Synthesis of LH-RH by rat hypothalamic tissue in vitro. II. Effect of short-term orchiectomy and estradiol benzoate therapy. Normal, castrate and estradiol benzoate (EB; 1 microgram/100 g b.w. x 6d, s.c.)-treated castrate male rats were utilized to study the short term effects of these treatments upon the incorporation of 3H-glycine into LH-RH in vitro. The rise in serum LH and FSH observed in the untreated castrates was prevented by EB therapy. The treatment had no significant effect upon serum LH-RH levels or the incorporation of 3H-gly into LH-RH. EB treatment markedly (p less than 0.01) increased the hypothalamic LH-RH concentration and significantly lowered the specific activity (nCi/ng) of the 3H-gly-LH-RH (p less than 0.05). These results suggest that EB acts both on the pituitary and hypothalamus to suppress gonadotropin (Gn) release, but that, at the time period studied, neither castration or EB-treatment had any apparent effect upon hypothalamic LH-RH synthesis.


Inhibition of prostaglandin-enhanced release of LH by antiserum to luteinizing hormone releasing hormone. Prostaglandin E2 (PGE2), PGF2alpha, PGF2beta was infused into a lateral ventricle of the brain of adult male rats, after pretreatment with normal rabbit serum (NRS) or anti-LH-RH serum, and the concentration of LH in arterial plasma was determined. I.v. administration of anti-LH-RH serum 2.5 min prior to the infusion of 2 microgram or 20 microgram of PGE2 significantly inhibited the PGE2-induced rise of plasma LH. Intraventricular infusion of 20 microgram of PGF2alpha or PGF2beta into NRS-pretreated animals caused a marked increase in the plasma LH concentration; whereas, prior i.v. administration of anti-LH-RH serum blocked the PG-induced rise in plasma LH levels. It is concluded that PGE2, PGF2alpha, and PGF2beta stimulate the release of LH primarily by enhancing the release of LH-RH.


The status of the corticotropin releasing factor (CRF). Early in the history of studies on the release of ACTH by stress there were indications that ACTH might be released by multiple factors. But the neurohumoral theory, as formulated by G.W. Harris, suggested that every hypophysial hormone had its unique hypothalamic controlling agent and a search for the unique ACTH-releasing hormone went on for about 20 years. This review reexamines the case for multiple releasers of ACTH.


Advances in the study of diffusion of innovation in health care organizations. Federal government programs of the 1960s to rapidly diffuse technologies have been displaced on the '70s by efforts to constrain costly technological growth. As a guide to action, the understanding of reasons for adoption of innovation is essential; but the utility of available diffusion theory is limited by its focus on the speed of diffusion rather than any reasons for its adoption by organizations. In a practical sense, more is known about the administrator as decision maker than about those increasing situatiions in which physicians play a more central part. Until coherent, empirically grounded theories of organizational innovation are available, large-scale "tests" are premature and wasteful.


The smear technique in the diagnosis of neurosurgical biopsies. This paper reviews 216 consecutive neurosurgical biopsies examined by the immediate smear technique, and the smear diagnoses are compared with the final diagnoses made on paraffin processed sections of the same material. Ninety three percent (93%) of the diagnoses were correct. The majority of errors were due to the incorrect classification of malignant tumours. The diagnosis of malignancy, however, was clearly established in all of these cases. The smear technique is suitable for application to material obtained at craniectomy, laminectomy, and also the small, soft pieces of tissue obtained by needle biopsy through a burr hole.


Sodium valproate (Epilim) in the treatment of refractory epilepsy. Sodium valproate was given to seven children with refractory epilepsy and mental retardation. Four of the children became fit free while another was much improved. Plasma levels of sodium valproate correlated well with the dose prescribed and did not approach the theoretical top-desirable level of 200 microgram/ml despite larger than recommended doses. Side effects were minimal and it is concluded that the drug is safe and useful.


Rheumatic fever and streptococci: the Wairoa College study. The decline in incidence of rheumatic fever seen in many countries is not evident in New Zealand. Wairoa county has the highest hospital admission rate within New Zealand, 232 per 100 000 per year, five times the national average, 43 per 100 000. Studies in Wairoa included a cross-sectional survey of the local secondary school. Throat swabbing yielded 13.6% of subjects positive for beta-haemolytic streptococcus group A. Boys had a higher rate than girls, and girls aged 14 and over had a lower rate than younger girls. Discriminant analysis failed to identify ethnic, social or geographic factors as contributing to positivity. Sibling concordance was not significant. ASO titres were high in comparison with another New Zealand study (Rotorua Lakes). There was an association between high ASO titre and throat swab positive for group A and group C streptococci. The prevalence of definite rheumatic fever and rheumatic heart disease was established as 11/715 (1.5%). A wide range of residential geographic, climatic and socioeconomic factors failed to discriminate between cases and noncases. Ethnicity alone was a significant discriminator, the cases being more Maori than noncases.


Goodpasture's syndrome complicated by nocardia asteroides infection. A case of Goodpasture's syndrome--an immunological disorder characterised by a proliferative glomerunlonephritis with haemorrhagic pulmonary alveolitis--is described. There has been complete functional recovery of the presenting renal failure, but the immunosuppressive therapy was complicated by a severe episode of metastasising nocardiosis.


The biologic activities of cystic fibrosis serum. II. Ultrastructural aspects of the effect of cystic fibrosis sera and calcium ionophore A23187 on rabbit tracheal explants. Ultrastructural and cytochemical observations indicate that both cystic fibrosis (CF) sera and calcium ionophore A23187 induce a swelling or an increase in the size and possibly the number of secondary lysosomes and an increase in mucus secretion in epithelium of the rabbit tracheal bioassay system. Extended incubation of the rabbit tracheal explants with either CF or control sera produces a cytotoxic effect on the tracheal epithelium, but only after the termination of the normal bioassay time period. Comparative ultrastructural study of the effect of both CF sera and calcium ionophore A23187 on the rabbit tracheal bioassay system indicates that increased membrane permeability to calcium may be important in the production of the ciliary dyskinesia response by CF serum factor(s) in the rabbit tracheal bioassay system.


Increased secretion of Müllerian inhibiting substance after immunological blockade of endogenous luteinizing hormone releasing hormone in the rat. In order to evaluate the role of leuteinizing hormone releasing hormone (LHRH) and gonadotropins in the control of secretion of Müllerian inhibiting substance, groups of pregnant rats were injected intraperitoneally with high potency antiserum from a rabbit immunized with LHRH. Pregnant females were injected at 13 and 20 days of gestation with LHRH antiserum or an equal volume of normal rabbit serum as a control. The testes and penis were reduced in weight and size in 6-day-old pups of the experimental group indicating the luteinizing hormone (LH) was blocked and that LHRH antiserum was active. Testicular fragments of 17-day fetuses and 6-day-old pups showed an increase relative to controls in Müllerian inhibiting substance activity in a graded organ culture bioassay system. These studies suggest that secretion of Müllerian inhibiting substances is curtailed by one or both gonadotropins.


Effects of diet and behavior therapy on social and motor behavior of retarded phenylketonuric adults: an experimental analysis. The effects of a low phenylalanine diet on six retarded phenylketonuric adults were assessed. An ABA individual-subject design was used in experiment I to assess the effects of a low phenylalanine diet on social and motor behavior. Following a baseline during which the subjects ingested a normal phenylalanine diet (phase A), a low phenylalanine diet (phase B) was administered in a double blind fashion. Finally, the baseline condition (phase A) was reinstated (normal diet). The low phenylalanine diet resulted in few significant behavioral changes for those subjects with which proper methodologic controls were employed. However, for two of six subjects motor behavior, including stereotypy and tremor, seem to have ameliorated. In experiment II, applied behavior analysis techniques, including differential reinforcement of other behavior and time out, were combined to radically reduce the frequency of stereotypy and self-abuse exhibited by one of the six subjects of experiment I.


Primary pediatric care in one community. Primary pediatric practice in one community was studied by using a household interview survey, a pediatrician mail questionnaire, and an ambulatory care survey of nine practices reporting on all visits over a four-week period. The results for the study year 1975 are compared with those for 1971 and 1967. Pediatricians provided an ever-increasing proportion of ambulatory care. Of all the children who had a regular physician in 1967, only 47% had a pediatrician; by 1975, this proportion had increased to 74%. Well-child care continues to be the largest diagnostic category (30%), followed by treatment for upper respiratory tract infections (24%), otitis media (14%), and lower respiratory tract infections (6%). Variations by practice and patient characteristics are examined. If the observed changes indicate a nationwide trend, a larger number of pediatricians will be needed to cover their growing share in primary care for children. Working in multiple settings and delegating part of the work load to nurse practioners have helped to meet the growing demand.


Renal transplantation in children ages 1 to 5 years. Renal transplantation was carried out in 21 children ages 1 to 5 years. Eighteen received grafts from a living, related donor (LRD). Four children died, one following rejection, and three because of infection. Five children lost their initial grafts and two have received new transplants. Cumulative patient survival two and four years following LRD transplantation was 94% and 76%, respectively. This was similar to results found in children ages 6 to 14 years. Accelerated growth rates were seen in the first posttransplant year in those small children who were severely growth-retarded at the same time of transplantation and who achieved normal graft function. However, only one of these children ultimately reached the tenth percentile for height for chronological age. We conclude that renal transplantation is warranted in the very young child with renal failure.


Deep hypothermia in infant cardiac surgery. The value of infant cardiac surgery using deep hypothermia remains a debate. A steady number of cardiac centers have consented to this approach in spite of some filibuster. Physiologists are frightened, anesthetists may find it cumbersome, but surgeons using it enjoy the ease of correction in a bloodless and relaxed heart. The cardiologists may document acceptable results, but we also need the alert feedback from the provider of long-term health care--the pediatrician--to document possible flaws of this pristine modality. This article is intended to familiarize the pediatrician with the method of deep hypothermia: its origin, application, and appeal for consumer protection.


The projective process: inferences derived from structural analysis. It is hypothesized that projection is an organizational process involving a synthesis of psychological functions which results in a response which in uniquely representative of a class of important psychological experiences. Implications of this interpretation are discussed.


