Kinetic analysis of plasma insulin disappearance in nonketotic diabetic patients and in normal subjects. A tracer study with 125I-insulin. The studies so far reported on the metabolic clearance rate of insulin in human diabetes mellitus have given conflicting results, probably because they have been conducted on few patients and have used a variety of experimental techniques and data treatments. We investigated the kinetics of insulin distribution and degradation in 35 normal subjects and in 42 nonketotic, nonobese, overtly diabetic patients, of whom 26 were above 40 yr old and 16 were 40 yr old or less at diagnosis. The design of the study combined (a) the use of a tracer to perturb minimally the steady state and to avoid glucose infusion; (b) the preparation of purified [(125)I]-monoiodoinsulin, which has a metabolic behavior similar to that of native insulin; and (c) noncompartmental analysis of the plasma immunoprecipitable (125)I-insulin disappearance curves, which were recorded for 2 h after pulse i.v. injection of the tracer.Metabolic clearance rate was found to be similar in diabetics (404+/-18 ml/min.m(2), mean+/-SEM) and in normals (420+/-14), although the latter-onset patients had slightly, if not significantly, lower metabolic clearance rate values than the earlier-onset diabetics (385+/-19 and 443+/-36, respectively). The initial distribution volume of the hormone also did not significantly differ in diabetics and normals and was similar to plasma volume. The reentry rate into the initial distribution volume of the hormone and the total, plasma-equivalent distribution volume of insulin were both significantly raised in diabetics (251+/-12 ml/min.m(2) and 10.3+/-0.5 liters/m(2)) in comparison with normals (195+/-8 and 7.5+/-0.3). The posthepatic delivery rate of insulin was found to be slightly raised in later-onset diabetics (194+/-20 mU/h.m(2)), but somewhat reduced in earlier-onset diabetics (133+/-15) in comparison with normals (172+/-14); these differences reflected the different basal plasma insulin concentrations in these three groups. Chronic treatment with oral hypoglycemic drugs, age, duration of the disease, and degree of metabolic control appeared to have only little effect on the kinetics of insulin.On the basis of these results, we conclude that insulin-independent adult diabetics show, already in the fasting state, a combination of insulin resistance and insulin deficiency and a derangement in insulin distribution, the precise significance of which is uncertain.


Activity of (des-Aspartyl1)-angiotensin II and angiotensin II in man. Differences in blood pressure and adrenocortical response during normal and low sodium intake. This study was designed to compare the effect of [des-Aspartyl(1)]-angiotensin II ([des-Asp]-A II) and angiotensin II (A II) on blood pressure and aldosterone production in man under conditions of normal and low sodium (Na) intake. Seven normal male subjects in balance on constant normal Na intake (U(Na) V 160.3+/-5.0 meq/24 h) for 5 days received A II and [des-Asp]-A II infusions on two consecutive days; 1 mo later they were restudied after 5 days of low Na intake (U(Na) V 10.5+/-1.6 meq/24 h). Each dose was infused for 30 min, sequentially. During normal Na intake, [des-Asp]-A II from 2 to 18 pmol/kg per min increased mean blood pressure from 85.2+/-3 to 95.3+/-5 mm Hg and plasma aldosterone concentration from 5.2+/-1.1 to 14.3+/-1.9 ng/100 ml. During low Na intake, the same dose of [des-Asp]-A II increased mean blood pressure from 83.7+/-3 to 86.7+/-3 mm Hg and plasma aldosterone concentration from 34.4+/-6.0 to 51.0+/-8.2 ng/100 ml. In contrast, A II from 2 to 6 pmol/kg per min during normal Na intake increased mean blood pressure from 83.3+/-4 to 102.3+/-4 mm Hg and plasma aldosterone concentration from 7.0+/-2.2 to 26.8+/-2.0 ng/100 ml; during low Na intake, A II increased mean blood pressure from 83.0+/-3 to 96.0+/-4 mm Hg and plasma aldosterone concentration from 42.0+/-9.7 to 102.2+/-15.4 ng/100 ml. A II and [des-Asp]-A II were equally effective in suppressing renin release. Plasma cortisol and Na and K concentration did not change. The effects of two doses (2 and 6 pmol/kg per min) of each peptide on blood pressure and aldosterone production were evaluated. During normal Na intake, [des-Asp]-A II had 11-36% of the pressor activity and 15-30% of the steroidogenic activity of A II. Na deprivation attenuated the pressor response and sensitized the adrenal cortex to both peptides, but the increase in steroidogenesis was greater with [des-Asp]-A II than with A II. The dose-response curves for [des-Asp]-A II with respect to blood pressure and aldosterone production were not parallel, and although no maximum was established for A II, [des-Asp]-A II was less efficacious.In summary, (a) [des-Asp]-A II has biologic activity in man, (b) [des-Asp]-A II is less efficacious than A II in stimulating aldosterone production, (c) Na deprivation sensitizes the adrenal cortex more markedly to [des-Asp]-A II than A II, and (d) dose-response curves for the two peptides differ, suggesting the possibility that they act at different receptor sites in vascular smooth muscle and the adrenal cortex.


IgA localisation in glomerular diseases. The structural changes found on light and electron microscopy study of 25 renal biopsy specimens that showed significant glomerular IgA deposition on immunofluorescence were correlated with relevant clinical data. The morphology of a wide range of glomerulopathies seeen included mesangial proliferative (60%), membranous (12%), rapidly progressive proliferative (8%), mesangio-capillary (8%), and no light microscope change (8%). Four of the 15 cases (60%) of mesangial proliferative glomerulonephritis were associated with focal segmental sclerosis and 10 with focal segmental and focal global sclerosis. In addition, 7 of the 15 cases showed capsular crescents. The clinicopathological correlations indicated that the prognosis in this group is unfavourable when focal global sclerosis and capsular crescents are present, particularly when both occur in the same biopsy specimen.


Klebsiella: taxonomy, nomenclature, and communication. Differences in the delineation of Klebsiella spp. in the United Kingdom from that in the majority of other countries is discussed. An attempt is made to trace and interpret the reasons for these differences and suggestions are made for a rapid resolution of this problem which hazards communication.


Incidence of K1 antigen in Escherichia coli isolated from blood and cerebrospinal fluid of patients in the United Kingdom. Altogether 411 cultures of Escherichia coli isolated from blood and 60 from cerebrospinal fluid (CSF) of patients in the United Kingdom were identified biochemically and serologically. They were tested for the presence of K1 antigen by an antiserum-agar method using horse meningococcus group B antiserum and by slide agglutination using E. coli 07.K1.H-antiserum. In total 71 cultures from blood (17%) and 29 from CSF (48%) gave positive results by both methods and were considered to possess the K1 antigen. Among the cultures from patients less than 3 years of age the K1 antigen was found significantly more often in those isolated from CSF (53%) than in those from blood (29%). The K1 antigen was found significantly more frequently in cultures isolated from the blood of patients less than 3 years old (29%) than in those from the blood of older patients (13%). Cultures which gave negative results in the slide agglutination test also gave negative results by the antiserum-agar method but positive results obtained by slide agglutination were not always confirmed using the antiserum-agar technique. Slide agglutination was considered to be valuable for the elimination of K1 negative cultures, but positive results required confirmation using the antiserum-agar method.


Formaldehyde induced anti-N: a possible cause of renal graft failure. Treatment of human red cells with low concentrations of formaldehyde induces an antigenic change which makes them react very strongly with the anti-N sera found in certain patients treated by haemodialysis. This supports the idea that formaldehyde sterilisation of reusable home dialysers leads to the development of anti-N in these patients' sera. The clinical problems produced by this antibody are discussed together with ways of overcoming them.


Effect of renal transplantation on marrow mast cell hyperplasia of chronic renal failure. Marrow mast cells have been counted in iliac bone from patients with chronic renal failure treated by renal transplantation. Mast cell numbers were initially increased but returned to the normal range in many patients after renal transplantation. Improvement in osteitis fibrosa and osteomalacia after transplant was not clearly related to this diminution in the number of mast cells. The use of prednisone in renal transplant patients may have some effect in reducing the numbers of mast cells. There is no fully acceptable explanation for the increase in marrow mast cells which occurs in chronic renal failure.


Group B streptococci in women fitted with intrauterine devices. A survey was made of group B streptococcal carriage at various sites in 100 women attending a clinic for the insertion of an intrauterine contraceptive device (IUD). Twenty-three women carried streptococci at one or more sites at the preinsertion visit, the vaginal carriage rate being 16%. Six months after insertion changes in carrier status were noted and there was evidence of a change of strain in four patients. Twenty-nine women were carriers at one or more sites at some stage of the study. There was no evidence that symptoms attributable to infection in patients fitted with an IUD were caused by group B streptococci.


Bacteriological findings in cultures of clinical material from Bartholin's abscess. Purulent exudate from 28 cases of Bartholin's abscess were examined for aerobic, anaerobic, and microaerophilic bacteria. Three cases gave no bacterial growth, five cases grew facultative bacteria only, and a further three grew a mixture of facultative and anaerobic bacteria. One case gave a pure growth of a microaerophilic streptococcus. Anaerobic bacteria were the only isolates in 16 cases and Bacteroides species were the most common organisms isolated; they were present as 62.5% of the total anaerobes cultured and accounted for 45.4% of the total bacteria cultured. Escherichia coli was the most common of the facultative organisms, accounting for 18% of the total bacteria. Most infections seemed to be caused by a single organism, anaerobic types predominating.


Double-blind crossover clinical pharmacology study comparing moxestrol (R 2858) and ethinyl estradiol in postmenopausal women. The potency of 5 migrogram moxestrol (R 2858). 11beta-methoxy-17alpha-ethinyl-estra-1,3,5-[10]-triene-3,17-diol, administered orally, was compared to that of 25 microgram ethinyl estradiol in a double-blind crossover clinical pharmacology study of six postmenopausal women. At these doses, both compounds increased the eosinophilic index and decreased serum LH and FSH levels. A marked effect on circulating prolactin was observed only during ethinyl estradiol treatment.


