[Corrected transposition of the great arteries without associated abnormalities]. We studied 5 cases of corrected tansposition of big arteries without associated defects. Four of them showed situs solitus with apex to the left, and the fifth one showed dextroversion. In four of the cases the second sound was the only one, strong and to the left of the precordium; in four we found mild sistolic murmur in the third left intercostal space. In all of them, XR plates showed the largest liver lobe to the left, apex to the left in four and to the right in one, being possible to see the ascending aorta to the left in four cases. A patient with complete auriculoventricular block showed cardiomegaly and excavated middle arch. Three of them presented sinusal rithm, one had auriculoventricular block of variable degree and the last had complete auriculoventricular block. In four cases the AQRS showed a deviation to the left, and the other one to the right. In the foreground of the first septal vector was going from right to left. The analysis of the unipolar and thoracic morphologies had alterations in the intraventricular conduction which suggested a right branch block in derivations exploring the ventricle located to the left and potential QS in the right pre-cordials. We found a pattern of sistolic overload of the sistemic ventricle. Through determination made by the His Ecg we found that the alterations in conduction were distal. The electro-mechanic latent period of the ventricle located to the right was shorter than the opposite. The angiographic studio helped to establish the auriculoventricular discordant relations and to identify the ventricles position through their angiographic morphology. In the cases showing point to the left, the ventricle anatomically considered as the left one showed a triangular form and smooth walls, while the ventricle anatomically consider being the right one presented trabeculated walls. In dextroversion the anatomically left ventricle was egg-shaped with smooth walls. All of them presented the aorta above the pulmonar artery.


Morphometric comparison of capillaries in muscle spindles, nerve, and muscle. Morphometric study was performed on transverse sections of microdissected muscle spindles from rabbit tenuissimus muscles. It showed a statistically significant difference in size and structure between the intrafusal capillaries and those of extrafusal muscle. The former are larger in diameter, circumference, and area due to a proportionate increase in the number of endothelial cells. Vesicles within spindle endothelial cells are fewer, mitochondrial counts are greater, but in proportion to the increased number of endothelial cells, intercellular junctions are tight and pericyte coverage is greater. The basement membrane around endothelial cells and pericytes is thicker and more often multilayered. The endoneurial capillaries of tenuissimus intramuscular nerve are morphologically identical to intrafusal capillaries. The similarity of the capillaries of spindles to those in brain suggests that a blood-nervous system barrier extends from brain into the peripheral nerves and muscle spindles.


Chalazia and rosacea.

Chalazia and rosacea. Fifty-seven percent of patients scheduled for excision of chalazia over 19 years of age and 64% of patients over the age of 29 were found to have rosacea. This compares to an incidence in our control group of 12% and 13%, respectively. Rosacea was almost twice as common in patients with recurrent chalazia as in those with only one occurrence.


Effect of neocarzinostatin on the nucleus, kinetoplast and microtubules of Trypanosoma gambiense and Trypanosoma evansi. The antibiotic neocarzinostatin (NCS) induces the anucleate form, not the dyskinetoplastic form, of Trypanosoma gambiense and Trypanosoma evansi. Light and electron microscopic studies indicated that production of the anucleate form is due to delay or inhibition of nuclear division. Excess pellicular microtubules are formed after treatment of trypanosomes with NCS, suggesting that in trypanosomes the microtubules replicate by induction, not by division. NCS also causes deformation of the axonemal and spindle microtubules. The K clone of T. evansi is more sensitive than the AK clone to the effects of NCS in inhibiting nuclear division and inducing the anucleate form.


Cross-linking experiments with the adenosine triphosphatase of sarcoplasmic reticulum. The proteins of sarcoplasmic reticulum were cross-linked by rapid oxidation of thiol groups with I2. About two-thirds of the thiols were oxidized without any significant cross-linking, implying an extensive formation of intramolecular disulphide bonds. When the thiols were completely oxidized at room temperature a series of oligomers containing up to five molecules were observed, as well as large aggregates which were excluded from the gels. Complete oxidation at -10 degrees C left most of the ATPase (adenosine triphosphatase) as monomer. Similar results were obtained when copper-phenanthroline complexes or dimethyl suberimidate were used as cross-linking reagents. We conclude that most of the cross-linked species arise by linking of randomly colliding ATPase molecules which are present in the membrane at very high concentration.


Identification of N-sulphated disaccharide units in heparin-like polysaccharides. 1. Preparations of heparin and heparan sulphate were degraded with HNO2. The resulting disaccharides were isolated by gel chromatography, reduced with either NaBH4 or NaB3H4 and were then fractionated into non-sulphated, monosulphated and disulphated species by ion-exchange chromatography or by paper electrophoresis. The non-sulphated disaccharides were separated into two, and the monosulphated disaccharides into three, components by paper chromatography. 2. The uronic acid moieties of the various non- and mono-sulphated disaccharides were identified by means of radioactive labels selectively introduced into uronic acid residues (3H and 14C in D-glucuronic acid, 14C only in L-iduronic acid units) during biosynthesis of the polysaccharide starting material. Labelled uronic acids were also identified by paper chromatography, after liberation from disaccharides by acid hydrolysis or by glucuronidase digestion. Similar procedures, applied to disaccharides treated with NaB3H4, indicated 2,5-anhydro-D-mannitol as reducing terminal unit. On the basis of these results, and the known positions and configurations of the glycosidic linkages in heparin, the two non-sulphated disaccharides were identified as 4-O-(beta-D-glucopyranosyluronic acid)-2,5-anhydro-D-mannitol and 4-O-(alpha-L-idopyranosyluronic acid)-2,5-anhydro-D-mannitol. 3. The three monosulphated [1-3H]anhydromannitol-labelled disaccharides were subjected to Smith degradation or to digestion with homogenates of human skin fibroblasts, and the products were analysed by paper electrophoresis. The results, along with the 1H n.m.r. spectra of the corresponding unlabelled disaccharides, permitted the allocation of O-sulphate groups to various positions in the disaccharides. These were thus identified as 4-O-(beta-D-glucopyranosyl-uronic acid)-2,5-anhydro-D-mannitol 6-sulphate, 4-O-(alpha-L-idopyranosyluronic acid)-2,5-anhydro-D-mannitol 6-sulphate and 4-O-(alpha-L-idopyranosyluronic acid 2-sulphate)-2,5-anhydro-D-mannitol. The last-mentioned disaccharide was found to be a poor substrate for the iduronate sulphatase of human skin fibroblasts, as compared with the disulphated species, 4-O-(alpha-L-idopyranosyluronic acid 2-sulphate)-2,5-anhydro-D-mannitol 6-sulphate. 4. The identified [1-3H]anhydromannitol-labelled disaccharides were used as reference standards in a study of the disaccharide composition of heparins and heparan sulphates. Low N-sulphate contents, most pronounced in the heparin sulphates, were associated with high ratios of mono-O-sulphated/di-O-sulphated (N-sulphated) disaccharide units, and in addition, with relatively large amounts of 2-sulphated L-iduronic acid residues bound to C-4 of N-sulpho-D-glucosamine units lacking O-sulphate substituents.


The effect of amphiphilic phenylalkyl derivatives on platelet energy metabolism. Stimulation of glycolysis through activation of membrane ATPase. In order to obtain information about the target of membrane-active inhibitors of platelet aggregation two phenylalkanoles and two phenylalkylamines were examined with respect to their influence on membrane ATPase and energy metabolism. The phenylalkanoles, 2-phenylethanol and 3-phenylpropanol, strongly enhanced the liberation in washed platelets of inorganic phosphate (Pi) from endogenous substrate or added ATP. A simultaneous decrease was found in the ATP/ADP ratio while glucose uptake, glycogen utilization and lactate formation increased. The effects of 2-phenylethanol and 3-phenylpropanol on Pi liberation and ATP/ADP ratio were detectable only with starving platelets; the stimulation of glycolysis could also be seen when glucose was added. It is concluded that presence of glucose enabled the platelets to reincorporate additionally liberated Pi into their ATP pool by virtue of the higher metabolic rate. The data suggest that a membrane-ATPase, possibly thrombosthenin ATPase, is the target of the phenylalkanoles. The phenylalkylamines, 2-phenylethylamine and 4-phenylbutylamine, appeared to inhibit Pi liberation and energy metabolism. Hence the aggregation inhibition produced by amphiphilic phenylalkylamines and phenylalkanoles is not due to a uniform metabolic effect of both classes of derivatives.


Interaction of halothane with non-depolarizing neuromuscular blocking drugs in man. 1 Tetanic and single twitch contractions of the adductor pollicis muscles, in response to indirect stimulation of each ulnar nerve, were recorded in patients anaesthetized with thiopentone and nitrous oxide in oxygen. 2 Concentrations of 1 and 2% halothane were administered for 10 min during recovery from neuromuscular paralysis by tubocurarine, dimethyl tubocurarine and gallamine. 3 During exposure to halothane, the peak contraction of the tetanic response was reduced and tetanic fade was increased whereas the single twitch was unaffected. 4 The effects of halothane on the tetanic responses were readily antagonized by intravenous neostigmine preceded by atropine. 5 Halothane could act post-synaptically by a non-depolarizing block or by desensitizing the post-synaptic receptors, but a pre-synaptic action seems more likely since neuromuscular block was only evident when tetanic stimulation was applied. Such an effect could be caused by impairment of the release of acetylcholine.


Suppressive effect of ferritin on in vitro lymphocyte function. This study describes the effect of ferritin on lymphocyte function in vitro. Peripheral blood lymphocytes isolated from normal donors were incubated with purified human splenic ferritin, and the mitogenic effect of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and mixed lymphocyte reaction (MLR) were assessed by the uptake of 3H-thymidine (3H-TdR). Ferritin (0.25--5.0 micrograms/ml culture) caused a marked suppression of PHA nad Con A blastogenesis but had no suppressive effect on PWM-induced transformation. Maximal suppression was obtained at a ferritin concentration of 1 microgram/ml and this was not enhanced by increasing ferritin concentrations. Ferritin also reduced the Con A capping phenomenon in normal lymphocytes from 22% to 6%, suppressed the MLR reaction but had no effect on the ability of normal lymphocytes to form E, EA and EAC rosettes or on in vitro lymphocyte cytoxicity against the K-562 cell line. Visual proof of the suppressive effect of ferritin on mitogen induced blastogenesis was provided by scanning electron microscopy, and direct evidence for the ability of lymphocytes to bind ferritin was obtained from studies with radioiodine labelled ferritin. The above findings indicate that ferritin suppresses certain parameters of T-lymphocyte function in vitro. The relation of the present findings to recognized abnormalities of T-cell function encountered in certain neoplastic disorders associated with high serum ferritin levels is at present unknown.