An exploratory study of the draw-a-person as a measure of racial identity. The race of the figure drawn on the Draw-A-Person Test is proposed as a measure of acceptance of racial identity. Reliability and validity of this measure were explored in a two-part study. Part 1 confirmed the hypothesis that the race of the figure drawn is related to the race of the child producing the drawing. Comparison of the figures drawn by black (n = 157) and white (n = 167) children confirmed three other hypotheses based on the voluminous literature suggesting that black children are less accepting of their racial group membership than whites. These hypotheses were: (a) whites should be more likely to draw figures that are clearly white than blacks are to draw figures that are clearly black, (b) whites should be less likely to draw blacks than blacks are to draw whites, and (c) blacks should be more likely to avoid giving clear indication of the race of the figures they draw than are whites. Inter-rater reliability for the race of the figure drawn was .79. Five weeks after the initial drawing, a subsample of 28 black children drew a second figure and performed a picture choice task designed to assess acceptance of racial identity. The race of the figure drawn showed a test-retest reliability of .53 and correlated significantly with the other measure of racial identity (r27 = .39).


[Evaluation of some methods for study of the pathogenecity and toxicity among enteropathogenic suspect E. coli strains (author's transl)]. The current methods for testing enteropathogenic E. coli have been revised and slightly modified for use in our laboratory. Their applicability as screening tools in epidemiological surveys is discussed. It is concluded that the current methods for detecting these E. coli in epidemiological surveys are inadequate and laborious and the need for a simple field method is stressed.


[Hypogonadotrophic hypogonadism. Pituitary and testicular reactivity--receptivity to androgens (author's transl)]. Six subjects aged between 19 and 29 years were studied. Gonadotrophins, follicular stimulating hormone or FSH and luteotrophic hormone or LH, were low in all cases. Under the influence of a single dose of 150 microgram of hypothalamic gonadotrophin liberation factor (LHRH), there was a preferential increase in FSH whilst levels of LH were little influenced. The continuous infusion of LHRH was associated with the same phenomenon. Only prolonged administration (for approximately 12 months) of chorionic gonadotrophins, resultes in a significant rise in plasma testosterone levels (low in all cases in the absence of stimulation). The level of urinary 3alpha-androstanediol represents a good parameter of androgenicity. Urinary 3beta-androstanediol is a metabolite of androgens formed in the liver. In hypogonadotrophic hypogonadism, and in particular in de Morsier's syndrome, the essential element would seem to be the absence of solicitation of the pituitary gonadotrophic cells by virtue of inadequate secretion of LHRH. The results of stimulation with chorionic gonadotrophins reflects the existence of inadequate maturation of testicular receptors to these hormones.


[Microangiopathic anaemia with thrombocytopaenia. Cure following excision of an angioma of the small intestine (author's transl)]. The association of a mixed anaemia (by occult haemorrhage and microangiopathic haemolysis) with a thrombocytopaenia led to a search for a digestive angioma. Arteriography, followed by exploratory laparotomy with preoperative enteroscopy and frozen section histological examination, led to the discovery of a small bowel angioma (multiple phlebectasias) which was partially resected. A review of the literature emphasised the rarity of intestinal angiomas with thrombocytopaenia (Kasabach and Merrit syndrome) and forms a basis for the discussion of haematological abnormalities (intravascular coagulation, microangiopathic anaemia) which may be induced by such vascular malformations.


[Arterial hypertension: the role of the central nervous system. I. The nervous control of blood pressure (author's transl)]. Arterial pressure is rapidly and precisely readjusted by various reflexes. They are described from the anatomical and functional level. The most important is the medullary baroreflex. In spite of the complexity of their nervous connections and the numerous mediator substances involved, the cardiac vagal center and the sympathetic vasomotor centers are today better understood. The role of the brain is not purely reflex because it may also respond to biochemical variations (anoxia, circulating angiotensin). Finally, we shall describe the central mechanisms which play a role in situations as orthostatism, physical effort or stress. In relation to stress, we shall discuss the influence of suprabulbar structures on the baroreflexe and this will allow a description of three connected centers at different levels controlling arterial blood pressure via nervous mechanisms (i.e. diencephalic, medullary and spinal centers).


The nucleoside sequence of tyrosine tRNA from Bacillus stearothermophilus. The nucleotide sequence of tRNATyr from B. stearothermophilus has been determined: pG-G-A-G-G-G-G-s4U-A-G-C-G-A-A-G-U-Gm-G-C-U-A-A-m1A-C-G-C-G-G-C-G-G-A-C-U-Q-U-A-ms2i6A-A-psi-C-C-G-C-U-C-C-C-U-U-U-G-G-G-U-U-C-G-G-C-G-G-T-psi-C-G-A-A-U-C-C-G-U-C-C-C-C-C-U-C-C-A-C-C-AOH. A combination of classical fingerprinting methods, partial nuclease P1 digestion and two-dimensional homochromatography and a rapid "read off" sequencing gel technique were used to establish the complete nucleotide sequence.


Application of a rapid gel method to the sequencing of fragments of 16S ribosomal RNA from Escherichia coli. A gel sequencing method has been applied to two 5' end-labelled fragments of the 16S ribosomal RNA from E. coli. The procedure involves partial enzymatic hydrolysis by ribonucleases T1, U2 or A, in order to generate series of end-labelled subfragments terminating in guanine, adenine, or pyrimidine residues, respectively. The two fragments concerned were approximately 75 and 90 nucleotides in length, and both arose from the 3' region of the 16S RNA. The sequences deduced are compared with the published sequence of 16S RNA, and contribute information to the final ordering of the ribonuclease T1 oligonucleotides in the latter, as well as revealing some probable errors.


1H NMR of valine tRNA modified bases. Evidence for multiple conformations. Methyl and methylene protons of dihydrouridine 17 (hU), 6-methyladenosine 37 (M6A), 7-methylguanosine 46 (m7G), and ribothymidine 54 (rT) give clearly resolved peaks (220 MHz) for tRNA1val (coli solutions in D2O, 0.25 m NaCl, at 27 degrees C. Chemical shifts are generally consistent with a solution structure of tRNA1val similar to the crystal structure of tRNAphe (yeast). At least 3 separate transitions are observed as the temperature is raised. The earliest involves disruption of native tertiary structure and formation of intermediate structures in the m7G and rT regions. A second transition results in a change in structure of the anticodon loop, containing m6A. The final step involves unfolding of the m7G and rT intermediates and melting of the TpsiC helix. Low salt concentrations produce multiple, partially denatured conformations, rather than a unique form, for tRNA1val. Native structure is almost completely reformed by addition of Na+ but Mg2+ is required for correct conformation in the vicinity of m7G.


The nucleotide sequence of formylmethionine tRNA from Mycoplasma mycoides sp. capri. The nucleotide sequence of Mycoplasma mycoides sp. capri PG3 formylmethionine tRNA has been determined, using in vitro labeling techniques, to be pC-G-C-G-G-G-G-s4U-A-G-A-G-C-A-G-U-D (U)-G-G-D-A-G-C-U-C-G-C-C-G-G-G-C-U-C-A-U-A-A-C-C-C-G-G-A-G-G-C-C-G-C-A-G-G-U-psi- C-G-A-G-U-C-C-U-G-C-C-C-C-C-G-C-A-A-C-C-AOH. This tRNA contains only three modified nucleosides s4U, D and psi, all of which are derived from uridine. Both in the structural features which distinguish eukaryotic from prokaryotic initiator RNAs and in the overall sequence, this tRNA resembles a typical prokaryotic initiator tRNA. A comparison of the sequence of this tRNA with those of other prokaryotic initiator tRNAs suggests that taxonomically the Mycoplasma may be less related to the Cyanophyta (Anacystis nidulans) than to the bacteria and less related to the Enterobacteriaceae (Escherichia coli) than to the Bacillaceae (Bacillus subtilis).


The identification of the tRNA substrates for the supK tRNA methylase. Purified preparations of the tRNA methylase deficient in supK strains of Salmonella typhimurium transfer methyl groups from S-adenosylmethionine (SAM) to at least two tRNA species, an alanine tRNA and a serine tRNA. The identity of the tRNA substrates for this enzyme was determined by a change in the elution position of the methyl-labeled tRNA from BND-cellulose columns before and after aminoacylation with a specific amino acid followed by derivatization of the free primary amino group with phenoxy- or naphthoxyacetate. The radioactive methyl group enzymatically added to these tRNAs is both acid and base labile and can be hydrolyzed to a volatile product at pHs above 7.5 and also at pH 1. The methylated 3'-nucleotide isolated from digested tRNA is a pyrimidine derivative and chromatographs like a modified uridylic acid. Its identity has not been established, but it is likely that it corresponds to the methyl ester of V, uridin-5-oxyacetic acid.


Preparation and properties of insolubilized restriction endonucleases. Type II restriction endonucleases Bam HI and Eco RI were covalently coupled to Sepharose. These insolubilized enzymes generated fragment patterns for several viral DNAs identical to those produced by the respective free enzymes. Conditions for optimal activity were similar for both bound and unbound forms of the enzymes. Insolubilization improved thermal stability of Bam HI and Eco RI. The bound enzyme can be recovered from reaction mixtures and reused several times. Upon storage at 4 degrees C, coupled endonucleases remained stable for several months.


Template specific inhibitors of E. coli RNA polymerase. Electroneutral analogs of polynucleotides, poly-9-vinyladenine and poly-1-vinyluracil inhibit E. coli RNA polymerase in all combinations where the single stranded polynucleotides are used as templates and the vinyl analogs are complementary to them. As templates both the ribo- and deoxyribopolynucleotides were tested; variation of the template concentration in the presence of vinyl analogs produced a competitive pattern of inhibition. The electroneutral analogs do not inhibit the enzyme activity when non-complementary single stranded polynucleotides or double stranded polynucleotides are used as templates; the latter fully supports transcription even when one of the strands is complementary to the analog.


Studies on ribosome structure and interactions near the m62Am62A sequence. Antibodies raised against N6, N6-dimethyl adenosine were used to study the environment and role of the m62Am62A sequences in the E. coli ribosome. It is observed that this sequence is exposed on the surface of isolated 30S subunits, but becomes inaccessible for IgG interaction upon heat activation. The m62Am62A sequence is also inaccessible for IgG interaction in 70S ribosomes or 30S subunits immediately after dissociation of 70S particles. The presence of IgGs results in a significant inhibition of IF3 binding to unactivated 30S particles. IF3 binding to activated 30S subunits is unaffected by the IgGs. Crosslinking of 30S proteins S18 and S21 with the bifunctional phenylene dimaleimide reagents results in a reduction in the extent of 30S-IgG interaction. From what is already known about the location of S18, S21 and the IF3 binding site, it is suggested that the m62Am62A sequence is located close to the initiator tRNA binding site of the 30S subunit during initiation of protein synthesis.


