[Pregnancy-connected hypotension - the influence of mineralo-corticoids on fetal nutrition (author's transl)]. A considerable number of nutritionally deficient newborns are to be expected when over an extended period of time during pregnancy, the mother's bloodpressure readings are 110/65 or below and when no therapy to increase this bloodpressure was administered. We therefore instituted blood pressure raising therapy on a total of 40 pregnant patients with bloodpressure values under 115/70 (25 mg Desoxycorticosteron-trimethylacetate i.m.) even though these patients did not voice any subjective complaints. This treatment resulted in an increased utero-placental perfusion which lead to a significant improvement of the placental perfusion values. Compared with the "fetal outcome" of untreated controls, the infants delivered by patients who had received therapy were considerably heavier at birth and showed almost no signs of prenatal malnutrition. Based on this study we feel that patients although completely free of pregnancy-connected hypotonic complaints (RR 110/65 or below) should be placed on a bloodpressure-raising VASODILATINg therapy for the improvement of fetal nutrition.


[Results of the intraperitoneal application of radioactive gold in cases of ovarian cancer (author's transl)]. Radioactive gold was instilled once into the peritoneal cavity of 248 patients with ovarian carcinoma of varying stages. The criterium for the radioactive gold instillation was either for the post-operative treatment in stage 1A or for the treatment of ascites in more advanced stages. The treatment had no clear cut influence on the five year survival rate. The treatment with radioactive gold Au 198 was very effective in the treatment of ascites and had less side effects than other radioactive colloidal materials.


[The use of partusisten in the delivery of triplets with an incarcerated fetus (author's transl)]. A triplet delivery is reported. The multiple pregnancy was undiagnosed prior to labor. Twins were diagnosed on admission for delivery. The ultrasonic and abdominal EKG findings at term are discussed. The hitherto undiagnosed third triplet became incarcerated following the administration of two units of syntocinon after the delivery of the second triplet. The intrapartum tocolysis with partusisten became life saving for the third triplet on three counts. 1. The progressive acidosis was stopped. 2. Time was gained to prepared for delivery of the last triplet. 3. Internal podalic version and extraction was much easier.


[The desire to have children (author's transl)]. During the past fourtytwo years the birth statistics of Bavaria show that the percentage of intramarital first children increased from 1/3 to 1/2 of all children born within marriages. The percentage of the marital second born children increased relatively less from 25% in 1935 to around 30% in 1977. During the same time the percentage of third and fourth children decreased from 38,8% to 19,2% by approxiamately 1/2. For some time now close correlation exists between economic competition and achievement stress and social, sexual, and generative behaviour. Not the modern contraceptives are responsible for the random and sensitive characteristics of the desire for children in couples since contraceptives only increase the planning of children but the vagaries of the future expectations in a dubious economic and social system are responsible.


[The importance of regressive changes in the placenta during the so-called migration of the placenta (author's transl)]. Starting from the tenth to the sixteenth week of pregnancy ultrasonic placental localizations were performed in 22 pregnant women at four week intervals. In all cases the placenta was located in the anterior wall of the uterus and bordered or covered the internal os of the cervix. In 17 cases a cephalad migration of the placental localization was registered. In 5 cases the low implantation of the placenta did not change until delivery. In 14 of 19 cases marginal atrophic changes of the placenta were found. No morphologic abnormality was detected in five placentas from patients who showed migration of the placental localization. Since the placenta is tightly implanted in the endometrium a true migration of the placenta is unlikely. Our investigations show that areas of low implantation of the placenta are stretched with increasing growth of the uterus and then undergo regressive and pressure atrophy changes. It is likely that the cervical margin of the placenta cannot be detected by ultrasound in a large number of cases.


Mutants of sexual maturity in Paramecium caudatum selected by erythromycin resistance. Cells of Paramecium caudatum, syngen 3 usually become sexually mature about 50 fissions after conjugation. In order to study the genetic mechanisms that control fission-department expression of maturity, an attempt was made to obtain early mature mutants by treatment with N-methyl-N'-nitro-N-nitrosoguanidine. A new cytoplasmic marker, erythromycin resistance, was used to eliminate nonconjugant and macronuclear regeneration clones. Twenty early mature clones were obtained from five different mutagenized cultures. Three of them were genetically analyzed by crosses to wild-type stocks. The results show all three mutants to be controlled by incompletely dominant genes, i.e., the homozygotes became mature 20-25 fissions and the heterozygotes 15 fissions earlier than the wild-type clones. At least two different loci are suggested for the early maturity.


Osmotic avoidance defective mutants of the nematode Caenorhabditis elegans. A wild-type strain of the nematode Caenorhabditis elegans has been shown to avoid high concentrations of a number of sugars and salts. Individual and population assays for this response were developed and mutants were selected for their inability to avoid high concentrations of fructose or NaCl, Seven nonavoiding mutants representing six complementation groups were isolated and characterized. Genetic studies indicate that the mutants each carry a single recessive mutation responsible for the defective osmotic avoidance behavior. The map locations of the six complementation groups identified by these mutations have been determined. Mutants isolated for their inability to avoid fructose are also unable to avoid NaCl and vice versa. The mutants move normally, exhibit normal touch sensitivity, and, like wild type, follow isotherms in a radial thermal gradient. All of the mutants are at least partially defective in the attraction to sodium chloride exhibited by wild type. None of the mutants is temperature sensitive, and all exhibit defective osmotic avoidance behavior as young L1 larvae. Preliminary anatomical studies indicate selective sensory neuron changes in at least one mutant.


Organization of the chorion genes of Bombyx mori, a multigene family. I. Evidence for linkage to chromosome 2. The chorion genes of silkmoths comprise a multigene family that codes for 50 or more highly specialized structural proteins found in the eggshell. A detailed study of the chromosomal organization of these genes was initiated, using inbred stocks of Bombyx mori as a source of electrophoretic variants for genetic markers. Chorion protein patterns were screened on thin-slab polyacrylamide isoelectric focusing gels. A wide range of polymorphism was observed between stocks. However, isoelectric focusing patterns obtained within a stock were nearly homogeneous, indicating that inbreeding has produced a high degree of homozygosis. Testcrosses were carried out to examine the linkage relationships between electrophoretic markers in four inbred stocks. One race (C108) was selected as a standard against which to compare the inheritance of the variants found in the other three stocks. Chorion markers behaved like codominant Mendelian traits in F, crosses. A total of 15 out of 16 C108 markers cosegregated in subsequent testcrosses, indicating that they are linked. These genes were mapped to the second chromosome, using markers Gr and Y.


Bromodeoxyuridine-induced mutations in synchronous Chinese hamster cells: temporal induction of 6-thioguanine and ouabain resistance during DNA replication. Mutations were induced in synchronous Chinese hamster cells by bromodeoxyuridine (BUdR) incorporated into cells for one-hour periods in the cell cycle. There was a very pronounced temporal dependence during the first half of the DNA synthesis period for the induction of damage leading to 6-thioguanine (6TG) and ouabain resistance. No mutants above background were induced by exposure to BUdR in G1 and G2 cells, and very few mutants were induced in the latter part of the DNA synthesis period. The peak for the induction of 6TG resistance occurs at about two hr in the DNA synthesis period; one hour later there is a peak for the induction of ouabain resistance. Both peaks occur before the time of maximum incorporation of BUdR into DNA. These results suggest that the mutagenesis by BUdR is associated with at least two nuclear genes, which replicate at two hr and three hr in the DNA synthesis period.


Isolation and genetic characterization of a mutation affecting ribosomal resistance to cycloheximide in Tetrahymena. A dominant mutation at a new locus affecting resistance to cycloheximide has been isolated by exploiting a synergistic relationship with a previously known mutation for cycloheximide resistance in Tetrahymena. The new mutation (ChxB) was induced in a line homozygous for ChxA and was recovered from that background by a new technique termed interrupted genomic exclusion. Segregation data from the interrupted genomic exclusion suggest that ChxA and ChxB are separate, linked loci showing 30% recombination. Minimal lethal doses of cycloheximide for the four possible combinations of the wild-type and mutant alleles of these two genes are: wild type 6 microgram/ml, ChxA 125 microgram/ml, ChxB 10 microgram/ml, ChxA-ChxB 175 microgram/ml.


Regulation of mouse major urinary protein production by the Mup-A gene. A method was developed to quantitate the daily excretion of the three major urinary proteins (mups) to test which parameters of the mup phenotype are controlled by the the Mup-a gene. Electrophoretic separation of the mup proteins, followed by staining and spectrophotometric scanning was used to characterize the phenotypes of various inbred strains. The mup phenotype of a strain proved to have two components: the absolute levels and the relative proportions of the mups present in the urine. Testosterone treatment alters both components of the mup phenotype, increasing mup excretion and aftering their relative proportions. The induced proteins are the same as the basal proteins as judged by electrophoretic mobility, molecular weight, and reactivity with antibody. All strains excrete all three mups when induced. The Mup-a gene appears to be a single, codominantly expressed regulatory locus that controls the induced proportions of the three proteins. However, other genes in addition to Mup-a participate in controlling the basal mup proportions, as well as individual and total mup levels before and after testosterone treatment.


Physical mapping of cleavage sites recognized by restriction endonucleases on the genome of bacteriophage T5. The DNA of bacteriophage T5 has been treated with restriction endonucleases EcoRI, HindIII, BamI, SmaI, PstI, SalI, KpnI and the electrophoretic pattern obtained in agarose gel has been analyzed in order to localize the specific cleavage sites on the T5 DNA. The localization of cleavage sites has been reduced from the electrophoretic pattern of double and partial digests, the digests of isolated restriction fragments and the digests of deletion mutant T5st(o) DNA. Four BamI cleavage sites have been found and localized on the physical map of T5 DNA at 0.21, 0.225, 0.685 and 0.725 fractional length. Endonuclease SmaI cleaves at 0.39, 0.59 and 0.69 fractional length. Endonuclease PstI cuts T5 DNA at 11 sites: 0.090, 0.210, 0.320, 0.510, 0.635, 0.670, 0.705, 0.770, 0.815, 0.840, 0.875 fractional length. Six KpnI cleavage sites have been mapped at 0.170, 0.215, 0.525, 0.755, 0.830, 0.850 fractional length. A complete cleavage map of the phage genome is presented for seven restriction enzymes.