Reduced number of peripheral blood granulocytic progenitor cells in patients with Down's syndrome. The number of granulocytic progenitor cells (colony forming units in culture: CFUc) in the blood of patients with Down's syndrome was found to be reduced by 73.2% when compared to a group of age and sex matched controls. However, the blood CFUc of the Down's syndrome patients and the controls showed similar sensitivity to hydroxyurea which suggests that the low number of progenitor cells in Down's syndrome is not compensated by a marked increase in their cellular proliferation. The colony size distributions were similar for both the patients and the controls and, in addition, repeated assays at various intervals revealed no marked fluctuation in the number of blood CFUc in either group. The significance of the reduced number of circulating CFUc in Down's syndrome in relation to the known susceptibility of such patients to leukaemia is discussed.


Purification of the energy-transducing adenosine triphosphatase complex from Rhodospirillum rubrum. The oligomycin- and N,N'-dicyclohexylcarbodiimide-sensitive adenosine triphosphatase complex extracted with Triton X-100 from the chromatophores of Rhodospirillum rubrum was extensively purified. The purification procedure included (diethylamino)ethylcellulose chromatography and glycerol gradient centrifugation. The specific activity of Mg2+-dependent ATP hydrolysis in the purified preparation increased about 11-fold, while that of Ca2+-dependent ATP hydrolysis increased 50-fold as compared with chromatophores. The purified adenosine triphosphatase complex dissociated into a maximum of eight different polypeptides upon electrophoresis in the presence of sodium dodecyl sulfate. The estimated subunit molecular weights were as follows: 56 000 (alpha), 50 000 (beta), 33 000 (gamma), and those ranging from 17 000 to 9400 for the remaining smaller subunits. The purified preparation was incorporated into phospholipid vesicles by using the freeze--thaw technique. The reconstituted vesicles catalyzed [32P]ATP exchange, which was almost completely inhibited by both oligomycin and N,N'-dicyclohexylcarbodiimide as well as by a protonophorous uncoupler, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone.


Proteochondroitin sulfate synthesized in cartilages induced in vivo and in vitro by bone matrix gelatin. Implanted allogeneic demineralized bone matrix gelatin induced sequential development of cartilage and bone in the recipient rat muscle tissue. Proteoglycans of the implants labeled in vivo with [35S]sulfate at different stages of development were analyzed by sucrose density gradient centrifugation. The major proteoglycan synthesized in day-5 implant, just prior to onset of chondrogenesis, was a dermatan sulfate-containing proteoglycan with relatively slow sedimentation rate. Additionally, a small amount of a faster sedimenting component could be detected. The faster sedimenting proteoglycan, in which chondroitin 4-sulfate accounted for 85% of total radioactivity, became predominant in day-10 sample when cartilage formation was maximal. By day 30, when cartilage had been replaced by newly formed bone, the synthesis of this faster sedimenting component had ceased. A similar, if not identical, proteoglycan was found to be a major one synthesized by the in vitro-induced cartilage. This proteoglycan was smaller in overall size and shorter in length of its chondroitin sulfate chains than a major proteoglycan component obtained from neonatal rat epiphyseal cartilage. Concurrent with these changes in proteoglycan type, there appeared to be a change in collagen type, since type II collagen, in addition to type I collagen, was synthesized in day-10 implant. These results indicate that the proteoglycan can be used as a molecular marker for chondrogenesis by bone matrix gelatin.


Selective exposure of mucopolysaccharides is involved in macrophage physiology. Surface and intracellular mucopolysaccharides of guinea-pig peritoneal macrophages maintained in suspension and monolayer culture were studied. At least five classes of compound (hyaluronic acid, heparan sulfate, dermatan sulfate, chondroitin 4-sulfate and chondroitin 6-sulfate) were resolved and characterized by electrophoresis and enzymatic degradation. The results reported here suggest that modulation of mucopolysaccharide exposure is involved in macrophage physiology. The possible biological role of surface mucopolysaccharides in macrophage activity is discussed.


The effectiveness of EMG biofeedback training in low back pain. Eighteen patients with chronic low back pain (lbp) of muscle tension origin were given an EMG biofeedback training. Compared to seven controls they showed a significant decrease during training in muscle tension and subsequently in pain. However, at follow-up EMG levels dropped to the initial (high) level. Pain scores of patients with high pain decrements during training showed further improvement during follow-up, which was not the case with patients showing less substantial improvement. The importance of cognitions was discussed.


Temporal variations in androgens and stress hormones in control and schizophrenic subjects. Radioimmunoassay methods were employed to study the steroid hormones dehydroepiandrosterone (DHEA), cortisol, testosterone, and androstenedione in schizophrenic and control subjects. Observations were made at four different times during the day. Cortisol, testosterone, and androstenedione demonstrated no significant differences between the two subjects groups. DHEA was significantly below normal in the morning for the schizophrenic group, but within the range of the controls for subsequent determinations during the day. Control subjects show a similar circadian secretion pattern for both DHEA and cortisol. Schizophrenics show almost the same circadian secretion patterns for cortisol as do the controls.


T lymphocytes in patients with Down's syndrome. Individuals with Down's syndrome (DS) are thought to have abnormalities in their immune system, and a tendency to infection and malignancy. Studies to quantify the number of T lymphocytes in the peripheral blood of 82 unselected institutionalized patients (50 DS, 27 controls matched for sex and age, 2 chronic lymphocytic leukemic, 2 acute leukemic, and 1 Hodgkin's disease) were conducted. The numbers of circulating T cells in DS patients did not differ significantly from the control group, and were in the upper limits of normality. Number of "avid" T cells, however, were significantly higher in the DS than in the control group. The blastogenic response of the T cells to mitogen was significantly depressed. The data did not exclude the existence of qualitative abnormalities. Except for DS patients with congenital heart disease, those older than 15 years were not more prone to upper respiratory infections than other institutionalized mentally retarded patients.


[Temperature-dependent functional changes in sarcoplasmic reticulum membranes]. Temperature effect on changes in calcium ion transport and activity of Ca-ATPase of sarcoplasmic reticulum vesicles (SRV) was studied. Several temperature intervals of the change of SRV functional activity parameters were found: 8-12 degrees C-beginning of accumulation of SRV Ca2+, 12-19 degrees sharp activation of Ca2+ accumulation, 27-32 degrees-activation of passive yield, 36-43 degrees-reversible change of the activity of the accumulation system and activation of Ca yield, 48 degrees and higher--irreversible denaturation of transport Ca-ATPase. Coincidence of temperature intervals of SRV structural reconstructions, detected by means of fluorescent probes and functional changes points to a close relationship between structural reconstructions and functional responses of biological membranes.


Granulocytic chalone inhibits rapidly proliferating committed murine progenitor cells (CFU-C). Bovine leucocyte extract containing the granulocytic chalone inhibited proliferation of rapidly, but not slowly, prliferating murine CFU-C. The precursors of CFU-C, i.e. multipotent colon-forming stem cells (CFU-S), were apparently not affected. Inhibition of proliferation was detected as a decreased killing of DNA synthesizing cells in diffusion chamber cultures by hydroxyurea, after pre-treatment with the extract.


A new type of organization of the genetic material in eukaryotes. An investigation of the properties of a number of genes of Drosophila, obtained by cloning recombinant DNAs, led to the detection of a new type of organization of genetic material. It was found that a number of actively working structural genes of Drosophila are represented by a large number of copies, scattered over its chromosomes. Their localization in the chromosomes is variable, although they are always detected in regions of intercalary heterochromatin. The latter evidently is a site of accumulation of various multiple genes.


[Further purification of a tissue specific inhibitor in lymphopoiesis (lymphocyte chalone?) (author's transl)]. A partially purified calf spleen extract, which exhibits the properties of a lymphocyte chalone (tissue-specific, species non-specific, non-toxic and reversible acting, endogenous inhibitor of cell proliferation) as concerning biological activities, has been described earlier. This fraction has been further purified by ion exchange chromatography with DEAE-Sephacel to a 10,000-fold purification. The most active fraction inhibited 3H-thymidine incorporation into phytohemagglutinin- or pokeweed-mitogen-stimulated lymphocytes by 86% resp. 70%, when given in a concentration of 100 ng/ml. Ehrlich-ascites-cells were not inhibited by the same concentration. The inhibiting activity is compared to other published lymphocyte inhibitors.


Pseudocholinesterase activity and phenotypes in mentally ill patients. Pseudocholinesterase activities and phenotypes have been determined in 103 affectively ill patients, 168 schizophrenics and 73 Huntington's disease sufferers and compared with those of a sample of healthy controls. The distributions of phenotypes in the patient samples did not differ significantly from those of the controls. When corrections were made for sex, age and E1 phenotypes, the Huntington's disease patients showed a reduced level of cholinesterase activity. Normal levels were found in affective disorders and schizophrenia.


Adenomatoid tumour of the epididymis: histochemical and ultrastructural study of 2 cases. Two cases of adenomatoid tumour of the epididymis are described. Both the histochemical and ultrastructural studied support the concept that it is of mesothelial origin. The histochemical study showed the presence of acid mucopolysaccharides in the lumen of the tubular structures. The epithelial cells presented numerous microvilli in the free surface, junction complexes, wide intercellular channels and a well-developed Golgi complex. Abundant bundles of microfilaments and intracellular spaces were observed in the cytoplasm. Lymphocytes and histiocytes were identified both in the tubular lumen and between the epithelial cells. The stroma of the tumour was made up of dense connective tissue with abundant bundles of elastic fibres. The presence of intracytoplasmic spaces in the epithelial cells and elastic fibres in the stroma had not been previously observed in this tumour.


Inhibition of reticuloendothelial function by gold and its relation to postinjection reactions. A patient with rheumatoid arthritis developed severe exacerbation of symptoms 18 hours after an injection of gold thiomalate (sodium aurothiomalate). Immune complexes were present in his serum and synovial fluid; in the synovial fluid they were associated with intense complement activation. The effect of gold salts on splenic reticuloendothelial function was determined by measuring the clearance of heat-damaged erythrocytes from the circulation. Gold thiomalate (50 mg) substantially delayed clearance in the patient but had no effect in four other patients with rheumatoid arthritis who had not had a postinjection reaction. Severely impaired clearance also occurred in three out of four healthy people given 100 mg gold but they remained asymptomatic. The postinjection reaction may be an immune-complex disease that is triggered in certain patients because gold transiently inhibits reticuloendothelial function.