The effect of specific structural modification on the biological activity of E. coli arginine tRNA. Escherichia coli arginine tRNA1 has been modified at position s2C32 with iodoacetamide and a spin labelled derivative. The small effects on the charging ability of tRNA by the modifiications suggest that the synthetase does not bind to the tRNA in this region of the anticodon loop before the anticodon. A ternary complex of elongation factor Tu, GTP and the modified Arg-tRNA, can be formed allowing future studies of enzymatic binding to the ribosome. Using the triplet binding assay the native Arg-tRNA1 decodes all 4 codons beginning with CG. The modified Arg-tRNA1 has a restricted decoding but the decoding pattern is still unusual according to the Wobble Hypothesis.


Recombinant plasmids containing Xenopus laevis globin structural genes derived from complementary DNA. Details are presented of the in vitro synthesis of double-stranded DNA complementary to purified Xenopus globin messenger RNA, using a combination of reverse transcriptase, fragment 'A' of E. coli DNA polymerase 1 and S1 endonuclease. After selection of duplex DNA molecules approaching the length of Xenopus globin messenger RNA by sedimentation of the DNA through neutral sucrose gradients, the 3'-OH termini of the synthetic globin gene sequences were extended with short tracts of oligo dGMP using terminal transferase. This material was integrated into oligo dCMP-extended linear pCR1 plasmid DNA and amplified by transfection of E. coli. Plasmids carrying globin sequences were identified by hybridization of 32P-labelled globin mRNA to total cellular DNA in situ, by hybridization of purified plasmids to globin cDNA in solution, by analysis of recombinant DNA on polyacrylamide and agarose gels, and by heteroduplex mapping. The results show that extensive DNA copies of Xenopus globin mRNA have been integrated into recombinant plasmids.


Binding of E. coli RNA polymerase to chromatin subunits. Chromatin subunits were prepared from purified rat liver nuclei and the template properties of the nucleosome preparation studied. It was found that: 1) The fundamental template restriction of chromatin (as compared to deproteinized DNA) is retained in the isolated nucleosomes, 2) On the average one molecule of RNA polymerase is bound to one molecule of DNA purified from nucleosomes, 3) The number of RNA polymerase binding sites on chromatin subunits is 6 to 20 times lower than that of the DNA extracted from these subunits, 4) Transcription can proceed through nucleosomes resulting in RNA chains approximately 150 nucleotides long.


Influence of gonadotropic releasing hormone, luteinizing hormone and pineal extracts on testes of immature cockerels. Two, seven, and ten-day-old S.C.W.L. cockerels were injected with pineal extract (PE), gonadotropic releasing hormone (GnRH) and luteinizing hormone (LH), alone or in combination, to determine the effect of PE on the action of exogenous GnRH and LH on the testis in immature cockerels. Radioactive phosphorus (P-32) uptake by the testis was used as an assay for gonadotropic activity. GnRH had no effects on cockerels aged two days. However, LH caused increased P-32 uptake compared to the saline control at this age. In seven- and ten-day-old cockerels, PE in combination with GnRH resulted in lower P-32 c.p.m./g. of testis compared to the non-PE treated birds at the same doses of GnRH. On the other hand, PE did not cause any decrease in testis response to LH. These results indicate that PE is acting to inhibit release of gonadotropins by GnRH.


[Effect of L-DOPA administration on brain bioelectrical activity in hypothalamo-hypophyseal diseases]. The influence of the L-DOPA preparation on the bioelectrical activity of the brain was studied in 15 patients with Itsenko-Cushing's disease and in 12 patients with diencephalic obesity. L-DOPA administration caused an increase of the theta-rhythm index in the anterior leads in comparison with the initial recording, although the periods of detection of this elevation differed in various patients. No changes of the character of the EEG recording during the test with L-DOPA in comparison with the background recording was revealed in the patients with Itsenko-Cushings disease.


[Choice of the optimal method in the mathematical diagnosis of thyroid gland diseases]. On the basis of analysis of case histories of patients with various functional conditions of the thyroid gland it was found that the use of the stage-by-stage program of mathematical diagnosis of the thyroid diseases was more expedient in clinical and economic respect than the use of a one-stage program with single introduction of the whole initial information concerning the patient's condition.


[Creation of an artificial vagina in persons with male pseudohermaphroditism]. The author elaborated a method of creation of an artificial vagina in patients with false male hermaphroditism during puberty from the skin of the removed clitoris, with the correction of external genitalia in the female direction. This method is harmless, the operative technique is simple. Positive anatomical and cosmetic results were obtained in two patients with the mentioned pathology.


[Effect of Complamin on the intrahepatic blood flow and pancreatic secretion of enzymes in diabetes mellitus]. Complamine (xanthinol-nicotinate) injected intravenously in a dose of 300 mg caused in patients with diabetes mellitus a significant, although short-lived improvement of the indices of intrahepatic circulation (by the rheohepatographic criteria). By itself complamine failed to influence the pancreatic secretion of amylase, lipase, and trypsin, but regularly intensified the stimulating action of pancreosimine on the pancreatic secretion of the enzymes in the patients with diabetes. In addition to the known influence of complamine on the circulation in the lower limbs of the patients with diabetes mellitus, information presented in the given work widened the circle of indications to the therapeutic use of complamine in patients with diabetes mellitus with disturbances of intrahepatic hemodynamics and the enzyme-secretory insufficiency of the pancreas. Complamine should be administered after meals at the period of the greatest release of the endogenous pancreosimine, for the intensification of the pancreatic enzymes secretion.


[Segmental transplantation of the pancrease from a living donor (an experimental anatomical study)]. The results of the investigation of the blood supply by the splenic vessels of the human and dog pancreatic segment (120 observations) and the results of 98 chronic experiments with pancreatic resection and grafting on the vascular pedicle formed by the splenic artery and vein are presented. Experiments showed transplantation of the caudal pancreatic segment (about 1/5 of the whole organ) to be possible. Resection of the segment failed to affect the dog health. The grafted segment insured normal glycemia in depancreatized dogs.


[Further study of the hormonal regulation of natural immunity to weak transplantation antigens in inbred mice]. Blood plasma corticosterone level and the extent of immunological reaction to sex-antigen of skin transplant in inbred mice CBA, C57Bl/6, F1 (CBA X 57Bl/6), C3H, AKR was compared. Mice CBA had a high blood plasma corticosterone level and no immunological reaction to sex-antigen. A lower blood corticosterone level and the presence of reaction to sex-antigen was characteristic of mice C57Bl/6, AKR, C3H, F1(CBA X C57Bl/6). The number of endogenous colonies in the spleen of mice CBA was less than in mice C57Bl/6. Mice CBA had a narrow cortical thymus layer in comparison with the wide thymus cortex of mice AKR and C57Bl/6. Adrenalectomy of mice CBA caused a sharp widening of the thymus cortex.


Site-specific initiation of a DNA fragment. The first step in the replication cycle of the single-stranded DNA phages is the conversion of the infecting positive strand circle to a duplex ring. This event involves the de novo initiation of a negative strand, using the infecting positive strand cycle as a template. The synthesis of the negative strand is in many respects analogous to the formation of a fragment during cellular DNA replication. In this paper we describe the initiation of the negative strand of bacteriophage G4. The data establish that, in vivo, the synthesis of the G4 negative strand is initiated at a specific site, which we have mapped on the 5400-base viral chromosome.


Cyclopenta[c,d]pyrene: a highly mutagenic polycyclic aromatic hydrocarbon. A polycyclic aromatic hydrocarbon recently isolated from carbon black and identified as cyclopenta[c,d]pyrene (CPP) is highly mutagenic. By the criteria of the Salmonella/mammalian-microsome mutagenicity test, the mutagenic potency of CPP is equalled by only two other naturally occurring polycyclic aromatic hydrocarbons--benzo[a]pyrene and dibenz[a,c]anthracene. The potent mutagenicity of CPP is noteworthy for two reasons: (i) CPP is a mutagenic polycyclic aromatic hydrocarbon without a "bay-region" and (ii) there is evidence that it is distributed widely in the environment. On the basis of experimental observations and perturbational molecular orbital calculations we propose that a mutagenic metabolite of CPP will be the 3,4-oxide. The carbonium ion derived from opening of CPP 3,4-oxide is identical to that derived from opening of benzo[a]pyrene 7,8-diol-9,10-oxide, the metabolite now thought to be an ultimate mutagenic and carcinogenic species.


Positive control of D-serine deaminase synthesis in vitro. Efficient constitutive synthesis of D-serine deaminase [D-serine hydro-lyase (deaminating); EC 4.2.1.14] is obtained in vitro by using a slightly modified Zubay system programmed with dsdO6 dsdA+DNA. Synthesis from a dsdO+ dsdA+ template requires active dsdC gene product and 3':5'-cyclic AMP. In vitro synthesis of dsdC product is obtained with a dsdC+ dsdO+ dsdA+ or a dsdCc dsdO+ dsdA+ template; this synthesis is thermosensitive and can be uncoupled from D-serine deaminase synthesis by temperature shift.


Excision of DNA segments introduced into cloning vectors by the poly(dA-dT) joining method. A method is described for excising cloned DNA segments that have been inserted into their vectors by poly(dA-dT) joins. The recombinant DNA is cleaved within the vector DNA portion by one or more restriction endonucleases to generate a linear DNA molecule with the insert DNA sequence flanked by the poly(dA-dT) joins. After denaturation, the single strands "snap back" because of the intrastrand poly(dA) and poly(dT) sequences to form circular structures with "tails" of vector DNA. The vector portion of the DNA is then digested by Escherichia coli exonuclease VII, while the insert portion remains resistant to attack. The resistant strands are annealed and purified by electrophoresis in agarose. The insert DNA segment free of contaminating vector sequences can be used as a hybridization probe and for insertion into a new vector since suitable cohesive termini are generated from the retained poly(dA) and poly(dT) tails by an appropriate exonuclease.


