[Renal kallikrein-kinin system and control of blood pressure (author's transl)]. Kallikrein excreted with the urine appears to be formed in the kidney. The kallikrein-kinin system in the kidney is localized in the distal nephron from the juxtaglomerular apparatus to the collecting duct. It has been shown that intrarenal infusion of kinins produces an increase in renal blood flow as well as diuresis and natriuresis. Part of the effect of kinins appears to be mediated by the release of prostaglandins. However, the precise role of the renal kallikrein-kinin system in sodium and volume homeostasis and in blood pressure regulation still remains to be determined. Mineralocorticoids as well as the diuretics furosemide, bumetanide and bendroflumethiazide increase, spironolactone decreases kallikrein excretion. Urinary kallikrein has been shown to increase acid-as well as cryoactivation of prorenin in vitro. It is unclear as yet, however, whether the renal kallikrein-kinin system takes part in converting inactive prorenin into active renin in vivo. There are reports on subnormal, normal as well as increased kallikrein excretion in spontaneously hypertensive rats. In rats susceptible to the hypertensive effect of salt a substantially decreased excretion of kallikrein has been observed. Kallikrein excretion has been described to be increased in primary aldosteronism and to be reduced in a proportion of patients with established essential hypertension. In patients with labile hypertension, however, kallikrein excretion appears to be normal suggesting that decreased urinary kallikrein in essential hypertension is a consequence rather than a cause of hypertension. The renal kallikrein-kinin system does not appear to play a primary role in the pathogenesis of hypertension.


Salivary kallikrein excretion in hypertension. According to immunohistochemical investigations kallikrein in the majors salivary glands is located predominantly at the apical border of the striated duct cells and as a luminal rim in the main excretory ducts. Comparatively the highest concentrations are observed in the submandibular gland of rats and cats in the cytoplasmic granules of the granular tubules. In normal humans and rats the kallikrein activity of parotid saliva is inversely related to flow rate and sodium concentration. An increased salivary kallikrein concentration is found in human essential hypertension and renoparenchymal hypertension associated with impaired kidney function. Furthermore in rats with various forms of hypertension (genetic hypertension, DOCTMA salt and renovascular hypertension) the salivary kallikrein secretion - as determined by the BAEE-esterase activity - is enhanced. In contrast to the kallikrein secretion the flow dependent sodium concentration of parotid saliva is reduced in human essential and renoparenchymal hypertension as well as in rats with various forms of experimental and genetic hypertension, which indicates an enhanced sodium reabsorption in the glandular duct system. Furthermore in most forms of hypertension, there is a tendency of higher potassium levels in the saliva. The pathogenesis of the enhanced glandular kallikrein secretion in hypertension is discussed with regard to a counterregulatory mechanism in hypertension as well as to a sympathicoadrenergic activation. The enhanced sodium reabsorption in the duct system in the various forms of hypertension could be the cause as well as a consequence of the enhanced kallikrein secretion.


[Vitamin D metabolism in kidney insufficiency: disorders of an endocrine regulatory zone]. The vitamin metabolite 25(OH)D is transformed into the active secosterole 1.25(OH)2D3 in the proximal tubular epithelium of the kidney. This transformation is disturbed in patients with renal insufficiency. However, this review shows that presumably not all vitamin D dependent disturbances in patients with renal insufficiency are explicable merely as the consequence of reduced renal synthesis of 1.25(OH)2D3 secondary to nephronal loss. In incipient renal failure, vitamin D dependent functions (calcemic action of PTH, intestinal absorption of Ca) are disturbed. Yet, circulating 1.25(OH)2D3 levels are slightly elevated. This finding is compatible with an inadequate response of the renal 1-alpha-hydroxylase system to activating stimuli (hyperparathyroidism, hypocalcemia, fasting hypophosphatemia) and/or end-organ resistance to the action of 1.25(OH)2D3. Osteomalacia in renal insufficiency cannot entirely be explained as the consequence of a reduction of the serum-concentration of any of the known vitamin D metabolites [25(OH)D3; 1.25(OH)2D3; 24.25(OH)2D3]. The relatively poor response of osteomalacia of uremic patients to the administration of 1.25(OH)2D3 leads to the question of whether other vitamin D metabolites or non-vitamin D related factors are important in its genesis. Critical information is lacking with respect to 1.25(OH)2D3 receptors, post receptor events and interaction between vitamin D metabolites and PTH in bone cells of such patients. A specific action of 1.25(OH)2D3 on longitudinal growth of uremic children has been described. However, several clinical and experimental studies failed to provide evidence of normalization of growth by 1.25(OH)2D3 and failed to show differences in this respect between vitamin D and 1.25(OH)2D3. Currently, it remains undecided whether vitamin D metabolites affect PTH secretion, and if so which vitamin D metabolite is involved. Clarification of this problem is of paramount importance for the therapeutic suppression of the parathyroids of uremic patients. Vitamin D metabolites play an important role in some organ functions unrelated to homeostasis of Ca-Pi-metabolism (e.g. muscle, testis, pancreas, etc). The loss of such function is of potential importance in the genesis of the uremic syndrome and its imcomplete reversal by hemodialysis.


Role of parathyroid hormone in the pathogenesis of the uremic manifestations. A multitude of clinical and experimental data points toward the role of the elevated blood levels of parathyroid in the pathogenesis of the uremic syndrome. The possible pathways through which parathyroid hormone may exert its deleterious effects and evidence for its toxicity are discussed.


[Principles of epithelial transport in the kidney and intestines]. Epithelia of kidney and small intestine consist of one layer of cells which, at their luminal edge, are linked together by terminal bars. Solute transport proceeds either across the cells, which is true of all active transports, or it proceeds paracellularly through the basolateral spaces and terminal bars and is then passive. The driving force for the active transport of a substance is derived either directly from metabolism (primary active transport), or from the gradient of another solute, usually Na+, which in turn is created by primary active transport. In the latter case the transport is referred to as secondary active. The driving forces of passive transport are the electrochemical gradient of the respective substance and solvent drag. The proximal parts of the kidney as well as of the intestine are leaky so that a considerable part of net reabsorption proceeds passively. Their distal parts, however, where the transport is regulated, are tight so that large concentration differences can be created and maintained. Transcellular active transport is only possible if the cells are polar, i.e., the transport characteristics of the luminal cell membrane differ from those of the contraluminal cell membrane. By measuring the cellular electrical potential difference or by measuring transport into isolated plasma membrane vesicles from either cell side the driving forces for the two transport steps, the luminal and contraluminal, have been elucidated. Schemes for the transport steps in the proximal tubule and in the small intestine are given. They show the principal similarity of the transport of many substances in both epithelia.


Systemic involvement in tuberculoid leprosy--pathogenesis of leprosy. Occurrence of leprous pathology/bacilli in the internal organs in cases of polar tuberculoid leprosy, support the systemic nature and haematagenous transmission and spread of the disease process. Pathogenesis of leprosy has been postulated.


'Pulsed' rifampicin therapy in leprosy. A clinical study. A trial of monthly administration of Rifampicin in 2 doses of 900 mg each on successive days for 3 months along with DDS 100 mg daily has been undertaken. The results have been compared with 2 groups of controls, one, which was administered 300 mg Rifampicin daily for 3 months followed by DDS, and the other which received 100 mg DDS alone. The findings show that the efficacy of this pulsed regimen is almost similar to continuous rifampicin administration and better than DDS alone. No significant adverse effects were encountered in the trial. The regimen thus merits large scale trials in the field.


The keratoacanthoma: a review.

The keratoacanthoma: a review. The keratoacanthoma (KA) is a relatively common tumor which most often occurs on the sun-exposed areas of light skinned individuals of middle age and older. It may be viewed as an aborted squamous cell carcinoma that only in rare instances evolves into a progressively growing squamous cell carcinoma. As such, the recognition of the true nature and the proper management of this tumor is of considerable practical importance. The rapid evolution of a KA may be divided into a proliferative stage, a fully developed tumor, and an involuting stage. Within weeks it develops from a rapidly growing, firm, smooth nodule into a mature bud or dome-shaped tumor with a central keratotic core that finally degenerates into an involuting keratinous mass. Although the KA usually appears as a solitary lesion, multiple tumors may be found, as may a number of morphologic and syndromic variants, including the appearance of the KA in the Torre syndrome. The KA is likely to be derived from cells of the hair follicle. Its etiology is unclear, although ultraviolet light, viruses, oncogenic chemicals, and epidermal growth factor have been considered. The histologic features of the KA are often very similar to those of a cutaneous squamous cell carcinoma; however, the tumor architecture usually provides a basis for their distinction.


Chemoimmunotherapy with or without oophorectomy in premenopausal patients with advanced breast cancer. Ninety-eight premenopausal patients with stage IV breast cancer were treated with chemoimmunotherapy alone, or with combination oophorectomy-chemoimmunotherapy either simultaneously (chemoimmunotherapy within four weeks of oophorectomy) or sequentially (delayed chemoimmunotherapy until evidence of progressive disease or no response to oophorectomy). The chemoimmunotherapy consisted of a three-drug combination of Adriamycin, cyclophosphamide, and 5-fluorouracil or Ftorafur; immunotherapy consisted of either oral levamisole, BCG by scarification, or a combination of both. Forty patients underwent simultaneous oophorectomy-chemoimmunotherapy, with a response rate of 85% and a median duration of response of 25 months. Response rate of 69% and a median duration of response of 16.6 months was observed with the 29 patients who received sequential oophorectomy-chemoimmunotherapy. Another 29 patients were treated with chemoimmunotherapy alone and achieved a response rate of 87% and a median duration of response of 11.8 months. Though there were no significant differences in the response rate, patients treated with chemoimmunotherapy alone had a significantly shorter median duration of response (P less than 0.05). This would suggest that oophorectomy in combination with chemoimmunotherapy is the most favorable treatment modality for premenopausal patients with advanced metastatic breast cancer.


Para-aortic node biopsy in staging women with cervical, ovarian and endometrial carcinoma: a review. In women with gynecologic malignancies the para-aortic lymph nodes are not routinely treated. However, pretherapy surgical staging has now disclosed an incidence of para-aortic node metastasis of 10.3% for presumed stage I and II ovarian cancer, 8.0% for stage I endometrial carcinoma, and 23.5% for stage II, III, and IV cervical cancer. Prospective trials to evaluate therapy directed to the para-aortic nodes in women with early ovarian and endometrial carcinoma have not been carried out. Moreover, the results of high dose irradiation to biopsy proven metastasis to the aortic lymph nodes from cervical cancer has resulted in only 11.9% survival without recurrence at two years.