Pharmacokinetics of iodamide in normal subjects and in patients with renal impairment. The pharmacokinetic characteristics of iodamide, a contrast agent for excretion urography, were studied in seven normal subjects and in 15 patients with various degrees of renal impairment. Two different formulations were administered, namely, a 65% solution (iodamide 300) by slow intravenous injection and a 24% solution by slow intravenous (drip) infusion. Both preparations of iodamide exhibited characteristics of an open two-compartment model. In both normal subjects and patients, the contrast agent was excreted almost exlusively in urine. In normal subjects, the pharmacokinetic parameters of both formulations were similar, with a distribution half-life (1/2alpha) of about 3 minutes and a disposition half-life (t1/2beta) of about 69 minutes. An average of 84 per cent of the dose was excreted in urine within 4 hours after administration of iodamide with net renal tubular secretion of about 38 per cent. The binding of iodamide to plasma proteins was negligible, and the extent of biotransformation of iodamide was minimal. In patients with renal impairment, the disposition half-life (t1/2beta) of iodamide ranged from 4.1 to 16.4 hours. Other changes in pharmacokinetic parameters were also seen in patients with renal impairment.


A long-term study of the efficacy of oxandrolone in hyperlipoproteinemias. Oxandrolone, an anabolic steroid, significantly reduced serum triglycerides in type III, IV, and V hyperlipoproteinemia, with a concomitant decrease in pre-beta lipoproteins. Its slightly enhancing effect on serum cholesterol and absolute increase in beta lipoproteins might eventually discourage its administration in type II patients. Alpha lipoproteins always remained at low levels. In addition to its hypotriglyceridemic action,, oxandrolone induced a slight reduction in uric acid and alkaline phosphatases. Untoward side effects were not observed even after prolonger therapy. Therefore, oxandrolone might deserve a place among the few available triglyceride-reducing therapies.


Evaluation of amoxicillin therapy in ill children. Ampicillin and amoxicillin were evaluated in 37 ill children. Detailed pharmacokinetic studies in 27 of these children demonstrated an advantage in oral absorption of amoxicillin over ampicillin at dosages of both 12.5 and 25 mg/kg per dose. Individual variation was great for both drugs. No sequence effect was noted for patients receiving ampicillin before either ampicillin or amoxicillin. Amoxicillin was tolerated well by the majority of patients, and the drug was not discontinued because of side effects in any patient. No toxicities were noted for amoxicillin in any of the 20 patients studied for abnormalities in hematologic hepatic, and renal functions. Pharmacokinetics, clinical efficacy, tolerance, and toxicity studies support the clinical usage of amoxicillin in pediatric infectious diseases. However, comparative, controlled clinicalinvestigations are needed to better define the clinical advantages of this drug over ampicillin.


Sodium nitroprusside therapy in congestive cardiomyopathy-variability in hemodynamic response. Twelve of 17 patients (group A) with congestive cardiomyopathy improved hemodynamically during sodium nitroprusside (NP) infusion. Five patients (group B) failed to increase their cardiac output. The two groups were identical in clinical presentation and had comparable cardiomegaly and left ventricular filling pressure (LVFP). However, group A had a baseline cardiac index (CI) lower than 2.5 L/min/m2 and high peripheral systemic (PSR) and total pulmonary vascular resistance (PR). In contrast, group B had a control of CI of higher than 2.5 L/min/m2 and near normal PSR and PR. Furthermore, a highly significant correlation was observed between the calculated levels of control PSR and their subsequent reduction during NP infusion. The higher the initial resistance, the more marked was its fall on NP as documented in group A. In group B, the PSR was probably not high enough for NP to be effective in increasing the cardiac output further by vasodilatation. We conclude that NP infusion may not increase cardiac output in congestive cardiomyopathy, in spite of a high LVFP, if the PSR is near normal.


Immunofluorescence studies in scabies.

Immunofluorescence studies in scabies. Direct and indirect immunofluorescence investigations performed for 11 patients with scabies. All patients had punch biopsies taken from (1) a lesion containing Sarcoptes scabiei, (2) an inflammatory papule which did not contain a mite, and (3) normal skin. In four patients IgE deposits were found in the vessel walls of the upper dermis both in biopsies containing mits and biopsies of inflammatory papules with no mites. No IgE deposits were found in biopsies of normal skin from the same patients. Two patients had IgM and/or C3 deposits along the basal membrane in biopsies containing mites and one of them also had C3 in this area in the biopsy from a papule with no mite, as well as normal skin.


Mammary blood flow during experimental Escherichia coli endotoxin induced mastitis in goats and cows. The effect of intramammary infusion of Escherichia coli endotoxin upon mammary blood flow was studied in lactating goats and cows. Blood flow was recorded by means of an electromagnetic flow probe chronically implanted around one mammary artery. Endotoxin mastatis was always accompanied by a significant increase in mammary blood flow, characterized by 2 conspicuous peaks. The flow returned to control values by the thirteenth hour after infusion. Other symptoms of acute mastitis were: fever, increased heart rate, swelling, heat and pain of the gland, increased chloride and total cell count in milk.


Suturing techniques for Dermatologic Surgery. Various suture techniques that are commonly used in dermatologic surgery are discussed and illustrated. They are applicable to operations as simple as closure of elliptical excisions and as complex as cosmetic surgery.


Reconstruction of facial defects resulting from Mohs' chemosurgical procedures. A philosophy of reconstruction after removal of cutaneous neoplasms from the face is presented and differences in reconstruction required after Mohs' fixed-tissue and fresh-tissue techniques are discussed. The indications for repair at once or later of facial defects after Mohs' procedures are reviewed and reconstructive alternatives are presented. Illustrative case reports of such cases that have been reconstructed are recounted and commented on. It is likely that the practice of the fresh-tissue technique will stimulate more interest in reconstructing facial defects resulting from that type of operation immediately, or at least sooner than later.


Pigmentary correction of piebaldism by autografts. I. Procedures and clinical findings. Full-thickness and epidermal autografts of normally pigmented skin were transplanted within hypopigmented areas in each of two patients with piebaldism. Full-thickness punch grafts 2 to 4 mm in size retained their pigmentation (donor dominance) and within 4 months pigment was found to have spread around them. Within a year, melanization covered roughly triple the diameter of the grafts (or 9 times their areas) and then came to a standstill. Epidermal grafts (about 12 mm in diameter) healed with no visible scars at either donor or recipient sites. These grafts, too, retained their pigmentation, but no pigment was seen to spread from them in 8 months of observation. Controls of hypopigmented, full-thickness autografts placed into comparable hypopigmented areas showed either no change or but slight pigmentation along the rim of the graft and no spread of pigment.


The effects of PEEP on arterial oxygenation. An examination of some possible mechanisms. The effect of positive and expiratory pressure (PEEP) on arterial oxygenation depends on many factors. Two of the most important are the "quality" and the "quantity" of the physiological shunt. The "quality" depends on the mixed venous oxygen tension, and the "quantity" on the shunt fraction. Each of these factors may rise or fall with PEEP, depending on the pulmonary and circulatory state of the patient. Their ultimate balance influences the change in arterial oxygen tension.


Intermittent positive pressure breathing (IPPB) versus incentive spirometer (IS) therapy in the postoperative period. The increase of the inflationary lung volume created by a respiratory maneuver is critical for preventing postoperative alveolar collapse. We measured this volume as achieved with IPPB or incentive spirometry (IS) in 20 postoperative surgical patients. Using IPPB, with gas flow and peak airway pressures carefully adjusted for each patient, a value of 2240 +/- 630 cc (mean +/- 1 SD) was obtained compared to 1960 +/- 650 cc with IS. This difference is highly significant (p less than 0.0005 by the Wilcoxon test). We conclude that IPPB, by careful application, and with monitoring of tidal volumes, is likely to provide better prophylaxis of postoperative pulmonary complications, particularly in patients with compromised lung function and in an intensive care unit, where enough trained personel are available.


Evaluation of techniques and material used in pulpal therapy based on a review of the literature: part II. A healthy and functional dental pulp is the goal of any treatment procedure, but at present there does not seem to be any material that will regularly induce dentinal bridge formation and healing of an exposed, inflamed pulp. The usefulness of various capping agents, including corticosteroids and isobutyl cyanoacrylates, is interpreted. In determining treatment, all the clinician's experience is needed in correlating clinical evidence, history, size of the filling in relation to the tooth crown and periodontal condition.


Magnetic enzyme immunoassay for measuring human IgE. This paper reports a solid-phase sandwich technique for the assay of human IgE using anti-IgE antibodies bound to magnetic polyacrylamide-agarose beads. Following this technique, IgE to be determined is allowed to bind to the magnetic beads bearing the anti-IgE antibodies. After washing on a magnetic rack, the beads are incubated with enzyme-labeled antibodies, washed again, and then the enzyme activity associated with the beads is measured. The use of magnetic polyacrylamide-agarose beads and of enzyme-labeled antibodies makes the measurement of IgE in human sera easy to perform, safe, and reproducible. This procedure allows the measurement of IgE concentration in serum containing more than 2 IU/ml. The values obtained from 104 human sera closely corresponded to those obtained by radioimmunoassay (correlation coefficient, r = 0.9751).


Clinical research and the noninstitutional elderly: a model for subject recruitment. Two approaches (normative and symptomatic) are presented for recruiting volunteers for a study of the effects of a vasodilator on the psychophysiologic functioning of elderly patients with mild to moderate cerebroarteriosclerosis. The subjects had to be at least 60 years old, in good physical and emotional health, of at least average intelligence, manifesting cognitive impairment by at least one of several test measures, maintaining themselves in the community, and active in a senior citizens program. Results of both approaches were compared for rates of volunteer response, study eligibility, and admission to the study. The normative approach emphasized data on the normal cognitive changes associated with the aging process. The symptomatic approach focused on the early diagnosis and treatment of an existing cognitive impairment. A combined total of 1,030 potential volunteers, nearly equally divided according to the two techmiques, were addressed in group meetings. With the normative approach, 33 percent volunteered; of this group, 27 percent were found eligible for the study, and of these, 10 percent entered the study. With the symptomatic approach, 36 percent volunteered; of this group, 54 percent were found eligible for the study, and of these, 51 percent entered the study. Thus the symptomatic approach was five times more effective than the normative approach.


Studies of body image. IV. Figure drawings in normal and abnormal geriatric and nongeriatric groups. Figure drawings were obtained from 72 normal adults, 48 adult psychiatric inpatients, 30 senior citizens, and 33 elderly inpatients in a mental hospital. Blind analyses were carried out for "emotional indicators" and other characteristics such as body image disturbance and intellectual impairment. Significant differences were found on almost all measures between the normal elderly and the normal adult. They were also found to discriminate between the normal adult group and the adult psychiatric patients. Very few differences were found between the normal elderly and elderly psychiatric patients, or between normal elderly and adult psychiatric patients. These results imply that norms based upon figure drawings of children or adults may not apply to the elderly and that, therefore, figure drawings may be a less useful diagnostic tool for elderly people than they are for children or adults.