The major intracellular alkaline deoxyribonuclease activities expressed in wild-type and Rec-like mutants of Neurospora crassa. Over 95% of the deoxyribonuclease (DNase) activity of log-phase mycelia of Neurospora crassa is expressed as single-strand (ss) specific endonucleolytic activity. This activity is associated with three nucleases (D1, D2, and D3) which after partial purification from extracts, express activity with double-strand (ds) DNA as well. All three enzymes also degrade RNA at approximately the same rates that they degrade ss-DNA. D3 has been identified as endoexonuclease, an enzyme previously shown to have endonuclease activity with ss-DNA and RNA and exonuclease activity with ds-DNA, both of which are inhibited by ATP. D3 is inhibited by ATP, is relatively resistant to p-hydroxymercuribenzoate (PHMB), and sediments with an apparent molecular weight of 75 000. D2 has the properties of the previously described mitochondrial nuclease. It is a relatively unstable Mg2+-dependent endonuclease with no appreciable strand specificity for DNA. In addition, it is not inhibited by ATP and is strongly inhibited by PHMB and by the ethylenediamine tetraacetic acid (EDTA). It also sediments with an apparent molecular weight of 75,000. The properties of D1 are quite variable from one preparation to another. Freshly isolated D1 sediments with an apparent molecular weight of 180 000. It often shows some inhibition by ATP, but is relatively resistant to both PHMB and EDTA. However, on 'ageing,' the properties of D1 gradually convert to those of D2 with concomitant decrease in molecular weight, loss of inhibition by ATP, and increase in sensitivities to PHMB and EDTA. The results indicate that D1 is very likely a second form of the mitochondrial enzyme. Evidence was obtained for the presence of protein inhibitor(s) in crude extracts which may account for the masking of the ds-DNase activities of these enzymes in extracts. Two Rec-like mutants of Neurospora (uvs-3, and nuh-4) are deficient mainly inexpressed levels of D3, the endo-exonuclease. However, the levels of inactive endo-exonuclease precursor in these two mutants are higher than in the wild type. There may, therefore, be some defect in the conversion of precursor to active enzyme in these two mutants. Another mutant, which is not sensitive to mutagens relative to the wild (nuh-3), has depressed levels of both endo-exonuclease and the mitochondrial enzyme. Nuh-3 has some defect in the conversion of D1 to D2. Proteinases probably play some role in vivo in these enzyme conversions.


Thymidine incorporation into Rhizobium meliloti. Thymidine is rapidly catabolized to thymine, beta-aminoisobutyric acid, and carbon dioxide by Rhizobium meliloti cells. The incorporation of labelled thymidine into the DNA of R. meliloti cells can be enhanced by the addition of low concentrations (10-20 micrograms/mL) of deoxyadenosine or other nucleosides (adenosine, uridine, guanosine). However, at high concentrations ( greater than 50 micrograms/mL) these compounds inhibit thymidine incorporation. Conditions to obtain highly radioactive DNA of Rhizobium are described.


Prolonged and continuous percutaneous intra-arterial hepatic infusion chemotherapy in advanced metastatic liver adenocarcinoma from colorectal primary. Sixty patients with advanced metastatic adenocarcinoma of the liver from a colorectal primary were treated by prolonged and continuous intra-arterial hepatic arterial infusion chemotherapy over a period of time from December 1969 through July 1976. A 10-day course of 5-FU was administered in the hospital, and patients were discharged receiving 5-FUDR by continuous arterial infusion through a chronometric infusion pump. Objective responses of 100% were obtained in 15% of patients, 50% response in 39% of patients, and 25% response in 21% of patients. The median survival from onset of treatment was 8.5 months, 6.9 months, and 7 months, respectively, for 100%, 50%, and 25% responders versus 3.6 months for nonresponders. Survivals from onset of treatment were generally less in those with no disease-free interval. No relationship of response to sex and age was found. Patients previously treated with 5-FU intravenously responded to intra-arterial chemotherapy; 13% had a 100% response, and 54% had a 50% response. No relationship of drug dose to response was observed. Drug toxicity was frequently systemic and mild to moderate. Numerous complications occurred due to the catheter, complete or partial thrombosis occurring in 18.6% and 20.8%, respectively, and 30% of patients had displacement of the catheter. The role of partial arterial occlusion in terms of response and survival may be significant. Future studies should involve comparison of direct surgical placement versus percutaneous placement of catheters.


Experimental squamous cell lung tumors in Sprague-Dawley and murine pneumonitis-free rats. Squamous cell bronchogenic carcinoma was produced in 34% of a group of specific pathogen-free rats in a mean time of 139 days by the use of point-source irradiation. In a group of Sprague-Dawley rats, identical tumors developed in 54% of animals after an average exposure time of 147 days. This study was undertaken to clarify whether the bronchogenic squamous cell carcinomas produced by this method are due to the effects of the point source of irradiation alone or to the additive effects of irradiation and chronic murine pneumonitis. The results of this study in specific pathogen-free rats indicate that murine pneumonitis is not a prerequisite for the development of neoplasia by this method. The electron microscopic findings presented support the histologic diagnosis of a well-differentiated squamous cell bronchogenic carcinoma, similar in appearance to the tumor found in humans.


Phase I trial of N-(phosphonacetyl)-L-aspartate. A Phase I clinical trial of N-(phosphonacetyl)-L-aspartate, an antimetabolite which inhibits a key enzyme in the de novo pathway of pyrimidine biosynthesis, was conducted. N-(Phosphonacetyl)-L-aspartate was given as an i.v. 15-min infusion once daily for five days; cycles of treatment were repeated every three weeks. Thirty-four patients received treatment. Dose-limiting toxicity was observed at 1500 to 2000 mg/sq m/day and was manifested by skin rash, diarrhea, and stomatitis. Rash and diarrhea usually began during the first week of treatment and persisted up to Day 17 of a cycle of therapy. No consistent hematopoietic, hepatic, or renal toxicity was observed. One partial response in a patient with colon carcinoma was seen and continues at more than eight months. Stable disease was observed in three patients with colon carcinoma, two patients with hypernephroma, one patient with pancreatic carcinoma, and one patient with melanoma. The predictability and reversibility of toxicity and the suggestion of antitumor activity in humans are observations which support the further evaluation of N-(phosphonacetyl)-L-aspartate in Phase II studies.


Interaction of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate with cells in mixed-lymphocyte culture. 12-O-Tetradecanoylphorbol-13-acetate (TPA) inhibits DNA synthesis in bovine lymph node lymphocytes in mixed-lymphocyte cultures. Using a radioautographic study, we determined that TPA also blocked morphological changes in these cultures. Pretreatment of cultures of isologous lymphocytes with 10(-7) M TPA for three days prior to mixing was sufficient to block their subsequent response in mixed culture. Thus, TPA did not need to be present during the initial cell-to-cell interactions of the mixed lymphocyte response. The inhibition was not due to the death of the responding cell population because the effect was reversible. In one-way mixed-lymphocyte cultures, TPA pretreatment of either responding or stimulating cells could block DNA synthesis. The responding cells were more sensitive to TPA than were the stimulating cells. The inhibitory effect of the stimulators increased with an increase in the stimulating-to-responding cell ratio. In one-way cultures, it was also seen that lymphocytes from different animals varied both in their sensitivity to TPA and in their response to TPA-treated cells from other animals. The data taken together are consistent with the idea that TPA acts by changing cell surface recognition structures and/or indirectly, through activation of a subpopulation of cells to block the proliferative response. TPA may prove to be a valuable tool in studying cell-cell interactions and lymphocyte differentiation in vitro.


Abnormal kinetics of DNA synthesis in ultraviolet light-irradiated cells from patients with Cockayne's syndrome. Cells from patients with the hereditary disorder Cockayne's syndrome and from the sun-sensitive individual, 11961, are sensitive to the lethal effects of ultraviolet light (UV) but have no detectable defect in either excision- or postreplication repair after UV irradiation. In normal cells and in Cockayne heterozygotes, UV causes a depression in the rate of DNA-replicative synthesis followed by a recovery of normal rates 5 to 8 hr after irradiation. In Cockayne and 11961 cells, the initial depression in DNA synthesis is the same as that in normal cells, but no subsequent recovery is observed. The recovery of DNA synthesis in normal cells appears to be unaffected by fluorodeoxyuridine but inhibited by cycloheximide. This suggests a possible requirement for de novo protein synthesis, but there are a number of alternative interpretations of these data.


Effects of estrogen to alter amino acid transport in R3230AC mammary carcinomas and its relationship to insulin action. The effects of estrogens on transport and incorporation of amino acids into the R3230AC mammary adenocarcinoma were studied in vivo and in vitro. Dissociated tumor cells from ovariectomized rats, like those from diabetic rats, displayed elevated transport of proline, representing entry by the A system; transport of phenylalanine (L system) was unaltered, as was glucose transport and its utilization. Administration of estradiol valerate decreased the entry of proline into tumor cells from intact, diabetic, or ovariectomized animals; the response to the steroid hormone was greater in ovariectomized or diabetic rats compared to intact animals. The time course of the effects of estrogen treatment was examined in diabetic rats. By 72 hr, transport of both proline and leucine was significantly decreased; incorporation of leucine into proteins and uridine into RNA was significantly reduced by 24 hr after injection of estradiol valerate. The effects of estrogen in vivo to reduce transport of amino acids and their incorporation into proteins appeared to correlate with the reduced tumor growth observed. Experiments were performed to examine the effects of 17 beta-estradiol in vitro on amino acid transport into dissociated cells from ovariectomized or diabetic rats. Under these experimental conditions, 17 beta-estradiol (10(-6)M) inhibited proline transport with little or no effect on leucine transport in cells from ovariectomized rats; in cells from diabetic rats, proline transport and leucine incorporation were significantly reduced by estradiol, whereas phenylalanine transport was slightly inhibited (approximately 20%). The effect of estradiol in vitro was also manifest in tumor cells obtained from diabetic rats treated in vivo with estradiol valerate; estradiol in vitro caused a further reduction in proline transport but not in leucine transport, results that imply some specificity to the action of estrogen on the A system. Since we had earlier shown that insulin action on transport in these tumor cells were directed towards the A system, we examined the effects of insulin, estradiol, and their combination in vitro on proline and leucine transport. Insulin (10(-8) M) stimulated proline transport; 17 beta-estradiol, at a selected lower level of 10(-8) M, inhibited proline transport. When both were added in vitro, estradiol (10(-8 M) was capable of significantly reducing the insulin (10(-8) M)-induced increase in proline transport. Leucine transport was not altered in any of these experiments. Together, these data suggest that estrogens are capable of inhibiting amino acid transport into the R3230AC mammary carcinoma, an effect that is compatible with reduced tumor growth. The possible relationship of estrogen and insulin at the level of amino acid transport remains to be elucidated.


