Failure of neutral-red photodynamic inactivation in recurrent herpes simplex virus infections.

Because photodynamic inactivation of herpes simplex virus infections may not be free of hazard, the efficacy of photodynamic inactivation with neutral red and light was evaluated in a placebo-controlled study of 170 episodes of recurrent herpes simplex virus infection in 96 patients. The preparation of neutral red that was used was shown to photoinactivate herpes simplex virus in vitro, but had no significant effect on the rate of resolution of herpetic lesions (P greater than 0.10) or on the frequency of subsequent recurrences (P greater than 0.10), except for orolabial lesions, in which an adverse effect on the rate of subsequent recurrences was observed (P less than 0.05). In the absence of demonstrated efficacy, the routine use of neutral red and light in patients with recurrent herpes simplex virus infections should be discontinued. Furthermore, other photoactive dyes should not be used until their efficacy has been demonstrated by suitably controlled clinical trials.


Immunization of pigs with the attenuated S- strain of Japanese encephalitis virus.

The attenuated S- strain of Japanese encephalitis virus was produced from a wild strain of this virus by serial cultivation in primary bovine kidney cell cultures at 30 degrees C. Pigs were inoculated with it and examined for ability to produce antibody and protect themselves from infection with a wild strain used for challenge. In pigs inoculated with a single dose of 10(6.5) approximately 10(7.5) TCID50 of the S- strain, the neutralizing antibody titer or hemagglutination-inhibiting antibody (HI) titer increased to 10 approximately 320. An antibody titer exceeding 10 was maintained for 2 approximately 9 weeks. In pigs inoculated twice with 10(6.5) approximately 10(7.0) TCID50 of the S- strain, HI titer increased to 80 approximately 640. In many of these pigs, HI titers of 80 approximately 160 persisted for more than 6 weeks. Pigs inoculated once or twice with 10(7.0) approximately 10(7.5) TCID50 of the S- strain were challenged by inoculation with 10(4.5) approximately 10(5.5) TCID50 of a wild strain and examined for the occurrence of viremia. As a result, an ability to protect from infection was demonstrated in pigs which showed an antibody titer surpassing 10 at the time of challenge. Pregnant sows inoculated with 10(7.0) TCID50 of the S- strain were challenged by inoculation with 10(7.0) TCID50 of a wild strain. Neither death nor infection occurred to any fetus harbored by them. From these results, it is concluded that the S- strain can be used as live virus vaccine for porcine practice.


Histopathology of hemorrhagic enteritis in turkeys.

In the summer of 1972, a disease of turkeys manifesting hemorrhagic diarrhea as a main clinical symptom and hemorrhagic enteritis as a necropsy finding broke out on a turkey farm in Japan. Seven-week-old Large White turkeys suffering from this disease were studied histopathologically and electron microscopically. Clinically, affected birds showed bloody diarrhea. Death occurred to them after an acute course. In the blood film, immature monocytes were higher in count in them than in healthy birds. Necropsy revealed a number of dark red bloody clots in the intestinal tract, many petechiae in the mucous membrane of small intestine and ceca, and atrophy of the spleen. The histopathological changes characteristic of this disease were acute hemorrhagic enteritis, degenerative changes of lymphatic tissue, proliferation of reticuloendothelial cells all over the body, and formation of intranuclear inclusion bodies in these cells. By electron microscopy, viral particles showing a crystalline array were found in the nuclei of reticuloendothelial cells. Viral particles which had electron-dense nucleoids and a naked hexagonal shape were about 80 nm in average diameter. The ultrastructural features of those inclusion bodies were identical with those of avian adenovirus.


Histopathology of feline panleukopenia in domestic cats.

Histopathological observations were carried out on 17 domestic cats naturally affected with feline panleukopenia. Principal lesions were found in the intestine, bone marrow, and lymphoid organs. Intestinal lesions were characterized by degenerative changes accompanied by the appearance of intranuclear inclusion bodies in the epithelial cells of the crypts. In contrast to the crypts, the villi were seldom involved. Hypoplasia, parenchymal degeneration, and activation of the reticuloendothelial system were observed in the bone marrow and lymphoid organs. Intranuclear inclusion bodies were found occasionally also in the reticular and parenchymal cells of the bone marrow, lymphoid organs, liver, adrenals, and pancreas. Most of the inclusion bodies were amphophilic when stained with hematoxylin and eosin and occupied the whole area of the nucleus without producing any zone of clear halo. While cells bearing inclusion bodies underwent degenerative changes constantly in the intestinal crypts, the formation of inclusion body was not accompanied by the degeneration of corresponding cells in any other organ. Pathological changes as mentioned above were considered to be closely related to the systemic infection of feline panleukopenia virus.


Mode of action of sodium nitroprusside on vascular smooth muscle.

1. Sodium nitroprusside is a potent relaxant of smooth muscles with a predominantly tonic response, e.g. rat aorta contracted by noradrenaline, angiotensin II, Phe2-Lys8-vasopressin, BaC1(2), or KC1, and guinea-pig tracheal smooth muscle contracted by carbachol. 2. Smooth muscle preparations from the splanchnic region and with varying degrees of phasic contractility are less sensitive and develop tachyphylaxis (portal vein, duodenum of the rat) or are unresponsive to sodium nitroprusside (vas deferens, uterus of the rat). 3. Cardiac auricles of the guinea pig are not affected by sodium nitroprusside in either frequency or amplitude or spontaneous contractions. 4. Sdium nitroprusside causes a parallel shift of the dose-response curve of rat aorta to noradrenaline to the right and reduces the maximum response. 5. The drug has no blocking or stimulant effect on alpha- or beta-adrenoceptors, respectively. 6. Sodium nitroprusside inhibits the contractile response of calcium-depleted depolarized rat aorta to extra-cellular calcium. Like verapamil, it inhibits the increment in 45calcium uptake of rabbit aorta elicited by K+. Sodium nitroprusside significantly reduced 45calcium binding by microsomes prepared from rabbit aorta. 7. Rabbit aorta was incubated with lanthanum chloride to prevent calcium influx; sodium nitroprusside reduced the maintained rapid contraction phase in response to noradrenaline which is believed to be based on the intracellular activation of calcium. 8. In rat aorta, cellular cAMP and ATP levels were not found to be affected by the drug. 9. Rabbit aorta, "skinned" by glycerination is unresponsive to sdoium nitroprusside. 10. It is concluded that sodium nitropruside acts on exictation-contraction coupling predominantly in tonic smooth muscle by interfering with both the influx and the intracellular activation of calcium.


The effect of Solanum malacoxylon on rachitic bone lesions in the rat.

The plant Solanum malacoxylon (S.M.) is known to cause severe soft tissue calcifications in cattle and sheep and has recently become of special interest since it exerts biological actions which resemble those of vitamin D. In order to investigate whether S.M. is capable to improve the rachitic bone changes in vitamin D and phosphate deficient rats, a watery extract of 50, 100 and 200 mg S.M. was fed daily to these animals over a period of 10 days. The width of epiphyseal plates was compared after the time with those of rats treates with 0, 0.225, 0.45, and 0.9 IU of vitamin D3 daily. There was a dose related curative effect of S.M. on the epiphyseal lesions very similar to that of vitamin D3. The hypercalcemic and hyperphosphatemic effect of S.M. was identical to that of vitamin D3. The 25-hydroxy-vitamin D serum levels remained almost undetectable in the S.M. treated rats as well as in the vitamin D3 treated animals.


Physiology of antidiuretic hormone and the interrelationship between the hormone and the kidney.

This paper reviews the physiology of antidiuretic hormone, including the factors involving the formation, storage and release of the hormone, the metabolism of vasopressin and its physiologic and pharmacologic effects on water and electrolyte transport. The consequences of both deficiency and excess of the hormone are also discussed.


Catecholamines and renal water excretion.

The in vivo mechanisms whereby systemic alpha- and beta-adrenergic stimulation exert opposing effects on renal water excretion are reviewed. An extrarenal mechanism is suggested since the effect of intravenous infusion of norepinephrine or isoproterenol on water excretion cannot be mimicked by the intrarenal administration of these agents. A ROLE OF VASOPRESSIN IS IMPLICATED SINCE NEITHER MAN NOR DOG WITHOUT A PITUITARY SOURCE OF VASOPRESSIN DEMONSTRATE THE SAME EFFECT OF CATECHOLAMINES ON WATER EXCRETION AS OBSERVED IN INTACT MAN AND DOG. Evidence also is presented that systemic alpha- and beta-adrenergic stimulation affect vasopressin release primarily by altering baroreceptor tone. The potential role of the autonomic nervous system in mediating other nonosmotic stimuli for vasopressin is discussed.


Kidney and calcitonin.

Calcitonin, whatever its origin, produces a decrease in the renal tubular reabsorption of sodium, phosphate and calcium in man and in the rat. Renal receptors for calcitonin have been demonstrated in the membranes of rat tubular cells using 125I salmon calcitonin as a tracer. Hormone-receptor interaction initiates the activation of membrane adenyl cyclase. In the rat and in man, the kidney plays a major role in degradation of both human and salmon calcitonin. Plasma levels of immunoreactive calcitonin are high in chronic renal failure. The question of the physiological role of calcitonin on kidney function is still unsettled.


Vitamin d and the kidney.

The biologically active form of vitamin D3, 1,25-dihydroxycholecalciferol is produced by the kidney. The biosynthesis of 1,25-dihydroxycholecalciferol from 25-hydroxycholecalciferol is apparently controlled and important factors in this control are dietary calcium and phosphorus, and parathyroid hormone secretion. The direct effects of vitamin D and its metabolites on renal function are uncertain. Patients with chronic renal failure have defective synthesis of 1,25-dihydroxycholecalciferol. Uremic patients treated with small doses of 1,25-dihydroxycholecalciferol or 1 alpha-hydroxycholecalciferol show increased intestinal calcium absorption and bone healing.


Morphological changes of astrocyte-like cells induced by serum beta-lipoprotein in brain cell culture.

When added to brain cell cultures of newborn rats, serum and, in particular, its beta-lipoprotein fraction caused significant morphological transformations of astrocyte-like cells present in the culture. The changes were instantaneous as they appeared within 1 min after addition of beta-lipoprotein and they were characterized by swelling and loss of cellular processes of all astrocyte-like cells present. The lipoprotein effect was reversed after a period of about 7 h. Since the blood-brain and blood-spinal fluid barrier in multiple sclerosis is decreased towards serum macromolecules, i.e. the serum beta-lipoprotein, this protein may enter the central nervous system and thereby initiate a demyelinating process.


Effect of intraventricular glutamate on ACTH release.