Chromosomal rearrangements by an IS2 insertion in phage Mu-1. We have isolated and characterized a mutant of temperate phage Mu-1 carrying an IS2 insertion in the middle of its beta region. This mutant gives rise spontaneously to secondary mutants which have deletions of different sizes adjacent to IS2. One particular derivative however, was found to have acquired an additional insertion sequence adjacent to IS2. This derivative gave rise to tertiary mutants carrying a deletion next to the tandem insertion. The tandem insertion was located at the same place in the Mu beta region as another 2.6 kb insertion independently isolated by Chow et al. (1977) and was found to be homologous to that insertion. The properties of this particular secondary mutant show that Mu phage particles lacking their S end are defective for growth and lysogenisation.


Physical mapping of bacteriophage lambda DNA with restriction endonuclease HpaI. The restriction endonuclease from Haemophilus parainfluenzae, endoR.HpaI cleaves lambdacI857s7 DNA into 14 fragments. The sizes of these fragments were determined and a physical map was constructed. The ordering of the fragments was carried out using different deletion and substitution mutants of lambda phage, double cleavages with another restriction enzyme, endoR.BamHI, and partial protection of individual HpaI recognition sites by the antibiotics distamycin A and actinomycin D. HpaI produces fragments from the left arm of the lambda DNA genome, which may help in investigating the structure and function of this part of the phage.


Portal fibrosis in the livers of alcoholic patients. Liver biopsies in nine of 70 male alcoholics seen during a 12 month period showed predominantly portal fibrosis with fatty change, but little or no alcoholic hepatitis. None of the 30 female alcoholics seen during the same period showed this appearance. The nine men were younger and of lower socioeconomic class than the other male alcoholics, but had similar alcoholic history. Seven of the nine had chronic pancreatitis, diagnosed in six patients on the results of the pancreatic scan, Lundh meal and endoscopic retrograde pancreatography and in one because of pancreatic calcification and steatorrhoea. Serum tests for hepatitis B surface antigen were negative but five showed hepatitis B antibody. Four had serological evidence of previously treated or active syphilis compared with only one of the remaining 61 male alcoholics. Two had pulmonary tuberculosis and both had received isoniazid. Four of the other 61 alcoholics gave a history of tuberculosis similarly treated. At least one cause for the portal fibrosis other than primary alcoholic liver disease was found in all nine patients. Portal fibrosis in an alcoholic in the absence of severe alcoholic hepatitis should lead to a search for other causal factors. In particular, chronic pancreatitis should be excluded even if the patient is asymptomatic.


Ultrasonic scanning in pancreatic disease. We have analysed retrospectively the pancreatic ultrasound scans (using a bistable machine) in 138 consecutive patients, and have related the results to the clinical status and the final diagnosis in each case. The scans were read without knowledge of the patient's clinical state. When technically unsatisfactory scans were excluded from consideration, the overall diagnostic accuracy of ultrasonography proved to be 82%, with a false positive rate of 8%. The scan was abnormal in all 10 patients with cancer of the pancreas: a positive diagnosis of cancer was made in six. All patients with chronic pancreatitis in relapse had abnormal scans, but in 53% the scans were normal in patients in whom the disease was in clinical remission. In seven patients with chronic pancreatitis who suffered relentless pain, the head of the pancreas was swollen and contained cystic areas or emitted abnormal echoes. In acute pancreatitis ultrasonic scanning proved useful in following the progression of the disease to final resolution, or to development of complicating pseudocyst, abscess, or ascites. Random echoes in the early stages of acute pancreatitis are features of haemorrhagic necrosis. In alcoholic relapsing pancreatitis the persistence of abnormal echoes, disposed linearly along the axis of major ducts, suggests the presence of chronic pancreatitis.


Mucosal-associated bacterial flora of the intestine in patients with Crohn's disease and in a control group. The bacterial flora intimately associated with the intestinal mucosa of patients with Crohn's disease has been examined and compared with the mucosal flora of a control group. Specimens were obtained at operation from patients undergoing intestinal surgery. Whole thickness intestinal sections were taken from the diseased segment and from a portion of uninvolved intestine from patients with Crohn's disease as well as from a control group. A section of each specimen was examined histologically. Twenty-two specimens of Crohn's tissue (12 ileum, 10 colon) and 46 control samples from small and large bowel were examined using strictly anaerobic bacteriological techniques in an anaerobic chamber. Organisms were grown under both aerobic and anaerobic conditions. A mucosal flora was found to exist in all the large bowel samples and in three-quarters of the small bowel samples. It was qualitatively similar in all the samples, consisting mainly of Gram positive bacteria, aerobic Gram negative rods and bacteroides. Greater numbers of bacteria were associated with colonic tissue (10(7) - 10(8) per g) than with tissue from the jejunum (10(3) - 10(4) per g). This difference was statistically significant (p<0.03). Samples from the terminal ileum were quantitatively intermediate between jejunum and colon. There was no statistical difference in the numbers of bacteria associated with Crohn's tissue compared with histologically normal tissue from the same patients and from the control group of patients. Among the bacterial isolates, however, Enterobacteria were more commonly associated with Crohn's tissue.


Measurement of fasting and postprandial plasma VIP in man. A specific radioimmunoassay has been developed capable of detecting 1.5 pmol VIP/l plasma with 95% confidence. The antisera employed reacted most avidly with whole VIP, partly with C terminal, but not with N terminal fragments. In 110 healthy fasting volunteers plasma VIP concentrations were estimated to lie between 0.5 and 21 pmol/l (median 1.7). No significant change was seen after ingestion of a standard test meal.


Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Graded doses of 0.6, 1.3, and 3.3 pmol/kg/min of vasoactive intestinal peptide (VIP) were intravenously infused over 30 minute periods in four healthy volunteers and plasma VIP levels were measured by radioimmunoassay. Even with the smallest dose of VIP, plasma concentrations rose markedly above normal values. Infusion of higher VIP doses resulted in mean plateau levels of circulating VIP which were in the range of VIP values found in the Verner-Morrison syndrome. After cessation of the VIP infusions, plasma VIP levels fell strikingly by first order kinetics with an average disappearance half-time of one minute. The apparent metabolic clearance rate was about 9 ml/kg/min and the apparent volume of distribution for VIP was approximately 14 ml/kg. During infusion of the highest VIP dose, previously shown to induce one-fifth maximum pancreatic juice secretion, plasma concentrations of glucose, free fatty acids, and calcium were slightly but significantly raised, the pulse rate and the amplitude of blood pressure were increased, and cutaneous flushing occurred. The spectrum of effects accords well with some abnormalities seen in the Verner-Morrison syndrome. The present data, however, do not support a role for VIP as a circulating hormone, at least under physiological conditions.


Prevalence of diverticular disease of the colon in patients with ischaemic heart disease. In view of the similar patterns of incidence of diverticular disease of the colon (DD) and ischaemic heart disease (IHD) in different communities, the prevalence of diverticular disease was investigated in male patients after recovery from acute myocardial infarction. A significantly higher prevalence of DD was found among infarct patients (57%) than among male control subjects (25%) matched for age and social class.


Venous prostaglandin-like activity in diarrhoeal states. Prostaglandin E2-like activity was determined in peripheral venous blood of control subjects and in patients with acute gastroenteritis and active ulcerative colitis, using a bioassay method. No significant diurnal variations of prostaglandin levels were detected in the control group, while significantly raised venous plasma prostaglandin-like activity was detected in acute gastroenteritis and in active ulcerative colitis.


Is hypergastrinaemia associated with rheumatoid arthritis? In an attempt to confirm the reported high incidence of raised serum gastrin levels in patients with rheumatoid arthritis (RA), gastrin concentrations were estimated in 54 patients. Only three patients (6%) had basal hypergastrinaemia. The heptadecapeptide (G17) and total carboxyl-terminal immunoreactive gastrin responses to a standard protein meal were measured by specific radioimmunoassay in these three patients and in nine normogastrinaemic RA patients displaying the same age range. The three hypergastrinaemic patients showed significantly greater and more prolonged G17 and total carboxylterminal immunoreactive gastrin responses to the meal compared with the normogastrinaemic RA patients (P less than 0.02). Two of these three patients agreed to have an acid output study (pentagastrin 6 microg/kg subcutaneously) and gastric mucosal biopsies taken for histology. Both were found to be achlorhydric and to have atrophic gastritis. This study suggests that basal hypergastrinaemia in RA patients is considerably less common than previously reported and, when present, is associated with achlorhydria. In addition, the incidence of achlorhydria in rheumatoid arthritis is similar to that found in a normal age-matched population.


Plasma ratio of valine, leucine and isoleucine to phenylalanine and tyrosine in liver disease. The molar ratio valine + leucine + isoleucine/phenylalanine + tyrosine was determined in the plasma of patients with liver disease of varying aetiology and severity and in an age and sex matched control group. In the control group of 58 subjects the mean ratio was 3.3 +/- 0.5 (ISD). The mean ratio was significantly lowered in groups of 25 patients with alcoholic cirrhosis (P less than 0.001), 25 patients with chronic active hepatitis (P less than 0.001), 23 patients with primary biliary cirrhosis (P less than 0.001), and 11 patients with cryptogenic cirrhosis (P less than 0.001). In a group of 50 patients with cirrhosis, the ratio was significantly lowered (P less than 0.001) irrespective of the presence of hepatic encephalopathy. A good correlation existed between the value of the ratio and the severity of the liver disease as judged histologically, with values of the ratio appearing to reflect histological change irrespective of the patient's clinical condition. There was no significant diurnal variation in the value of the ratio. Lowering of this plasma amino acid ratio appears to be secondary to liver disease and quite independent of the presence of hepatic encephalopathy.


Effects of cerebral oedema and arterial hypotension on cerebral blood flow in an animal model of hepatic failure. The effects of arterial hypotension and a raised intracranial pressure on cerebral blood flow (CBF) have been investigated in an animal model of hepatic failure. Arterial hypotension was associated with a fall in CBF in the animals with liver failure but not in the controls. Significant differences in mean CBF between the two groups of animals could be demonstrated when the systolic blood pressure was in the 30-60, 60-90, and 90-120 mmHg range, but not in the 120-150 mmHg range. A raised intracranial pressure also resulted in a fall in CBF in the animals with liver failure, and a significant difference could be demonstrated between the two groups when the intracranial pressure was in the 20-40 mmHg range but not in the 0-20 mmHg range. Furthermore, in the animals with liver failure the cerebral metabolic rate for oxygen (CMRO(2)) fell as the CBF fell, there being a highly significant correlation between these two parameters. In the controls no such relation existed. Treatment with neither charcoal haemoperfusion nor high dose corticosteroids affected the fall in cerebral blood flow that occurred during arterial hypotension in the animals with liver failure. Corticosteroids, however, did reduce the fall in cerebral blood flow associated with a high intracranial pressure. These results suggest a disruption of the cerebral circulatory responses in hepatic failure. They also raise the possibility that CMRO(2) and cerebral blood flow may be maintained at normal levels in hepatic encephalopathy if cerebral oedema and arterial hypotension can be prevented.