Purification of subunits of Escherichia coli DNA gyrase and reconstitution of enzymatic activity. Extensively purified DNA gyrase from Escherichia coli is inhibited by nalidixic acid and by novobiocin. The enzyme is composed of two subunits, A and B, which were purified as separate components. Subunit A is the product of the gene controlling sensitivity to nalidixic acid (nalA) because: (i) the electrophoretic mobility of subunit A in the presence of sodium dodecyl sulfate is identical to that of the 105,000-dalton nalA gene product; (ii) mutants that are resistant to nalidixic acid (nalA(r)) produce a drug-resistant subunit A; and (iii) wild-type subunit A confers drug sensitivity to in vitro synthesis of varphiX174 DNA directed by nalA(r) mutants. Subunit B contains a 95,000-dalton polypeptide and is controlled by the gene specifying sensitivity to novobiocin (cou) because cou(r) mutants produce a novobiocin-resistant subunit B and novobiocin-resitant gyrase is made drug sensitive by wild-type subunit B. Subunits A and B associate, so that gyrase was also purified as a complex containing 105,000- and 95,000-dalton polypeptides. This enzyme and gyrase reconstructed from subunits have the same drug sensitivity, K(m) for ATP, and catalytic properties. The same ratio of subunits gives efficient reconstitution of the reactions intrinsic to DNA gyrase, including catalysis of supercoiling of closed duplex DNA, relaxation of supercoiled DNA in the absence of ATP, and site-specific cleavage of DNA induced by sodium dodecyl sulfate.


DNA-dependent single-step addition reactions catalyzed by Escherichia coli RNA polymerase. The addition of a single nucleotide to a short oligonucleotide, catalyzed by RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) in the presence of synthetic DNA templates, has been studied. The reactions A-U + ATP leads to A-U-A and U-A + UTP leads to U-A-U occur in the presence of poly[d(A-T)], while the reactions G-C + GTP leads to G-C-G and C-G + CTP leads to C-G-C take place in the presence of poly[d(I-C)]. These reactions proceed with a turnover of enzyme. The products U-A-U and C-G-C are formed rapidly, while A-U-A and G-C-G are formed much more slowly. Another poly[d(A-T)]-dependent reaction, which occurs with a turnover of enzyme, is U-A-U + ATP leads to U-A-U-A. All of these reactions are only partially inhibited by rifampicin. ATP can be replaced by 3'-deoxyadenosine 5'-triphosphate in the reactions A-U + ATP leads to A-U-A and U-A-U + ATP leads to U-A-U-A, though the rate of formation of the products becomes somewhat slower. The reactions involving 3'-deoxyadenosine 5'-triphosphate are almost completely inhibited by rifampicin, indicating that the 3'-hydroxyl group is necessary for these reactions to occur in the presence of rifampicin.


Attack of sea urchin eggs by dogfish phagocytes: model of phagocyte-mediated cellular cytotoxicity. To test whether lysosomal degranulation of phagocytes is associated with antibody-dependent cytotoxicity, eggs of Arbacia punctulata were used as targets for blood phagocytes of Mustelus canis. Eggs were coated with heat-aggregated dogfish IgM and exposed to phagocytes, and cytolysis of eggs was observed by Nomarski optics. Phagocytes adhered, degranulated, and raised fertilization membranes resembling those induced by sperm or ionophore A23187. Lysis was then observed as damage radiating from the point of phagocyte-egg contact. By 4 hr, coated eggs exposed to phagocytes released 8.9, 12.3, and 7.4% of total catalase (EC 1.11.1.6), beta-glucuronidase (EC 3.2.1.31), and superoxide dismutase (EC 1.15.1.1) into the medium. Cytotoxic enzyme release significantly exceeded that from uncoated eggs incubated with phagocytes or eggs alone (uncoated or coated). Because activated eggs release a neutral protease, it was considered possible that this enzyme might be responsible for autolysis of eggs. This possibility was excluded because (i) lysis of eggs was not inhibited by soybean trypsin inhibitor (SBTI) whereas the egg protease was sensitive to SBTI, and (ii) the major trypsin-like activity of phagocytes was not inhibited by SBTI. These experiments demonstrate that Ig-coated cells are first activated, and then killed, when exposed to degranulating phagocytes and suggest that enzymes from attacking phagocytes, and not target cells, are responsible for cell death.


Promotion of monolayer formation in cultured whole pancreatic islets by 3-isobutyl-1-methylxanthine. Normal adult rat islets usually remained intact and encapsulated, even after many days in culture. In contrast, islets cultured in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.1 mM) attached more readily to the surface of plastic culture dishes and almost uniformly formed monolayers of endocrine cells. The mechanism of this effect is not known but presumably involves increases in cellular cyclic AMP content. Fibroblast growth did not appear to be stimulated by the inhibitor. These adult pancreatic endocrine monolayer cultures can be produced readily and provide useful preparations for further morphological and biochemical studies of factors affecting the differentiation, growth, and regenerative capacity of islet cells.


Mutagenesis during in vitro DNA synthesis. The error frequency of in vitro DNA synthesis using a natural DNA template has been measured with a biological assay for nucleotide substitutions. phiX174 DNA containing an amber mutation was copied in vitro by Escherichia coli DNA polymerase I, and the reversion frequency of the progeny DNA was determined by transfection of E. coli spheroplasts. E. coli polymerase I makes less than 1 mistake at the am3 locus for every 7700 nucleotides incorporated under standard reaction conditions. Substitution of Mn2+ for Mg2+ and unequal concentrations of deoxynucleoside triphosphate substrates raises this mutation frequency to greater than 1 in 1000. Thus, E. coli DNA polymerase I can copy natural DNA templates with high fidelity and its accuracy can be affected by alterations in reaction conditions.


Transformation of yeast.

Transformation of yeast. A stable leu2- yeast strain has been transformed to LEU2+ by using a chimeric ColE1 plasmid carrying the yeast leu2 gene. We have used recently developed hybridization and restriction endonuclease mapping techniques to demonstrate directly the presence of the transforming DNA in the yeast genome and also to determine the arrangement of the sequences that were introduced. These studies show that ColE1 DNA together with the yeast sequences can integrate into the yeast chromosomes. This integration may be additive or substitutive. The bacterial plasmid sequences, once integrated, behave as a simple Mendelian element. In addition, we have determined the genetic linkage relationships for each newly introduced LEU2+ allele with the original leu2- allele. These studies show that the transforming squences integrate not only in the leu2 region but also in several other chromosomal locations.


Erythrocytic mechanism of sickle cell resistance to malaria. The physiological basis for the resistance to falciparum malaria individuals with sickle cell trait has not been understood. Recent advances in erythrocytic Plasmodium falciparum culture have made possible a direct investigation of the development of the malaria parasite in cells with sickle cell homoglobin. In a high (18%) oxygen atmosphere, there is no apparent sickling of cells, and the growth and multiplication of P. falciparum is identical in normal (AA), hemoglobin S homozygous (SS), and hemoglobin S heterozygous (SA) erythrocytes. Cultures under low (1-5%) oxygen, however, showed clear inhibition of growth. The sickling of SS red cells killed and lysed most or all of the intracellular parasites. Parasites in SA red cells were killed primarily at the large ring stage, probably as a result of a disruption of the parasite metabolism. Incubation in cyanate prior to culture reversed the resistance of SA erythrocytes to plasmodium growth, but had no effect on SS red cell sickling or resistance. Thus, the mechanism of resistance in vivo may be due solely to intraerythrocytic conditions.


Epidemiological research on the relationship between tobacco, alcohol and cancer. Several studies of descriptive and analytic epidemiology have permitted the investigation of cancers linked to the use of tobacco and alcohol. The tobacco and alcohol cancer group consists of the upper respiratory and alimentary tract, lung and bladder, which accounts for 50% of the cancer in men. When both factors are implicated, the proper role of each could be established. These data should be considered in decision-making for cancer prevention.


The effect of a quaternary ammonium-containing mouthwash on formed plaque. The effect on formed dental plaque of a commercial mouthwash containing cetylpyridinium chloride (CPC) was evaluated in forty-one adults. During this fourteen day study no oral hygiene other than the use of a mouthwash was provided. Plaque and gingival indices were scored on sixteen teeth at days 0, 7 and 14. The results of this study suggested that subjects using the CPC containing mouthwash formed less plaque than those using the placebo mouthwash. No change in the Gingival Index was observed. Of those patients using the CPC containing mouthwash, four showed a slight staining of the anterior teeth and five reported a mild burning sensation of the tongue.


Epinephrine absorption from retraction cord: a study in dogs. This report re-opens the question of epinephrine absorption from gingival retraction cord during fixed prosthodontic impression procedures. The conflicting evidence exposed by this and other studies is probably related to the experimental models utilized. Some suggestions for further investigation are given.


Soft tissue responses to high frequency use of experimental and commercial mouthwashes. A recent study reported that regular use of commercial mouthwashes produced a significant incidence of oral reactions, including epithelial peeling, inflammation, ulceration and geographic tongue-like lesions. In view of the widespread use of these preparations, without apparent deleterious effects, an investigation of two commercial preparations (Scope, Listerine) and an experimental mouthwash containing cetyl pyridinium chloride was undertaken to assess the possible irritant effects on the oral soft tissue under stringent test conditions. A double blind design was used and soft tissue effects were measured over a two week period. Rinses were used full strength, 20 cc 3 times daily. Examinations were conducted by an oral pathologist at the start and conclusion of the test period, and a record was made of the occurrence of erythema, hyperemia/prominent vasculature, inflammation, petechia, keratosis, tongue coating, and ulceration. These observations did not reveal any soft tissue conditions beyond those which would be expected in the normal population.


Historical view on ergot alkaloids.

Historical view on ergot alkaloids. A short survey of the history of ergot, of the original and, for a long time, only source of ergot alkaloids, is given. Once a dreaded poison, ergot has changed its role over the centuries to become a rich treasure house of valuable pharmaceuticals. In the Middle Ages it was the cause of epidemics of ergotism, which cost tens of thousands of people their lives. Ergot was first mentioned by the German physician Lonitzer in 1582 as a remedy used by midwives for quickening childbirth. The isolation of pharmacologically useful alkaloids started in 1906 with the discovery of ergotoxine and its adrenolytic activity by Barger, Carr and Dale. In 1918, Stoll isolated ergotamine, the first chemically pure ergot alkaloid, which found widespread therapeutic use in obstetrics and internal medicine. In 1935 the specific oxytocic principle of ergot, ergonovine, was discovered simultaneously in four separate laboratories. Since then, worldwide investigations on ergot alkaloids resulted in the elucidation of their structures and total syntheses and preparation of valuable therapeutics such as Methergine, Hydergine, Dihydergot, and others.


The clinical assessment of brain failure in the elderly. Dementia is a symptom complex probably arising from cerebral metabolic insufficiency. The testing of drugs thought to improve cerebral metabolism is difficult and many problems have to be overcome. Assessment of brain failure requires objective tests of intellect and memory. Subjective tests are used for disorders of personality and affect. The most useful and practical tests are described in detail. Clinical trials have to be double-blind with strict control of all factors which may influence the tests. Hydergine has been tested in 1,300 patients and shown to be an effective therapeutic agent.


