Linear dose--response relationships after prolonged expression times in V-79 Chinese hamster cells.

The expression time for induced mutants resistant to 6-thioguanine, in V-79 Chinese hamster cells, was determined by respreading the cells in the selective medium, at various times after treatment. The length of the expression time for mutants induced by X-rays, ethyl methane sulphonate and ultraviolet irradiation was dose dependent. For the highest dose used this was 7 to 8 days, beyond which there was no further changes in mutant frequency. The dose-response relationship of these agents does not appear to deviate from linearity; this permits the calculation of mutation rate per unit dose. For X-rays this value was 1.35 - 10(-7) per rad per locus, for ethyl methane sulphonate, 2.2 - 10(-2) per mole per locus and for ultraviolet irradiation, 6.3 - 10(-6) per erg per mm2 per locus. The effectiveness of the 3 different mutagens for the induction of mutations was compared by calculating the increase in mutant frequency per unit of decrease in survival (Do). These increments in frequency were: 5.6 - 10(-5) for X-rays, 69.5 - 10(-5) for ethyl methane sulphonate and 16.1 - 10(-5) for ultraviolet irradiation.


Host-cell reactivation of ultraviolet-irradiated SV40 DNA in five complementation groups of xeroderma pigmentosum.

Host-cell reactivation of UV-irradiated double-stranded SV40 DNA was studied in BSC-1 monkey cells, normal human cells, heterozygous Xeroderma pigmentosum (XP) cells, representative cell strains of the five complemention groups of XP and in XP "variant" cells. The following percentages of survival of the plaque-forming ability of double-stranded SV40 DNA were found in XP cells compared with the value found in normal monkey and human cells: group A, 13%; group B, 30%; group C, 18%; group D, 14%; group E, 59%; and in the heterozygous XP cells almost 100%. The survival in XP "variant" cells was 66%. The survival of single-stranded SV40 DNA in BSC-1 cells was much lower than that of double-stranded SV40 DNA in XP cells of complementation group A, which possibly indicates that some repair of UV damage occurs even in XP cells of group A.


Formaldehyde-induced hemolysis during chronic hemodialysis.

We investigated an outbreak of hemolytic anemia among patients on hemodialysis shortly after the installation of a new water-filtration system. Using in vitro technics, we demonstrated that a water-soluble inhibitor of red-cell metabolism could easily be extracted from the intact filters. Subsequent experiments showed this toxic substance to be formaldehyde, a potent reducing agent whose mechanism of action involves conversion of NAD to NADH. This alteration of the redox state of the erythrocyte leads to inhibition of glycolysis at the level of glyceraldehyde 3-phosphate dehydrogenase and rapid decline in cellular energy (ATP) stores. Because formaldehyde is widely used as a preservative for dialysis equipment, the toxicity of this agent for red blood cells is of clinical importance.


Low activities of the pyruvate and oxoglutarate dehydrogenase complexes in five patients with Friedreich's ataxia.

Since patients with Friedreich's ataxia appear to oxidize pyruvate slowly, we measured the activity of the pyruvate dehydrogenase complex in disrupted fibroblasts from four patients with this syndrome and one patient with a clinical variant. The activity was 43 +/- 4 per cent of that in 16 controls (mean +/- S.E.M., P less than 0.001). The activity of the 2-oxoglutarate dehydrogenase complex was also lower in the patients' cells than in those of controls (50 +/- 2 per cent, P less than 0.001). However, the activity of cytochrome-c oxidase was normal (126 +/- 43 per cent of controls). Mixing experiments gave no evidence of soluble enzyme inhibitors or activators, and the addition of excess substrate or cofactor did not ameliorate the deficiencies. White blood cells from one of the patients had low activities of both complexes. Mutations of these dehydrogenase complexes occur in some patients with Friedreich's ataxia and lead to abnormally low activity of an enzyme of the tricarboxylic acid cycle.


[Relation between quality of dietary protein, plasma corticosteroid concentration and various enzyme activities in liver and mucosa of small intestine].

Comprehensive studies were performed in Wistar rats on the relations between the dietary protein quality and the function of the adrenocortical system. The authors determined: the increase in body mass, the urea and corticosteroid concentrations in the blood plasma, the GOT (EC 2.6.I.I.) and GPT (EC 2.6.I.2.) activities in the liver, the reactivity of the adrenocortical system in vitro, the ACTH content in the hypophyses and the content of corticosteroid-binding globulin in the blood plasma. In adrenalectomized and normal rats as well as in rats treated with corticosterone or cortisol, the authors determined the GPT, GOT, amino-acid aryl amidase (EC 3.4.I.2.) and tripeptidase (EC 3.4.I.3.) activities in the liver and the mucosa of the small intestine, and the total, alpha and beta-amylase activities in the small intestine.


Production of yeast alcohol dehydrogenase isoenzymes by selection.

Mutants of yeast alcohol dehydrogenase have been produced that protect the cell against the poisonous aldehyde acrolein by increasing the NADH-NAD ratio. The altered properties include changes both in binding constants and in cooperativity. Such mutants may be useful in exploring the nature of adaptation at the molecular level.


Evolution of type C viral genes: evidence for an Asian origin of man.

Old World monkeys and apes, including man, possess, as a normal component of their cellular DNA, gene sequences (virogenes) related to the RNA of a virus isolated from baboons. A comparison of the viral gene sequences and the other cellular sequences distinguishes those Old World monkeys and apes that have evolved in Africa from those that have evolved in Asia. Among the apes, only gorilla and chimpanzee seem by these criteria to be African, whereas gibbon, orang-utan and man are identified as Asian, leading us to conclude that most of man's evolution has occurred outside Africa.


Cell-cycle, cell-shape mutant with features of the Go state.

A cold-sensitive mutant of CHO cells has features of "reverse transformation" at the non-premissive temperature of 33 degrees C. Cells accumulate at G1 with altered morphology and remain viable and quiescent for more than 40 d. Such cultures are synchronised by a temperature shift back to the permissive 39 degrees C.


[Synchronization of the background activity of skeletal musculature, autonomic nerves and cerebral structures in cats].

The background electrical activity of skeletal muscles, autonomic nerves and several brain structures was recorded in cats under acute and chronic conditions. The spectrum-correlation analysis showed that the spatial synchronization within the range of 25 to 35 Hz between autonomic nerves and brain formations (established in previous experiments) comprises the skeletal muscles as well. One of the possible mechanisms by which the rhythm of 25 to 35 Hz facilitates activity in the nervous system is suggested to be related to the frequency potentiation of the synaptic transmission.


[Endocrinological evaluation of sellar and suprasellar tumor cases (author's transl)].

1) Pituitary function of 9 cases of tuberculum sellae meningioma was examined, before and after surgery (3 weeks, 1 year and 2 years after surgery). 2) In all cases ACTH, LH, FSH and prolactin responses were normal throughout pre- and postoperative courses. 3) GH and TSH were normoreactive in almost all cases preoperatively. Postoperatively GH and TSH were hyporeactive 3 weeks after surgery, but recovered to normal 1 or 2 years after surgery.


[Endocrinological evaluation of sellar and suprasellar tumor cases (the fifth report) - on pituitary function of 5 cases of ectopic pinealoma in the Chiasmal Region (author's transl)].

The anterior pituitary hormone secretion of 5 patients with ectopic pinealoma in the chiasmal region was studied. 1) GH response in ITT was hyporeactive in all cases. Two of 4 cases showed hyporeactive ACTH secretion in Metyrapone test. Two of 5 cases decreased TSH secretion in TRH test. Prolaction secretion was normal in all 5 cases. All 5 cases showed hyporeactive FHS response. LH secretion was negligible in 2 of 5 cases, but other 3 cases showed abnormal LH response in LH0RH test with abnormally high basal level and no response to LH-RH. 2) In 3 cases with abnormal LH response blood HCG was determined and identified by radio-immuno-assay using HCG-beta-subunit antiserum. 3) Precocious puberty was recognized in 2 boys with identified blood HCG. 4) Abnormally high blood LH levels in those 3 cases were significantly decreased after lineac irraiation.


CRF activity in fetal rat hypothalamus, in late pregnancy.

The corticosterone content of the adrenal glands was determined in 21-day-old rat fetuses: (1) before and after encephalectomy or decapitation (hypophysectomy); (2) after ACTH treatment of the encephalectomized or decapitated (hypophysectomized) fetuses; and (3) after administration of crude extracts (0.1 N HCl) of hypothalamic or cortical tissue from 20-day-old rat fetuses. A peak in the corticosterone content of the adrenals was observed 10 min after ACTH injection to enceaphlectomized or decapitated fetuses. A rise in corticosterone concentration was noted 5 and 10 min after the encephalectomized fetuses were given an injection of hypothalamic extract. This extract was devoid of appreciable ACTH activity when tested in decapitated fetuses. Cortical extract was inactive in encephalectomized or decapitated fetuses. These data suggest that fetal hypothalamic extract contains some CRF activity and that the fetal pituitary gland is responsive to the CRF.


Effects of carbohydrate-active steroids and ACTH on visually-evoked responses in patients with adrenal cortical insufficiency.

Visual average evoked responses (AERs) to 4 intensities of light were studied in 5 patients with adrenal cortical insufficiency. Patients were tested off all medications, on ACTH while off all medications, and during replacement with carbohydrate-active steroids. Off treatment, when steroid levels were low, AERs were of small amplitude and short latency. Treatment with ACTH alone decreased the amplitude-intensity response, suggesting extra-adrenal effects. Both with amplitude and latency effects, stimulus intensity was an important parameter in determining steroid and ACTH effects.


White sponge nevus (leukoedema exfoliativum mucosae oris): ultrastructural observations.

Biopsy specimens from the oral lesions of white sponge nevus (WSN) in thirteen patients were analyzed by electron microscopy. Several marked deviations from the normal ultrastructure were recorded. Similarities and dissimilarities with other hereditary disturbances affecting the epithelium are discussed. Profound disturbance of the tonofilament system, with atypical aggregation of tonofilaments, was observed. Odland bodies, which are numerous in keratinized epithelia and are extruded into the intercellular space prior to the exfoliation of the surface cells, were also abundant in the WSN specimens. Very little material originating from Odland bodies appears, however, in the intercellular space in WSN. Presumably, the Odland bodies fail to properly function enzymatically in WSN.


Multifocal adenoid cystic carcinoma of the lip.

A 62-year-old Caucasian woman had several distinct and separate adenoid cystic carcinomas which involved both sides of the upper lip. Microscopic examination of the surgical specimens suggested that at least one of these malignant neoplasms arose from a pre-existing basal-cell adenoma.


[Definition and significance of carcinoma in situ of the breast gland].