Experimental evaluation of rigor mortis. IV. Change in strength and evolution of rigor mortis in the case of physical exercise preceding death. Evolution of rigor mortis in rats exercised before death shows the following characteristics with respect to controls: (1) Its intensity is increased in the initial phase. (2) It reaches its maximum development at the same time. (3) Higher maximum values are reached (in our experiments 1.39 times the maximum values for controls). (4) Higher values are maintained from 100 minutes to 16 hours with statistically significant differences. (5) It attains resolution at the same time.


Four deaths due to intravenous injection of cocaine. Cocaine is a potent psychotropic drug that alters mood and behavior by stimulating the central nervous system. Deaths from abuse of cocaine are relatively rare. Most such deaths appear to be related to the intravenous injection of the drug. Acute fatal cocaine intoxication is characterized by headache, cold sweats, rapid pulse, tremors and nausea, followed by convulsions, unconsciousness and death. The prime mode of death appears to be respiratory paralysis, secondary to the effects of cocaine on the medullary portion of the brain. This paper presents four deaths due to acute cocaine intoxication following intravenous injection. Blood concentrations of cocaine were 0.11, 0.37, 0.36 and 0.75 mg/dl.


[Electromyographic abnormality in patients with idiopathic cardiomyopathy (author's transl)]. Using electromyographic techniques, we examined the possibility that idiopathic cardiomyopathy might be a cardiac manifestation of a general myopathy. The EMG studies were done on sixteen normal subjects and seventeen patients with idiopathic cardiomyopathy, including six with hypertrophic obstructive cardiomyopathy (HOCM), six with hypertrophic cardiomyopathy (HCM), and five with congestive cardiomyopathy (CCM). The action potential duration in the brachial biceps were determined exactly by a special recording technique. In the normal subjects, the mean action potential duration was 5.42 +/- 0.12 msec. In the patients with idiopathic cardiomyopathy, the mean action potential duration was 4.43 +/- 0.15 msec, which was significantly shorter than that of the normal subjects; 4.06 +/- 0.30 msec in HOCM, 4.45 +/- 0.20 msec in HCM, and 4.48 +/- 0.13 msec in CCM. These findings suggest that idiopathic cardiomyopathy is only one aspect of a larger disease spectrum, with abnormalities in both voluntary and cardiac muscles.


Injuries caused by home-made explosives. Eighty-six cases of injuries caused by home-made unconventional explosives were studied. The use of this type of explosive is common in India, Sri Lanka and other Eastern countries. Injuries are due to the blast effect, shrapnel and flash. The blast effect is seen only when the explosion occurs at close range. Accidental injuries to handlers and manufacturers conform to a particular pattern.


[Statistical observation of urolithiasis at the Hokkaido University Hospital (1959-1975) (author's transl)]. In recent 17 years from 1959 to 1975, 32296 patients were visited to the Urological department of Hokkaido university hospital. 1192 patients (male 818, female 374) were diagnosed as urolithiasis in this period. The incidence was 3.7%. Among them, 1324 urinary calculi were seen. In detail, renal stone 509 (38.4%), ureteral stone 717 (54.2%), bladder stone 84 (6.4%), urethral stone 14 (1.1%). The tendency of upper urinary stone-wave was increasing gradually. Especially after 1965, it was increasing sharply. The tendency of lower's was stable. There was 15 urolithiasis in childhood in this duration. Most of them were upper urinary stone. 9 patients were under 5 years of age. The cause of urolithiasis was found in 9.5%. The upper urinary stone was found only 4.7% but, 57% was found in lower urinary stone. In this report, statistical studies of this work was compared and discussed with already published data in 1961 of our department.


[Immunoelectrophoresis used for identification of blood stains in forensic medicine]. Conclusive evidence was obtained in this study that immunoelectrophoresis could be used in the identification of blood-stains in two particular cases: for diagnosis or approach to diagnosis of the age of a blood-stain, and for diagnosis of the human origin of a blood-stain that had been treated with petroleum products. Although many aspects should be investigated in more detail, it is certain that this method can be employed in combination with other methods.


[Experimental studies on extracorporeal liver perfusion.--Development and evaluation of an improved circuit (author's transl)]. Clinical application of the extracorporeal liver perfusion has been rather limited mainly because of cumbersome procedure, not infrequent circulatory insufficiency due to large priming volume, and bleeding tendency due to hepatic insufficiency itself and heparinization, which are inherent with most of the currently available systems. A circuit was developed which employs siliconized tubings to eliminate heparinization. The liver is gravity perfused added with arterial pressure by utilizing A-V type blood access, thus eliminating the blood pump and oxygenator. A heat exchanger is eliminated by placing the liver in a moist liver chamber kept at 30 degrees C. Feasibility of the circuit was confirmed by 5 in vivo runs with healthy mongrel dogs who tolerated the procedure well. This circuit was further evaluated in dogs with acute hepatic failure induced by portacaval anastomosis and subsequent ligation of the proper hepatic artery 48 hours later. They were connected to the circuit when convulsion developed. Along with clinical observation, biochemical analysis were performed for samples obtained at the inlet (In-blood) and the outlet (Out-blood) of the liver chamber. Oxygen consumption with carbon dioxide production by the liver was confirmed in previous control experiment. Although temporarily, all animals showed recovery from convulsion. Ammonia level was invariably lower in Out-blood than in In-blood by approximately 70 gamma/dl. Blood sugar level was always higher in Out-blood by 40-70 mg/dl than in In-blood. Other parameters such as bilirubin, total protein, GOT and GPT levels were not significantly different. Technical feasibility and acceptable performance of the system were established in this study and its clinical evaluation is warranted.


[Studies on the estimation of the postmortem interval. 6. The putrefaction (author's transl)]. The authors have investigated ten kinds of putrefactive findings on 368 cadavers which were subjected to medico-legal autopsies in our laboratory and have come to the following conclusions. 1) Concerning the occurrence of the putrefactive findings, seasonal variation was not seen on the cadavers which had remained indoors in the Hokkaido districts. No variation due to age and sex was seen. The occurrence of the findings was less frequent in death from exsanguination, traumatic shock and cardiac tamponade. 2) The putrefactive findings can be utilized as a criterion for estimating the postmortem interval; the interval is estimated to be over 6 hours when the pericardial fluid is turbid, over 12 hours when exudation of putrefactive fluid, gas formation, blood-stained peritoneal fluid or blood-stained pericardial fluid is present, over 18 hours when greenish discoloration of the skin, network of the skin or blood staining of the endocardium or the endothelium is seen, over 2 days when bullae is present on the skin, over 5 days when the pericardial cavity is dry, within 6 days when none of them are present.


Experimental evaluation of rigor mortis. III. Comparative study of the evolution of rigor mortis in different sized muscle groups in rats. The use of new methods and an appropriate apparatus has allowed us to make successive measurements of rigor mortis and a study of its evolution in the rat. By a comparative examination on the front and hind limbs, we have determined the following: (1) The muscular mass of the hind limbs is 2.89 times greater than that of the front limbs. (2) In the initial phase rigor mortis is more pronounced in the front limbs. (3) The front and hind limbs reach maximum rigor mortis at the same time and this state is maintained for 2 hours. (4) Resolution of rigor mortis is accelerated in the front limbs during the initial phase, but both front and hind limbs reach complete resolution at the same time.


Immunoreactive granulocyte elastase in human serum. A specific radioimmunoassay has been developed for determination of human granulocyte elastase in blood. THE granulocyte elastase employed as radioiodinated tracer in the assay was inactivated with diisopropylfluorophosphate in order to prevent binding of the tracer to the serum inhibitors alpha2-microglobulin and alpha1-anti-trypsin, while still retaining its immunoreactivity. The labelled tracer showed, however, a pronounced tendency to nonspecific binding to serum proteins such as albumin and alpha2-macroglobulin and also to the Sephadex particles. The binding of the labelled tracer to alpha2-macroglobulin caused a false increase in the immunoreactive granulocyte elastase in serum. But the binding of the labelled tracer and its consequences could be circumvented by increasing the NaCl concentration of the reaction mixtures and/or gel filtration buffers. Freshly drawn normal human serum contains about 135 microgram granulocyte elastase/l measured as diisopropylfluorophosphate-inactivated granulocyte elastase. The results of experiments in which serum was fractionated by Sephadex G-100 gel filtration suggest that essentially all of the immunoreactive material in normal human serum is granulocyte elastase bound by alpha1-antitrypsin. This finding implies that granulocyte elastase is released from the cells in an active form and then rapidly bound by the inhibitors.


[Asymmetric synthesis with unlimited stereoselectivity--the synthesis of isomer-free peptide derivatives by stereoselective four-component condensation (author's transl)]. The development of methods for the synthesis of peptides by stereoselective four-component condensations led to new ways to prepare pure chiral chemical compounds with high yield by asymmetric syntheses. A scheme of asymmetric syntheses is described, which begins with a productively stereoselective synthesis affording a high yield of the desired product, accompanied by a minor amount of a diastereomeric byproduct. This is converted into an easily removable non-isomeric compound by a subsequent reaction with unlimited destructive stereoselectivity which is due to non-linear effects. In general, only small losses of the main product occur during the latter step. The efficiency of such asymmetric syntheses is enhanced by the use of chiral templates which can be recycled. As an illustration we describe the synthesis of a stereoisomer-free tetravaline derivative by a productively stereoselective four-component condensation, followed by conversion of the contaminating diastereoisomer into an easy to remove non-isomeric compound by destructively stereoselective partial acidolysis which yields the main product in 73% and with a purity of greater than 99.98%.


Disulfide-linked cyanogen bromide peptides of bovine fibrinogen. III. Isolation and identification by sequence analysis of the chain constituents in peptides F-CB2, F-CB4 and F-CB5. Three disulfide-linked peptides with molecular weights of about 6000, 7000 and 45000, respectively, were isolated from bovine fibrinogen cleaved with cyanogen bromide. The chain constituents of these peptides were separated after reduction and alkylation and identified by partial amino acid sequence analysis. Of the five polypeptide chains of the largest fragment F-CB2, three are derived from the central region of Bbeta chain, one from the Aalpha chain and one from the gamma chain. The smaller peptides F-CB4 and F-CB5 consist of one and two polypeptide chains and originate from central regions of the Bbeta and gamma chains, respectively, indicating that they represent intrachain disulfide loops. These and previous data show that the disulfide-bonded regions of bovine fibrinogen are similar to those in human fibrinogen.