Physiological defence against xenobiotics at their portals of entry to the organism. The size and relatively high enzyme activity of the liver means that it has the major role in the biotransformation of xenobiotics in mammals. The tissues through which xenobiotics enter the body, lungs, skin, and gastrointestinal tract, have, however, quite a significant capacity for biotransformation, too. Major fractions of small doses of xenobiotics are therefore already metabolized and inactivated before the compounds have penetrated into the body. Most xenobiotics appear in the food and fluid ingested. This emphasises the importance of the gastrointestinal mucous membrane as the first line of defence of body against foreign chemicals. The biotransformation capacity varies with age and environmental chemical exposure, and depends on species and strain.


Ligandin: review and update of a multifunctional protein. Ligandin is an abundant soluble protein of relatively short half life which is induced by many drugs and chemicals and stabilized in the absence of thyroid hormone. The protein is strategically concentrated in cells associated with transport and detoxification of a large variety of potential endogenous ligands such as bilirubin and perhaps heme, and exogenous, such as a multitude of drugs and chemicals. The protein is a dimer in rat liver. Whether it is a primary gene product or whether at least two genes are involved is not known. The protein has broad, low affinity catalytic activity for ligands having electrophilic groups and hydrophobic domains. It either catalyzes formation of GSH conjugates (e.g. bromosulphophthalein), noncovalently binds prior to biotransformation or excretion in bile (e.g. bilirubin), or covalently binds (e.g. activated carcinogens) potential ligands. Recent studies expand the scope of ligandinology to include its possible role in chemical carcinogenesis, diagnosis of inflammatory and neoplastic disease of the liver and kidney, and participation in intracellular transport. Although some of the roles that have been outlined are speculative, any single function is important. These are primitive enzymes and nonspecific binding proteins but "it is precisely their simplistic design that allows such protein serviceability".


[Late results of frontal bone reconstructions using Paladon]. Report about 12 cases of defect of the frontal bone: state after radical operation of the frontal sinus (Riedel's operation) or after removal of bone splinters after injury. 6--12 months later a paladon-inlay (acrylate prosthesis) can be implanted to fill the defect and to restore the profile. Description of the production, forming, sterilization and operative implantation of the prosthesis. The patients have been observed up to 18 years. In one case the implanted material was removed after 10 years because of recurrent local suppurations. All the other patients showed an uncomplicated course until today; the cosmetic and functional result was permanently good.


[Replacement  of the tympanic membrane by corneal transplantation (keratomyringoplasty)]. The authors present a new method of the substitution of the ear-drum with cornea transplantation, applied with success in 28 cases. They have established that the various tissues (skin, veins fascia, etc.) applied up to now for myringoplastic are not so suitable as the cornea, because the latter is similar to the ear-drum, according to its histological construction and physical properties. The execution of the operation, the technique of the removal of the cornea from a corpse, as well as the preparation of the auditory meatus and the inserting of the cornea are discussed in detail. The removal of the cornea can be carried out in its whole or lamellated. In contrast to ceratoplastic, the cornea need not remain transparent in ceratomyringoplastic, because, in the latter case, only its tectorial and sound-conduction effect is needed.


[Beginnings of endoscopy].

[Beginnings of endoscopy]. At the beginning of the 19. century emphasis was put on the research for possibilities to get a look into the interior of the abdominal cavity. The "body-cavity" which seemed to be most easily to access was the bladder and thus the development of the endoscopy is practically identical with the elaboration of the cytoscopy. This survey shows the starting phases as well as the further developement of the endoscopy as oesophagus-, gastro- and proctoscopy, the application on the gynaecological sector and the beginning of the laryngoscopy by Czermak and Türck in 1885, although already before their experiments in London in 1829 an instrument being similar to the laryngoscope was described by Babington.


[Hereditary storage diseases of the liver (author's transl)]. Storage diseases of the liver are reviewed, classified according to the clinical symptoms. Glycogen storage diseases go along with enlargement of the liver, - the size of the spleen being normal in the beginning; presenting symptoms in many cases are metabolic disturbances as for instance hypoglycemia. Acute symptoms due to derangement of liver function occur in galactosemia and in hereditary fructose intolerance when uptake of the hexoses is not tolerated. Splenomegaly and hepatomegaly are typical in certain lipid storage diseases; these diseases may as well exhibit hematologic symptoms. Bone dysplasias are discussed finally, which use to go along with enlargement of the liver due to storage of compounds not metabolized.


The nature of the genetic determinant for the SHV-1 beta-lactamase. In two unrelated plasmids of incompatibility groups FII and N the gene for the SHV-1 beta-lactamase exists as part of a transposable element of molecular weight 9.5 megadaltons. This transposon has moved onto plasmids of at least three incompatibility groups; PI, Ialpha and J. This confirms the suggestion that the recent spread of the SHV-1 beta-lactamase has been associated with the transposition of the genetic determinant of this enzyme between unrelated plasmids.


Altered chemical properties in three mutants of E. coli RNA polymerase sigma subunit. We have analyzed some chemical properties of the sigma subunit of RNA polymerase from the sigma mutants: rpoD1 (Gross et al., 1978), rpoD2 (formerly known as alt-1) (Silverstone et al., 1972; Travers et al., 1978), and rpoD800 (Gross et al., 1979). Each of the three mutants is located at about 66 min on the E. coli genetic map and exhibits an alteration in the enzymatic properties of its sigma subunit. The tryptic peptides and isoelectric focusing behavior were analyzed for mutant and wild type sigma. A single, but different altered lysine tryptic peptide was observed for each mutant. No altered arginine tryptic peptides were observed. The rpoD800 mutant sigma showed an altered isoelectric point. These studies provide chemical evidence that the sigma polypeptide in all three mutants is altered and strongly support the conclusion that the mutations are in the structural gene for sigma.


Abolition of the cyclic variations in radiosensitivity during meiosis in a sporulation mutant blocked in premeiotic DNA synthesis. The response to ultraviolet light (254 nm) of two sporulation mutants during the meiotic process was compared to that of a wild type diploid strain of Saccharomyces cerevisiae. The cyclic pattern for cell killing and rho- induction characteristic of diploid wild type cells persists in a strain able to perform the premeiotic DNA synthesis but which is blocked in the further steps of meiosis (spo8 DMS1). On the contrary, these fluctations are abolished in a derived mutant (spo8 dsm1) which is blocked in the premeiotic DNA synthesis. Under these conditions, the response to cell killing can be dissociated from the observed for rho- induction.


A novel priming system for conjugal synthesis of an IncI alpha plasmid in recipients. Synthesis of DNA complementary to the transferred strand of an IncI alpha plasmid has been shown previously to require DNA polymerase III. The possible involvement of the two defined priming proteins of Escherichia coli K12, RNA polymerase and primase, in initiating this conjugal DNA synthesis had been examined. Primase was inactivated using temperature-sensitive dnaG3 mutants and RNA polymerase was inhibited using rifampicin. When these two proteins were simultaneously inactivated in both parental strains, the average recipient synthesised at least one single-stranded equivalent of R144drd-3 before the rifampicin-treated donors lost the ability to transmit DNA. It is proposed that the product of a plasmid transfer gene is responsible for initiating this DNA synthesis in recipients. The results imply that this protein is supplied by the donors.


Natural premature protein synthesis termination can be reduced in Escherichia coli by decreased translation rates. Peptidyl tRNA hydrolase is an essential enzyme for normal growth inasmuch as a mutant strain of Escherichia coli with a temperature-sensitive hydrolase cannot continue protein synthesis at the non-permissive temperature. In the absence of hydrolase peptidyl tRNA rapidly accumulates. Why peptidyl tRNA should be formed is the subject of this report. The rapid rate of protein synthesis is likely one mechanism of formation of peptidyl tRNA. A strA mutant of the hydrolase (pth-1) mutant strain that has a 40% reduction in amino acid polymerization rate can grow at 42 degrees C. StrA mutants with normal polymerization rates, however, cannot grow at 42 degrees C when pth-1 is present. Furthermore, addition of low levels of chloramphenicol (2--4 micrograms/ml) but not several other tested drugs, phenotypically suppressed pth-1 at 42 degrees C. Chloramphenicol, at these concentrations, was found to reduce the amino acid polymerization rate 30--40%. On the other hand, no evidence could be found that amino acyl tRNA selection errors are incorporated into pseudo revertants of the pth-1 strain.


A cold-sensitive mutant of Saccharomyces cerevisiae defective in ribosome processing. Cold-sensitive mutants of Saccharomyces cerevisiae isolated by tritium suicide were screened for defects in ribosome biosynthesis. The biochemical defects of mutant dip-1 (defective in processing) were characterized; it is defective in ribosome biosynthesis at the level of production of the primary 35S transcript. At restrictive conditions mutant dip-1 accumulates abnormal rRNA in addition to wild-type rRNA. In the mutant the first observable transcription product was a 14SRNA species which had sequence homologies to 18S rDNA and was the major rRNA component of the 40S ribosomal subunit. In addition, the ribonucleoprotein particles of dip-1 harbored RNA molecules with homologies to yeast rDNA which comprises the spacer region between 18S and 25S rDNA cistrons. Possible causes for the defective production of rRNA and its assembly into subunits are discussed.


Outer membrane protein a and other polypeptides regulate capsular polysaccharide synthesis in E. coli K-12. capR (lon) mutants of Escherichia coli K-12 are mucoid on minimal agar because they produce large quantities of capsular polysaccharide. When such mutants are transformed to tetracycline resistance by plasmid pMC44, a hybrid plasmid that contains a 2 megadalton (Mdal) endonuclease EcoR1 fragment of E. coli K-12 DNA joined to the cloning vehicle-pSC101, capsular polysaccharide synthesis is inhibited and the transformed colonies exhibit a non-mucoid phenotype. Re-cloning of the 2 Mdal EcoR1 fragment onto plasmid pHA105, a min-colE1 plasmid, yielded plasmid pFM100 which also inhibited capsular polysaccharide synthesis in the capR mutants. A comparison of the polypeptides specified by both plasmids pFM100 and pMC44 in minicells demonstrated that seven polypeptide bands were specified by the 2 MDal DNA, one of which was previously demonstrated to be outer membrane protein a; also known as 3b or M2 (40 kilodaltons, Kdal). Plasmid mutants no longer repressing capsular polysaccharide synthesis were either unable to specify the 40 Kdal outer membrane protein a or were deficient in synthesis of 25 Kdal and 14.5 Kdal polypeptides specified by the 2 Mdal DNA fragments. Studies with a minicell-producing strain that also contained a capR mutation indicated that the capR gene product regulated processing of at least one normal protein, the precursor of outer membrane protein a.


