Heparinized bottles for the collection of body cavity fluids in cytopathology.

A method of preparing cytopathology specimen collection bottles with a heparin solution is described. The need and benefits of using heparinized bottles for the collection of body cavity fluids are discussed briefly. The formulation of the heparin solution and procedure for preparation of the bottles are given in detail. Collection techniques are discussed briefly. Use of the heparinized bottles results in more reliable diagnostic procedures.


Harvey A.K. Whitney lecture. The patient's pharmacist.

The concept of the patient's pharmacist, the clinical pharmacist who directs his efforts to the individual patient with prospective and concurrent drug use review, is discussed. A patient's pharmacist is familiar with the patient's medical and social history and his present health problems, and ensures that the patient's drug therapy is appropriate at all times. His knowledge base includes an understanding of the clinical use and actions of drugs, pharmacokinetics, optimum clinical response expected from drug therapy, monitoring and evaluating clinical response and communication skills for medication counseling. The patient information the pharmacist needs is discussed in detail. The pharmacist should record his patient care activities in the medical record; this record can serve as a basis for evaluating the pharmacist's activities.


Drug therapy reviews: nitrofurantoin.

Mechanism of action, antimicrobial spectrum, pharmacology, adverse reactions and therapeutic uses of nitrofurantoin, a broad-spectrum antimicrobial agent, are discussed. The frequency and potential severity of reactions attributed to nitrofurantoin, plus its inability to achieve therapeutic blood concentrations, relegate this drug to a position of secondary importance. Nitrofurantoin compares favorably with other standard agents for the therapy of acute and recurrent urinary tract infections in women which may be caused by susceptible organisms, and it is an effective chemoprophylactic agent for patients with recurrent urinary tract infections. The compound has no apparent adverse effects on the developing fetus and can be used in pregnant women. This is not sanctioned by the package insert, however. Nitrofurantoin should not be administered when the possibility of bacteremia exists, as the drug does not achieve therapeutic serum levels when administered orally. Nitrofurantoin is contraindicated for patients with renal insufficiency. The value of this compound for men with acute urinary tract infection, recurrent urinary tract infection, acute bacterial prostatitis or chronic bacterial prostatitis has not been established. There are no indications for prescribing parenteral nitrofurantoin.


Drug therapy reviews: treatment of sarcoidosis.

Sarcoidosis, the possibility of its spontaneous remission, and its responsiveness to corticosteroid and other drug therapies are discussed. Sarcoidosis is a disease of unknown etiology characterized histologicaly by a granulomatous process with cellular infiltration. The granulomatous changes may remit spontaneously or may develop into fibrosis that, at times, is severe; factors that influence these progressions of the disease are not known. Cellular and humoral immunological abnormalities may be associated with this disease. Any organ can be affected although there is a high frequency of pulmonary involvement. Sarcoidosis may be benign and remit spontaneously in as many as 70% to 80% of cases, but the overall case fatality rate can be as high as 10%. Corticosteroids, the most effective therapy, cause temporary remission of the granulomatous changes but do not influence established fibrosis. Corticosteroids only temporarily influence the natural progression of sarcoidosis; however, corticosteroid therapy can preserve the function of vital organs. Other forms of treatment, such as chloroquine, methotrexate, oxyphenbutazone, allopurinol and levamisole hydrochloride, also produce remissions of the granulomatous infiltrate of sarcoidosis but offer no therapeutic advantages over corticosteroids. The decision to treat is often a difficult one, since corticosteroids and these other therapies have potentially hazardous side effects.


Therapeutic neutrophil transfusions: are controlled studies no longer appropriate?

The aim of this review is to determine whether sufficient data have been reported to completely define the role and/or efficacy of neutrophil transfusions in the treatment of specific types of infections in neutropenic patients. Data were collected from the literature pertaining to the use of therapeutic neutrophil transfusions. When only the controlled studies are analyzed, a significant therapeutic advantage for neutrophil transfusions plus antibiotics can be demonstrated when this treatment is compared to treatment with antibiotics alone. However, the controlled studies are vulnerable to critical analysis, and several points argue against applying data from these studies indiscriminately to all infected, neutropenic patients encountered in practice. Moreover, it is apparent when all of the data (controlled and uncontrolled studies) are tabulated, that information is insufficient to establish the efficacy of neutrophil transfusions as treatment for most types of specific bacterial infections. Several problems exist in the wholesale acceptance of liberal transfusion policies, and the benefits that justify continued controlled studies deserve emphasis.