Sodium glutamate infused into the 3rd ventricle is a potent stimulus of ACTH release, as shown by the rise in plasma corticosterone levels. Glutamate failed to consistently increase the plasma corticosterone level in rats with deafferentation of the medial basal hypothalamus (MBH). We suggest that intraventricular glutamate interferes with central nervous function outside the MBH and stimulates ACTH release via afferent neural pathways.


[Immunoglobulin G level in the serum of patients with polyneuropathies].

In the serum of patients with polyneuropathies of various aetiology the immunoglobulin G level was determined quantitatively using the so-called disc precipitation test. Fifty serum samples were investigated. The IgG level was higher (p less than 0.05) in the group of patients with polyneuropathy as compared with the control group. No differences were observed in the IgG level between different types of polyneuropathy which may be due to small number of cases in various groups.


[Surgical management and therapeutic results in 114 cases of pituitary adenoma].

In the reported group of 114 cases the overall operative mortality was 3,5% and when two incurable cases are escluded this mortality falls to 1,7%. An essential change in the management of this disease was abandoning of postoperative radiotherapy and increasing of the extent of tumour removal. This decision was based on the view that despite weak antigenicity of the neoplasm immune mechanisms mobilized after radical operation are sufficient to inhibit or even destroy the remaining tumour tissue. In the light of eight years of experience with this method it seems that it will pass the test of time.


Cytosome morphology and distribution of generalized ceroidlipofuscinosis in a twenty-eight month old boy with normal myeloperoxidase activity.

A brain biopsy obtained from a twenty-eight month old boy with ceroidlipofuscinosis was studied by light and electron microscopy. There were widespread intracellular deposits of autofluorescent material taking the fat stains. Cytoplasmic inclusions were plentiful in neurons, astrocytes, oligocytes, M cells and vascular elements. Their substructure ranged from that of variably dense aggregates of essentially homogeneous or granular appearance to that of miscellaneous collections of lamellar pairs and/or tubular structures of variable length. Stacks of 2 to 4 linear profiles with a curved outline were rarely seen and then almost exclusively inside cytosomes of endothelial cells. Similar observations were made in peripheral nerve, skin and liver biopsies. The granules of peripheral blood neutrophilic leukocytes were unremarkable. A small percentage of lymphocytes contained granular cytoplasmic bodies not unlike those known to be an ordinary feature of some lymphocytes of the average blood sample. However, a certain resemblance between these bodies and some of the cytosomes seen in the patient's tissues was also apparent. Myeloperoxidase activity was tested with paraphenylenediamine and was found to be normal on two occasions. The patient's age, cytosome morphology and distribution and results of peroxidase assay add special interest to this case of generalized ceroidlipofuscinosis. However, none of these features, either singly or in combination, warrants creation of a distinct subtype within this group of disorders. Myeloperoxidase deficiency is probably just another phenotypical marker of some patients with generalized ceroidlipofuscinosis rather than the genetic defect of Batten disease.


Adipose tissue metabolism in essential fatty acid deficienty. Effects of prostaglandin e1, epinephrine, and ACTH.

In an effort to better define some of the metabolic changes that accompany essential fatty acid deficiency (EFAD), we studied glucose metabolism in adipose tissue of EFAD and normal mice under basal conditions and in the presence of prostaglandin E1 (PGE1), epinephrine, and ACTH1-18. Isolated fat cells were incubated in Krebs-Ringer bicarbonate medium containing glucose 1(-14C) or 6(-14C), and the incorporation of radioactive carbon into CO2, total fat, fatty acids, and glyceride-glycerol was determined. It was found that EFAD increased glucose uptake over controls which could be attributed to increased oxidation to CO2 and fatty acid synthesis. The contribution of the pentose cycle to glucose oxidation was 50-80% higher in EFAD adipocytes as compared to controls. ACTH1-18 (0.1 mug/ml) suppressed this by 18 and 30% in the control and EFAD groups, respectively, while epinephrine decreased pentose cycle activity by 83 and 55% in the two groups, respectively. PGE1 alone had no significant effect, but in combination with epinephrine it abolished the inhibitory action of the catecholamine in both groups. It is suggested that, although EFA serve as prostaglandin precursors, the effects of EFAD on the metabolism of fat cells cannot be reversed by PGE1, in vitro. However, these fat cells retain their responsiveness to the action of both lipolytic (ACTH and epinephrine) and antilipolytic (PGE1) agents.


Food poisoning--four unusual episodes.

Four unusual outbreaks of food poisoning occurring in the Dunedin Health District during the period 1971-1973 are described. These involved a contaminated cordial, a death associated with a Clostridium perfringens outbreak, salmonellosis and infectious hepatitis in persons eating uncooked shellfish and symptoms associated with the ingestion of a normally edible fish--the trumpeter.


Electron microscopic demonstration of hormone-producing metastatic carcinoma of the choroid from the bronchus.

Clinical, laboratory and pathological findings of a patient in bronchial carcinoma with choroidal metastasis were presented. X-ray examination of the chest suggested the tumor shadow in the posterior segmental bronchus of the right upper lobe of the lung (r-B2b), while funduscopy and fluorescein angiography revealed the presence of choroidal tumor. ACTH levels in tumor tissues at autopsy and in serum were measured and definitely demonstrated and elevated. Histopathologically, the primary lesion was r-B2b and diagnosed as a mucocellular type of adenocarcinoma. The choroidal lesion was metastatic carcinoma. Electron microscopic examination of the choroidal lesion reembedded for electron microscopy from celloidin-embedded materials for light microscopy could reveal the presence of characteristic cytoplasmic granules referred to as neurosecretory-type granules. It is extremely rare that a hormone-producing metastatic carcinoma of the choroid from the bronchus has been proved.


[Serological screening of streptococci. Comparison of 2 methods of slide agglutination, one with streptolysin alone, the other with several enzymes (Streptozymes)].

Using 100 sera randomly selected, the clinical characteristis of which were known, we compared two methods of rapid detection of streptococcal infections by slide agglutination. One was the classical latex test for detection of anti-streptolysin O, the other was the streptozyme test. The latter reagent detects the presence of 5 streptococcal antibodies, anti-streptolysin O, anti-streptokinase, anti-streptohyaluronidase, anti-desoxyribonuclease and anti-nicotinamide-adenine-dinucleotidase. It was found to be more sensitive than the latex test, for antistreptolysin O. Estimations of A.S.K. and A.S.H. confirmed also the greater specificity of the streptozyme test and showed that, thanks to the presence of supplementary enzymes, it may be positive earlier than the A.S.O. latex test. Finally, used as a semi-quantitative method, streptozyme is useful to follow up approximately in the laboratory, the course of streptococcal infections.


Infectious mononucleosis: histopathologic aspects.

The main histopathologic features of infectious mononucleosis are described. In the lymph nodes, the principal change is the appearance of numerous large pyroninophilic cells (immunoblasts), initially expanding the paracortical zone but later extending throughout the node. Similar, large lymphoid cells appear as infiltrates in many other organs and tissues. Cells morphologically similar to Sternberg-Reed cells may be found in the lymph nodes of patients with infectious mononucleosis and other conditions apart from Hodgkin's disease. The diagnostic importance of considering not only the Sternberg-Reed cells but their milieu is stressed. A possible relationship between infectious mononucleosis and lymphoreticular malignancy is suggested by a number of observations, but a definite etiologic link is yet to be established.


The ultrastructure of smooth muscle tumors with a consideration of the possible relationship of glomangiomas, hemangiopericytomas, and cardiac myxomas.

Tumors classified as being of smooth muscle origin by light microscopy were studied with the electron microscope. Their ultrastructure verified the diagnosis in all of the seven leiomyomas but in only eight of the twelve (66 percent) tumors that were finally classified as leiomyosarcoma. The discrepancy of the light microscopic and ultrastructural findings in these four sarcomas may be due to sampling problems likely to be encountered in poorly differentiated tumors or simply the failure of development of specific ultrastructural features in the face of a characteristic growth pattern at the light microscopic level. Among other tumors that have been considered to be of smooth muscle origin--hemangiopericytoma, glomangioma, and cardiac myxoma--only the glomangioma showed ultrastructure features identical to those of smooth muscle.


[Poly-epiphyseal dysplasia, probably autosomal recessive. Contribution of the ultrastructural study to the discovery of this autonomous form].

An ultrastructural study of growth cartilage permitted individualization of a particular form of polyepiphyseal dysplasia which differs clinically and radiologically only slightly from the dominant form. The main difference concerns the superior femoral epiphyses which are more flattened and spread out. Inclusions, probably of lysosomial origin and containing granulous or filamentous material, were observed. This aspect is different from that observed in the dominant form and consisting of swellings of the endoplasmic reticulum with a suggestion of a periodical structure. The mode of inheritance could not be firmly demonstrated. Some degree of consanguinity of the second patient's parents favours an autosomal recessive inheritance.


Angioscintiphotography with 99mTc in 310 cases of space-occupying kidney lesions.

Angioscintiphotography with 99mTc has been performed in 310 cases of space-occupying kidney lesions with the purpose of establishing the diagnostic value of the kidney perfusion. In the presence of a neoplasm, a more or less marked blood flow in the lesion generally appears as a hot area. This pattern is not observed in poor vascularized carcinomas or in Wilms' tumors. The percentage of poorly vascularized tumors is moderate and does not affect the value of the method. Cystic lesions appear usually to be cold. Large cysts exhibit no uptake; on the contrary, the degree of vascularization in the small cysts is more difficult to evaluate, as the normally supplied surrounding parenchyma overlaps the cold area caused by the cyst. In the evaluation of the angioscintiphotographic picture, we must take into account the concomitant hepatic or splenic vascularization, which may cause some doubts of interpretation because of projection interferences. The renal angioscintiphotography has an important rule in specifying the nature of a space-occupying kidney lesion and may be regarded as a useful screening test.


A precise chromatography system for specific technetium-99m radiopharmaceuticals.

New chromatographic procedures are needed to accurately determine the radiochemical purity of technetium-99m labeled radiopharmaceuticals. A chromatography system has been developed for technetium-99m diethylenetriaminepentacetic acid, technetium-99m diphosphonate, and technetium-99m pyrophosphate. The technique involves spotting the radiopharmaceuticals on instant thin layer chromatography-silica gel and developing with acetone (solvent from migrates approximately 12 cm from the origin), air drying, and redeveloping the strip in normal saline (solvent front migrates approximately 6 cm from the origin). The procedure is simple to perform, rapid, accurate, and clearly separates technetium-99m pertechnetate, the technetium-99m radiopharmaceutical, and hydrolyzed reduced technetium-99m. It can be applied in most nuclear medicine laboratories and has the potential to predict the quality of radionuclide images obtained.