The diffusion of hospital technologies: some econometric evidence. This paper examines the diffusion of five hospital technologies that have spread widely since 1950: the postoperative recovery room, the intensive care unit, the respiratory therapy department, diagnostic radioisotope facilities, and electroencephalograph. The regressions show that the logistic function describes the diffusion of hospital innovations as well as it does the diffusion of innovations in other industries, that the rates of diffusion for these technologies fall within the range established by work on other industries, and that the rates for technologies that were not yet widespread in the middle 1960s increased with the advent of Medicare and Medicaid.


Solid-phase radioimmunoassay for detection of antibodies to myelin basic protein. A solid-phase double-antibody radioimmunoassay was developed for the detection of anti-myelin basic protein (BP) in sera. Antigen was adsorbed to glass test tubes, reacted with rat anti-BP sera, followed by 125I-labeled rabbit anti-rat IgG. This assay was capable of detection of specific antibody at low nanogram per ml levels, was technically simple, and the results correlated well with established procedures.


Isolation, lactoperoxidase catalyzed radioiodination, and recovery of proteins bound to insoluble immunoadsorbents. A method for the direct radioiodination and recovery of proteins specifically absorbed to an insoluble immunoadsorbent is described. The optimal conditions for adsorption, washing, radiolabelling by lactoperoxidase catalyzed iodination, and elution of radiolabelled proteins from the immunoadsorbent have been determined. The technique is a rapid and efficient means of isolating and radioiodinating specific proteins present in biological fluids and has been applied to the detection of immunoglobulin and histocompatibility antigens in mouse cell culture supernates. This method should be particularly applicable in research situations in which the specific antisera are available but the antigen concentration is low or the volume of material to be analyzed is limited.


A method for autoradiographic studies of single clones of plaque forming cells. By limiting dilution of B lymphocytes from spleens of immunized mice, microcultures were obtained that contained only one clone of plaque forming cells (PFC). The cultured cells were labelled with [14C]thymidine for varying periods of time. Plaques were obtained in monolayers of sheep erythrocytes in plastic dishes. After fixation with glutaraldehyde, the bottoms of the dishes were stripped off and autoradiograms prepared. By this method, it is possible to determine the proportion of labelled PFC within a given clone and to quantitate the incorporation of label. The method described can be applied to study the incorporation of other labelled molecules and for cytochemical investigations.


In vitro culture of lymphocyte colonies in agar capillary tubes after PHA-stimulation. Human peripheral lymphocytes were stimulated with phytohemagglutinin (PHA) in liquid culture, suspended in agar and incubated in glass capillary tubes. Compact colonies of lymphocytes were found growing along the tube bottom in a buffer film, while compact clusters and rare diffuse colonies were observed inside the agar. Several parameters affecting the clonal growth were studied and optimized: PHA-dose, agar concentration, gel length (volume), quantity and density of seeded cells per capillary and gel length. Colony yield mainly depends on the seeded-cell density with a sharp optimum at 2 X 10(5) cells/ml irrespective of gel length; higher cell densities reduce the colony yield, suggesting that colony growth is the result of both stimulatory and inhibitory factors produced by cooperating cells. Following the daily clonal growth was only possible with undisturbed tubes; the number of colonies steadily increased from day 2 until day 7. Densitometric colony scanning is possible, yet problematic. Colony yield (plating efficiency is 10--50-fold higher in agar capillaries than in the usual Petri dishes. An additional advantage is that the capillaries provide a basis for a simple and reliable assay system for determining regulatory factors of lymphocyte proliferation (including chalones).


Nephelometric assay of antigens and antibodies with latex particles. Antigens and antibodies covalently bound to latex particles have been used to detect specifically corresponding antibodies and antigens by nephelometry. A systematic study of factors such as wavelength, angle of observation, concentration of latex particles, and reaction time has permitted us to develop a procedure suitable for routine estimation of antigens and antibodies in the nano and picogramme range.


A simple microscopic method for identifying and quantitating phagocytic cells in vitro. A simple method is described for distinguishing phagocytic cells from non-phagocytic cells in a mixed population of leukocytes.


A useful technique applicable to the immunofluorescence test. A simple techinque for carrying out the immunofluorescence procedure is described that eliminates the problem of drying of antiserum and reduces cost per test.


Utilization of the buccal fat pad for closure of oro-antral and/or oro-nasal communications. Defects in the posterior alveolus and hard palate up to a diameter of 4 cm can sometimes be closed by covering them with the buccal fat pad and grafting the latter with a split thickness skin graft. In addition local flaps may be necessary. 4 cases have been treated so far with complete success.


Bioenergetics in clinical medicine-X. Survey of the adjunctive use of coenzyme Q with oral therapy in treating periodontal disease. Approximately 60% of young adults and 80% of middle-aged Americans have periodontal disease. Effective treatment of this widespread affliction is needed. It is generally believed that bacterial plaque on teeth and gingiva is the only direct cause of periodontal disease, and that control of plaque makes possible a normal periodontium in all age brackets. The fallacy in this common belief is the knowledge that effective oral physiotherapy can be ineffective in a small percentage of patients in periodontal practice. There is increasing knowledge and awareness that good nutrition is related to good periodontal health, and that many known vitamins influence the biochemistry of teeth, periodontium, and related bone.


Antihypertensive effect and serum potassium homeostasis: comparison of hydrochlorothiazide and spironolactone alone and in combination. Hydrochlorothiazide (HCT) and spironolactone (SP), alone and in combination, were utilized in the treatment of 79 adult men with mild to moderate essential hypertension. Comparative effects were determined with regard to anti-hypertensive action, serum potassium homeostasis and BUN. Both HCT and SP, alone and in combination, produced significant anti-hypertensive effects. Anti-hypertensive response to SP was clearly dose-related. All medications produced a moderate and transient elevation of BUN. The most marked differences were observed with regard to serum potassium levels (K). HCT produced a marked decrease in K which persisted through 12 weeks of therapy. SP produced moderate dose-related elevations of K which reverted toward baseline levels between the 4th and 12th weeks of treatment. The "safety advantage" of SP is discussed relative to its role in producing K homeostasis due to its unique mechanism of action.


Circadian rhythm of luteinizing hormone secretion in the ovariectomized rat implanted with oestradiol. Implantation of a solid source of oestradiol into ovariectomized rats produced constant plasma concentrations of the hormone over a long period of time. Under these conditions, LH is released in a circadian pattern with a very marked peak in the afternoon. This circadian rhythm is synchronized to the light--darkness cycle, since it follows exactly a shift in the nycthemeral cycle. The first peak appeared on day 3 after placement of the oestrogen implant; its amplitude was constant from days 3 to 9 after implantation, and decreased gradually during prolonged implantation. The afternoon peak was not correlated with changes in the pituitary sensitivity to exogenous LH releasing hormone (LH-RH), since the LH response to increasing doses of the peptide could be superimposed in the morning and in the afternoon. However, the decreased amplitude of the rhythm observed after more than 9 days of implantation seemed to depend upon a progressive desensitization of the pituitary gland to LH-RH. Pituitary LH content also decreased as a function of implantation time. It is concluded that, under conditions of constant plasma oestradiol concentrations and of constant pituitary sensitivity to LH-RH, a daily activation of the neural trigger releasing pituitary gonadotrophins occurs.


Isolation and characterization of cysK mutants of Escherichia coli K12. cysK mutants, deficient in O-acetylserine sulphydrylase A [O-acetyl-L-serine acetate-lyase (adding hydrogen-sulphide); EC 4.2.99.8], were isolated as strains resistant to selenite or giving a black colour reaction on bismuth citrate indicator medium. All were resistant to the inhibitor I,2,4-triazole. Four independent mutants were found which possessed lowered levels of O-acetylserine sulphydrylase activity and also partially constitutive levels of NADPH-sulphite reductase [hydrogen-sulphide: NADP+ oxidoreductase; EC I.8.I.2]. Strains containing both a cysE mutation and a cysK mutation lacked the constitutive levels of NADPH-sulphite reductase showing that these levels were due to the in vivo concentration of the inducer, O-acetylserine. The cysK locus was found to be 81% cotransducible with the ptsI gene.


Plasma proteins in human peripheral nerve. Using the immunofluorescent technique, the distribution of nine plasma proteins, differing in molecular weight, was studied in sural nerve biopsies from 25 neurological patients. The results of this study show that endoneurial vessels are normally permeable to all plasma proteins, though not to an equal degree. Permeability of the nerve blood vessels may be increased in pathological conditions. Proteins of molecular weight equal to or greater than 340,000 tend to accumulate at the site of the perineurium, indicating a slow removal from this structure. A marked accumulation of plasma proteins at the site of the perineurium was observed in hypertrophic neuropathy.


Studies on the phagocytic capacity of macrophage polykaryons. Following the demonstration by Chambers (1977a,b and c) that simultaneous attachment of macrophages to endocytogenic material in vitro leads to fusion, as analysis of the phagocytic potential of giant cells has provided evidence that the same mechanism is operating in macrophage polykaryon formation in vovo. Unlike previously proposed models for macrophage fusion, fusion by simultaneous attempted endocytosis is associated with the interiorisation of surface membrane during fusion. This has been shown to have occurred during glass coverslip-induced fusion in vivo. Evidence has also been presented that it is the endocytogenic material produced in the granulomatous environment which leads to fusion, not necessarily the simulaneous attempted endocytosis of the implanted foreign material.


Comparative ultrastructural morphology of aurosomes produced by colloidal gold and soluble gold salts. Intra-articular administration of colloidal gold produced aurosomes which contained spherical electron-dense granules and also often some very fine electron-dense particles. Intra-articular administration of aurothioglucose produced aurosomes of a morphology similar to that reported to occur after administration of sodium aurothiomalate. These aurosomes produced by soluble gold salts are characterised by particle and granule-studded membranous formations which present in profile as rod-like and curled filamentous structures. On the basis of morphological differences two types of aurosomes should be recognised, the "Type I or granular aurosome" and the "Type II or membranous aurosome".


The effects of therapy on the developmental scores of iron-deficient infants. To test the hypothesis that iron deficiency in infants and children is associated with behavioral alterations, 24 infants with iron deficienty anemia, ages 9 to 26 months, were randomly assigned to a treatment and control group. Bayley Scales of Infant Development were administered before treatment with intramuscular iron or placebo; the test was readministered in five to eight days. Children treated with iron showed a significant increase in their scores on the Mental Development Index averaging a mean gain of 13.6 points in a mean time of 6.8 days. The treated group was found to become more alert and responsive and demonstrated improvement in tests of gross and fine motor coordination. These findings support the hypothesis that iron deficiency in infants produced developmental alterations and that these changes are rapidly reversible with iron therapy.