Behaviour of young and old desialylated rabbit erythrocytes in vivo. Young and old rabbit erythrocytes, separated by density gradient centrifugation, were desialylated by neuraminidase treatment and reinjected into the animal after 51Cr labelling. Both red cell populations are quickly removed from the circulation and trapped by the liver; then a large percentage of the young cells reappear in the peripheral blood and behaves like untreated erythrocytes; old cells, on the contrary, do not return to the blood stream and are probably lysed in the liver. These results suggest that a sialic acid repair can occur on the membrane of young erythrocytes and confirm that the loss of this molecule is not by itself sufficient to determine the death of the cell.


Well-defined insoluble primers for the enzymatic synthesis of oligo- and polynucleotides. Two methods are described by which primer molecules like UpU and oligodeoxythymidylates can be coupled with high efficiency to an insoluble polymer, like hydroxypropylated Sephadex G-50, by one covalent linkage. In one procedure aliphatic dicarboxylic dichlorides (e.g. adipoyl dichloride) are used to serve as spacers of variable length and for anchoring the primer molecule UpU. The other method involves pU as an anchor for (pdT)3 and (pdT)6, which are coupled to the polymer using condensation reactions with 2,4,6-triisopropylphenylsulfonyl chloride. In both cases the homogeneous primer molecules are bound specifically to the polymer. The insoluble primers are tested for their priming efficiency using polynucleotide nucleotidyltransferase from Micrococcus luteus and DNA nucleotidylexotransferase from calf thymus. The primers and synthesized polynucleotides can be cleaved from the polymer under conditions which are not damaging to ribo- and deoxyribopolynucleotides.


Capillary haemangiomatosis of the lungs. A case of capillary haemangiomatosis affecting both lungs. The angiomatous growth involved particularly the intralobular fibrous septa and appeared locally aggressive as it had destroyed and obstructed the pulmonary veins and venules. Some pulmonary arteries and bronchi were affected to a lesser extent. Pulmonary venous obstruction, sometimes simulating pulmonary veno-occlusive disease, caused severe haemosiderosis and interstitial fibrosis. The clinical features and the lung biopsy erroneously suggested a diagnosis of primary pulmonary haemosiderosis. No comparable case has been found in the literature.


Ultrastructure of airways in children with asthma. This study describes the histopathology and ultrastructure of bronchial mucosa in lung biopsies from two children with bronchial asthma in remission, and compares them with lung samples from two children who died in status asthmaticus. Light microscopy of all samples showed changes typical of bronchial asthma, e.g. mucus plugging, goblet cell hyperplasia, 'thickening of bronchial basement membrane', peribronchial smooth muscle hypertrophy and eosinophilic infiltration. Electron microscopy revealed that the mucus plugs consisted of moderately electron-dense floccular material containing degenerate epithelial cells, macrophages and cell fragments. The luminal surfaces of ciliated cells showed cytoplasmic blebs and abnormal cilia. Mast cells in various stages of degranulation were scattered between bronchial epithelial cells. The subepithelial hyaline layer, commonly referred to as "thickened basement membrane", consisted of collagen fibrils in plexiform arrangement. The basement membrane proper appeared intact. These electron microscopic changes, particularly the presence of mast cells and subepithelial collagen deposits, were also found in autopsy samples. This combined light and electron microscopic study shows that marked, possibly irreversible changes may be present in the lungs of patients with severe bronchial asthma, even when they are asymptomatic. These pulmonary changes could be the direct consequence of mast cell activation and the release of various mediators. No evidence of immune complex deposition was found.


Idiopathic arterial calcification in infancy. Three fatal cases of idiopathic arterial calcification in infancy are reported. The infants' ages ranged from 9 days to 3 months. Death was due to cardiac failure; in two cases caused by myocardial ischaemia, and in one by pulmonary hypertension. The histological findings are described and aetiology of the condition is discussed.


Pure Sertoli cell tumour of the ovary: report of a case with ultrastructural observations. A case of pure Sertoli cell tumour of the ovary is described. Unusual features were its great size, lack of clinical hormonal activity and the presence of granulomas in its interstitium. Mitochondria with tubular christae are described for the first time in such a tumour. These, together with lipid droplets and plentiful smooth endoplasmic reticulum, suggest a potential for steroid hormone synthesis which was not expressed clinically. Dense membrane-bound granules of undetermined type were present in large numbers. The presence of cilia and microvilli, and the absence of annulate lamellae and Charcot-Böttcher crystalloids, suggests that the tumour cells may not be truly of Sertoli type.


The nephron in transport of sodium, amino acids, and glucose. The ability of the kidney to maintain overall control of sodium and fluid balance appears greater than the sum of its parts, yet microperfusion and dissection studies that have assigned particular transport processes to individual segments of the nephron are helping to clarify a number of clinical states. Among those that can be so localized are certain congenital disorders accompanied by glycosuria and aminoaciduria.


Endoscopic management of biliary calculi. In a logical extension of the diagnostic capability of endoscopic retrograde cholangiopancreatography, a number of procedures have been developed to relieve biliary tract obstruction, with the indication for each depending mainly on stone size. Thus the smallest stones can be flushed or extracted through an intact papilla of Vater, larger ones after the papilla or sphincters are cut endoscopically. Clinical results are detailed.


Yersinia enterocolitica: a significant 'new' pathogen. It thrives in the cold, defies conventional culture methods, does not respond to most antibiotics, and may mimic other disorders in its manifestations. Fortunately, most cases of yersinial enterocolitis are mild and self-limiting, but infection can be life-threatening, especially in neonates or when immunologic defenses are impaired. Clinical and laboratory diagnostic criteria and epidemiologic clues are described.


Management of osteoporosis.

Management of osteoporosis. Accelerated bone loss and diminished new bone formation in primary involutional osteoporosis far outstrip the rates seen in "normal aging." Their serious consequences can be mitigated with pharmacologic agents and adjunctive regimens.


Effective utilization of clinical laboratories. Effective utilization of clinical laboratories requires that underutilization, overutilization, and malutilization be appreciated and eliminated or reduced. Optimal patient care service, although subjective to a major extent, is reflected in terms of outcome and cost. Increased per diem charges, reduced hospital stay, and increased laboratory workload over the past decade all require each laboratory to examine its internal operations to achieve economy and efficiency as well as maximal effectiveness. Increased research and development, an active managerial role on the part of pathologists, internal self-assessment, and an aggressive response to sophisticated scientific and clinical laboratory data base requirements are not only desirable but essential. The importance of undergraduate and graduate medical education in laboratory medicine to insure understanding as well as effective utilization is stressed. The costs and limitations as well as the accuracy, precision, sensitivity, specificity, and pitfalls of measurements and examinations must also be fully appreciated. Medical malpractice and defensive medicine and the use of critical values, emergency and routine services, and an active clinical role by the pathologist are of the utmost value in assuring effective utilization of the laboratory. A model for the optimal use of the laboratory including economy and efficiency has been achieved in the blood bank in regard to optimal hemotherapy for elective surgery, assuring superior patient care in a cost effective and safe manner.


Malignant histiocytosis of the intestine. Its relationship to malabsorption and ulcerative jejunitis. The clinical and histopathologic features in seven patients with intestinal lymphoma are reported. Three of these presented with ulcerative jejunitis and four with overt lymphomas. A short history of abdominal pain with weight loss followed by intestinal obstruction, hemorrhage, or perforation characterized all the patients except one in whom a nine year history of malabsorption preceded the acute phase of the disease. Malabsorption was demonstrated in four of the patients, and all showed villous atrophy with crypt hyperplasia of the jejunum remote from areas of ulceration or frank lymphoma. The malignant lymphoma cells showed varying degrees of pleomorphism and exhibited phagocytosis of platelets, red cells, and cell debris. The accompanying infiltrate of inflammatory cells often overshadowed the neoplastic histiocytes, and in those cases showing little pleomorphism these cells could be easily overlooked. In the intestine the tumor cells were usually present as a diffuse infiltrate in the lamina propria or within the bases of ulcers and in five of seven cases did not give rise to macroscopic tumor masses. In all patients dissemination of tumor cells to the lymph nodes, liver, spleen, and bone marrow was evident, the infiltrate in all these organs resembling that seen in malignant histiocytosis. The morphology of the tumor cells, their phagocytic nature, the diffuse character of the tumor infiltrate, and the pattern of dissemination suggest that this lesion should be designated malignant histiocytosis of the intestine rather than histiocytic lymphoma (reticulum cell sarcoma). It is suggested that the tumor may arise from cells of monocyte-histiocyte lineage normally present in the lamina propria of the gut and that a prolonged cryptic phase accompanied, and often overshadowed, by an inflammatory reaction may give rise to malabsorption and ulcerative jejunitis before overt lymphoma is manifest.


Nuclear fragmentation in colon carcinoma cells. The nuclei of the epithelial cells of well differentiated adenocarcinoma of the large intestine show characteristic appendages, the nucleotesimals, connected with the main nucleus by lamellar bridges. We interpret this phenomenon as being the result of a hitherto unknown type of amitosis that permits rapid cancer growth in spite of a low mitotic index.


Gelatinous transformation of the bone marrow. A study of so-called gelatinous transformation of the bone marrow in 14 patients is presented. The condition is characterized by the presence of extracellular "gelatinous" material, fat atrophy, and associated focal marrow hypoplasia and is often mistaken as representing edema, necrosis, or amyloid. Histochemical studies indicate that the extracellular substance is hyaluronic acid. Though the lesion is usually associated with severe weight loss and cachexia, it appears that factors other than malnutrition must play a significant role in the pathogenesis of gelatinous transformation. Anemia, frequently seen in these patients, does not appear to be a consequence of gelatinous transformation.