1. Preinvasive phases of the cancer of the breast are observed with the intraductal cancers of the bigger ducts and with the so-called lobular carcinoma in situ. It shows, however, that the carcinoma of the ducts, above all the comedo-carcinoma, have to be considered as invasive cancers in more than 75%. These forms extend to the lobuli of the breast. 2. The Morbus Paget bases in one third on an intraductal preinvasive carcinoma, in two thirds on an invasive cancer. 3. This chapter deals with the differential diagnosis of the papilloma and papillary carcinoma. 4. Intralobular proliferations of the epithelium are observed at the periphery of undifferentiated cancers as secondary intraductal carcinoma and as primary lobular carcinoma. The so-called intralobular carcinoma in situ is in 15,2% followed by an invasive carcinoma after an interval of up to 28 years, and in 23% ipsilateral, in 9,5% contralateral. As therapy the subcutaneous or simple mastectomy is proposed.


[Pathological and anatomical aspects of organ-preserving therapy in the early stages of breast cancer].

In the treatment of breast cancer a worldwide trent towards selective and more individualized methods can be observed. Selective treatment depends to a considerable extend on precise morphological diagnosis. Conservative surgery combined with radiotherapy seems to be justified in cases of smallsized carcinomas of stage T0, N0, M0, and T1, N0, M0. There are different opinions on the adequate treatment of non-infiltrating carcinomas (i.e. intraductal comedo carcinoma, non-infiltrating lobular carcinoma). Up till now standard methods are not applicable. The high frequency of multicentric and bilateral development, and the unfavorable mode of segmental canalicular outgrowth are critical factors that must be taken into consideration for individual therapeutic planning.


[Multicentric carcinoma and atypical hyperplasia of the mammary gland (author's transl)].

A study for multiple primary cancer in the female mammary gland was performed. In 145 cases of mammary cancer, blocks for histological analysis were taken in a special system following routine examination of the specimen. Three sagital sections each of one inch width were taken from the outer, medium and inner region and from each of these 6 small blocks were cut. By this constant pattern of histological screening, 9 cases out of 145 were found showing multiple primary cancers. Among these Carcinoma solidum scirrhosum was the most frequent tumor type. This percentage of 6.2 is considerably lower than that given in the pertinent literature. Residual cancer following biopsy was found in 81% of the 145 cases, although extensive excision had been tried by the first operation. The entity of atypical epithelial hyperplasia which has to be differentiated from Carcinoma in situ was observed in 40.5% including ductal and ductular system.


[Virus infections in man during immunodepression (author's transl)].

The authors review virus infections observed in patients undergoing immunosuppressive treatment. The herpes virus, in particular the cytomegalovirus, are the most important cause. However, the role of the virus itself in an unfavourable course is variously assessed. The mechanism of the virus infection is discussed, whether primary infection, exogenous or endogenous re-infection. The latter seems to be the most frequent, at least in the case of the herpes viruses.


Influence of age and sex on carcinoma and cirrhosis of the liver in AXC strain rats ingesting 0.025% N-2-fluorenyldiacetamide.

Inbred A X C male and female rats, 4, 12, 24, and 52 weeks of age, ingested 0.025% N-2-fluorenyldiacetamide in a semisynthetic diet. Both age and sex were important in the development of hepatic lesions. The 4- and 12-week-old males developed a higher incidence of carcinomas and cirrhosis of the liver than did the females of the same ages or the males and females 24 and 52 weeks of age. Four-week-old male rats had more carcinomas per liver, larger carcinomas, more poorly differentiated (as compared with well differentiated), and some carcinomas were cholangiocellular as well as hepatocellular. There were a few hepatic lesions in the younger female rats; however, female rats of all ages were relatively resistant to hepatic carcinogenesis.


Role of adenosine 3', 5'-monophosphate in maturation of fetal lungs.

Fetal lung cyclic AMP phosphodiesterase, cyclic AMP, phosphatidyl choline, and incorporation of precursors into phosphatidyl choline were measured in rabbits after maternal administration of hydrocortisone phosphate and aminophylline. Both agents inhibited lung phosphodiesterase activity and augmented cyclic AMP concentrations (Table 1). Aminophylline administration was associated with a significant increase in lung saturated phosphatidyl choline (Table 2). Incorporation of [14C] choline and [3H] methionine was increased by both aminophylline and hydrocortisone (Table 3).


Effect of two experimental sets on sleep structure.

The effect of four perceptual sets--First Night in a sleep laboratory, Second Night in a sleep laboratory, Shock Avoidance Night, Reward Night--on the distribution of sleep was examined with 12Ss. Both the shock avoidance and the reward conditions gave results similar to those characteristically found in the First Night Effect, i.e., increases in Stage 0, Stage 1, the latency to Stage 4, the number of Awakenings, and the number of Stage Changes coupled with a decrease in Stage 1-REM. The observed effects, however, were minimal and were interpreted as giving evidence for the sturdiness of the sleep process.


[Total vascular exclusion of the liver in extensive hepatic exeresis. Value and limits].

Three cases of right hepatic lobectomy performed under complete hepatic vascular exclusion with aortic clamping in normothermia are reported. Hemostasis of the row surface of the liver is obtained with application of a biological glue. Hepatic vascular exclusion (from 24 to 30mn) was harmless to the remnant liver and the kidneys. Blood loss was minimal. The hemodynamic tolerance was good all along the procedure, but there is a high risk of overloading and acute congestive heart failure immediately after removal of the clamps. The continuous monitoring of pulmonary artery pressures must be emphasized. This procedure may be advised for massive and hypervascular tumors of the right lobe of the liver.


Electrophoretic analysis of covalently closed SV40 DNA: Boltzmann distributions of DNA species.

Covalently closed relaxed SV40 DNA [SV40(I')] generated by polynucleotide ligase closure of nicked circular SV40 DNA was analyzed by agarose gel electrophoresis. The DNA can be resolved into a series of bands differing in superhelical density whose intensities are approximately symmetrical about a central most intense band. Densitometric analysis of the gel pattern has revealed that the distribution of DNA species conforms to a Boltzmann distribution and has enabled us to derive an equation for the free energy of superhelix formation for SV40 DNA. We believe the observed bands reflect the time-averaged distribution of thermally induced fluctuations in DNA chain conformation in solution at the time of ligase catalyzed phosphodiester bond formation. Densitometric analysis of native supercoiled SV40 DNA, partially unwound in the presence of ethidium bromide, demonstrates that the separation between adjacent bands is approximately half that seen with SV40(I'). Agarose gel electrophoresis was also used to measure the change in average base rotation angle as a function of temperature by a procedure independent of ethidium dye binding.


Isolation and characterization of poly(A)-containing polyoma "early" and "late" messenger RNAs.

During late lytic infection of mouse kidney cell cultures polyoma 16S and 19S (late 19S RNA) were isolated by oligo(dT)-cellulose chromatography. Approximately 60-80% of total cytoplasmic polyoma RNA contained tracts of poly(A) which were retained by oligo(dT)-cellulose. Early in lytic infection when viral DNA synthesis and the production of capsid protein are blocked by the addition of 5-fluorodeoxyuridine, approximately 100% of polyoma "early" 19S RNA was quantitatively retained by oligo(dT)-cellulose indicating the presence of poly(A) tracts on most 19S mRNA molecules. In addition, 2 classes polyoma RNA, synthesized after the onset of cellular RNA synthesis under conditions where DNA synthesis is inhibited with 5-fluorodeoxyuridine, were found to contain tracts of poly(A). These species sedimenting at 16S and 19S in aqueous sucrose density gradients were also quantitatively retained by oligo (dT)-cellulose.


Spin labeled nucleic acids.

Homopolyribonucleotides and E. coli DNA wer spin labeled with an iodoacetamide-nitroxide compound. The extent of labeling is highly dependent upon the nature of the base and the secondary structure of the nucleic acid. This spin label-polymer linkage is unstable at high temperatures and in phosphate buffers. In order to determine the effect of changes in the environment of nucleic acids on the esr signals of their attached spin labels, the polynucleotides were subjected to temperature and viscosity perturbations. An increase in temperature (T) affects a linear decrease in the anisotropy factor of the esr signal. The log tau (tau = correlation time) versus (1/T) profile is linear with a positive slope when the spin label is attached to single stranded polynucleotides but exhibits discontinuities at certain critical temperatures when attached to the duplexes poly (As-U) and poly (I-Cs). These critical temperatures are lower than the optical Tm. Logarithmic increase in viscosity was found to produce a linear increase in tau in aqueous sucrose solutions.


[Animal experimental studies of positive tumor demonstration with radio-iodine labelled albumin macroaggregates].

131I-labeled macroaggregates were injected into the femoral artery of rats bearing a Yoshida sarcoma at the lower extremity and of healthy control animals. The radioactivity was measured in tissue samples taken from the tumour and in unaffected muscle tissue. The tumour tissue showed a considerably higher uptake of radioactivity than the not-neoplastic tissue of control animals. The difference was increased when more time elapsed between the injection and the measurement. After 48 hours the ratio was 25:1 in favour of tumour tissue. In contrast to the transplanted Yoshida sarcoma, hepatomas in Wistar rats induced by N-nitroso-morpholin showed a considerably smaller increase of radioactivity than the control group when injected with 131I-MAA. The fixation ratio between tumour and normal liver tissue was 1:5.9. In contrast to autochtone liver tumours rats with transplanted tumours are considered as a suitable model for testing labeled albumin particles like 131I-, 111In- or 99mTc-labelled albumin microspheres developed for angioscintigraphic purposes.


A physiologic approach to cardiac rehabilitation.

Rehabilitation of the patient with atherosclerotic coronary heart disease is a longitudinal, comprehensive care program that ends only on the death of the patient. Although much remains to be learned about cardiac rehabilitation, there is a rational basis predicated upon causes of disability, healing of myocardial damage, energy cost of activities, a rational approach to the activity and exercise prescription, and the potential benefits from exercise to justify a concerted national rehabilitation effort. The potential benefits in terms of more rapid return to work, maintenance of the patient's psychosocial integrity, and modification of natural history of the disease make the institution of a cardiac rehabilitation program a prudent activity for a practitioner, clinic, or hospital.


Hypertension: medical and nursing implications.

Hypertension is a major public health problem affecting 20 to 30 million people in the United States, many of whom are undetected, untreated, or inadequately treated. Because hypertension often is asymptomatic for decades, it must be systematically sought out in apparently well persons if the condition is to be treated in its earliest stages and complications prevented. With the recent advent of effective antihypertensive medications treatment is available, once the patient has been diagnosed. Physicians and nurses have a major responsibility to direct the patient into treatment and to assure the effectiveness of his follow-up care. Noncompliance is a direct challenge to everyone seeing the patient. The patient must be motivated to accept and continue therapy through education and, most important, by the establishment of a good interpersonal relationship with the nurse and/or the physician.


