[Observations concerning the moment of delivery in 144 gestational diabetics (author's transl)].

Report is made, in a comparative examination, about infant mortality and early morbidity, as well as about several further perinatal criteria in gestational diabetics, 85 of whom were delivered before/on the calculated date and 59 after the term. With the exception of weight and length of the newborn, no significant differences are occurring in any of the symptoms selected. The same situation appears in a control group consisting of people with healthy metabolism. Conclusion is made thereof that gestational diabetes per se does not represent an indication to terminate pregnancy at any rate on the calculated date.


[Experiments of electro-acupuncture-analgesia during delivery (author's transl)].

We report about 20 patients who underwent electroacupuncture therapy during delivery with intent to reduce labor pains. Acupuncture steel needles situated in the thoracal, lumbal, sacral region and in the region above the symphysis were stimulated by a rectangular impulse current. A good effect for the reduction of labor pains could be observed in 5 cases, a moderate one in 6 cases. An absolute analgetic effect could not be achieved in any case, and in 9 cases no analgetic effect of acupuncture therapy on labor pains was visible. Acupuncture had no influence on labor or fetal heart rate, monitored by cardiotocography.


Rehabilitation performance and adjustment in stroke patients: a study of social class factors.

In a prospective follow-up study comparing the adjustment of hemiplegics in rehabilitation programs in a public institution (N = 100) and a private university facility (N = 105) measures were taken one month after admission and 18-24 months after discharge. Initially, the groups differed in social profiles (social class, ethnicity, marital status), incidence of secondary medical conditions and attitudes, including expectancies and F scale and sick role questionnaire. They did not differ in performance and motivation on the programs. At follow-up treatment. Many more went to nursing homes. Implications for rehabilitation programs are presented.


Characterization of T4 mutants that partially suppress the inability of T4rII to grow in Lambda lysogens.

In the course of isolating viable T4 deletions that affect plaque morphology (HOMYK and WEIL 1974), two closely linked point mutant, sip1 and sip2, were obtained. They map between genes t and 52, cause a reduction in plaque size and burst size, and partially suppress the lethality of rII mutants for growth in lambda lysogens. The characteristics demonstrate that sip1 and sip2 are similar to mutants previously reported by FREEDMAN and BRENNER(1972). In addition, D. Hall (personal communication) has shown that sip1 and sip2 are similar to the mutant farP85, which affects the regulation of a number of early genes (Chace and Hall 1975).--Sip suppression of rII mutants can be demonstrated in one-step growth experiments, even when both rII genes are completely deleted. This indicates that sip mutants do not simply reduce the level of rII gene products required for growth in a lambda lysogen. Instead, they alter the growth cycle so as to partially circumvent the need for any rII products.--Mutations at two other sites, designated L1 and L2, reverse the poor phage growth caused by sip and, in the one case tested, reverse the rII-suppressing ability of sip.


Inducible monooxygenase activities and 3-methyl-cholanthrene-initiated tumorigenesis in mouse recombinant inbred sublines.

The induction of a certain group of hepatic monooxygenase activities by polycyclic aromatic compounds is regulated by the same locus or gene cluster controlling the formation of cytochrome P1-450 (P-448) in mice. Certain inbred strains of mice are "responsive" (Ahb) to such induction, whereas others are "nonresponsive" (Ahd). A pair of closely related sublines that differ with respect to the Ah locus (for aromatic hydrocarbon responsiveness) were used to identify or confirm the pleiotropic effects of this gene. The lines were derived by sibling-mating without selection from (C57L/J x AKR/J)F2 mice; the two sublines were separated at the F12 generation. Ten microsomal monooxygenase activities and one cytosol enzyme activity known to be associated with the Ah locus were similarly associated with cytochrome P1-450 formation in these recombinant inbred sublines as well. Nine additional hepatic monooxygenase activities studied were found not to be associated with the Ah locus; certain of these activities were increased slightly, following treatment of nonresponsive as well as responsive mice with polycyclic aromatic compounds. The Ahb-containing subline was highly susceptible to 3-methylcholanthrene-induced subcutaneous sarcomas, whereas the Ah-d-containing subline was relatively resistant. These results emphasize the potential importance of this particular enzyme for the study of coordinated regulation in mammals.


Simulation of X-linked selection in Drosophila.

The change in gene frequency for two X-linked mutants, gamma and omega, in a number of experiments was compared to that predicted from a genetic simulation program which utilized estimated differences in relative mating ability, fecundity, and viability. The simulation gave excellent predictions of gene frequency change even when experiments were started with different initial gene frequencies in the males and females or when the two loci were segregating simultaneously. The rate of elimination was slower when there were unequal initial gene frequencies than when males and females had equal initial gene frequencies. Simulation demonstrated that this was a general phenomenon when there is strong selection but that the opposite is true for weak selection. In two other experiments, the mating advantage of wild-type males was balanced by a fecundity advantage in mutant females. In all four replicates of both experiments, the mutant was maintained for several generations at the high initial frequency but then decreased quickly and was eliminated. Results obtained restarting one of these experiments with flies from a generation after the decline in gene frequency indicated that a linked gene and not frequency-dependent selection was responsible for the unpredictable gene-frequency change in the mutant. Using a least squares technique, it was found that a recessive fecundity locus 15 map units from the omega locus gave the best fit for both experiments.


The evolution of one- and two-locus systems.

Assuming age-independent fertilities and mortalities and random mating, continuous-time models for a monoecious population are investigated for weak selection. A single locus with multiple alleles and two alleles at each of two loci are considered. A slow-selection analysis of diallelic and multiallelic two-locus models with discrete nonoverlapping generations is also presented. The selective differences may be functions of genotypic frequencies, but their rate of change due to their explicit dependence on time (if any) must be at most of the second order in s, (i.e., O(s2), where s is the intensity of natural selection. Then, after several generations have elapsed, in the continuous time models the time-derivative of the deviations from Hardy-Weinberg proportions is of O(s2), and in the two-locus models the rate of change of the linkage disequilibrium is of O(s2). It follows that, if the rate of change of the genotypic fitnesses is smaller than second order in s (i.e., o(s2)), then to O(s2) the rate of change of the mean fitness of the population is equal to the genic variance. For a fixed value of s, however, no matter how small, the genic variance may occasionally be smaller in absolute value than the (possibly negative) lower order terms in the change in fitness, and hence the mean fitness may decrease. This happens if the allelic frequencies are changing extremely slowly, and hence occurs often very close to equilibrium. Some new expressions are derived for the change in mean fitness. It is shown that, with an error of O(s), the genotypic frequencies evolve as if the population were in Hardy-Weinberg proportions and linkage equilibrium. Thus, at least for the deterministic behaviour of one and two loci, deviations from random combination appear to have very little evolutionary significance.


Remarks on the evolutionary effect of natural selection.

The so-called "Fundamental Theorem of Natural Selectiion", than the mean fitness of a population increases with time under natural selection, is known not to be true, as a mathematical theorem, when fitnesses depend on more than one locus. Although this observation may not have particular biological relevance, (so that mean fitness may well increase in the great majority of interesting situations), it does suggest that it is of interest to find an evolutionary result which is correct as a mathematical theorem, no matter how many loci are involved. The aim of the present note is to prove an evolutionary theorem relating to the variance in fitness, rather that the mean: this theorem is true for an arbitrary number of loci, as well as for arbitrary (fixed) fitness parameters and arbitrary linkage between loci. Connections are briefly discussed between this theorem and the principle of quasi-linkage equilibrium.


[Mutagenic effect of small doses of diethylsulfate in laboratory mice studied by specific locus method].

Diethylsulphate solution was injected intraperitoneally twice a week to male mice B10.C3H having the wild-type colour at a 5 mg/kg dose. The treatment lasted 10 weeks, so that the total dose administered was 5-20 = 100 mg/kg. In fifth week after the end of the treatment these males were crossed to YT females homozygous for seven recessive mutant genes. In the control group all the F1 descendants were of wild-type colour, while in the experimental group among 5042 F1 mice derived from DES-treated spermatogonia there was one mutant d and 4 mosaics (3 with respect to the locus c and 1 with respect to the locusa). These results are interpreted as the evidence of the mutagenic effect of DES.


[Possibility of using dermatoglyphic markers for assessment of genetic hypotheses in schizophrenia].

Dermatoglyphic alterations in schizophrenic patients are considered in virtue of literature data and the author's own investigations. The absence of obvious and regular difference between healthy people and schizophrenic patients in the incidence of finger and palm patterns is revealed. Only statistically insignificant tendency of different manifestations of some features in patients and healthy persons is observed. Skin patterns doubtly may be used as additional diagnostic paraclinical method and applied to work out genetic aspects of schizophrenia. The addiitonal investigations and particularly and the investigations of "family forms" of schizophrenia are suggested for suggested for complete solution of this problem.


[Polymorphism of near-centromeric heterochromatin in a population of normal humans].

Polymorphism of constitutive heterochromatin of metaphase chromosomes 1,9 and 16 in 6 normal humans (both men and women) in studied by means of C-staining. Only slight variability in size of C-blocks in one individium (from cell to cell) and a high frequency of C-chromation heteromorphism variants within the population studied is observed. 8 variants of C-heterochromatin (heteromorphic homologues) are found: 4 individuals had 1-2 variants and 1 individual - 3 variants. Quantitative analysis based on measurements of C-blocks confirmed the reliability of the existence of these variants.


[Stimulation of ribonuclease activity under the influence of nitrosoethylurea].

Nutrosoethyl urea-induced activation of alkaline ribonuclease was accelerated with the increase of the temperature from 22 to 32 degrees C. The reaction rate at 32 degrees C was more than 8 fold increased as compared with the control. Further increase of temperature to 42 degrees C decreased the stimulating effect of nitrosoethyl urea. The effect observed may be taken into consideration when studying a molecular mechanism of the effect of chemical mutagens on cell metabolism.


[Comparison of the radiosensitivity of chromosomes during the S and G2 periods in regenerating rat liver cells].

Radiosensitivity of chromosomes at S and G2 periods was studied by means of autoradiography technique in cells or regenerating liver of rats treated with X-rays at the doses of 150 and 300 r. The experiments were made so that the interval between irradiation and mitosis in S and G2 cells was equal. The results have shown that under the experimental conditions there are significant differences in the yield of chromosome aberrations between the labelled and intact cells. This withnesses for the existence of differences in radiosensitivity of chromosomes at different periods of mitotic cycle.


The types of headache that affect the elderly.