[Double blind study on maprotiline, an example of a multidimensional psychopharmacologic experiment (author's transl)]. Antidepressive therapy with maprotiline was accompanied by blood level determinations psychological clinical and electroencephalographical assessments. It was the aim of the study to introduce objective methods in psychotropic drug therapy and to look for a relationship between blood level and clinical outcome, EEG and psychological data. We found a "therapeutical window" of blood levels between 300 to 600 ng/ml of maprotiline (oral dose of 75 or 150 mg per day). There is also a relationship between clinical outcome rated by the Hamilton-Depression-Scale and the d2-cancellation-test.


Plasma concentrations of diazepam, noradiazepam and amylobarbitone after short-term treatment of anxious patients. Twenty-four anxious inpatients were treated with diazepam, amylobarbitone and placebo, each given in flexible dosage for one week, according to a fully-balanced design. Plasma concentrations of diazepam and of its metabolite nordiazepam and of amylobarbitone were determined after two, four and seven days of treatment. Clinical and psychological assessments were made after seven days of each treatment by means of psychiatrist rating scales, patient's self-rating and a comprehensive battery of performance measures. Diazepam and nordiazepam but not amylobarbitone were accumulating over the seven days of treatment. In patients on diazepam without previous amylobarbitone, nordiazepam accumulated more rapidly than diazepam over the week so that the ratio of diazepam to nordiazepam was 2.21 after two days but only 1.14 after seven days; those with previous amylobarbitone on the other hand always had nordiazepam concentrations higher than those of the administered drug and both were accumulating equally. Diazepam and nordiazepam were still detectable in most patients two weeks after the interruption of treatment. No correlations were found between drug concentrations and clinical and psychological effects.


CSF-changes of HVA and 5-HIAA during intermittent and continuous Parkinson therapy with particular regard to prodipin application. The influence of prodipin, a putative dopamine releasing compound, on the concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the spinal liquor of 28 patients with Parkinson's disease was investigated. The patients were divided into three groups. In group 1 the combined antiparkinson therapy was interrupted, and 20 mg prodipin was infused. In group 2 and 3 the therapy was continued, while an additional 20 mg of prodipin was administered by infusion only to group 3. 4 Liquor-samples were obtained from each patient: 1 basic value and three additional samples 5, 8 and 24 hours after administration of 2 g probenecid. The base concentration of HVA was 15 ng/ml and this was not increased by probenecid in group 1; the concentration of 5-HIAA was 11.6 ng/ml and this was doubled by probenecid to 22.9 ng/ml. The HVA concentration increased to a maximum of 28.9 ng/ml during continued therapy (group 2); the elevated 5-HIAA remained unchanged. Prodipin does not cause an alteration in metabolite concentration in cases of interrupted therapy (group 1), but leads, in the case of continued therapy, to a 1.8-fold increase in HVA, and a 1.6-fold increase in 5-HIAA (group 3).


The great potential of the intercostal flap for torso reconstruction. The intercostal flap has many uses for torso reconstruction, whether employed as an island flap or a free flap. With modifications, it can be used as a sensory skin flap, or as a compound osteocutaneous flap to restore stability in a chest wall construction, or as a skin flap with a permanent blood supply to provide stable cover after excision of radiation ulcers.


Breast reconstruction after a radical mastectomy. Breast reconstruction after a radical mastectomy remains a complex problem. We describe the use of a latissimus dorsi myocutaneous flap, a transverse abdominal flap, or a pedicled flap of the greater omentum to obtain satisfactory cover for the implant and enable us to correct the deformity in one operation.


Immediate reconstruction of a resected segment of the lower jaw, using a compound flap of clavicle and sternomastoid muscle. A brief account is given of the experimental data and the laboratory findings relative to the use of compound bone flaps of clavicle on a pedicle of sternomastoid muscle for restoration of mandibular defects. The clinical data on this method in 18 consecutive patients are presented and discussed.


Prevention of skin flap necrosis by a course of treatment with vasodilator drugs. Large island skin flaps, comprising the entire abdominal covering in rats, were raised on one neurovascular pedicle in the groin. A standard area of necrosis was produced on the other side from the pedicle. However, when the animals were treated with certain vasodilator drugs for 15 days before and 7 days after the flaps were raised, there was little or no necrosis. The effect of the drug therapy was the same as a surgical delay.


Skin flap necrosis in guinea pigs: limitation of glucose supply and accumulation of lactate. The distribution of glucose and lactate within skin flaps was determined in full-thickness guinea pig skin (excluding the panniculus carnosus). The distal end of the flaps had a low glucose content (less than 50 percent of normal) but high lactate level (2 to 3 times normal) during the 3 days after flap elevation. Progressively decreasing gradients of glucose content, and increasing gradients of lactate content, were demonstrated from the mid-region to the distal end of the flaps at 3 hours postoperatively. The decrease in glucose and the accumulation of lactate may play a significant role in skin necrosis.


The lotus position--bilateral cross-thigh flaps for simultaneous coverage of both feet: case report. A 6-year-old girl with an avulsion injury of the dorsum of both feet had multiple fractures of the ankles and the tarsal and metatarsal joints. She was treated by wet dressings followed by simultaneous coverage of both feet with bilateral cross-thigh flaps.


[Correlation of pathological specimen sections with corresponding computer tomography (author's transl)]. The importance of correlation of pathological specimen sections and computer tomograms is postulated emphazising examination of the same sectional level. First results are reported and false positive and false negative diagnoses are discussed.


Lung cancer in chronic leukemia and lymphoma. Review of the number of lung cancers subsequently developing in patients with chronic leukemia or lymphoma revealed a statistically significant (p less than .001) increase in the incidence of lung cancer in these patients. Of 684 patients with chronic leukemia seen between 1961 and 1972 (followed through 1976), 19 developed lung cancer versus 3 expected cases. Of 2708 patients with lymphoma seen in the same period, 23 developed lung cancer versus 7 expected cases. These data indicate that lung cancer be given serious consideration when a new pulmonary lesion is noted in these patients, and biopsy may be warranted.


Late sequelae of adult-onset acute bacterial nephritis. The late manifestations of adult-onset acute bacterial nephritis were studied in four patients from 4 months to 5.6 years following initial infection. An unusual combination of generalized (global) wasting of the kidney and focal calyceal clubbing developed within a few weeks of the acute infection. The pattern of calyceal deformity strongly suggests papillary necrosis; it may develop during the acute phase, but go unrecognized during excretory urography at that time because of impaired contrast material excretion. The combination of a small, smooth kidney and papillary necrosis previously has been associated only with the more severe forms of analgesic nephropathy. Observations in these patients indicate that the same urographic findings may also occur as a result of a single earlier episode of acute bacterial infection of the kidney.


Immediate pathologic confirmation of radiologic interpretations by computer feedback. A computer system is used to provide automatic pathology diagnostic feedback to radiologists. This feedback occurs on a daily basis whenever surgical specimens are obtained for which pertinent radiologic examinations have been performed. On-line inquiry capability is also provided. The implementation relies on linkage between two operational computer systems at Massachusetts General Hospital, for pathology specimen accession management and radiology examination scheduling.


Echocardiographic evaluation of valvar and shunt lesions in children. An evaluation of valvar and shunt lesions in children is directed toward appraising the need for, and timing of, surgical repair or palliation as well as demonstrating the cardiac anatomy which will, in turn, direct the type of surgery to be chosen. Static dimension measurements as well as dynamic measurements of wall velocity and time intervals are atraumatic and easily obtained values that increase our sensitivity to early cardiac decompensation. Contrast studies add both functional and anatomic information. Although one-dimensional time-motion scanning remains an invaluable source of anatomic detail, two-dimensional imaging has made positional information clearer and more reliable. The combined use of these three techniques offers the most complete evaluation of children with volume and pressure overload lesions.


Different yield and properties of mitochondria from skeletal muscle of normal hamsters. Yield and properties of mitochondria, isolated from hind leg muscles of normal hamsters, are different, when 4 preparation procedures are applied simultaneously: 1. mechanical homogenization of muscle with a glass-Teflon homogenizer followed by rehomogenization of the isolated nuclear fraction for 1--6 times. The procedure yields impure mitochondria showing the highest amounts of mitochondrial enzymes (50--65% of total), protein and DNA; the isolated mitochondria exhibit disrupted outer membranes and loosened inner membranes causing a better supply with substrates of enzymes located at the inner membrane and in the matrix. 2. Single mechanical homogenization of muscle for increasing periods (2--40 min) yields lower amounts of all constituents (25--40% of total). 3. The yields of Nagarse treatment with one step of 2 min mechanical homogenization range between 20--35% of total. Mitochondria isolated with the latter procedure exhibit compact membranes and are very pure, but still contaminated with Nagarse, causing destructions of mitochondrial membranes already after 24 h storage in buffer with sucrose and mannitol at 2 degrees C. 4. One single Nagarse treatment of muscle for 40 min produces a minor yield of these these constituents. Therefore, at least two different isolation procedures are proposed for optimum investigation of skeletal muscle mitochondria.


Orthotopic and heterotopic autotransplantation of the rat kidney. End-to-end anastomosis of the kidney vessels and ureter can easily be done without suture. Artery and ureter are connected via an intraluminal silicone tube, anastomosis of the vein is performed with a cuff-technique. In case of orthotopic transplantation the left kidney is transplanted to the right side after right nephrectomy. Furthermore heterotopic transplantation was tried: kidney vessels were either connected with jugular or femoral vessels. In contrast to orthotopic transplantation higher thrombosis rate was observed, probably due to varying sizes of donor and recipient vessels. Our method of orthotopic autotransplantation is easier, less time consuming and has a lower complication rate than homologous kidney transplantation with suture techniques.


[Automatic analysis of M.U.A.P.s (author's transl)]. The authors have studied the Motor Unit Action potentials derived from Extensor Digitorum Brevis and tibialis anterior muscles in normal subjects, using a new method of automatic analysis by means of a digital computer. In the light of the results they have obtained they discuss the validity and the sensitivity of the method as well as the opportuneness of the choice of the muscular region to examine when it comes to determining subclinical or "border-line" cases.