Assay of intracellular free and macromolecular-bound metabolites of 5-fluorodeoxyuridine and 5-fluorouracil. Methods have been developed to assay several aspects of 5-fluoro-2'-deoxyuridine and 5-fluorouracil metabolism in tissue culture cells. These methods allow measurement of (a) intracellular levels of the covalent complex formed between 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP), 5,10-methylenetetrahydrofolate, and thymidylate synthetase; (b) incorporation of drug into RNA; and (c) analysis of drug metabolites. The methods were developed using radioactively labeled drugs, but they should be adaptable to studies using nonlabeled compounds. Sephadex G-25 chromatography or trichloroacetic acid precipitation were utilized for isolation of the macromolecular cell fraction; prior treatment of this fraction with RNase or heating at 65 degrees for 15 min resulted in selective removal of RNA or the thymidylate synthetase complex, respectively, from the precipitable fraction. Free intracellular drug metabolites present in the acid-soluble fraction were analyzed by high-pressure liquid chromatography. Following incubation of HTC cells with [6-3H]-5-fluoro-2'-deoxyuridine, a radioactive macromolecule was isolated and identified as a FdUMP-5,10-methylenetetrahydrofolate-thymidylate synthetase complex. Intracellular formation of this complex was shown to be dependent on the presence of the enzyme thymidine kinase. Dissociation of the complex in vivo was first order with a t1/2 of 6.2 hr; in contrast, a t1/2 of 2 hr was determined for dissociation of the complex in cytosol. Incubation of L1210 cells with [6-3H]-5-fluorouracil for 22 hr resulted in formation of 80 fmol of FdUMP-5,10-methylenetetrahydrofolate-thymidylate synthetase complex per 10(6) cells, as compared with 400 fmol of drug incorporated into RNA per 10(6) cells. Intracellular FdUMP could not be detected in the acid-soluble fraction of these cells unless the cells were first heated to dissociate the complex.


Restoration of cyclophosphamide-induced suppression of thymus-derived cytotoxic cell generation by normal thymocytes. Spleen cells from mice treated with cyclophosphamide (100 to 200 mg/kg) were unable to generate effective cytotoxic thymus-derived cells to allogeneic tumor cells in vitro. The inability of lymphoid cells from cyclophosphamide-treated mice to generate thymus-derived cytotoxic cells became more apparent as the number of responding cells became limited. This depressed response was not due to the elimination of cytotoxic precursor cells since normal response levels were restored by the addition of thymus cells. The added thymus cells did not provide cytotoxic cells in the culture. The thymus cells active in restoring cytotoxic activity were sensitive to mitomycin C, cyclophosphamide, and anti-theta serum and complement. In addition, the active thymus cells were located in the cortisone-resistant pool and did not adhere to nylon wool columns.


Clinical trial of weekly pyrazofurin.

Clinical trial of weekly pyrazofurin. Pyrazofurin was administered to 21 patients with solid tumors at a dose of 200 mg/m2 iv weekly, because this dose had been shown to be well-tolerated and pharmacologic effects of a single dose at this level persisted for up to 7 days. An anemia consistent with a disturbance in rbc production was seen in most patients. Other toxic effects included stomatitis, rash, and myelosuppression. No complete or partial responses were noted, but two patients with alveolar cell carcinoma of the lung each had stable disease for 12 months. Most of the patients in this study tolerated the weekly dosage schedule well with only minimal myelosuppression, suggesting that this agent and schedule might be acceptable for use in combination chemotherapy. Several theoretic reasons favor the use of pyrazofurin in this manner. Pyrazofurin should also be evaluated more fully in patients with polycythemia vera, mycosis fungoides, and psoriasis, since other orotidylate decarboxylase inhibitors have been shown to be effective in these diseases.


Phase I study of 5-fluorodeoxyuridine plus cytosine arabinoside infusions in patients with solid tumors. A phase I trial was conducted in 30 patients with solid tumors, using infusions of 5-fluorodeoxyuridine (5-FUdR) plus cytosine arabinoside (ara-C). Doses of 5-FUdR administered over 2 hours daily X 5 ranged from 0.02 to 1.0 mg/kg, and these doses immediately preceded a 1-hour infusion of ara-C. These schedules were selected because 5-FUdR pretreatment had been shown to sensitize L5178Y cells in culture to acute cell death by ara-C. Dose-limiting toxicity was myelosuppression. Based upon results in this study, the recommended dose of 5-FUdR to be used in phase II trials of this combination is 0.04--0.05 mg/kg (1.6--2.0 mg/m2) given prior to ara-C at a dose of 100 mg/m2. Antitumor responses were seen in patients with head and neck cancer, breast carcinoma, and carcinoid syndrome.


Host resistance to tumor after cure of advanced LSA lymphoma by treatment with BCNU and chlorozotocin. C57BL mice carrying the syngeneic advanced LSA ascites lymphoma initiated with a 10(6)-cell LSA inoculum were treated with four combinations of BCNU and/or chlorozotocin (CLZ) on Days 5 and 6 after tumor inoculation. The percentage of mice surviving greater than or equal to 60 days was greater than 80% for all four combinations. Surviving mice were then challenged with live LSA cells beginning with 100 cells and increasing the inoculum by factors of 10 every 3 weeks until a 10(7)-cell inoculum level was reached. The latter dose was repeated four times. A marked difference in resistance to tumor challenge was observed for the various groups. Surviving tumor-resistant mice at the end of the experiment, classified by original treatment, were as follows: BCNU-BCNU, 86.7%; CLZ-BCNU, 56.3%; BCNU-CLZ, 23.5% and CLZ-CLZ, 0. Various hypotheses are presented which might explain these differences.


Effect of intravenous glibornuride and tolbutamide on myocardial contractility. The acute effects of therapeutic doses of intravenous tolbutamide and glibornuride on the systolic time intervals (QS2c, LVETc, PEPc and PEP/LVET) were examined in 5 healthy volunteers. Blood sugar was maintained constant throughout the study. No significant changes of these intervals as well as of heart rate and blood pressure were observed. Therefore, it is concluded that tolbutamide and glibornuride have no acute positive inotropic action.


Effects of adenine nucleotides on calcium binding by rat heart sarcoplasmic reticulum. The purpose of the present study was to investigate the interactions between ATP, ADP and calcium binding by rat heart sarcoplasmic reticulum vesicles (SR), and to re-evaluate the assay method used to study calcium binding. Calcium binding or transport was studied by the Millipore filtration method. Rat heart SR has an unusually high Mg2+ stimulated ATPase activity (1.37 +/- 0.16 mumol Pi per min per mg at 25 degrees C) so that previous incubation with ATP in calcium binding studies releases ADP and Pi. By maintaining ATP at high and ADP at low concentrations with an ATP-regenerating system (phosphoenolpyruvate and pyruvate kinase), calcium binding capacity was increased by two to three times that of a non-ATP-regenerating system and there was a direct relationship between the amount of Ca-binding and SR protein concentration. When Ca2+ and Mg2+ concentrations were controlled and ATP and ADP concentrations were varied independently the initial rate of Ca-binding was inhibited 25% by 1 mmol.litre-1 ADP and 48% by 3mmol.litre-1 ADP. ATP limited the initial rate of Ca-binding only at ATP levels below 2mmol.litre-1. At low ATP concentrations Ca-release was observed. However, in the presence of an ATP-regenerating system no Ca-release was observed, even at low concentrations of ATP. This study shows that ADP is an inhibitor of Ca-binding by rat heart SR. However, the possibility that high ADP concentrations in the presence of Pi from ATP hydrolysis, could facilitate calcium release cannot be excluded. In addition to the possible physiological importance, these effects must be regarded when assaying rat cardiac SR calcium binding.


Organization of tRNA and rRNA genes in N. crassa mitochondria: intervening sequence in the large rRNA gene and strand distribution of the RNA genes. Through analysis of cloned fragments of N. crassa mitochondrial DNA, we have derived a physical map for the region of the mitochondrial genome which encodes the ribosomal RNAs and most of the tRNAs. We have located RNA genes on this map by hybridization of purified 32P end-labeled RNA probes, and our findings are as follows. First, the gene for the large ribosomal RNA contains an intervening sequence of approximately 2000 bp. Second, the genes for the small and large ribosomal RNAs are not adjacent, as previously reported, and the region between them contains a number of tRNA genes, including that for the mitochondrial tRNATyr, which is located close to the small rRNA gene on the same strand of the mitochondrial DNA. Third, there is a second cluster of tRNA genes on the mitochondrial DNA following the large ribosomal RNA gene, but there is no evidence for the presence of tRNA genes in the intervening sequence of the large ribosomal RNA. Fourth, hybridization of labeled ribosomal and transfer RNAs to the separated strands of a cloned 16 kbp DNA fragment covering this region indicates that the two ribosomal RNAs and most, if not all, of the mitochondrial tRNAs are encoded on one strand of the mitochondrial DNA.


Changes in mitochondrial DNA in cardiac hypertrophy in the rat. We studied DNA (mtDNA) replication in adult female rat hearts undergoing hypertrophy secondary to constriction of the ascending aorta. MtDNA was measured in isolated mitochondria by a fluorometric method adapted for that purpose. The conditions for removal of contaminating nuclear DNA were developed, and the purity of the mtDNA was assessed from its molecular conformation (open and closed circles) and by renaturation-kinetic analysis. The mtDNA concentration in mitochondria, expressed as micrograms of DNA per milligram of mitochondrial protein, increased 2, 4, and 7 days postoperatively by 21, 73, and 98%, respectively. Similar results were obtained when mtDNA was expressed per nonomole of cytochrome a. The population of replicative intermediates of mtDNA was analyzed by electron microscopy. In normal hearts, we observed molecular forms characteristic of animal mtDNA, such as circular monomers and dimers, catenated molecules, D-loops, expanded D-loops, and gapped molecules. D-loop frequency, which was near 50% in the mtDNA of control hearts, was markedly reduced to 5-7% in hypertrophying hearts. This result indicates that the increase in replicative flux of mtDNA is associated with the removal of a block in the conversion of D-loops to other intermediates.


Lack of effect of prolactin suppression on plasma dehydroepiandrosterone sulphate. In twelve patients with hyperprolactinaemia, treatment which reduced plasma prolactin from a mean of 531 microgram/l (range 68-3500 microgram/1) to 8.3 microgram/l (0-27 microgram/l), caused no significant change in plasma dehydroepiandrosterone sulphate (DHA-SO4). Pre-treatment levels of DHA-SO4 were within the normal range in eleven out of twelve cases. The results do not support for claims that prolactin excess is associated with an increase in circulating DHA-SO4.