Coronary artery surgery. Operative technique and patient education.

Coronary artery surgery, the preferred technique for myocardial revascularization in patients with ischemic heart disease, promptly increases blood flow to areas of the myocardium distal to the coronary obstruction. CAS completely relieves angina in 90% of patients. The risk of 1 to 5% is decreasing as operative technique and patient selection improve. Patients having CAS need comprehensive preoperative and discharge teaching to restore them to normal, active, optimistic lives.


[Cyclic AMP and asthma].

Recall is made of the essential notions concerning cyclic AMP, its biosynthesis, catabolism, mood of action, circumstances of its discovery. The relations with the alpha and beta adrenergic receptors allow to consider the part played by cyclic AMP in the physiopathology of the bronchial spasm.


[State of the central regulation of glucocorticoid function of the adrenals in brain tumors].

Clinico-biochemical study of patients with tumours of the great hemispheres (75 observations) showed differences in the direction of reaction of the adrenal cortex to some actions. There was found a normal metopyron test, an inadequate activation in intensive stress action (an operation of removal of brain tumour) and a marked prolonged reaction to low stress stimulus (administration of low adrenaline doses). Several tests characterizing the function of negative reverse association mechanism and also reactions to stress actions of various intensity are necessary to assess the state of the central regulation of the glucocorticoid activity.


[Aminoacyl-tRNA formation in the liver and skeletal muscles of rabbits under the influence of multiple injections of ACTH alone and in combination with sodium ribonucleinate].

A study was made of the action mechanism of ACTH. ACTH (10 Units/kg) alone or in combination with sodium ribonucleinate (10 mg/kg) was injected to rabbits for 14 days, daily. Sum total tRNA and aminoacyl-tRNA-synthetases were extracted from the liver and the skeletal muscles. tRNA acetylation with lysine-1-C14, leucine-1-C14 and alanine-1-C14 was investigated in vitro in homologous systems. It was found that repeated ACTH injections led to a decrease in the intensity of aminoacyl-tRNA formation in the liver and the skeletal muscles. When ACTH was injected in combination with sodium ribonucleinate formation of aminoacyl-tRNA was much more intensive in both organs than when ACTH was injected alone.


[Binding of H3-aldosterone to cytoplasmic receptors of the kidney in various functional states of the organ target].

A study was made of the capacity of the cytoplasmic cell fraction of rat kidney to bind H3-aldosterone, depending on the level of Na uptake with food, and, consequently, on the intensity of aldosterone secretion by the adrenal glands. It was shown by Sketchard's method that there existed in the cytoplasmic fraction of the kidney cells of rats with a high and low level of aldosterone secretion two classes of receptors binding aldosterone with a different degree of affinity. The number of binding sites for aldosterone in the 1st class of receptors, more specific for mineralocorticoids in the animals with a low level of aldosterone secretion (Na loading), was double that in comparison with the animals with a high level of aldosterone (Na deficiency). It is supposed that an increased aldosterone concentration in the organism in Na deficiency increased the transport of the specific hormone-receptor complex from the cytoplasm into the nucleus.


[Specificity of the tibia test].

Studies on hypophysectomized immature female rats showed that the so-called tibia-test was highly specific only in testing the relatively pure preparations of growth hormone. Use of this test for determination of the content of growth hormone in the hypophysis or in the medium after the hypophysis incubation could lead to serious mistakes, since the majority of hypophysis hormones and many of the hormones of the peripheral endocrine glands were capable of influencing the width of the tibial cartilage in the hypophysectomized animals.


The solid phase synthesis of a protein activator for lecithin-cholesterol acyltransferase corresponding to human plasma apoC-I.

Apolipoprotein C-I, a protein constituent of the very low density lipoproteins of human plasma, consists of a single chain of 57 amino acids. The total synthesis of a protein corresponding to apolipoprotein C-I in physical properties and compositions was accomplished by solid phase techniques employing a modified polystrene incorporating spacer groups between the point of attachment of the first residue and the polymer matrix. The synthetic apoprotein was shown to activate lecithin:cholesterol acyltransferase to the same extent as the native protein. Comparative lipid-binding studies with dimyristoyl phosphatidylcholine gave complexes for native and synthetic apoprotein which floated at the same density after ultracentrifugation in KBr gradients and had virtually the same lipid:protein ratios.


Binding of insulin to isolated nuclei.

Specific binding sites for 125I-labeled insulin were detected in purified nuclei isolated from rat liver. Binding was rapid, reversible and directly proportional to the number of nuclei employed. Unlabeled native insulin, at concentrations as low as 1ng/ml, significantly inhibited the binding of labeled hormone, whereas unlabeled proinsulin and desoctapeptide insulin were less potent. In contrast, glucagon, thyrotropin, growth hormone (somatotropin), and prolactin were without effect. Under identical incubation conditions, 125I-labeled glucagon bound to liver plasma membranes 5- to 10-fold more strongly than did insulin; in contrast glucoagon did not bind to liver nuclei. These studies demonstrate the presence of specific binding sites for insulin in purified nuclei isolated from rat liver. In addition, they suggest that the nucleus may be an intracellular site of insulin action.


Mapping of the three species of polyoma mRNA.

The polyoma mRNA's present in the cytoplasm of primary cultures of mouse kidney cells during lytic infection were characterized by sedimentation velocity analysis and by hybridization to polyoma DNA fragments generated by a specific endonuclease of Hemophilus parainfluenzae (Hpa II).


Sequential transcription of the genes of vesicular stomatitis virus.

Increasing exposure of vesicular stomatitis virus particles to ultraviolet radiation caused differential inhibition of the synthesis in vitro of individual mRNA species which code for the viral structural proteins L, G, M, NS, and N.


Isolation and propagation of a segment of the simian virus 40 genome containing the origin of DNA replication.

Heteroduplex DNA molecules formed from two DNAs that differ from each other by a deletion can be cleaved at the mismatched region (a deletion loop) with the single-strand-specific S1 endonuclease. A heteroduplex DNA molecule, constructed from the DNA of simian  virus 40 (SV40) mutant with a deletion of the map region 0.54-0.55 and the DNA of a second SV40 mutant having a deletion of the map segment  0.70-0.73, is cleaved twice with S1 endonuclease. One of the products is a DNA fragment of about 0.13 the length of SV40 DNA which contains the origin of SV40 DNA replication (0.67 on the SV40 DNA map).


High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine.

Unlike normal cells, malignant rat and two simian virus 40-transformed human cell lines can neither grow nor survive in B12-and folate-supplemented media in which methionine is replaced by homocysteine. Yet three lines of evidence indicate that the malignant and transformed cells synthesize large amounts of methionine endogenously through the reaction catalyzed by 5-methyltetrahydropteroyl-L-glutamate; L-homocysteine S-methyltransferase (EC 2.1.1.13). (1) The activities of this methyltransferase were comparable in extracts of malignant and normal cells. (2) The uptake of radioactive label from [5-14C]methyltetrahydropteroyl-L-glutamic acid (5-Me-H4PteGlu) was at least as great in the malignant cells as in the normals and was nearly totally dependent on the addition of homocysteine, the methyl acceptor; furthermore, 59-84% of the label incorporated by cells was recovered as methionine.


Hormone and neurotransmitter receptors in an established vascular endothelial cell line.

A cell line from the intima of the rabbit aorta has been established. This cell line exhibits strict contact inhibition, and morphologically resembles intimal endothelial cells. B-type blood group antigens and the presence of fibrinolytic activity also distinguish these cells from smooth muscle cells and from fibroblasts of the aortic wall. Endothelial cells were assayed for changes in levels of adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) in response to a series of vasoactive drugs. Control levels for cAMP and cGMP are 7.01 +/- 0.82 and 1.50 +/- 0.06, respectively (mean +/- SEM). Norepinephrine, acetylcholine, 5-hydroxytryptamine, and phenylephrine increased the levels of both nucleotides significantly. Propranolol (10-5 M) and phentolamine (10-5M) inhibited, respectively, the cAMP and cGMP response to norepinephrine. Angiotensin II and histamine significantly increased cGMP levels but not cAMP levels of the endothelial cells. The cGMP increases with acetylcholine were inhibited by atropine. These results indicate that the established cell line is endothelial in nature and contains cellular receptors to a variety of vasoactive agents.


Sodium-stimulated amino acid uptake into isolated membrane vesicles from Balb/c 3T3 cells transformed by simian virus 40.

Mediated uptake of amino acids by membrane vesicles isolated from Balb/c 3T3 cells transformed by simian virus 40 has been demonstrated. Initial rates of transport of radioactively labeled L-leucine and alpha-aminoisobutyric acid were enhanced by the addition of NaCl (100 mM) to the reaction mixture at the start of the uptake process. This enhancement included a prominent "overshoot" during initial uptake. Slight stimulation of alpha-aminoisobutyric acid uptake was seen with K+, but none with Li+. The mediated nature of the uptake event for L-leucine was shown by saturation kinetics and by inhibition with L-valine. The transport assay measured predominantly intravesicular amino acid uptake rather than binding, as shown by the variation of uptake in response to changes in extravesicular osmolarity. Electron microscopy confirmed the presence of closed vesicles. Thus, amino acid transport has been characterized in an in vitro membrane vesicles system which should prove useful for studies of growth control.


Resting state in normal and simian virus 40 transformed Chinese hamster lung cells.

Normal cell deprived of amino acids or serum factors enter a resting state, whereas cells transformed by wild-type simian virus 40 do not. The ability to enter a resting state is temperature-sensitive (ts) in cells transformed by a tsA mutant of simian virus 40. We shown further: (i) that when complete medium is added to resting cells, the length of time until the onset of DNA synthesis often exceeds the length of G1 in growing cells; (ii) that the length of this interval depends upon the conditions used to arrest cell growth; but (iii) that transferring cultures from medium depleted for one factor to medium depleted in a second factor never leads to a round of DNA synthesis; and (iv) that DNA synthesis does not resume rapidly when a resting culture of cells transformed by the tsA mutant is transferred to the permissive temperature in suboptimal medium. A model proposing that in suboptimal conditions cells leave the cell cycle and traverse a branch pathway to enter the resting state is consistent with these findings.


Hormonal control of meiosis: specificity of the 1-methyladenine receptors in starfish oocytes.

The specificity of the 1-methyladenine receptors, which are localized on the cell membrane of starfish oocytes, has been investigated in Marthasterias glacialis and Asterias rubens. Ability of N-1-substituted adenines to trigger the release of meiosis inhibition is conserved, or even increased, when the methyl group is replaced by larger substituent groups.


Cholera toxin interactions with thyrotropin receptors on thyroid plasma membranes.