Surface and transmission ultrastructural characteristics of desquamative interstitial pneumonitis. A prospective study of eight patients with desquamative interstitial pneumonitis was performed, correlating surface ultrastructure as elucidated by scanning electron microscopy, transmission electron microscopy, viral cultures of fresh sterile lung tissue obtained at thoracotomy, and immunomicroscopy. The hypothesis that environmental pollutants may act as sensitizing agents to induce macrophage migration was pursued using high resolution elemental analysis to obtain a profile of the inorganic content of phagolysosomes in the free alveolar cell population. Four surface ultrastructural changes were observed: mild alveolar septal thickening, an apparent decrease in the number of pores of Kohn, alteration of the predominant alveolar lining population from membranous to granular pneumonocytes, and prominent intra-alveolar collections of cells with broad based ruffled projections and pseudopodia representing a macrophage population. Transmission electron microscopy corroborated these observations. Individual pneumonocyte degeneration manifested as cytoplasmic dissolution, mitochondrial swelling, chromatin disruption, and loss of lamellar bodies and endoplasmic reticulum was identified; occasionally degenerating granular pneumonocytes were displaced into the alveolar space by a supraseptal bulla containing fibrin and extracellular fluid. Viruses were not identified by ultrastructural or tissue culture techniques. High resolution elemental analysis of individual phagolysosome contents failed to reveal the presence of heavy metals or other inorganic compounds. Immune complexes were not identified by immunofluorescence microscopy. However, alveolar transeptal macrophage migration was observed by transmission electron microscopy. These observations suggest that desquamative interstitial pneumonitis represents a disease in which cellular, rather than humoral, immune processes predominate. Other nonspecific cellular immune responses under the influence of various lymphokines may be responsible for the observed morphologic alterations.


Aluminum induced pulmonary granulomatosis. The association of aluminum dusts and pulmonary fibrosis with emphysema in workers in the aluminum processing and manufacturing industries is well established. The early and minimal reactions of the lungs to the aluminum dusts are not known. This report presents the first case of pulmonary granulomatosis associated with aluminum inhalation. The occupational history of this patient was thoroughly examined, and the aluminum was identified by electron probe microanalysis of the lung biopsy specimen. The granulomatous response in this patient was similar to that observed in rabbits following aluminum dust inhalation. Hypersensitivity or individual idiosyncrasy may play a role in the development of the pulmonary granulomas following exposure to aluminum.


Hepatic leiomyosarcoma: ultrastructural study and review of the differential diagnosis. A primary leiomyosarcoma of the liver in a 12 year old female is reported. It is the eleventh such tumor to be recorded, the first to be documented in an adolescent and the first to be studied electron microscopically. By light microscopy the well differentiated portions of the tumor were characteristic of leiomyosarcoma. Ultrastructurally a minority of tumor cells contained myofilaments along with cytoplasmic dense bodies and marginal dense plaques, the most distinctive subcellular markers of smooth muscle cells. A brief review of the differential diagnosis is provided.


An "abnormal" lymphoid proliferation simulating Hodgkin's disease in a burn patient. A particularly exuberant and unusual lymphoid proliferation in the spleen of a burn patient is presented. Many Reed-Sternberg cell variants and occasional diagnostic Reed-Sternberg cells strongly suggested a diagnosis of Hodgkin's disease. The pattern of distribution and cytology of this lymphoid infiltrate, however, are incompatible with Hodgkin's disease or a non-Hodgkin lymphoma. Morphologic features in this case suggest that the Reed-Sternberg cell is a B lymphocyte. The most probable etiologies of this unusual lymphoid proliferation are reviewed.


Ovarian myxoma.

Ovarian myxoma. A case of primary ovarian myxoma is reported. The tumor is rare as there are only two previously reported cases in the literature.


Chondrosarcoma of the uterus: report of a case and review of the literature. The clinical and pathologic features of a case of primary chondrosarcoma of the uterus and 12 previously described similar cases are reviewed. Pathologically the tumors resemble chondrosarcoma of bone. The clinical features, including a high degree of malignancy, resemble those of other types of pure heterologous sarcomas and the typical müllerian mixed tumors of the uterus.


Inversion of 'flourescent' segment in chromosome 3: a polymorphic trait. The frequency of the 'inversion' of flourescent constitutive heterochromatin in chromosome 3 was the same in a sample of 370 retarded persons as in a sample of 222 mentally normal men. It can be concluded that this 'inversion' is not associated with mental retardation. This variant is more common (4%) in the Canadian population we studied than in samples reported by most other authors (0-1.7%). Possibly the founder effect could play a role in the differences. Two cases of homozygotes for this 'inversion' were identified.


Familial and sporadic porphyria cutanea: two different diseases. Uroporphyrinogen (URO) decarboxylase was measured in hemoglobin-free erythrocytes from subjects with familial porphyria cutanea: the mean activity was about 50% of that found in erythrocytes from normal subjects. Asymptomatic carriers were always found in the family. No enzyme deficiency was found in erythrocytes from subjects with sporadic porphyria cutanea. The measurement of URO decarboxylase in erythrocytes seems to allow an easy distinction between these two groups of porphyria cutanea.


Familial basal cell nevus syndrome.

Familial basal cell nevus syndrome. The basal cell nevus syndrome is characterized by multiple basal cell nevi and basal cell carcinoma, cysts of the jaw, anomalies of ribs and spine, abnormal calcifications, and additional anomalies of the facial skull. A German family is described with manifestations of the syndrome in the mother and her three daughters. Expressivity was variable, in part due to age effects. The observation conforms to the assumed autosomal dominant mode of inheritance with high penetrance.


Sister chromatid exchanges in the peripheral blood of cigarette smokers and in lung cancer patients; and the effect of chemotherapy. Peripheral blood sister chromatid exchange (SCE) rates in chronic cigarette smokers and in subjects with cancer do not differ from those in healthy nonsmokers. SCE patterns were normal in 69 chronic cigarette smokers, including 62 patients with untreated lung cancer. In three chronic smokers with lung cancer, high SCE levels were related to recent intravenous chemotherapy.


Isozyme variations in acetaldehyde dehydrogenase (e.c.1.2.1.3) in human tissues. NAD-dependent acetaldehyde dehydrogenase (ALDH) of human tissues was investigated by electrophoresis and enzyme assay. ALDH is located mainly in the liver and kidney. The isozymes consist of at least six different components. Five different phenotypes were found in a total of 68 human liver and kidney specimens. It is likely that three isozyme sets are concerned in determining ALDH types. The distribution of various phenotypes of ALDH isozyme sets is presented.


Suppression of the frequencies of sister chromatid exchanges in Bloom's syndrome fibroblasts by co-cultivation with Chinese hamster cells. The effect of co-cultivation of Bloom's syndrome fibroblasts with Chinese hamster ovary cells (CHO) on the incidence of sister chromatid exchanges (SCEs) was studied. The results show that suppression of the frequency of SCEs in Bloom's syndrome cells occurs only if cell to cell contact is present with CHO cells, without any effect on the SCE frequency in the latter. It is suggested that possible genetic heterogeneity between different Bloom's syndrome patients can be studied using the method of co-cultivation.


Partial monosomy of the short arm of chromosome 9: a distinct clinical entity. A 10-year-old girl with partial deletion of the short arm of chromosome 9 is reported; karyotype: 46,XX,del(9)(p22). This syndrome results in a distinctive craniofacial dysmorphism with trigonocephaly and contrasting midfacial hypoplasia. Partial monosomy 9p was the result of a paternal de novo germinal deletion in this case.


Partial trisomy 18q in a newborn with typical 18 trisomy phenotype. This paper describes a case of partial trisomy of almost the entire long arm of chromosome 18 in a newborn with classic trisomy-18 phenotype, resulting from a de novo unbalanced 181/21p translocation: karyotype: 46,XX,-21,t(18;21)(18qter leads to 18q11 ::21p12 leads to 21qter). A review of the other reported cases of partial trisomy 18 suggests that a critical segment in chromosome 18, corresponding to bands q11-q12, might be responsible for most of the signs of trisomy 18, including failure to thrive and early death.


Mosaicism for an additional partial chromosome 8: 46,XX/47,XX+der(8)(p21 leads to qter). Report on mosaicism of an additional deleted chromosome 8 in a 12-year-old girl. She exhibits several typical but minor features of the trisomy-8 syndrome. Her IQ is 77 (Hawik).


18p-Mosaicism: case report and review.

18p-Mosaicism: case report and review. The case of a 5-month-old male infant with 18p- mosaic, who has intractable seizures and severe ophthalmological abnormalities in addition to many clinical manifestations usually described in the 18p- syndrome, is reported. The proportions of abnormal cells are 7-8% in blood and 55% in skin. About 35% of the short arm of chromosome 18 is deleted. to our knowledge the present report is the fifth one of 18p-mosaic. The main interest of this case resides in the fact that it shows a serious clinical picture despite the low proportion of abnormal cells in blood and the small degree of deletion of the short arm of chromosome 18.


[A case of bilateral retinoblastoma with monosomy 13 (q12 leads to 114) (author's transl)]. A partial monosomy 13 by interstitial deletion was found in the complement of a girl with mild mental retardation and bilateral retinoblastoma. Break points were at 13q12 and 13q14. After comparison with other known observations of retinoblastoma with deletion of chromosome 13, it is suggested that the deletion common to these patients may be band 13q14. The most likely pathogenic hypothesis seems to be the haplo-insufficiency.


Partial trisomy of chromosome no. 1 in two adult brothers due to maternal translocation (1q--;6p+). Extra chromosome material on the short arm of chromosome no. 6 (46,XY,6p+) was found in two  mentally retarded adult half-brothers with mildly dysmorphic features. The phenotypically normal mother had a balanced translocation between the long arm of chromosome no. 1 and the short arm of chromosome no. 6:46,XX,t(1;6)(q32;p25). Thus the two affected brothers were trisomic for the long arm segment of chromosome no. 1, distal to q 32. These patients, with mildly dysmorphic features and mental retardation, represent the first cases of partial trisomy 1q surviving to adult-hood. The clinical and cytogenetic data obtained from eight individuals with partial trisomies for different long arm segments of chromosome no. 1 suggest that partial trisomy of the distal two-thirds of the long arm in characterized by severe malformations, growth retardation, and early death. Conversely, partial trisomy for the distal one-third of the long arm is associated with milder malformations and longer survival time as well as growth and mental retardation.


Mapping of the linkage group GLO--Bf--HLA-B,C,A--PGM3. 1. Recombination frequencies. This study confirms close linkage for the GLO--Bf--HLA-B,C,A complex, and proves linkage between the MHC loci and PGM3. For GLO--PGM3 and Bf--PGM3, respectively, loose linkage seems to be likely, and close linkage can be excluded. Our mapping data on chromosome 6 favor the hypothesis that the PGM3 locus is situated on the HLA-A side of the MHC complex. Yet fine-structure mapping should be confirmed only by segregation analyses in crossover families by testing simultaneously all of the relevant marker loci within uniform family material.