Plasmid cistrons controlling synthesis and excretion of the exotoxin alpha-haemolysin of Escherichia coli. The synthesis and secretion of the toxic exoprotein alpha-haemolysin of E. coli PM152 is coded by the transmissible plasmid pHly152 (41 x 10(6) dalton) as shown by the transformation of the plasmid DNA and the isolation of mutants that are specifically altered in the synthesis and transport of haemolysin. These mutants were obtained by chemical mutagenesis and insertion of the ampicillin transposon (Tn3) into pHly152. Tn3 transposition was also used for the identification and the location of the cistrons on pHly152 essential for haemolysis. The EcoRI and HindIII fragments of the haemolytic plasmid pHly152 were cloned and used for the complementation of the haemolysis negative Tn3 insertion mutants. A DNA segment of 3.2 x 10(6) dalton could be thus identified which consists of at least three clustered cistrons necessary for haemolysis. Two of these cistrons are required for the formation of active haemolysin. At least one other cistron seems to be involved in the secretion of active haemolysin through the outer membrane of E. coli. The gene products determined by these cistrons were identified in minicells of E. coli. Their molecular properties were determined and their possible function in the formation and secretion of haemolysin will be discussed.


IS4 is found between eleven or twelve base pair duplications. Three mutations caused by the integration of IS4 in galT in both possible orientations were shown by DNA sequence analysis to be integrated between a duplication of eleven base pairs of gene galT. IS4 has been cloned from its single position on the E. coli K12 chromosome. Here, 12 base pairs are duplicated adjacent to IS4. This sequence is unrelated to the duplicated sequence in galT.


The gene for ribosomal protein L25 (rplY) maps at 47.3 min near nalA in Escherichia coli K-12. A temperature sensitive mutant, termed JE1306, derived from Escherichia coli strain PA3092 was found to have an alteration in the ribosomal protein L25. Crosses with various Hfr strains and transductions with P1 kc phage have revealed that the mutation maps at 47.3 min between nalA and fpk, in a region where no ribosomal protein gene has so far been located. The gene affected by this mutation is most probably the structural gene for protein L25 (rplY), because a strain heteromerozygous for the region shows both wild type and mutant forms of protein L25.


Stable yeast transformation with chimeric plasmids using a 2 micron-circular DNA-less strain as a recipient. By using two chimeric plasmids containing yeast URA3 gene as a selection marker and 2 micron yeast DNA linked to the bacterial plasmid pCR1, a yeast strain devoid of any 2 micron DNA sequence was transformed. Recovery in E. coli of plasmids from yeast transformants showed that the 2 micron-less strain was able to maintain the chimeric plasmids as autonomous replicons, with very infrequent plasmid recombination. Hybridization experiments gave no evidence for integration of the URA3 DNA sequence in the chromosomal DNA. The transformed clones showed a high stability of the ura+ character during vegetative multiplication, even in the absence of selective pressure. The specific activity of orotidine 5' monophosphate decarboxylase (coded by the URA3 gene) was 5 to 10 fold higher than in the wild type. These features should offer new possibilities for cloning with yeast.


Three additional genes involved in pyrimidine dimer removal in Saccharomyces cerevisiae: RAD7, RAD14 and MMS19. The ability to remove ultraviolet (UV)-induced pyrimidine dimers from the nuclear DNA of yeast was examined in two radiation-sensitive (rad) mutants and one methyl methanesulfonate-sensitive (mms) mutant of the yeast Saccharomyces cerevisiae. The susceptibility of DNA from irradiated cells to nicking by an endonuclease activity prepared from crude extracts of Micrococcus luteus was used to measure the presence of dimers in DNA. The rad7, rad14 and mms19 mutants were found to be defective in their ability to remove UV-induced dimers from nuclear DNA. All three mutants belong to the same epistatic group as the other mutants involved in excision-repair. All three mutants show enhanced UV-induced mutations. The rad14 mutant also shows epistatic interactions with genes in the other two UV repair pathways.


Ozone response in wild type and radiation-sensitive mutants of Saccharomyces cerevisiae. The effect of ozone exposure on Saccharomyces cerevisiae was studied. Factors such as ozone concentration, treatment time, media, initial cell concentration and growth phase were shown to influence ozone response in this organism. Logarithmic phase cells were much more sensitive than stationary phase cells to the lethal effect of ozone. The radiation-sensitive mutants rad3, rad6, rad51 and rad52 of S. cerevisiae were exposed, in water, to 50 ppm of ozone for 30 min. On comparing their survival curves, the rad51 and the rad52 mutants showed a greater sensitivity to ozone exposure than the wild type.


Sporulation of mitochondrial respiratory deficient mit- mutants of Saccharomyces cerevisiae. The role of mitochondrial protein synthesis, electron transport, and four specific mitochondrial gene products on sporulation were studied in respiratory deficient mit- mutants. These mutants were isolated in an op 1 strain and localized on the mitochondrial genome by petite deletion mapping. All 153 mutations studied could be assigned to the four mitochondrial regions OXI1, OXI2, OXI3 and COB, known to affect cytochrome c oxidase and cytochrome b. The specific loss of one mitochondrially translated polypeptide was found in some mutants of each locus: OXI1--cytochrome c oxidase subunit 2, OXI2--subunit 3, OXI3--subunit 1, and COB--cytochrome b. The ability of diploid mit- mutants to sporulate was systematically investigated. About one third of the mutants, representing three loci, were incapable of forming spores. All other cultures produced either respiratory competent mit+ tetrads, both mit+ and mit- tetrads, or only mit- tetrads. Mutants forming mit- tetrads mapped in all four loci. These results demonstrate that in contrast to petite mutants some mit- mutants have retained the ability to perform meiosis and sporulation.


Isolation and characterization of further cis- and trans-acting regulatory elements involved in the synthesis of glucose-repressible alcohol dehydrogenase (ADHII) in Saccharomyces cerevisiae. Starting with yeast cells lacking the constitutive alcohol dehydrogenase activity (ADHI), mutants with partially glucose-insensitive formation of ADHII were isolated. Genetic analysis showed that four mutants (designated ADR3c) were linked to the ADHII-structural gene, ADR2, and were cis-dominant. On derepression, two of them produced elevated ADHII-levels, indicating a promotor function of the altered controlling site. The other ADR3c-mutant alleles affected the ADHII-subunit association in diploids carrying two electrophoretically distinct alleles of the structural gene ADR2. Twelve semidominant constitutive mutants could be attributed to gene ADR1 (ADR1c-alleles) previously identified by recessive mutants with blocked derepression. This suggested a positive regulatory role of the ADR1 gene product on the expression of the ADHII-structural gene. A pleiotropic mutation ccr1 (Ciriacy, 1977) was epistatic over glucose-resistant ADHII-formation caused by ADR1c-alleles. From this it was concluded that CCR1 specifies for a product co-activating the structural gene or modifying the ADR1-gene product. A further regulatory element (gene designation ADR4) not linked to the structural gene could be identified upon isolation of recessive constitutive mutants adr4 from a ccr1 ADR1c-double mutant.


Cloning of bacteriophage PM2 DNA in Escherichia coli K12. DNA fragments of phage PM2 restricted with Hin dIII endonuclease was cloned in the vector pBR 322 in an Escherichia coli K12 host. The attempt to clone full length PM2 DNA restricted with PstI endonuclease has been unsuccesful. From six randomly chosen recombinant clones DNA was purified and analysed with EcoRI, PstI and Hin dIII endonucleases. The physical map of three chimeric plasmids was unequivocally established. It was shown, that the whole PM2 genome was cloned, although in separate fragments. However, most of the recombinant clones were instable in the absence of selective pressure.


[Morphometry of breast tissue (author's transl)]. In conventional tissue slides it is possible to describe quantitatively the dysplasia of the breast with the aid of the Quantimet 720 and the image editor equipment. From several slides of each breast the areas of epithelium, lumina and connective tissue were measured out of 5 to 20 lobuli. The data were transformed into a descriptive index according to the formula: (epithelium--lumen): connective tissue. In normal mammae the indices are clustered and lower than 100. In the cases of increasing dysplasia the indices are scattered and elevated. In glands with carcinoma the normal values disappear, but the scattering and rising of indices increase. With these findings it seems possible to identify dysplasia in a precancerous state by morphometrical analysis.


[Quantitative fluorometry at the ocular fundus (author's transl)]. Description of a videodensitometric method for the quantitative evaluation of fluorescence angiography photographs using the Quantimet 720 image analysis computer system. The clinical value of the new method is demonstrated in a case of central serous retinopathy. With the aid of these measurements the activity of leakage points can be assessed more exactly than by mere subjective inspection of the gained pictures, thus allowing a better control of the effects of a chosen therapy.


[Selective contrast enhancement of microscopical specimen by optical procedures for automatized quantitative image analysis (author's transl)]. One of the most important problems in automatic image analysis is the discrimination of features by, a certain range of grey levels. To obtain as many as possible different grey levels sufficient contrast is achieved mainly by specific staining. Alternative and supplementary methods are some micrscopical methods, not routinely used. Interference microscopy, interference reflexion microscopy and microfluorimetry are discussed in detail. These optical procedures enhance the contrast of specimen specifically without the necessity for the application of specimen specifically without the necessity for the application of sophisticated staining methods. In interference contrast, tissues can be separately detected by grey level discrimination due to varying concentration of dry mass; this is shown for a cornifying part of fish skin (breeding tubercle of Rutilus rutilus L.). Furthermore, very small amounts of dry matter can be determined with high precision, as demonstrated for a single tissue culture cell (XTH-cell). Automatisation of image analysis provides a unique opportunity for routine application of interferometric measurements. The principles of the procedures are outlined. By interference reflexion microscopy cellular attachment areas to a glass surface are visualized, providing a powerful tool in cellular diagnosis based on grey level discrimination (darkest parts correspond to zones of closest contact to the substratum). A fast migrating lymphocyte and stationary endothelial cells have been chosen for demonstration. Various histochemical problems can be solved elegantly by fluorescence methods, e.g. mitochondria in living cells are specifically stained by a fluorochrome (DASPMI) and the distribution of fluorescence intensity can be followed within the mitochondrial population of a cell. Fluorescence was recorded from fotographic negatives taken with a fluorescence microscope. Additionally a short comment is given on the application of polarisation microscopy for feature detection.