Unlabeled cholera toxin inhibits [125I]thyrotropin binding to thyrotropin receptors on thyroid plasma membranes. Maximal inhibition by cholera toxin does not exceed 40%, whereas unalbeled thyrotropin completely inhibits [125I]thyrotropin binding to these same membranes. Kinetic analyses of the binding data are compatible with the view that the cholera toxin decreases the number of receptor sites available to thyrotropin and that the mechanism by which the cholera toxin inhibits [125I]thyrotropin binding to these receptor sites involves both competitive and noncompetitive elements.


Effects of concanavalin A and a succinylated derivative on lymphocyte proliferation and cyclic nucleotide levels.

To better define cell surface-related changes involved in lymphocyte activation, we studied native concanavalin A (Con A) and succinylated concanavalin A (Suc-Con A) for their effects on proliferation and cyclic nucleotide levels of human peripheral blood lymphocytes. At optimal mitogenic concentrations, the two forms of Con A induce equivalent proliferation; however, the mitogenic activity of Con A progressively decreases above 50 mug/ml. In contrast, the mitogenic activity of Suc-Con A is not decreased even at 250 mug/ml.


Search for antigens and antibodies crossreactive with type C viruses of the woolly monkeys and gibbon ape in animal models and in humans.

Several reports have indicated the presence of type-C viral antigens in human tumors and of viruses closely related to those of the woolly monkey and gibbon ape in cultured human cells. In the present studies, attempts to detect woolly monkeys viral antigens in human tissues, or antibodies directed against structural polypeptides of woolly monkey viruses in human sera, were unsuccessful, In contrast, it was possible to demonstrate viral antigens in tissues and antibodies reactive to viral components in several animal and even primate model systems. Further evidence against the presence of woolly monkey viruses in humans is our failure to identify spontaneous or chemically induced viruses of this group in more than 200 individual cultures of human origin examined. These findings argue against the likelihood that viruses closely related to the woolly monkeys virus are associated with human tumors or are common infectious agents of man.


Differential effect of phosphonoacetic acid on the expression of Epstein-Barr viral antigens and virus production.

The effects of phosphonoacetic acid on cell growth, expression of Epstein-Barr virus antigens, and virus production in human and marmoset lymphoblastoid cell lines have been studied. The drug had no significant effect at concentrations up to 100 mug/ml on cell growth or total cell DNA synthesis. Higher doses induced not only a drastic decrease in DNA synthesis and cell grwoth, but also a dramatic cell enlargement. Immunofluorescence studies showed that greater than or equal to 30 mug/ml of phosphonoacetic acid inhibited viral capsid antigen synthesis without affecting the expression of the nuclear antigen or the spontaneous and 5-iodo-2'-deoxyuridine-induced early antigens. Production of transforming Epstein-Barr virus was also blocked.


Evidence for tandem integration of avian myeloblastosis virus DNA with endogenous provirus in leukemic chicken cells.

The integration site of avian myeloblastosis virus (AMV) proviral DNA in DNA from leukemia chicken myeloblasts has been studied by three sequential nucleic acid hybridizations that can localize the proviral DNA according to the repetitiveness of the adjacent cellular DNA regions. First, large denatured cellular DNA fragments (2.1 x 10(6) daltons) were reassociated and fractionated according to sequence reiteration frequenct. Next, DNA remaining single-stranded in each fraction was immobilized on nitrocellulose filters hybridized with an excess of unlabeled 70S RNA from Rous-associated virus-0 to saturate the endogenous proviral DNA sequences.


Lipid mobilizing hormones of the hypothalamus and pituitary.

Lipid mobilizing substances (LMS) are present in the hypothalamus and pituitary of mammals and probably are involved in the central neural control of obesity. Most of these have direct lipolytic effects, like lipid mobilizing factor (LMF) and LH-RH from the hypothalamus as well as lipotropin (LPH), melanocyte-stimulating hormone (MSH), corticotropin (ACTH), and growth hormone (GH) from the pituitary gland. Some of the substances, like GH-release inhibiting hormone (GH-RIH), affect lipolysis by secondary actions on pancreatic hormones such as insulin and glucagon. Other hypothalamic hormones, like GH-releasing hormone (GH-RH) may influence lipolysis secondarily through the pituitary hormones (e.g. GH) whose release they control. Regardless of how lipid mobilization is affected, investigations into the problem of obesity should take these LMS into consideration.


Mechanism of actions of adrenaline and ACTH in fat mobilization.

Starvation did not cause increase of hormone-sensitive lipase in rat epididymal adipose tissue. Adrenaline did not activate lipase in the fat cells, although it accelerated the release of free fatty acids from the cells. The results suggest that the mechanism of the stimulation of lipolysis by adrenaline is different from that in the cyclic AMP theory. Adrenaline-sensitive fat globules were prepared by hypotonic treatment of fat cells. Lipolysis in the fat globules was stimulated by adrenaline. It was shown that adrenaline-induced lipolysis in the fat globules was not due to activation of lipase but to initiation of a reaction between lipase and triglyceride. It is well known that calcium ions are essential for ACTH-induced lipolysis and that the hormone stimulates calcium uptake into adipose tissue. It was demonstrated that calcium ions accelerated formation of a complex between fat and lipase. The mechanism of the actions of adrenaline and ACTH are discussed on the basis of these results.


Fiber connections in the hypothalamus and some autonomic functions.

The ventromedial hypothalamic nucleus (VMH) belongs to area sympathica B of the SPH-System and its fibers to make up the dorsal longitudinal fasciculus and the hypothalamicotegmental tract. Blood glucose increases by rapid increase in active phosphorylase and G-6-Pase activities in liver following VMH stimulation. From the changes of ultrastructure of the hypophysis and the pancreas, GH, ACTH, LH, FSH and TSH (but not prolactin) are thought to be released by each releasing hormone increased by VMH stimulation. D cell hormone is also released and insulin is not released following VMH stimulation. The lateral hypothalamic nucleus (LH) belongs to area parasympathica C of the SPH-System and its fibers to make up the medial forebrain bundle and stria medullaris. Blood glucose decreases by relatively rapid increase in glycogen synthetase activity in the liver following LH stimulation. From the changes of ultrastructure, GH, ACTH, LH, FSH, TSH and D cell hormone are not released, but prolaction and insulin are released following LH stimulation. By giving lesions in VMH or LH, some degenerated fibers could be seen in LH or VMH, homolaterally.


Control of asthma in children.

Programs designed for the control of asthma are complex. Implementation of a number of modalities may be necessary, and the mean and level of treatment may need to be varied from time to time. Medical treatment is a primary concern but preventive measures and education of the family are essential as well.


[Differential diagnosis of neck tumors by angiography (author's transl)].

Angiographic criteria and differential dignosis of tumors of the lateral neck are demonstrated in 200 examined patients. There is a typical angiographic pattern in chemodectomas. Extreme vascularization and localization in the area of the carotid bifurcation are characteristic for these tumors. Neurinomas are avascular or minimally vascularized. The character of carotid artery deviation allows to distinguish neurinomas from other neoplasms of the neck. Metastases of thyroidal carcinoma are usually represented by pronounced vascularized tumors with a smooth border. Metastases of squamous cell carcinomas as primary mesenchymal tumors are minimally vascularized or sometimes avascular. There is increased vascularization in combination with perifocal inflammation. It is impossible to differentiate metastases of squamous cell carcinomas from primary mesenchymal tumors by angiography.


Effect of anti-mouse macrophage serum on murine cytomegalovirus infection.

Rabbit anti-mouse macrophage serum (AMS) was used to study the role played by macrophages against murine cytomegalovirus infection. Treatment of mice with AMS enhanced morbidity and mortality following virus infection. These results are discussed in relation to the role of macrophages against virus infections.


On the formation of hydrogen peroxide and oxygen radicals in heart mitochondria.

The mitochondrial respiratory chain has been shown to produce H2O2 under certain conditions (Loschen, Flohe, and Chance, 1971; Boveris, Oshino, and Chance, 1972; Loschen, Azzui, and Flohe, 1973; Boveris and Chance, 1973). At least 1 percent of the total oxygen uptake in State 4 (Chance and Williams, 1956) in the presence of succinate is caused by H2O2 formation (Boveris et al., 1972). It was shown that the component responsible for mitochondrial H2O2 formation is located between the sites of the antimycin and rotenone inhibition (Loschen et al., 1971; Boveris et al., 1972). The possible physiological consequences of a respiratory chain-linked H2O2 formation is not yet understood. It would therefore be of significance to know whether oxygen radicals are involved in this process or not. It was recently suggested by Rotilio et al. (1973) that enzyme systems producing H2O2 via oxygen radicals are always closely associated with a superoxide dismutase. Thus, the existence of a mitochondrial superoxide dismutase located in the matrix space (Weisiger and Fridovich, 1973) prompted us to look for oxygen radicals as possible intermediates in the mechanism of the formation of mitochondrial H2O2. In the present communication we show that, under the same conditions in which H2O2 is formed in the mitochondrial respiratoy chain, oxygen radical formation can be demonstrated also. A possible relationship of this finding with lipid peroxidation and the toxic effects of hyperbaric oxygen is likely.


Adrenaline, noradrenaline, and adenosine 3',5'-monophosphate levels in plasma of healthy persons during ergometric work with and without beta-receptor blocking agents.

After endogeneous increase of noradrenaline and adrenaline during a submaximal exercise test, plasma levels of adenosine 3',5'-monophosphate (cyclic AMP) show no significant change. After effective beta-receptor blockade due to propranolol plasma levels of cyclie AMP do not change significantly, either during rest or during exericse. After effective beta-receptor blockade due to propranolol the plasma levels of noradrenaline and adrenaline, reached during exercise, are significantly reduced compared with the plasma catecholamine levels obtained under the same exercise conditions wtihout beta-blockade. In contrast to the findings of other investigators, increased plasma catecholamine levels after administration of propranolol could not be observed.


Catecholamine antagonism of acetylcholine and dibutyrl guanosine 3',-5'-monophosphate in the mammalian ventricular myocardium.

After chemical sympathectomy we could demonstrate a negative inotropic effect of acetylcholine (ACh) on the cat ventricular myocardium as a direct catecholamine antagonism. Dose-response relationships for isoproterenol (IP) reveal a noncompetitive inhibition of the inotropic action of the catecholamine by ACh. A concentration of 10(-6) M ACh reduced the maximal IP-induced increase in tension by 58 +/- 13 percent (6-hydroxydopamine pretreatment) and by 65 +/- 10 percent (reserpine pretreatment); inhibition by endogenous ACh (released by field stimulation) was 36 +/- 10 percent and 38 +/- 8 percent, respectively. A concentration of 10(-3) M bibutyryl guanosine 3',5'-monophosphate (cAMP) produced a 17 +/- 7 percent reduction of the catecholamine-induced increase in tension (reserpine pretreatment). A cholinergic influence on the myocardial mechanics and metabolism of the heart may be relevant under stress situations. Vagal inhibition of the ventricular function is accentuated by an elevated sympathetic tone (Levy, 1971). If catecholamine-induced myocardial necrosis in addition to secondary effects of altered vessels are produced also by direct damage of the myocardial cell, then an influence of acetylcholine as a "natural" antagonist may be important.