Chemotactic defects in severe combined immunodeficiency. Cellular and humoral components of leukotaxis were studied serially in four male infants with severe combined immunodeficiency disease. Two of the four, both lacking B and T cells initially, had a significant defect in neutrophil and monocyte chemotaxis. The other two, who had a high number of immunoglobulin-bearing cells (B cells), did not have these cellular abnormalities. It contrast, defective generation of chemotactic factor following endotoxin activation was observed in all patients. The defects were corrected coincident with or soon after successful engraftment of either bone marrow or fetal tissues. The reported deficiencies may be another manifestation of the heterogeneity in SCID.


Atypical ichthyosiform erythroderma and congenital neurosensory deafness--a distinct syndrome. A patient has been studied in whom an atypical ichthyosiform erythroderma was associated with congenital neurosensory deafness, vascularization of the corneas progressing to blindness, alopecia totalis, abnormalities of the teeth and nails, and postnatal growth deficiency. Twelve other patients with a similar pattern of malformation have been reported previously. This syndrome appears to represent a distinct disorder with a pattern of inheritance which is most likely autosomal recessive.


Free amino acids in brain, liver, and skeletal muscle tissue of voles infected with Trypanosoma brucei gambiense. The concentrations of several acidic and neutral amino acids of brain, liver, and skeletal muscle were determined in field voles, Microtus montanus, and compared to values obtained from voles harboring a chronic infection of Trypanosoma brucei gambiense. All of the amino acids examined were found at comparable levels in brain tissue from both groups of animals with the exception of tyrosine, which was reduced by approximately 45% in the infected voles. Similarly, the only difference noted in liver tissue was 32% decrease of free tyrosine in the infected animals. With respect to muscle tissue, in addition to a 45% reduction of free tyrosine in the infected voles, decreases of a smaller magnitude were also noted for threonine, glutamate, and valine. The relatively specific alteration of free tyrosine concentrations in the investigated tissues of trypanosome-infected animals suggests an alteration in host metabolism of this amino acid and/or parasite utilization.


Management of neonates and children with male pseudohermaphroditism. Twenty-five patients with male pseudohermaphroditism were treated. Causes included (1) inadequate testosterone production, (2) incomplete conversion of testosterone to dihydrotestosterone, and (3) insufficient androgen-binding protein at the target cell. These various problems can be defined accurately today. These infants should be studied early to define which gender role is more appropriate. Change in gender assignment later can be disastrous. An individual raised in the female role, but with incomplete internal structures, can cope with life better than one raised in the male role but lacking a satisfactory phallus. In general, we believe most male pseudohermaphrodites should be raised as females, performing appropriate alterations at an early age.


Successful renal transplantation in infancy. This infant's post renal transplantation course, representing apparently the smallest long term survivor, illustrates that neither age nor size are contraindications to successful renal transplantation in infants with end stage renal failure. Additional experience with the transplantation of a single kidney into a 1-yr-old baby weighing 4650 gm with congenital bilateral renal hypoplasia has also been successful with a 3-mo follow-up. Both cases demonstrate that single or double renal transplantation in infants is feasible and should be considered when indicated.


Serum polyamine and octopamine changes following partial hepatectomy and portacaval shunt. Factors influencing hepatic regeneration following major hepatic resection are poorly understood and often may be modified by associated surgical procedures. Experimental and clinical evidence would suggest that hepatic regeneration may be impaired following hepatectomy performed in conjunction with portacaval shunting. A patient is described who offered a clinical situation in which it was possible to evaluate the effects of complete portal-venous diversion on hepatic regeneration following massive hepatic resection. The usefulness of biogenic amines as a monitor of the course of hepatic regeneration is demonstrated. The potential development of hepatic encephalopathy was evaluated by serial determinations of serum ammonia and the biogenic amine, octopamine, which correlated well with the patient's clinical state.


Gingival fluid and serum in periodontal diseases. II. Evidence for cleavage of complement components C3, C3 proactivator (factor B) and C4 in gingival fluid. 1. C3 activation products  C3c and C3d can be demonstrated in gingival pocket fluid from patients with severe periodontitis. 2. Quantitatively, C3d levels in GF are comparable to levels attained consequent to immune-complex and tryptic activation of human serum. 3. The alternate pathway of complement activation occurs in the periodontal pocket, as demonstrated by conversion of C3 proactivator (Factor B) to C3-activator Bb. 4. C4 is present in an altered form in some, but not all, GF's. This form is electrophoretically similar to that generated from serum by C1s and several proteolytic enzymes.


l-Bunolol metabolism in rats: identification of urinary metabolites. Urine collected for 24 hr from rats given a single oral dose of 3H-l-bunolol (10 mg/kg) was found to contain only 25.8% of the dose and more than 30 labeled compounds. Nine compounds were identified and quantified as follows: bunolol (0.35% of urinary tritium), bunolol glucuronide (5.12%), bunolol sulfate (0.08%), dihydrobunolol (0.08%), dihydrobunolol glucuronide (0.74%), dihydrobunolol sulfate (0.12%), hydroxydihydrobunolol (0.58%), beta-(5-oxytetralonyl)lactic acid (0.74%), and (5-oxytetralonyl) acetic acid glucuronide (1.12%). The total quantity of identified labeled compounds was only 2.3% of the dose and 8.9% of the urinary radioactivity.


In vitro studies on drug--antibiotic interactions I: analgesics, antipyretics, antimalarials, and tranquilizers. The antimicrobial effects of some analgesics, antipyretics, antimalarials, and tranquilizers were determined. The phenothiazines were the most active group. The effect of the chosen drugs when combined with a selected number of antibiotics was studied on Staphylococcus aureus and Escherichia coli to determine the type of interaction. Most analgesics, antipyretics, and antimalarials showed either no effect or a synergistic action. However, some exhibited antagonistic effects. All tested tranquilizers were synergistic. Preliminary studies, using electronic absorption spectrometry, indicated that the antagonistic action may be attributed to a physical interaction.


Inhibition by paromomycin of R-factor transfer of tetracycline resistance between Escherichia coli and Salmonella pullorum. In vitro assays showed that low concentrations (5--10 and 20 microgram/ml) of the antimicrobial paromomycin sulfate are able to block or diminish significantly the transfer of the tetracycline resistance R-factor between Escherichia coli and Salmonella pullorum. This observation is important because it offers the possibility of preventing the formation of tetracycline-resistant pathogens, a limiting factor of tetracycline use in both human and veterinary medicine.


DNA and protein changes in the spermatozoa of bulls treated orally with ethylene dibromide. Oral treatment of bulls with ethylene dibromide caused a temporary reduction of the DNA and protein content and head area of epididymal and ejaculated spermatozoa.


Nitramino acids. Synthesis and biological evaluation of 1-nitroproline, 1-nitropipecolic acid, and N-nitrosarcosine. The N-nitro derivatives of secondary alpha-amino acids, viz., 1-nitroproline (1a) (L and D), 1-nitro-DL-pipecolic acid (2a), and N-nitrosarcosine (3a), were prepared by the oxidation of the corresponding nitrosamino acids with peroxytrifluoroacetic acid. These nitramino acids (1a-3a) were not active against Escherichia coli, Candida albicans, Pseudomonas aeruginosa, or Mycobacterium smegmatis, and 1a and 2a did not show mutagenic activity in a Salmonella typhimurium TA-100 system, with or without added rat liver 9000g supernatant fraction. The marginal mutagenicity of 3a in this system suggests that additional work should be done to assess its carcinogenic-mutagenic potential.


Studies of antitumor agents. 1. Resolution of racemic 1-(tetrahydro-2-furanyl)-k-fluorouracil into the R and S isomers and examination of the biological activities of the isomers. 1-(Tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU), which is named Ftorafur or FT-207 and is used clinically as an antitumor agent, was conveniently synthesized by condensation of the trimethylsilyl derivative of 5-fluorouracil with 2-acetoxytetrahydrofuran using NaI as a catalyst. This optically inactive Thf-FU was resolved into optically active (R)-(+)- and (S)-(-)-Thf-FU in high optical purity and excellent yield by formation of diastereoisomers with brucine. 13C NMR data were obtained on Thf-FU and related compounds and the antibacterial activities and in vivo antitumor activities of these isomers were tested. The degradations of these isomers to 5-fluorouracil by liver microsomes were also examined. No significant differences were found in any of these properties of these isomers.


Nonapeptide ethylamide inhibitors of the luteinizing hormone-releasing hormone (LH-RH) having a D-alanyl residue in position 6 and variations at positions 2 and 3. A series of ten analogues, of structure des-Gly10-[amino acid2, amino acid3,D-Ala6]-LH-RH ethylamide, was synthesized by solid-phase methods. L-Aromatic and alkylamino acids were substituted into position 2 and alkylamino acids into position 3. Highest in vitro inhibition of LH-RH action was obtained with analogues having aromatic residues in position 2. Des-Gly10-[Trp2,Leu3,D-Ala6]-LH-RH ethylamide inhibited the action of 0.6 ng/mL of LH-RH, in an isolated pituitary assay, at a dosage as low as 1 microgram/mL, and the corresponding Phe2 analogue inhibited the effect of 0.3 ng of LH-RH at 0.1 microgram/mL. The Trp2 analogue inhibited ovulation in rats at the dosage of 1.5 mg per rat.


Inhibitory analogues of the luteinizing hormone-releasing hormone having D-aromatic residues in positions 2 and 6 and variation in position 3. A single sc injection of 750 microgram/rat of [D-Phe2,Pro3,D-Phe6]-LH-RH on proestrus completely inhibited ovulation in 4-day cycling rats. Ovulation was inhibited partially at 375 microgram/rat. At the 720 microgram/rat dosage, analogues of LH-RH with D-Phe in positions 2 and 6, and with Sar, Arg, or Hyp in position 3, resulted in partial inhibitors and an inactive analogue with Thr substitution. In the same assay, analogues with D-Phe in position 2 and D-Trp in position 6 were partial inhibitors when D-Phe, Met, or Val were in position 3 and inactive with Ile substitution.