Down's syndrome in Western Australia: mortality and survival. An epidemiological investigation of 231 cases of Down's Syndrome born in Western Australia between 1966 and 1976 confirmed the importance of congenital heart disease as a determinant of early mortality. An unexplained and hitherto unreported high incidence of Sudden Death in Infancy Syndrome if survival rates with those of other investigators show, that mortality amongst cases of Down's Syndrome with no congential heart defect has decreased and longevity is no longer a rate occurrence. As a result of these changes, and despite a demonstrable fall in the incidence of Down Syndrome in Western Australia, the prevalence of the condition is expected to rise.


The Burns' test in low back pain: correlation with the hysterical personality. Twenty-five postoperative lumbar laminectomy and diskectomy patients were administered the MMPI and evaluated by physical examination which included the Burns' Bench Test. In this test the patient is asked to kneel on a bench with knees and hips flexed and place his fingers on the floor. The kneeling position relieves stress on the low back and tension on the siatic nerve, so that patients with organic causes of low back pain are able to perform the test. Conversely, inability to perform the test is indicative of functional symptoms as in hysteria. All patients were males and the average age was 54. The average interval from surgery was 2 1/2 years. Sixty-seven per cent of those patients unable to perform the Burns' test were classified as hysterical on the basis of the MMPI, while 73% of patients classified as hysterical using the MMPI criteria failed to perform the Burns' test. The correlation between the Burns' test and hysteria as determined by the MMPI was 0.48. In terms of sensitivity and specificity, the sensitivity of the Burn's test in distinguishing patients with an hysterical MMPI was 73%. The specificity for normal subjects was 71%. The Burns' test is a useful clinical test for differentiating between organic and non-organic causes of low back pain. However, the test by itself should not be construed as an unequivocal measure of hysteria as defined psychologically by the MMPI. Failure to perform the test indicates a need for further psychological study.


The management of atlanto-axial subluxation with neurologic involvement in Down's syndrome: a report of two cases and review of the literature. A review of 5 cases in the literature and our 2 additional cases of atlanto-axial sublux-ation in Down's Syndrome with associated neurologic deterioration suggests that posterior stabilization and fusion should be carried out initially. Posterior decompression alone, with excision of the posterior arch of C-1, may further increase atlantoaxial instability and contribute to neurologic deterioration. Lateral radiographs in flexion and extension and contrast studies are recommended to assess the reducibility of the lesion and the site of neural impingement. It is further recommended that if significant neurologic deterioration persists or worsens, an oral transpharyngeal odontoidectomy should be considered for cord decompression.


Relaxation rate of constituent muscle-fibre types in human quadriceps. 1. Muscle fibres may be subdivided into type I (with slow-twitch contractile properties) and type II (fast-twitch) depending on their myosin adenosine triphosphatase activity. In voluntary isometric contractions type I fibres are utilized at low forces (less than 20% of maximum) whereas type II fibres are recruited in addition at high forces. This physiological recruitment order has enabled us to measure the relaxtion rate of type I and II fibres in vivo in normal human subjects. 2. Relaxation rate was measured in 16 subjects from low (10% of maximum) and maximum isometric quadriceps contractions and the muscle-fibre type composition determined from needle-biopsy specimens in 10 subjects. The relaxation rate of type II fibres was calculated to be twice as fast as that of type I. 3. It was not possible to estimate, from studies in 33 quadriceps muscles (25 normal subjects), the contribution of type II fibres to overall fibre area from the relaxation rate as determined from electrically stimulated isometric contractions.


Cardiac effects of angiotensin antagonists in normotensive rats. 1. Angiotensin II (AII) antagonists, namely Sar1,Ile8-AII, Sar1,Ala8-AII and Sar1,Thr8-AII, were administered daily for 4 weeks to normotensive rats to study their effect on cardiac hypertrophy. 2. None of the antagonists altered blood pressure significantly but Sar1,Ile8-AII and Sar1,Ala8-AII produced a significant increase in heart weight, as compared with untreated age-matched control rats. Administration of Sar1,Thr8-AII did not produce cardiac hypertrophy. 3. A significant increase in catecholamine concentration was observed in the ventricles of rats treated with Sar1,Ile8-AII and Sar1,Ala8-AII but no change was found in the group treated with the Sar1,Thr8-AII analogue. The production of cardiac hypertrophy by Sar1,Ile8-AII was prevented by bilateral adrenalectomy, suggesting an important role for catecholamines in modulating cardiac hypertrophy.


Effect of chronic clonidine treatment and its abrupt cessation on mean blood pressure of rats with a normal or an elevated blood pressure. 1. Clonidine (6 mg of base/l of water) was given as drinking fluid to normotensive rats or rats with established or early hypertension. 2. Spontaneous hypertensive rats (6 months old: average dose of clonidine, 0.6 mg 24 h-1 kg-1) showed a sustained fall in blood pressure over 3 weeks. 3. The same clonidine solution given for 6 weeks to two-kidney Goldblatt rats with early-stage hypertension (average dose of clonidine: 1 mg 24 h-1 kg-1) or spontaneously hypertensive rats (clonidine dose: 1 mg) induced a fall in mean blood pressure, but no change in normotensive rats. 4. Replacement of clonidine by water induced hypertension and lability which led to death in hypertensive but not in normotensive rats.


Functional analysis of the replicator structure of lambdoid bacteriophage DNAs. In our hybrid-plasmid reconstruction analysis of lambda (lambdoid) DNA signal structures involved in phage DNA replication, we have detected a dual system alternatingly able to initiate a first primer-RNA synthesis. Both of them--the major, primase-dependent ori system and the minor and usually suppressed, RNA-polymerase-dependent oop system--act in conjunction with a common signal structure for inception of DNA synthesis. It appears that in situations such as this, where one has to deal with the existence of regular as well as backup systems serving the same function, straightforward conclusions are no longer possible in their genetic analysis. For example, even though the oop-DNA segment can be deleted entirely from bacteriophage lambda DNA without disturbing its ability to replicate, it may not be valid to conclude that the oop system has no function in DNA replication. Dual systems of this type or organization in general have also been observed previously for some other replicons such as the R-factors R6-5 and R6K (Timmis et al. 1978; Crosa et al., this volume) or the F factor (Helinski et al., this volume), and they may be more common than presently expected.


Effects of the second (ethanol) extract of ginseng on the cardiovascular dynamics of dogs during halothane anesthesia. An electromagnetic flowmeter probe was chronically implanted around the ascending aorta in a group of dogs. Subsequently, ten dogs were lightly anesthetized with halothane (0.75%), and a second (ethanol) extract of ginseng (40 mg/kg) was administered intravenously. Five dogs were anesthetized without the administration of ginseng. Eleven cardiovascular variables including cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2, and base deficit were compared for two hours. The heart rate and mean arterial pressure were significantly decreased following ginseng. There were no other meaningful changes in either group.


Effects of the third (aqueous) extract of ginseng on the cardiovascular dynamics of dogs during halothane anesthesia. An electromagnetic flowmeter probe was chronically implanted around the ascending aorta in a group of dogs. Subsequently, ten dogs were lightly anesthetized with halothane (0.75%) and the third (aqueous) extract of ginseng (40 mg/kg) was administered intravenously. Five dogs were anesthetized without the administration of ginseng. Eleven cardiovascular variables including cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2, and base deficit were compared. The cardiac output, stroke volume, and central venous pressure were decreased significantly, while total peripheral resistance was increased significantly following ginseng.


Fluorimetric determination of DNA in papain digests of cartilage, using ethidium bromide. A fluorimetric procedure for the determination of the DNA content of cartilage is described. The tissue is initially solubilised by digestion with papain, and ethidium bromide is used for the subsequent quantitation of DNA. The basis of the procedure is the enhancement of fluorescence which occurs when ethidium bromide complexes with native nucleic acids, fluorescence due to DNA being distinguished from that due to RNA through the use of ribonuclease. The method provides reproducible results, allowing determination of DNA in papain digests containing greater than 1.25 microgram DNA/ml, and is a rapid alternative to more laborious colorimetric or fluorimetric methods, which require the separation of DNA from other tissue components. The procedure is highly specific for DNA and is useful in metabolic studies in which various parameters of chondrocyte activity are being studied.


Effect of methods of preservation on the arrangement of collagen fibrils in connective tissue matrices: an x-ray diffraction study of annulus fibrosus. Samples of annulus fibrosus were dissected from the anterior of lumbar intervertebral discs from adult rabbits. X-ray diffraction was used to provide a measure of the distribution of collagen fibrils in each sample. The sample was then preserved and the experiment repeated twice. Three methods of preservation were used: (1) fixation in formol saline, (2) freezing, (3) freezing in liquid nitrogen. Frozen specimens were subsequently thawed. None of the three methods of preservation affected the distribution of collagen fibrils in the tissue significantly. However, fixation does cause the collagen molecules to become more closely packed within a fibril. The method of choice for preserving annulus fibrosus and, by implication, other connective tissue matrices for ultrastructural studies is discussed.


The effect of contaminant proteases in testicular hyaluronidase preparations on the immunological properties of bovine nasal cartilage proteoglycan. Commercial testicular hyaluronidase preparations are contaminated by a small amount of protease activity which is partially inhibited by serine-protease inhibitors or pepstatin. These protease inhibitors can be shown by Sepharose gel column chromatography to abolish or reduce hyaluronidase-induced degradation of bovine nasal cartilage proteoglycan subunit without affecting the ability of the enzyme to degrade chondroitin sulfate. In addition, immunodiffusion studies indicate that pretreatment of hyaluronidase with these protease inhibitors reduces or abolishes the ability of the enzyme to produce a second "link-related" immunoprecipitin line upon digestion of link protein-containing proteoglycan fractions. Thus, the enhancement of immune reactivity and the unmasking of an additional antigen noted after digestion of cartilage proteoglycan with testicular hyaluronidase are most likely due to the exposure of additional antigenic sites or the the release of more highly immunoreactive fragments by the contaminant proteases rather than to the action of hyaluronidase itself.


The content of dityrosine in chick and rabbit aorta proteins. The possible presence of dityrosine in elastin derived by two different methods and in structural glycoproteins from aortas of 1 day old chicks, adult rabbits and fetal rabbits was determined by a sensitive spectrofluorimetric procedure. Only chick tissues were found to contain dityrosine, 0.3 residues/100,000 total amino acid residues in aortic elastin and 12-15 residues/100,000 residues in the structural glycoproteins. No dityrosine could be detected in any of the fetal or mature rabbit tissues. However, related fluorescent compounds with different excitation-emission maxima and different elution times were obtained by ion exchange chromatography of structural glycoproteins partially hydrolyzed under alkaline conditions.