Recruitment and discharge frequency of phrenic motoneurones during inspiration.

The discharges of 107 phrenic motor axons were recorded from cats under chloralose-urethane anaesthesia with spinal cords transected at T1 or with intact neuraxis. During inspiratory occlusions in spinal cats, each motoneurone was recruited at a mouth pressure constant at a given end tidal CO2; no motoneurone was recruited at a pressure greater than 70% of maximum. In eupnoea (32.3 torr CO2) 73% of motoneurones were recruited during the first 30% of inspiration; during CO2 rebreathing (60.8 torr CO2), 89% were recruited in the first 30% of inspiration. Neurones recruited earlier in inspiration had a lower onset frequency than later recruited units; all increased instantaneous frequency in a linear relation to pressure. Early recruited units showed a smaller increase in frequency per unit change in pressure than did later recruited units. During CO2 rebreathing, mean and peak frequencies increased on average 0.92 and 1.78 spikes.sec(-1) (%CO2)(-1), respectively, these increases being significantly less for early than for late recruited neurones. The data show that a stable order of recruitment of phrenic motoneurones exists during inspiration, the excitability of each motoneurone likely determining its time of recruitment. Above threshold, later recruited motoneurones are more 'sensitive' to a change in input. Recruitment of motoneurones is responsible for pressure generation at the start of inspiration and increase in discharge frequency (rate coding) is the dominant mechanism in the second half of inspiration.


[The hemarthroses of articular chondrocalcinosis].

Spontaneous haemarthrosis may occur during the evolution of articular chondrocalcinosis. It occurs mainly in older women and involves the knee in particular. The disorder may recur in the same or in different joints. A study of 11 case histories and counts of red blood corpuscles in samples of synovial fluid confirm that bleeding occurs more readily in chondrocalcinosis than in arthrosis alone. The proposed mechanism of haemarthrosis is only a hypothesis, but it is possible to imagine the onset of microcrystalline flow in a joint that is senile and affected by arthrosis. It is suspected that repeated haemarthrosis favours an oseolytic evolution in certain cases of chondrocalcinosis.


Thyroxine, triiodothyronine, and thyrotropin in serum during long-term diphenylhydantoin therapy.

Clinical laboratory tests for assessment of thyroid function were performed in 31 patients receiving long-term diphenylhydantoin (DPH) therapy. Reduced serum total thyroxine and free thyroxine index were found. The decrease in serum total triiodothyronine and free triiodothyronine index was smaller but statistically significant. DPH had no significant effect on the serum thyrotropin (TSH) concentration and maximal TSH response to TSH-releasing hormone. The absence of reciprocal changes in TSH and serum thyroxine might be due to the near-normal triiodothyronine concentration. Such an explanation would also conform with previous findings that the pituitary contains specific receptors for triiodothyronine but not thyroxine.


Determination of cyclic adenosine 3',5'-monophosphate in urine.

A modification of Aurbach & Houston's enzymic method for measuring cAMP is presented. The procedure is relatively simple and in several respects new. Urinary cAMP is separated from other nucleotides and phosphate by ZnSO4-Ba(OH)2 precipitation and column chromatography. The eluate is concentrated by evaporation. Recovery at this stage is 60-82%. The cAMP from urine and the standards are dissolved in a reaction mixture and converted to 5-AMP with cyclic 3',5'-nucleotide phosphodiesterase (PDE) and further to ATP with adenylate kinase and pyruvate kinase. The ATP formed is labelled with 32P by an exchange reaction catalysed by glyceraldehyde phosphate dehydrogenase and phosphoglycerate kinase. The remaining 32P used to count the [32P]ATP in the aqueous phase. Daily human urinary cAMP excretion is 3380 +/- 836 nmol (S.D.). After an injection of 100 USP units of parathormone intravenously into a patient with idiopathic hypoparathyroidism, urinary cAMP excretion increased 40-fold above the basal concentration within 30 min. Drinking of coffee or water did not affect cAMP excretion. The limit of detection of the method is 170 pmol of cAMP, and the variation coefficient for urine ranges from 7 to 10%. When the enzymic cAMP method was compared with a radioimmunological procedure, the correlation coefficient was found to be 0.98.


Effect of streptozocin on gastrin release.

As streptozocin has a toxic effect on gastrin producing cells in some patients with gastrinomas, the action of the drug upon normal gastrin release was evaluated in patients with carcinoid tumours (n=6) and malignant insulinomas (n=2). No acute effects were recorded in 22 instances where gastrin levels were followed during the first 24 hours after infusion of streptozocin. When gastrin levels were compared throughout a course of repeated infusions during months a significant increase was noted. Concentrations were doubled after 6 g streptozocin given during a four months period, and tripled after 10 g in nine months period. One patients developed bleeding duodenal ulcer after a total dose of 6 g. It is concluded that streptozocin does not damage normal G cells, but by some action seems to stimulate gastrin relase. Peptic ulceration may be an important side effect during a long term treatment.


Multiple vacuoles formation in erythroblasts in an erythroleukaemic patient.

Peculiar erythroblasts with multiple vacuoles were observed in the bone marrow of an erythroleukaemic patient. Some erythroblasts contained more than 80 vacuoles on a thin section. The contents of vacuoles were amorphous with low electron density. No transitional form from mitochondria or other organelles was observed. Since these vacuolated erythroblasts were clearly distinguishable from megaloblastoid erythraemia cells, multiple vacuoles formation is presumably attributable to the disturbance of microconnection net work in the normal red cell series.


mu-chain disease in a case of chronic lymphocytic leukaemia and malignant histiocytoma. I. Clinical aspects.

A 27-year-old woman with proteinuria and normal serum creatinine for 10 years developed chronic lymphocytic leukaemia (CLL) and after further 2 years during treatment with prednisone and chlorambucil a malignant histiocytoma appeared. Free mu-chains were demonstrated in serum, but it is possible that mu-chain disease (mu-CD) and Bence-Jones proteinuria had persisted unrecognized for 12 years, since vacuolated plasma cells were found when the primary bone marrow smear was re-evaluated and no glomerular disorders were found. The clinical findings from the now 11 known cases of mu-CD are reveiwed and the immunochemical findings are reported ain part II (Axelsen et al 1976). The patient's mother died of acute leukaemia at the age of 24. The mother's sister has mammary carcinoma and several members of the mother's line apparently have increased tendency to infections. Of 27 family members, none exhibited immunoglobulin defects, but 10 members of the mother's line had B- as well as T-lymphocytosis and 5 members had leukocytosis.


Mu-chain disease in a case of chronic lymphocytic leukaemia and malignant histiocytoma. II. Immunochemical studies.

Agarose gel electrophoresis of serum from the eleventh case of mu-chain disease (mu-CD) showed two distinct abnormal bands due to free light chains and  kappa-complexes with other serum proteins. This caused diagnostic difficulties on conventional immunoelectrophoresis, and crossed immunoelectrophoresis with intermediate gel is demonstrated as a superior tool for investigation of mu-CD. A simple rocket immunoelectrophoresis method foe mu-CD screening is also shown. The mu-CD protein had alpha-2-mobility and a part of the protein carried kappa-determinants probably due to secondary binding. Preparative ultracentrifugation and size chromatography on serum demonstrated that the mu-CD protein was present in serum in several sizes, the smallest being a dimer of mu-chains. Due to scarcity of material the abnormal protein could not be characterized further.


A health survey of granite workers in Finland: radiographic findings, respiratory function, hearing, electric sensory thresholds of the fingers and subjective symptoms.

Results from a health survey of 777 granite workers, exposed to quartz dust, noise and/or machine vibration, and 122 unexposed "controls" are reported. The survey included chest X-rays, pulmonary function tests, a hearing examination, the determination of the electric sensory thresholds of the fingers, and questionnaires on the subjective symptoms of the respiratory system and upper limbs. The exposed workers' radiographic findings (except for a 2.6 % rate of silicosis), respiratory functions, and sensory thresholds did not differ significantly from those of the controls. Granite drillers had a high prevalence of hearing defects. Respiratory symptoms  were common among drillers and sandblasters, and subjective symptoms of the upper limbs due to vibration occurred among the granite dressing workers who used pneumatic hammers. Both primary and secondary measures of prevention are strongly recommended for the granite industry, primarlily for quartz dust exposure and its health effects.


Dissolution of silicic acid from amosite and quartz dusts under physiological conditions.

The dissolution of silica from amosite dust in human serum and in Ringer buffer at 37 degrees C was found to be significantly higher than that from quartz. The significance of this finding in relation to their fibrogenic effects has been discussed.


[Cystosarcoma phylloides of the breast. Analysis of 58 cases].

Cystosarcoma phylloides (c.p.) is a rare fibroepithelial neoplasm of the mammary gland exhibiting considerable histological variations ranging from the aspect of hypercellular fibroadenoma to that of pleomorphic sarcoma. In this study, 58 cases of c.p. were graded according to their histology into 3 groups of increasing malignancy-benign tumors: 23 cases (42%), borderline tumors: 16 cases (27%) and malignant tumors: 18 cases (31%). Their clinical properties and evolution have been compared. These tumors were found exclusively in women, most often during the 5th and 6th decade of life (age range from 19 to 81 years). In two thirds of the cases, the history of the disease was shorter than 6 months. The symptoms were generally scant. Only in 2 cases were severe local lesions observed. The postoperative clinical course has been followed for at least 5 years in 32 instances. Recurrences were observed in 5 patients, the histology being as a rule the same as that of the primary tumor. The 12 patients with benign tumors are well 5 years or more after operation. One of the patients presenting a malignant tumor died of lung embolism soon after mastectomy. 2 out of 10 patients with borderline tumors died within 6 years with metastases of the mammary tumor. Our analysis confirms the experience that c.p. are relatively benign but often recurring neoplasms that rarely disseminate. As far as prognosis and treatment are concerned, tumors of questionable dignity should be considered malignant. To avoid such vague terms as "benign or malignant  c.p." we support OBERMANN'S suggested separation of c.p. into "cellular fibroadenoma" and "periductal fribrosarcoma". Wide local excision for small and benign tumors is recommended. All other forms require simple mastectomy. Prophylactic dissection of the axillary lymph nodes is not necessary as these tumors usually disseminate hematogenously. Roentgen therapy or chemotherapeutic agents are not useful in treatment.


[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors].

