.

The intestinal absorption and the urinary excretion of calcium were compared in two groups of diabetic patients during periods of satisfactory and poor control. In a first group of ten patients, periods of isolated high glycosuria were obtained by giving an oral glucose load. The second group consisted of ten patients with a severe endogenous insulin deficiency. The subjects of this latter group were investigated before and after a few days of insulin therapy. In group I, the oral glucose load induced a significant increase in the intestinal calcium absorption and had a tendency to lower the urinary calcium excretion. Furthermore, an inverse relationship was found between the changes in the intestinal calcium absorption and the variations of the urinary calcium excretion. In group II, both intestinal absorption and urinary excretion of calcium fell significantly after recovery of satisfactory metabolic control by insulin therapy. From the results as obtained in group I one can conclude that glucose enhances the calcium transfer from the luminal to the serosal pole of both intestinal and renal tubular cells. During severe ketosis as observed in group II, calcium metabolism is considerably accelerated and the increase in the intestinal calcium absorption rate may be interpreted as compensatory mechanism for the high urinary loss of calcium.


Plasma renin substrate sensitivity to oestrogens and oestrogen metabolism in cirrhosis.

Oestrogen stimulation of plasma renin substrate (PRS) was studied in men with alcoholic cirrhosis. PRS values, before and 1, 2, 4 and 6 days after a single oral administration of 100 microgram of an oestrogen derivative, 11beta-methoxy-17-ethynyl-1,3,5(10)-estratriene-3,17beta-diol (Moxestrol), were measured by radioimmunoassay of generated angiotensin I in five men with normal liver function and five men with alcoholic cirrhosis. Basal PRS was 0.93 +/- 0.22 nmol/ml (mean +/- 1 SD) in the normal men and significantly lower (P less than 0.01) in the men with cirrhosis (0.33 +/- 0.14 nmol/ml). Two days after administration of Moxestrol, PRS rose significantly but transiently (P less than 0.05) to 1.41 +/- 0.42 nmol/ml in the normal men and to 0.47 +/- 0.15 in the cirrhotic men, the relative increase (approximately 50%) being similar in both groups. A study of the plasma kinetics and urinary excretion of Moxestrol was also performed to evaluate its metabolic clearance rate and absorption. Since the intestinal absorption of [14C] Moxestrol was not depressed in cirrhotic men, the low PRS values recorded are probably the consequence of hepatocyte dysfunction.


Biochemical, genetic and ultrastructural study of a family with the sea-blue histiocyte syndrome/chronic non-neuronopathic Niemann-Pick disease.

Deficient leucocyte sphingomyelinase activity has been demonstrated in a patient with the sea-blue histiocyte syndrome. Family studies revealed that two other cases previously diagnosed on clinical and histochemical criteria also had a pronounced diminution of sphingomyelinase activity. Both parents of the affected individuals were carriers of the disease as indicated by sphingomyelinase activity intermediate between normal and diseased subjects. Additional heteroxygous carriers were found among the siblings and other relatives of the patients. This family study supports further the hypothesis that the sea-blue histiocyte syndrome and chronic Niemann-Pick (Type B) disease are the same.


Double-blind study of interferon administration in renal transplant recipients.

In a double-blind trial renal allograft recipients were treated with fibroblast interferon preparations for 3 months in an attempt to prevent viral infections. Interferon therapy did not reduce the overall incidence of viral infections. No adverse effects were noted on liver function, platelet counts, or leucocyte counts, or acute rejection episodes.


Maternal serums and amniotic fluid levels of human placental lactogen in gestational diabetes.

Human placental lactogen (hPL) levels were measured radioimmunologically in maternal serum and in amniotic fluid between the 37th and 39th weeks of gestation in sixteen gestational diabetic and thirty normal pregnant women. There was no significant difference in maternal serum hPL levels between diabetic (6.1 microgram/ml) and normal pregnant women (6.4 microgram/ml). In contrast, the diabetic group was found to have significantly (P less than 0.001) higher concentrations of amniotic fluid hPL (1.2 microgram/ml) than normal pregnant women (0.8 microgram/ml).


Is thallium-201 of use in the measurement of total exchangeable potassium in man?

Simultaneous measurements of exchangeable potassium were made in seven normal male subjects using potassium-43 and thallium-201. Exchangeable potassium values obtained using the 'thallium-201 space' were unreliable.