Topical clindamycin in acne: a preliminary study. A solution of clindamycin in 50 percent alcohol used topically in the treatment of acne was found to be an adequate therapy to replace systemic tetracycline. Patients followed over a two to three month period showed improvement in lesion counts and subjective improvement as evaluated by the investigator and patient.


Psoriasiform eruption induced by propranolol. The appearance of a psoriasiform eruption in a seventy-eight year old patient after one year of treatment with propranolol is presented herein. The histologic picture was not compatible with psoriasis vulgaris, although it contained some of the same features. Immunologic investigation revealed immune deposits at the junction of the dermis and epidermis and in blood vessel walls as well as monoclonal gammopathy. The rash, which was followed by a reduction in tear secretion, is suggested to have been a drug reaction associated with propranolol. This is supported by the positive results of a migration inhibiting factor test towards propranolol, the clearing of the eruption which took place three weeks after withdrawal of the drug, and the negative result of the same test obtained soon afterwards.


Cutaneous reaction to spironolactone resembling lupus erythematosus. A cirrhotic male patient was admitted with a skin eruption. He had been taking spironolactone and hydrochlorothiazide for two months prior to admission. The morphology and distribution of skin lesions resembled that of systemic lupus erythematosus (SLE). Histologic changes in the skin biopsy specimen were consistent with SLE. Biopsy specimens of normal and affected skin were reported to show weak focal deposition of IgM and complement at the dermal-epidermal junction. However, there was a striking absence of serologic evidence of SLE. The rash disappeared when all medications were discontinued and reappeared when the patient was given spironolactone. The character and distribution of the rash after spironolactone administration was identical to the previous lesions. It disappeared again when spironolactone was withdrawn. This response to spironolactone is good evidence that it and not chlorothiazide was responsible for the rash. The latter drug has been reported to cause SLE-like skin changes.


Vitamin B-12 induced acnes.

Vitamin B-12 induced acnes. A type of acne induced by vitamin B-12 deserves a special place among acneiform eruptions. The eruption is monomorphic and of a particular type. It consists of voluminous folliculitis lesions which develop acutely after the first injections of vitamin B-12 and disappear rapidly when treatment is discontinued. The etiologic and pathogenic mechanisms of the disease are not know.


Biofeedback training in the therapy of dyshidrosis. Biofeedback training for hand warming and relaxation was used with five patients with severe dyshidrotic eczema who were poorly responsive to conventional therapy. Improvement was seen in all five patients, especially those who most noted flaring of their disease under stress. Biofeedback is being used in the treatment of diverse stress-related disorders, and may have potential in dermatologic diseases.


Cutaneous reaction rates to penicillins--oral versus parenteral. Rates of skin reactions for oral and parenteral administration of various types of penicillin were compared in an extensive series of carefully monitored patients. The rate with orally administered penicillins was consistently lower than when administered parenterally.


Partial anomalous pulmonary venous connection to the azygous vein with intact atrial septum. A five-year-old girl with partial anomalous pulmonary venous connection to the azygous vein with intact atrial septum is reported. The clinical and roentgenographic features suggested the correct diagnosis. Surgical correction of this previously unreported defect was accomplished by creating an atrial septal defect and constructing a baffle to direct the blood flow from the azygous vein to the left atrium.


[Contact eczema caused by isonicotinic acid hydrazide]. In the treatment of an ulcerous reaction to BCG vaccination with isonicotinic acid hydrazide cones, a 20 year old nurse developed a contact eczema within four weeks under the influence of this tuberculostatic.


[Decrease of earning capacity. Results of evaluation of proposals for the estimation of earning capacity decrease in occupational disease according to No.5101 of the Occupational Diseases Act]. The table elaborated for estimating the diminution of earning capacity has proved useful. A questionnaire programme revealed that classification of occupational dermatological disorders becomes a problem as soon as insurance-legal factors have to be considered.


[Actinic reticuloid in a florist].

[Actinic reticuloid in a florist]. Actinic Reticuloid in a Florist A 63 year old florist developed after primary sensibilisation against Chrysanthemum and other flowers and plants the typical clinical and histological features of an actinic reticuloid with considerably augmented sensitivity to UV A and UV B.


[Contraception in androgenised women with a low-dose cyproterone-acetate containing one-phase preparation (author's transl)]. 101 hirsute women received Diane, a combination of 2 mg cyproterone acetate and 50 micrograms ethinyl oestradiol per capsule, from the fifth to twenty-fifth day during a total of 1105 cycles. The treatment was satisfactory in 96% of women with acne, 84% with androgenic alopecia, 79% with seborrhoea, and 50% of those with mild or moderate hirsutism. The effectiveness of treating hirsutism or alopecia depended on its severity and duration. There was no correlation between various measures of androgen levels before and during treatment and the clinical results. Side effects were similar to those after contraceptive one-phase preparations, both in kind and incidence. None of the women became pregnant. Diane is thus the drug of choice in hormonal contraception of patients with acne, seborrhoea, androgenic alopecia or mild hirsutism. It is also suitable in the follow-up or interval management of high-dose cyproterone acetate treatment of severe hirsutism, in order to maintain the effect obtained with lower hormone doses.


Participation of serotonin in thyrotropin release. II. Evidence for the action of serotonin on the phasic release of thyrotropin. During a 12-h light 12-h dark schedule (lights off at 1900 h), male Sprague-Dawley rats show a circadian rhythm of plasma TSH with a zenith near midday. The participation of serotonin (5HT) in the phasic release of TSH was studied using both pharmacological and surgical-stereotaxical approaches. Animals treated with parachlorophenylalanine methyl ester (pCPA), an inhibitor of 5HT synthesis (one or two injections of 250 mg/kg each) showed a reduction or a disappearance of the diurnal peak of TSH, respectively. Additional treatment by 5-hydroxytryptophan, a precursor of 5HT, completely, restored the diurnal TSH peak. Treatment with 5,6-dihydroxytryptamine creatine sulfate, a neurotoxin which selectively destroys 5HT terminals, also induced alterations of the diurnal peak of TSH. There were no major modifications observed in the low nocturnal levels of TSH in rats treated with pCPA, 5-hydroxytryptophan, or 5,6-dihydroxytryptamine. The major serotoninergic innervation of the hypothalamus originates from the raphe dorsalis or centralis; destruction of these two nuclei caused a quasiabolition of the diurnal TSH peak (only a low amplitude TSH circadian rhythm persisted). Hypothalamic 5HT content was measured in the majority of these experiments; the greatest depletions (near 90%) were observed after two injections of pCPA or in rats bearing raphe lesions. We conclude that the diurnal peak of TSH, observed during the physiological circadian rhythm, is serotoninergic dependent.


A controlled study of prednisone therapy in infantile spasms. A controlled study of 12 patients with infantile spasms was performed to determine the effectiveness of prednisone treatment. Patients were monitored serially, using a time-synchronized polygraphic and video system. Three patients (25%) showed prompt reduction in seizure frequency and normalization of the EEG after institution of treatment. The remaining patients showed no improvement in seizure frequency or significant change in the EEG.


An outbreak of eosinophilic bronchitis in horses possibly associated with Dictyocaulus arnfieldi infection. Eight mature horses which had been affected with a moist cough for six weeks were found to have large numbers of eosinophils in tracheal mucus samples taken by transtracheal washing. These horses were kept on irrigated pasture and fed a hay-free diet. A companion yearling donkey was found to be passing Dictyocaulus arnfieldi larvae in its faeces. Two oral treatments with a dose of thiabendazole (440 mg/kg) resulted in the resolution of the clinical signs and the disappearance of eosinophils from transtracheal washings. The eosinophilic bronchitis seen in these horses was presumed to be a manifestation of prepatent D arnfieldi infestation.


Ionized and bound calcium inside isolated sarcoplasmic reticulum of skeletal muscle and its significance in phosphorylation of adenosine triphosphatase by orthophosphate. Calcium loading of skeletal muscle sarcoplasmic reticulum performed passively by incubation with high calcium concentrations (0.5--15 mM) on ice gives calcium loads of 50--60 nmol/mg sarcoplasmic reticulum protein. This accumulated calcium is not released by EGTA [ethyleneglycol bis-(2-aminoethyl)-N,N,N',N'-tetraacetic acid], but almost completely released by ionophore X-537A plus EGTA or phospholipase A plus EGTA treatment and is therefore assumed to be inside the sarcoplasmic reticulum. This calcium is distributed in one saturable and one non-saturable calcium compartment, as derived from the dependence of the calcium load on the calcium concentration in the medium. These compartments are assigned to bound and ionized calcium inside the sarcoplasmic reticulum, respectively. Maximum calcium binding under these conditions was 33 nmol/mg protein with an apparent half-saturation constant of 5,8 nmol/mg free calcium inside, or between 1.2 and 0.6 mM free calcium inside, assuming an average vesicular water space of 5 or 10 microliter/mg protein, respectively. Calcium-dependent phosphorylation of sarcoplasmic reticulum calcium-transport ATPase from orthophosphate depends on the square of free calcium inside, whilst inhibition of phosphorylation depends on the square of free calcium in the medium. Calcium-dependent phosphorylation appears to be determined by the free calcium concentrations inside or outside allowing calcium binding to the ATPase according to the two classes of calcium binding constants for low affinity calcium binding or high affinity calcium binding, respectively. It is further suggested that the saturation of the low-affinity calcium-binding sites of the ATPase facing the inside of the sarcoplasmic reticulum membrane is responsible for the greater apparent orthophosphate and magnesium affinity in calcium-dependent phosphorylation than in calcium-independent phosphorylation from orthophosphate. Maximum calcium-dependent phosphoprotein formation at 20 degrees C and pH 7.0 is about 4 nmol/mg sarcoplasmic reticulum protein.


Turnover rates of hexokinase I, phosphofructokinase, pyruvate kinase and creatine kinase in slow-twitch soleus muscle and heart of the rabbit. Hexokinase I was purified from rabbit heart to a specific activity of 70 U/mg protein. The purified enzyme was electrophoretically homogeneous with an apparent molecular weight of 102,000. Purified immunoglobulins from sheep were used to titrate the percentage of hexokinase I in various tissues of the rabbit. Precipitating antibodies from sheep were also prepared against rabbit muscle MM-creatine kinase, phosphofructokinase and pyruvate kinase. Apparent turnover rates of these phosphotransferases and of hexokinase I were determined in rabbit heart and soleus muscle by means of the immunoprecipitation technique after single pulse labelling with [U-14Cl]leucine in vivo. Apparent half-lives of phosphofructokinase, pyruvate kinase and hexokinase I were 0.56 d, 0.73 d and 0.93 d in rabbit heart. In slow-twitch soleus muscle half-lives of phosphofructokinase, pyruvate kinase, hexokinase II and creatine kinase were 0.63 d, 0.72 d, 0.85 d and 0.82 d. The similarity of the rate constants of degradation of these enzymes is interpreted as an indication that different tissue concentrations result primarily from different rates of synthesis.