The new semisynthetic epipodophyllotoxin VP 16-213 has been tested for antitumor activity and toxicity in a non-randomized phase II trial. The study included 33 patients with solid tumors and acute leukemias. The drug was given in 5-day courses every 3 weeks, parenterally for the first 2 courses and thereafter orally. Subjectively VP 16-213 was well tolerated in both i.v. and oral administration, but almost universally induced leukothrombopenia and hair loss. The best results were achieved in 12 patients with oat cell carcinoma of the lung (4 good and 4 less good responses). Remissions of lesser quality were also observed in anaplastic lung cancer, ovarian carcinoma and acute myelomonocytic leukemia. VP 16-213 possesses proven, clinically valuable cytostatic activity against various human neoplasms. Complementary studies to establish its optimum dosage and administration, and its place in combination chemotherapy, are in progress.


Characterization of the androgen receptor from a Syrian hamster ductus deferens tumor cell line (DDT1).

The hamster ductus deferens cloned tumor cell line (DDT1) contains a complex steroid receptor protein that binds 3H-labeled 5 alpha-dihydrotestosterone,. Diethylaminoethyl (DEAE) chromatography of cytosol from these cells yields two major receptor peaks of activity. Identification of this steroid binding protein as a cytoplasmic receptor was confirmed by salt dissociation on sucrose gradients, stability of the hormone-receptor complex at 0 degrees C, and the retention patterns on phosphocellulose and DEAE cellulose. Multiple forms of the receptor exist in a single homogeneous cell type. The data support the theory that steroid hormones bind to a cytoplasmic protein receptor composed of dissimilar subunits as the initial step in steroid hormone action.


Neural properties of cultured human endocrine tumor cells of proposed neural crest origin.

Cells from human endocrine tumors of proposed neural crest origin--five pheochromocytomas, two medullary carcinomas of the thyroid, and two bronchial carcinoids--were grown in monolayer culture. Cells from all nine tumors, including epithelial forms of medullary carcinoma of the thyroid and bronchial carcinoid cells, and epithelial and neuron-like pheochromocytoma cells demonstrated all-or-nothing, short-duration action potentials.


Bovine leukemia virus genes in the DNA of leukemic cattle.

Reverse transcripts of the rna genome of the bovine leukemia virus (BLV) as well as 125I-labeled BLV RNA hybridize to the DNA of tissues from leukemic cattle with the adult form of the disease but not to bovine thymic lymphoma or normal bovine tissues.


Ion-exchange in melanin: an electron spin resonance study with lanthanide probes.

Changes are induced in the electron spin resonance signal amplitude and microwave power saturation of the naturally occurring free radical in melanin by bound paramagnetic ions. The changes serve as experimental observables in competition experiments between diamagnetic and paramagnetic metal ions for melanin binding sites and between melanin and ethylenediaminetetraacetic acid for paramagnetic metal ions. Evidence is presented for the existence of several specific types of metal binding sites. The interaction of copper with free radicals leading to loss of electron spin resonance signal amplitude is magnetic in nature and not, as has been supposed, chemical.


Oncogenic transformation of human embryo lung cells by human cytomegalovirus.

Persistent infection of human embryo lung fibroblasts with a genital isolate of cytomegalovirus resulted in oncogenic transformation of these cells. Immunofluorescence techniques detected virus-specific antigens, while microcytotoxicity tests established that the transformed cells share a membrane antigen with hamster cells transformed by inactivated cytomegalovirus. The transformed human cells induced progressively growing tumors in weanling athymic nude mice.


Increased sarcoma virus RNA in cells transformed by leukemia viruses: model for leukemogenesis.

A morphologically flat revertant of mink cells nonproductively infected with Moloney sarcoma virus exhibited contact inhibition and lacked detectable sarcoma virus RNA. Superinfection by usually nontransforming type C mammalian leukemia-causing viruses induced transformation and increased sarcoma virus RNA. The results suggest a model for leukemogenesis in animals by increasing, during replication of usually nontransforming leukemia viruses, the levels of RNA from potentially oncogenic cell or integrated virus transforming genes.


Lethal interaction of ubiquitous insecticide carriers with virus.

Large quantities of presumably nontoxic petroleum oil by-products are introduced into the environment as pesticide dispersal agents and emulsifiers. An increase in viral lethality with a concomitant influence on the liver and central nervous system occurs in young mice previously primed with such chemicals.


Diagnosis of infectious mononucleosis.

Infectious mononucleosis continues to be an important medical problem of young adults. Diagnosis is based on three principal criteria: (1) a compatible clinical picture, (2) characteristic hematologic changes, and (3) a positive serology. A relative lymphocytosis of 60% or higher with at least 20% atypical lymphocytes is a common feature. Laboratory diagnosis is dependent on proper application and interpretation of the various serologic tests. Evidence of abnormal liver function is of particular value in differentiating this disease from bacterial and viral pharyngitis.


Studies on the inhibitory activities of human serum lipoproteins for Japanese encephalitis virus.

Human serum lipoproteins were purified by ultracentrifuging and their concentrations adjusted as required to be within the normal male/female serum range for all assays. The activities in inhibition of hemagglutination (HAI) for Japanese encephalitis virus were--low density lipoprotein (LDL) greater than very low density lipoprotein (VLDL) greater than high density lipoprotein (HDL). Heating (56 degrees C/30 minutes) caused the LDL titer to fall and freeze-thawing (20 degrees C/room temperature) the VLDL titer to rise slightly, possibly as a result of alteration in lipoprotein structure. The additon of lipoprotein depleted serum appeared to dampen these effects and there was no nett change in titer when it was added to a lipoprotein mixture. Similarly, unfractionated normal serum showed no significant change in titer after these treatments. The lipoproteins lacked significant virus neutralizing (VN) activity and this remained so in spite of fluctuations in HAI titer after heating and freeze-thawing.


The prevalence of entamoeba histolytica and Toxoplasma gondii antibodies in Central Java, Indonesia.

Sera collected from people living along the slopes of Mt. Merapi and Mt. Merbabu (900-1900 m) in Boyolali Regency, Central Java, Indonesia were tested by indirect hemagglutination tests for antibodies to Entamoeba histolytica and Toxoplasma gondii. A total of 695 sera from 439 males and 256 females, 2 to 75 years of age were tested for amoebiasis and 17.6% had positive antibody titers of 1:128 or greater. The prevalence of antibodies was the same for males and females and increased with age. The seropositivity rate for Toxoplasma gondii antibodies among 438 males and 255 females was 2% at titers of 1:256 or greater. The prevalence was higher in females (2.7%) than in males (1.6%), and was highest in the oldest age groups.


Radiation injury to abdominal aorta and iliac artery sustained in infancy.

Late complications of radiation therapy will become more common as treatment of neoplasms in childhood becomes more successful. A patient with a successfully treated Wilm's tumour presented with hypertension 3 years after therapy. Angiography revealed extensive damage to the aorta and left common iliac artery, probably caused by the radiation therapy. The hypertension was the result of renal artery stenosis.


A site of action for zinc in neoplastic tissue.

The effect of dietary zinc levels on DNA synthesis in transplanted hepatomas induced by 3'-methyl-4-dimethyl-amino-azobenzene was investigated. DNA synthesis was found  to be reduced (P less than 0,01) in rats maintained on diets low in zinc (0,5 mug/g) and high in zinc (less than 500 mug/g) when compared with the control animals given 60 mug zinc/g ration. Subsequently, the effect of dietary zinc intakes on the activity of 2 zinc-dependent enzymes associated with DNA synthesis--thymidine kinase and DNA polymerase--was studied. Both thymidine kinase and DNA polymerase activity was significantly reduced in animals receiving the zinc-deficient (0,5 mug/g) and zinc-supplemented (less than 500 mug/g) diets when compared with the control animals (60 mug/g). The data indicated that the DNA synthesis was the primary locus associated with zinc deficiency and zinc supplementation in proliferating tumour tissue, and that the site of action of zinc in this process was probably thymidine kinase, since there was considerable doubt concerning the role of DNA polymerase in DNA synthesis.


Collagenase and elastase released during peritonitis are complexed by plasma protease inhibitors.

Peritoneal fluids from patients with diffuse peritonitis secondary to perforation of the appendix contained large quantities of collagenase and elastase. The enzymes, which existed in the form of complexes with plasma protease inhibitors, probably had been released from the granulocytes. The two enzymes had linked almost half of the alpha 1-antitrypsin and four fifths of the alpha 2-macroglobulin in the fluid. Evidence that regional defense against protease had failed was obtained by finding the C3 component of complement completely converted. Toxic peptides probably had been released. Recognition of plasma protease inhibitors as an important part of the regional defense against protease also suggested use for therapy. We lavaged the peritoneum postoperatively with fluid that did not contain plasma inhibitors but with volumes large enough to eliminate the accumulation of enzymes for the granulocyte.


Metastatic potential of metastases.

Nine cases of known metastases originating from other metastatic foci were documented at operation. The primary tumors included four melanomas, two osteosarcomas, a synovial sarcoma, an anaplastic lung carcinoma, and a rhadbomyosarcoma. Secondary metastatic sites to the regional lymph nodes were noted in the pulmonary hilum (one), mediastinum (one), pulmonary hilum and mediastinum (three), small bowel mesentary (two), retroperitoneum (one), and axilla (one). All patients were immunocompetent as evidenced by their ability to be sensitized to 2,4-dinitrochlorobenzene (DNCB) and/or their positive response to common skin test antigens. The metastatic potential of cells from metastases does not appear to differ from cells of the primary.


The effect of portacaval shunt on plasma lipids and tissue cholesterol synthesis in the dog.

Portacaval shunt (PCS) has been proposed as a therapy for hyperlipidemia; however, its lipid-lowering mechanism is unknown. In this study PCS was performed on ten mongrel dogs to measure its effect on plasma lipids and on the cholesterol synthesizing ability of the liver and intestines, the major indodenous cholesterol synthesizing tissues. Plasma was analyzed for total cholesterol (CHOL), triglycerides (TG), and the CHOL content of three plasma lipoprotein fractions. Jejunal, ileal, and hepatic cholesterol synthetic rates were determined by 14C-acetate incorporation to CHOL in tissue slices obtained at operation before PCS and 44 +/- 4.1 (S.D.) days after PCS. Plasma CHOL decreased by 18 +/- 7 (S.E.), 34 +/- 8 (S.E.), and 57 +/- 14 (S.E.) mg. per 100 ml. by 4, 6, and 16 weeks after PCS, respectively. TG decreased by 13 +/- 5 (S.E.), 27 +/- 5 (S.E.), and 30 +/- 9 (S.E.) mg. per 100 ml. at corresponding time intervals. Paired Student's test analysis of CHOL and TG changes are significant at the p less than 0.05 level. CHOL content of the three plasma lipoprotein fractions decreased correspondingly. Intestinal tissue CHOL synthesis rates changed only slightly. Hepatic synthetic rates increased by 30 to 40%; however, no synthetic rate changes were statistically significant at the p less than 0.05 level. PCS is associated with decreased in plasma CHOL [42% (see article)] AND TG [53% (see article)] in dogs up to 16 weeks following operation. Statistically significant changes in endogenous CHOL synthesis were not demonstrated by this study. The mechanism by which PCS affects plasma lipids in the dog is unknown as yet.