Older people often describe their headaches as starting with vague neck discomfort and eventually moving to the temples and forehead. These are muscle-tension headaches, by far the most common type in the elderly. Although cervical osteoarthritis often is at fault, depression can be a significant factor, patricularly when headaches are chronic. There is no sure cure for tension headache, and often, several of the many remedies-ethyl chloride spray, moist heat, massage, antidepressant drugs, analgesics, local anesthetics, etc.-must be tried before an effective one is found. But just as important to successful therapy are concern, compassion, and a willingness to listen on the part of the physician. True migraine headaches are rare in the elderly. More prevalent is the type of vascular headache associated with giant cell arteritis, which is severe and resistant to any form of analgesic except the strongest narcotics. Vascular headaches also may result from congestive heart failure (which produces venous congestion in the cranial cavity), transient ischemia, increased intracranial pressure, and a variety of metabolic disturbances.


Conservative management of chronic renal failure.

Failing kidneys can play havoc with other parts of the body. Specific treatment of these associated problems may help ward off uremia and preserve whatever renal function remains. Sodium levels may drop if too much water is mistakenly given to counteract kidney failure. Hyperkalemia can lead to cardiac arrest if potassium levels aren't reduced without delay. Acidosis also may reach life-threatening proportions, especially if diarrhea occurs. Almost all patients with chronic renal failure have a bleeding tendency and anemia, with the hematocrit dipping as low as 20 percent. Over half have decreased tolerance to carbohydrares, although severe hyperglycemia is rare. Disorders of calcium metabolism also are common, ranging from asymptomatic hypocalcemia to osteomalacia. The kidneys' impaired filtration ability should be kept in mind when drugs are prescribed. Dosages may need to be cut to avoid an adverse reaction.


Outpatient management of chronic bronchitis and emphysema.

Proper treatment relieves the symptoms of chronic bronchitis and emphysema to a large extent and helps patients remain active and useful until the last stages of the disease. Not much can be done to halt the natural course, since the disease is well advanced by the time that symptoms appear. Respiratory infections pose a constant threat. They are the primary cause of increased morbidity and mortality in these patients and may well accelerate the disease process. Annual prophylaxis against influenza is recommended, and antibiotic suppression should be considered for patients who have repeated bouts of acute bronchitis. Airways obstruction in emphysema is irreversible, but oral bronchodilators may remedy bronchospasm in chronic bronchitis and in emphysema with a bronchitic component. If sputum is thick and tenacious, postural drainage and chest physiotherapy may be helpful. Corticosteroids should be used only as a last resort. Patients tend to become inactive as the disease progresses. Exercise is important to increase exercise tolerance and overall physical fitness, and the physician should prescribe a specific daily program within the patient's limitations.


Gastrointestinal carcinoma: diagnosis, staging, and follow-up.

When cancer of the gastrointestinal tract is suspected, thorough studies should be made to determine the presence, type, and severity of the primary tumor and whether it has spread. Besides routine x-ray studies, angiography, scanning, and sonography may furnish valuable information. Endoscopy, which has revolutionized diagnosis of these tumors, not only makes it possible to obtain a specimen for histologic analysis without laparotomy but also reveals gross involvement as a guide to surgery. Staging of the lesion helps the physician select which patients would benefit from surgery and which instead should be treated with palliative chemotherapy or irradiation, or both. The patient's quality of life during treatment also must be considered. The side effects of multiple-agent chemotherapy, for example, may take too great a toll on the patient's ability to function. Continuous, long-term follow-up is essential. Metastases may develop after three to five years in particularly indolent tumors, and new primary lesions are far from rare.


Factors influencing food choices and intake.

To find out what elderly people eat and why, researchers interviewed 303 noninstitutionalized persons over 65. In addition to questions about the kinds and amounts of foods eaten, they quizzed the subjects on their eating patterns and their attitudes and knowledge about food and nutrition. The intakes of eight essential nutrients, calculated and compared with the Recommended Daily Dietary Allowances, were high overall. Some subjects, however, thought they ate better than they did. Eighty-three percent rated their own intake as good or excellent, but only about 60 percent actually fit this category. Diet did not correlate significantly with income, education, age, religion, or culture-probably due in part to the homogeneity of the sample-but some trends emerged. Even though the ratio of women to men was 3:1, the percentage of men who ate an excellent diet was higher than that of women in all four age groups. Also, each successive age group had a higher percentage of good or excellent scores.


Recognizing spontaneous spinal epidural hematoma.

Sudden, often severe pain in the spinal region that is followed-sometimes within minutes-by paraplegia may signal spontaneous spinal epidural hematoma. This is a true surgical emergency calling for immediate laminectomy. Otherwise, the neurologic deficit becomes irreversible and the patient probably will die. The cause may be a fall or straining but in most cases there's no history of trauma. A myelogram reveals a block at the level of the hematoma, usually in the thoracic region or in the cervicothoracic or thoracolumbar area. Manometric tests shouldn't be done because they can increase the neurologic deficit. Urinary retention and sensitivity to pinprick at the level of the hematoma are additional diagnostic clues. The case reported here and 13 others from the literature point up the importance of prompt surgical treatment. Eight of the 12 patients who had laminectomy improved and five of them recovered completly, but both of the patients who were not treated surgically died.


Lysosomal acid hydrolase activities in the lungs of fetal, neonatal, adult, and senile mice.

The activities of four lysosomal acid hydrolases (LAH) in the lungs of two strains of mice changed significantly throughout the life cycle. In the CK7B1/6J animals, acid phosphatase (AP) and beta-glucuronidase (beta-G) were maximally active during early neonatal life then gradually declined the adult levels by 4-5 weeks of age. After reaching the adult level, acid phosphatase activities did not change significantly tcreased markedly with advanced age. N-Acetyl-beta-D-glucosaminidase (GAD) activities did not change significantly duringlate fetal, neonatal or young adult stages but increased significantly with advancing age. In the lungs of the CFW animals, the increase in activities of beta-G and GAD between young adult life and advanced age was highly significant, whereas there was no notable change in the activities of acid phosphatase or arylsulfatase (AS). The specific activities of the hydrolases in the lungs of the C57B1/6J strain were quite similar to those in the lungs of the CFW strain. The activities of all four hydrolases were markedly elevated in two spontaneous adenomatous tumors found in the lungs of old mice. The data indicate that LAH play a significant role in lung growth and maturation, and in changes associated with aging.


Concerning the estimation of biological age.

The conditions which must be satisfied by an index of biological age are discussed, and a high correlation with chronological age is shown to be neither a necessary nor a sufficient condition to be satisfied by any such index.


Aging and accuracy of protein synthesis in man: search for inactive enzymatic cross-reacting material in granulocytes of aged people.

Enzyme activities and immunological reactivities of seven different enzymes have been assayed in the polymorphonuclear leukocytes from 10 newborns, 10 aged (over 80 years old) and 10 young adults (20-30 years old). Polymorphonuclears have been chosen because both in the newborns, and in the aged people, they are young cells whose life span is a few hours only. Five cytoplasmic enzymes have been immunologically studied by means of monospecific antienzyme sera: leukocyte pyruvate kinase by immunoinactivation, glucose-6-phosphate dehydrogenase and glucose phosphate-isomerase by electroimmunodiffusion, lactic dehydrogenase (muscle-type) by radial immunodiffusion. Two lysosomal enzymes (alpha-mannosidase and beta-glycuronidase) have been titrated immunologically with the same polyvalent antihuman leukocyte rabbit serum. Small but significant differences in activity were observed for several of the enzymes. By contrast, no significant difference was found, for any of the seven enzymes, as regards the ratio enzyme activity/immunological reactivity, between newborns, young adults and aged people. These results of not support the theory that a decreased accuracy of the protein synthesis machinery is responsible for aging and death. By contrast, the authors emphasize that the enzyme abnormalities reported by various authors in old animals or in old fibroblast cultures closely resemble those demonstrated to be "post-translational modifications" in the case of human glucose-6-phosphate dehydrogenase.


[Swelling of collagen fibers in neutral salt solutions (author's transl)].

When applying various concentrations of NaC104 (0.15-7 M) to tendon fibres from rat tails, we found denaturation beginning at 2M, and with increasing concentration a linear increase of the maximal contraction tension and an expoential shortening of the contraction time down to a minimal value of 7.5 min. In a second group of experiments we investigated the weight changes of tendons of old (26-30 months) and young (8 months) rats treated with 5M NaC104 and compared the weight curves and the tension curves. We found an increase in weight up to 900% as the tension decreased. This indicates a connection between the swelling and the relaxation of collagen fibres. Other solutions of neutral salts (5M NaC103, NaC1; 0.15 M NaC104, NaC103, NaC1) tested on young and old tendons did not produce any tension nor other visible changes. The weight curves show an immediate increase up to about 200% which remains constant and which is low compaired with the effect of 5M NaC104. The reason for the contraction of tendon fivres seems to be the denaturation caused by the increased lipophilia of the aqueous salt solutions, while the relaxation is merely the result of the subsequent swelling of the collagen fibre.


Lithocholate metabolism during chenotherapy for gallstone dissolution. 1. Serum levels of sulphated and unsulphated lithocholates.

Serum levels of total sulphated and total unsulphated lithocholates were each measured by a specific radioimmunoassay in 66 patients ingesting chenodeoxycholic (chenic) acid for gallstone dissoultion and in 35 gallstone patients ingesting either cholic acid or placebo. No changes occurred in serum lithocholate levels in the control groups. In patients ingesting chenic acid, there was a twofold increase in serum levels of total lithocholate, but the percent sulphation (greater than 75%) remained unchanged during chenotherapy. There was no correlation in the chenic acid treated group  between serum lithocholate levels and the proportion of lithocholate in biliary bile acids or changes in serum SGOT. The data suggest that there is effective sulphation of lithocholate in such patients; this may explain the lack of hepatotoxicity observed during ingestion of chenic acid.


Lithocholate metabolism during chemotherapy for gallstone dissolution. 2. Absorption and sulphation.