Differential behavioral effects of sulpiride in the rat and squirrel monkey.

Despite its clinical efficacy as an antipsychotic agent, sulpiride differs from other neuroleptics in that it has been reported to exert erratic effects in several animal models. The effects of sulpiride were investigated on Sidman avoidance responding by the rat and squirrel monkey. At 100 mg/kg i. p. or orally, sulpiride failed to impair rat Sidman avoidance responding appreciably while exerting marginally toxic effects, but at 30 mg/kg orally, this drug strongly impaired Sidman avoidance responding by the squirrel monkey. This effect, which manifested delayed onset, was reversed by benztropine, indicating that dopamine receptor blockade was most likely responsible for the impairment of responding. The gross behavioral effects of sulpiride in the squirrel monkey resembled those of haloperidol, and dyskinetic postures induced by haloperidol could be mimicked by sulpiride in some instances. It is concluded that the behavioral effects of sulpiride in the rat may not be representative of its action in primates or in the clinic.


Cerebellar regulation of phonation in rhesus monkey (Macaca mulatta).

Five rhesus monkeys (Macaca mulatta) were trained to emit a "coo" vocalization with a duration of at least 500 msec. After stable performance was achieved cerebellar lesions were introduced, and various pre- and postlesion measures of phonation and of laryngeal EMG activity were compared to assess the effects of the lesions. The phonatory changes were interpreted with respect to possible laryngeal or respiratory modifications. The relation between fundamental frequency and intensity of phonation was changed in some animals, with no obvious alterations in either fundamental frequency or intensity considered separately. Intensity of phonation was decreased while duration was prolonged in two animals. Fundamental frequency of phonation was also affected in some animals. Reliable laryngeal EMG was obtained in two animals and was affected by cerebellar lesions. These results indicate that normal cerebellar function is involved in the control of fundamental frequency, intensity, duration, and the coordination of the laryngeal and respiratory systems for the control of phonation.


Neural pathways common to vestibular and optokinetic eye movements.

To determine how vestibular and optokinetic eye movement signals share the central oculomotor neural organization, optokinetic afternystagmus was superposed on vestibular nystagmus in the monkey. To a first approximation there was algebraic additivity in the velocity domain. This result suggests that vestibular and optokinetic eye movements are integrated at a level of neural organization above the ocular motoneurons, at a level in which neural signals are coded in terms of eye movement velocity rather than eye position.


Conflicting visual-vestibular stimulation and vestibular nucleus activity in alert monkeys.

In alert Rhesus monkeys (Macaca mulatta) neuronal activity of vestibular nuclei was recorded during pure vestibular and conflicting visual-vestibular stimulation. Pure vestibular stimulation consisted of rotating the monkey about the vertical axis in complete darkness. During conflicting visual-vestibular stimulation the monkeys were rotated in the light within a vertically striped cylinder mechanically coupled to the turntable. The conflict is that although the monkey is accelerated, there is no relative movement between visual surrounding and the animal. In the conflict situation thresholds of neuronal modulation and of nystagmus were raised compared with those during pure vestibular stimulation. Nystagmus slow-phase velocity could always be dissociated from the neuronal activity, the nystagmus often being totally suppressed whereas the neuronal activity was only attenuated. This suggests a further information processing between vestibular and oculomotor nuclei in the generation of nystagmus.


Progressive resistance against the male recombination factor 31.1 MRF acquired by Drosophila melanogaster.

A genetically abnormal but structurally normal second chromosome (31.1 MRF) which induces recombination in the male sex, was introduced by outcrossing into the cytoplasm of a normal strain. In this new combination, male recombination frequency induced by females dropped from 3.81% to 0.17% within 10 generations, indicating a gradual acquisition of resistance against the activities of the 31.1 MRF.


Possible explanation for interictal-ictal transition: evolution of epileptiform activity in hippocampal slice by chloride depletion.

In thin hippocampal slices, paroxysmal epileptiform discharge was generated in high potassium medium. Removal of chloride from the high potassium medium caused explosive potentiation of the paroxysmal discharge and emergence of clonic relapsing discharges. Evolution of the paroxysm to regenerative seizure was attributed to the reduction of inhibitory postsynaptic potentials.