[Concentration of 99mTc-tin-phosphate complexes in soft tissues].

The concentration of 99mTc-pyrophosphate was determined in the lower extremities of rabbits (normal, abacterial and bacterial affected soft tissues), in osteoarthritis of the hip joint (capsule and muscle) as well as in knee joint effusions. Compared with the 85Sr-concentration, reflecting the calcification capacity, concentrations of 99mTc-pyrophosphate in soft tissues were found to be lower 2 hours p.i., but were up to elevenfold higher 24 hours p.i. These findings should be due to a fixation of 99mTc-pyrophosphate in collagen containing tissues as in the soft tissue tumors (myosarcoma, synvialioma, breast cancer) presented. A mechanism of delayed equilibration could explain augmented uptake in lymph-edema, ascites and effusions in florid osteoarthritis of the knee joint. The possible dependence of 99mTc-pyrophosphate concentration in bone and soft tissue on collagenous contents is discussed.


Rat hepatoma cells nucleolar DNA. 2. Analysis of nucleolar DNA.

The analysis by CsCl density gradient of nucleolar DNA has revealed that the 1.700 g/cm3 main component can be subdivided in three subcomponents with buoyant densities of 1.707 g/cm3, 1.700 g/cm3, 1.690 g/cm3. The 1.707 g/cm3 and 1.690 g/cm3 components contain all the repetitive sequences which comprise 15 % of the total nucleolar DNA. The ribosomal cistrons are found in components having buoyant density between 1.707 g/cm3 and 1.725 g/gm3. Sodium-p-aminosalicylate-DNA interactions have revealed that only the 1.700 g/cm3 fraction has a destabilized secondary structure. The possible localization of these different fractions on peri and intranucleolar fractions is discussed.


[A cell-line with 27 chromosomes in a human acute leukemia (author's transl)].

Chromosomal analysis of the bone-marrow aspirate of a five years old girl suffering acute leukemia revealed a cell-line carrying 27 chromosomes. Banding by controlled heating denaturation showed that, in these cells, all chromosomes are haploid, except chromosomes: X, 10, 18, 21. This cell-line, not seen during remission, was found during relapse, in addition to another one with 54 chromosomes. The caryotype of this last clone corresponded to the duplication of the chromosome set found in the first cell-line. The authors discuss two problems: the possible correlations between the clinical evolution and the biological data; the problem raised by the survival and proliferation of such an hypodiploid cell-line.


Rat hepatoma cells nucleolar DNA. II. A possible model of nucleolar DNA organisation.

A model of nucleolar DNA organization has been established. Three clearly defined main components are found in ascites hepatoma cell nucleolar DNA by CsCl gradient analysis. A linear arrangement for nucleolar DNA and a model of DNA organization in the neighbourhood of a set of ribosomal genes, which may play a fundamental role in the elaboration of nucleolar chromatin tertiary structure, are presented.


Polynucleotides. XXXII. Further studies on the synthesis of oligonucleotides containing 8,2'-S-cycloadenosine.

A dinucleoside monophosphate, 8,2'-anhydro-8-mercapto-9-beta-D-arabinofuranosyladenine phosphoryl-(3'-5')-inosine (AspI) was synthesized by the condensation of protected 8-mercapto-adenosine 2',3'-cyclic phosphate and 2',3'-isopropylideneinosine with diphenylphosphorochloridate. 8-Mercaptoadenosine 2',3'-cyclic phosphate was polymerized by using tetraphenyl pyrophosphate as the condensing reagent. As oligonucleotides, thus obtained, contained some uncyclized 8-mercaptoadenosine residues and were cleaved at these sites with 0.3N KOH. As 5'-phosphate was synthesized and polymerized with DCC to give oligonucleotides with chain lengths 2 to 9.


Temperature dependence of strand separation of the DNA molecules containing integrated SV40 DNA in transformed cells.

It has previously been demonstrated that the DNA molecules containing a genetic marker from one region of a bacterial genome undergo complete strand separation at temperatures usually different from the molecules containing a genetic marker from another region of the genome. The experiments also showed that if a group of molecules undergo complete strand separation over a narrow temperature range, of the order of one to three degrees, it is highly likely that they all come from one region of the bacterial genome. The purpose of the work reported here was to establish appropriate procedures for doing a similar analysis of the DNA molecules containing the integrated SV40 DNA in transformed mouse cells. One result of interest is that in the 11A8 cell line about 40 per cent of the integrated SV40 DNA detectable by an RNA-DNA hybridization assay can be accounted for by a group of molecules which undergo complete strand separation within a 1.0 degree C interval.


The preparation of a bacterial collagenase containing negligible non-specific protease activity.

A three stage procedure for the purification of crude bacterial collagenase is described. The three stages were ion exchange chromatography on SP-Sephadex and DEAE-cellulose, followed by molecular sieve chromatography on Sephadex G-200. The end product was eluted from Sephadex G-200 as a single peak of absorbance at 280 nm, and a single zone of activity against gelatin. The active eluate was divided into two halves, designated fraction 1 and 2 collagenase. Their activities were greater than those of commercially available collagenases when assayed viscometrically against pepsin solubilized collagen from guinea-pig skins. The non-specific protease activities in both fractions were much less than in the commercially available purified collagenases, and fraction 1 collagenase liberated only 2.6% of a [3H]-tryptophan label from a substrate of 2 mg of labelled chick embryo proteins, after an 18 hour incubation. When polymeric collagen was incubated with fraction 1 collagenase, at a final enzyme : substrate ratio of 1:160, the collagen was digested, resulting in the loss of 99.8% hydroxyproline as dialysable material.


Transformation by polyoma virus alters expression of a cell mutation affecting cycle traverse.

A temperature-sensitive mutant of hamster BHK 21/13 cells, tsAF8, which at 39 degrees becomes arrested in the G1 (G0) phase of the cell cycle, is phenotypically altered with respect to temperature sensitivity after transformation with polyoma virus. Polyoma transformation does not produce reversion to a non-temperature-sensitive phenotype but causes increased entry into S and increased rate of cell death at the nonpermissive temperature, compared to untransformed tsAF8 cells. The increased frequency of cells synthesizing DNA is not accompanied by an increased frequency of mitosis, since most of the polyoma-transformed tsAF8 cells that synthesize DNA at the nonpermissive temperature do not divide. At the permissive temperature, polyoma-transformed tsAF8 cells, unlike tsAF8, also lose viability when exposed to other methods of arresting cells in G1. The most likely explanation for this phenomenon is that polyoma virus transformation interferes with the cellular response to this mutation as well as to other conditions that cause cell cycle arrest in G1.


Coupled in vitro transcription and translation of vesicular stomatitis virus messenger RNA.

The virion transcriptase (nucleosidetriphosphate: RNA nucleotidyltransferase, EC 2.7.7.6) of vesicular stomatitis virus was fully active when ribonucleoprotein cores from purified virions were added to cell-free protein synthesizing systems of eukaryotic origin. Synthesis of mRNA was linear for at least 3 hr and the newly synthesized viral mRNA was efficiently utilized for the synthesis of viral proteins N (nucleoprotein), NS, and M (matrix); small amounts of a putative G (glycoprotein protein precursor and several unidentified polypeptides were regularly synthesized. The ratio of the various newly synthesized viral proteins was identical after different periods of coupled mRNA and protein synthesis. Identical proteins were obtained when the cell-free protein synthesizing systems were programmed with purified VSV mRNA synthesized in vitro. No detectable L protein was synthesized, even though transcripts complementary to the complete viral genome were detectable in the mRNA preparation by hybridization.


Characterization of purified DNA-relaxing enzyme from human tissue culture cells.

Superhelical simian virus 40 DNA migrates more rapidly during electrophoresis in agarose gels than covalently closed DNA free of superhelical turns (relaxed DNA). The difference in electrophoretic mobility between superhelical and relaxed DNA was used to monitor the activity of a protein from human tissue culture cells which converts superhelical DNA into relaxed DNA. Purified DNA-relaxing protein removes both negative and positive superhelical turns and acts in a catalytic manner. The relaxation of DNA proceeds in a stepwise fashion and DNA intermediates with decreasing numbers of superhelical turns are seen during the course of the reaction.


Homology and relationship between the genomes of papovaviruses, BK virus and simian virus 40.

A number of hybridization techniques have been used to assess the homology between the genomes of BK virus (BKV) and simian virus 40 (SV40). A noncontiguous set of homologous sequences has been localized primarily within the late region of the SV40 genome, and these sequences presumably account for the cross-reaction between V-antigens of the two viruses. The reason for the relatively strong crossreaction between SV40 and BKV T-antigens is still unclear. The sequence homology and similarity in genomic organization suggest a close relationship between these papovaviruses.


RNAs of simian virus 40 in productively infected monkey cells: kinetics of formation and decay in enucleate cells.

We demonstrate here the usefulness of cytochalasin B enucleate cells for the study of the metabolism of cytoplasmic mRNA and for determining its half-life in animal cells. Simian virus 40 infected monkey cells in which the RNA had been labeled with [3H]uridine were enucleated, and the decay of the two prominent RNAs of simian virus 40, the 19S and 16S species, was measured by analysis on sucrose gradients. The results of these experiments, together with kinetic analysis of nuclear and cytoplasmic viral RNA, indicate a precursor-product relationship between the 19S and 16S cytoplasmic viral RNA species, which decay by first-order kinetics with a mean half-life of about 3 hr and 6 hr, respectively.


Interaction of f1 histone with superhelical DNA.

The superhelicity of double-stranded, closed circular SV40 DNA was altered by the addition of various amounts of ethidium bromide. The interaction of f1 histone with the series of molecules of various superhelicities was studied. The extent of interaction increases with increasing superhelicity regardless of whether it is of the positive or negative sense. The interaction of f1 histone with superhelical DNA is shown to be reversible.


Separation of "estrogen-induced" protein from phosphoprotein phosphatase activity of immature rat uterus.

Preparations of the "induced protein" which appears in the rat uterus within 40 min of estradiol administration have recently been reported to contain phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) activity. We found that these two proteins distribute differently on ammonium sulfate fractionation of uterine cytosol. Preparative cellulose acetate electrophoresis afforded complete (greater than 99.9%) separation of phosphoprotein phosphatase activity from the induced protein. The specific activity of phosphoprotein phosphatase in uterine cytosol was unchanged 1, 4, 12, or 24 hr after estradiol administration. These results are incompatible with the view that the induced protein mediates estrogen action by virtue of an inherent phosphoprotein phosphatase activity.


Association of mouse liver adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels with histocompatibility-2 genotype.