The amount of lithocholate input and the size of the total lithocholate exchangeable pool were measured using isotope dilution in three patients ingesting chenodeoxycholic acid for gallstone dissolution and two healthy control subjects.  Because the specific activity decay curve was biexponential in appearance, input was calculated  using a stochastic analysis employing the  Stewart-Hamilton equation. By this method, the lithocholate input and the size of the exchangeable pool in gallstone patients during chenic acid ingestion was four to five times that observed in the healthy control subjects. It was calculated that about one-fifth of the newly formed lithocholate was absorbed in both gallstone patients and healthy control subjects. The extent of sulphation of absorbed lithocholate was then measured in seven gallstone patients whto had been ingesting chenodeoxycholic acid for gallstone dissolution by defining the chemical form of radioactivity in bile after intravenous administration of labelled lithocholate. Similar studies were carried out in eight healthy control subjects, but, in addition the extent of sulphation of injected lithocholylglycine and lithocholyltaurine was also defined. When lithocholate was injected, the majority of radioactivity in bile (50-60%) was present as sulphated conjugates, both in gallstone patients and healthy control subjects. The degree of sulphation was greater for glycine than taurine conjugates, and these findings, which suggested preferential sulphation of the glycine conjugates of lithocholate, were confirmed by showing that injected lithocholylglycine was sulphated to a much greater extent than injected lithocholyltaurine. These findings indicate that in patients receiving chenic acid there is effective sulphation of lithocholate, especially its glycine conjugates, despite a considerable increase in lithocholate absorption; they may provide an explanation for the lack of hepatotoxicity of chenic acid in man.


Plasma oestrogens in men with chronic liver disease.

A highly specific radioimmunoassay was used to measure the total plasma concentrations of the three principal unconjugated oestrogens: oestrone E1, oestradiol E2, and oestriol E3 in normal males and in 21 males with various forms of chronic liver disease. In addition, the unbound concentration of plasma E2 was established in the same group. About half of the patients with liver disease had overt feminising changes. Total and unbound plasma E2 concentrations were within the normal range in all patients. Total plasma E1 was significantly elevated only in those patients with liver disease and gynaecomastia, and a similar trend was seen for total plasma E3.


Use of caerulein with submaximal doses of secretin as a test of pancreatic function in man.

The pancreatic exocrine secretory response to different combinations of the pancreozymin-like peptide caerulein and secretin was studied in 110 healthy control subjects and 32 patients with pancreatic disease. A combination of 0-5 CU/kg-h secretin and 75 ng/kg-h caerulein provided maximal or near-maximal stimulation of the secretion of both bicarbonate and pancreatic enzymes. The combination of stimulant peptides in the above doses was found to give excellent separation between the secretion of bicarbonate, lipase, and chymotrypsin of the control group and patients with chronic pancreatitis. A combination of caerulein and secretin represents a safe, reliable, and effective mean of stimulating pancreatic exocrine secretion for the purpose of testing pancreatic function.


Effect of intraduodenal magnesium sulphate on pancreas and gallbladder of man.

Magnesium sulphate has previously been used as a purgative in a test involving the measurement of the faecal excretion of pancreatic enzymes. In order to validate the use of magnesium sulphate for this purpose, in 18 individuals the pancreatic and biliary response to intravenous infusion of secretin (1 CU/kg-h) plus CCK(1IU/kg-h) were compared with the responses to one of three dose-rates of magnesium sulphate infused into the duodenum. The effect of magnesium sulhphate was  also studied during the coincident intravenous administration of the hormones. Intraduodenal magnesium sulphate did not stimulate the secretion of bicarbonate into the duodenum but did  evoke the secretion of pancreatic enzymes and discharge of bile. The pancreatic response to the exogenous hormones was not altered by coincident intraduodenal infusion of magnesium sulphate. We conclude that magnesium sulphate is a satisfactory purgative for speeding the intestinal transit of pancreatic enzymes.


Radiographic evaluation of pancreatico-jejunal shunts.

This paper describes opacification and identification of two surgically constructed pancreatico-jujunal shunts. A fibreoptic panendoscope was used with retrograde injection via the ampulla of  Vater (ERCP). This procedure makes possible more accurate anatomical evaluation and so more precise clinical appraisal of both pre- and post-surgical states.


Electrogenic glucose absorption in untreated and treated coeliac disease.

Using a method for measuring changes in transmural potential difference across the human jejunum in vivo, the operational kinetic parameters of 'Apparent Km' and PD max for the active electrogenic component of glucose absorption were estimated in a group of healthy volunteers and in patients with coeliac disease. Both the 'Apparent Km' (17+/2mM; mean +/SEM) and the PD max (8.6+/0.7 mV) in nine patients with untreated coeliac disease were significantly lower (p less than 0.005) than in the control group ('Apparent Km' = 74+/5mM; PD max 12.8+/0.9mV, n=20). Treatment of five coeliac patients by gluten withdrawal for less than three months  increased significantly the values of both the "Apparent Km (35+/6mM) and the TPD max (11.4+/1.2mV). Treatment of five patients for more than six months caused a further increase in the values of both kinetic parameters ('Apparent Km' = 108+/13mM; PD max  =15.6+/2.7mV) to levels which exceeded those in healthy subjects. The possible interpretations  of the differences in the kinetic characteristics of electrogenic glucose transport between coeliac patients and healthy subjects are discussed.


Factors affecting the absorption of vitamin K-1 in vitro.

Factors which might affect the absorption of vitamin K of dietary origin were investigated using everted small bowel sacs. Increasing the bile salt concentration to 20 mM or the addition of long chain fatty acids, monoolein, or lecithin all resulted in significant (P less than 0-05) decrease in the absorption rate of the vitamin. The addition of 2-5 mM short and medium chain fatty acids did not change the absorption rate of vitamin K-1 (P greater than 0-05). The absorption rate of vitamin K-1 appears to be modified by the presence of compounds in the incubation medium which either alter the partition of the vitamin between the micelle and the cell membrane or which change the permeation characteristics of the compound through the unstirred water layer or modify the physical characteristics of the cell membrane itself. It is possible that some of the above factors modify the absorption of lipid soluble compounds in general.


Relation between body weight and the gastric and intestinal handling of an oral caloric load.

The gastric and intestinal handling of a standard liquid 300-ml meal (0.89 kcal/ml) was examined in 10 healthy, non-obese subjects by a quantitative multiple-indicator dilution technique. Such a meal contains about one-tenth of the daily energy requirements. The heavier the subject the more energy was transferred from the stomach to the intestine during the first 80 minutes after taking the meal. A high body weight was also associated with a rapid transit through the proximal 70 cm of intestine and the passing of a substantial part of the meal calories to the lower intestine. These circumstances favour a fast incorporation of fed calories. In subjects with lower body weights eneryg  was delivered more slowly from the stomach. The absorbed an equal amount of energy in the proximal intestine as did the heavier subjects, but during the longer transit times. The percentage absorption in the investigated segment was therefore higher.


Gastric mucosa after partial gastrectomy.

A partial gastrectomy of Billroth I  or II type was performed in a series of 146 patients with peptic ulcer. Gastric biopsy was carried out two years later and the histology of the specimens compared with that of the body mucosa at the time of operation. In 138 patients without body atrophic  gastritis (AG) before operation this condition was found in 74 (54%) two years after (46% of DU patients and 73% of GU patients). Those with antral or pyloric  canal ulcers were particularly liable to develop AG (81%). Apart from site of ulcer various other factors possibly associated with the development of AG were examined: no positive correlations were found with the possible exception of anaemia. Gastric parietal cell antibodies were not found in any patient with AG tested. The cause of gastritis after partial gastrectomy and its possible relationship with gastric carcinoma are discussed.


Highly selective vagotomy plus dilatation of the stenosis compared with truncal vagotomy and drainage in the treatment of pyloric stenosis secondary to duodenal ulceration.

Twenty-three consecutive patients with duodenal ulceration complicated by pyloric stenosis who came under the care of one surgeon were treated by highly selective vagotomy (HSV) combined with digital dilatation of the stenosis through  a gastrotomy. No form of drainage procedure was used. Thus the antral "mill" and the pyloric sphineter were left intact. Since the stenosis is usually distal to the pylorus rather than truly pyloric such dilatation does not damage the pyloric ring, although it may on occasion lead to perforation of the first part of the duodenum. The subsequent progress of these patients was compared with that of a similar, consecutive series of 23 patients with pyloric stenosis who were treated by truncal vagotomy with a drainage procedure by other surgeons on the same surgical unit. Patients were followed up for between four months and five years. The clinical assessment was carried out in "blind" fashion at a special gastric follow-up clinic. No evidence of recurrent ulceration was found in either group of patients. Two patients from each group subsequently  came to reoperation for the relief of gastric stasis. Twenty-two of the 23 patients (96%) who had undergone HSV plus dilatation eventually achieved a good-to-excellent clinical result (Visick grades 1+2), wheras only 17 of the 23 patients (74%) who had undergone truncal vagotomy with drainage achieved such a result. The main clinical difference between the two groups was that side effects such as diarrhoea and abdominal pain or discomfort were more common after vagotomy with drainage than after HSV. These results bear witness to the remarkable propulsive powers of the gastric antrum after HSV,  which were evidently sufficient to overcome any tendency to re-stenosis in more than 90% of patients. The 9% incidence of failure due to re-stenosis could perhaps be avoided if a small duodenoplasty were performed instead of simple digital dilatation. The results support the hypothesis that damage to the antral mill and pyloric sphincter can be avoided in the course of operations for "pyloric" stenosis secondary to duodenal ulceration. Avoidance of the drainage procedure is of benefit to the patient, just  as it is in patients who have duodenal ulceration without stenosis.


Proctocolitis and Crohn's disease of the colon: a comparison of the clinical course.

This study suggests that proctocolitis is an illness with an acute and potentially dangerous onset but which appears to become less severe after survival for one year, whereas Crohn's colitis tends to be a more chronic and progressive illness over several years with a greater need for surgical treatment and a greater tendency to anal complications.


Fibrin thrombi, a cause of clindamycin-associated colitis?

Rectal biopsies from five patients with clindamycin-associated colitis were studied with the intention of identifying fibrin thrombi in capillaries. Capillary thrombosis was present in all five cases, three with pseudomembranous colitis and two with non-specific colitis. The significance of capillary thrombosis and its relationship to other ischaemic lesions of the gut are discussed.


New early tertiary primates and a reappraisal of some Plesiadapiformes.

A new study of specimens of paromomyid and microsyopid primates clarifies evolution in these primates and reuslts in new concepts of each family. The paromomyid Phenacolemur and its former synonym, Ignacius, are distinct genera, each with new Early Wasatchian species, Plesiolestes, Palaechthon, Torrejonia, Palenochtha, Navajovius, Micromomys, and Tinimomys are removed from the Paromomyidae and transferred to the Microsyopidae. The Plesiadapiformes are classified in three groups which may be differentiated on incisor and molor structure: Plesiadapoidea (Plesiadapidae, Carpolestidae, and Saxonellidae), Microsyopidae, and Paromomyidae. The Paromomyidae, Microsyopidae (and its two subfamilies), and several genera are rediagnosed in the light of new comparative evidence.