Conformational analysis of the molecule luteinizing hormone-releasing hormone. 3. Analogue inhibitors and antagonists. Conformational energy calculations have been carried out on analogues of luteinizing hormone-releasing hormone which have been shown to be potent inhibitors of the release of luteinizing hormone and follicle-stimulating hormone. The analogues included in this study have D-amino acid substitutions in the 2 and/or 3 positions, such as [D-X2]-LH-RH, [D-X2,D-Y3]-LH-RH, [D-X2,Pro3]-lh-rh, and [D-X2,Leu3]-LH-RH. A configurational property which was common to the low-energy conformers of all the analogues is the directional change of the cis-peptide bond of the pyroglutamate ring. Further, there was no overall structural change in the analogues relative to the conformation of native LH-RH, and the orientation of the aromatic side chains relative to one another remained the same throughout this series of analogues.


A comparison of alternate metabolic strategies for the utilization of D-arabinose. Mutants of Klebsiella aerogenes W70 that metabolize the uncommon pentose D-arabinose were isolated. These mutants were found to be either constitutive or indicible by D-arabinose for the synthesis of enzymes in the L-fucose pathway. Such mutants could then utilize L-fucose isomerase to convert the structurally similar D-arabinose molecule to D-ribulose. D-Ribulose is an intermediate and the inducer of an existing ribitol pathway and could thus be metabolized. In those D-arabinose-positive mutants where the ribitol pathway was blocked by mutation, D-ribulose could alternatively be metabolized by using the remaining L-fucose pathway enzymes. When the two D-arabinose catabolic routes were compared, catabolism of D-arabinose via the ribitol pathway was found to be more efficient. Catabolism of D-arabinose using the L-fucose pathway permitted D-ribulose to escape into the media and produced an unmetabolizable end product, L-glycolic acid. A comparison of growth using constitutive versus inducible control of the borrowed L-fucose isomerase did not reveal an advantage for one control type over the other. Several differences were observed, however, when we determined the degree to which these control mutations perturbed the normal functioning of the L-fucose and associated pathways. Growth of the constitutive mutant was impaired with L-fucose as substrate. The inducible-control mutant had altered growth characteristics on ribitol and L-rhamnose.


Mutagenic activity of major mammalian metabolites of cyclophosphamide toward several genes of Escherichia coli. Representative intermediates of the major mammalian metabolic pathway of cyclophosphamide, a drug that is not mutagenic as such unless it is metabolically activated, were assayed for their direct mutagenic activity toward a bacterial indicator strain, Escherichia coli 343/113. The compounds tested were 4-hydroperoxycyclophosphamide and the two urinary metabolites, carboxyphosphamide and 4-ketocyclophosphamide. Further, the degradation products of 4-hydroxycyclophosphamide, phosphoramide mustard, acrolein, and nornitrogen mustard, were also tested. The mutagenicity test systems were those used previously to demonstrate the liver enzyme-mediated mutagenic activity of cyclophosphamide in E. coli 343/113: stationary cell suspensions were treated for 180 min at 37 degrees C with different concentrations of the compound under test; the induction of forward mutations from 5-methyltryptophan sensitivity to resistance (MTR) and from galRs18 to gal+ as well as back mutations from arg56 to arg+ was measured by plating aliquots of the treated bacterial population on different selective mutation media. Except for acrolein, all cyclophosphamide metabolites tested are directly mutagenic toward E. coli 343/113. With all substances the highest induced mutation frequency is that of arg+ mutations, followed by gal+ and MTR  mutations; this indicates that mostly base-pair substitution type mutations are induced. The mutagenic potential, however, differs greatly between compounds at concentrations between 0.1 and 20mM. The results show that the first step in the mammalian biodegradation of cyclophosphamide gives rise to compounds that are directly mutagenic, and that this mutagenicity is retained and even enhanced through all further metabolic steps to produce the compound of highest mutagenicity, nornitrogen mustard.


Experience with the use of proteolytic enzyme (Travase) in burn patients. In an effort to find an enzyme preparation for chemical debridement of burns, we treated 463 burn patients with Sutilains ointment (Travase) from 1972 through 1975. This method allowed earlier application of the first skin graft and resulted in a shorter hospital stay without significantly altering mortality compared with results obtained before 1972 and with national results. Travase appears to be effective in the treatment of burn patients when used in this method.


"Host shutoff" function of bacteriophage T7: involvement of T7 gene 2 and gene 0.7 in the inactivation of Escherichia coli RNA polymerase. The "host shutoff" function of bacteriophage T7 involves an inactivation of the host Escherichia coli RNA polymerase by an inhibitor protein bound to the enzyme. When this inhibitor protein, termed I protein, was removed from the inactive RNA polymerase complex prepared from T7-infected cells by glycerol gradient centrifugation in the presence of 1 M KCl, the enzyme recovered its activity equivalent to about 70 to 80% of the activity of the enzyme from uninfected cells. Analysis of the activity of E. coli RNA polymerase from E. coli cells infected with various T7 mutant phages indicated that the T7 gene 2 codes for the inhibitor I protein. The activity of E. coli RNA polymerase from gene 2 mutant phage-infected cells, which was about 70% of that from uninfected cells, did not increase after glycerol gradient centrifugation in the presence of 1 M KCl, indicating that the salt-removable inhibitor was not present with the enzyme. It was found that the reduction in E. coli RNA polymerase activity in cells infected with T7(+) or gene 2 mutant phage, i.e., about 70% of the activity of the enzyme compared to that from uninfected cells after glycerol gradient centrifugation in the presence of 1 M KCl, results from the function of T7 gene 0.7. E. coli RNA polymerase from gene 0.7 mutant phage-infected cells was inactive but recovered a full activity equivalent to that from uninfected cells after removal of the inhibitor I protein with 1 M KCl. E. coli RNA polymerase from the cells infected with newly constructed mutant phages having mutations in both gene 2 and gene 0.7 retained the full activity equivalent to that from uninfected cells with or without treatment of the enzyme with 1 M KCl. From these results, we conclude that both gene 2 and gene 0.7 of T7 are involved in accomplishing complete shutoff of the host E. coli RNA polymerase activity in T7 infection.


I protein: bacteriophage T7-coded inhibitor of Escherichia coli RNA polymerase. Bacteriophage T7-coded inhibitor of Escherichia coli RNA polymerase, termed I protein, was purified from an inactive E. coli RNA polymerase-I protein complex isolated from phage T7-infected cells. A molecular weight of about 7,000 to 9,000 was assigned to the purified I protein by acrylamide-sodium dodecyl sulfate gel electrophoresis, Sephadex G-50 gel filtration, and glycerol gradient centrifugation analysis. I protein inhibits initiation of RNA synthesis by directly binding to the RNA polymerase holoenzyme and prevents the binding of the enzyme to the promoter sites on the template T7 DNA. However, once a highly stable transcriptional preinitiation complex between RNA polymerase holoenzyme and T7 DNA is formed at the promoter site on T7 DNA in the absence of nucleoside triphosphates, I protein does not inhibit the initiation of RNA synthesis by this preformed complex upon addition of nucleoside triphosphates. RNA synthesis by the core RNA polymerase and the binding of core RNA polymerase with template DNA are not inhibited by I protein, although a partial association between the core enzyme and I protein can be observed. I protein does not bind to sigma factor or T7 DNA. Therefore, binding of I protein with the RNA polymerase, which results in the inhibition of initiation of RNA synthesis, requires the presence of sigma factor in the RNA polymerase holoenzyme form.


Hepatitis B antigen and polymyositis.

Hepatitis B antigen and polymyositis. Concomitant polymyositis diagnosed by muscle biopsy developed in a 51-year-old man with hepatitis B surface antigen (HBsAg) hepatitis. Findings from immunofluorescent studies showed deposits of gamma-globulins and complement in both muscle and liver. The HBsAg and HBsAg-antibody complexes were detected in the liver by immunofluorescence using fluorescein-labeled antibody to hepatitis Bs.


[Clinical experience with S-6436 in patients with urinary tract infections (author's transl)]. Forty eight patients with urinary tract infections including a case of acute prostatitis were treated with S-6436 and the following results were obtained: 1. Thirty eight patients with acute cystitis resulted in 19 excellent, 15 good and 4 poor with effectiveness rate of 89.5%. 2. Ten patients with complicated urinary tract infections resulted in 1 excellent, 5 good and 4 poor with effectiveness rate of 60%. 3. Infecting organisms from 38 patients with acute cystitis were occupied by 28 strains of E. coli. The sensitivity rate of the infecting organisms to cephalexin was 96.4%. 4. In a few cases (6.25%) side effects of S-6436 were observed. 5. S-6436 will be one of the good first choice antibiotics for acute cystitis.


Suspecting thoracic aortic transection.

Suspecting thoracic aortic transection. Deceleration accidents produce a complex of potentially fatal thoracic injuries. Because early detection is the key to successful management of blunt trauma to the great vessels, emergency physicians must be knowledgeable of signs indicative of these complex injuries. Among more than 10,000 patients presenting to the Ben Taub Emergency Center over an 11-year period with thoracic injuries, 100 had clinical or radiographic clues suggestive of blunt trauma decelerative injury to the great vessels. Of these 100 patients, 23 had transection of the descending thoracic aorta and five had avulsion of the innominate artery. One patient had a double transection. Six patients died in the Emergency Center before proximal control could be achieved.


["Primary" reticulum-cellsarcoma of the retina. I. Clinico-pathologic study of 5 patients (author's transl)]. Between 1964 and 1974 a primary reticulum-cellsarcoma of the retina was diagnosed histologically in 5 patients (between 44 and 71 years), in one already clinically. The initial diagnosis had been "uveitis" (2), "panuveitis" (1), "iridocyclitis with central retinal artery occlusion" (1), and "chorioretinitis" (1). The usual antiinflammatory therapy was without effect in every instance. All patients showed neurological symptoms with cerebral manifestations. Twice the cerebral biopsies had been misinterpreted initially as "atypical glioblastoma multiforme", once as Neuro-Behçet. The disease progressed over a course of 2--10 years from the initial ophthalmic symptoms to death. A review of the literature is given and the differential-diagnosis to necrotizing forms of retinitis, dissiminated chorioiditis neoplastic processes of retina and uvea and degenerative diseases are discussed. The primary reticulum-cellsarcoma of the retina must be considered in the differential-diagnosis of uveitis or panuveitis if 1. there is progression in spite of the usual antiinflammatory therapy, 2. the initial infiltrations are seen in the deep layers of the sensory retina.