Mapping of the linkage group GLO--Bf--HLA-B,C,A--PGM3. 2. Segregation analysis. Segregation analysis of informative families for chromosome 6 markers confirmed the map order GLO--Bf--HLA-(B, C)--HLA-A, and, surprisingly, implies that PGM3 is more probably located on the HLA-A than on the HLA-B side of the linkage group. Therefore the map position of PGM3 should be reconsidered, i.e., more informative families should be tested for all the relevant marker loci available.


Organization in vitro of ovarian cells into testicular structures. While it has been shown previously (Zenzes et al., 1978; Ohno et al., 1978) that when dissociated testicular cells are exposed to anti H-Y antiserum in vitro they are prevented from reorganizing into testicular structures, forming ovarian follicular structures instead, the most conclusive evidence for the action of H-Y antigen would be the conversion of ovarian cells into testicular organization. Testing for H-Y antigen of the medium collected from cultivated testicular cells revealed a positive reaction. Dissociated ovarian cells of newborn rats cultivated in this medium reorganize into testicular structures. It is concluded that H-Y antigen is responsible for this histomorphologic change.


Red cell glucose-6-phosphate dehydrogenase deficiency and haemoglobin variants among ten endogamous groups of Maharshtra and West Bengal. Over 900 individuals from ten endogamous groups in the Indian states of Maharashtra and West Bengal were studied for G-6-PD deficiency and haemoglobin variants. The incidence of G-6-PD varied from nil to 17.3%, while that of Hb-S varied from nil to 22.3%. In general, the tribal populations of Maharashtra are characterized by the presence of a high incidence of both Hb-S and G-6-PD deficiency. The caste Hindus showed an absence of Hb-S and rather low G-6-PD deficiency. Immigrant Parsis possessed the highest incidence of G-6-PD deficiency (17.3%).


Interstitial deletion of the long arm of chromosome 7 46,XX,del(7)(pter leads to q2200::q3200 leads to qter). A newborn girl with multiple anomalies had an interstitial deletion of the long arm of chromosome 7 (46, XX,der(7)mat). The patient's mother and maternal grandmother were carriers of a balanced translocation, 46,XX, inv ins(5;7)(q14;q3200q2200). Both cytogenetic and clinical findings were similar to those in the two cases already described.


Unusual in vivo rearrangements of the Y chromosome with mitotic instability in vitro. An unusual structural rearrangement of the Y chromosome resulting in seven different cell lines was found in a male infant with coronal synostosis as the only major clinical symptom. At least three different events must have occurred to explain the patient's karyotype: nondisjunction, chromosome breakage followed by translocation, and tetraploidization followed by somatic recombination. In addition, the structurally abnormal Y chromosome appeared to be unstable in vitro.


Regional mapping of the gene for human lysosomal acid phosphatase (ACP2) using a hybrid clone panel containing segments of human chromosome 11. A clone panel containing various segments of human chromosome 11 has been selected and use for regional assignment of the gene for human lysosomal acid phosphatase (ACP2) to the short arm of chromosome 11, in the region 11p11 leads to 11p12. Further evidence has also been presented to update the regional assignment of the gene for lactate dehydrogenase A (LDHA) to 11p12 leads to 11p13, and to support a previous assignment of the genes for the two components of the human cell-surface antigens of the SA11 (previously designated AL) group, SA11-1 and SA11-3 (previously designated AL-a1 and AL-a3), to 11pter leads to 11p13. This regional clone panel will be useful for rapid regional mapping of other genes assigned to chromosome 11.


Mosaicism in XX males.

Mosaicism in XX males. Three males with a 46,XX karyotype are described. In two of them, evidence of a Y-containing line was found. In the first case, 1 of 500 lymphocyte metaphases was 48,XXY. In the second, 1 of 400 oral mucosa cells contained a Y body. The proportion of low-grade XX/XXY mosaics found among XX males now stands at about 17%.


Rapidly adhering cells in two cases of anencephaly. We report the successful use of a new method described by Gosden and Brock (1977) in two cases of anencephaly; according to this method 'rapidly adhering cells' are identified as neural cells of a specific morphology. Although the original method described adherence of cells during the first 20 h, we were able to identify a considerable number of such cells after a delay of three days due to mailing of the amniotic fluid.


Three new electrophoretically normal glucose-6-phosphate dehydrogenase variants associated with congenital nonspherocytic hemolytic anemia found in Japan: G6PD Ogikubo, Yokohama, and Akita. Three new glucose-6-phosphate dehydrogenase (G6PD) variants, which showed electrophoretically normal mobility and were associated with chronic nonspherocytic hemolytic anemia, were found in Japan. G6PD Ogikubo, found in a 17-year-old male whose red cells contained 3% of normal enzyme activity, had normal Km G6P, normal Km NADP, normal utilization of deamino-NADP, decreased heat stability, and a normal pH curve. G6PD Yokohama, characterized from a 15-year-old male, had 1.9% of normal enzyme activity, normal Km G6P, normal Km NADP, low Ki NADPH, normal utilizations of both 2-deoxy-G6P and deamino-NADP, decreased heat stability, and normal pH curve. G6PD Akita, characterized from a 56-year-old male, had an undetectably low activity when hemolysate was examined, normal Km G6P, normal Km NADP, normal Ki NADPH, normal utilizations of both 2-deoxy-G6P and deamino-NADP, decreased heat stability, and normal pH curve. The degree of hemolytic anemia was moderate to mild in all three patients.


Deficiency of DNA ligase activity in Fanconi's anemia. A significant decrease in DNA ligase activity was observed in lymphocytes and fibroblasts of a patient with Fanconi's anemia (FA). This decrease is related to the observed DNA repair deficiency indicated by the delayed closing of repair DNA strands following UV irradiation. Other steps of DNA repair were analyzed in the FA fibroblasts, including endonucleolytic incision of DNA, repair DNA synthesis, and exonucleolytic removal of the photoproducts. No differences were found against control cells. The action of DNA ligase is delayed during replication in the FA cells, as seen by an accumulation of replicative intermediates.


A cytogenetic survey of an institution for the mentally retarded. II. C-band chromosome heteromorphisms. Heteromorphisms of chromosomes 1, 9, and 16 were studied by C-banding in a population of 403 mentally retarded individuals from diverse ethnic groups. A significant difference in the distribution of heteromorphisms was found among the different racial groups. The Orientals had a larger C-band on chromosome 1 and a smaller C-band on chromosome 9 than the other racial groups while the Caucasians had a larger C-band on chromosome 9. The Oriental group also had a significantly greater proportion of inverted C-bands. No differences were found in the distribution of C-band heteromorphisms among different etiologic categories of mental retardation.


The problem of partial endoreduplication. Partial endoreduplication (PE) as defined by Lejeune et al. (1966) has only been found in a few instances. Similar configurations, also called PEs, seem to originate from a different process. A series of 12 PEs is presented in this paper, discovered in metaphases from healthy individuals, and in patients with or without chromosome-breakage syndrome and after treatment with chromosome-breaking agents. Interpretations of the microscopic appearance of each configuration led to the conclusion that there are three different modes of origin for such rare events, one being true partial endoreduplication, the second a partial pseudoendoreduplication, and the third a homologous triradial chromatid translocation.


Gene dosage effect for human triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase in partial trisomy 12p13 and trisomy 18p. An 8-year-old girl with profound mental retardation and a neurologic syndrome associated with morphologic abnormalities was found to have a supernumerary small submetacentric chromosome. Several members of her family carried a balanced translocation t(12;18)(p12;q11), and the child's karyotype could be explained by 3:1 maternal segregation (tertiary trisomy). The proband was trisomic for 12p13 and 18p. A gene dosage effect was demonstrated for triosephosphate isomerase and glyceraldehyde-3-phosphate in erythrocytes and leukocytes allowing us to assign the corresponding loci to the tip of the chromosome 12 short arm.


Brother and sister with trisomy 10p. 46,XY,(22p+)mat; 46,XX,(22p+)mat. Since the usefulness of chromosome differential banding techniques has become fully established, several descriptions of chromosome 10 short arm trisomy have been published (Schleiermacher et al., 1974; Roux et al., 1974; Cantu et al., 1975; Grosse et al., 1975; Moric-Petrovic et al., 1976; Turleau et al., 1976; Johnson et al., 1977; Yunis and Lewandowski, 1977). The present report deals with a mother who is a carrier of a reciprocal translocation between chromosome 22 and 10, which has resulted in two children with a 10p trisomy.


GLO polymorphism in two Polish population samples. The red cell GLO phenotypes were determined in two Polish population samples. A total of 1310 people from the region of Lublin (Southeastern Poland, n = 797) and Wrocław (Southwestern Poland, n = 513) were investigated. The gene frequencies were calculated for GLO1 (= 0.4427) and GLO2 (= 0.5573). The evaluation of 372 mother-child pairs showed no deviation from a hereditary hypothesis.


A new rare phenotype of glycine-rich beta-glycoprotein. A rare phenotype of serum glycine-rich beta-glycoprotein was found in a healthy Swiss woman. The rare gene product was also observed in three of her four sons.


Partial trisomies 13 and 22 due to nondisjunction of a maternal reciprocal translocation, t(13;22)(q22;q11). A family is reported in which the propositus has an extra G-like chromosome with an unusual G-banding pattern. Cytogenetic family studies showed that the mother is a carrier of a balanced reciprocal translocation t(13;22), which does not affect the size and morphology of the chromosomes involved. The propositus has a 47,XY,+der(22),t(13;22)(q22;q11) karyotype and is therefore partially trisomic for the distal third of the long arm of chromosome 13 and for a very small part of chromosome 22. The clinical findings are presented and compared with those of other reported cases of partial trisomies 13 and 22.


The problem of partial trisomy 22 reconsidered. A patient with partial trisomy 22(PT22) is presented. Inheritance is presumed to be due to secondary nondisjunction in her mother, who has a balanced translocation t(11;22)(q25;q13). The problem of the phenotypic heterogeneity observed with this chromosome change is discussed.