[Surgical use of the laser].

The suitability of the laser for use in surgery is discussed. The mode of action as well as the advantages and disadvantages of electro-cautery are described together with a discussion about the use of the laser as an alternative. After preliminary remarks about the physical aspects, the effects of laser rays on biological tissue are illustrated and the most important properties of the laser with regard to its use in surgery are pointed out. An outline is given of the present use of the laser in the experimental and clinical areas; the properties required of a cutting instrument in surgery are listed. Finally the influence of the rays on the cutting characteristics of a Nd-high-power-laser is investigated in experiments using a rat liver model. This laser has substantial advantages over the CO2-laser in its practical application. The cutting mechanism and the development of the necrotic areas are discussed, together with a description of the cessation of hemorrhage and wound healing. The results obtained indicate that as soon as technical problems can be solved, the use of a pulsed high power YAG laser as a cutting instrument in surgery is highly promising.


[Imprint cytology. Advantages and possibilities].

Imprint cytology is a special variation of applied cytology, which can be used for quite different purposes. In scientific research cytologic imprints are very apt for cytophotometric measurements of DNA contents in nuclei as well as for karyologic studies, for instance on the different distribution of chromatin in the nuclei of benign and malignant tumors. Furthermore, imprint cytology is of great importance in teaching and learning results of aspiration biopsies, as the cellular patterns obtained with both methods are looking identical and moreover every imprint can be compared with the corresponding histologic slide. Last but not least in diagnostic procedures cytologic imprints are very helpful as an adjuvant to frozen and paraffin sections: They set off also very discrete changes and make possible diagnostic statements in a shorter time than it is possible with histologic slides.


[Fibrinogen degradation products in gynecologic neoplasms].

Concentration of fibrinogen degradation products in sera of 12 healthy women and 163 patients with gynecological tumors was determined by Staphylococcal-clumping-test. In sera of healthy women and patients with benign tumors the highest titer was 8. On the other hand in 53 of 97 cases with malign tumors higher concentrations were evaluated.


[Radiotherapy in the treatment of breast carcinoma].

In the treatment of breast cancer a radiation therapy is indicated under the following conditions: 1. Postoperative irradiation only of the regional lymph-nodes also in stage I (T1, N0). 2. Postoperative irradiation of the regional lymph-nodes and the thorax wall in cases with great primary tumours (T2), in cases with involved axillary lymph-nodes and, of course, in all cases with "grave signs". 3. Preoperative irradiation only in those cases when it seems possible that an inoperable tumour would become operable. 4. As the sole local treatment only in cases with very large inoperable tumours or in special cases (e.g. very high risc or refusal of the operation). 5. As local treatment of a local recidive or of isolated metastases. 6. As supporting local therapy (e.g. threatening fracturation of our fracturated bone metastases; brain metastases) in cases of generalized metastatic disease treated by hormonal or cytostatic therapy.


[Polychemotherapy of the advanced and metastasizing carcinoma of the breast].

The course of treatment with polychemotherapy for the progressed and metastasized breast-carcinoma is discussed. The therapy with cytostatics must be continued for the patients entire life. A sample of 27 patients from the Chir; Univ.-Klinik Innsbruck with a course of treatment lasting from 15 to 29 months (October 1973 resp; December 1974 to February 1976) showed a success rate of 81%.


[Cancer therapy using intermittent high doses of cytostatics].

The results of intermittent high-dose-therapy, especially with Doxorubicin and Amethopterin, are encouraging, particularly, against those malignant tumors which were difficult to influence until now. The damage to normal tissue and especially the therapy-limiting cumulative toxicity, seem to be lower if compared with the continuous low-dose-treatment because of the possibility for complete recovery of normal tissue during therapy-free intervals. Correlations between tumor, normal tissue and cytotoxic agent are discussed on the basis of cellkinetic findings to contribute to a better understanding of the way of action of a high-dose-therapy.


[Unusual angiographic examination methods in bronchial carcinoma. Attempt at critical evaluation].

The examination of mediastinal and pulmonary processes with angiographic methods play a decisive role in diagnosis. The results could be improved by combination of the procedures.


[Changes in the mouth mucosa during pregnancy and hormonal contraceptive treatment].

The oral mucous membrane, especially the gingiva, may undergo changes during pregnancy which, from clinical and histological observations, should be termed pregnancy gingival hyperplasia. Such rare cases of hyperplasia mimic pregnancy gingival tumours (granuloma gravidarum) within the buccal cavity. The gingival changes observed occasionally in women taking oral contraceptives may also be due to hormonal causes.


[Frequency of epithelial changes in the uterine cervix in adolescents and young women].

From 1967 to 1974 vaginal and cervical smears of about 46,000 teenage girls and young women up to the age of 25 were examined. Among these were 250 doubtful and positive cases (0,54%). Of the 67 positive ones 46 cases were known to be histologically examined (69%); 8 times an invasive carcinoma and 38 times a carcinoma in situ were found. Women under the age of 25 should therefore be included in routine check-up with cervical and vaginal smears.


[Consultation for abortion. Experiences and results].

During the 12 month period June 1974-June 1975, 170 patients were advised on termination of pregnancy in the University Department of Obstetrics and Gynaecology, Mannheim, the results from 145 women are discussed. 74% of the women were married, the majority of whom were between 34-39 years old. 39% lived in bad, 40% in average and 21% in good social conditions. In 77 women the pregnancy was terminated after permission was granted from the health authority. In 43 patients the termination was not granted and 25 women did not return to the clinic when an expert opinion was demanded. In 50 women a definitive sterilisation was carried out at the same time as termination of the pregnancy.


[Probability of malignant degeneration of ovarian tumors. Clinical study on the probability of malignant degeneration].

More than 600 cases of ovarian tumors were analyzed for histological type, age of patient, bilateral occurrence, mobility and malignant degeneration in restant ovaries. Tumors of germinal epithelial origin show the highest incidence (24%) of malignant degeneration, tumors of germ cells the lowest (3,5%). Incidence of malignant degeneration increases in relation to the age of the patient from 2% (and under 30 years) to 36,5% (60-70 years). Each form of tumor has its typical age peak, which is about 20 years higher for carcinomas than for their benign counterpart. Bilateral ovarian tumors are malignant in 29%, one-sided only in 13%. Among freely movable ovarian tumors, only 6% enclose a malignant tumor, among adhaerent ones 34%. The examination of the prognosis of granulosacell-tumors, dysgerminomas and teratoblastomas is based on a larger material.


[Results of therapy in ovarian neoplasms].

35 patients with carcinoma of the ovary were treated at the University Hospital Department of Gynaecology and Obstetrics Ulm between January 1st, 1967 and March 1st, 1970. Stage Ia patients had the highest five year crude survival rate. Histological diagnosis did not play any role in these patients. A 20% crude survival rate was noted in stage III-patients. In this group of carcinoma of the ovary the best results with a survival rate of 38 months on average were found in those women who were treated by "Second look method".


[Heart injury due to blunt violence].

One case of non-penetrating injury of the heart is reported. The problem of the causal relation between accident and injury of the heart as well as the problems of the pathophysiological mechanisms of non-penetrating traumatic injury of the heart are discussed. The localisation of the non-penetrating traumatic injury, the volume and the energy of the object causing the injury as well as the preexisting degree of coronary sclerosis is of some importance for the severity of heart damages after non-penetrating traumatic injuries of the heart.


[Urate nephrolithiasis. Cause of consequence?].

After World War II the incidence of urolithiasis increased consistently among the general population in this country. Nearly 25% of all examined renal calculi contain uric acid, sodium acid urate or ammonium acid urate as constituents. There are two peaks in lifespan of occurring urate stones: in the adolescence and in the age between 40 and 60 years. The following conditions are due to the formation of uric acid-containing stones: 1. Gout and primary hyperuricemia; 2. secondary hyperuricemia; 3. idiopathic cases with normal renal excretion of uric acid and normouricemia, but with a higher degree of acidity of the urine than normal considering the total renal excretion of acid products; 4. iatrogenic hyperuricemia during insufficient uricosuric therapy. Up to more than 30% of all the patients with recurrent formation of oxalate stones show a clear association with hyperuricemia, hyperuricosuria and increased renal excretion of calcium. In the presence of sodium urate a considerable promotion of precipitation of crystals consisting of calcium oxalate from a meta-stable solution may occur (so-called epitaxy). Frequently the existence of uric acid stones is without any symptoms. Modern views with regard to prophylactic procedures, diet, general and specific medical management including surgical intervention are presented.


[Worm-diseases].

Intestinal parasites are common among labourers from foreign countries and in immigrants. Some worm-infections like ascaridiasis or enterobiasis occur in children quite often even in the cold climates. In cases of ascaridiasis only a heavy infection causes clinical symptoms. The diagnosis is made through the detection of eggs in the stools, as all the other worm-infections are diagnosed from the stool-test. Piperazine-derivatives are highly effective against ascaris; another useful drug is Pyrantel-Pamoate. Toxocara canis, which affects normally only dogs, can occur occasionally in humans. Its larvae migrate in the body and cause granulomas. The main clinical symptom of threadworms (enterobiasis) is itching around the anus. This parasite can be eradicated through Pyrvinium-Pamoate. The first symptom a patient notices in cases of taeniasis are proglottides--parts of the worms--which are passed with the stools. The drug of choice against all kinds of tapeworms is Niclosamide. Hookworms are rampant in tropical countries. Heavy infections can cause severe anemias, especially in children. Bephenium-Naphthoate and Bitoscanate are effective drugs against this parasite. The whipworm (Trichuris trichura) is very common in the warm countries. It can be treated by Tiabendazole and nowadays also with Mebendazole, which is virtually atoxic. Infections with Strongyloides stercoralis are difficult to eradicate, as there are different ways of reinfection. In case an infection with strongyloides is accompanied by other serious diseases cachexia and even fatal outcome has been seen.


[Therapy and prevention of chronic respiratory tract diseases].