["Primary" reticulum cell sarcoma of the retina. II. Clinical diagnosis and course after radiotherapy (author's transl)]. A 59-year-old patient with "exudative chorioretinitis" progressed from confluent infiltration of the deep layers of the sensory retina, perivascularly and at the level of the pigmentepithelium to total infiltration of the vitreous. This occurred in spite of all the conventional antiinflammatory therapy. A clinical diagnosis of primary reticulum-cellsarcoma of the retina was made because diagnostic vitrectomy for cytologic study was refused. Radiotherapy with 4000 R by Betatron led to a rapid disappearance of the infiltration in the vitreous and retina and to diffuse subretinal scaring of the entire fundus (histologically confirmed). One year later the patient died in a psychiatrically disoriented state. It is thought that the course after radiotherapy and the histological findings support, although not definitely confirm, the clinical diagnosis. Clinical criteria may suffice for the diagnosis in desperate situations to initiate effective radiotherapy in these fatally ill patients.


[Experiences in the medical treatment of progressive myopia (author's transl)]. In order to judge the effect of anthocyanosides and vitamine E (Difrarel E) on refraction, visual acuity and eye-fundus, we treated 36 patients with this speciality in progressive myopia. After an observation period of 14.5 months an average increase of myopia by 0.53 dpt per eye was demonstrated. The final examination of 29 patients showed a stabilization of the fundus-alterations, as well as a stable, or an improved visual acuity respectively. In 7 patients a moderate deterioration of the partial or overall medical findings occured. Our observations allow the conclusion that Difrarel E achieves therapeutically valuable results in the treatment of progressive myopia.


[Lens induced myopia in steroid cataracts (author's transl)]. Longterm investigations of patients on immun-suppressive corticosteroid therapy showed that the development of advanced corticosteroid cataracts is accompanied by a marked increase of lens myopia up to 7.5 dpt. It can be assumed that this phenomenon is due to the optical effect of the discoid posterior subcapsular opacities.


[Application of a muscle-localisator for the "Fadenoperation" according to Cüppers (author's transl)]. A new muscle-localisator for the "Fadenoperation" according to Cüppers in demonstrated. In some points this new instrument reduces the difficulties of this operation: 1. Careful fixation of the eye with sufficient exposure of the operation-field. 2. Exact measurement of the new position of the muscle. 3. Exact localisation of the U-sutures for the new functional fixation of the muscle.


[Immunologic HLA-typing. A tool for selection of recipients in transplantation and for detection of disposition to certain diseases (author's transl)]. Some decades ago, animal experiments have shown that inbred mice with completely identical genetic characteristics accept transplants between each other without any problem while transplants between individuals of genetically different strains are being rejected after a few days. It was also proven later that with men, genetical factors are responsible for acceptance or rejection of homologous transplants. These genetic factors, although they are called the HLA system, are located on the sixth chromosome. Methods were developed to determine the inherited HLA antigens with the help of antibodies present in the blood serum of pregnant women. The determination is of great importance in preparing transplants organ, especially of kidneys, because chances of successful transplantation are the greater, the better the correspondence of HLA antigens between donor and recipient. Furthermore, there exists growing indication that HLA antigens are coupled or even partly identical with the immune response gene products. These determine whether an individual is more or less suited to develop an immunity against bacterial or viral infections. Finally, there subsist associations of certain HLA antigens and diseases such as gluten enteropathy, myasthenia gravis, multiple sclerosis, diabetes mellitus and many others.


A transplantable immunocytoma of the rat as a model for the study of immunoglobulin secretion. An immunoglobulin secreting tumor appeared spontaneouldy in the LOU/Dec rat strain in an incidence of about 3--5% at age 8-20 months. Attempts to increase the incidence using such things as genetic selection, carcinogens, immunosuppressants, adjuvants, cell-free fumor material, and antigenic stimulation were unsuccessful. The tumor was found to be easily transplanted. It secreted monocolonal immunoglobulins related to most of the normal rat immunoglobulins: IgG, IgA, IgM, IgE, and some light chains. Some tumor lines were found to be sensitive to chemotherapy. Tumor-bearing rats, cured by chemotherapy, were found to be resistant to subsequent challenge graft of the tumor. The resistant state could be transferred from one animal to another by parabiosis or peritoneal exudate, but not by way of serum. It was concluded that the tumor-bearing LOU/Dec rat is an excellent model for studies of immunoglobulin secretion, and the cured, resistant rat is an excellent model for studies of cell mediated immunity.


Radiation induced osteogenic sarcoma in the rat as a model of hormone-responsive differentiated cancer. An osteogenic sarcoma was induced in an inbred strain of the Sprague Dawley rat using seven serial injections of 32P-orthophosphate. The tumor was maintained by transplantation over a 3-year period in the same inbred strain. During this time it retained its bone-like differentiation. Tumor membranes and freshly isolated tumor cells also retained responsiveness to parathyroid hormone and to prostaglandins of adenylate cyclase and cyclic nucleotide formation respectively. The potencies of these agents and their analogues and metabolites were found to be proportional to their efficacies as bone resorbing agents. Thus, the tumor was shown to be a model for the study of hormone-responsiveness for tumor growth and differentiation, and also of the effects of agonists which act on bone-like cells.


The increasing value of congenic mice in biomedical research. The development of congenic mouse strains, strains which differ from their inbred partner strains by only a single selected character, was described; and three a examples of important finding made possible by the use of such strains were given. The first example showed how a gene in a major histocompatibility complex influences susceptibility to spontaneous leukemia. The second example illustrated how a particular constellation of genes in a congenic hybrid may lead to autoimmune disease that does not occur in either parental strain. The third example was concerned with function of major histocompatibility genes as identification markers which enable individual mice to recognize one an other by scent.


Clinical trial with rifampicin in the treatment of leprosy (final report). A controlled trial of Rifampicin plus Dapsone had been in progress for two years in the Department of Leprology, School of Tropical Medicine, Calcutta. Interim results of this trial after six months treatment were reported in 1976. The present paper is the final report of the study after two years of treatment. The study reveals that with Rifampicin, MI falls rapidly after six months, but changes in BI are not better than in the DDS group. As a matter of fact, regarding BI, treatment with DDS has given better results as two cases have become negative in the DDS group while no case has become negative in the Rifampicin group. It is, therefore, concluded that clinical improvement with Rifampicin is similar to that with DDS.


Hydnocarpus oil as an antileprotic agent in footpad technique. Hydnocarpus oil alone and mixed with dapsone in food and fed to the mice infected with Mycobacterium leprae; showed inhibition of the growth of the lepra bacilli, both sensitive and resistant to dapsone. There was an additive inhibitory effect of the combination of dapsone and oil on the growth of bacilli.


Methods for rapidly altering the permeability of mammalian cells. Various agents alter mammalian cells so that they rapidly become nonspecifically permeable to substances that ordinarily do not penetrate intact cells. Thus, toluene renders liver cells permeable to nucleotides and macromolecules. Tween 80 and Tween 60 act on similar fashion, and the effect is reversible. Dextran sulfate reversibly alters the permeability of Ehrlich ascites tumor cells, which offers a tool for studying the control of macromolecular syntheses and other processes. Brief exposure to external ATP alters the permeability of certain transformed mouse cells but not of untransformed cells. The effect of ATP is rapidly reversible.


L-Arabinose transport and the L-arabinose binding protein of Escherichia coli. The active accumulation of L-arabinose by arabinose induced cultures of Escherichia coli is mediated by 2 independent transport mechanisms. One, specified by the gene locus araE, is membrane bound and possesses a relatively "low affinity". The other, specified in part by the genetic locus araF, contains as a functional component the L-arabinose binding protein and functions with a "high affinity" for the substrate. The L-arabinose binding protein has been purified, partially characterized, crystallized, and sequenced.


Chemical and immunological studies of cell surfaces from normal and transformed cells. Immunological and chemical studies of cell surfaces from normal and transformed BALB/c fibroblasts have shown alterations associated with transformation. The cells studied include normal lines which do not cause tumors when injected into BALB/c mice, viral transformants, and spontaneous transformants which cause tumors that either regress or grow progressively, killing the host. The spontaneously transformed progressors include cell lines which are immunogenic and nonimmunogenic as determined by the ability of tumor excision to protect an animal from subsequent rechallenge by tumor cells. Tumor-bearing mice produce lymphocytes which are nonspecifically cytotoxic for all the normal and transformed lines. Some of the cell lines induce specific antibody formation in BALB/hosts. Antisera have been prepared in rabbits which are specific for the transformed cell lines. These antisera can be used to determine specific surface changes on the transformed cells. Chemical studies have shown glycolipid alterations between the normal cells and some, but not all, of the transformants. Glycoproteins labeled by lactoperoxidase-125I or [3H] glucosamine were compared by SDS gel electrophoresis. Results from these studies do not show changes associated with malignancy. Individual glycoprotein regions from gels were treated with pronase, and the glycopeptides compared by Sephadex G50 chromatography. Alterations in glycopeptides from several cellular glycoproteins are the only changes which appear to be associated with malignancy.


The mechanism of sugar-dependent repression of synthesis of catabolic enzymes in Escherichia coli. Previous studies have indicated that the Escherichia coli adenylate cyclase (AC) activity is controlled by an interaction with the phosphoenolpyruvate (PEP): sugar phosphotransferase system (PTS). A model for the regulation of AC involving the phosphorylation state of the PTS is described. Kinectic studies support the concept that the velocity of AC is determined by the opposing contributions of PEP-dependent phosphorylation (V1) and sugar-dependent dephosphorylation (V2) of the PTS proteins according to the expression percent VAC=100/[1 + (Max V2/Max V1)]. Physiological parameters influencing the rate of the PTS are discussed in the framework of their effects on cAMP metabolism. Factors that increase cellular concentration of PEP (and stimulate V1) appear to enhance AC activity while increases in extracellular sugar concentration (which stimulate V2) or internal levels of pyruvate (which inhibit V1) inhibit the activity of this enzyme.


The ideology of a therapeutic social movement: Alcoholics Anonymous. Some of the medical, psychological and religious origins of Alcoholics Anonymous are traced, and aspects of A.A. and the Washingtonian Movement are compared.