In vivo exploration of the tensile strength of the abdominal wall after repair with different prosthetic materials. Experimental study in the rat. The problem of parietal herniation seems to be a simple mechanical one for which there should be a safe method of repair. In the present study, the bursting strength of abdominal wounds was explored by mechanical investigation and the repair process evaluated at a cellular level by quantitative microscopy. Both methods of investigation show that mesh materials have advantages over nonporous cloth materials in the repair of large defects of the abdominal wall.


Alterations of the nucleus ruber in 3-acetylpyridine intoxication. A light and electron microscopic study. 3-acetylpyridine (3-AP) given in one single dose near to LD50 causes hydropic-vacuolic degeneration and cellular necrosis of varying degree and extension in the red nucleus of white rats in more than 50 percent of the cases. Less frequently similar alterations have been observed in some neighbouring nuclei of the mesencephalon. The regressive damage is remarkably rare if a smaller dose of 3-AP is given and none if the animal is pretreated with nicotine amide. Ultrastructurally the damage of mitochondria is dominant, they might be transformed to cystic lamellar figures. One reason of the enhanced vulnerability to antimetabolite is the outstanding enzyme activity of the red nucleus. In some of the intoxicated animals the six oxidative enzymes tested histochemically show different type of alterations which probably are related to the regressive damage.


Appearance of growth-inhibiting activity (G1 chalone) during ontogenetic development of rat and chick epidermis in vivo and in vitro. A comparative study was carried out between the stage of embryonic development of epidermis and its content of growth-inhibitory activity (G1 chalone). Injections of aqueous extracts from keratinized fetal rat or chick embryo epidermis led to a depression of DNA-synthesis in adult mouse epidermis, whereas extracts from undifferentiated epidermis did not contain such an activity.


Glomerular filtration rate and kidney blood flow in alloxan and streptozotocin diabetic rats. Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow.


[Decurarization using the cation-anion molecular interaction of a myorelaxant and its antagonist]. In experiments on the cat neuromuscular preparation the authors investigated the anticurare action of the new compound IEM-931 having sulphonate-anionic groups 20 A apart. The new compound administered in a dose of 184 mkM/kg prevents and removes the curare effect of rythetronium which is its structural analogue. Regarding tubocurarine the antagonism is displayed, however, only from the dose of 384 mkM/kg. This indicates that efficacy of the anticurare action of IEM-931 is directly related to complimentarity of the interacting molecule structure. The experiment with regional relaxation of the cat muscles shows that the anticurare action of IEM-931 is realized both in the blood and on the cholinoreceptor. Moreover, as a result of molecular interaction the inactive complex is formed.


The sensitizing capacity of Compositae plants. III. Test results and cross-reactions in Compositae-sensitive patients. 25 patients known or suspected to be allergic to different Compositae plants were tested epicutaneously with ether extracts of different Compositae species. 14 persons revealed a chrysanthemum hypersensitivity, 2 were allergic to arnica and 2 to camomile. In 1 patient a positive reaction to tansy was obtained. In the case of the chrysanthemum allergy, this was induced occupationally. All other patients had sensitized themselves by non-occupational contact. Cross-reactions were seen to tansy [14], yarrow [11], camomile [10], arnica and sunflower [5]. The components which are responsible for the sensitization as well as for the crossreactions are sesquiterpene lactones.


[Experimental study of the action of Bunium persicum oil on the functional state of the liver and pancreas]. The effect of Bunium Persicum oil on the indices of lipid-lipoid and protein-nitrogen metabolism and of the enzymes (histidase, arginase, transamidinase, trypsin and trypsin inhibitor) reflecting the function of the liver and pancreas was studied in experiments on white rats. There was an improvement of the indices of protein nitrogen metabolism in administration of the oil alone and combined with ethanol and CCl4. At the same time the content of total lipids and cholesterol in the blood serum and in the liver increased. The activity of the enzymes of the blood serum, liver homogenates and the pancreas reflected organ specificity and changed simultaneously with alterations in the general trend of the metabolism.


Two cases of penicillamine-induced pemphigus erythematosus. 2 women, 62 and 69 years old, both suffering from rheumatoid arthritis, were treated for 1 and 1 1/2 years, respectively, with penicillamine. Both developed a bullous eruption which according to clinical and histological picture, immunofluorescence studies and to light provocation, as well as in 1 case to antinuclear antibody findings corresponded to pemphigus erythematosus. In spite of treatment with prednisone and azathioprine, they still keep developing bullae.


Neutrophil functions in acne conglobata. Chemotaxis, random migration, phagocytosis, spontaneous and stimulated NBT reduction were evaluated in neutrophils from the peripheral blood of 8 patients with acne conglobata and were found to be normal. Only 2 patients had an increased spontaneous NBT reduction, and another exhibited a defect in neutrophil adhesiveness. On this basis, intrinsic defects of the major neutrophil functions, as evaluated in vitro, can be excluded in acne conglobata.


Epidermodysplasia verruciformis in Nigerians. An analysis of the clinical and pathologic characteristics of 12 Nigerian patients with epidermodysplasia verruciformis (EV) is presented. Two morphological variants have been observed, typical wart-like flat-topped papules and larger confluent plaques. Seborrhoeic keratoses were observed in patients with the second morphological variety of EV. Solar elastosis was found in biopsies taken from EV lesions in this subgroup of patients. A particular rarity of seborrhoeic keratosis in Africans is emphasized as no single African case of seborrhoeic keratosis was found apart from patients with EV. No malignant epithelial skin tumours were found in the whole group. Factors underlying an apparently more benign course of EV in Africans are discussed, and the literature on EV in African is reviewed.


Percutaneous absorption of clioquinol (Vioform). The percutaneous absorption of clioquinol from three different preparations for skin treatment (Vioform cream, Locacorten-Vioform cream and Vioform-Hydrocortisone cream) was evaluated. After topical dosages corresponding to 30 mg clioquinol, concentrations in the blood were below the detection limit of the analytical procedure, i.e., smaller than 0.02 micrograms/ml; therefore the percutaneous absorption was evaluated by measuring cumulative urinary excretion of clioquinol and was compared to that found after an equivalent oral dose. The study was carried out in 4 healthy volunteers. The topical preparations were applied under occlusive dressings. Following epicutaneous application of the three topicals in quantities containing 30 mg clioquinol each, the urinary excretion of the drug was between 1.2 and 3.6% of the applied dose. When the same dose of clioquinol was administered orally to two volunteers, 52.4 and 92.9% of the dose was excreted in the urine. Taking the urinary elimination as the minimal amount of drug absorbed, the extent of percutaneous absorption from the three dermatological preparations amounted to 1.2-3.6% of the applied dose. There was no difference in the pattern of urinary excretion products among the three topicals and the oral formulation. The bulk of clioquinol was excreted as glucuronide (mean: 96 +/- 3%) and only a small fraction was excreted as sulfate (mean: 3.8 +/- 3%). A small amount of free clioquinol (1.1%) was measured in 1 subject only after the oral dose.


[The endocardial ventricular activation map in a case of intermittent BBS in phase III (author's transl)]. To obtain information on endocardial activation-sequence, unipolar recordings at seven left ventricular and six right ventricular points were performed in a 37-year-old man suffering from cardiomyopathy and tachycardia-dependent left bundle branch block (LBBB). Results were as follows: 1) the recovery time was longer in anterior than in posterior portion of left bundle branch fibers; 2) an high posterior left ventricular point was directly activated via posterior left bundle branch fibers; 3) the directly activated left ventricular zone was too small and relatively too late excited in respect of the right interventricular septum, from which the stimulus reached the left septum, to mask the LBBB electrocardiographic pattern; 4) in the presence of tachycardia-dependent LBBB the duration of left ventricular endocardial activation was about twice (62 msec) that found in the absence of tachycardia-dependent LBBB (28 msec).


[The intra-operative proof of occlusion of the tubes in tubal sterilizations (author's transl)]. In tubal sterilization operations with a plastic clip failures with subsequent pregnancies become only known by misplacement of the clips. Failures are more frequent when the clips are placed through a posterior colpotomy. In 163 laparoscopic tubal sterilization with the Tuplar-clip during the last 2 1/2 years no subsequent pregnancy was observed. The carbon-dioxide pertubation or the chromo-pertubation after occlusion of the tubes with a clip permits an immediate intra-operative proof of secure bilateral tubal occlusion. A pregnancy due to faulty placement of the clip is then no longer possible. Other advantages of this method of tubal sterilization are mentioned.


[Lesion of the aorta abdominalis in gynecologic laparoscopy (author's transl)]. Two cases with lesions of abdominal aorta during gynecological laparoscopy are described. One case was fatal. The second patient could be saved from death. The misadventures occurred in diagnostic respectively operative laparoscopy.


[Hybrid plasmid pSD1 containing the immunity region of bacteriophage lambda]. Hybrid plasmid pSD1 carrying the immunity region of the coliphage lambda and bio operon have been obtained by means of studying the efficiency of transcription DNA fragments in the plasmid RSF2124. The molecular weight of this plasmid is 17.2 Md. The growth inhibition of phage lambdavir has been observed in cells carrying the new hybrid plasma. The properties of the plasmid pSD1 and probable reasons of the growth inhibition of phage lambdavir are discussed. The hybrid plasmid pSD2 carrying genes R, A and J of phage lambda has been constructed on the basis of the plasmid RSF2124. There are cohesive ends in this plasmid which make possible its packing in the phage lambda head. Hybrid plasmid pSD3 carrying genes P and Q of phage lambda has also been constructed.


[Inheritance of human fingerprints].

[Inheritance of human fingerprints]. Polygenic threshold model of finger dermatoglyphics inheritance is worked out on the basis of family and population data. According to the model, ulnar loops are subthreshold patterns, which transforms into whorl or arch under the control of SU and SR gene complexes. Epistasis-hypostasis interactions take place between genes of SU and SR complexes. Classification of phenotypes for finger dermatoglyphics is offered and the frequency of these phenotypes in three populational samples of Kiev is studied.