[Machine based chromosomes investigations with the Quantimet 720 (author's transl)]. A system is described, looking in a short time and automatically for metaphases qualified for further usings. Scanning time for 1 cm2 is about 8 minutes. The accepted metaphases are relocatable immediately. Chromosomes are classified in a further routine using chromosome area and area ratio of the chromosome arms. The characters are displayed on the screen near the single chromosomes. Furthermore there is the possibility to measure the banding of whole chromosomes or of single chromatides and display it in form of histograms on the screen.


Computer assisted instruction for retraining family doctors in hypertension and hyperlipoproteinemia. In an attempt to retrain family doctors in hypertension and hyperlipoproteinemia, computer assisted instruction (CAI) was assessed in fourteen doctors (Group 1) and its efficiency was compared to that of traditional lectures given to twenty-one doctors (Group 2). The same objectives, contents and illustrations were used in both teaching approaches. There was no significant difference for age, year of graduation and type of practice in the two groups. Comparison between pre-test and immediate post-test revealed a significant gain of knowledge for hyperlipoproteinemia (group 1, 33% and group 2, 22%) and hypertension (group 1, 16% and Group 2, 19%). A year later a similar post-test was done in both groups, and no significant difference was found between this late post-test and the pre-test. CAI applied to family doctors is as efficient for learning as traditional lectures, and both approaches failed to show retention of knowledge after one year. This is perhaps the result of having selected instructional objectives of theoretical more than practical value.


Cultivation requirements for Treponema pallidum, Mycobacterium leprae and other microbial and mammalian microaerophilic cells. Atmospheric and biological evolution progressed simultaneously and today certain cell types flourish only at oxygen tensions which were ambient 600 million years ago, i.e., at 5 to 10 mm Hg. In man, a continuous oxygen flow at these pressures is supplied in the skin where Treponema pallidum, Mycobacterium leprae and members of the genus Rickettsia grow best. In vitro studies support the microaerophilic status of these organisms and of certain other microbial and mammalian cells. Vigorous growth in pure culture will await the development of techniques which can maintain these low oxygen tensions at the cell walls of the microbes as they replicate and consume increasing amounts of oxygen. Continuing failure to consistently isolate microbes from active lesions in patients with rheumatoid arthritis or systemic lupus erythematosus may reflect the universal absence of suitable methods for isolation of microaerophilic microbes.


A less invasive approach to monitoring acute respiratory failure. In a general ICU with a predominant surgical census, patients with acute respiratory failure can usually be treated on a clinical assessment and a minimum of invasive monitoring. An algorithm was used to manage the ventilatory support and weaning. When it failed (15% of the time), the patients' functional diagnoses were questioned and more advanced monitoring was used. The algorithm led to expeditious weaning of patients who did not need mechanical support and to a reduction of invasive monitoring.


Evaluation of automated multiphasic health testing in the survey of the north-west region of Melbourne. The results of automated multiphasic health testing (AMHT) in a randomly selected population of 664 subjects are reported. AMHT revealed a number of conditions that had not been diagnosed previously. A total of 535 newly diagnosed conditions in 301 patients could be attributed to the survey. The yield of new diagnoses by AMHT was not affected by previous surgery attendance or by attendance intervals. Follow-up over one year revealed that treatment was recommended for 342 of the 535 newly diagnosed conditions and that the response was satisfactory in 189 (55%), but the "uncertain" response of 124 (36%) should be investigated by more thorough follow-up in future projects. It is concluded that AMHT is beneficial because of the amount of information that is revealed, because of the financial value and because of the benefit to patients.


[Acute meningo-encephalitis in adolescents and adults: II. Germs, signs, symptoms and sequels (author's transl)]. This survey on diverse types of meningo-encephalitis in adolescents and adults is based upon 1244 observations at the Neurologic Clinic of the University at Cologne during the years from 1950 til 1975. Important factors concerning differential diagnosis such as various psychopathological and neurologic signs and electroencephalographic findings are discussed at extent. The influence of precursing and concomitant illnesses on the acute signs and sequels of the meningo-encephalitis is stressed upon.


[Surgical procedure in exploratory incision of the mamma (author's transl)]. A comparison was made between two groups, each consisting of 50 women who had undergone an exploratory incision of the mamma because of suspected cancer at least one year and not more than two years previously. The women in group A underwent an operation in clinic A in which a radial incision was performed in the skin immediately above the tumor (GB: tumour). In contrast to this group B in clinic B had the tumor removed via parariola incision independent of the location of the tumor. In clinic A the incision was closed by subcuticular suture using individual button stitches on the surface. In clinic B subcutaneous stitching was not used; after thorough blood-staunching procedures the skin was closed with intracutaneous atraumatic techniques. Both groups were subsequently examined and post-operative complications and the complaints of the patients were registered. In addition the cosmetic result of the operation was taken into consideration. The examinations show that the parariola incision is the ideal technique for almost all exploratory operations of the breast. Although the post-operative phase is accompanied by a slightly higher incidence of haematomas these rarely require further corrective surgical procedures if blood-staunching is efficient and Redon drainage techniques are used. Between 1 and 2 years after surgery the parariola approach shows definite advantages when compared with radial incision directly over the tumor. The scars are almost invisible, definitely cause fewer problems for the patient, and rarely spoil the appearance of the breast.


[Vigilance of patients with chronic renal insufficiency (author's transl)]. Psychological achievement tests were applied to 56 patients with chronic renal insufficiency for measuring the vigilance. The comparison of test parameters showed a significant impairment with progression of renal insufficiency, an improvement under chronic dialysis treatment depending on complications by medical problems and normal values after successfull transplantation. The vigilance was not influenced by dialysis per se. We conclude that the behaviour of reaction speed, attention performances, and mental concentration reflect the autointoxication of central nervous system in chronic renal insufficiency.


[Prophylaxis of gastroduodenal complications after renal transplantation (author's transl)]. Gastroduodenal bleeding or perforation following renal transplantation constitute a serious complication with a high lethality. 82 patients with terminal renal insufficiency were grouped in 4 categories with increasing gastroduodenal risk factors. Parameters for judging gastroduodenal risk consisted of gastric acid secretion, history and endoscopic demonstration of acute or chronic ulcer disease. 33 transplant candidates of groups I (hypochlorhydria, no ulcer) and II (normochlorhydria, no ulcer) were treated by medical prophylaxis alone. 23/33 were transplanted without prophylactic surgery, 1 patient in group II with erosive duodenitis before transplantation died from bleeding duodenal ulcer. Patients of group III (hyperchlorhydria up to 40 mval/h, MAO, no ulcer) received selective proximal vagomty, patients of group IV (hyperchlorhydria, 40 mval/h MAO and/or ulcer) underwent selective gastric vagotomy and 50% gastric resection. In 25 of 49 patients of group III and IV prophylactic operations were performed without serious complications. In 16 later on transplantated patients no gastrointestinal bleeding occurred. 2 patients of group III without gastric operation had minor bleedings out of erosive lesions in the gastric antrum and duodenal bulb, that could be managed by medical treatment. The positive experience with prophylactic gastric surgery in this limited number of patients seems to advocate a broader application of such a protocol. A considerable rise in gastric secretion was demonstrated in 19/21 patients during the first 3 years following the commencement of dialysis, BAO rose by an average of 72,2%, MAO by 41%. Thus, gastric analysis should be repeated once a year. Erosive gastritis and duodenitis seem to predispose for bleeding episodes after renal transplantation, this diagnosis should prompt prophylactic SPV.


Electrochemical determination of glucose concentration in saline solutions. Reproducible and reliable quantitative glucose determinations in physiological solutions of saline can be obtained by using platinum powder incorporated in a thin plastic layer on a platinum wire as the test microelectrode, while applying analytic and regenerative pulses of alternating voltage of +/- 1 V (sce). The results are the beginning of further investigations leading to continuous determinations of glucose concentration in body fluids.


Histological reaction to percutaneous epidural neurostimulation: initial and long-term results. Percutaneously inserted spinal epidural neurostimulation has been derived as a simplified safe alternative to surgically implanted, dorsal column stimulation that is used in the effective treatment and control of spasticity and intractable pain. Twenty-seven tissue specimens from fifteen patients having had percutaneous epidural neurostimulation systems implanted were studied with the aid of light microscopy. The biopsies from tissues around the cables, around the receivers, and at the actual site of epidural stimulation (at the metallic contact), were studied at time intervals varying from one week to two years postimplantation. Long-term results, which only show dense fibrous encapsulation of the cables and the receiver, substantiate clinical belief regarding the "histological safety" of this electronic modality.


Mutagenicity of fluorene derivatives: a proposed mechanism. Several derivatives of fluorene, a tricyclic, organic molecule, have been found to induce both frameshift mutations and base-pair substitutions in Salmonella typhimurium strains developed by Ames. Comparisons of the mutagenic potency of these derivatives for several strains of Salmonella suggest the importance of a carbonyl group substituted at the carbon-9 position of mutagenic derivatives, with respect to mutagenic potency. In this study, we present a feasible mechanism for the interaction of mutagenic fluorene derivatives with deoxyribonucleic acid. This mechanism requires the interaction of the mutagenic molecule with carbon-8 of guanine and a second concurrent interaction with the C-4 amino group of an adjacent cytosine residue.


Effects of spermine on the detection of induced forward mutation at the Can1 locus in yeast: evidence for selection against canavanine-resistant mutants. The effect of exogenous spermine tetrahydrochloride (0.5 mg/ml) on hydrazine- and nitrous acid-induced forward mutation to canavanine resistance (CAN1 leads to can1, normal to defective arginine permease) was examined in stationary-phase haploid Saccharomyces cerevisiae. Post-treatment cell division (specifically DNA replication) is required for hydrazine mutagenesis at this locus, whereas nitrous acid mutagenesis exhibits, in addition, a significant post-treatment-independent component. Spermine addition only during mutagenic treatments in buffer did not affect mutagen cytotoxicity, but did result in a slight yet consistent decrease in induced mutation frequencies. Addition of spermine to the yeast extract--peptone--dextrose (YEPD) post-treatment growth medium resulted in dramatic reductions of induced mutation frequencies, which could be alleviated by pregrowth in spermine-containing YEPD. Such a medium was found to cause an apparent temporary growth inhibition for almost 40 h, after which the growth rate of the culture increased rapidly. Cultures "recovering" from spermine inhibition were no longer inhibitable by spermine in fresh medium, suggesting an outgrowth of spontaneous and/or induced spermine-resistant derivatives. Genetic analysis of one isolate revealed a single dominant nuclear gene conferring resistance by some means other than defective spermine uptake. Growth of this mutant was only slightly inhibited by spermine (20% increase in doubling time), while mutation expression remained high. Results of competitive growth experiments indicated that spermine-containing YEPD exerted a selection pressure against canavanine-resistant cells, while YEPD by itself did not. The mechanism for this selection is not presently understood. With respect to replication-dependent induced mutation at CAN1, our initial observation of a strong apparent antimutagenic action of spermine was found to be best explained by this specific selection against can1 mutants. This underscores the need for caution in the interpretation of experiments designed to study physiological modification of mutagenic potential.