Effects of azathioprine therapy on the MCV of patients with renal grafts: evidence for alterations in the kinetics of erythropoiesis over a prolonged period. The changes in MCV at various times after renal transplantation were studied in a group of patients with functioning cadaveric renal grafts who had received azathioprine from the time of transplantation and in a constant dose from 2-8 weeks later. A post-transplantation increase in the MCV was seen in the majority of the cases studied and in these cases the MCV did not reach a maximum value until as long as 11-40 months after transplantation. In most cases the MCV then feel although frequently not to within the normal range and in some cases it showed further fluctuations. These data suggest gradual alterations over a period of years in the various cytokinetic changes which serve to maintain a reasonably high output of red cells from the marrow despite the cytotoxic effects of azathioprine.


[Therapy of the unstable thorax in serial fractures of the ribs]. The histories of patients with flail chest and respiratory insufficiency caused by blunt chest injury have been analyzed. The first group represented patients with surgical stabilization of 3-4 ribs by introduction of "Rehbein plates" into the medullary cavity (10 patients 1972-1975). The patients of the second group have been supported by controlled mechanical respiration (11 patients 1972-1975). Patients with chest and further injuries (polyblessés) of comparable degree have been selected for both groups. The two groups were compared with regard to duration of intubation and artificial ventilation (average of 8.8 days for the operated and 21.4 days for the mechanically ventilated patients), stay in the intensive care unit (15.2 days after operation and 28.3 days for treatment by respirator) and average total hospitalization time (33.5 days after surgical management and 54.2 days after nonsurgical treatment). Severe bronchial infections caused by hospital germs have occurred more frequently in patients on long-term intubation and mechanical respiration. The average age of patients was almost the same in both groups. The technique of surgical stabilization of the ribs is described, and the advantages and limits of surgical and conservative management of respiratory insufficiency caused by flail chest are discussed.


[Analgesics: pharmacologic properties as a basis for rational therapy]. Current concepts of the mode of action of analgesics are presented, together with some pharmacokinetic characteristics. This information may serve as a basis for rational therapy, and may also help in understanding important side effects of these drugs.


[Epidemiology of resistance factors to antibiotics]. Resistance factors are small independent extrachromosomal DNA molecules (plasmids) conferring resistance on one or more antibiotics to the bacteria which harbour them; in Enterobacteriaceae and other gramnegative bacteria they are transferable by conjugation. The work is reviewed which has been undertaken to underline the importance of the R factors in nature, and more precisely in the current environment of the intestinal bacteria (animal and human gut, sewage) under the selective pressure of antibiotics or otherwise.


[Double-blind study on the anti-convulsive effect of phenobarbital and valproate in the Lennox syndrome]. In a double-blind crossover trial valproate was compared with phenobarbital with regard to anticonvulsive activity and tolerance in 17 epileptic children (mean age 55 +/- 26 months) with Lennox syndrome. Valproate in association with a phenobarbital dose reduced by about 40% proved to be to a statistically significant degree more active against epileptic seizures than phenobarbital alone. No difference in the effect on the EEG tracings was observed. Valproate appeared to be somewhat more active than phenobarbital with regard to behaviour, but the difference was not significant. Tolerance to both products was equally good.


[The removable partial prosthesis--review of the literature]. Early and late checkups on partial dentures demonstrate clearly, that insufficient cleaning of the remaining dentition and of the prostheses along with an unsatisfactory design are one of the main causes of failures in partial denture therapy. They invariably lead to tissue damages. Hence it has become one of the paramount goals to educate and motivate the patient for adequate mouth and denture hygiene. Also, proper occlusion and the avoidance of parafunction upon the remaining teeth and their supporting tissues must be observed strictly. Therefore, it is important to prepare the remaining dentition carefully and to organize the patients to be recalled for checkups at given intervals. In modern literature on the subject the psychological aspects of difficulties in denture adaptation are more frequently discussed.


Mianserin hydrochloride: a new anti-depressant drug. The tetracyclic anti-depressant drug mianserin hydrochloride has been assessed in an open clinical study in 24 psychiatric out-patients, who were prescribed 30 mg. mianserin daily, and were rated on the Hamilton Rating Scale and on the Wakefield Self-Assessment Inventory on day 0, before starting therapy, and on days 7 and 28 of their treatment. The results support the view that mianserin has anti-depressant properties, and the patients' self-rating scores confirm that the level of anti-depressant action is similar to amitriptyline. Drowsiness was the only side effect reported.


Morton's ranking of races by cranial capacity. Unconscious manipulation of data may be a scientific norm. Samuel George Morton, self-styled objective empiricist, amassed the world's largest pre-Darwinian collection of human skulls. He measured their capacity and produced the results anticipated in an age when few Caucasians doubted their innate superiority: whites above Indians, blacks at the bottom. Morton published all his raw data, and it is shown here that his summary tables are based on a patchwork of apparently unconscious finagling. When his data are properly reinterpreted, all races have approximately equal capacities. Unconscious or dimly perceived finagling is probably endemic in science, since scientists are human beings rooted in cultural contexts, not automatons directed toward external truth.


Schizophrenic symptoms improve with apomorphine. Eighteen chronic schizophrenic patients received subcutaneous doses of apomorphine, a dopamine receptor agonist, and of placebo in separate trials. A significant improvement in psychotic symptoms occurred after apomorphine compared to placebo. The results are interpreted as a consequence of presynaptic dopamine receptor activation by apomorphine with a subsequent decrease in dopamine-mediated neural transmission.


Models for the specific adhesion of cells to cells. A theoretical framework is proposed for the analysis of adhesion between cells or of cells to surfaces when the adhesion is mediated by reversible bonds between specific molecules such as antigen and antibody, lectin and carbohydrate, or enzyme and substrate. From a knowledge of the reaction rates for reactants in solution and of their diffusion constants both in solution and on membranes, it is possible to estimate reaction rates for membrane-bound reactants. Two models are developed for predicting the rate of bond formation between cells and are compared with experiments. The force required to separate two cells is shown to be greater than the expected electrical forces between cells, and of the same order of magnitude as the forces required to pull gangliosides and perhaps some integral membrane proteins out of the cell membrane.


Another flame retardant, tris-(1,3-dichloro-2-propyl)-phosphate, and its expected metabolites are mutagens. A flame retardant used in children's sleepwear, tris-(1,3-dichloro-2-propyl)phosphate (Fyrol FR2) is a mutagen in the Salmonella-mammalian tissue homogenate test after it has been activated by mouse or rat liver homogenate. The expected enzymatic hydrolysis product, 1,3-dichloro-2-propanol, is similarly a mutagen after activation by liver homogenate. A proposed metabolite of the flame retardant, 1,3-dichloro-2-propanone, is a potent mutagen in the absence of such activation. A flame retardant with similar structure, tris-(2,3-dibromopropyl)phosphate (tris-BP), was shown previously to be a mutagen, to cause sterility in animals, to be a carcinogen, and to be absorbed through human skin. These and other flame retardants have characteristic nuclear magnetic resonance spectra that can be used to determine which flame retardant is present in commercially purchased sleepwear. Sleepwear treated with tris-BP, Fyrol FR2, and other chemical additives was being sold in late 1977.


Immunization against infectious disease. Mortality and morbidity from infectious diseases in the United States have declined more than 90 percent since 1900. Factors believed to be responsible for this decline include changes in the natural history of disease, sanitation, quarantine measures, control of nonhuman vectors, antibacterial drugs, and immunization. The contributions of each of these factors differ among the various infectious diseases; except for smallpox and diphtheria control, immunization had little effect until after World War II. The success of present and future immunization programs is endangered by public and physician complacency and by complex legal and ethical problems related to informed consent and responsibility for rare, vaccine-related injury.


Computer use in diagnosis, prognosis, and therapy. Computers are used to influence diagnostic and therapeutic decisions. The computer's information-handling capabilities allow it to serve as a reliable extension of the physician's memory and expander of the physician's information and synthesized knowledge resources. Computers have been used to facilitate decisions through organization of patient data, improved classification of patients, decision analysis in clinical settings, and simulation of expert clinical reasoning. Computer programs are more successful in narrow, constrained, single arenas of medicine with much underlying pathophysiologic understanding and where decisions are based largely on hard laboratory data. New models of synthetic reasoning that simulate expert clinical behavior show promise of supporting complicated decisions concerning problems of multiple diseases. All systems are confronted by problems of consensus and authority of the underlying information used.


Surgical innovation and its evaluation.

Surgical innovation and its evaluation. Early clinical trials, observational or randomized, hasten the prompt evaluation of new operations. Early clinical surveillance facilitates the design and implementation of randomized clinical trials when they are necessary. Of equal or greater importance, long-term surveillance of operations allows continuing evaluation when their use becomes widespread. Standards, coordination, review, and funding of the evaluation of new operations we believe should be centralized in a single national agency, for which an Institute of Health Care Assessment might be created. Implementation and regulation of the evaluation we believe should remain at the local or regional level with existing mechanisms and agencies being used, such as institutional human research committees and local health systems agencies.


Treatment of Nocardia asteroides infection with trimethoprim-sulfamethoxazole. Although sulfonamide therapy has reduced the case fatality rate in infection due to Nocardia asteroides from nearly 100% to 25% to 45% there remains a need for a still more effective chemotherapeutic regimen. We describe three cases of serious infection due to N asteroides treated successfully with trimethoprim-sulfamethoxazole (TMP-SMX) and review an additional 15 cases from the world literature. Trimethoprim and sulfamethoxazole exhibit a synergistic interaction in vitro against N asteroides, and the agent reaches antibacterial concentrations in blood, lung, and the central nervous system. Clinical results have been satisfactory in the limited number of patients treated to date.


Treatment of intracranial aneurysms associated with other entities. Considering the current state of surgery for intracranial aneurysm, a philosophy for treating intracranial aneurysms associated with other entities is presented. The premise is based on a comprehensive review of the literature relative to the risk factors applied to intracranial aneurysms and personal experience in dealing with the combination of problems of aneurysms diagnosed in association with other intracranial aneurysms, vascular malformations, neoplasms, trauma, and inflammatory diseases. A patient's problem must be considered individually and comprehensively, using all known prognostic factors and the specific features of the case for an appropriate therapeutic regimen to be designed. Current mortality and morbidity rates warrant the surgical intervention for the incidentally diagnosed aneurysm, but the occurrence of an aneurysm in conjunction with another serious entity demands careful, comprehensive evaluation. The surgical challenge of these complex problems should take second priority to a careful therapeutic deliberation to promote the best final outcome.