Goodpasture's syndrome with normal renal function.

Two male patients with Goodpasture's syndrome manifesting as severe pulmonary hemorrhage with minimal renal abnormalities are described. Both patients had microscopic hematuria with normal renal function, and one had transient proteinuria. Renal glomerular histology was normal and electron microscopic findings revealed no electron-dense deposits, but immunofluorescence of immunoglobulin G (IgG) was positive in a linear fashion along glomerular capillary basement membranes in both patients. Pulmonary hemorrhage was arrested following prednisone therapy, and both patients have normal pulmonary and renal function at five and 13 months of follow-up. The literature on patients with Goodpasture's syndrome, pulmonary hemorrhage and normal renal function with minimal proteinuria is reviewed. It is suggested that a subset of patients with Goodpasture's syndrome have pulmonary hemorrhage as their major manifestation. Since prednisone seems to have an apparent beneficial effect on pulmonary hemorrhage, and relatively good prognosis, this diagnosis should be considered in patients with idiopathic pulmonary hemorrhage.


Cytogenetic and endocrine studies in a 45,X female subject with spontaneous sexual development.

Cytogenetic and endocrine evaluation of a postpubertal 45,X female subject with Turner's stigmas and spontaneous sexual development was performed. A 45,X chromosomal complement was found in the peripheral blood lymphocytes, bone marrow, and fibroblasts derived from skin and ovaries. Menarche, pubarche, and thelarche occurred at age 12; at age 16 she developed menstrual irregularities, with endometrial bleeding occurring every 60 to 90 days. The ovaries were normal in size, and histologic examination revealed a marked paucity of primordial follicles, increased collagenization, and absence of corpora albicans. Anovulatory cycles with moderately elevated levels of luteinizing hormone (LH) and low follicle-stimulating hormone (FSH) levels were observed. LH-releasing hormone pituitary stimulation induced a normal LH release with a very slight FSH increase. Administration of clomiphene citrate successfully induced a normal-length ovulatory cycle. Similarities in the hormonal situation of this patient and that seen in the Stein-Leventhal syndrome are pointed out.


Accumulation of norethindrone and individual metabolites in human plasma during short- and long-term administration of a contraceptive dosage.

Blood levels of free, sulfate, and glucuronide conjugates of norethindrone (NE) and its ring A reduced metabolites 17alpha-ethynyl-5beta-estrane-3alpha, 17beta-diol and 17alpha-ethynyl-5alpha-estrane-3alpha, 17beta-diol were measured in a female volunteer who received six consecutive daily doses of 2.5 mg. of NE and in four female volunteers undergoing chronic treatment with Orthonovum 2 mg. (2 mg. of NE and 0.1 mg. of mestranol [ME]). The blood levels were quantified by gas chromatograph-mass spectrometry. During treatment for 6 days with 2.5 mg. of NE daily, the 3 hour blood levels of NE and the ring A reduced metabolites increased in a stepwise fashion. During long-term treatment the concentrations of NE, NE sulfate, and the conjugates of the ring A reduced metabolites were seen to build up to a peak at approximately the midpoint of the treatment phase of each cycle, and drop to near baseline during the time when no drug was administered. Individuals varied as to their tendency to accumulate the drug and metabolites, and as to the relative proportion of metabolites formed.


Group B streptococcal colonization and antibody status in lower socioeconomic parturient women.

This investigation was undertaken to determine the prevalence of group B streptococcal vaginal and throat colonization among lower socioeconomic pregnant women and the antibody concentration to the capsular polysaccharide antigen of type III group B streptococcus in their sera. Group B streptococci were recovered from 28.6 per cent of the 112 women studied; vaginal colonization was detected in 23.4 per cent, throat colonization in 4.7 per cent, and colonization at both sites in 0.9 per cent of the patients, respectively. Among these isolates of group B streptococci, serotypes III (39.5 per cent) and II (30.3 per cent) predominated. No differences were found between colonized and noncolonized women with respect to age, race, marital status, or parity. The majority of all women studied had low concentration of antibody in serum (less than 1.0 microgram per milliliter). However, women with isolation of type III group B streptococci from cultures at the time sera were collected had significantly higher concentrations than did women without group B streptococci from cultures at the time sera were collected had significantly higher concentrations than did women without group B streptococcal colonization.