When the content of cyclic AMP (cAMP) was compared in livers of a series of congenic mouse strains differing at the H-2 locus, significant variation in concentration of cAMP per unit wet weight was found among strains, and also for animals of a given strain with increasing age. For a given age, from 8 to 22 weeks, cAMP levels in liver of H-2a and H-2b genotype animals were significantly higher than that in liver of H-2k type animals. This difference was seen whether the H-2 gene was on the genetic background of strain C57BL/10, C3H, or A. Levels of cAMP in livers of H-2d animals were between those of H-2a and H-2k animals.


Relationship of the first step in protein synthesis to ppGpp: formation of A(5')ppp(5')Gpp.

In the presence of purified Escherichia coli lysyl-tRNA synthetase [L-lysine:tRNALys ligase (AMP-forming) EC 6.1.1.6], L-lysine, and ATP, addition of the nucleotide ppGpp results in formation of a unique product-A(5')ppp(5') Gpp. The same compound is also formed very rapidly in a cell-free protein-synthesizing system when ppGpp is added. The possible significance of this reaction in the rapid turnover of ppGpp and as a more general mechanism by which an AMP residue is activated and introduced onto a 5'-diphosphorylated species, including the 5'-end of an RNA, is further discussed.


Solid tumor models for the assessment of different treatment modalities: I. Radiation-induced changes in growth rate characteristics of a solid tumor model.

A computer program has been developed to quantitatively evaluate changes in tumor growth rates of a solid tumor model (hepatoma 3924A) after a series of radiation doses from 375 R to 3750 R. The computer-derived growth curves are simulated from the volumes of the individual tumors rather than from the mean tumor volume at any specific time point after treatment. The ability to generate data from a family of tumor growth curves permits a more precise evaluation of therapeutic effects on tumors than can be obtained with conventional methods. The quantitative determination of equivalent amounts of radiation needed to produce comparable 5-fluorouracil-induced changes in tumor growth rate has been made. The ability to determine quantitatively radiotherapeutic and chemotherapy equivalents on these solid tumor models has direct implications in regard to our effort to improve the treatment of cancer. At present no specific solid tumor or groups of solid tumors have provided all of the necessary information for clinical utilization in therapeutic scheduling of different forms of cancer treatment. Since solid tumors comprise the majority of human cancer, one of the primary objectives of these studies has been the establishment of a solid tumor model that could serve both as a system for devising improved therapeutic scheduling and for a better understanding of solid tumors.


Follicle-stimulating hormone stimulates estradiol-17beta synthesis in cultured Sertoli cells.

Sertoli cells isolated from testes of 20-day-old rats and maintained in primary culture synthesized estradiol-17beta [1,3,5(10)-estratriene-3,17beta-diol] (measured by specific radioimmunoassay) when testosterone (17beta-hydroxy-4-androsten-3-one) 0.5 muM, was added to the culture medium. No detectable estradiol synthesis occurred when cells were incubated in medium containing pregnenolone (3beta-hydroxypregn-5-en-20-one), 0.5 muM, or containing no added steroid substrate. Follicle-stimulating hormone (FSH) (NIH-FSH-S10, 5 mug/ml) stimulated estradiol synthesis 12- to 80-fold when added to medium containing testosterone, but not when added to medium containing pregnenolone or no exogenous steroid substrate. A highly purified FSH preparation, with FSH potency 50 times that of the NIH-FSH, caused a similar stimulation at a concentration of 0.25 mug/ml of medium, whereas luteinizing hormone (NIH-LH-S18, 5 MUG/ML) Caused only marginal stimulation. Dibutyryl-adenosine 3':5' cyclic monophosphate, 0.1 mM, caused a 30-fold increase in estradiol synthesis by Sertoli cells cultured in medium containing testosterone. These studies provide direct demonstration of estradiol-17beta production by Seroli cells from normal animals, and offer evidence that the synthesis of this steroid is regulated at the level of the aromatizing enzyme system by FSH and adenosine 3':5' cyclic monophosphate.


Appearance of smaller mannosyl-glycopeptides on the surface of a human cell transformed by simian virus 40.

When fucosyl surface glycopeptides from growing normal human cells (WI 38) were compared with those derived from nongrowing cells the former were enriched in high-molecular-weight species. However, a line of human cells (WI 18Va) transformed by simian virus 40 appeared to have fucosyl-glycopeptides similar in size distribution to those from rapidly growing non-transformed cells (WI 38). I propose that the enrichment in high molecular weight species in these cells might be growth- rather than transformation-dependent. Using radioactive mannose to label surface glycopeptides, I observed that those derived from transformed cells (WI 18Va) were smaller than those from rapidly growing normal cells. Thus differences in size distribution may not be adequate criteria to evaluate the growth-dependent alterations in cell surface glycopeptides.


New histones found in mature mammalian testes.

Two new histones have been found in sexually mature testes of several mammals. The new histones have been identified as a new F1 (TF1) and F2b (TF2b) on the basis of their behavior upon chemical fractionation procedures and electrophoresis at several urea concentrations. The new testis-specific histones are absent in very immature animals and in somatic tissues. However, by day 20, in the rat, the histone pattern is that of the adult, displaying nearly a full complement of TF1 and TF2b. The new histone complement evidently is characteristic of prespermatid germ cells. The degree of evolutionary variations in these histones and in other basic sperm proteins, as detected by change in electrophoretic mobility, appears to be much greater than that seen in somatic histones.


Initiation of cell proliferation in cultured mouse fibroblasts by prostaglandin F2alpha.

Prostaglandin (PG) F2alpha added to quiescent Swiss mouse 3T3 cell cultures initiates DNA synthesis and cell proliferation in a small proportion of the cells. Insulin, which markedly potentiates the effect of PGF2alpha on the initiation of cell division when added with PGF2alpha, causes a simultaneous reduction in intracellular cyclic AMP and an increase in cyclic GMP concentrations similar to those observed after serum addition. Prostaglandins E1 and E2 are less effective than PGF2alpha in initiating DNA synthesis and this effect is only observed at higher concentrations. Therefore, some prostaglandins can act as extracellular factors to regulate cell proliferation.


Transmission of human leukaemia to nonhuman primates.

The experiments described show that inoculation of two monkey species, M. arctoides and P. hamadryas, with human leukaemic blood or its filtrates causes a viral disease with the characteristics of malignant lymphoma of mixed type. The disease was passed in subsequent passages. The virus was isolated and identified as an oncornavirus of C-type by its characteristic morphological appearance and buoyant density (1.16 g/cm3 in sucrose and 1.21 g/cm3 in caesium chloride), and by the presence of 60-70S RNA and RNA-dependent DNA polymerase. There is some evidence that it differs immunologically from other known oncornaviruses of mammals including primates. It is postulated that both horizontal and vertical transmission of this oncornavirus can occur.


Splenocyte plaque assay for the detection of murine leukemia virus.

A modified XC assay for murine leukemia virus (MuLV) employing splenocytes taken directly from the animal is described. This modification can be more than 1000 times more sensitive than XC plaque assays employing tissue extracts. This technique should lend itself readily to the quantitation of infectious MuLV in defined populations of lymphoid cells.


Transplatation resistance to adenovirus-induced hepatocellular carcinomas.

Two transplantable hepatic carcinomas of the hamster contained CELO virus-induced TSTA, confirming the etiological role of this avian adenovirus in the induction of hepatic tumors. Transplantation resistnace could not be induced with oncogenic adenoviruses of human, simian, or canine origin.


Concerning the subcellular distribution of 3beta-hydroxysteroid dehydrogenase/isomerase in the rat adrenal.

The distribution of 3beta-hydroxysteroid dehydrogenase/isomerase in the subcellular fractions of rat adrenal gland has been determined. Based on the total activity found, 55% was in the microsomal fraction, 10% in the heavy-mitochondrial fraction, 3% in the light-mitochondrial fraction and 26% in the fraction consisting of cell-debris plus nuclei. Ninety-five percent of the total activity was recovered in the fractions. Approximately half the activity in the heavy-mitochondrial fraction could be accounted for by microsomal contamination.


Antibody titers by mixed agglutination to varicella-zoster, herpes simplex and vaccinia viruses in patients with multiple sclerosis.

Antibody titers to varicella-zoster (V-Z), herpes simplex (HSV) and vaccinia viruses were determined in sera collected in Buffalo, NY, from patients with multiple sclerosis (MS), patients with other diseases, and normal individuals. The mixed agglutination test employing cell cultures infected with one of the above viruses as a source of antigen was used to determine antibody titers. The geometric mean titer (GMT) for V-Z in 59 MS cases was significantly higher than that observed in patients with other diseases and in normal individuals. The GMT for vaccinia was also higher in MS patients but the difference was not as great as for V-Z. No difference was observed in the titer of antibodies for HSV. Similar results were obtained for 51 MS patients compared to healthy controls matched for sex and age. Higher antibody titers for V-Z and HSV were observed in cerebrospinal fluids from MS cases than in those from non-MS CNS patients in Baltimore, MD. Antibodies to V-Z, HSV and vaccinia were detected in washing fluids from brain homogenates of MS cases.


Growth inhibitory and arginase activities in liver and hepatoma extracts.

The growth-inhibitory activity against H.Ep. No 2 cells observed in phosphate buffer extracts of rat liver appears to be due to the enzyme, arginase. This conclusion is based on the findings that (1) extracts of hepatomas containing lower levels of the enzyme also contain less inhibitory activity; (2) partial purification of the inhibitory factor results in a similar purification of the enzyme; (3) molecular weights of the enzyme and of the inhibitory factor are similar; and (4) various treatments alter the enzyme and inhibitory activities similarly.


Poly (adnenosine diphosphoribose) synthase activity of isolated nuclei of normal and leukemic leukocytes.

Poly(adenosine diphosphoribose) (ADPR) synthase activities of nuclei isolated from normal human and leukemic leukocytes were assayed by incubation with radioactive NAD+. The synthase activity of leukemic leukocyte nuclei was significantly higher than that of normal leukocyte nuclei. The average length of polymers formed by isolated leukemic nuclei under the prescribed experimental condition ranged from 3.1 to 5.3 ADPR residues per chain, while those produced by normal leukocytes nuclei was 1.7 and 2.6 residues per chain. Isolated leukemic and normal leukocyte nuclei were incubated with and without NAD+ and the ability to carry out DNA synthesis was measured. The endogenous DNA synthesis of NAD-treated and untreated nuclei was the same. This finding parallels the result obtained with Novikoff hepatoma cell nuclei and differs from the observation with rat liver or testis nuclei.


A clinical evaluation of a sodium fluoride dentifrice.