[The "Vaccination Reaction" syndrome of broilers after vaccination against Newcastle disease and infectious bronchitis (author's transl)].

In a part of the broiler flocks vaccinated against Newcastle disease (N.C.D) and infectious bronchitis (I.B.), disease symptoms of lingering nature have been observed, generally in the second half of the rearing period. In a practical investigation with weekly examinations of chickens, supplemented by a serological examination of twenty-four animals per flock at the age of six weeks, it was hoped to establish the factors responsible for this "vaccination reaction". In the district under notice the vaccination reaction syndrome had been responsible for widspread abandoning of twice spraying against N.C.D. in the first and fourth week in favour of drinking-water vaccination (generally combined with I.B. vaccination) in the second week and spray-vaccination in the fourth week or of combined drinking-water vaccination in the second week, either with or without N.C.D. drinking-water vaccination in the fourth week. Admittedly the incidence of vaccination reaction in flocks vaccinated exclusively via the drinking water was less frequent (32%) than in flocks in which the second vaccination was administered as a spray (48%), but this difference was largely accounted for by infection with Mycoplasma gallisepticum and/or Mycoplasma synoviae, complicated by infection with Escherichia coli. Of the thirty-three flocks free of mycoplasmosis, 24% exhibited the vaccination reaction, while the incidence to the fifteen infected flocks was 73.4%. In flocks infected with mycoplasmosis the course of E. coli infections was serious in 46.7% of the birds, while this figure was 18.2% in flocks free of mycoplasmosis. In flocks free of mycoplasmosis, the percentage of serious E. coli infections was lower after spray vaccination (14.3%) than after drinking-water vaccination (21%). The strains of E. coli brought in by one-day chicks from the hatchery disappear rapidly and play no role of any significance in the problem of colibacillosis observed at an age of three weeks or older. Of the 310 isolated strains of E. coli, 52 could not be typed and the others belonged to eighty different serotypes. With respect to the effect of infectious bronchitis the investigation does not provide sufficient evidence to permit of drawing conclusions. A significant role in the occurrence of the syndrome was played by coccidiosis and Gumboro's disease. With respect to environmental factors the available data did not allow of drawing conclusions. The authors recommend continuing with all available means to free the breeding animals from M. gallisepticum and M. synoviae, undertaking scientifically based research into the role of infectious bronchitis in the "vaccination reaction" syndrome, an effective programme of hygiene to control E...


[Intrapulmonary fibromas (author's transl)].

Based on 5 individual cases over a period of 8 years (1 fibroma, 1 angiofibroma, 2 adenofibromas, 1 xanthous neurofibroma) the characteristics of the rare intrapulmonary fibroma and the therapeutic consequences are discussed. Any suspicious tumor demands a thoracotomy with careful preoperative treatment and the subsegment or segment resection depending on the histological diagnosis reported during the procedure.


[Therapeutic problems in the radiotherapy of bladder tumors].

The indications of different radiation techniques are reviewed. Out of these, the interstitial therapy should be regarded more attentively in future, unless too large a tumor is present in the fixed part of the bladder. The spatial distribution of the dose during percutaneous megavoltage therapy depends on the tumor stage. Irradiation is not allowed to be confined to the bladder except in case of primary findings corresponding to T1-2N0, the tumor being confined to the mucous or to the internal muscular tunica respectively, the degree of its malignancy being low and transitional cells having been revealed histologically. In all other cases, irradiation has to encompass the whole small pelvis. The split-course-technique has proved its value. If available, ultrahard bremsstrahlung is to be preferred. For radiation therapy of small volumes, fast electrons should be tested also in future.


Characterization of the androgen receptors in the hypothalamus, preoptic area and brain cortex of the rat.

The specific androgen receptors for testosterone (T) (1) and 5alpha-dihydrotestosterone (DHT) in the cytosol fraction of the hypothalamus, preoptic area and brain cortex of the rat have been characterized using electrophoresis and isoelectric focusing in polyacrylamide gels. After labeling of the cytosol fractions in vivo and in vitro we were able to demonstrate androgen-receptor complexes moving with an electrophoretic mobility (R(f) of 0.5 in 3.25% acrylamide gels containing 0.5% agarose and 10% glycerol. Polyacrylamide gel electrophoresis was used as a quantitative assay for androgen receptors in the tissues. The hypothalamus, preoptic area and brain cortex were found to possess a single class of high affinity binding sites for androgens and the dissociation constants (K(D) were estimated to be 3.4, 4.3 and 2.6 X 10 (-10M) respectively. The binding capacities were 3.7 (hypothalamus), 3.5 (preoptic area) and 1.8 X 10 (-15) (brain cortex) moles of high affinity binding sites per mg protein. Like other androgen-receptor complexes, the testosterone-receptor complexes of the hypothalamus, preoptic area and brain cortex were temperature labile, sulfhydryl dependent and revealed a very slow rate of dissociation at o degrees C (t1/2 greater than 36 hr). The receptors in all the tissues had an isoelectric point of 5.8. The steroid specificity of the cytoplasmic androgen receptors was tested in vitro by the competing efficiency of different unlabeled steroids for (3H)-testosterone binding. In the three tissues in investigation the following order of affinity was found: DHT greater than T greater than Cyproterone acetate greater than progesterone greater than androstenedione greater than 17beta-estradiol. Cortisol did not effect androgen binding significantly. Thus, the physiochemical characteristics of the cytoplasmic androgen receptors of the hypothalamus, preoptic area and brain cortex are very similar, if not identical, to those of the androgen receptors described in the anterior pituitary, ventral prostate, epididymis and testis.


Effects of estrogen and testosterone on specific prolactin binding in the kidneys and adrenal of rats.

The effects of estradiol benzoate in the female rat, testosterone propionate in the male rat, and castration in both sexes on specific prolactin binding sites in the particulate membranes of the kidneys and adrenals were studied. Castration resulted in a significant increase in PRL binding activity in the kidneys of both males and females, and in a significant increase in PRL binding activity in the adrenals of the females. The increase in PRL binding with castration and the decrease seen with testosterone treatment were similar in both immature and mature rats. Progesterone administration to castrate females failed to alter PRL binding in both tissues. The present results suggest that estrogen and testosterone participate in the PRL osmoregulatory system in rat.


Antibacterial activity of 15-azasteroids alone and in combination with antibiotics.

A new class of 15-azasteroid analogues has been synthesized and tested for antimicrobial activity. The compounds 1, 10, 11, 11a-tetrahydro-7-methoxy-11a-methyl-2H-naphth (1,2-g) indol (methoxyimine) and 1,10,11,11a-tetrahydro-11a-methyl-2H-naphth (1,2-g) indol-7-ol (hydroxyimine) inhibit the growth of Bacillus subtillis and Escherichia coli at concentrations as low as 10-5 M. Addition of either compound to the growth medium casued a rapid inhibition in the transport of radioactive glucose, uracil and several amino acids. The inhibition of growth  and substrate transport was reversed following removl of the steroid from the medium. The evidence is consistent with a site of steroid action at the cell periphery. Combining the methoxyimine with polyor circulin at subinhibitory concentrations produced greatly enhanced antimicrobial activity against Pseudomonas fluorescens. Similar action was observed against B. subtilis when the azasteroid was combined with vancomycin or chloramphenicol. The inhibitory action of other antibiotics such as penicillin or erythromycin was not affected by addition of the test compound. The results suggest formation of a molecular complex between the azasteroid and antibiotic which is responsible for the enhanced biological activity.


Suppression of mixed lymphocyte response in mice bearing primary tumors induced by murine sarcoma virus.

Mixed lymphocyte culture (MLC) responses of spleen cells from mice bearing tumors induced by murine sarcoma virus of the Moloney type (MSV) against allogeneic spleen cells were found to be markedly depressed, as estimated by three parameters: lymphoblast counts, 3H-thymidine incorporation (TI), and cell-mediated lysis (CML). While all three parameters were definitely depressed in comparison to the normal controls, TI was depressed to a greater degree than lymphoblast counts and CML. MSV spleen cells also had a suppressive effect on the MLC responses of normal spleen cells in third party type of experiments. The cells mediating this effect were radioresistant non-T cells, which were removed by adherence columns and were inactivated by carrageenan. These data suggested that the supressor cells were macrophages. Serum from MSV tumor-bearing mice had a greater suppressive effect than did normal mouse serum. Both the suppressor cells and the suppressive serum factors may play an important role in the immunosuppression observed in tumor-bearing hosts.


Serum lipoprotein concentration and composition in healthy 50-year-old men.

The classification of hyperlipoproteinaemias (HLP) is based on arbitrary limits between "normolipidaemia" and "hyperlipidaemia". 92 randomly selected healthy 50-year-old men were studied regarding serum lipoprotein (LP) lipid composition to define limits for "normality". Cholesterol and triglyceride concentrations were determined and the individual ratios between cholesterol and triglycerides were calculated in the ultracentrifugally isolated LP density classes. A significant linear correlation between cholesterol and triglyceride concentrations was found in the very low density lipoproteins (VLDL) and low density lipoproteins (LDL) but not in the high density lipoproteins (HDL). When different percentile limits for LDL cholesterol and VLDL triglycerides were used as cut-off points for "normality" not only the absolute prevalence but also the relative frequency of different types of HLP was influenced. 26 overweight men studied separately showed significantly increased VLDL cholesterol and triglyceride levels with maintenance of the normal ratio cholesterol/triglycerides of this LP class compared with non-obese subjects. Three different kinds of "extra bands" were occasionally seen on agarose electrophoresis: a "double pre-beta" band in whole serum (3%), a "sinking pre-beta" band with density greater than 1.006 (17%) and a "late pre-beta" band in VLDL (22%). While "sinking pre-beta" is identical with Lp (a) LP the "late pre-beta" band probably represents a certain accumulation of "intermediary particles".


[Bilateral tumors of the parotid glands. (author's transl)].

Bilateral parotid tumors occur very rarely; they account for 0.5% of 544 cases of parotid tumors recorded at the National Cancer Institute of Milan from 1945 to 1974. Three cases of bilateral tumors are described; two tumors were synchronous and one metachronous. The patients were women of 51, 46 and 52 years. The histologic type was the same on both sides in all cases, namely adenolymphoma, mucoepidermoid carcinoma and mixed tumor respectively. Surgical exicston was the treatment of choice; according to the histology of the tumors partial (adenolymphoma) or total parotidectomy (mixed and malignant tumors) was performed. As to the case of mucoepidermoid cancer of both parotid glands no recurrence was observed after five years.