Nasopharyngeal carcinoma in children and adolescents in Tunisia: clinical aspects and the paraneoplastic syndrome. Of 485 cases of NPC collected from the files of our institute between March 1969 and December 1974, 82 (17%) were in children and adolescents (0--19 years old). This relatively high frequency of NPC in young people was not suggested by reports from high-incidence areas (Southern China, for example) but appears to be a characteristic feature of areas of intermediate incidence (Uganda, Kenya, Sudan, Tunisia). NPC is the tumour that occurs most frequently in young people between 1 and 20 years old in Tunisia, showing a peak in those 16 years of age. The male:female sex ratio was 3:1. Advanced stages of the disease occured frequently; no clinical anomalies were noted in this age group. The 'nasopharyngeal' type of carcinoma was the histological form seen most frequently; poorly-differentiated squamous-cell carcinomas were not uncommon; and well-differentiated squamous-cell carcinomas were not seen in this series. The five-year survival rate was 32.5% for children and only 20% for adults. This can perhaps be explained by the fact that the 'nasopharyngeal' type of tumour has a better prognosis than other histological types, and, compared to adults, younger patients more frequently have distant metastases (37%) than local recurrences (18.5%). A paraneoplastic syndrome, consisting of hypertrophic pulmonary osteoarthropathy with occasional generalized lowering of pituitary function, was seen in 12 of the patients. This syndrome has been described only in children, and no cases were found in our series of adult NPC patients. Epidemiological, clinical and histological aspects suggest that NPC in young people is different from that found in adults.


Variations in nasopharyngeal cancer incidence among specific Chinese communities (dialect groups) in Singapore. A total of 729 cases of NPC (93.6% confirmed histologically) were diagnosed among the Singapore Chinese population during a five-year period (1968--1972). Age-standardized incidence rates for the total Chinese population were 18.4 per 100,000 per year for males and 7.0 for females; the respective rates for the specific Chinese communities were 14.1 and 4.7 for Hokkien, 18.3 and 6.2 for Teochew, 29.1 and 11.0 for Cantonese, 14.2 and 3.3 for Hainanese, 12.6 and 4.8 for Hakka and 12.2 and 6.0 for the other dialect groups. It is evident that all of the Chinese communities in Singapore have high risks for NPC; only the Cantonese have risks significantly higher than that for the rest of the Chinese population. NPC incidence rates for males and females of the other major racial groups in Singapore were 4.7 and 0.6 for Malays and 0.9 and 0.0 for Indians, respectively.


Etiological factors in nasopharyngeal carcinoma: a hospital-based, retrospective, case-control, questionnaire study. A total of 379 Singapore Chinese patients with NPC were interviewed by use of a questionnaire covering the following items: occupation, level of education, language medium of education, personal and family history of nasal illnesses, types of medicines used, use of Chinese medicines for the nose and throat, use of soya sauce, Chinese tea, cooling drinks and alcohol, cigarette smoking (number and duration), cooking fuels and use of incense (frequency and duration) and of anti-mosquito coils. The same questionnaire was given to two groups of controls: 595 patients with diseases of the ear, nose and throat other than NPC and 1 044 patients with diseases other than cancer or otorhinolaryngeal disease. NPC patients differed significantly from both groups of controls in that they showed stronger associations with personal history of nasal illnesses, family history of nasal illnesses, use of Chinese medicines for the nose and throat and exposure to smoke from anti-mosquito coils.


Environmental factors in the etiology of nasopharyngeal carcinoma: report on a case-control study in Hong Kong. A case-control study was undertaken of Cantonese NPC patients hospitalized in the Queen Elizabeth Hospital, Hong Kong. One age- and sex-matched control was selected for each NPC case from hospitalized patients with cancers other than NPC. A total of 150 NPC patients and 150 controls were interviewed in order to compare the two groups with respect to socio-economic status, dietary habits and health status. In addition to the individual patients and controls, healthy members of their respective households were also interviewed, in order to obtain information not influenced by the experience of having cancer. Weaning habits were compared in the households of NPC patients and those of controls by asking women who had ever breast fed a child about food supplements they had given to the baby during, and immediately after, weaning. The following factors were found to be positively associated with NPC: (1) belonging to the four lowest occupational classes; (2) practicing Buddhism or ancestor worship and having religious altars in the house; and (3) having a history of previous illnesses of the ear or nose after the age of 15 years. The following factors were found to be negatively associated with NPC: (1) eating of bread; (2) eating of tinned food; and (3) use of spices. The study of weaning habits disclosed that salted fish was given to babies just after weaning more often in households with an NPC case than in control households. A multivariate analysis showed that traditional lifestyle and the consumption of salted fish during weaning are independent risk factors for NPC. This analysis also revealed that two or three of the many expressions of a traditional lifestyle included in the study could account for the total increase in NPC risk associated with this way of life, although it is quite possible that other, as yet unidentified, factors are just as important.


Epidemiology of malignant tumours of the nasopharynx in France: retrospective and prospective studies. Certain epidemiological conclusions have been drawn from a retrospective study of 509 cases of NPC treated in France. NPC was found to represent 3% of cancers of the upper digestive and respiratory tracts and 80% of nasopharyngeal malignancies in adults; 30% are squamous-cell carcinomas. The sex ratio was found to be 3:1. Less than 50% of cases occur in natives of France. A prospective study initiated by the Institut Gustave Roussy lead to the collection of data on 133 new cases of NPC treated in France in 1975 and 1976. The annual rate of NPC in France is about 0.3/100,000. A number of factors set apart well-differentiated epidermoid carcinomas from other forms of NPC: sex ratio (20:1), age of patients, geographic origin and the use of tobacco were similar to those seen in cases of epidermoid carcinomas of the upper digestive and respiratory tracts.


Nasopharyngeal carcinoma and histocompatibility antigens. New data are presented concerning the relationship between NPC and HLA antigens among Chinese. When attention is confined to newly diagnosed cases, it can be shown that, apart from the increased risk associated with the joint occurrence of A2 and B-Sin 2, there is also an increased risk associated with BW17 and a decrease in risk associated with A11. Among long-term survivors, however, BW17 is appreciably decreased, whereas A2 in the absence of B-Sin 2 or BW17 is increased. Among Malays, a non-Chinese group, there is an excess among NPC patients of a locus A blank, a blank which is probably associated with the AW19 complex.


Genetic components in susceptibility to nasopharyngeal carcinoma. A series of blood samples from more than 200 histologically confirmed Chinese patients with NPC in Singapore were typed for 25 genetically controlled red-cell enzyme and five serum protein systems. A comparable number of patients suspected of having NPC but histologically negative and a series of healthy unrelated Chinese were typed for the same systems. The gene frequencies of NPC patients and controls differed by 4% or more in four of the 11 systems that showed variation; a further system, G6PD deficiency, also showed a significant difference between the two series but was excluded because of possible unreliability of the results from patients. Smaller differences existed in several other systems, including chromosome 6 markers closely linked to HLA. An analysis of differences within dialect groups showed a consistent effect for PGD, but for red-cell acid phosphatase there was a reversal of the difference between patients and controls among the Cantonese. These results need a larger series to confirm their validity. A breakdown of patients into those 30 years of age or older and those under 30 slightly enhanced the differences in gene frequencies. A multivariate analysis, using genetic distance statistics, showed a significant difference between NPC patients and controls, which is evident also when they are compared in the separate dialect groups. The histologically negative patients occupied an intermediate position. The study indicates that etiological factors resulting in clinically and histologically confirmed NPC operate on a genetically distinct subpopulation of Chinese in Singapore.


Cytogenetic observations on the malignant epithelial cells and infiltrating lymphocytes of nasopharyngeal carcinoma. Because of the presence of a No 14 chromosome marker abnormality in EB virus-carrying cells from African Burkitt's lymphoma (BL) but not from other origins, and the association of EB virus with nasopharyngeal carcinoma (NPC) as well as BL, both the malignant epithelial cells and the non-malignant lymphoid cells of NPC have been investigated cytogenetically. Chromosome spreads from seven NPC-derived lymphoblastoid lines were examined after banding; five lines were diploid and two were tetraploid. No consistent no. 14 chromosome abnormalities were found. Apart from a secondary constriction near the centromere of both no. 1 chromosomes in all cells of one diploid line, no consistent significant abnormalities were seen. Five NPC tumours, freed of infiltrating lymphoid cells by passage through nude mice, were similarly examined after spindle arrest in vivo. Two tumours were near-diploid, and three were hypo-tetraploid. Near-diploid cells had only minor chromosomal changes, but the hypotetraploid spreads from all tumours showed gross changes  of uncertain origin, including frequent, major translocations. No. 14 chromosome marker changes were not seen, and there was no other consistent pattern of abnormality in tumour cells.


Carcinoma of the nasal and paranasal regions in rats fed Cantonese salted marine fish. Cantonese salted fish is suspected on epidemiological grounds to be an etiological factor in human NPC. To determine whether this food contains a carcinogen which acts on the upper respiratory epithelial lining, WA albino rats and Syrian golden hamsters were given Cantonese salted fish in their diet for one to two years from the age of one month and examined for tumours in that area. Three of 20 treated rats, but no control rats and no treated or control hamsters, developed carcinomas (two adenocarcinomas and one undifferentiated) in the nasal or paranasal sinus cavities after 12 to 24 months' treatment. NDEA was given orally to a similar group of animals as a positive control, and NDMA, the only volatile nitrosamine detected in salted fish, was added to the drinking-water of a third group. Three of 14 NDEA-treated rats developed adenocarcinomas in the nasal cavities, but none of the other animals developed nasal or paranasal tumours. These findings lead us to suspect that salted fish may contain a carcinogen or procarcinogen that can act systematically on the epithelial cells of the nasal and paranasal cavities.


Detection and quantitation of adenovirus type 12 transforming DNA segments and their application in etiological studies of human neoplasia. The oncogenic capacity of the tumour virus lies in a small region of the viral genome, and tumour cells and cells transformed by DNA tumour viruses often contain only a part of the viral genome, the portion including the transforming gene(s). The detection and quantitation of these gene(s) in tumour cell DNA can provide evidence for or against a possible etiological role of the virus in human neoplasia. In this communication, the isolation, purification and identification of the transforming segment of Ad 12 are described.


The histopathological spectrum of nasopharyngeal carcinoma. Nonglandular carcinomas of the nasopharynx originate in the epithelium of that anatomical region. Although numerous morphological patterns exist at the level observable by light microscopy, ultrastructurally, all have features of squamous-cell carcinoma. The most useful and consistent classification on the basis of light microscopy is that which separates keratinizing squamous carcinomas from nonkeratinizing carcinomas. Approximately 25% of tumours have abundant and easily recognized keratin. The nonkeratinizing types are more confusing, since many variants exist, both from tumour to tumour and, frequently, within the same tumour. Variable tissue reactions to infiltrating tumours, ranging from marked desmoplasia to complete absence of reaction, add to the confusion. The descriptive names applied to the variants of nonkeratinizing squamous carcinomas are well engraved in medical communications, and there is little chance that they will be abandoned.