A double-blind study to determine the anticaries efficacy of a neutral pH dentifrice containing sodium fluoride and a high Beta-phase calcium pyrophosphate was conducted among elementary school children in Kansas City, Missouri. A sample of 567 children ages 8-13 were recruited and randomly assigned to test and control groups: the test group received a sodium fluoride  high Beta-phase calcium pyrophosphate dentifrice, and the control group received a calcium pyrophosphate dentifrice without the active ingredient. The sodium fluoride dentifrice contained fluoride at the level of 1000 ppm. Caried examinations were conducted at initiation, after 12 months, and again after 24 months at the study's termination. All examinations (clinical and radiographic) were performed by the same investigator. At 12 months the sodium fluoride dentifrice demonstrated a caries reduction of 24.1% (DMFS). At 24 months the reduction demonstrated was 30.1% (DMFS); this reduction is significant at alpha = 0.05.


Incubation as a form of psychotherapy in the care of patients in ancient and modern Greece.

Incubation or temple sleep in sanctuaries of Aesculapius, Amphiaraos, Trophonios, etc., for the care of patients was practised even in the older times of ancient Greece and may be viewed as a form of psychotherapy and especially as 'dream-psychotherapy'. In Greek antiquity, as it is known, dreams were considered as a way of communication between gods and men. Survival of the custom of incubation exists even in our times in modern Greece, but are disappearing slowly. An attempt is made to find an explanation, if any, of those miraculous cures in accordance with the scientific thought of today.


The use of corticosteroids in the treatment of acute asthma.

A study of 23 patients admitted to hospital with severe acute asthma is reported in which plasma cortisol level on admission was significantly correlated with the degree of acidaemia and pulse rate. Patients who had not previously received treatment with corticosteroids responded satisfactorily to repeated daily injections of tetracosactrin depot, the rate of improvement being comparable to that observed in other patients treated with intravenous hydrocortisone hemisuccinate. A prompt and sustained rise in plasma cortisol was also seen following tetracosactrin. The total daily dose of hydrocortisone required to achieve plasma cortisol levels above 100 mug/100 ml was less when given by continuous intravenous infusion compared with intermittent injections, and a regime of 3 mg/kg body weight every six hours by infusion appeared satisfactory. Most patients reported subjective improvement by about four hours after starting treatment but objective evidence did not appear until about six hours from the start. Measurements of FEV1 and FVC proved to be the most reliable indices of the beginning of improvement although pulse rate was the first index to show maximum improvement. Previous maintenance treatment with corticosteroids in patients with asthma did not appear materially to affect the plasma half-life of intravenous hydrocortisone (4 mgm/kg body weight) when compared with healthy subjects or other patients with asthma who had not previously been treated with corticosteroids.


Non-healing granuloma and the nervous system.

Three cases of non-healing granuloma with neurological complications are described. One case suffered from Stewart's form of the disease and two from Wegener's variety. The literature is extensively reviewed and the incidence and manner of neurological involvement in 374 cases is discussed. We suggest a classification to indicate four forms of nervous system involvement. First, granulomatous lesions of the central nervous system. Second, vasculitis of the central nervous system. Third, vasculitis of the peripheral nervous system and fourth, infection of the central nervous system. Of all cases 21 per cent had some form of neurological complication. Wegener's type showed more frequent neurological involvement that Stewart's, 26-5 and 12 per cent respectively. Infection of the central nervous system was limited to cases of the Stewart variety.


Radiologic approach to the pancreas. A decade of progress.

Radiologic diagnosis of the pancreas has undergone great progress in recent years and several valuable techniques are now available for examining the pancreas. Employed singly or in various combinations, as indicated by the individual patient's clinical and laboratory findings, they make possible an accurate diagnosis of pancreatic disease.


Inactive malignant endocrine tumors of the pancreas.

The angiographic pattern of four non-active endocrine tumors is reported. Three of the tumors were highly vascular and had a characteristic angiographic appearance as observed in a few case reports in the literature. One tumor was angiographically avascular with irregularly scattered calcifications. Similar calcifications in a malignant tumor of the pancreas causing the Zollinger-Ellison  syndrome are presented. Hypervascular tumor tissue was observed in the periphery of the calcification. The types of calcification and angiographic characteristics are of diagnostic importance in the differential diagnosis between endocrine tumors and other highly vascular tumors of the pancreas.


Phlebography of the pancreatic veins.

Transumbilical and percutaneous transhepatic catheterization is performed of pancreatic veins. The normal phlebographic anatomy is reported together with the findings in patients with carcinoma of the pancreas. Selective catheterization of pancreatic veins with hormone essay for tumor localization is performed in two patients with islet cell tumor of the pancreas. The authors suggest this to be a valuable method in the diagnosis of endocrine tumors of the pancreas.


Demonstration of growing casts of hepatocellular carcinoma in the portal vein by celiac angiography: The thread and streaks sign.

In 9 of 112 patients with hepatocellular carcinoma (HCC) examined by selective celiac and hepatic arteriography, an unusual finding, the "thread and streaks" sign, was observed. It began to appear shortly after the start of injection and was most clearly seen at 3.0-3.5 seconds. Histopathologic and radiographic studies of excised livers have demonstrated that these thin streaks correspond to the blood spaces and vessels which run longitudinally in and around a tumor cast growing in a large branch and trunk of the portal vein.


Selective carotid angiography in the diagnosis of fibrous histiocytoma. A case report.

Selective carotid angiography is of value in the diagnosis of an orbital fibrous histiocytoma, an uncommon tumor with a high local recurrence rate and frequent distant metastases. The angiogram shows the physical extent of the tumor and also suggests its general microscopic anatomy. Comparison is made with similar angiographic presentations seen in cerebellar hemangioblastomas, glomus tumors, meningiomas, and hemangiopericytomas.


Treatment of locally recurrent carcinoma of the nasopharynx.

Forty-two patients with recurrent nasopharyngeal carcinoma in the primary site and/or neck nodes were treated at the University of California, San Francisco, between 1940 and 1974. Sixty-nine per cent of the recurrences appeared within 3 years and 83% within 5 years after initial treatment. Retreatment included external radiotherapy and/or intercavitary radium or cobalt beads in the majority of cases. The actuarial survival rate was 41% at 5 years after first recurrence. Survival rates increased proportionally with increasing time between initial treatment and recurrence. There was no statistically significant difference in survival rates with respect to age, sex, race, or histology. Local soft-tissue or bone necrosis developed in 9 patients, but both conditions were tolerated well.


Effects of arachidonic acid on RNA metabolism in mammary gland explants of mice.

Arachidonic acid stimulated 3H-uridine incorporation into RNA in mammary gland explants of mice in a manner similar to that of prolactin. The onset of the effects of both prolactin and arachidonic acid occurred following a 2-4 hour lag period. Further, effects of maximally stimulatory concentrations of these agents were nonadditive. Finally, indomethacin abolished the effects of both prolactin and arachidonic acid. A tenable hypothesis to explain these data is that the action of prolactin in the mammary gland may be mediated by an increased availability of arachidonic acid followed by a subsequent enhanced rate of formation of the prostaglandins.


Effect of antithymocyte serum of murine cytomegalovirus emcephalitis in weanling mice.

The symptomatology and histopathological picture were studied in weanling mice inoculated intracerebrally with MCMV and treated with ATS. Increased mortality was observed and fatal encephalopathy developed. Lesions in the brain included areas of necrosis with neuronal degeneration without marked inflammatory cell response until the 21st day after infection. In contrast, the brain of mice inoculated with virus alone or with virus and treated with NSH showed perivascular cuffs and focal infiltration with little or no evidence of loss of neurons. These observations suggest that the degenerative lesions in the brain are directly related to virus multiplication and that the inflammatory response is beneficial rather than detrimental.


[Value and limitatious of scintigraphy of the sacro-iliac joints using technetium pyrophosphate].

Scintigraphic exploration of the sacroiliac (S.I.) joints by 99 m-technetium pyrophosphate is simple and free of all danger. The fixation of the isotope in the right sacroiliac (R.S.I.) and the "normal" limits of the fixation ratios R.S.I./L.R. and the lumbar rachis (L.R.), visible on the same film. A series of 28 controls having made it possible to calculate the "normal" limits of the fixation ratios R.S.I./L.R. and L.S.I./L.R., the isotopic fixation was measured in 25 patients with sacroiliac inflammation, 21 of whom were rheumatic, 3 infectious. It was shown that scintigraphy could yield useful information on the evolution of sacroiliac inflammation, making an early diagnosis possible, and also contributing to differentiation between rheumatic and infectious inflammation.


Trypsin activation of latent collagenase from several mammalian sources.

Latent collagenase, subject to activation by trypsin, was found in culture fluids of cells and tissues from several mammalian sources. The activation requires exposure to enzymatically active trypsin and cannot be achieved by inhibited or by heat-inactivated trypsin.


A new case of heavy mu-chain disease.

The tenth case of mu chain disease is described. The patient lives in Ivory Coast as in our previously reported case. He was not affected with chronic lymphocytic leukaemia and the main clinical feature was liver cirrhosis of unknown origin. The amount of abnormal protein in the serum was great enough to give an abnormal bond on the routine electrophoresis. The protein was devoid of light chains and was present in the form of disulfide linked polymers of incomplete mu chain. The molecular weight of the monomer was approximately 58,000. The  protein comprised the Fc fragment and a part of the Fd segment. Bence Jones protein was not found in the urine.


[Relationship between avascular necrosis and lipid and purine metabolisms].

The serum levels of uric acid, triglycerides, cholesterol, and lipoproteins were determined in 35 patients suffering from primary avascular necrosis. The results were compared with those of a control group and with those of patients suffering from gout. The frequency distribution of the results in the three groups was of the log-normal type and statistical calculations were made on logarithmic transformations of the serum values. In comparison with the control group, significant increases in the levels of triglycerides, cholesterol, pre-beta-lipoproteins, and uric acid were observed in patients presenting an avascular necrosis. No significant differences were observed between these patients and patients with gout in the levels of lipids and lipoproteins. Uricaemia was higher in the gout patients. Contrary to observations made on the gout patients, there was no correlation in the avascular necrosis patients between the uric acid level and the serum levels of lipids or lipoproteins. In an earlier study the authors put forward an hypothesis according to which the close relationship between the lipid and purine metabolisms in gout patients was due to a genetic linkage based on a common enzyme defect, which directly affected the two metabolisms. In avascular necrosis there is no common enzyme defect; the initial event is a disturbance in the lipid metabolism. The authors conclude with data which tend to show that the bone necrosis observed in patients using steroids or alcohol is not directly induced by these substances, but that once again the initial event is a disturbance in the lipid metabolism.


Antibiotic susceptibility of Clostridium species isolated from human infections.