Optometric management of Fuchs's endothelial dystrophy.

Fuchs's endothelial dystrophy interferes with removal of fluid from the cornea by the endothelium. It progresses through stages of corneal guttata, corneal edema, bullous keratopathy, vascularization, and scarring, and complications such as glaucoma or infection. The optometrist can detect this disorder and manage its early stages as well as provide counseling and proper referral. This paper includes a case study and a discussion of the course and treatment of this disease.


Diseases of the optic nerve, tracts, and visual cortex: an annual review of the ophthalmic literature.

The ophthalmic literature dealing with diseases of the optic nerve, tracts, and visual cortex was reviewed for the period November 1976 to November 1977. Thirty-three papers of interest to optometrists have been abstracted. Main areas of interest include response of posterior segment to anterior-segment disturbances; structural anomalies in nerve-head region, including a new potential cause for hypoplasia of optic nerve; speculation on possible common origins of RPE/Bruch's membrane disturbances and endothelium/Descemet's membrane disturbances; a vascular hypothesis for pathogenesis of optic-nerve-head drusen; an explanation for reversibility of infantile glaucomatous cupping; glaucomatocyclitic crisis; the role of axoplasmic flow in papilledema; new developments in field testing for early glaucomatous loss; effects of cerebral vascular accidents on color vision; and two interesting instances of systemic disease with ocular manifestations.


Acid etch bonded cast orthodontic retainers.

We have described a technique which involves the use of a cast orthodontic retaining appliance bonded by the acid etch technique and composite resin for semipermanent retention. The technique provides an alternative form of treatment which offers some unique advantages over previous retentive techniques.


Differential effects of somatostatin analogues on alpha- and beta-cells of the pancreas.

We examined the effect of somatostatin (SS) and its analogues on basal insulin and glucagon output from the right lobe of the in situ canine pancreas. Somatostatin (0.17 and 1.7 microgram/min, iv) significantly inhibited insulin (delta = -48 +/- 9% and delta = -88 +/- 3%) and glucagon (delta = -13 +/- 16%, P = NS and delta = -55 +/- 8%). Des-Asn5-SS Significantly inhibited insulin (delta = -40 +/- 9% and delta = -92 +/- 3%) but not glucagon (delta = +35 +/- 18% and delta = +4 +/- 12%). Likewise, [D-Ser13]-SS significantly inhibited insulin (delta = -40 +/- 14% and delta = -71 +/- 8%) with only slight inhibition of glucagon (delta = +26 +/- 15%, P = NS and delta = -16 +/- 6%, P less than 0.05). In contrast, [D-Cys14]-SS significantly inhibited both inhibited both insulin and glucagon. We conclude that structural changes of cyclic somatostatin can dissociate its ability to inhibit pancreatic insulin and glucagon secretion. Because the putative receptors on the pancreatic alpha- and beta-cell appear to recognize different configurations of the somatostatin molecule, it is suggested that the receptors themselves are different.


Stimulus-secretion coupling of glucose-induced insulin release. XXIX. Regulation of 86Rb+ efflux from perfused islets.

Glucose provokes a dose-related, rapid, sustained, and rapidly reversible reduction in the fractional outflow rate of 86Rb+ from perfused pancreatic islets. This efflux probably corresponds to a passive movement driven by the electrochemical gradient of K+ across the plasma membrane and mediated by a native ionphoretic system. Indeed, it is facilitated by valinomycin or cell membrane depolarization, little affected by ouabain, and inhibited by verapamil or omission of extracellular K+. The effect of glucose upon 86Rb+ efflux does not appear to be directly attributable to changes in either glucose transport, plasma cell polarization, Na+ influx, cyclic AMP concentration, or insulin secretion. Although a modulatory role of intracellular Ca2+ on K+ conductance cannot be ruled out, the experimental data suggest rather that the glucose-induced modification of 86Rb+ fractional outflow rate is directly linked, for its major part, to metabolic events such as an increase in the rate of glycolysis and/or generation of reduced pyridine nucleotides.


Effect of atropine and vagotomy on response of transplanted pancreas.