Ethidium bromide enhancement of frameshift mutagenesis caused by photoactivatable ethidium analogs. Ethidium azide analogs (3-amino-8-azido-ethidium monoazide and ethidium diazide) have been developed as photosensitive probes in order to analyze directly the reversible in vivo interactions of ethidium bromide. Our preliminary observations [11], relating the mutagenic potential of the monoazide analog of ethidium, have been extended and refined, using the highly purified ethidium azide analogs [5]. A number of physical-chemical studies indicate that the monoazide analog interaction with nucleic acids, prior to photolysis, resembles remarkably the interaction of the parent ethidium (unpublished). It was anticipated, therefore, that competition by ethidium for the ethidium monoazide mutagenic sites in Salmonella TA1538 would be observed when these drugs were used in combination. Previous results in fact showed a decreased production of frameshift mutants when ethidium bromide was added to the ethidium monoazide in the Ames assay [1]. However, more extensive investigations, reported here, have shown that this apparent competition was the result of neglecting the toxic effects of ethidium monoazide and its enhanced toxocity in the presence of ethidium bromide. Conversely, an enhancement of the azide mutagenesis and toxicity for both the mono- and diazide analogs was seen when ethidium bromide was used in combination with these analogs.


Some factors determining the concentration of liver proteins for optimal mutagenicity of chemicals in the Salmonella/microsome assay. In plate assays in the presence of S. typhimurium TA100 and various amounts of liver 9000 X g supernatant (S9) from either untreated, phenobarbitone- (PB) or Aroclor-treated rats, the S9 concentration required for optimal mutagenicity of aflatoxin B1 (AFB) depended both on the source of S9 and on the concentration of the test compound. In these assays, the water-soluble procarcinogen, dimethylnitrosamine (DMN) was mutagenic in S. typhimurium TA1530 only in the presence of a 35-fold higher concentration of liver S9 from PB-treated rats than that required for AFB, a lipophilic compound. In liquid assays, a biphasic relationship was observed in the mutagenicities in S. typhimurium TA100 of benzo[a]pyrene (BP) and AFB and the concentration of liver S9. For optimal mutagenesis of BP, the concentration of liver S9 from rats treated with methylcholanthrene (MC) was 4.4% (v/v); for AFB it was 2.2% (v/v) liver S9 from either Aroclor-treated or untreated rats. At higher concentrations of S9 the mutagenicity of BP and of AFB was related inversely to the amount of S9 per assay. The effect of Aroclor treatment on the microsomemediated mutagenicity of AFB was assay-dependent: in the liquid assay, AFB mutagenicity was decreased, whereas in the plate assay it did not change or was increased. As virtually no bacteria-bound microsomes were detected by electron microscopy, after the bacteria had been incubated in a medium containing 1-34% (v/v) MC-treated rat-liver S9, it is concluded that, in mutagenicity assays, mutagenic metabolites generated by microsomal enzymes from certain pro-carcinogens have to diffuse through the assay medium before reaching the bacteria. Thus the mutagenicity of BP was dependent on both the concentration of rat-liver microsomes and that of total cytosolic proteins and other soluble nucleophiles such as glutathione. At a concentration of 4.4% (v/v) liver S9, the mutagenicity of BP was about 3.6 times higher than in assays containing a 4-fold higher concentration of cytosolic fraction. Studies on the glutathione-dependent reduction of BP mutagenicity in plate assays has shown that, in the presence of liver S9 concentrations greater than that required for optimal mutagenicity, the reduction in mutagenicity was related directly to the concentration of liver S9. Thus, in the Salmonella/microsome assay, when the concentration of rat-liver S9 was increased over and above the amount required for the optimal mutagenicity of BP, the mutagenic metabolites of BP were inactivated (by being trapped with cytosolic nucleophiles and/or by enzymic conjugation with glutathione); this effect increased more rapidly than their rate of formation. The concentration of liver S9 for optimal mutagenicity of test compounds requiring activation catalyzed by mono-oxygenases seems, therefore, to be related to the departure from linearity of the relationship between the rate of formation of mutagenic metabolites and the concentration of liver S9.


Critical importance of microsome concentration in mutagenesis assay with V79 Chinese hamster cells. For optimum mutagensis in V79 Chinese hamster cells, the amount of liver postmitochondrial fraction in the assay was found to be of critical importance, depending on the chemicals being tested. Benzo[a]pyrene (BP) required lower (1-5%) concentrations of the liver 15 000 X g supernatant (S15) from methylcholanthrene pretreated rats for a maximum induction of cytotoxicity and mutagenicity, as determined by 8-azaguanine- and ouabain-resistance. A sharp peak of mutagenicity and cytotoxicity was induced by 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-diol BP) at a concentration of 1% of the S15 fraction. Little or no response was induced by these compounds with the S15 concentrations of more than 10%. Similarly, aflatoxin B1 induced a sharp peak of mutagenicity and cytotoxicity at a concentration of 2% of the liver S15 fraction from Aroclor-pretreated rats. Under the same condition, non-carcinogenic aflatoxin G2 did not induce cytotoxicity and mutagenicity. Analysis of BP metabolites by high-pressure liquid chromatography indicates that with the 30% S15 fraction, more than 80% of BP was metabolized during the first 15 min, while with the 2% S15 fraction, 7,8-diol BP increased continuously throughout the 120-min incubation period, suggesting a strong metabolic competition to rapidly remove BP and 7,8-diol BP with a high concentration of the S15. In contrast with these compounds, N-nitrosodimethylamine induced mutagenicity and cytotoxicity which increased linearly in proportion to the increasing amount of the S15 fraction from phenobarbitone- and Aroclor-pretreated rats. Various nitrosamines with different lipophilicity were examined at a high (30%) and low (2%) concentration of the S15 fraction from Aroclor-pretreated rats, in which ratios of mutation frequencies at 30% and 2% correlated inversely with lipophilicity of the compound. This result suggests that the lipid solubility of test compounds may be one factor which determines the concentration of post-mitochondrial supernatant for optimum mutagenesis.


Biological and chemical effects of mustard gas in yeast. Mustard gas induces inactivation and mutation in yeast. Both effects are dose-proportional, indicating single-hit events. Induction of both effects is influenced by the cell's capacity for DNA dark-repair, whereby the probability of reversion is highest in repair-proficient cells. Binding of mustard gas to cells and probably to DNA is independent of DNA-repair systems. The number of inter-strand cross-links, as determined by assaying for renaturability of alkalidenatured DNA, increases in a dose-proportional manner. At 37% survival an excision-deficient strain contains 55 inter-strand cross-links. Chromatographic analysis yields several alkylation products of DNA. Their relative frequencies resemble the values reported for E. coli and bacteriophage T7.


Mitochondrial mutagenesis in Saccharomyces cerevisiae. III. Nitrous acid. Nitrous acid (NA) induced mutations efficiently in mitDNA, conferring resistance to erythromycin and weakly induces mit- mutations. In some strains of yeast it also enhanced rho- mutations. The frequencies of nuclear and mitochondrial mutations induced with NA are compared.


Studies of DNA-strand induced in human fibroblasts by chemical mutagens/carcinogens. A method for the study of DNA-strand breaks using alkaline denaturation followed by hydroxylapatite chromatography has been modified and used for the detection of chemically induced DNA-strand breaks. A new procedure for the incubation of human fibroblasts with a metabolizing system and the detection of DNA-strans breaks is presented. With this method the induction and repair of DNA-strand breaks have been studied in human fibroblasts exposed to methyl methanesulphonate, melphalan, benzo[a]pyrene and cyclophosphamide. These agents all give rise to DNA-strand breaks. In cells exposed to methyl methanesulphonate, melphalan or benzo[a]pyrene these breaks disappeared within 21 h after re moval of the drug. In cells exposed to the bifunctional alkylating agent cyclophosphamide, studies of DNA-strand breaks suggest the presence of inter-strand cross links.


Point mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells. I. Application to genetic toxicological testing. We have systematically evaluated the mouse lymphoma TK+/- leads to TK-/- mutagenesis assay to determine if this somatic-cell test system would be a useful addition to the routine screening battery already used in our laboratory for the detection of chemical mutagens. During these investigations we observed that, with certain modifications of the basic assay, mutagenicity data could be obtained in as little as 9 days once the relative cytotoxic properties of the test substance were known. By improving the culturing conditions, we were able to reduce the serum requirements by as much as 50--75% without appreciably altering either cell viability or the recovery of chemically-induced mutants. Phenotypic stability of test-derived trifluorothymidine resistant (TFTR) mutants was confirmed by demonstrating cross-resistance to bromodeoxyuridine and concomitant sensitivity to methotrexate (THMG) in TFTR cells grown for 20 generations under non-selective conditions. While reduced growth rates resulting from temporary cell-division delay in treated cells is probably not a contributing factor to the observed mutation frequencies, only TFTR colonies which formed large distinct colonies in the presence of trifluorothymidine were clearly phenotypically stable mutants when spontaneous mutants were isolated and verified. When a non-mutagen, a weak mutagen, and a well-established mutagen were compared at equitoxic doses under these modified conditions, clear quantitative differences were seen in the respective mutation frequencies induced by these 3 types of agents. With these technical modifications, we feel this assay is both reliable and amenable to the screening of diverse chemical compounds for point-mutational activity in a mammalian cell.