Effect of levamisole on cell-mediated immune responses in patients with nasopharyngeal carcinoma. CMI functions, as monitored by responses in the Mantoux and PHA tests, can be augmented by a short oral course of levamisole. The augmentation is dosage dependent and, in some patients, of long duration.


Clinical evaluation of cytological diagnosis of nasopharyngeal malignancies. Between 1970 and 1975 cytological examination was applied to the diagnosis of nasopharyngeal malignancies in a series of 216 consecutive patients who had either a tumour in the nasopharynx or clinical signs of nasopharyngeal carcinoma, or who were locally asymptomatic but had enlarged cervical lymph nodes. Smears were taken by introducing a small rough pad of compressed gauze through the mouth into the nasopharynx with an upward-angled forceps. In each case the cytological smear was taken immediately before biopsy; often, a lymph node was removed subsequently. When morphological diagnoses were doubtful and histological findings were at variance with positive cytological findings, the patients were reexamined clinically, and diagnosis was postponed. The case material was made up of 90 nasopharyngeal carcinomas, 24 lymphomas, one malignant melanoma, one adenoid cystic carcinoma and 100 patients without malignancies. Cytological findings from the first smear were positive in 77.8% of nasopharyngeal carcinomas, in 66.6% of lymphomas and in the cases of melanoma and adenoid cystic carcinoma. There were no false-positive results. When the nasopharyngeal carcinomas were subdivided into undifferentiated carcinomas of the nasopharyngeal type and squamous-cell carcinomas, cytological findings were positive in ,0% and 73%, respectively. Positivity of histological findings was distributed as follows: 91.7% for malignant lymphomas, 86.6% for undifferentiated carcinomas and 86.6% for squamous-cell carcinomas. With respect to clinical suspicion of malignancy, positive cytological findings were obtained in 50% of clinically occult cases and in 84.6% of patients with obvious malignancies; intermediate figures were found for clinically doubtful (64.3%) and for highly suspicious (77.8%) cases. Cyto-histological concordance was shown in 70% of cases; false-negative histological results were obtained in 7.8% and false-negative cytological results in 16.6% of cases. Combined cyto-histological positive results allowed diagnostic accuracy from the first samples in 94.4% of cases. Undifferentiated carcinoma appeared to be the malignancy most accessible to cytological diagnosis, with positive results ranging from 65% in clinically negative or doubtful cases to 84.5% in those with obvious tumours. Assessment of the cytology of the nasopharynx, using the new sampling method described herein, may be a useful diagnostic tool in nasopharyngeal maliganancies.


Long-term human breast carcinoma cell lines of metastatic origin: preliminary characterization. Nineteen human breast carcinoma cell lines have been established as continuous cultures during the past 6 years in our laboratory. This preliminary report is designed to list the lines by their designated code numbers (MDA-MB) and present a brief summary of their morphological, cytogenetic and biochemical characteristics. Sixteen of our lines were obtained from pleural effusions, two from brain metastases, and one from pericardial fluid. All lines have been shown to be distinct entities and are uncontaminated by HeLa cells or each other. A lq marker chromosome is present in all but one of the lines examined.


The effect of donor age on the in vitro life span of cultured human arterial smooth-muscle cells. The number of population doublings of cultured human arterial smooth-muscle cells decreased as a function of donor age (0.5 to 82 years). Cells from older donors also showed longer latent periods for outgrowth from explants. These results extend other comparable observations with human skin fibroblasts to another cell type, and may have relevance to the pathogenesis of atherosclerosis with aging in vivo.


[Stability of MIC values from tetracyclines in different media (author's transl)]. The influence of nutrient-broth (NB), Mueller-Hinton-broth (MHB), isotonic-sensitive-broth (ISB) and tryptone-soya-broth (TSB) with respect to the determination of MIC values of three tetracyclines is shown. A difference of degradation of tetracycline derivates in the four media was found. The degradation in NB after 18 h was negligible, but in MHB after 18 h all the three tetracyclines were inactivated up to 42%. The MIC levels of staphylococcus aureus strains in NB were about twofold lower than those in MHB and TSB. The MIC levels in ISB were even three- to fourfold higher than in NB. From these results sensitivity testing of tetracycline derivates should be carried out with NB.


[Activity of antibiotics in body fluids (author's transl)]. MIC and kinetic of bactericidal activity was determined for various antibiotics in body fluids (plasmawater, bile, amniotic fluid and urine). Beta-lactam antibiotics demonstrated slight loss of activity against enterobacteriaceae. The newer cephalosporine compounds, cefoxitin, cefuroxime and HR 756 showed an increase in activity in plasmawater. Carbenicillin was more active in plasmawater, bile and amniotic fluid than in broth. There was a difference in gentamycin activity against enterobacteriaceae and pseudomonas aeruginosa: enhanced activity against E. coli in body fluids and diminished against pseudomonas. Tetracycline was less active in body fluids, specially in alkaline bile. The combination ampicillin/gentamycin against E. coli was more effective in plasmawater than in DST agar. Cefazolin/gentamycin demonstrated no synergism. Although carbenicillin/tobramycin were not synergistic against pseudomonas aeruginosa in plasmawater. The marked differences in different body fluids should be taken into consideration when new antibiotics are introduced.


[The formulation of semi-defined culture media to overcome antibiotic antagonism (author's transl)]. Semi-defined susceptibility media are a compromise between undefined and totally defined media. Antibiotic antagonism can still occur in semi-defined media. The undefined nutrients antagonizing sulphonamide/trimethroprim and the defined additives antagonizing other antibiotics. Methods used to overcome these problems are discussed.


[Growth of some pathogenic microorganisms on chemically defined media which were proposed for sensitivity testing (author's transl)]. The growth of 16 bacterial cultures, which belong to the frequently encountered pathogens, in three different chemically defined fluid media was investigated through turbidity measurements in comparison with Mueller-Hinton-broth. E. coli, Salm. dublin, Salm. typhi-murium, Enterobacter cloacae, Proteus mirabilis, Pseud. aeruginosa and Bac. cereus grew in two of the three tested defined media with approximately the same intensity as in the Mueller-Hinton broth. Staph. aureus grew well only in one of the 3 tested defined media. Listeria monocytogenes, Erysipelothrix rhusiopathiae, Pasteurella multocida, Neisseria gonorrhoeae and Brucella abortus showed only in one of the three tested media a barely descernible growth, whereas Strept. faecalis, Strept. pneumoniae, Strept. pyogenes showed no growth in the three tested defined media after 34 hours of incubation. None of the tested defined media can be used for routine sensitivity testing but the use of two of the three tested defined media as a reference medium for the standardization of the complex sensitivity testing media remains theoretically possible.


[Comparison of regression line analysis for several antibiotics on different media (author's transl)]. The method for performing regression analysis is described in detail. MIC values and zone sizes are determined on agar throughout. Applying these techniques, good correlation between MIC's and zone sizes (r = greater than -0.9) were found with 82% of 59 regressions (33 different antibiotics). Comparable results were found with DST- and Mueller-Hinton agar. In some cases a linear regression for MIC and zone size values could be demonstrated, independent from the correlation coefficient. Some theoretical aspects of regression analysis are discussed.


[The microtiter system for sensitivity testing (author's transl)]. In conclusion, the microtiter system has several advantages over conventional broth dilution methods. It is more rapid to set up, economical in its use of media and materials, and many more strains can conveniently be tested on the same occasion and under the same conditions, giving better comparability. Microtitration is almost as reproducible as large-tube dilution, and certainly adequately so for all laboratory and clinical purposes. Minimal bactericidal concentrations can be determined by microtitration, unlike agar plate dilution, and the system is readily adaptable to the measurement of antibiotic concentrations in body fluids where the accuracy can be increased if required (12) by the incorporation of an intermediate dilution series. Overnight incubation is, however, necessary and so rapid results are not possible.


Experience with the AO method in the treatment of 142 cases of fresh fracture of the tibial shaft treated in the UK. A prospective study was carried out on 142 fresh fractures of the tibial shaft treated by internal fixation according to the AO principles, 99 fractures being closed and 43 open. A total of 140 cases was reviewed at 1 year and 125 cases at 2 years following injury, at which times a functional assessment score was awarded by the surgeon and the patient himself, and a precise measurement of ankle range was made. The time taken for the fracture to unite and the incidence of non-union was greater if the fracture was comminuted (whether open or closed) than if there was no comminution. For patients with closed fractures the minor infection rate (erythema and increased local temperature) was 4.1 per cent and the major infection rate (pus present) was 4.1 per cent, no infection being severe enough to warrant removal of the plate. In open fractures, the overall infection rate was 14 per cent, 7 per cent having major infection and only 1 case requiring removal of the plate. The functional results and complications are discussed.


The radiological diagnosis of posttraumatic effusion of the elbow joint and its clinical significance: the 'displaced fat pad' sign. Alterations occur in the radiological appearance of the soft tissues after injury to the elbow joint.  These are due to displacement of the intra-articular fat pads by capsular distension when an effusion is present. A prospective study of 89 consecutive elbow injuries was undertaken in an attempt to assess the usefulness and reliability of these changes in the diagnosis of minor elbow injuries and the assessment of their clinical progress. In 61 elbows (69 per cent) there was no radiological evidence of an effusion and no evidence of bony injury. All quickly returned to normal. In 28 elbows (31 per cent) radiological evidence of an effusion was present. Twenty-three (80 per cent) of these were also found to have a fracture in, or adjacent to the elbow joint. In 9 elbows the fracture could not be seen on the initial radiographs. Because of the presence of an effusion, repeat radiographs were taken and a fracture discovered. The presence of an effusion was associated with an increase in the time required for full recovery.


The comparison of steel and titanium dynamic compression plates used for internal fixation of 256 fractures of the tibia. A consecutive series of 256 fractures of the shaft of the tibia treated by internal fixation with a narrow dynamic compression plate (DCP) is presented. In 123 cases the plates were made of titanium and in 133 cases they were made of stainless-steel. In both groups the age distribution of the patients, the period between operation and the final review and the time of removal of the metal were comparable. All these fractures resulted from skiing accidents. Eighty-six per cent of the 256 fractures were reviewed between 1 and 2 years after the operation. Ninety-one per cent of the titanium group and 93 per cent of the stainless-steel group showed full recovery without any loss of movement in the joints. In both groups there was the same number of refractures, which were chiefly due to subsequent accidents. There were no cases of local wound infection, osteitis or non-union. Furthermore, there was no difference to be seen between the radiological patterns of fracture healing in the two groups. In this series stainless-steel and titanium plates gave the same excellent results.