In antibacterial susceptibility testing by the agar plate dilution method with 252 strains of Clostridium perfringens, 22 strains of C. novyi type A and 7 of C. novyi type B, with 21 strains of C. bifermentans, 12 strains of C. sordellii and 18 of C. sporogenes, the majority of the strains were inhibited by penicillin G, cephalothin, chloramphenicol, erythromycin, tinidazole and metronidazole. Resistance to lincomycin and clindamycin was noticed among strains of all clostridia species as well as to tetracycline and doxycycline among strains of C. perfringens.


[Use of new osteotropic isotopes in osteoarticular diseases, with special reference to phlogistic arthropathies].

By using an osteotropic complex (99mTc pyrophosphate) scintigraphic and scintiphotographic images were obtained with a view to studying the bone changes in inflammatory arthropathies. In rheumatoid arthritis there is an increase in radioactivity next to affected joints and this phenomenon which seems to contrast with the osteoporosis of the juxta-articular regions is confirmed, since the reduced density that is observed in the radiograms is a result of the lack of equilibrium between bone formation and bone resorption, but only if these two processes are proceeding actively. The "warm" zones, which are very close to the joints, are just as easy to see in relation to inflamed joints as they are in relation to joints in which the inflammation has ceased. Not all the inflamed joints accumulate the radioactive osteotropic complex. The bone changes can occur in cases of chronic inflammatory arthropathies only if the inflammation has been present for at least several months. The images obtained with the polyphosphate correspond to those that can be obtained with other calcium-mimetic and osteotropic isotopes (Sr etc.).


Regression line analysis for five antibiotics with strains of Clostridium species.

The susceptibility of 90 strains of clostridia to 5 antibacterials was determined by the agar plate dilution method and the disc diffusion test. The correlations between minimum inhibitory concentration and inhibition zone were quite acceptable for lincomycin, clindamycin, tetracycline and doxycycline to calculate regression lines by the least square method. The strains showed comparatively wide ranges of susceptibility. For erythromycin, no regression line could be calculated, since all the strains tested were susceptible over a narrow range of concentrations.


Cytarabine treatment of herpes simplex encephalitis in infants and small children. A report on three cases with a short review of the literature.

Three cytarabine-treated infants and children with herpes simplex encephalitis are presented. The effect of the treatment was excellent in 2 cases. One boy who had a CP syndrome died. It is assumed that the treatment with cytarabine should be started as early as possible with a dosage of 3 mg/kg body weight given intravenously once a day in a single injection for 5 days. No serious side effects have been noted. The advantage of cytarabine over idoxuridine, especially when treating small children and herpetic infections in the central nervous system, are emphasized.


Survey of a neonatal population for the prevalence of cytomegalovirus.

A neonatal population of 542 was tested for cytomegaloviruria. 293 were normally grown and full term, 172 normally grown but premature, and 77 were undergrown. Two normally grown term infants and one premature were excreting the virus (o.55%). Only one, a normally grown term infant, had signs of classical cytomegalic inclusion disease. None of the undergrown infants was infected.


[A rare dental abnormality: "the phantom tooth" or "odontodysplasia". Apropos of a case].

"Phantom tooth" or "odontodysplasia" is one of the most unusual and rare of dental abnormalities, being characterised: Clinically, by the topography of the lesions, the involvement of both sets of teeth and abnormalities in the size and form of the teeth which remain unrupted or only partially evolved. Radiologically, by transparency of the teeth to X-rays. Histologically, by disorganisation of the dental structures and a highly characteristic appearance of the enamel and, in particular, dentine. On the basis of one case, the authors review in detail each aspect of these characteristics, paying special attention to histology and the information obtained using the sweep electron microscope.


Prolonged survival of non-multiplying Staphylococcus aureus cells undergoing autolysis in the presence of certain inhibitors of cell wall synthesis.

Certain antibiotic compounds including penicillin, cloxacillin and 6-APA caused a prolonged survival of Staph. aureus cells undergoing autolysis in physiologic saline. The retardation of the death rate was dependent upon the type of compound and its concentration. The results suggest that the compounds inhibit the autolytic function of the bacteria.


Bronchial cancer - a clinical and pathological study. I. Histopathology and metastases.

Among 16,394 necropsies during the 12-year period, 1958-1969 (representing about 60% of all persons who died in Malmö during this period, 747 cases of bronchial cancer were found in 744 individuals. There were considerable differences in frequency of different histologic types with regard to sex. Two main classes have therefore been distinguished: Group I, comprising squamous epithelial cancer and anaplastic cancer (including oat-cell cancer), which was predominant among men; and Group II, comprising adenocarcinoma, bronchiolar carcinoma, carcinoid and bronchial gland tumour, which was of more or less equal frequency in both sexes. Compared with other malignant tumours, bronchial carcinoma had a strong tendency to metastasise to the adrenals, brain, kidneys and skeleton. Bronchial cancer did not differ from other tumours with regard to lymphogenous spread but had a stronger tendency to spread via the blood stream. Squamous epithelial cancer showed the strongest tendency to remain confined to the thoracic cavity.


Bronchial cancer - a clinical and pathological study. II. Frequency according to age and sex during a 12-year period.

A necropsy series of bronchial cancer combined with a retrospective clinical study comprising 747 cases of bronchial cancer from a defined population is described. A significant successive increase in the frequency of bronchial cancer during the 12-year period 1958-1969 was found. The increase during three successive 3-year periods will be as much as 45, 86 and 146%, respectively, if the 1958-1960 frequency is set to 100%. In contrast to many other investigations this increase was found in both women and men (the relative increase was exactly the same in both sexes) and for both Group I and Group II tumours. The ratios between men and women and between Group I and Group II tumours in the present material were thus constant throughout the investigation. This may be explained by the assumption that the female population today has smoked cigarettes for a sufficiently long period to stimulate the development of bronchial cancer and that there seems also to be a correlation between Group II tumours and cigarette smoking.


[Hypolipidemias].

Hypolipidemias can be divided in primary, familial and hereditary forms and symptomatic forms which may accompany other diseases. The primary hypolipidemias (abetalipoproteinemia, hypobetalipoproteinemia and analphalipoproteinemia) are very rare. Severe hypolipidemia can be found in some peoples (e.g. the Masai). This article is chiefly devoted to secondary hypolipidemias such as those associated with malabsorption, malnutrition and maldigestion including protein-losing gastroenteropathy, with liver diseases, endocrine diseases (hyperthyroidism, hirsutism) and anemia. Finally, the hypolipidemias secondary to the formation of autoantibodies against HDL and LDL in M-gradient, carcinoma and rheumatoid arthritis are briefly reviewed.


Enhancement of mouse cytomegalovirus infection during host-versus-graft reaction.

C3H/He mice chronically infected with murine cytomegalovirus were given skin allografts from histoincompatible BALB/c donors. A significant increase in cytomegalovirus titers occurred within 3 days after placement of the graft in the spleens and kidneys of the allograft recipients as compared with control animals. No significant changes in virus titers were detected in the salivary gland, lung, liver, or blood of allograft recipients. These results indicate that the host-versus-graft reaction alone can enhance murine cytomegalovirus in a chronically infected host and may help explain the high incidence of cytomegalovirus infection seen after renal and other allograft transplantation in man.


Increased urinary excretion of cyclic guanosine monophosphate in rats bearing Morris hepatoma 3924A.

Urinary excretion of cyclic guanosine monophosphate (GMP) increased in rats bearing Morris hepatoma 3924A, and a correlation coefficient of .842 was observed comparing nucleotide excretion and tumor size. Irradiation of tumor or 5-fluorouracil administration delayed the increases in urinary cyclic GMP and tumor size. Surgical removal of tumors resulted in a rapid decline in cyclic GMP excretion to baseline levels. Cyclic adenosine monophosphate excretion was not altered by implantation, irradiation, or excision of tumor.


Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance.

Six patients with a unique form of diabetes associated with extreme insulin resistance have markedly reduced insulin binding to specific receptors on their circulating monocytes. When normal insulin receptors were exposed to serum or immunoglobulin fractions from three of these patients in vitro the specific binding defect was reproduced.


Magnetotactic bacteria.

Bacteria with motility directed by the local geomagnetic field have been observed in marine sediments. These magnetotactic microorganisms possess flagella and contain novel structured particles, rich in iron, within intracytoplasmic membrane vesicles. Conceivably these particles impart to cells a magnetic moment. This could explain the observed migration of these organisms in fields as weak as 0.5 gauss.


Heteropolypeptides from poly-alpha-cyanoglycine and hydrogen cyanide: a model for the origin of proteins.

Poly-alpha-cyanoglycine, a homopolymer synthesized from the N-carboxyanhydride of alpha-cyanoglycine, is converted by cumulative reaction of hydrogen cyanide to heteropolypeptides that can be hydrolyzed to protein amino acids, including glycine, alanine, valine, aspartic acid, and glutamic acid. These results are consistent with the hypothesis that the original heteropolypeptides on the earth arose spontaneously from hydrogen cyanide and water without the intervening formation of alpha-amino acids.


Thermal transitions in human plasma low density lipoproteins.

Thermal analysis of human plasma low density lipoproteins reveals a broad reversible transition encompassing body temperature. The calorimetric and x-ray scattering data identify this transition as a cooperation, liquid-crystalline to liquid phase change involving the cholesterol esters in the lipoprotein. This behavior requires the presence of a region rich in cholesterol ester within the lipoprotein.


Electron microscopy of albumin synthesis.

Albumin molecules appeared to be synthesized in the light hepatocytes of rats by bound polysomers on rough and endoplasmic reticulum and the nuclear envelope. The molecules were discharged directly into the cytosol, then to the external cellular spaces. This conclusion failed to support the current theory from biochemical studies that albumin is synthesized by bound ribosomes, discharged into the cisternae of rough endoplasmic reticulum, and transported to the smooth endoplasmic reticulum and then to the Golgi apparatus. In addition to the liver, positive syntheic activities were observed in the aorta, kidney, and hepatoma cells of rat. Earlier investigators have reported that only liver cells can synthesize albumin.


Visually evoked magnetic fields of the human brain.

Magnetic field variations from the human brain produced by visual stimulation have been observed in a normal laboratory setting with a superconducting quantum interference device and no magnetic shielding of the subject. Previously unknown temporal and spatial features of the field near the scalp are reported.


Malignant fibrous histiocytoma.

Two patients are presented who had malignant fibrous histiocytomas of the skin and soft tissue. These tumors characteristically consist of a solitary mass, 0.5 cm to 12.0 cm, which has skin fixation, is circumscribed and firm. Microscopically, there is a pattern of histiocytes and bizarre histiocytic giant cells intermingled in a fibrous stroma with fibroblasts arranged in a whirling pattern. The lesion is treated with wide excision and skin grafting. Local recurrence is common. Metastasis is less common, but with metastasis the prognosis is poor.