Intrahepatic mutagenesis assay: a sensitive method for detecting N-nitrosomorpholine and in vivo nitrosation of morpholine. An intrahepatic host-mediated mutagenicity assay capable of detecting low levels of N-nitrosomorpholine (NMOR) is described. The indicator organism was Salmonella typhimurium TA1530 which had been injected intravenously 10 min prior to the administration of the test compound. The bacteria were subsequently recovered from the liver and scored for revertants by standard methods. The lower limit of detectibility of this system for intubated NMOR was 0.2 microgram/g body weight. This assay was then used to study the formation of NMOR in vivo from morpholine and nitrite which had been sequentially gavaged to mice. Under acidic conditions (pH 3.4) 12--19% of the administered morpholine was converted to NMOR in the presence of excess nitrite. This nitrosation, and the subsequent uptake and activation of the NMOR, took place so rapidly that most of the total mutagenic response was complete within 15 min. This response was inhibited by prior intubation of ascorbic acid, a known inhibitor of nitrosation, and enhanced by sodium thiocyanate, a nitrosation catalyst.


Measurement of DNA-excision repair in suspensions of freshly isolated rat hepatocytes after exposure to some carcinogenic compounds: its possible use in carcinogenicity screening. When suspensions of freshly isolated rat hepatocytes were exposed to a number of carcinogenic compounds, it was possible to measure an increased UDS by a rapid procedure via liquid-scintillation counting. For a number of carcinogenic compounds and some of their non-carcinogenic structural analogues a good correlation between the carcinogenic property and the ability to induce UDS was demonstrable. Out of 12 carcinogenic compounds, belonging to several different chemical classes, 10 gave rise to an increased UDS, whereas only 2 compounds, the polycyclic aromatic hydrocarbons benzo[alpha]pyrene and benz[alpha]anthracene, did not. All 4 noncarcinogenic compounds tested were negative. Possibly this method can be of value as a routine screening test, in combination with other short-term test systems, thus improving the predictive value of screening in vitro with respect to carcinogenicity.


The mutagenicity of natural products from marine algae. 5 polyhalogenated hydrocarbon natural products isolated from the marine red alga Plocamium spp. were tested for mutagenicity in the Ames reversion assay. All 5 of the compounds induced revertants in Salmonella typhimurium strains TA100 and TA1535, indicating the mutational events involved base substitutions. One of the compounds, designated cross-conjugated ketone, was shown to be almost 200 times more effective as a mutagen than was ethyl methanesulfonate.


Mutagenicity of anthraquinone and azo dyes in Ames' Salmonella typhimurium test. 23 dyes belonging to different chemical classes--anthraquinones, mono- and bis-azo compounds--were tested for their mutagenic activity on Ames strains of Salmonella typhimurium. 5 dyes induced frameshift mutations.


Mutagenicity and metabolism studies on 12 thiuram and dithiocarbamate compounds used as accelerators in the Swedish rubber industry. 12 thiuram and dithiocarbamate compounds used in the rubber industry as accelerators, and to some extent as sources of sulfur, were tested, as well as carbon disulfide, a metabolite found in vivo after dithiocarbamate treatment, for mutagenicity in Salmonella typhimurium. A mutagenic effect on the base-substitution-sensitive strains TA1535 and TA100 was found for 7 compounds. The most potent directly acting mutagens were: tetramethylthiuram disulfide (TMTD), zinc dimethyldithiocarbamate (ziram), cadmium diethyldithiocarbamate and zinc diethyldithiocarbamate. Tetraethylthiuram disulfide (TETD), also known as Antabus, and carbon disulfide were non-mutagenic. The relatively low direct mutagenic effect of tetramethylthiuram monosulfide (TMTM) was enhanced in the presence of a metabolizing system (S9 mix). A hypothesis is given regarding the activation process of the monosulfide TMTM.


Effect of thymectomy on tumor development and on T and B lymphocytes in tumor-bearing rats. Tumor growth and changes in T and B lymphocyte ratio in spleen, draining lymph node and peripheral blood of thymectomized, irradiated rats, reconstituted with syngeneic bone marrow transplanted at various time intervals with MC-1 fibrosarcoma cells were followed. Control nonthymectomized or "sham" operated rats were transplanted an equal dose of tumor cells. Thymectomy and irradiation reduced the numbers of T lymphocytes in all lymphoid organs, while the enhanced numbers of B cells are probably related to reconstitution with cells of syngeneic bone marrow. The time interval between thymectomy, irradiation and transplantation of tumor cells proved to be a limiting factor for tumor growth and changes in T and B cell ratio. Early transplantation of tumor cells (7 days after irradiation) resulted in an enhanced resistance to tumor development, a reduced tumor growth rate and a progressing decline in the number of T cells. If the interval between thymectomy and tumor cell transplantation lasted 4 weeks, the T cell population became partially regenerated, and tumors grew progressively in correlation with a continuing T lymphocyte depletion. The results are discussed in terms of the role of various T cell subpopulations and the significance of residual, thymectomy- and irradiation-resistant T lymphocyte population, vital for a preservation of T cell immunological functions.


T and B lymphocytes of the regional lymph nodes in patients with carcinoma of uterine cervix. A comparative study of the peripheral blood and the regional lymph nodes lymphocyte subpopulations at 25 patients with carcinoma of uterine cervix was carried out by non-immune rosettes and immunofluorescence methods. The lymph nodes of ten women not affected with any disease, but operated on the occasion of the traumas were investigated as a control. The patients had a significant reduction of the relative amount of T cells and increase of number of B cells in their lymph nodes as compared with the control group. A significant variability of immune indices of the regional lymph nodes as compared to those of peripheral blood was shown. It was pointed out that the presence of the metastases in the regional lymph nodes is one of the possible reasons of this phenomena. The possible significance of the results is discussed.


Cell-mediated immune reactions directed against syngeneic methylcholanthrene-induced mouse sarcomas: low reproducibility of the results obtained with the tube modification of leukocyte adherence inhibition assay. The value of the tube modification of leukocyte adherence inhibition (LAI) assay for assessment of cell-mediated reactions directed against tumor-associated antigens of transplantable MC-induced murine sarcomas was examined. It was established that the adherence of leukocytes isolated from spleens of tumor-bearing mice is specifically inhibited with 3 M KCl extracts of corresponding tumor cells. However, the reproducibility of the results obtained with the tube modification of LAI assay was found to be rather low. Using the same experimental protocol and the same 3 M KCl extracts of the sarcoma and control tissues, significant differences between adherence in tumor specific and control samples were only found in approximately 50% of the experiments.


[Autosensitization of neurosurgical cases by normal brain tissue antigens (author's transl)]. The leukocyte reactions of 106 neurosurgical cases, including 63 brain tumors, 10 intracerebral hematomas, 10 cerebral infarctions, 10 subarachnoidal hemorrhages, 8 cerebral injuries and 5 chronic subdural hematomas, against the extracts of gliomas and normal brain tissues were tested by capillary migration (LMI) and adherence inhibition (LAI) assays. Both tests showed specific responses with autochthonous and allogeneic glioma extracts in glioma patients. The sensitivity of LAI was superior to that of LMI, although LAI also showed adherence enhancement in the presence of weakly sensitized leukocytes or weak antigenic stimuli. Leukocytes from glioma patients showed positive inhibition with normal brain tissues from patients with glioma and intracerebral hematoma. Positive leukocyte reactions with normal brain tissues were also confirmed in patients with intracerebral hematomas, cerebral infarctions and severe cerebral lacerations, but not in those with subarachnoidal hemorrhages, minor cerebral contusions and chronic subdural hematomas. These results suggest that the leukocytes of patients with destructive brain lesions were autosensitized by normal brain antigens. The autosensitization has some advantages in that destroyed brain tissues are eliminated, but the hyperimmune state might cause postictal brain edema and should be properly controlled by steroids.


Mechanisms of hyperventilation in head injury: case report and review. We report the case of a head-injured patient with spontaneous hyperventilation who had recurrent episodes of relative hypoventilation associated with increases in intracranial pressure. Detailed ventilatory studies were performed during the 2nd week after injury. Our findings in this patient prompted us to review the possible mechanisms underlying the observed changes. We suggest that spontaneous hyperventilation in head injury is secondary to a decrease in cortical inhibitory influences on respiratory control mechanisms and that the transient episodes of relative hypoventilation observed in our patient may reflect modified ventilatory responses dependent on the altered state of consciousness. (Neurosurgery, 5: 701--707, 1979).


Spinal metastasis: current status and recommended guidelines for management. An overview of the current status of various aspects of spinal metastasis, including pathology, diagnosis, and management is presented. The cell type of the tumor, particularly with reference to its radiosensitivity, seems to be positively correlated with treatment outcome, regardless of the treatment modality. Because pretreatment neurological status also seems to influence prognosis, early identification of spinal involvement in patients at risk is important; therefore, a high index of suspicion in patients known to have cancer is necessary. The most useful warning of impending spinal cord or nerve root compression is spinal or radicular pain, which usually precedes neurological deficit by days to years. An aggressive diagnostic evaluation of pain symptoms is therefore warranted; this should include plain spine films and, in questionable cases, radioisotope bone scan. Myelography should also be considered in any cancer patient with persistent spinal or radicular pain, even in the absence of neurological deficit and certainly if there is any neurological impairment. Therapeutically, radiation and surgery continue as the mainstays of management, whereas steroids and chemotherapy serve as adjuvants. The guidelines for management recommended in this paper are to be viewed as tentative because the ideal treatment for spinal metastasis has not been established. The proposed guidelines are based on an analysis of retrospective studies that suggest that radiotherapy should be the primary mode of treatment and that surgery should be reserved for situations in which radiotherapy fails or where there is bony compression or spinal instability. Cases are presented to illustrate the application of these guidelines. (Neurosurgery, 5: 726--746, 1979).


Myopathies.

Myopathies. This paper reviews the recent advances in our knowledge of muscle disease. The use of muscle biopsy for diagnosis is discussed. The etiology, pathogenesis, and treatment of polymyositis/dermatomyositis are considered. The author discusses the clinical patterns, inheritance, and pathogenesis of progressive muscular dystrophies, especially Duchenne muscular dystrophy; myotonic disorders; glycogen storage diseases; disorders of lipid metabolism; mitochondrial diseases; and congenital muscle diseases. (Neurosurgery, 5: 747--758, 1979).


[Various types of reducing diets].