196 patients suffering from chronic infections of the respiratory tract (bronchial asthma, spastic bronchitis, sinobronchitis, increased liability to infections during childhood) were treated with non-specific hyposensitization by Paspat as no improvements had been obtained with other methods. The patients were observed for at least one year after the termination of the therapy: Recovery in 62,2%, clear improvements in 23% of the cases; only 14,8% did not respond. The author can now rely on a total of 466 cases, who have been treated by this method for 21 years. The results obtained after the childhood were significantly improved by modifying the treatment and the remedies and by increasing the numbers of injections. Consequently, repeated applications of Paspat for treating and preventing chronic infections of the respiratory tract are considered a real progress.


The influence of thyroid function on the diabetogenic action of triamcinolone in man. Glucose, insulin and growth hormone patterns after on oral glucose load.

In subjects with varying thyroid function (12 hypothyroid, 11 euthyroid and 12 hyperthyroid) an oral glucose tolerance test was performed without sensitization (OGTT) and after sensitizing with triamcinolone (TGTT). The blood glucose, serum immunoreactive insulin (IRI) and growth hormone (HGH) levels were assessed. In hypothyroid subjects a marked deterioration of the glucose tolerance was found during the TGTT as compared with OGTT, a reduction of the glucose disappearance index (GDI) and almost unchanged IRI values. The decrease of insulinogenic index (II) was not significant. In euthyroid subjects the decrease of glucose tolerance after triamcinolone was only mild, GDI values remained unaltered, IRI values and II increased. In hyperthyroid persons the decrease of glucose tolerance during TGTT was even less pronounced than in the euthyroid group, although the IRI value increased only on fasting. No significant differences of HGH pattern were observed in any group. In our patients the diabetogenic effect of triamcinolone was inversely related to the saturation with thyroid hormones and an increased response of insulin to glucose load was observed only in euthyroidism. In hyperthyroidism the participation of non-insular factors in the mechanism of maintaining the glucose tolerance after triamcinolone should be assumed.


Hypoglobulinemia in acromegaly.

We have observed an apparent hypoglobulinemia in 17 of 35 patients (48.6%) with acromegaly. This unexpected finding was persistent and reproducible up to six years for five acromegalic patients, and more than one year for nine other patients. Serum globulin was analyzed by three different methods, and the deficiency was most noticeable in the alpha globulin fraction (alpha1 greater than alpha2). When hypoglobulinemia occurred in control hospital in-patients (11%) it was associated with chronic or severe illnesses, and limited nutritional intake, but similar medical problems were absent in the acromegalic patients. There was no correlation of the hypoglobulinemia in the 35 acromegalic patients to their growth hormone (GH) concentration (r = 0.07), ages, sex, treatment status, or to the seriousness or duration of the acromegaly. The pathophysiology of the apparent hypoglobulinemia in acromegaly is unknown, but may be related to transport and/or disposal of excess growth hormone, or a defect in protein synthesis.


Circulating levels of immunoreactive parathyroid hormone in endemic genu valgum.

Circulating levels of immunoreactive parathyroid hormone (PTH) were estimated in fifteen normal subjects and twenty-five subjects suffering from the skeletal fluorosis, ten of whom had associated endemic genu valgum. Levels of PTH were high in all the subjects with fluorosis as compared to normals, but among fluorosis subjects, those who had endemic genu valgum had values strikingly higher than those without. It is suggested that secondary hyperparathyroidism may have a significant role to play in the pathogenesis of osteoporosis seen in patients with endemic genu valgum.


Autoregulatory shift from fructolysis to lactate gluconeogenisis in rat hepatocyte suspensions. The problem of metabolic zonation of liver parenchyma.

Hepatocytes were isolated from fed rats with glucose and insulin and freom fasted rats with glucagon in all media in an attempt to obtain cells which might be fixed preferentially in either the glycolytic or gluconeogenic state. When tested enzymatically, both "fed" and fasted" cells catalyzed glucose formation from lactate (gluconeogenesis) and lactate formation from fructose (fructolysis); lactate formation from glucose may have occurred in "fed" cells. Thus it was impossible, at least in the C3 part of the metabolic pathways between triosephosphate and pyruvate, to fix the hepatocytes in either metabolic state. The shift from glycolysis to gluconeogenesis could be investigated for the C3 part in "fasted" cells with fructose as the glycolytic and lactate as the gluconeogenic substrate. Lactate was first formed from fructose and later reutilized to a large extent. This reconsumption was blocked by the gluconeogenesis inhibitor quinolinate, both when tested enzymatically and radiochemically. Thus fructolysis was shifted to lactate gluconeogenesis. This shift at the assumed phosphoenolpyruvate/pyruvate cycle was autoregulatory, i.e. dependent on substrates and independent of circulating horomes. Maximal velocities and half saturating concentrations were determined for fructose and for lactate as substrates. The kinetic data obtained, especially the sigmoidal pattern of fructolysis, could nicely explain phenomenologically the rather sudden slow-down of lactate production and the shift to lactate consumption. The levels of the metabolites ATP, ADP, AMP, fructose bisphosphate and alanine, which control the enzymes of the assumed phosphoenolypyruvate/pyruvate cycle, were determined in the cytosol and in the mitochondria before and after the shift from fructose glycolysis to lactate gluconeogenesis. The changes observed could not explain the shift. Experiments with [14C] fructose plus unlabelled lactate and reciprocally, with unlabelled fructose plus [14C] lactate, clearly reveled that within the C3 part, glycolysis and gluconeogenesis were catalyzed simultaneously. The simultaneity of and the shift between fructolysis and gluconeogenesis by the liver cell suspension can best be explained by assuming two metabolically different types of hepatocytes rather than one type of hepatocyte with metabolically equal or different cell compartment. In vivo, the different types of hepatocytes would form a gluconeogenic and a glycolytic zone within the liver parenchyma. Since, under normal conditions, the size of these metabolic zones should remain unaltered, the shift from net glycolysis to net gluconeogenesis would be dependent primarily on substrate concentrations (autoregulation).


Plant microbody proteins, III. Labelling of the peroxisomal membrane protein SP-63 in vitro and in vivo.

Methods were developed to charcterize membranes and membrane components of leaf peroxisomes from Lens culinaris. While microbodies from etiolated young leaves exhibited an equilibrium density of 1.19 g/cm3, older leaves or leaves exposed to light for increasing periods of time contained microbodies banding at higher densities up to 1.235 g/cm3. Similar values were also found for the corresponding microbody membranes, which could be labelled with diazotized [35S]sulphanilic acid. Labelling was also performed using proteins extracted from the membranes. Their main structural protein (SP-63) was solubilized with sodium dodecylsulphate and labelled with fluorescent compounds as well as with diazotized [35S]sulphanilic acid or [3H]iodoacetic acid. These conversions greatly facilitate all analytical procedures, e.g. tracing the migration of SP-63 in gels or the movement in sucrose gradients containing sodium dodecylsulphate during zonal centrifugation. Also, labelling of SP-63 in vivo was accomplished when labelled amino acids were infused into etiolated leaves while exposing them to light.


Response of isolated rat hepatocytes to D-galactosamine and uridine.

Isolated rat hepatocytes preserved for several hours their contents of ATP, CTP, GTP, UTP and UDPG. Leakage of intracellular and membrane-bound enzymes remained in the range observed with the isolated perfused rat liver. D-Galactosamine led to a rapid decrease of the UTP and UDPG contents while ATP and GTP levels remained unaffected. The sum of acid-soluble uracil nucleotides increased immediately after the addition of D-galactosamine, indicating release of the UTP-mediated feed-back inhibition of pyrimidine nucleotide de novo biosynthesis. Addition of uridine to a hepatocyte suspension resulted in a rapid increase in the levels of uridylate derivatives; the concentrations of UTP and UDPG, previously depleted by D-galactosamine, were restored within 1 h. Isolated hepatocytes appear suitable for studies on the pathogenic sequence of events elicited by D-galactosamine and on the regulation of pyrimidine biosynthesis.


Crystallographic structural studies of a human Fc-fragment. I. An electron-density map at 4 A resolution and a partial model.

The crystal structure of a human Fc fragment was analysed at 4 A resolution. A partial interpretation of the electron-density map in terms of domain structure was possible. The molecule has the shape of a mickey mouse. The spherical domain was interpreted visually and by domain Patterson function interpretation as the CH3 dimer. This dimer resembles closely the CH1-CL dimer found in Fab structures. The ellipsoidal "ears" of the molecule represent the CH2 domains. They are widely separated from each other, but closely connected to CH3. Their tertiary structure must be different from CH1, as Patterson domain interpretations were unsuccessful. A chain tracing in CH2 was not yet possible.


[The synthesis of motilin, I: Preparation of the sequence fragments 9 - 22 of [13-norleucine]motilin and [13-leucine]motilin (author's transl)].

The syntheses of two suitably protected tetradecapeptides corresponding to the sequences 9 - 22 of [13-norlecucine] motilin [H-Glu(OBut)-Leu-Gln-Arg(HBr)-Nle-Glu(OBut)-Glu(OBut)-Lys(Boc)-Glu(OBut)-Arg(HBr-Asn-Lys(Boc)-Gly-Gln-OBu] and [13-leucine] motilin, respectively, are described. The two building blocks for the total syntheses of the motilin analogs were obtained by fragment-condensation of smaller units, prepared by stepwise procedure and corresponding to the sequences 18 - 22, 14 - 17, 12 - 13 (norleucine- and leucine-derivatives) and 9 - 11.


[The synthesis of motilin, II: Preparation of the complete sequences of [13-norleucine] motilin and [13-leucine] motilin (author's transl)].

Syntheses of two analogs of the intestinal hormone motilin containing in position 13 norleucine and leucine, respectively, are described. For this purpose a suitably protected octapeptide-derivative, corresponding to the sequence 1-8, was prepared and condensed with the tetradecapeptides 9-22 of [13-norleucine]-motilin and [13-leucine] motilin (described in the preceding paper) to give to overall protectdd docosapeptides Boc-Phe-Val-Pro-IIe-Phe-Thr-(But)-Tyr(But)-Gly-Glu(OBut)-Leu-Gln-Arg-(HBr)-Nle-Glu(OBut)-Glu(OBut)-Lys(Boc)-Glu-(OBut)-Arg(HBr)-Asn-Lys(Boc)-Gly-Gln-OBut and its 13-leucine analog.


[The synthesis of motilin, III: Purification and characterization of (13-norleucine) motilin and (13-leucine) motilin (author's transl)].