Effect of anesthesia and surgery on immunity. The observed phenomenon that multiple distant metastases may appear and grow rapidly after operation on the primary cancer is very distressing. Many experimental results suggest that surgical procedures may precipitate dissemination and growth of tumor in some instances, but the overwhelming evidences document that surgical reduction of tumor bulk can achieve cure for the host and restore the immunity lost in the face of growing tumors. Various anesthetics were shown to interfere with many phases of the immune response. But recent studies suggest that the inhibitory effect of anesthesia alone is minimal. Depression of lymphocyte transformation, detectable as early as 2 hours after induction, was related primarily to the extent of tissue trauma, the amount of blood loss, duration of operation, and whether thoracic or abdominal cavity was entered. Posoperative changes of lymphocyte counts and transformation responses usually returned to normal values within a week, whereas depression of specific cellular immunity to tumor-associated antigen in vitro, and delayed cutaneous hypersensitivity reactions in vivo, persisted for about a week and gradually returned to normal by 3 weeks. Presently the clinical significance of such transitory depression of host immunity is not known. It is hoped that this review may stimulate interest in further experimental and clinical research.


Squamous cell carcinoma of the thyroid: a report of two cases. Two patients with squamous cell carcinoma, which accounts for 1.1% of all primary thyroid carcinomas, are described. Squamous metaplasia is the most likely etiology, but an occasional carcinoma may be derived from remnants of embryonic origin. Although squamous metaplasia has been documented in several conditions involving the thyroid, no evidence exists that this predisposes to squamous cell carcinoma. Metastases and direct extension of squamous cell carcinoma in the thyroid gland are much more frequent than primary involvement and are always part of a generalized carcinomatosis. A primary lesion must always be sought; however, diagnosis may not be possible until an initially occult tumor becomes evident or even until autopsy. Because this lesion typically runs a fulminant course, radical surgical resection at the earliest opportunity offers the best hope for cure. The lesions are usually radioresistant, and chemotherapy has not been shown to alter the course of this disease.


The effects of cardiopulmonary bypass upon pulmonary gas exchange. Cardiac output, venous admixture, physiological dead space, blood gas tensions, inspired gas distribution, and other respiratory variables were measured in 10 patients breathing both air and oxygen before and on five occasions up to 10 days after coronary artery vein-graft operations under cardiopulmonary bypass with moderate hypothermia. Cardiac output was unchanged at 8 hours but fell 8 percent by 22 hours. Thereafter it progressively increased and at 10 days was higher than before the operation. Venous admixture rose to a maximum at 28 to 48 hours, postoperatively, but the increase was inversely related to the magnitude of preoperative admixture. The part played by airway and alveolar closure in determining venous admixture is discussed. While admixture increased, the nitrogen-clearance curve improved, presumably due to progressive "dropout" of the worst-ventilated regions. Physiological dead space fell to a minimum at 28 hours after operation; this was attributed to a fall in the end-inspiratory position consequent upon a reduction in both functional residual capacity and tidal volume. There was an increase in ventilation after operation, and this persisted at 10 days; it appeared to be due to reflex stimulation from the lungs and chest wall.


The observation of collagen and elastin structures in wet whole mounts of pulmonary and aortic leaflets. Porcine pulmonary and aortic heart valve leaflets have been examined as wet whole mounts with the Nomarski differential-contrast imaging technique. The fibrous components, collagen and elastin, which comprise the load-bearing components of the tissue are imaged readily as a function of location on the leaflets as well as of depth through their section. The response of the collagen and elastin structures to applied stress was observed directly with a simple straining device fitted to the microscope stage. I believe that the method has considerable advantages over standard histologic or scanning electron microscope techniques in that detailed structural studies can be related easily to the gross leaflet structure and that there is no interference with the biologic properties of the tissue.


Management of trachea--innominate artery fistula. The case histories of three patients with trachea-innominate artery fistula are presented. Low tracheostomy was the etiologic factor producing the fistula in two patients. In both cases, the neck was hyperextended by placing a large roll behind the patient's shoulders and thereby elevating the trachea out of the mediastinum. In one patient a balloon cuff eroded the innominate artery. Management of these patients includes control of hemorrhage by cuff overinflation and/or by endotracheal intubation and packing of the tracheostomy site. The best surgical approach is via a right anterior thoracotomy and a separate neck incision to isolate the blood vessels involved. Median sternotomy should be avoided to prevent mediastinal infection and sternal dehiscence. Carotid stump pressures are a useful guide to determine the efficacy of innominate artery ligation. One patient was saved and is a long-term survivor.


Transplantation of the left lung into the right hemithorax to facilitate immediate reconstitution of bronchial artery flow. Immediate bronchial artery reconstitution may be important in the prevention of bronchial anastomotic problems in lung transplantation. To facilitate this reconstitution in circumstances requiring allograft replacement of the right lung, we developed a method for transplanting the left lung together with its bronchial arterial supply into the right hemithorax. With this method, left lungs were allotransplanted into the right hemithorax of nine immunosuppressed dogs. Six recipients survived 1 to 4 weeks. Death resulted from pneumonia or rejection, and there were no bronchial anastomotic problems. Roentgenograms showed that the bronchial artery was patent and that the inverted transplanted left lungs could conform exactly to the thorax without space problems or radiographic abnormalities. Except for the unusual position of the large pulmonary arteries, angiographic patterns, function, and perfusion of the transplanted lungs were often normal and equivalent to those of the recipient's normal left lung. Thus it is possible to transplant a left lung into either hemithorax and immediately reconstitute its bronchial arterial circulation. Bronchial anastomotic problems may thereby be decreased.


Total anomalous pulmonary venous connection. Long-term results following repair in infancy. Twenty-three infants, aged 5 days to 10 months, underwent repair of total anomalous pulmonary venous connection (TAPVC). Coronary sinus drainage was unusually common, accounting for 39 percent of the total. There were three early and four late deaths. Although the hospital deaths were related to perioperative errors, two of the infants appeared to have small left ventricles. Two late deaths in infants with coronary sinus drainage were due to obstruction to pulmonary venous return some distance proximal to the surgical anastomosis. All 16 survivors were well at last review, one after revision of his repair. Fifteen have undergone late reassessment, and one of these, also with coronary sinus drainage, showed evidence of pulmonary venous obstruction. Although the early survival rate is satisfactory, the late mortality rate has been significant and the high incidence of pulmonary venous obstruction in infants with coronary sinus drainage is of particular concern.


Lymphographic diagnosis of malignant lymphoma in the course of Sjögren's syndrome. Three patients with Sjögren's syndrome complicated by malignant lymphoma are presented. During the benign stage, two showed non-specific hyperplastic lymph node patterns on lymphography. When the disease had become malignant, all cases revealed generalized involvement of the retroperitoneal lymph nodes. The lymphographic pattern was that of a malignant lymphoma: enlarged nodes, with a foamy, linear or reticular appearance but mostly preserved marginal sinuses. On lymphographic follow-up, the node alterations were consistent with the histological findings and the clinical status, including the therapeutic response.


Autogenic biofeedback treatment for migraine. Autogenic biofeedback training appears to be a promising technique for the treatment of migraine headaches, as reflected in the literature reviewed herein and in the data from 21 patients who were followed up for an average of 10 months. Autogenic biogeedback training exemplifies an important trend in psychosomatic medicine, in shifting a major portion of responsibility for treatment process both depends on and facilitates greater understanding on the part of the part of the patient of psychosomatic events relevant to symptom development. Autogenic biofeedback training may also provide a useful tool for investigators exploring the relation between psychology and somatic medicine.


Effect of ethyl alcohol on sympathetic nerve cells in cultures. Sympathetic chain ganglia of newborn rats were cultured in Rose chambers and their structure was registered, examined and photographed with a phase contrast microscope. When 0.5% (v/v) (86 mM) ethanol was present in the culture medium from the start of culture, the nerve cell bodies appeared similar to those in control cultures for at least a week and there was a normal outgrowth of a nerve fibre network. Higher concentrations had a progessively deleterious effect, 1% (171 mM) ethanol causing the appearance of degenerating cells and 2% (343 mM) ethanol killing all the nerve cells in 4 days. Some nerve cells survived 4 days in the presence of 1.5% (275 mM) ethanol in the culture medium, although most cells died in 2 days. When ethanol was added to cultures grown for 7 days in a control medium, concentration of 0.5% ethanol in the medium had no apparent effect, while most nerve cells died within a week in 1% ethanol, and all cells were dead already after 24 hours in 2% ethanol. It is concluded that ethanol exhibits a remarkably low toxicity towards living nerve cells.


[External appearance and reconstructive surgery]. An attempt is made to interpret the significance of plastic and reconstructive surgery in terms of the historical evolution of German medicine. Difficulties with other operative specialties are mentioned as well as general viewpoints of financial medical problems in our country.


[Augmentation mammoplasty (author's transl)]. Three distinct methods have proved practicable: The dermafat-transposition (DeCholnoky), the skin flap procedures, and the retromammary implants. The motivation of the patient must be carefully balanced against various complications. Frequently a constrictive fibrosis impairs the primary pleasant shape, position, and consistency of the breasts soon or many years after implantation of soft polydimethylsiloxane material, due to phagocytosis and decomposition of plastic particles. Capsulotomy, capsulectomy, or squeezing of the implants can regain approximately the original good appearance, but does not solve the problem of continuous foreign body reaction. The malignancy risks require close follow-up examinations.


[Prophylaxis of fungal contamination (author's transl)]. Increased contamination by facultative pathogens such as coliforms and related gram-negative bacteria and Candida albicans in hospital areas of risk endangers the benefits of medical care and causes great concern. The patient himself is the predominant source of nosocomial infections. Furthermore the medical staff, ward personnel, and contaminated environment must be incriminated. By proper decontamination of certain groups of high-risk patients and of their surroundings as well as by interrupting the microbial transfer at all levels, the present menace can be considerably reduced.


Tensing and stiffening of skin grafts.

Tensing and stiffening of skin grafts. Many surgeons have difficulty in cutting small split thickness skin grafts of consistent thickness and width. We demonstrate techniques using equipment and supplies almost always available for expeditious cutting and handling of small split thickness skin grafts. The methods suggested should allow surgeons to eliminate some of the problems that they have had with this basic technique of reconstruction.


The thirty degree transposition flap.

The thirty degree transposition flap. The rhomboid and other 60 degrees transposition flaps have theoretical and practical disadvantages for many applications. A better flap for these is one having an angulation of 30 degrees at its distal end. When this 30 degrees flap is combined with the M-plasty, a versatile and cosmetically favorable repair is provided for many surface defects. In fact, over the years, it has become our most useful method of closure with flaps. Fundamentally, it allows sharing of tensions of closure better than does the rhomboid flap, produces less level disparities or protrusions than does any 60 degrees flap, and its resulting scar length is only fractionally longer than that of the rhomboid flap. Rhomboid and other 60 degrees angle flaps have been exceedingly valuable tools to many surgeons; the 30 degrees flap combined with M-plasty should be significantly more useful.