[Various types of reducing diets]. It must be readily understood that the only possibility of fighting obesity is by bringing about a reversal in the energy balance so that inputs are smaller than outputs. At least theoretically, then, obesity's special quality is that it does not present any therapeutic problem. Restriction in food intake is currently the treatment of choice; to be effective, food intake must be cut so that the energy provided is below the obese person's daily consumption, on average below 1200 calories per day, while at the same time holding a comparatively high intake of indispensable elements (proteins, vitamins, certain minerals and oligo-elements). The physician has a choice of various possibilities represented by fasting, a variety of free or controlled diets, protein diets or diets with low carbohydrate content and with a variable fat content; dissociated, zig-zag, one food diets etc. Substantially all these tend to limit the total quantity of glycides and boost the feeling of satiety by increasing the total volume of good while keeping total calories unvaried. It is clear that each of them has specific indications and clear-cut contraindications. The aim is to produce a calory shortfall, not cause denutrition. The diet must therefore be suited to the individual directed during subsequent stages of weight loss in relation to the patient's specific requirements (number of meals, etc.).


Anti-N in patients undergoing regular haemodialysis: a possible association with renal transplant failure. Six patients on regular haemodialysis in the Auckland renal dialysis unit developed the antibody anti-N. All utilised formaldehyde resterilisation dialyser procedures. Four patients with anti-N underwent renal transplantation unsuccessfully. Histological changes were difficult to interpret and could not be closely correlated with serological findings, although vessel thrombi and renal tissue infarcts were seen in some kidneys. It is recommended that renal patients should be screened at 4 degrees C and room temperature for anti-N and that resterilisation of dialysers be carefully controlled. Where transplantation is to be performed in a patient with anti-N, the organ should be warmed and perfused with warm saline prior to grafting.


[Results of the radiation therapy of malignant epipharyngeal tumors in 1953-1977]. 134 patients having carcinomas of nasopharynx were treated with megavoltage radiotherapy. Treatment results in relation to histology, stage and tumor dose are reported. Patients with squamous cell carcinomas showed a shorter survival in comparison with tumors of higher sensibility. Patients with smaller tumors survived longer than others in advanced stages and patients who received more than 5000 rads had a better prognosis both in squamous cell carcinomas and tumors of higher sensibility. The value of a combined treatment of radiotherapy with hyperthermia and/or chemotherapy is discussed.


[Double urologic tumors: reduced immunocompetence?]. 55 patients with primary multiple neoplasias underwent immunostaging with determination of the immunoglobulins, B- and T-lymphocyte counting, H3-lymphocyte stimulation (ConA, PWM, PHA) and DNCB-epidermal test. There were no significant differences between the PMN-group and a group of patients with solitary tumors, whereas both cancer patient groups revealed a diminished immunocompetence compared with a non-malignant control group of patients.


[Fine needle puncture of mesenchymal malignant growths of the mammary gland]. From 1967 to 1978 the author made 612 fine needle biopsies of the mamma (415 benignant, 197 malignant cases). Among malignant cases there were 11 primary (2 fusocellular, 1 rotundocellular sarcomas, 1 chondromyxosarcoma, 1 leiomyosarcoma, 1 melanoblastoma, 1 angiosarcoma, 4 malignant cystosarcomas phylloides) and 4 metastatic (1 rotundocellular, 1 reticulocellular, 2 melanoblastomas) sarcomas. The author gives a detailed report on cytomorphology, histology and diagnostical problems of mesenchymal malignomas. He thinks the practical value of fine needle biopsy important in the preoperative diagnostics of sarcomas in the mamma. On the basis of his experiences obtained during years,  he considers it undangerous and recommends its daily use in practice.


[Characterization and comparison of the clinical and morphological changes in adriamycin cardiomyopathy]. Through comparative clinical and pathological findings a dose-response relationship for the cardiotoxic effect of adriamycine could be proved. A myocardial damage without clinical relation could already be seen at a dose of 125 mg/m2 body surface by patho-histological examination. Therefore, all patients being treated with adriamycine should be regularly and carefully cardiologically supervised in order to avoid an irreversible cardiomyopathy.


[What prospects of success does Iscador therapy offer in advanced ovarian cancer?]. Having established the hypothesis that the carcinostatic effect of Iscador described in the literature and ascertained by own observations should also show in the treatment of carcinoma of the ovary, we compiled all respective cases treated since November 1969 in the Gynecological Ward of the Gemeinnütziges Gemeinschaftskrankenhaus Herdecke. The collective consisted of 25 patients with primary neoplasms of the ovary who received post-operative treatment with Iscador. The average age was 50.96 years. 20 women were in the advanced stages III and IV according to FIGO. Five-year survival rates were 100% in stages I and II, 23% in stage III and 0% in stage IV. After establishing best possible congruence, our group of patients was compared with a collective of 22 women with neoplasms of the ovary who had received post-operative treatment with Cytoval. Inspite of less favorable prognostic indicators for the Iscador patients, the latter reached an average survival rate of 16.2 months as compared to 5.2 months in the group treated with Cytoval (ratio 3.1:1). The survival period of Iscador patients in stage III was 4.2 times longer, in stage IV 1.6 times longer than that of the Cytoval patients. The difference is statistically significant (alpha less than 0.018). A comparison of the results of the two collectives shows that Iscador a special preparation of viscum album, is a useful and effective treatment of carcinoma of the ovary, particularly since it usually does not cause serious and undesired side effects. Thus the original working hypothesis was confirmed.


[Carcinogenic effect of the 3-di-(hydroxymethyl-)amino-6-(5-nitro-2-furylethenyl-)1,2,4-triazines in Panfuran-S on mice]. The carcinogenic activity of Panfuran-S containing 3-di-(hydroxymethyl-)amino-6-(5-nitro-2-furylethenyl-)1,2,4-triazine (DHNT) orally administered to mice for 35 weeks was studied. DHNT produced malignant tumors of the forestomach in the highest incidence and also, in decreasing order of frequency, of the duodenum and/or jejunum, esophagus and urinary bladder. Forestomach squamous cell carcinomas were produced dose-dependently in mice receiving more than 350 ppm DHNT and rose to 100% in mice receiving 3,500 ppm. The incidence of duodenal and/or jejunal adenocarcinomas were 8 of 28 mice (29%) receiving 1,750 ppm and 10 of 17 mice (59%) receiving 3,500 ppm. The incidence of esophageal squamous cell carcinoma was 3 of 11 mice (11%) receiving 1,750 ppm and that of urinary bladder transitional cell carcinoma was 2 of 28 mice (7%) receiving 1,750 ppm and 1 of 17 mice (6%) receiving 3,500 ppm DHNT.


[Attempt at objectifying the effect of obligatory lymphonodectomy in the context of radical abdominal surgery for cervical cancer]. An attempt is made to calculate both the primary and secondary effect of obligatory lymphonodectomy in the course of an abdominal radical hysterectomy for cervical uterine carcinoma, attributed to the histological stages Ib, IIa and IIb. Within the period from 1951 to 1972 both effects were intensified by increasing radicalization of lymph node dissection; the quotes of 13.96% and 10.81%, respectively, are as high as the best results reported by CHIEN-TIEN HSU and I. SEN LIU in 1966.


[High-dosage gestagen treatment in the therapy of advanced breast cancer]. The results obtained with a new hormonal treatment schedule involving the administration of medroxyprogesterone acetate in single and total doses never before used in the treatment of advanced breast cancer are reported. The results concern 100 patients, 13 of which in premenopause and 87 in postmenopause stage. 79 patients were treated with a single daily dose of 1500 mg i.m. for 30 days, subdivided into 2 equal doses administered at intervals of 12 hours, while 21 patients were treated with a dose of 2000 mg/day using the same modalities. In the 13 premenopausal patients, complete or partial objective remission was observed in 12/13 (92%) of cases, while the disease advanced in one of the patients (8%). Of the 87 postmenopausal patients, complete or partial objective remission was observed in 40/87 (46%) of cases, minimal remission in 9/87 (10%), while 18/87 (21%) remained stationary. The disease advanced in 20/87 (23%) of patients. In patients where metastasis mainly affected the bones and soft tissues complete or partial remission occurred in 41/52 (79%) of cases. Those where visceral metastasis was prevalent showed remission in 3/33 (9%) of cases. Median duration of remission was 6 months (range: 3--27). A significant reduction of pain was noticed in 68/74 (92%) of cases, of dyspnea in 20/25 (80%), of anorexia in 45/53 (85%), of asthenia in 49/70 (70%) and of restriction of movement in 24/39 (62%). On the basis of the present results, treatment with massive doses of medroxyprogesterone acetate should be considered: a) as first therapeutic measure in the treatment of postmenopausal patients with prevalent lesions in soft tissues and bones; b) as a subject of a particular study in premenopausal patients with breast cancer in an advanced stage, and c) as a possible alternative to polychemotherapy in the treatment of micrometastasis following mastectomy.


[Blood histamine level in chronic myeloproliferative diseases; a review]. Since the discovery of a very high blood histamine level in chronic myelocytic leukemia (CML) 1936, the author could ascertain that this parameter is very useful in the differential diagnosis between CML and various "leukemoid" reactions; in the early diagnosis of CML and in the differential diagnosis between CML and other myeloproliferative disorders. Recent researches proved that no correlation exists between blood histamine level and basophil count in the peripheral blood. Further investigations in this field have to clear up the questions whether it is possible by means of repeated controls of the blood histamine level to predict the development of a polycythemia vera into CML or to establish in a case of osteomyelosclerosis that this disease has been Preceeded by A CML.


[Lymphocytotoxic antibodies in cervical cancer]. Sera of 120 patients, suffering from cervical cancer (CCa) of different clinical stages (stage 0: n = 27; stage I: n = 29; stage II--IV: n = 64) as well as the sera of 116 healthy individuals as control group were examined for lymphocytoxic antibodies by microlymphocytotoxicity tests, variated in incubation temperatures (15 degress -- 22 degrees -- 37 degrees C) and incubation times (30--180 minutes). At an incubation temperature of 15 degrees C cold reacting lymphocytotoxic antibodies were detected in 26 patients' sera (21.7%) and in 13 control sera (11.2%). At an incubation temperature of 22 degrees C 36 CCa-sera (30%) were positive in comparison to 11 sera of the control group (9.5%). At an incubation 37 degrees C 40 CCa-sera (33.3%) and 7 control sera (6%) were positive. Relating these results to the clinical stages of the carcinoma, the highest percentage of lymphocytotoxicity was found in the sera of patients with an early stage of the disease. Increased evidence of lymphocytotoxic antibodies in the sera of patients with cervical carcinoma supports the assumption, that various immune reactions may be involved in this disease.