Arbovirus infections in reptiles: studies on the presence of Japanese encephalitis virus antibody in the plasma of the turtle, Trionyx sinensis.

This study was undertaken to examine further the natural infection of poikilothermic animals e.g. turtles, to Japanese encephalitis (JE) virus. Plasma samples from 75 soft-shelled fresh water turtles (Trionyx sinensis Wiegman) from China were examined in virus neutralization (VN) and hemagglutination inhibition (HAI) tests for the presence of specific antibody. The total incidence of antibody detected by either test to a titer of 10 or greater was 89% while 77% and 60% were positive by VN and HAI tests, respectively. Forty-one per cent were jointly positive by both tests. Mean HAI and VN titers were similar and showed no obvious differences between spring/summer and autumn/winter seasons. The HAI reactivity was associated with a 7S component for both seasons. The significance of this inhibition in the serology of poikilothermic hosts and the possible behaviour of T. sinensis in the natural history of JE virus is briefly considered.


[Spontaneous pneumomediastinum].

Spontaneous pneumomediastinum is a relatively rare disease, the clinical signs of which may be misleading, and the physiopathology is still unknown. The authors report 7 cases collected over a period of 3 years and note the etiology, the clinical findings and the X-ray findings. The disease often affectsyoung sybjects, without any sex predominance. The initial symptom is thoracic pain and is often accompanied by dispnea. Subcutaneous emphysema only appears secondarily and may be mild. The association with pneumothorax is not rare. Among the etiological circumstances, pneumomediastinum often occurs after an effort or a respiratory infection with dyspnea. The diagnosis depends on the discovery of subcutaneous emphysema and on radiological signs in A.P. and lateral chest views. Treatment should be as conservative as possible in the usual benign forms. It should be limited to bed rest, analgesics and sedatives. In severe cases, supra-sternal drainage permits decompression of the mediastinum. The physiopathological mechanisms are discussed, but the usually accepted theory is rupture of an alveolus into the pulmonary interstitial tissue. The pressure gradient necessary for this rupture may be due to variations in alveolar or vascular pressure.


[Information obtained by liver biopsy in 100 tuberculous patients].

The results of liver biopsy in 100 patients with tuberculosis are reported. In 8 patients, biopsy only occurred secondarily, during liver disease which appeared during antituberculous treatment. In five cases, the association of rifamycin and isoniazid was probably responsible and the mild histological signs noted suggested a favourable course after stopping one of the drugs or simply reducing the dose. The 3 other patients had virus hepatitis and biopsy was of prognostic interest by revealing the onset of post-hepatic cirrhosis. In 92 cases, liver biopsy was carried out before treatment. In 34 cases the liver was normal, in 38 patients there were hisotlogical changes which did not suggest tuberculosis but, probably, alcoholism. These were : steatosis, in 21 cases, cirrhosis in 8 cases, a mixture of steatosis and cirrhosis in 4 cases, and acute alcoholic hepatitis in 5 cases. Finally, in 20 cases, biopsy revealed an appearance of granulomatous hepatitis. Although this lesion is significant in the development of the disease, it is not characteristic of tuberculosis unless there is caseous necrosis, as in 2 cases, and unless culture of the biopsy material is positive, as in one case out of 9, i.e. the diagnostic interest of liver biopsy is not very great compared with prognostic interest. By determining the anatomical condition of the liver, often not obvious when simple liver function tests are carried out, it permits one to forsee to some extent the tolerance of the liver to antituberculous treatment, especially in alcoholics.


[Achillean reflexogram : its measurement and its correlations with various clinical and biological factors in 2 working male populations].

The achillean reflexogram has been recorded according to Gilson's photo-electric technique among two male populations during routine cardio-vascular screening. The first population concerns 706 men aged 21 to 55 and the second one 4 437 subjects aged 46 to 52. The frequency of bilateral areflexy increases with age (from 3% before 30 to 6% after 40); it is significantly associated with the presence of angina pectoris. However, no relation is observed with diabetes or clinical suspicion of myocardial infarction. Whereas fat body mass is positively associated with the reflex duration the latter is reduced with heart rate, systolic blooc pressure and number of blood erythrocytes and leucocytes increased. These results and the interest of systematic reflexogram recording during health check up are discussed.


Intracellular enzyme liberation in primate spinal cord injury.

Intracellular lysosomal and nonlysosomal enzymes, as well as tissue edema, were measured in spinal cords of monkeys up to 20 days following a 300 gm-cm open injury. Although edema was maximal between six hours and 11 days, enzyme elevation was delayed. Lysosomal enzyme acid cathepsin increased beginning at five days and the beta-glucuronidase and beta-glycerophosphatase increase began at 11 days. Nonlysosomal enzymes were either not elevated or showed a slight rise. These data suggest that edema, one of the secondary damaging factors in spinal injury, is not a result of release of these intracellular enzymes. Also it appears that intracellular enzymes do not participate in early secondary damaging processes in severe spinal injury.


Organization of peripheral and central pain pathways.

The organizational features of the somatosensory system that may be significant to the perception of noxious stimuli are reviewed, with emphasis on the integration that likely occurs among both ascending and descending pathways.


Clinical experience with the intravenous infusion of iodinated contrast material as an adjunct to computed tomography.

The intravenous infusion of iodinated contrast material is an important adjunct to computed tomography with a wide variety of lesions. Some arteriovenous malformations, metastatic lesions and tumors of the sella turcica and cerebellopontine angle which are undetectable by conventional computed tomography may be visualized by this method. Certain other metastatic lesions, primary tumors, abscesses and infarcts which are detectable in the preinfusion tomogram become better defined following infusion. The indications for this examination and the procedures involved are discussed.


Biological behavior of the primitive neuroectodermal tumors: significant supratentorial childhood gliomas.

Supratentorial gliomas in the pediatric age group at the University of Kentucky Medical Center accounted for 20% of all childhood brain tumors. Seventeen of the 20 children with these tumors, regardless of histologic type, mode of therapy, or other parameters died within five years after tissue diagnosis, and most were dead within two years. Unlike the astrocytic gliomas, the poorly differentiated primitive neuroectodermal tumors tended to spread diffusely throughout the central nervous system and accounted for 35% of the supratentorial gliomas in children at our institution. Results of this study suggest that therapy for the primitive neuroectodermal tumor, unlike other childhood supratentorial gliomas, should be considered for the entire neuraxis.


Effect of total hepatectomy on selected cerebral substrates and enzymes of the glycolytic pathways and Krebs cycle.

Posthepatectomy coma was produced in 13 dogs and the cerebrums were biopsied for analysis of concentrations of glucose, glucose-6-phosphate, dihydroxyacetone-phosphate, phosphoenolpyruvate, pyruvate, lactate, citrate, alpha-ketogulutarate, fumarate, malate, oxaloacetate, adenosinetriphosphate, ammonia, and glutamine as well as for activities of glucokinase, phosphofructokinase, pyruvate kinase, isocitrate dehydrogenase, glutamate dehydrogenase, malate dehydrogenase, and malic enzyme. There were no differences from normal in the brain glycolytic substrate concentrations. Four of the Krebs cycle substrates were significantly reduced, but not differently than in dogs sedated for 24 hours. The glycolytic pathway, Krebs cycle, and related enzyme activities were not significantly altered. Cerebral adenosine triphosphate concentration was unchanged but the concentrations of ammonia and glutamine increased threefold.


Bronchodilator drug efficacy via cyclic AMP.

Cyclic adenosine 3', 5'-monophosphosphate (cyclic AMP) as measured by radioimmunoassay is found in diced rat lung in an amount approximating one picomole per milligram of wet weight lung tissue. Incubation of rat lung with adrenaline, a beta adrenergic agent, produced a rapid increase in cyclic AMP, 100% increase at 15 seconds and 340% at 2 minutes. Isoprenaline was more stimulatory than adrenaline; noradrenaline was less stimulatory, and ephedrine produced a negligible effect. The methylxanthines, caffeine and theophylline, produced an increase in cyclic AMP concentration. Of these, caffeine was more potent, and synergism with adrenaline was demonstrated. The beta adrenergic blocking agent, propranolol, completely inhibited the expected rise in cyclic AMP secondary to adrenaline stimulation. In contrast, the alpha blocker, phentolamine, produced no effect. This animal model offers evidence that adrenergic agents and methylxanthines act to increase cyclic AMP in lung tissue. It is likely that many of the beneficial effects of these drugs in pulmonary patients occur through similar changes and modulation of the cyclic AMP system.


A review of routine tests for respiratory viruses in hospital inpatients.

During the period June 1967 to May 1972, viral tests were performed upon 1195 inpatients aged 12 and over in the Brompton Hospital. The overall diagnostic rate was 21-5%, comparing 9-3% by isolation and 14-9% by complement fixation (6-5% by four-fold rises in titre in paired sera, 8-4% by titres larger than or equal to 160 in single sera). Only 42% of all patients had an acute respiratory illness within one week prior to admission, which seriously curtailed the chances of isolating viruses and of obtaining early serological specimens. The value of complement fixation tests on single specimens in the clinical management of patients is discussed. The profound effect of infections by influenza A on respiratory morbidity and hospital admission is stressed.


Autoantibodies in patients with bronchial carcinoma.

No overall increase in the incidence of antinuclear, smooth muscle or reticulin antibodies was observed in a group of 105 patients with bronchial carcinoma of various classified histological types. Smooth muscle antibody was, however, demonstrated in 27% of patients with undifferentiated carcinoma compared to 5% of controls (P less than 0-05). A highly significant increase in antinuclear antibodies in patients with adenocarcinoma was found (31% compared with 5% of controls--P less than 0-01). There as no apparent correlation between the presence of these antibodies and age, sex or other clinical features studied. A detailed study of the reproducibility of the antibody results, studied by indirect immunofluorescence in patients with bronchial carcinoma, is reported.


Tetracosactrin for the management of asthmatic patients after long-term corticosteroids.

Thirty-five of 41 asthmatic patients, who had been taking oral corticosteroids regularly for between one and 12 years, recovered their adrenal function after courses of depot tetracosactrin, even those with apparently complete adrenal suppression. They all showed benefit by transfer to depot tetracosactrin, though steroid withdrawal symptoms could be troublesome. Skin pigmentation in three, and two severe reactions to tetracosactrin were encountered. We believe that it is advisable to give depot tetracosactrin when converting severe asthmatics to the use of beclomethasone dipropionate aerosols who have previously been treated by long-term steroids with consequent adrenal suppression.