Diabetic microangiopathy. I. Current status of the chemistry and metabolism of the glomerular basement membrane. In recent years, the nature of the renal glomerular basement membrane has been the subject of numerous investigations. In diabetes mellitus, the renal glomerulus is characterized primarily by thickening of the basement membrane and excessive accumulation of basement membrane-like material in the mesangial region. Compositional analyses have shown that basement membranes are glycoprotein in nature. Studies of the glomerular basement membranes in diabetes have indicated a change from normal chemical composition. Furthermore, studies of the metabolism of diabetic kidneys in experimental animals, using cortical homogenates and isolated glomeruli, have demonstrated higher anabolic and lower catabolic enzyme activities. However, contradictory data have been reported with regard to both the chemical composition and metabolism of the kidney in human and experimental diabetes. This review attempts to examine these reports in detail and discuss the possible causes for these discrepancies.


Whole-body protein synthesis and breakdown rates in children before and after reconstructive surgery of the skin. The effects of minor surgery on dynamic aspects of whole-body nitrogen metabolism were explored in healthy children aged 4--15 yr. A continuous administration of 15N-glycine was used to estimate rates of whole-body protein synthesis and breakdown both before reconstructive surgery of the skin and 5 days afterward. Mean preoperative values for protein synthesis and protein breakdown were 3.9 and 3.4 g protein/kg body weight/day, respectively. Protein synthesis decreased by 15% (p less than 0.05) postoperatively, but body weight, intake of protein and calories, nitrogen balance, and protein breakdown did not differ significantly between the two periods. Protein synthetic rate correlated (p less than 0.05) with protein (r = +0.75) and calorie (r = +0.58) intake. These results indicate that minor surgery causes a small decrease in the rate of whole-body protein synthesis even though calorie and nitrogen balance are maintained.


A new rapid modification for membrane fluorescence tests based on the Microtiter system. This paper describes the micro-membrane-fluorescence test (MMF), which is a new semiautomated technique employing units of the Microtiter system. This method allowing the performance of several hundred samples within a few hours may contribute to further standardization of immunofluorescence work on the cellular level. Furthermore, it can also be applied in immunofluorescence tests were antigen coated particles (beads) are used as antigenic substrate, instead of living cells.


The host-dependent restriction of growth of an RNA coliphage FI. Phage FIC is a spontaneous host-dependent mutant of phage FI which is classified into the fourth group of RNA Escherichia coli phages (RNA coliphages). The mutant phage (FIC) grows normally in E. coli strain Q13 (permissive host), but poorly in strain A/lambda (non-permissive host) (9). Attempts to elucidate the regulatory mechanism of growth of the mutant phage in the non-permissive host revealed the following: (a) growth of the mutant phage was specifically restricted in E. coli strains that have certain suppressor genes for amber mutation; (b) the mutant phage RNA (FIC-RNA) could not produce progeny in the spheroplasts of the non-permissive host; (c) adsorption of the mutant phage to, and penetration of the mutant phage RNA into, the non-permissive host were normal; and (d) biosynthesis of the phage-specific late protein and RNA did not occur in the non-permissive host. Based on these results we conclude that phage FIC is a spontaneous azure-type mutant of the fourth group of RNA coliphage FI.


Mechanism of defective lysogenization by phage P1 in a lon-mutant of Escherichia coli K-12. Phage P1 cannot lysogenize a lon- mutant of Escherichia coli K-12, which is defective in the regulation of cellular division cycle to result in snake formation (14). P1 mutants, called P1pla, can lysogenize the lon- host. These mutations have been classified into two complementation groups: one is cis-dominant; the other is trans-dominant. A temperature-sensitive lon- mutant was isolated, which exhibited the lon- phenotype at 42 C but not at 33 C. A temperature-shift experiment of the P1-lysogenic derivative of the lon- ts mutant showed lysis of the culture and induction of the phage production. It is proposed that P1 plasmid may be under a certain regulatory circuit of the division cycle of the host bacterium by indirectly regulating the production of P1 immune repressor, or alternatively by directly derepressing the functions of P1 prophage.


Effect of dihydroxymethyl furatrizine on cell division of Escherichia coli. Antibacterial activities of 3-di(hydroxymethyl) amino-6[2-(5-nitro-2-furyl)vinyl]-1,2,4-triazine, (dihydroxymethyl furatrizine) were investigated using mutant strains of Escherichia coli lacking repair systems for DNA damage, i.e. polA, uvrA, uvrA, uvrC, recA, recB, recC and uvrArecA. All of the mutant strains were more sensitive to the drug than the parent sgrains, as was the case with the sensitivity to UV-irradiation. These results indicate that the drug acts lethally on sensitive bacteria by damaging their DNA, and parts of the damaged DNA are repaired by excision and recombinational repair systems. Filamentous cell formation was induced in all strains except the uvrArecA strain by sublethal concentration of the drug, as well as by UV-irradiation. It is possible that the occurrence of the short period of "unbalanced growth" induced by such DNA damaging agents leads to filament formation. In the cells of the double mutant, filament formation was induced by the drug but not by UV-irradiation, and the majority of the filamentous cells formed were multinucleated. This suggests that, in this double mutant, the drug directly reacts with the septation mechinery of the cell envelope, resulting in filament formation. This hypothesis is supported by the electron microscopic observations that septation is interrupted in the filamentous cells induced by the drug.


Reduction of population levels of some indigenous bacteria by lactobacilli in the gastrointestinal tract of gnotobiotic rats. Effects of each of three indigenous Lactobacillus groups on other bacterial populations were separately investigated in gnotobiotic rats. In the wall of the non-glandular part of the stomach, contents of the stomach and contents of the upper part of the small intestine, some pre-associated indigenous bacteria were reduced to conventional population levels by introducing three groups of lactobacilli: Group I (Lactobacillus acidophilus and related strains), Group II (L. fermentum) and the groups mixed. However, no obvious reduction in cell numbers of the pre-associated bacteria occurred in the case of Group III (L. murini).


[Influence of (+)-cyanidanol-3 on acute hepatitis. Results of a double blind study (author's transl)]. 42 cases of acute hepatitis diagnosed from 1970 to 1974 were reviewed retrospectively. The effect of (+)-Cyanidanol-3 on the course of acute hepatitis was controlled on 35 patients in a double blind study. During acute hepatitis, bed rest had an essential influence on the time needed to normalize the transaminases. Based on these observations, we proved the effect, that during treatment with (+)-Cyanidanol-3 the patients showed a positive influence regarding the time for normalization of the transaminases in contrast to the placebo-group. During the first weeks the depression of the transaminase-activity in the blood was noticeable. Because of the small number of patients in that group, this effect could not yet been proved statistically. The stimulation of ATP synthesis as the main therapeutic principle can show a favourable result in the treatment of acute hepatitis.


Chronic homeostatic vagal efferent activity turndown: a theory of asthma. There is an abundance of evidence of an autonomic nervous system (ANS) imbalance in asthma, and most theories have suggested that a defect in the ANS is the fundamental pathology in asthma. This paper proposes that there is no ANS defect in asthma. It assumes that the normal homeostatic response to bronchial obstruction is a reduction in the vagally mediated, normal bronchoconstricting tonus of the airways. It then discusses how many of the pathological features of asthma may be shown to result from chronic vagal efferent activity turndown which itself results from protracted intense and continuous bronchial obstruction.


Repair of DNA double-strand breaks requires two homologous DNA duplexes. DNA repair and cell survival in haploid and its diploid derivative strains of Saccharomyces cerevisiae were studied after 100 krad X-ray irradiation. The cells were in the G1 stage of the cell cycle, where haploid cells had only one copy of genetic material per genome and diploid had two copies. It was found that diploid could repair double-strand breaks in its DNA after 48 hr of liquid holding which was accompanied by a four-fold rise in survival. In contrast a haploid strain failed to repair its DNA and showed no increase in survival after liquid holding. It is concluded that (1) repair of DNA double-strand breaks requires the availability of two homologous DNA duplexes, (2) restoration of cell viability during liquid holding is connected with repair of DNA double-strand breaks and (3) this repair is a slow process possibly associated with slow finding and conjugation of homologous chromosomes.


The action of structural analogues of ethidium bromide on the mitochondrial genome of yeast. We have studied the effects on the yeast mitochondrial genome of four analogues of ethidium bromide, in which the phenyl moieyt has been replaced by linear alkyl chains of lengths varying from seven to fifteen carbon atoms. These analogues are more efficient than ethidium bromide in inducing petite mutants in Saccharomyces cervisiae. The drugs also cause a loss of mtDNA from the cells in vivo; however these analogues are in fact less effective inhibitors of mitochondrial DNA replication per se, as shown by direct in vitro studies. It is concluded that these analogues are more efficient than ethidium bromide in causing the fragmentation of mitochondrial DNA in S. cervisiae.


Spontaneous mutability in UV-sensitive excision-defective strains of Saccharomyces. The genes RAD1, RAD2, RAD3 and RAD4 encode enzymes in the pathway leading to excision repair of UV-induced DNA damage in Saccharomyces cerevisiae. Four mutant alleles of these loci (rad1-1, rad2-2, rad3-12, and rad4-3) were studied for their effect on spontaneous reversion rate to lysine and histidine independence, by means of the 1000-compartment fluctuation test of von Borstel, Cain and Steinberg. Of these four excision-defective alleles, only rad3-12 was found to substantially increase the spontaneous reversion rate of the nonsense-suppressible lys1-1 allele, both through locus reversion as well as  by forward mutation at one of eight suppressor loci. Similarly, only rad3-12 conferred a considerable increase in the reversion frequency of the missense his1-7 mutant. As the RAD3 gene product is believed to mediate the first step in the excision-repair pathway, it is assumed that spontaneous lesions in the  rad3 strain are channelled into a mutagenic repair pathway, thus accounting for  the enhanced spontaneous mutation rate.


Cytogenetic assays of chemical clastogens using mammalian cells in culture. A protocol is described for cytogenetic assays of chemical mutagens using mammalian cells in vitro. The system employs continuous drug treatment (3 concentrations) for up to 8 h and recovery-cell populations after pulse treatments with a high dose. Both direct fixation (for recording spindle anomalies in anaphase) and colcemid-hypotonic fixation (for reading metaphase chromosome aberrations) are used in order to estimate the effects of an agent as a mitotic poison and as a clastogen respectively. Some DNA intercalating dyes (acridine orange, quinacrine mustard, neutral red) were found to be highly clastogenic whereas others (quinacrine dihydrochloride, 33258 Hoechst) are not.