It is well established that atropine and vagotomy inhibit pancreatic enzyme secretion in response to intestinal stimulants such as fat or amino acids. These effects are usually attributed to interference with hypothetical vagal cholinergic mechanisms that facilitate release of cholecystokinin. To determine whether atropine or vagotomy interferes with release of humoral stimulants of pancreatic enzyme secretion, we studied their effect on protein secretion from an autotransplanted portion of pancreas in response to intestinal stimulants in dogs. The transplanted pancreas was as sensitive as the intact pancreas to stimulation by exogenous caerulein, a cholecystokinin-like peptide, and this response was not altered by atropine or vagotomy. Therefore, if vagotomy or atropine interferes with release of humoral pancreatic stimulants, they would be expected to reduce the response of the transplanted pancreas just as they do of the intact pancreas. Truncal vagotomy caused no significant change in protein secretion from the transplant in response to intestinal perfusion with sodium oleate or tryptophan. Atropine was tested only against sodium oleate and caused no change in response. We conclude that release of humoral pancreatic excitants of protein secretion in response to intestinal stimulants is not significantly changed by atropine or vagotomy.


Early insulin and glucagon response to subsequent pulses of arginine, glucose, and tolbutamide in normal man.

To determine the dynamics of insulin and of glucagon secretion in response to several sequential stimuli administered shortly after an arginine pulse (5 g), 20 nonobese, apparently healthy volunteers were given arginine (5 g), glucose (5 g), and tolbutamide (1 g) by rapid intravenous injection. The early insulin and glucagon area 0-8 min was studied. At the intervals and with the dosages used in this study, different stimuli with and without prestimulation with arginine did not lead to changes in early secretion of insulin. There was no exhaustion of the pool of insulin released after multiple sequential pulses. These results suggest a pattern in which stimulation induces a rapid release of insulin and activates the interchange between the stored and labile insulin pool; the 8-min interval is sufficient for the rapid return of the two compartments to a state of equilibrium. Also for glucagon, subsequent different stimuli did not exhaust glucagon release; nevertheless, glucagon is immediately suppressed by a submaximal glucose pulse.


Calcium dependency of glucagon release: its modulation by nutritional factors.

The calcium dependency of glucagon release by the perfused rat pancreas was investigated in the presence of different nutrients: glucose, arginine, and a mixture of "fumarate + glutamate + pyruvate" (FGP, 5 mM of each salt). At a 3.3 mM glucose concentration, FGP-induced glucagon release was inhibited by the removal of calcium or addition of verapamil. At a higher glucose concentration (16.6 mM), the glucagonotropic action of FGP was again inhibited by verapamil, but the removal of extracellular calcium enhanced transiently glucagon release. Comparable results were obtained when arginine (10 mM) instead of FGP was used to stimulate the alpha cell. These findings suggest that the glucagonotropic effect of FGP or arginine depends on the availability and inward transport of calcium, whereas extracellular calcium per se may be required for glucose to be sensed by the alpha cell as an inhibitor of glucagon secretion. Thus, the nutritional environment offered to the alpha cell may condition the expression of the different mechanisms involved in the control of glucagon release by calcium.


Effective luminal hypotonicity: the driving force for isotonic proximal tubular fluid absorption.

This Editorial Review summarizes certain considerations relevant to the mechanism(s) of isotonic fluid absorption by the mammalian proximal nephron. Recent evidence indicates that the paracellular pathway in this epithelium has a low diffusion resistance. Therefore it is possible that lateral intercellular spaces are in diffusion equilibrium with the peritubular medium. For such a circumstance, the driving forces for isotonic fluid absorption may reside in external solutions. But since the hydraulic conductance of mammalian proximal tubules is remarkably high, the effective osmotic pressure gradient between luminal and pertibular solutions required to drive isotonic fluid transport is relatively small. In the mammalian proximal nephron, effective luminal hypotonicity may provide the driving force for isotonic fluid transport. At least two mechanisms could account for the development of effective luminal hypotonicity. First, preferential absorption of bicarbonate results in a rise of luminal Cl- concentration. And because proximal tubules are more permeable to Cl- than to HCO3-, there develops a driving force for isotonic fluid transport. Second, trivial degrees of luminal hypotonicity may develop attendant on active Na+ absorption. We provide evidence that, of these two mechanisms, axial anion asymmetry is the dominant force for isotonic fluid transport.


Actively circulating blood volume in endotoxin shock measured by indicator dilution.