The HL-A and ABO antigens in trophoblastic disease.

No statistically significant deviations in phenotype frequencies of the 25 HL-A antigens or the ABO antigens were seen when 111 Caucasian patients with trophoblastic disease were compared with 1,259 healthy Caucasian controls. However, an increasein the incidence of HL-A11 was found in 39 patients who currently had the disease, but not in 72 who had recovered from the disease. Further, an increase in the frequency of W18 was observed among 18 patients who currently had 'invasive' disease (choriocarcinoma or invasive mole), but not in 44 who had recovered from such disease. If valid for larger patient population, these increases may suggest association of HL-A11 and W18 with the 'morbidity' of the trophoblastic disease. No increase in histocompatibility was seen in 45 patient-couples over 67 control-couples in terms of decrease in the number of male spouse's HL-A incompatibilities, and no significant difference was seen in the distribution of pregnancies in the two groups. No significant difference was observed in the incidence of different male-female combinations of ABO blood groups between 95 patient-couples and an equal number of control-couples. Lymphocytotoxic antibodies were found in 64 patients (158 sera) or 36% of the 178 patients (413 sera) examined. HL-A specific antibodies were found in 30 or 17% patients (39 sera). Of these 30, 24 patients had molar pregnancies and six had choriocarcinoma. Whether these antibodies have a role in the destruction of neoplastic tissue remains to be determined.


Fine structure of the compound eye of Porcellio scaber in light and dark adaption.

The compound eyes of the terrestrial isopod Porcellio scaber comprises about 20 ommatidia. The dioptric apparatus of each ommatidia includes a biconvex corneal lens and a spherical crystalline cone that is secreted by two cone cells. The closed rhabdom is formed by the microvillar extensions of seven pigmented retinula cells and one apical eccentric cell. All retinular axons exit the eye in one bundle. During dark-adaption pigment granules in the retinula cells rapidly withdrew from around the rhabdom and the cell periphery, and migrated basally. Rhabdoms thickened because of movement of the microvilli, and mitochondria moved medially and basally. During light adaption these processes were reversed. Multivesicular bodies became less numerous and rough endoplasmic reticulum and ribosomes proliferated during the initial stages of light adaption.


Secretory end-feet, extracerebral cells, and cerebral sense organs in certain limicole oligochaete annelids.

Secretory end-feet (or SEF) systems are present in Limnodrilus and Stylodrilus but are less highly organized than those of polychaetes. SEF contain secretory vesicles and abundant mitochondria. Typical neurosecretory terminals are not found within the brain although "neurosecretory" perikarya are present in all four species studied. In Limnodrilus, Stylodrilus and Enchytraeus extracerebral cells, of probable neurosecretory function, are invested by the pericapsular epithelium. Characteristically such cells bear several cilia. In these species and in Stylaria a pair of sensory cell groups is located anteriorly within the brain. These cells are ciliated but lack associated supporting cells.


Alveolar type II cells: studies on the mode of release of lamellar bodies.

There is increasing evidence that type II alveolar cells are capable of synthesizing surface active material like that obtained from the airways. However a number of problems remain to be solved before it can be stated conclusively that type II cells synthesize the surface active material of the terminal airspace. Among these problems is that of secretion. A number of previous studies have given evidence of the release of lamellar bodies by merocrine secretion. In this study morphologic evidence is presented which supports the view that secretion of lamellar bodies is accomplished by exocytosis. At the apical surface of type II cells, sites can be found where the limiting membrane of the lamellar body is clearly fused with the type II cell plasma membrane and an open channel exists between the contents of the lamellar body and the alveolar space. At these sites the lamellar contents extrude into the airspace with consequent loss of the highly compact organization of intracellular lamellar bodies. The intactness and continuity of the membranes can be traced for the full extent of the exocytosis site. Freeze-etch replicas of the membranes of type II cells show depressions which may represent the sites of discharged lamellae. In addition, tongue-like folds are seen which could be explained as the extensions of cytoplasm which surround the releasing lamellar body and which may flap over the exocytosis pit after discharge. Micrographs of the alveolar space show disorganized lamellar whorls which appear to be unravelling to produce tubular myelin. In view of the unusually large size and lipid composition of lamellar bodies, a mechanism involving hydration of mucopolysaccharide contents as an aid to expulsion of lamellar contents is suggested.


Diagnostic value of intravenous glucagon test in insulinoma.

The intravenous glucagon test was performed in 11 patients with insulinoma and the diagnostic significance of the test was studied in comparison with the glucose test, the tolbutamide test and the arginine test. The curves of plasma insulin following the intravenous administration of glucagon were markedly different and strange in those patients with insulinoma compared with the normal controls. The maximal levels of plasma insulin ranged from 85 to 400 muU/ml, exceeding the normal range in 10 out of 11 patients, or 91%. Increased levels in the maximal plasma insulin were observed in 63%, 100% and 56% through the glucose test, the tolbutamide test and the arginine test, respectively. The distribution of the insulin areas, calculated from the insulin curves during these tests, was shown to be similar to that of the maximal levels of plasma insulin. There was no significant correlations between the maximal levels of plasma insulin in the glucagon test and the glucose test, the tolbutamide test or the arginine test. The present experiment demonstrated that the intravenous glucagon test, next to the tolbutamide test, caused a large increase in plasma insulin, and therefore, that this test is one of the most useful tools among the provocation tests, for the diagnosis of insulinoma.


Direct effects of cyclic AMP and dibutyryl cyclic AMP on renal blood flow.

The direct effects of adenosine 3',5'-cyclic monophosphate (cAMP) and dibutyryl adenosine 3',5'-cyclic monophosphate (D-cAMP) on renal blood flow were studied in dogs under renal perfusion with constant pressure. Cyclic AMP caused a marked phasic decrease in renal blood flow in doses more than 1 mg, while D-cAMP produced a slight increase in that in doses more than 10 mg. The vasoconstrictive effect of cAMP was not blocked by the pretreatment with phenoxybenzamine, but was markedly depressed during the infusion of aminophylline. On the other hand, the vasodilative effect of D-cAMP was not affected either by the pretreatment with propranolol or during the infusion of aminophylline. These findings indicate that cAMP and D-cAMP have an opposite direct effect on the renal artery, independently of the adrenergic receptors. However, there may be a possibility that cAMP produces its vasoconstrictive effect on the renal artery partly through the action of its metabolites.


[Demonstration of skeletal metastases using the bone marrow biopsy and the radiographic skeletal survey within the scope of pretherapeutic diagnosis in bronchial carcinoma].

In the course of pretherapeutic diagnostics of bronchogenic carcinoma, bone marrow biopsy revealed in ten out of 116 patients (9%) and radiographic skeletal survey in 16 out of 62 patients (26%) metastases to the skeleton. The two methods are complementary with reference to anaplastic and oat-cell carcinomas. On account of our experiences, we never fail to control the skeleton before the beginning of a local curative therapy in bronchial carcinoma.


The effect of dianabol on the postirradiation disturbances of kininogenesis in rats.

The effect of Dianabol on the irradiation-induced disturbances in kininogenesis in rats was studied. It was found that Dianabol inhibits the postradiation increase of the kininforming activity in tissues of rats and decreases the level of kinins in irradiated animals. A probable role of these properties of Dianabol in its radioprotective activity is discussed.


Evidence for two cell populations involved in the rejection of a xenograft in mice.

Rejection of a xenograft by BALB/c mice results in a highly potent immune peritoneal cell population. By using two in vitro assays in parallel, it has been possible to show that there are at least two active cell types. The first assay detects the detachment of target cells from plastic, which is referred to as direct cytotoxicity. The second reflects the inhibition of incorporation of a deoxyribonucleic acid precursor, 125I-iododeoxyuridine, into target cells, which could occur either as a result of direct cytotoxicity or as a consequence of growth inhibition (cytostasis). With a rabbit antimouse brain serum which is cytotoxic for thymus-derived T cells, it has been shown that direct cytotoxicity requires T cells, whereas the cytostatic response can be largely independent of T cell function during the assay.


[Ultrastructure of the nuclear apparatus of the infusorian Loxodes magnus. I. The macronuclei, macronuclear anlagen and the interphasic micronuclei].

The nuclear apparatus of Loxodes magnus Stokes (Holotricha) consists of numerous macronuclei which belong to the diploid type and never divide, and of numerous micronuclei. No nuclear groups exist; individual nuclei often lie in cytoplasmic islets surrounded by large lacunae of the smooth endoplasmic reticulum. Interphasic micronuclei have two-membraned envelopes with numerous pores, usually lined at the cytoplasmic side with a layer of vacuoles, channels, or flattened vesicles of the smooth endoplasmic reticulum. The chromatin of the micronuclei consists of anastomosing threads, 0.1--0.2 mum wide, between which several nucleolus-like bodies of microfibrillar structure occur. Adult macronuclei have a similar nuclear envelope and a similar system of vacuoles, channels, and flattened agranular cisternae outside it. The macronucleus contains a single large composite nucleolus with 3 or 4 fibrillar cores inside the common granular cortex. The fibrillar cores are pierced by channels containing nucleolar organizers in the form of strands of condensed chromatin. The peripheral zone of the macronucleus is filled with decondensed chromatin fibrils and contains a number of small chromocenters and several aggregates of RNP granules. No protein inclusions (spheres) have been observed in Loxodes macronuclei. The macronuclear anlagen, developing in the cycle of every cell division, show progressive decondensation of the chromosomes and formation of several nucleoli, each with its own organizer. Later on, the nucleoli fuse into a single nucleolus. The small chromocentres are the last to form.


[Some characteristics of the process of forming autophagocytic vacuoles in the hepatocytes of regenerating rat liver].

This work deals with the previously described process of cellular autophagocytosis in regenerating rat liver. The experimental data obtained indicate that the early appearance of acid phosphatase positive cytoplasmic vacuoles (with diameter more than 2 mu) occur only in a certain portion of the parenchymal cell population (nearly 30% of the total number of hepatocytes) and mainly in the central area of the hepatic lobule. It may be concluded that the observed reaction of the cell vacuolar apparatus concerns hepatocytes that undergo the entry into the mitotic cycle much later than does the main part (ca 60%) of cell population.


[Structure of Candida tropicalis K-41 thermotolerant yeasts at various growing temperatures on a mineral medium with hydrocarbons].

In the C. tropicalis K-41 cells fixed by glutaraldehyde and osmium most membranes consisted of two electron-transparent and one electron-dense layer. Morphologo-structural peculiarities of the cell fraction grown at 39 degrees testify to a certain disconnection of energetic and constructive metabolism, inhibition of synthetic processes. Cell division was more active at 29 degrees.