Herpesvirus type 2: isolation from seminal vesicle and testes.

Reproductive tissues from 10 recent male cadavers were examined. Herpesvirus type 2 was isolated from testes, seminal vesicle, or both in 4 cases. This is the first report of the isolation of herpesvirus type 2 from human seminal vesicular tissue. The data support previous evidence that herpesvirus type 2 can be isolated from the reproductive tissues of males without active or prior infection and suggest that these tissues may serve as a reservoir for transmission of this virus. The study also documents, for the first time, the ability to culture herpesvirus type 2 in organ explants from cadaveric reproductive tissues with the subsequent release of infectious virus.


The isolation and some biological properties of a variant avian infectious bronchitis virus.

A virus isolated from a respiratory disease in chickens was identified as infectious bronchitis virus (IBV). By serum neutralisation tests the virus was shown to be serologically distinct from the Massachusetts type but to possess a one-way relationship with the Connecticut type. Experimentally, it caused a relatively mild respiratory disease in baby chicks. Vaccination of young chicks with H-120 Massachusetts IBV vaccine afforded a high degree of protection against challenge with the isolate. Some problems relating to the isolation and classification of field strains of IBV are briefly discussed.


[Study of the pathogenic qualities of 4 celo-virus strains isolated in Bulgaria].

Four CELO virus strains, isolated in this country, were used to infect 3-day-old chicks via the trachea, muscularly, orally, subcutaneously, and cerebrally. The chicks were killed on the 2nd, 4th, 6th, 9th and 16th day following inoculation. Material was taken from each chick for morphologic, virologic, and serologic examination. The clinical course of the disease was also followed up. Prior to killing some birds showed infirmity, difficult breathing, slightly expressed diarrhia, going off food, and more sporadically there was fecal mass around the cloaca matting the plumage. Some manifested nervous symptoms similar to those observed in cases of Newcastle disease and encephalitis of birds. In some of the chicks there were hyperemia of the lungs, trachea, and intestins as well as necrotic foci in the liver.


[Study of the indirect complement fixation test for use in the differentiation of foot-and-mouth disease viruses and the determination of immunity].

Studies were carried out to establish the optimal conditions for the indirect complement-fixation test (ICFT) and explore the possibility to use the test in differentiating the foot-and-mouth disease (FMD) viruses and checking the immunity obtained in survivals or in animals that had been vaccinated against FMD. It was demonstrated that the proper use of ICFT necessitates in turn the use of a minimal amount of antigen, which in the presence of 1-2 E homologous hyperimmune serum completely binds the 1 E complement. Results showed that the sera of survived or vaccinated animals contain specific antibodies of titers of 1:4 up to 1:256. The latter depended on the type of vaccine, the amount of antigen in the vaccinal dose, and the time period from the immunization or survival up to the time of taking the serum samples. It is pointed out that ICFT is a sensitive and specific method for the differentiation of FMD viruses and the study of animals' immunity against FMD.


[Use of temperature, trypsin and biological tests for the intraspecies differentiation of local strains of Aujeszky's disease virus].

Studies were carried out with 8 strains of Aujeszky's disease virus using a temperature test (50 degrees C for 1 hour), a trypsin test (0.5 mg per cu. cm at 37 degrees C 1 hour), and a biologic test. The strains were isolated from the brain of dead pigs that have presumably been affected with encephalitis. They proved sensitive when studied with the temperature and the trypsin tests sharply lowering their titer. The viruses isolated from pneumonic foci in the lungs of pigs in which the disease had assumed a chronic course turned out to be considerably more resistant with the use of the two tests. The vaccinal strain MK was shown to be the most resistant in all tests. Comparable results were obtained also with the study of the viruses employing a modified test with young albino mice weighing 7-8 grams. The cerebral inoculation of the viruses aimed in this case at establishing the intracerebral pathogenetic index (IPI). Test rabbits were also used for the same purpose. The virulent strains had correspondingly a shorter incubation period and in rabbits there was a well pronounced clinical course, the IPI value being higher than 1.50. To latent viruses the rabbits responded with a protracted clinical course, and IPI ranged between 0.20 and 0.95.


[Hepatoma in artificially raised trout].

Cases were described of a hepatoma in the liver of trout, Salmo irideus, Gibb., originating from three fish-breeding farms in the district of Sofia. Histologically, three were tumor cells arranged in the form of trabeculae and paths or distributed focally. The tumorous growths had trabeculous, more rarely alveolar structure. Some of the neoplasms had carcinomatous character. The tumor stroma had weakly developed, however, in some parts three was rich fibrous stroma, and the gross appearance resembled fibroadenoma. Infiltrative growth was also observed. It is concluded that the hepatoma observed in poikilothermic animals (rainbow trout) is similar to the liver tumors found in birds and mammals.


Multiple hepatocellular tumours in a patient treated with oral contraceptives.

A case of multiple hepatic tumours in a patient treated for four years with high doses of oral contraceptives is described. Solitary hepatocellular lesions associated with conventional doses of oral contraceptives have been reported previously in twenty nine cases. Haemorrhage has been a common mode of presentation and is attributed to the marked vascularity of the lesions, an appearance referred to as peliosis hepatis. Radiographic studies show this term to be inappropriate as the vessels are of arterial origin. Another finding not previously reported is the presence of diffuse hyperplasia in the non-tumourous parts of the liver.


Ultrastructure of tubular inclusions in endothelial cells of pituitary tumors associated with acromegaly.

Tubular inclusions were present in 13 out of 43 pituitary adenomas of acromegalic patients and in a single chromophobe pituitary adenoma. There were none in 76 other pituitary adenomas with differing endocrinological symptomatology. The arrays were usually located in the perinuclear cistern of capillary endothelial cells. The tubule diameter in osmium fixed material measured 19-26 nm and the light core averaged 6-11 nm. A longitudinal period of about 4.5 nm could be demonstrated with PTA block staining. Fixation with glutaraldehyde and block staining with ethidium bromide as well as permanganate fixation followed by RNAse treatment showed only the core of the tubules consisting of globular subunits. Several histochemical reactions (perchloric acid extraction, methenamine-silver staining, trypsin and DNAse digestion of frozen sections) suggested that the particles consist of a core of DNA coated with protein. No virus multiplication could be detected in cell cultures or in mice innoculated with fresh tumor material. No significant antibody titers against several virus antigens could be demonstrated.


[Central giant cell granuloma: histochemical and ultrastructural study on its histogenesis (author's transl)].

Until now numerous studies on central giant cell granuloma of jawbones have not been able to reveal the histogenesis of this tumourlike lesion. The aim of the present investigation in two surgically proven cases was to study this question by means of histochemical and electron-microscopic methods. Rather similar histochemical properties were shown in giant cells and pericytes of capillary sproute penetrating the granuloma. Cell fusion occurred between both cell types as was observed by electron microscopy. The process of cell fusion is defined by characteristic interdigitations of cell membranes. Therefore pericytes are believed to be the stem cells of multinucleated giant cells in giant cell granuloma. The abundance of giant cells usually occurring in the granuloma might be explained by plenty of capillary sprouts made up by clusters of pericytes. The factors inducing the pericytic cell fusion process are still unknown. The question arises whether cytogenesis of giant cells in giant cell granuloma might be similar in other giant cell lesions or even in the development of multinucleated osteoclasts.


Pituitary growth hormone and somatotrophs in rats bearing chemically induced hepatomas.

Measurement of pituitary growth hormone (GH) content by polyacrylamide gel electrophoresis (PAGE) showed that rats bearing diethylnitrosamine (DENA) induced hepatomas contained significantly less GH than age-related controls. Light microscopy of these pituitaries revealed many apparently dying somatotrophs in tumour bearing rats. By electron microscopy the somatotrophs of DENA hepatoma rats were relatively inactive and some clearly dying, which could account for the reduced hormone content. However, electron microscopy of somatotrophs of rats with 2-acetyl-aminofluorene (2-AAF) hepatic tumour nodules revealed many very active cells with greatly increased content of free ribosomes and many granules poised for imminent release. Other somatotrophs of these rats showed lysosomal activity indicating reduced secretion after an active phase.


[Correlation between immunological reactivity and the fat-carbohydrate metabolism. Influence of phenformin].

Based on the conceptions of the relationship between energy and adaptation-immunological systems a number of hormone-metabolic indices were compared with immune reactivity as evidenced by skin tests and rosette-formation reaction. It is shown that lowering of immunological indices in oncological patients is associated with a decreased sensitivity of dexametasone suppression of cortisol, an increased concentration of 11-oxycorticosteroids in blood, a higher level of triglycerides, cholestrol, beta-lipoproteins and less glucose tolerance. The use of phenformin during 3 months in patients with atherosclerosis resulted in a considerable increase of the index of phytohemagglutinin stimulated blasttransformation of lymphocytes and rosette-formation reaction. This effect was associated with normalization of lipid metabolism indices.


[Hematopoiesis in children with retroperitoneal neurogenic tumors].

Under observation were 140 children with retroperitoneal neurogenic tumors. In 69 of 125 patients with malignant neoplasms metastases were detected. Hemographic and myelographic findings were analysed depending on the degree of malignancy and tumor spread. Anemia usually moderate and normochromatic was observed only in neuroblastomas. This group of patients is also characterized by frequent shifts to the left leucograms and high sedimentation test, contrary to benigh tumors. The investigation of bone marrow allows one to reveal the suppression, and more rarely irritation of various blood stems.


[Scintigraphy of the pancreas in insuloma].

The results from the scintigraphic investigations of 28 patients are analyzed. In 11 o them-comparative observations are carried out between the scintigraphic and operative data, revealing a complete coincidence. Focal changes are predominantly observed in the scintigraphic image of pancreas-75 per cent in insuloma disease. Pancreas scintigraphy has a leading role in insuloma disease diagnosis.


[Localization of genome RNA synthesis in Sendai virus].

Localization of Sendai virus 50S RNA in Ehrlich ascitic carcinoma cells was studied. At 48 hours postinfection virus-specific 50S RNA was found in the nucleus after 30 min exposure to 3H-uridine, and its amount increased after 1-hour exposure to the precursor reaching 18% of the total nucleus virus-specific RNA. After 2-hour or longer exposure to the precursor the amount of 50S RNA in the nuclei decreased considerably and in the cytoplasm in this gradient region a considerable radioactivity appeared. Rapid utilization of 3H-uridine by the cells under these experimental conditions suggests that 50S RNA is synthesized in the nucleus and migrates to the cytoplasm.