The preparation of the pure docosapeptide H-Phe-Val-Pro-I1e-Phe-Thr-Tyr-Gly-Glu-Leu-Gln-Arg-Nle-Glu-Glu-Lys-Glu-Arg-Asn-Lys-Gly-Gln-OH ([Nle13]motilin) and of the analogous [Leu13]motilin from the crude synthetic materials obtained after deblocking of the overall protected docosapeptide derivatives by means of trifluoroacetic acid is described. In a preliminary experiment the separation of crude [Nle13]-motilin into several components, some of which being indistinguishable by thin layer chromatography, was achieved by repeated ion-exchange chromatography on QAE-Sephadex A-25 and SP-Sephadex C-25. Subsequent characterization of some of the isolated side-products, using amino acid analysis as well as spectroscopic (UV, CD) and enzymatic methods, in comparison to the major product enabled conclusions on the reasons of their formation. The undesired formation of des-(Thr6 -Tyr7 Gly8)[Nle13] motilin and of [D-Phe5-Nle13]motilin could be avoided during the subsequent major synthesis of [Nle13] motilin and during the preparation of [Leu13] motilin by changing certain synthetic conditions and, respectively, by using a specially purified protected fragment of the sequence 1-8, being free of diastereomers. Single ion-exchange chromatography on SP-Sephadex C-25 was sufficient for the purification of the so obtained crude synthetic end-products.


A new semisynthesis of human insulin.

A new semisynthesis of human insulin starting from porcine insulin is described. NalphaA1, NalphaB1-di-Boc-desoctapeptide-(B23-30)-insulin bearing 6 free carboxyl groups is coupled with the suitably protected human insulin-(B23-30)-octapeptide. The preferred reaction site is the carboxyl group of ArgB22. Side products are eliminated by extensive chromatographic purification.


[Large scale purification of the acetylcholinesterase from bovine caudate nucleus by affinity chromatography (author's transl)].

The acetylcholinesterase from bovine caudate nucleus was solubilized with 0.6-0.8% Triton X-100. It was purified and freed from Triton X-100 by means of a two-fold affinity chromatography procedure. A simple three-step synthesis of the inhibitor with attached spacer arm used in affinity chromatography is described. Starting from 3 kg of caudate nucleus, nearly 11 mg of the purified acetylcholinesterase with a spec. act of 4250 U/mg (13 500-fold purification) could be obtained in an over-all yield of 49%. On gel electrophoresis the enzyme produces several enzymatically active glycoproteinbands of oligomeres. On sodium dodecylsulfate gel electrophoresis in the presence of a disulfide-reducing agent it yields a molecular weight of 72000 +/- 2000 for the smallest subunit. In the absence of a disulfide-reducing agent a band for a dimer besides the band for the monomer could be detected and a molecular weight of 142000 +/- 3000 was estimated for this species.


[Physico-chemical characterisation and crystallisation of immunoglobulins and their fragments: a contribution to the three dimensional structural determination of antibodies, III. Human immunoglobulin Kol, a myeloma protein of the type IgG, gamma2 kappa2, Gm (f)+. Comparative studies on dissolved and crystalline material (author's transl)].

Immunoglobulin Kol has been isolated and characterised as the intact molecule, which consists of an antigen binding part (Fab) and the C-terminal fragment (Fc). Crystals of the protein are suitable for X-ray diffraction resolution of the fine structure, down to atomic dimensions; but this does not permit the representation of the Fc-part of the molecule. The following studies were performed on the protein in solution before and after crystallisation; the results were the same in both cases, thus showing that crystallisation does not alter the molecule: After enzymic cleavage of the protein, the products were isolated and identified by immunological reactions and by analytical ultracentrifugation; the behaviour of the protein in disc electrophoresis following reductive cleavage was also studied.


[Physico-chemical characterisation and crystallisation of immunoglobulins and their fragments: a contribution to the three-dimensional structural elucidation of antibodies, IV. The Fab fragment and the Fc fragment of human immunoglobulin Kol; isolation and crystallisation (author's transl)].

The X-ray fine structure analysis of intact crystalline immunoglobulin Kol indicates that the conformation of the Fab region differs essentially from that determined for the free Fab fragment. For this investigation, the free Fab fragment Kol was prepared and characterised, and crystalline preparations of the whole protein were obtained, that were suitable for an elucidation of atomic structure, and the appropriate measurements were made. In the crystal structure analysis of immunoglobulin Kol, it has not been possible to determine the Fc region. The Fc fragment was therefore separated from the whole molecule to facilitate its study. The isolation of this Fc fragment, its characterisation and subsequent crystallisation are described.


[Bis(monoacylglycero)phosphate--a marker lipid of secondary lysosomes? (AUTHOR'S TRANSL)].

Rats were treated with triton, dextran, silver and iron. The lysosomal fractions from their livers were isolated and the lipids analysed. (MAG)2P could be detected in every phospholipid fraction, accounting for 6-28 per cent of the total lipid phosphorus. The composition of the fatty acids from this acidic glycerophospholipid shows an extraordinarily high amount of polyenoic fatty acids (58-82 per cent of the total), of which docosahexaenoic acid is a main compound.


1,8-disubstituted analogues of (Ile5) and (Val5)angiotensin II: difference in potency and specificity of angiotensin II-antagonistic activity.

Depending on the species, position 5 in angiotensin II is occupied by isoleucine or valine. 1,8-disubstituted analogues of [Ile5]angiotensin II show distinct differences from the corresponding [Val5]angiotensin II analogues in the potency and specificity of their inhibitory action. The syntheses of new analogues are described.


Carboxypeptidase N from pig serum.

Carboxypeptidase N has been purified 865-fold from pig serum. The enzyme has a molecular weight of approximately 315 000. In the presence of dodecylsulfate and mercaptoethanol, it dissociates into three subunits of Mr = 90 000, 50 000, 30 000, respectively. The native enzyme and the subunit of Mr = 90 000 contain carbohydrate; no carbohydrate is found in the subunits of Mr = 50 000 and 30 000. Trypsin transforms carboxypeptidase N into a form having a smaller molecular weight and enhanced activity.


System links nurse call/locator, patient intercom, emergency call.

The communications system has improved patient care; nursing personnel have found it to be extremely valuable and easy to use; and physicians are pleased with it, because their patients are receiving better care and because communications are speeded when they call a floor for information or to give instructions. Installation and use of the system have proved that, with proper planning, hospitals can incorporate custom-designed systems and features into new construction at reasonable cost. Memorial Hospital now is in the process of proving that these innovations also can be incorporated into a remodeling and modernization program. Of course, among the key elements in the success of such endeavors are the willingness and the ability of equipment designers and manufacturers to satisfy specialized needs.


Structural variability of human chromosome 9 in relation to its evolution.

Human chromosome 9 shows a high susceptibility for structural rearrangements, particularly pericentric inversions, which often are transmitted. Three types of pericentric inversions can be observed on No. 9: 1) Type I, showing the total constitutive heterochromatin in the short arm. 2) Type II with part of the C heterochromatin on the short arm, the rest located on the long arm proximal to the centromere. 3) Type III: a subtelocentric chromosome with part of the C heterochromatin in the very short arm and the rest located interstitially on the long arm. With these inversions as well as with other structural rearrangements, e.g. translocations, the break-points are located preferentially within the C heterochromatin or close to the heterochromatic-euchromatic junctions. These findings are in contrast to the findings in lymphocytes from 5 patients with fancomi's and after irradiation in vitro, reported in the literature. In lymphocytes break-points seem to be distributed more or less by chance. These observations together led us to speculate that human chromosome 9 primarily was an acrocentric chrosome; in morphology and at least in some functions similar to D- and G-group chromosomes. During evolution this acrocentric chromsome changed to a submetacentric one due to a pericentric inversion.


[Karyotype-phenotype correlation in a 46,Xdel(X) (p22) diagnosis (author's transl)].

In a patient with a height of 1.46 m, short neck and cubitus valgus the unbalanced karyotype 46,Xdel(X)(p22) was found. The mother of the proband has the balanced karyotype 46,Xt(X;15)(p22;p1). The mother is 1.56 m tall and has a short neck and cubitus valgus too. For this reason the deletion of the Xp22 band seems to cause the short stature of Turner patients. Our proband has had 2 pregnancies which ended as abortions in the 2nd and 4th month. As Giraud et al. (1974) have shown the deletion of the dark middle bande of the short X chromosome arm induces a slight dysgenesie of the gonade.


47,+(9q-) in unrelated three children with plasma growth hormone deficiency.

Marker chromosomes carried by unrelated 3 cases were identified as a part of No. 9 chromosome through the analysis of the chromatid fine structure after trypsin-giemsa treatment. They showed characteristic features of that 9p trisomic syndrome which were described by Rethoré et al. (1973). In addition to those features, some clinical and laboratory findings on growth hormon deficiency were disclosed in this report.


Serum immunoglobulin M, G, and A concentration levels in Turner's syndrome compared with normal women and men.

Serum concentrations of immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) were determined in 15 women with a lack of X chromsome material (Turner's syndrome), and compared with the immunoglobulin concentrations in normal men and women. Further, the investigation is supplemented by a comparison of normal women and the Turner group matched according to age. The serum concentrations of IgG and IgA in women with Turner's syndrome were very close to the concentration in serum from normal men, whereas the concentration of IgM was significantly lower. Compared to normal women the concentrations of IgG and IgM were significantly lower, and the concentration of IgA significantly higher in the Turner group. Whether these differences in serum immunoglobulins are determined by hormonal factors or under direct genetic control linked to the X chromosomes, is discussed.


Biochemical characteristics of collagen produced by long term cultivated amniotic fluid cells.

The synthesis of the most common type I of collagen was proven in human amniotic fluid cell culture with fibroblast morphology in the cells as well as in the culture medium. Mesenchymal origin of long term cultivated amniotic fluid cells is indicated and the possibility of prenatal investigation of hereditary disorders of connective tissue is pointed out.


The trisomy 18 syndrome with an E/G translocation.

An infant with a typical Edwards syndrome and a modal chromosome number of 46 is reported. In all cells analyzed one chromosome G was missing and an additional chromosome similar to a pair No. 16 was present. The phenotype of the child indicates that the extra element is a translocation between G and 18 chromosomes as in one case described previously.


A female infant with monosomy 21.

A female infant with total monosomy 21 identified by Q banding is described. The main clinical features were hypertonia, prominent occiput, hypertelorism, antimongoloid slant of the eyes, broad nose, "antimongoloid", character of dermatoglyphics. Both parents are phenotypically as well as karyotypically normal.


9p trisomy identified by Giemsa-11.

The Giemsa-11 technique specifically stains the secondary constriction region of chromosome 9. We report cytologic evidence for 9p trisomy in a 4 1/2-year-old girl with moderate retardation and multiple anomalies, using the Giemsa-11 technique.