[Therapy results in hairy cell leukemia]. 20 patients with hairy cell leukemia were treated between 1966 and 1978. All modalities of treatment for lymphoproliferative disorders have been used in at least some patients. Besides prednisone, vincristine, cyclophosphamide and their combinations as well as irradiation of enlarged spleens, cell depletion was achieved by splenectomy and leukapheresis. Cytostatics had no beneficial effect. Cytostatic therapy exposed some patients to the hazards of severe infections. On the contrary splenectomy lead to the improvement of some blood parameters. Leukapheresis seemed to work nearly identically. The survival of the splenectomized patients was longer than of controls. Because of the variability of the duration of the disease no definite statement could be made concerning the survival of both groups. 12 patients died during the observation period. Splenectomy was followed by one death, 11 patients died of septicemia.


[Effectiveness of gnotobiotic measures in the treatment of acute leukemia: the results of a prospective randomized clinical study]. 60 adult patients with acute leukemia (AL) previously untreated or in relapse received induction chemotherapy with different types of supportive care. Group A was decontaminated by nonabsorbable antibiotics in strict reverse isolation, group B was isolated only and group C was treated under routine hospital conditions. There were less infections in group A and B compared with group C. 76% of patients in group A achieved remission, in contrast to 57% in group B and 59% in group C. Late evaluation three years after termination of the study showed that all patients were dead except four patients being in first remission after discontinuation of maintenance treatment. Three patients were treated in group A, one patient in group C. However, the differences of survival and remission rates were not significant. Failure to demonstrate significant advantage of isolation and decontamination in treatment of AL was caused by insufficient suppression of microbes by the applied antimicrobial measures. Thus, it is suggested to investigate better antimicrobial treatment before gnotobiotic care is accepted as routine supportive treatment in AL.


[Perioperative behavior of prostaglandin E2 (PGE2) and 13,14-dihydro-15-keto-PGF2 alpha (DHK-PGF2 alpha) in the serum in bronchial cancer]. The perioperative behaviour of PGE2 and DHK-PGF2 alpha was studied in peripheral blood of patients undergoing lung surgery. The measurement of prostaglandins was performed by RIA after an extraction procedure. Common control criteria were observed. In 39 patients blood sampling was performed preoperatively and 2 weeks postoperatively. PGE2 and DHK-PGF2 alpha were significantly elevated in 8 patients with lung cancer before the operation. Postoperatively the concentrations decreased; 2 weeks later, DHK-PGF2 alpha was still slightly increased, PGE2 had normalized. 9 patients suffering from tuberculosis had normal serum concentrations of PGE2 and DHK-PGF2 alpha before and after resection procedures. In 8 cases the resection of benign lung diseases did not cause any abnormal reactions. In 2 special groups blood sampling was performed the following way: in 4 cancer patients and 3 tuberculosis patients blood was collected preoperatively, 5 times in the first hour after lung resection and 1 day and 2 weeks after operation. It could be demonstrated that PGE2 and DHK-PGF2 alpha almost completely normalized within the first postoperative hour in cancer patients, whereas no significant alterations could be found in tuberculosis. After discussion of technical problems in the measurement of prostaglandins the alterations of PG concentrations after lung cancer resection are emphasized.


[Monochemotherapeutic treatment of advanced stage III and IV ovarian cancer]. 45 patients with ovarian cancer stage III and IV were treated with melphalan, which was injected intravenously over a time period of six hours. None of the patients had been treated previously with chemotherapeutic drugs. 30 of the patients suffered from ovarian cancer stage III, and 17 of this group went into remission which in three cases lasted longer than twelve months. Six of 15 patients suffering from stage IV ovarian cancer went into remission as well. In comparing monochemotherapy with polychemotherapy, which is applied intravenously as well over a much longer time interval we found approximately the same remission rate. Because of the lower toxicity in the treatment with melphalan and the short period of application, there is a significant advantage to using monochemotherapy rather than polychemotherapy for stage III and IV ovarian cancer.


[Epidemiology of ovarian cancer].

[Epidemiology of ovarian cancer]. At the Gynecological University Hospital in Marburg/Lahn, 190 women with cancer of the ovary who had been under clinical treatment from 1962--July 1976 were studied epidemiologically. Special risk factors which seem to predispose to the development of cancer of the ovary were determined. Higher social standing, having no children or having born more than four children, a shortened menarche-menopause interval, having had radiation of the pelvis, as well as having had an appendectomy seem to be factors overrepresented among cancer patients in Marburg. More patients had blood group A and fewer had blood group O than would be expected from the distribution in the population as a whole. Polyps of the corpus uteri were often seen to precede cancer of the ovary. Diabetes mellitus, adiposity, hypertension and varicosis were frequent accompanying diseases. Many patients had a fmily history of cancer.


[Social class and bronchial cancer: the social structure in comparison to the total population]. 400 male lung cancer patients were analysed according to their social class distribution and compared with the relevant age group of the Austrian population. There are significantly more lower class people among lung cancer patients than in the general population. The higher lung cancer risk in lower social classes, therefore, may be associated with social factors. These may influence smoking habits, the main cause of lung cancer: lower class people are more often cigarette smokers, less exsmokers and prefere high tar cigarettes.


[Epidemiology of cervical cancer in Austria]. In cooperation with the Austrian National Institute for Statistics the incidence rates of cancer of the cervix uteri in Austria in the period of 1971--1975 were investigated. Not only the different federal countries but also the political districts were concerned by this study. The main findings were a relative high rate of women less than 40 years of age and severe regional differences. Problems in the registration of incidence rates of cancer are pointed out.


[Papillomatous changes in the cervix uteri]. A case of condyloma acuminatum of the uterine cervix and a case of papilloma on the cervix with concomitant adenocarcinoma of the cervix are described. The diagnostic biopsy revealed only the papillomatous lesion, whereas the adenocarcinoma was diagnosed in the surgical specimen after hysterectomy. Referring to the studies of Meisels et al. on condylomatous lesions of the cervix, the possible frequent incidence of this cervical lesion and its role as one possible first step in the pathogenesis of cervical cancer are discussed. The in toto excision is recommended because of diagnostic and therapeutic reasons. Clinical, colposcopic and cytologic check-up has to be done carefully for years after primary treatment.


[Treatment procrastination time in breast cancer and personality structure]. Sixty patients with mammary cancer were studied in order to determine whether a connection between the tendency to delay medical treatment and a neurotic personality structure exists. The results are based on different personality factors that were investigated by means of the 16-PF test by Cattell. It could be shown that for patients who had delayed treatment (D2) the personality traits "limited inner tension" and "slightly inhibited" were present. On the other hand patients who had not delayed treatment (K1) displayed the personality traits "higher inner tension" and "free of inhibitions".


[Colorectal cancer].

[Colorectal cancer]. Incidence of colorectal cancer is increasing during the last years. 5% of the population get affected. From these a group of patients with a higher carcinoma risk must be separated: that with adenomas, familial polyposis and ulcerative colitis. Nourishment seems to be one of the main factors for the development of cancer. Although all important principles of radical surgery are realized, this 5-year survival rate for colorectal cancer is less than 40%. Prophylaxis, early diagnosis and the effect of irradiation and drug therapy must improve the relatively poor prognosis of colorectal cancer, which has reached in Germany the highest mortality and even -- with the exception of skin cancer -- the highest morbidity of all malignant neoplastic diseases.


[Neuroblastoma sympathicum problem: our own experiences with 10 neuroblastoma patients]. Special problems of neuroblastoma sympathicum are being demonstrated by means of 10 cases. Although in the past 20 years therapy ahs been improved considerably, the 2-year survival rate in 35--40% was hardly increased. Three children are specially presented: case I with myoclonus encephalopathy, case II with spontaneous regression and case III, where therapy was carried through by radical surgery. Various possible causes of myoclonus encephalopathy are being discussed and, regarding prognosis, assessed favourably. Several samples of excision should be required, since the tumor substance varies histologically. It is further reported about immunological phenomena. We point out especially that, if a tumor is manifested in a child under one year of age, the prospect is very good. The tumor should be excised by radical surgery, and, if vital structures are included, a resection en bloc might be necessary, with re-implantation of important blood vessels. Favourable factors with regard to prognosis are being counted up. Therapy should be carried out individually, depending on a low risk or high risk case.


[Has the calculation of the rate of tumor growth clinical significance?]. In 142 circular lung foci of 78 patients we determined the tumor doubling times (13 bronchial carcinomas, 7 benign pulmonary tumors, and 122 pulmonary metastases). They fluctuated between + 12 and + 8,863 days of tumor growth and a diminuation of -1,810 days of half-life. 44% of all pulmonary metastases doubled their volumes within 60 to 250 days. During the observation period the times of tumor growth varied not only in different pulmonary metastases of the same patient, but also in solitary circular lung foci of the same person considerably. There is no connexion between tumor doubling time and histological tumor type as well as the interval between surgery of the primary tumor and occurrence of pulmonary metastases. Though we found in patients of 10 to 30 years of age only quickly growing pulmonary metastases with a tumor doubling time of less than 60 days a corrlation between time of tumor growth and age could not be proved. By the determination of the tumor doubling time neither binding statements on the nature of a circular lung focus can be made nor clinical consequences for diagnostics or therapy be drawn.


A review of one thousand cases of intracapsular cataract extraction: I. Complications. A comprehensive review of 1,000 cases of intracapsular cataract extraction in the hands of a single surgeon was undertaken. Eyes with identifiable pathology in addition to cataract noted prior to surgery have an increased incidence of complications. Eyes operated at a younger age have an increased incidence of inadvertent extracapsular extraction, vitreous loss, flat anterior chamber, conjunctival bleb formation, and retinal detachment. Adoption of cryosurgery for lens removal reduced the incidence of inadvertent extracapsular extraction in eyes predisposed to complication. The use of monofilament nylon suture in a continuous closure reduced the incidence of bleb formation and eliminated the necessity for re-operation for complications of wound closure.


A review of one thousand cases of intracapsular cataract extraction: II. Visual results and astigmatic analysis. A review of 1,000 cases of intracapsular cataract extraction revealed that in eyes in which no factor predisposed to complication, the early visual results were equal to or better than 20/40 in 97% of the cases. Complications of surgery in this group accounted for decreased visual acuity in only 1.7% of the eyes. In the group of patients with high myopia, previous surgery, known corneal disease, or some other factor thought to predispose to a complication, the visual acuity was equal to or better than 20/40 in only 74% of the cases, most of the decrease being due to preexisting factors within the eye rather than complications themselves. In the first group, the total amount of astigmatism produced by all the suturing techniques reviewed was similar. With interrupted suturing techniques, the axis of the correcting cylinder was more often against the rule while continuous closures with monofilament nylon more frequently produced with the rule astigmatism.