Erythema multiforme and the Stevens-Johnson syndrome. Erythema multiforme (EM) is clinically characterized by a "minor" form and a "major" form. The latter is known as the Stevens-Johnson syndrome. Infections (particularly herpes simplex and Mycoplasma pneumoniae) and drugs seem to predispose toward the development of EM. The pathogenesis is poorly understood. The treatment is supportive. Prognosis varies with the severity of the eruption. Recurrences are commonly seen.


The basic kinematics of the human spine. A review of past and current knowledge. Spinal kinematics concerns the kinds and amounts of motion the human spine undergoes during its normal physiologic movements. This paper is a review of the research in this area and provides information about past and current knowledge. The biomechanic terms essential for the precise and accurate description of spinal kinematics are defined, described, and exemplified. Requirements for a comprehensive description of spinal kinematics are presented to provide a perspective for present knowledge and future research. Finally, the current status of spinal kinematic research is described, and information about the ranges of motion of the human spine for various vertebral levels and for motion in different directions is provided.


Fluid collections associated with renal allografts. In a series of 50 consecutive renal allograft patients, 4 developed lymphoceles and 1 developed a seroma which later became infected. In no instance could the fluid collection be held responsible for deterioration in graft function. Two of the lymphoceles occurred with ureteric strictures and perirenal abscess was associated with acute rejection. The significance of a perirenal collection with deteriorating renal function is discussed.


Squamous cell carcinoma of the vagina.

Squamous cell carcinoma of the vagina. Squamous cell carcinoma of the vagina is one of the least understood malignant tumors arising from the female genital tract. Vital facts on its clinical and biologic behavior are difficult to collate in a cumulative way. Its intermediate position in the pelvis makes it a difficult site to which to apply conventional methods of treatment without associated morbidity; its rareness precludes developing expertise by no more than a few therapists and allows few the opportunity to test new ideas encased in research protocols; and its variegated presentations invite individualization as the only therapeutic approach. Squamous cell carcinoma of the vagina remains an enigma among gynecologic neoplasms.


Diagnostic ultrasound in the evaluation of patients with gynecologic cancer. In the early 1960's, obstetricians realized the usefulness of diagnostic ultrasonography and were largely responsible for much of the early development and advancement of the ultrasonic technique. Recently gray scale ultrasonography has resulted in the ability to conclusively differentiate solid from cystic masses. Research is currently underway regarding tissue identification based on ultrasonic patterns. The combined use of ultrasonic instrumentation and computers may some day enable the ultrasonographer to identify specific tissues within the body. Fine needle aspiration biopsy in combination with cross-sectional ultrasonic scanning in some cases circumvents the need for repeat laparotomy to obtain tissue for histologic diagnosis.


C controlled trial of taurolin in established bacterial peritonitis. Taurolin administered intraperitoneally has effected a significant reduction in morbidity in peritonitis even when all other methods of intensive care, including powerful antibiotics, have been used. Easy to use clinically, it is effective locally against all fecal pathogens and is nontoxic.


The treatment of malignant melanoma of the skin. This review of 117 melanomas occurring in 115 patients treated by a single surgeon suggests the appropriateness of the therapeutic decisions to be mentioned based upon tumor behavior, determined by microstaging. Local control of level II lentigo maligna melanoma was achieved, in most instances, by local excision with visibly free margins and primary closure. In most of the other instances of melanoma, adequate local control was accomplished by wide three-dimensional excision, 5 centimeter margins--closure usually required grafting. Minor amputation was performed with satisfactory results in those patients with appropriate lesions in the volar-subungual area. Regional lymphadenectomy in patients with level IV and V disease in whom the tumors drained to a single node basin revealed occult metastases in 25 per cent of the patients and, therefore, appears warranted as prophylactic treatment. Preliminary data on recurrences suggest that the frequency of the recurrence paralleled the biologic aggressiveness of the tumor, determined by microstaging in association with the presence or the absence of lymph node metastases.


Clinical experience with prophylactic antibiotic bowel suppression in burn patients. An oral prophylactic antibiotic regimen (neomycin-erythromycin-nystatin) aimed at suppression of the bowel flora was utilized in 20 patients with thermal injury treated in a laminar flow burn unit with strict sterile technique and reverse isolation. The regimen was utilized for an average of 24 days. Surface cultures were obtained twice weekly from multiple areas of the burn wound, and burn wound biopsies were performed one to two times weekly. These patients were compared prospectively with a group of 10 patients treated in otherwise identical fashion, save for the omission of the antibiotic suppressive regimen. Bacterial colonization of the burn wound occurred an average of 19 days after admission in the group receiving antibiotics compared to 4 days after admission in the control group (p less than 0.01). Positive burn biopsies (more than 10(5) bacteria per gm of tissue) were observed twice as often in the group not receiving antibiotics (p less than 0.16) as were infectious complications of several types: bacteremia, burn wound sepsis, urinary tract infections, pneumonitis, cellulitis (0.10 less than p less than 0.20). Staphylococcal or fungal overgrowth were not encountered in the patients receiving prophylactic antibiotics, nor was there an adverse effect on serum creatinine levels with the prolonged use of neomycin.


Serum autoleukocytotoxic activity and the positive cross-match in potential allograft recipients. To evaluate possible causes of the false-positive cross-match test for clinical renal transplantation, the incidence of serum autoleukocytotoxic activity and its relationship to allogeneic sensitization to HLA antigens (the positive cross-match) were determined in 234 sera from 28 sensitized and eight nonsensitized chronic renal failure patients. Seven sera from four patients had autoleukocytotoxic activity. The autoleukocytotoxic activity was detected only in patients who showed transient allogeneic sensitization at some point. This activity could be adsorbed either by autologous or allogeneic platelets, but adsorption with autologous platelets did not remove the synchronous allogeneic leukocytotoxicity. This autoleukocytotoxic activity appears to coexist with alloreactive antibody, and in such a setting the positive alloreactive cross-match should contraindicate the proposed transplant until adsorption studies prove the false-positiveness of the test.


Computer-assisted instruction in surgery. Computer-assisted instruction (CAI) is an educational medium which provides a highly interactive, adaptive, and individualized learning experience for the student or physician. A CAI system has benn developed to prepare a curriculum in general surgery. The surgical seminars written on this system have been used enthusiastically by students, residents, and interns for the past 18 months. Using a computer terminal (printer or television screen) connected by telephone to a minicomputer, the user participates in simulated seminars with the authors, viewing information and answering questions based on the material presented. The student responds by typing the answer in his own words, and the computer (author) responds with further information designed specifically for that answer. This response may support or contest what the student said, may branch the student to material covered previously, or instead may lead the student through as much remedial material as he needs. A more sophisticated student will progress rapidly through the seminar. Twenty-five surgeon/authors (at 15 medical schools) are preparing seminars, and it is planned that a complete library in general surgery will be available to departments of surgery nationally by September, 1978, via the Health Education Network.


Evaluation of the mechanism of zymosan-induced resistance to experimental peritonitis. Three injections of intraperiotoneal (IP) zymosan-induced profound resistance to E. coli peritonitis in Sprague-Dawley rats. IP zymosan had minimal effects on organ weights and systemic phagocytic clearance ability, suggesting that this mode of administration had few systemic reticuloendothelial system (RES) effects. Hemoglobin (a known inhibitor of local phagocytosis) reduced the protection induced by zymosan, giving further evidence that IP zymosan acts locally. IP zymosan stimulation results in an initial marked influx of polymorphonuclear cells followed by a greater percentage replacement of mononuclear cells by the third day. Examination of these cells via chemiluminescence studies demonstrated that the phagocytic capacity of zymosan-stimulated peritoneal cells was markedly greater than the control group on a cell-for-cell basis. IP zymosan also gave some protection against intravenous (IV) E. coli, but IV zymosan did not significanly protect against IP E. coli. Possible mechanisms of action are discussed. These findings suggest that a technique of local RES stimulation could have a place in preparation of certain high-risk patients for elective abdominal surgery where peritoneal contamination is likely.


Cell-mediated immunity to donor antigens in renal allograft recipients. The antigen-stimulated active rosette-forming T-cell (AgARFC) assay was adapted for the preoperative study of 21 consecutive kidney transplants (17 cadaver donors and four living related donors; five retransplants). Recipient peripheral blood lymphocytes were incubated for 15 minutes with donor histocompatibility antigens preparaed by sonication of donor peripheral blood or splenic lymphocytes. Recipient presensitization to donor antigens was expressed as the difference between active rosette formation in the presence (%AgARFC) and in the absence (%ARFC) of donor antigens. This antigen-induced difference is rosette formation (%AgARFC - %ARFC) for all patients ranged from - 7.0% to 24.2%. Of those patients with pretransplant sensitization greater than 6.3% (group I: mean, 13.2 +/- 3.0; n = 7), 71% had severe acute rejection requiring dialysis within the first 2 weeks of transplantation. In contrast, none of the patients with pretransplant values below 6.3% (group II: mean, -0.8 +/- 1.0; n = 14) had rejection requiring dialysis within the first 2 weeks. Group I patients had 43% graft survival at 1 month and 14% survival at 2 months, whereas group II had 86% graft survival at 1 month and 71% at 2 months. The AgARFC assay provided a rapid means of measuring recipient T-cell presensitization to donor alloantigens, which was correlated with the accelerated rejection of renal allografts.


Appearance and evolution of anti-Da (B cell-specific) antibodies after planned immunizations. Appearance and evolution of anti-Da antibodies has been followed in eight volunteers immunized by whole blood transfusions or leukocyte intradermal injections form a single donor incompatible for HLA--A,--B,--C and--D specificities. Several unabsorbed bleedings from each recipient were studied against the specific immunizer with three different complement-dependent lymphocytotoxicity (CdL) techniques: (1) standard NIH CdL on total peripheral blood lymphocytes (PBL); (2) VII Workshop standard CdL technique on B cell-enriched suspensions; (3) beta2 microglobulin blanketing test ("bb" test) on B cells. Results obtained with the "bb" test were confirmed with platelet-absorbed sera. The "bb" and the absorbed sera allow discrimination between anti-Da and anti-HLA--A,--B,--C antibodies. Stage of appearance and evolution are rather similar for an anti-HLA--A,--B,--C and anti-Da. An early appearance of antibodies positive only against B cells is due to weak anti-HLA--A,--B antibodies which react better with B cells than with total PBL. Immunogenicity of Da antigens seems to be of the same order as HLA--A, and--B. In fact, Da reactivity was present in all eight recipients studied. These reactivities always segregated in familes with these HLA haplotypes. On a small panel of unrelated D-typed donors, three sera showed a significant positive association with D alleles.