[Transposition of the deo operon structural genes in Escherichia coli K-12 to plasmid RP4 using bacteriophage mu]. Transposition of the structural genes of the deo operon of Escherichia coli K-12 into plasmid RP4 by means of temperate bacteriophage Mu was carried out. Some variants of composite RP4-deo-Mu plasmids were obtained and the expression of the deo genes integrated into the RP4 plasmid genome was studied. It was shown that the expression of these genes remains under the control of the chromosomal regulatory genes (deoR and cytR); although the activity of thymidine phosphorilase in the strain E. coli which contains hybrid plasmid is 4-6 fold greater than that in strains of E. coli with chromosomal localization of the deo operon.


[Population genetics of the population of the European north of the RSFSR. IV. The level of blood relationship in 5 villages of Pinega District, Archangel Province]. Computer program "RODAN-1" is used for inbreeding coefficient estimation. The population studied consists of two communities of 5 villages. 385 marriages were computed. The coefficient of inbreeding is 0.00145 for pedigree for rural Russian population (the Arkhangelsk region). The inverse dependence between a village size and corresponding data of inbreeding coefficient is suggested. An attempt was undertaken to estimate the genealogical information value for each pedigree and average information value for a village.


Construction and analysis of recombinant lambda phages containing mitochondrial DNA fragments. Rat mtDNA has a molecular length of about 16 kilobase (kb) pairs and is cleaved into seven fragments by restriction endonuclease EcoRI. These fragments were cloned in Escherichia coli K-12 host using lambda gtWES.lambda B' (lambda gtWES.lambda B, for short, in this paper) as a vector. Recombinant DNAs containing one or a few fragments of the mtDNA were transfected to CaCl2-treated E. coli, and the plaques containing specific recombinant phages were selected. DNA amplified in the recombinanat phage lambda gt.mt was shown to contain the same restriction endonuclease cleavage sites as those found in the mtDNA. Present results permitted the DNA sequencing of any portion of the mitochondrial genome.


Inceptor and origin of DNA replication in lambdoid coliphages. I. The lambda DNA minimal replication system. In a pBR313-lambda dv hybrid plasmid system, stepwise deletion and serial cloning procedures have led to a functional dissection of the DNA replication region of lambdoid bacteriophages lambda, 434 and 21. A simple system for initiation of DNA replication has been detected within lambdoid replicator DNAs, which is active in the absence of several normal replication elements, including the origin of replication (ori) and product of gene O. This "minimal" (or "mini") initiation system depends on the p0 or substitute leftward promoter in conjunction with the newly discovered "inceptor" (ice) element, which is located within the cII gene. Even the fragments containing ori are unable to initiate replication in these hybrid plasmids as long as fragments containing ice are missing. The base sequence of ice resembles transcriptional terminators and it appears to control both termination of primer RNA and inception of daughter strand DNA synthesis. Initiation in the p0-ice mini system of lambda or 21 phages requires the gene P product. Hwever, mini replication of 434 DNA hybrid plasmids required neither O nor P proteins, although there are only two single-base changes in the 434 inceptor sequence. The mini system is repressed by the elements of the maximal lambda replication system, as described in the accompanying publication.


Inceptor and origin of DNA replication in lambdoid coliphages. II. The lambda DNA maximal replication system. In pBR313-lambda dv hydrid plasmids a second system for initiation of DNA replication has been detected in lambdoid replicator DNAs (in the absence of the p0 promoter). The "maximal" (or "maxi") initiation system depends on the origin of replication (ori) sequence, in conjuction with the "inceptor" (ice) element located in the lambdoid cII genes. Only leftward, but not bidirectional, primer RNA synthesis seems to be initiated at ori in its newly defined boundaries, and it appears to be catalysed by dnaG-coded primase. Only if transcriptionally activated, will ori effectively initiate lambda specific, O and P-dependent "maximal" hybrid-plasmid replication. In addition, it will repress a complete lambda "minimal" initiation system in cis, i.e., if present on the same plasmid molecule. This newly discovered repressive activity of the ori system depends on only three factors: an intact left section of ori, the O product, and transcriptional activation of ori (rightward or leftward). A repressed minimal initiation system will regain its activity as soon as a segment carrying either part of the O gene or a promoter for transcriptional activation is delected from such a plasmid which was combining both the "mini" and "maxi" systems of lambda replication.


Atypical leukodystrophy with accumulations of sulfatide and mucopolysaccharide. 1. Follow-up studies of two siblings with mental retardation, progressive paraplegia and dementia were reported. 2. The brain and visceral organs of a patient (elder brother) who died recently were investigated histopathologically, electronmicroscopically and neurochemically. a. Moderate, diffuse demyelination occurred throughout the white matter of the central nervous system. b. Two abnormal materials were deposited in the white matter: one showed metachromasia containing sulfatide and another had staining characteristics of acid mucopolysaccharide histochemically. Electronmicroscopically, the former was a conglomerate of electron-dense materials of various degrees and the latter had a membrane-limited granular structure. The myocardium contained the same mucopolysaccharide material as that in the brain. c. Slight increase of sulfatide was found in the cerebral white matter. Arylsulfatase A activities were preserved in the brain as well as in the liver. Contents of hexosamine and uronic acid in the white matter were about three or five times as much as that of the controls. Electrophoresis on cellulose acetate membrane showed that acid glucopeptide was the main component of the mucopolysaccharide extracted from the brain.


[Predictive diagnostic value of renal blood flow measurement in renovascular hypertension (author's transl)]. To improve diagnostic procedures and preoperative prognosis in hypertensive patients with angiographically proven renal artery stenosis pre- and postoperative studies of renal hemodynamics (133xenon washout technique) were carried out in patients with normalized, improved and unchanged hypertensive blood pressure values following renovascular surgery. The results demonstrate that renal blood flow in both the operated and non-stenosed kidneys has to be in a normal range expecting a normalization of blood pressure. The existence of a preoperative normal cortical flow rate in the stenosed kidney may be a hint to a normalization of hemodynamic of the involved kidney following reconstructive surgery.


[Long-term follow-up after spontaneous contrast extravasation during infusion urograms (author's transl)]. In 1978 we described 18 patients with acute spontaneous rupture of a pelvi-calycine system; these have now been followed up with the exception of four patients. The aim was to determine whether, and how frequently, long-term complications occur, such as chronic persistent rupture and particularly whether local retroperitoneal fibrosis develops. The clinical history, infusion urograms and cinematography provided no evidence of any abnormalities except in one case. In this patient changes interpreted as retroperitoneal fibrosis were found, but this was the only patient in whom surgery had been performed. It is thought that the operation played a significant part in the development of this complication. Our observations confirm that infusion urograms in acute urinary tract obstruction are an acceptable method of investigation and that extravasation should be treated conservatively. The exception to this rule is the presence of preexisting infection of the urinary tract.


[The treatment of idiopathic varicocoeles by transfemoral spiral occlusion of the left testicular vein (author's transl)]. The standard surgical procedures for the treatment of idiopathic varicocoeles are unsuccessful in, or show a recurrence rate of, up to 25%. An alternative method is transcutaneous embolisation using the Seldinger catheter technique. For this technique of transcutaneous catheter embolization, we have used the Gianturco spiral. The embolization is carried out following diagnostic transfemoral phlebography of the left testicular vein, which also provides the indications or contra-indications for this procedure. The method has been used on nineteen patients with varicocoeles requiring treatment; amonst these were three patients who had had unsuccessful operations. Follow-up period so far is six months. In all cases the varicocoele had disappeared, including one patient who had suffered complications following previous surgery.


[Grey-scale ultrasound in the diagnosis of cystic lesions of the kidney (comparison with excretory urography) (author's transl)]. In a total of 155 cystic renal lesions diagnozed by means of ultrasound the correct differentiation of cystic or solid consistency could be determined in 96.8% of cases. The sonographic result was inaccurate or false in only 2.6%. Sonography also determined the correct morphological and anatomical type of the liquid space-occupying formation in 89%. Pathological cavities of the renal pelvis as well as hydronephroses were the cause of incorrect diagnoses. 36.6% of solitary renal cysts revealed by ultrasound (average diameter of cyst: 3.9 cm), could not be detected by pyelography; radiology most frequently failed to determine cortical renal cysts. Sensitivity and specificity of nephrosonography for detection of cystic malformation of the kidney were distinctly better than pyelography. Out of a total of 34 patients with hereditary polycystic renal disease (HRPD) sonography diagnozed multiple cysts of the liver in 15 cases (44%). The use of ultrasound in examining relatives of patients with HPRD enables an earlier diagnosis of the chronic progressive disease.


[Sonographic findings in blunt renal trauma (author's transl)]. The kidneys are beautiful organs for ultrasonography, because of their position, well defined characteristic appearance and excellent acoustic qualities. This is highly important for assessing all pathologies leading to macromorphological changes of the kidneys including these in blunt renal trauma. We could'nt find any paper on this topic in the recent literature available for us. Our own material in renal blunt trauma includes 17 patients. There were no pathological findings in 7, and pathological findings in 10 of them. Sonographic accuracy in severe trauma of the kidney is about 100%, excluding hydronephrotic kidneys, which cannot always be distinguished from a bigger parapelvic cyst. Urogramm resp. Uronephrotomogramm should be performed and studied thoroughly. Exceptions are Iodine allergy and pregnancy.


[The value of the excretion urogram following cerebral angiography (author's transl)]. Routine abdominal films were obtained after 100 carotid angiograms in order to see the excretion urogram. In 64 patients the contrast was adequate for diagnosis. In twelve of these a significant finding was observed. This simple additional examination was particularly valuable in searching for a primary tumour when the angiogram had demonstrated cerebral metastases.


Barium enema in pediatric intussusception; a review of 108 cases. A material of 108 patients with 125 intussusceptions was evaluated retrospectively. Barium enema is recommended as an excellent diagnostic tool. Reduction should be tried in all cases except those with signs of peritonitis, because the enema causes fewer complications and leads to a considerably decreased hospital stay.


[Double colon--a rare case of intestinal duplication (author's transl)]. A case of duplication of the entire colon, in which the supernumerary colon had no communication with the small intestine, is presented and illustrated. After review of the literature the special clinical and radiologic problems of these intestinal duplications are discussed.


[Retropneumoperitoneum and pneumomediastinum following proctoscopy (author's transl)]. A 66-year-old patient developed a retropneumoperitoneum and pneumomediastinum after a proctoscopy. Following the examination, which was done as an out patient, he had some pain but was able to reach home without difficulty. Radiography of the abdomen on the next day showed definite gas collection round the right kidney and below the middle of the diaphragm. The mediastinum showed some translucencies consistent with cranial spread of air from the retropneumoperitoneum; it was particularly marked round the aorta. The film also showed supraclavicular emphysema. After being placed supine the patient's symptoms rapidly disappeared. There were no complications and no treatment was necessary. The case is discussed in relation to the relevant literature.