Pigment granules in choroidal melanophores of the albino goldfish.

Pigment granules in choroidal melanophores of the albino goldfish contained fine particulate materials which were in various degrees aggregated in clumps. Tyrosinase was considered to be present in an inhibited state in these pigment granules.


Histochemical localization of cholinesterases in the neural tissue of the pineal in the rhesus monkey.

The neural tissue of the monkey pineal contains both acetyl and butyryl cholinesterases. Acetylcholinesterase was localized in the cisternae of the nuclear membrane, rough endoplasmic reticulum, on the plasma membrane of the neurones, and on the axolemma of both non-myelinated and myelinated fibres. The enzyme was not found in the axosomatic or axo-dendritic synapses. It is therefore suggested that the pineal neurones have a cholinergic function rather than a cholinoceptive one.


Comparative study of the sensitivity of acetylcholinesterases and cholinesterases from animal and bacterial sources to inhibition by serotonin and its derivatives.

Serotonin was found to inhibit human erythrocyte and electric-eel acetylcholinesterase activities. The serotonin amino group, free of negative charges in its vicinity and its hydroxyl group, were important for the inhibition. Serotonin precursors and several related compounds had little or no effect. Human plasma cholinesterase was also inhibited by serotonin and tryptamine. In contrast to these animal enzymes, the cholinesterase of Pseudomonas aeruginosa was refractory to serotonin and its derivatives under the same experimental conditions.


Experience with high doses of ibuprofen in the long-term treatment of rheumatoid arthritis.

Ibuprofen (Brufen) is a non-steroidal anti-inflammatory drug well-established in the symptomatic treatment of rheumatoid arthritis. In view of its exceptionally good tolerance it has become fashionable to prescribe increasingly large doses for severe cases or in those patients unable to tolerate other anti-rheumatic compounds. This study illustrates the sustained therapeutic benefit and almost complete lack of toxicity in fify-nine rheumatoid patients treated with up to 1,600 mg ibuprofen daily over six months. Significant improvement occurred in all clinical parameters and gastro-intestinal upset leading to discontinuance of therapy was reported in just two patients. There were no abnormalities in any of the biochemical tests performed.


Susceptibility of 327 clinical isolates to netilmicin.

Netilmicin, a semisynthetic derivative of sisomicin, was tested against 327 isolates of Staphylococcus aureus, Pseudomonas aeruginosa and Gram-negative enteric bacilli. Seventy-two per cent of the isolates were inhibited at a concentration of 0.5 microgram netilmicin per ml, and 93% of the isolates were susceptible to 4 microgram per ml or less. The MICs of netilmicin and gentamicin for 24 Providencia and 38 Pseudomonas isolates were compared. The activity of netilmicin closely paralleled that of gentamicin, 46% of the Providencia isolates and 32% of the Pseudomonas isolates not being inhibited by 4 microgram per ml of either drug.


A comparison of the antibiotic activities of sisomicin, gentamicin and aminosidine sulphate against pseudomonas aeruginosa.

Sisomicin, gentamicin and aminosidine sulphate were compared for their antibiotic activity against Pseudomonas strains freshly isolated from clinical material. The activity of the three agents, expressed as a minimum inhibitory concentration, was determined using the same automatized system.


Effect of duodenal fat on plasma levels of gastrin and secretin and on gastric acid responses to gastric and intestinal meals in dogs.

The effects of duodenal instillation of sodium oleate (10 mmoles per hr) on plasma levels of gastrin and secretin and on gastric acid secretion in response to gastric and intestinal meals were determined. Four dogs prepared with a septum between stomach and duodenum were provided with a special cannula that allowed separate access to the stomach or duodenum. Each dog received a 10% liver extract meal introduced either into the stomach (gastric phase) or into the duodenum (intestinal phase). Sodium oleate administered during the gastric phase caused approximately a 30% reduction in plasma gastrin level and a 25% inhibition of gastric acid secretion. Sodium oleate given during the intestinal phase completely abolished the plasma gastrin response and resulted in a 75% inhibition of gastric acid secretion. Plasma secretin levels were not changed during the gastric phase or the intestinal phase by instillation of sodium oleate. These results show that fat in the duodenum is a potent inhibitor of gastrin release and gastric acid secretion; the intestinal mechanism involved does not appear to affect plasma secretin concentrations.