Studies of haptoglobin and transferrin types in four castes of the Panjab, Northern India.

Serum samples from 197 individuals belonging to the caste groups of Brahmin (37), Bania (39), Khatri (73) and Jat (48) were electrophoretically examined for the haptoglobin and transferrin systems. Intercaste variation was considered and comparisons made between these North Indian populations and those in other parts of the Indian subcontinent. A single Khatri individual was typed CB.


On the geographical variability of the red cell PGM1 and acid phosphatase gene frequencies.

Based on the hitherto published population data of the human red cell PGM1 and acid phosphatase polymorphisms, the geographical distributions of their gene frequencies were analyzed. As far as the acid phosphatase alleles are concerned, a marked geographical gradient was found as the Pa and Pb alleles showed significant correlations with the mean annual temperatures of the various human biotopes (Pa:r = -0.706; Pb:r = +0.812). Against that, the world distribution of the PGM1 alleles did not show a comparable correlation (PGM1 1:R = +0.063; PGM2 1:R = -0.063). The possible reasons for the distribution pattern of the acid phosphatase alleles are discussed.


Superoxide dismutase variants in Newfoundland--a gene from Scandinavia?

An electrophoretic survey of variant red cell enzyme phenotypes in an isolated community in Newfoundland gave gene frequencies in marked contrast to those found in the capital, St. John's. In particular, a variant of red cell superoxide dismutase (SOD) gave a high variant frequency. Possible origins of the variant SOD allele are discussed.


Human red cell acid phosphatase: quantitative evidence of a silent gene PO, and a Danish population study.

In a forensic case of disputed paternity an apparent mother/child incompatibility with respect to red cell acid phosphatase was found, the mother appearing as type A and the child as type B. Determination of electrophoretic type and of acid phosphatase activity in 8 of the family members strongly suggested the presence of a silent gene PO in 4 of the individuals. The phosphatase levels in the four heterozygotes were about half the values expected from normal values determined in 100 healthy adults representing the different phenotypes. The distribution of red cell acid phosphatase types in 3,735 unrelated Danish adults and in 1,109 mother/child pairs is reported; gene frequencies Pa = 0.369, Pb = 0.566 and Pc = 0.065. The PO gene frequency was roughly estimated as 0.001. Results are reported on the application of the red cell acid phosphatase system to 300 2-men cases of disputed paternity.


Pancreatic amylase polymorphism: another example of a distinctive gene frequency among Sardinians.

The authors investigate the distribution of electrophoretic patterns of pancreatic amylase in 319 Sardinians and in 476 blood donors living in Naples. The results obtained show a difference in the phenotype frequency of the Amy2 duplication variant between Sardinians (1.25%) and Neapolitans (5.25%) which is statistically significant (p less than 0.01). This further confirms that Sardinians show peculiar ethnic characteristics as compared to other Caucasian groups, even to those living in the Mediterranean area.


The G syndrome. A four-generation family study.

A male infant with hypertelorism, hypospadias, swallowing difficulties with tendency to regurgitation and cough, high arched palate, and a delicate voice, consistent with the G syndrome, is reported. In the family the same symptoms in addition to cleft lip and palate were known in several family members through four generations. In the females only slight manifestations of the syndrome were found, and in the males variable expression of symptoms was observed. Autosomal dominant inheritance is likely, but X-linked inheritance cannot be ruled out.


On the genetics and population genetics of Gm(4).

Investigations on 70 German families with 142 children confirmed the autosomal-dominant inheritance of Gm(4). However, in our material as well as in the materials published so far, Gm(4) X Gm(-4) parental combinations show clear surplusses of Gm(4) and deficits of Gm(-4) children, which might indicate prenatal selection. The world distribution of Gm4 alleles reveals a remarkable racial heterogeneity. Furthermore, marked North-South distribution gradients in Caucasoids and Mongoloids were found. The genetical and population genetical observations are discussed.


Two kindred with the rare dominant inhibitor of the lutheran and p1 red cell antigens.

Two kindred each showing the dominant inheritance of the rare phenotype lu(a-b-) in the Lutheran blood group system are recorded. The pedigrees illustrate the expected upset in the occurrence of the P1 antigen in the Lu(a-b-) members. A third Lu(a-b-) propositus of the dominant type was found after testing a further 3,197 donors on the East Anglian panel. The phenotype Lu(a-b-) may not be quite as rare as previously supposed.


Population genetic studies in kerala and the nilgiris (South West India).

A total of nearly 1,000 persons belonging to a number of caste, religious and tribal groupings in Kerala and the Nilgiri Hills of South India have been tested for genetic variation in 4 blood group, 5 serum protein and 17 enzyme systems as well as haemoglobin. The distribution of blood groups, serum protein and enzyme groups is similar to that reported for other South Indian populations. Abnormal  haemoglobins were detected in several populations. Abnormal haemoglobins were detected in several populations, HbS being present in more than 20% of the Irula and Kurumba in the Nilgiri Hills. In the Kerala populations there were 4 examples of Hb AD and 1 of Hb AE. Genetic distance estimates using the gene frequency data indicate that the closest groups are the Nayar and Izhava and the Brahmin and Nayar. The tribal populations are approximately twice as far from the Nayar as they are from the Izhava. The Todas of the Nilgiri Hills are somewhat closer to the Brahmin of Kerala than they are to the other tribal populations.


The study of genetic variation in Nigeria. II. The genetics of polydactyly.

The analysis of polydactyly in the Nigerian population has revealed a frequency of 22.78 per thousand, with slight variations from one region of the country to another. All polydactyly was post-axial and most was of type B. Although we expected this frequency to be the same in both males and females, we observed that females have a significantly lower frequency (17.92 per thousand) than the males (27.08 per thousand). This condition appears to be inherited as an autosomal dominant gene with a penetrance of 64.9%, and highly variable expressivity. There does not seem to be any phenotypic difference between individuals who are homozygous and those who are heterozygous for the gene.


Human saliva esterases: genetic studies.

Esterases from human saliva have been demonstrated by the zymogram technique. Three phenotypes were found in region 1. Family and population studies suggested that these phenotypes are the products of an autosomal locus with two alleles, Set-1F and Set-1S. Region 1 esterases are carboxylesterases.


Lymphocytocidal lymphocyte trapping by human lymph node cells: a tissue culture-ultrastructural study.

An ultrastructural study was carried out on 25 lymphocyte-trapping cells selected from tissue cultures of human axillary lymph nodes. The trapping cells contained several hundred intravacuolar lymphocytes, most of which showed degenerative changes. The principal findings are: (a) a braod spectrum of lymphocyte degeneration; (b) a consistent pattern of lymphocyte degeneration beginning with perinuclear vacuoles and ending with breakdown of the nuclear envelope; (c) the viable lymphocytes tended to be located in a  juxtanuclear region; (d) a lysosomal relationship was suggested for lymphocyte degeneration but not for lymphocyte  trapping; and (e) degeneration of the trapping cell, or lymphocytes associated with other cells, was not observed. The sequence of degenerative  changes differs from those reported for several classes of lymphocytocidal agents. There were no morphologic properties of the trapping cell which served to identify it more specifically. The findings, together with previous time-lapse film observations, warrant further investigation of the hypothesis that lymphocytocidal lymphocyte trapping may be involved in the control of lymphocyte populations.


Occurrence of minute ring-shaped nucleoprotein particles in culture media conditioned by mammalian cells.

Conditioned media of 21 mammalian cell lines have been examined by electron microscopic and biochemical techniques for the presence of a minute ring-shaped nucleoprotein particle (RSP). Electron microscopy showed the presence of RSP in 20 of the 21 cell lines tested. Comparative analyses of sex cell cultures for radioactive RSP, following 3H-thymidine incorporation, suggested that quantitative differences exist in the amount of RSP detectable in conditioned media of normal and pathologic cells. The cell lines tested included cells of different morphologies, origin and function


Incorporation and uptake of thymidine and uridine by HeLa cells: effect of DNA extracts prepared from normal human fibroblasts.

The incorporation and uptake of (3H) thymidine into HeLa cells markedly decreased in the presence of nuclear homogenates and DNA extracts that have been derived from normal diploid cell cultures. On the other hand, uridine uptake and incorporation were stimulated under the same conditions. The inhibition could be reversed immediately upon removal of the exogenous fraction from the culture medium. The inhibitory properties of the extracts are propagated by excreted cellular components as well as after DNAase treatment. The inhibitory factor is thermostable, resistant to pronase treatment, and seems to be related to nucleic acid.


Comparative study of extracellular amino acids in culture of human liver and fibroblastic cells.

Amino acid concentration are studied in the extracellular media of ten series of human fibroblast and liver cell monolayer cultures. These two cell types consume and produce ostensively the same amino acids. Among the nonessential amino acids, the most significant variations involve serine and aspartate which are decreased; alpha-alanine, glutamate, ornithine and proline are, on the contrary, increased. Among the essential amino acids, leucine, isoleucine and glutamine are preferentially decreased. The variations of some amino acids are correlated with the cell density. The interrelations which may exist between the variations of these different amino acids are discussed. Furthermore, the glycolytic acitivity of the cells studied is very high: 85% of glucose consumed is found in the form of lactate.


Effect of prolactin on maintenance of prelactating human mammary gland in vitro.

Human mammary tissue from a female at the end of the second trimester of pregnancy was studied in organ culture in a chemically defined medium. Sampling was carried out at 1, 2 and 3 weeks. Without hormones, there was nearly total lobuloalveolar degeneration in all specimens at all times. Addition of insulin, hydrocortisone and ovine prolactin, in combination at a concentration of 5 mug per ml each, did not affect the extent of degeneration. Raising the concentration of prolactin to 50 mug per ml resulted in greatly improved lobulo-alveolar maintenance in all specimens and continued epithelial cell DNA synthesis for up to 3 weeks in vitro.


The effect of cytophilic IgG2 on phagocytosis by ovine polymorphonuclear leucocytes.