Reactive lymphocyte blastogenesis in canine renal transplantation. Reactive lymphocyte blastogenesis was investigated by 3H-thymidine uptake of peripheral lymphocytes. Canine renal allotransplantations were performed in 19 dogs, which were divided into three groups by different immunosuppressive therapies. The first group, not treated with any immunosuppressants, showed the highest 3H-thymidine uptake, but the third group, treated with prednisolone (1.5 mg/kg/day) and azathioprine (4 mg/kg/day), did not show remarkable 3H-thymidine uptake except for 2 dogs which died of severe acute rejection. Single use of prednisolone (second group) was less effective in suppression of blastogenesis compared with the combined use of azathioprine and prednisolone. In addition to these experiments, the effects of surgical operation, blood transfusion, and infection on lymphocyte blastogenesis were investigated. Renal autotransplantation did not produce remarkable blastogenesis, but blood transfusion and infection caused strong lymphocyte blastogenesis. Periodical increases of 3H-thymidine uptake were observed in the infected animal.


Identification of T-lymphocytes in human renal allografts and urine by the fluorescent antibody technique using anti-human T-lymphocyte serum (AHTS). Immunopathological investigations of the small round cells infiltrating into the tissues of human renal allografts and also those in urinary sediments were performed, using anti-human T-lymphocyte serum (AHTS). AHTS made from ALS is highly specific for T cells, but not for B cells. Tissues obtained by needle biopsy were examined by immunofluorescent staining and conventional histopathological methods. Urinary sediments were obtained from centrifugated fresh urine. Sediments were checked by immunofluorescent and Giemsa staining. Fluorescent positive cells were seen in the interstitial tissues and occasionally in renal glomeruli. Clustered cell-debris in the lumen of renal tubules was also stained by AHTS. In the urinary sediments, about a half of the lymphoic cells were stained by AHTS. The relationship between lymphocyturia and numerous infiltrating cells in the grafts during the rejection crisis has not been clarified. In this experiments, we tried to identify the detailed process of excretion of T cells to urine from renal tissues, using immunopathological methods.


Morphometrical analysis on topographical difference in size distribution, number and volume of islets in the human pancreas. Seven pancreases from nondiabetic autopsy cases were submitted to morphometrical analysis of the islets of Langerhans as a preliminary investigation of the diabetic pancreas. The pancreatic islets were approximately simulated by spheres of different sizes randomly dispersed in the three-dimensional space; thereon the parameters of Weibull function assumed for the distribution of islet radii were estimated stereologically from chord length measurements on histologic sections taken from different portions of the pancreas. By means of the estimated parameters topographical comparison of the number, volume, mean radius and size distribution of islets in a unit volume were performed. This islet distribution appeared to change the pattern gradually according to the position from the pancreatic head to the tail: the head was characterized by abundance of small islets that corresponded to a slightly higher islet population threat, whereas the tail by moderate increase of larger islets that caused a steep increase of islet volume here. To estimate parameters for the whole pancreas a histologic section from a range between the midposition of the pancreas and the one-fourth position from the splenic end was regarded to be a fairly good representative.


[Explorative laparotomy combined with splenectomy in malignant lymphomas (evaluation of 52 medical records) (author's transl)]. 52 medical records of patients with malignant lymphomas, who had been treated by explorative laparotomy and splenectomy, were evaluated retrospectively. In all patients lymphography and splenic scintigraphy had been performed prior to surgical treatment, and in most of them additional liver scintigraphy. The splenic scintigram was true-positive in 11 cases, false-positive in 6, false-negative in 8, and true-negative in 27 cases. Lymphography was true-positive in 9 and false-positive in 17 cases, false-negative in 4 and true-negative in 22 cases. Comparison shows that explorative laparotomy and splenectomy, in spite of the postoperative complications which have been mentioned, cannot be replaced by modern diagnostic possibilities, provided that indication is carefully considered.


Cooperative erythropoietic assay of several steroid metabolites in polycythemic mice. A blinded cooperative assay of several androstane and pregnane steroid metabolites has been carried out in order to determine whether 5beta-H derivatives are as active as testosterone in stimulating in vivo erythropoiesis. The steroids tested were: testosterone, 5alpha-dihydrotestosterone, 5beta-dihydrotestosterone, 5beta-pregnane-3,20-dione, 3alpha-dihydroxy-5beta-pregnane-11,20-dione and 3beta-hydroxy-5beta-pregnan-20-one. The incorporation of radioactive iron into newly formed red cells in exhypoxic polycythemic mice was used to compare the effects of the steroids. Testosterone and 5alpha-dihydrotestosterone both produced significant increases in 59Fe incorporation. 5beta-dihydrotestosterone, 5beta-pregnane-3,20-dione, 3alpha-hydroxy-5beta-pregnane-11,20-dione and 3beta-hydroxy-5beta-pregnan-20-one were all devoid of significant erythropoietic activity in polycythemic mice in almost all instances. Thus, under the conditions chosen, this study failed to demonstrate that 5beta-steroids increase radioactive iron incorporation in red cells of exhypoxic polycythemic mice.


Immune response to tumour antigens.

Immune response to tumour antigens. In experimental tumour systems in a wide variety of species there is clear evidence for the existence of immunity mechanisms directed against the elimination of the tumour. This is particularly true when the tumours are those induced either by carcinogens or by viruses. With spontaneously arising tumours in animals, specific immune responses to tumour antigens have been more difficult to demonstrate. Nonetheless these experimental systems do show that tumour antigens exist and that tumour growth can be controlled by immune responses to them. Since the immune system is the natural mechanism of control, one hopes that, when more is understood about the nature of tumour antigens on human tumours, we shall be in a position to apply some of our basic experimental knowledge to the immunotherapy of cancer in man.


Controlled trial of ornithine alpha ketoglutarate (OAKG) in patients with stroke. A double blind controlled trial of ornithine alpha-ketoglutarate (OAKG) was carried out on 50 patients admitted to the Royal Free and Royal Northern Hospitals, London, suffering from a recent stroke. Significant improvement was found in patients treated with OAKG when examined on the fifth day of therapy as compared to their control cases. The therapy was given for 5 days. When the patients in the treated and the control groups were compared 10 days after the beginning of treatment, there were no differences between the 2 groups. Implications of these findings are discussed.


Demonstration of anti-Wrb in a second serum containing anti-Ena. Many persons who are of a "deletion" or "null" phenotype with regard to a particular blood group system, form a complex specificity antibody or mixture of antibodies, when immunized. Recently, we demonstrated that M.E.P., the En(a-), Wr(a- b-) proposita in a family described by Darnborough has at least, anti-Ena and anti-Wrb in her serum. We suggested that the same two antibodies might be present in the serum of G.W., the En(a-), Wr(a- b-) propositus in the family reported by Furuhjelm et al. We have now been able to confirm that G.W.'s serum does contain antiEna and anti-Wrb and that the antibodies can be separated by adsorption. Because, at this time, it is not known if En(a-), Wr(a- b-) people lack other common antigens from their red blood cells, the possibility remains that the anti-Ena, separated from the anti-Wrb, might be a mixture of antibodies. These findings are important in that they show that reported typings for Ena were actually performed with mixtures of at least anti-Ena and anti-Wrb. Anti-Ena, lacking antiWrb, can be made only by adsorption of a serum containing the two antibodies, onto En(a+), Wr(a+b-) red blood cells, with recovery of the anti-Ena by elution.


Naturally occurring anti-Kell stimulated by E. coli enterocolitis in a 20-day-old child. Anti-A and anti-K have been found in the serum of a 20-day-old child who had not been transfused but who was acutely ill with E. coli enterocolitis. Both antibodies are IgM proteins. The mother's serum does not contain either antibody and the anti-A and anti-K in the infant's serum are not of maternal origin. Both parents and the child are of the Kell phenotype K-k+. Stool cultures made from the child yielded E. coli O 125:B15, an uncommon B-variant pathogenic coliform. Cell-free preparations made from broth cultures of this organism have strong specific inhibitory activity against IgM anti-A and anti-K, and both antigens have been identified on the bacterial cells. At age 3 months the child had made a clinical recovery, stool cultures showed no pathogenic coliforms, and anti-A and anti-K were no longer detectable in her serum. These data indicate that absorption of metabolites with A-like and K-like activity produced by a pathogenic coliform in the intestinal tract were responsible for the appearance of apparent naturally occurring anti-A and anti-K in the child's serum.


Protein typing by disc electrophoresis of some species of trypanosomes with special emphasis to Trypanosoma cruzi. Proteins extracted from culture forms of T. cruzi, T. cruzi-like strains, T. rangeli, T. conhorrini and T. dionisii were separated by disc electrophoresis. The electrophoretic protein patterns of all strains examined were highly reproducible. The results indicate that each of these strains have their own "fingerprints" and the trypanosoma species could be identified by some typical specific protein bands. However, it was not possible to distinguish between the human strains of T. cruzi and the T. cruzi-like strains isolated from other sources.


Transplantation of hepatitis B surface antigen positive bone marrow. We considered for bone marrow transplantation a boy whose only histocompatible donor was positive for hepatitis B surface antigen (HBsAg). He was conditioned for transplantation with cyclophosphamide and total body irradiation. Hepatitis hyperimmune gamma globulin was administered following the bone marrow infusion. Fourteen months after transplantation, the recipient remains a chronic HBsAg carrier, but he has neither developed fulminant liver disease nor has there been any evidence of graft failure.


The generation of phospholipase A and hemolytic fatty acids by autolysing suspensions of Trypanosoma congolense. When T. congolense undergoes autolysis there is a concomitant appearance of phospholipase A activity and hemolytic fatty acids. The generation of enzyme activity is exponential, and the appearance of hemolytic activity corresponds to a free fatty acid concentration of 0.02 to 0.03 mg. per ml. The concentration of the trypanosome suspension markedly affected the kinetics of the generation process. In contrast, the autolysis of T. lewisi did not generate hemolytic activity unless exogenous phospholipase A was added to the organisms.


A standardization of microfilarial densities for epidemiological comparisons in periodic bancroftian filariasis. Microfilarial density in the peripheral blood changes with time. The average concentration in a population can only be calculated if the influence of circadian periodicity is eliminated from individual measurements. A transformation of the harmonic wave formula, describing the time dependent changes in density allows to calculate the number of microfilariae at the peak of the curve from the number observed at the time of examination. The equation was tested for strains of Wuchereria bancrofti from Liberia.