Non-lactating, multiparous ewes were immunized either by subcutaneous infection with live Staphylococcus aureus (seventeen ewes) or by intramuscular injections of a killed S. aureus-oil adjuvant vaccine (seventeen ewes). Polymorphs which were subsequently collected from the mammary glands of the animals were used in in vitro phagocytosis assays against Pseudomonas sp. or S. aureus. There was no difference between polymorphs from the two groups of ewes in their ability to phagocytose Pseudomonas organisms. Polymorphs from the infected ewes showed significant phagocytic superiority over cells from ewes given the killed vaccine when S. aureus was the target organism. This phagocytic superiority could be abrogated by removal of cytophilic immunoglobulin from polymorphs and restored by replacement of cytophilic immunoglobulin. It was shown by staining polymorphs with FITC-conjugated anti-immunoglobulin sera that cytophilic immunoglobulin on the surface of polymorphs belonged to the IgG2 class of immunoglobulins. When 'neutral' polymorphs (from non-immunized ewes) were coated with IgG2 purified from the sera of infected ewes, they exhibited enhanced phagocytosis of staphylococci compared with 'neutral' polymorphs carying IgG2 from the sera of ewes given the killed vaccine.


Secondary cytotoxic cell response to lymphocytic choriomeningitis virus. I. Kinetics of induction in vitro and yields of effector cells.

Secondary (memory) cell-mediated cytotoxic responses in lymphoid cells from CBA/H mice pre-primed with lymphocytic choriomeningitis virus (LCM) 5-7 weeks previously were induced by culturing these cells in vitro with syngeneic, infected peritoneal cells at 37 degrees for periods of up to 5 days. Cytotoxic effectors were assayed against LCM infected, H-2 compatible target cells in a 51Cr release assay. Response was greater with a higher ratio (1:10) of infected peritoneal cells:pre-primed cells than with lower ratios (e.g. 1:250). Separating responders from infected cells by a 450 mmum nucleopore membrane (coarse enough to allow passage of virus particles) still permitted induction of a secondary response whilst interposition of a 50 mmum nucleopore membrane (which apparently prevented transit of virus particles) virtually abolished the secondary response. Removal of phagocytic cells from responders prior to setting up memory cultures greatly reduced responders' capacity to be induced. Fixed, infected stimulators still induced strong secondary responses. Secondary response was maximal with spleen cells, peripheral blood lymphocytes, or pooled iliac and lumbar lymph node cells. Thymocytes responded less well, whilst mesenteric lymphoid cells and peritoneal cells gave minimal responses. Effector cells from memory cultures killed targets with single-hit kinetics and a rectilinear log effectors: log targets lysed relation held. Memory spleen cells developed increasing cytolytic activity from 2 to 5 days in culture. Memory-generated effectors were markedly potent by day 5, e.g. giving 70 per cent specific release at a killer:target ratio of 0-8:1. Peak DNA synthesis occurred on day 4. We conclude that memory effectors as a population differ in kinetics and potency from effectors obtained by primary viral challenge in the mouse.


Studies on the interaction of the Sophora japonica lectin and concanavalin A with erythrocytes and lymphocytes.

The agglutinating activity of lectins from the seeds of Sophora japonica and Canavalia ensiformis (concanavalin A) with human and murine erythrocytes and lymphocytes have been compared to one another and related to the mitogenic and immunosuppressive properties of these purified proteins. The S. japonica lectin, which demonstrates blood group specificity, is more active than concanavalin A with human erythrocytes, but has a much lower reactivity than concanavalin A with murine red blood cells. Ficin treatment of human erythrocytes results in an increase in agglutinability by both lectins as well as causing the appearance of S. japonica lectin receptors on type O cells. Treatment of murine reythrocytes with ficin alone or followed by beta-galactosidase causes the cells to be more reactive with concanavalin A. Beta-Galactosidase alone has no observable affect on the cells. In contrast, the agglutinability of cells by the S. japonica lectin increases after ficin treatment but is not affected by beta-galaetosidose treatment either after or in the absence of ficinization. Murine lymphocytes react with both lectins in a manner paralleling the agglutination patterns of murine erythrocytes. The S. japonica lectin appears to be devoid of mitogenic and immuno-suppressive activity, in contrast to concanavalin A which suppresses the T helper-dependent antibody response to sheep erythrocytes. These results are discussed in terms of the types of lectin receptors on lymphocytes related to agglutination, induction of blastogenesis and immuno-suppression.


Cell division and deoxyribonucleic acid (DNA) synthesis in cultures of stimulated lymphocytes.

The responses of lymphocytes cultured with various stimulants were analysed with respect to DNA synthesis and cell division. Autoradiographic labelling with [3H]thymidine indicated that similar proportions of cells had incorporated this labelled precursor for DNA synthesis during both short and long periods of exposure to this specific precursor for DNA synthesis. Changes in labelling index (LI) after pulsing these cells with [3H]thymidine showed that exchange of labelled material, which could not be chased out with unlabelled thymidine, was responsible for the increases of LI seen. Failure to prevent this increase with excess unlabelled thymidine indicated that direct incorporation of [3H]thymidine did not account for this exchange. Using hydroxyurea and colcemid arrest to analyse cell cycle events in these cultures, it was shown that approximately 70 per cent of the responding cells in cultures of stimulated lymphocytes, while actively synthesizing DNA, were not in cell cycle for division. It was concluded that DNA turnover, involving synthesis and exchange of newly synthesized material, possibly DNA, was occurring in these cells.


Inhibitory effect of carrier and hapten preimmunization on delayed hypersensitivity to the carrier.

The different components of the immune response to hapten-carrier conjugates have been supposed to interact with each other. In order to elucidate the interrelationship between hapten and carrier moieties of the antigen molecule at the cellular level, the homologous carrier alone or the hapten conjugated to an heterologous carrier were injected before immunization with the hapten-carrier conjugate. Delayed hypersensitivity to the carrier could be depressed by pretreatment with the hapten or with the carrier depending on which time interval was chosen to elapse between the two injections. The results could be explained by antigenic competition, occurring at the cellular level, between hapten and carrier moieties of the antigen molecule.


The mediation of tissue eosinophilia in hypersensitivity reactions. II. Separation of a delayed eosinophil chemotactic factor from macrophage chemotactic factors.

In anaphylactic cutaneous lesions induced by DNP-ascaris extract in the guinea-pig, the time-course of delayed tissue eosinophilia was found to parallel that of the macrophage reaction, reaching its peak in 24 h. Macrophages could be differentiated from lymphocytes by the numerous lysosomal granules which stained for acid phosphatase. Extracts from such skin lesions contained a delayed eosinophil chemotactic factor and two different macrophage chemotactic factors. Most of the delayed eosinophil chemotactic factor was separated from the two macrophage chemotactic factors by gel filtration on Sephadex G-100 and Sephadex G-200 in that order. The eosinophil chemotactic factor after re-chromatography on Sephadex G-I99 showed no or little chemotactic activity for macrophages.


Lectin-dependent neutrophil-mediated cytotoxicity. I. Characteristics.

Isolated normal human peripheral neutrophils became cytotoxic to chicken red blood cells (CRBC) in the presence of phytohaemagglutinin (PHA) and concanavalin A (Con A), a phenomenon which we have termed lectin-dependent neutrophilmediated cytotoxicity (LDNMC). Substantial cytotoxicity could be demonstrated by 1 h of incubation at 37 degrees. Isolated human peripheral lymphocytes were not cytotoxic to CRBC in the presence of these lectins, even after 18 h of incubation. Both PHA and Con A exhibited dose responses over a wide concentration range and displayed progressive, time-dependent cytotoxicity. Cytotoxicity for both PHA and Con A was greater at 37 degrees than at 22 degrees, and was undetectable at 4 degrees. CRBC as target cells were much more readily lysed than either sheep or human erythrocytes. Erythrophagocytosis did not appear to play a role.


Lectin-dependent neutrophil-mediated cytotoxicity. II. Possible mechanisms.

The mechanisms whereby neutrophils become cytotoxic to chicken erythrocyte (CRBC) target cells were investigated in a system of lectin-dependent neutrophil-mediated cytotoxicity (LDNMC). Through the use of drugs and specific metabolic inhibitors, LDNMC was found to be dependent on energy supplied by anaerobic glycolysis and on other active metabolic functions of the neutrophil. 2-Iodoacetamide, 2-deoxy-D-glucose, di-isopropyl-fluorophosphate, colchicine, cytochalasin B, and dibutyryl cyclic AMP all caused dose-dependent inhibition of cytotoxicity, while inhibitors of protein and nucleic acid synthesis were without effect. Cell surface membrane-active agents, such as chloroquine, hydrocortisone and chlorpromazine inhibited cytotoxicity, while vitamin A caused enhancement. Lectins which agglutinated neutrophils, but not necessarily CRBC, such as phytohaemagglutinin (PHA-P), concanavalin A (Con A), soybean agglutinin (SBA), and Ricinus communis agglutinin (RCA), mediated cytotoxicity while lectins which did not cause agglutination, such as pokeweed mitogen (PWM), did not mediate cytotoxicity. Preincubation of neutrophils, but not CRBC with PHA-P, resulted in time-dependent enhancement of cytotoxicity, while pre-incubation with Con A yielded progressive inhibition of cytotoxicity. These studies suggest that lectin binding to the cell surface causes alterations of the membrane, that LDNMC requires cell to cell surface contact, and that cytotoxicity depends on active metabolic processes.


Miliary mycoplasmal pneumonia: a report of six cases.

Six cases of miliary pneumonia are reported, in which the marked increase in antibody titers showed that Mycoplasma pneumoniae was the probable cause. The clinical picture of these patients showed an acute and severe onset, with the appearance of diffuse alveolitis. The outcome of the disease depended on the time of initiation of treatment in relationship to the onset of symptoms. One case was seen to progress to fibrosing alveolitis with persistent impairment of diffusion. This observation suggests the possibility that some cases of pulmonary fibrosis of unknown aetiology may be due to previous mycoplasmal infection.


Effect of Mycoplasma pheumoniae infection on cell-mediated immunity.

The effect of Mycoplasma pneumoniae infection on cell-mediated immunity was examined by two methods: the first method was the tuberculin skin test and the other was the measurement of the in vitro lymphocyte stimulation response to purified protein derivative (PPD) of tuberculin. Twenty-nine patients out of a total of 47 patients with a lower respiratory tract illness caused by M. pneumoniae had a negative tuberculin skin test when first tested. Twenty-three out of 26 patients with a negative tuberculin reaction in the early phase of the illness had a positive skin test when they were retested several weeks or months after the illness. The lymphocyte stimulation response to PPD was examined in 13 patients. In eight of these cases the lymphocyte response to PPD was significantly lower during illness than after recovery. Six control subjects showed no significant difference in their lymphocyte responsiveness to PPD when examined on two different occasions. These studies show that M.pneumoniae infection causes transient depression of cell-mediated immunity.