To estimate the size of the actively circulating blood volume of splenectomized dogs during control conditions and after endotoxin infusion, the pattern of concentration changes of 51Cr-labeled erythrocytes and 125I-labeled albumin was monitored. A dual exponential equation was fitted to the data. The total red blood cell and albumin volumes of distribution were determined from the slow exponential disappearance curves. The active red blood cell and albumin volumes were 89.8 +/- 5.3% and 92.0 +/- 2.0% of the total volumes, respectively. After endotoxin shock (mean arterial blood pressure 49.1 +/- 17.8 mmHg) the active volumes fell to only 60.0 +/- 10.3% and 56.2 +/- 20.0% of the total volumes, respectively. The fast-mixing time constants were similar (3.1 +/- 1.4 min and 2.5 +/- 2.7 min, respectively) and did not change significantly during the endotoxin shock, indicating that the albumin tag mixed into its larger volume of distribution as rapidly as the cells mixed into their indicated volume. We conclude that 1) an active blood volume can be distinguished, 2) it decreases for both red blood cells and albumin in endotoxin shock, and 3) a major part of the "extravascular plasma volume," as estimated by albumin dilution, is in the actively circulating circulation.


Overview: efficacy and safety of the rapid neuroleptization method with injectable haloperidol.

The authors review the literature on the rapid neuroleptization (titration) method with I.M. haloperidol. Most of the approximately 650 predominantly schizophrenic and manic patients represented in the studies calmed down rapidly on medication, and some demonstrated an early reduction in core psychotic symptoms. The initial doses varied widely, ranging from 1 to 30 mg, with a maximum total daily dosage of 100 mg. The medication seemed to have been well tolerated in all cases, with no reported major complications. The authors conclude that the method shows definite merit with agitated and belligerent patients. However, they make a number of specific recommendations for further research to clearly establish the effectiveness and safety of this method of neuroleptic administration.


Antipsychotic effects of lithium in schizophrenia.

The lithium carbonate therapy of 13 psychotic schizophrenic patients was evaluated in a placebo-controlled three-week study that was double-blind. Seven of the 13 patients were less psychotic while receiving lithium; 4 of these 7 patients relapsed after lithium withdrawal. Patients who improved during the third week on lithium could be differentiated from nonresponders on the basis of their improvement during the first week. Clinical factors such as diagnosis, prognosis, and symptoms failed to predict responders from nonresponders. To the authors' knowledge, this is the first controlled study to yield positive results with schizophrenic patients treated with lithium alone.


Gonadotropin response to synthetic gonadotropin hormone-releasing hormone (GnRH) in heroin addicts.

To determine whether the pituitary-gonadal deficiency in heroin addicts is related to heroin's effect on the hypothalamus, the authors administered gonadotropin hormone-releasing hormone (GnRH) to 10 male heroin addicts and 5 controls and measured follicle-stimulating hormone (FSH) and luteinizing hormone (LH) response. Basal FSH and LH levels were significantly lower in addicts; after GnRH stimulation the addicts' FSH and LH values increased but not significantly compared to controls. The difference between the two groups' response was highly significant. The authors suggest that heroin causes an incomplete blocking of gonadotropin secretion at the pituitary level, inducing a hypophyseal-gonadal deficiency and a long-lasting depletion of the endogenous releasing factor, which accounts for the reduced response to GnRH.


A theoretical reconciliation of competing views of time perception.

The time-perception literature is oriented around two opposing traditions, one of which, set forth by Ornstein in 1970, views time estimation as linearly and positively related to stimulus complexity, while the other, as published by Priestly in 1968, sees time as essentially linearly but negatively associated with the experiential complexity with which given intervals are filled. However, careful reading of the literature suggests that, contrary to the Ornstein and Priestly models, a linear correlation between stimulus complexity and time perception should not be expected to fully describe the range of possible relationships. What researchers appear to have ignored is the interrelated impact on time perception of the widely reported inverted-U effects of stimulus complexity and the conceptually related dimension of extroversion. With these latter considerations, comparative time perception thus becomes not a linear but rather a curvilinear, U-shaped function of both personality and stimulus complexity dimensions. The conceptual reconciliation growing out of the present literature review thus offers an explanation for previously reported empirical inconsistencies and suggests the redirection of future comparative time perception research.


Absorbable iris suture. An experimental evaluation of polyglycolic acid suture.

Suturing of traumatic or surgical iris wounds has proved to be a safe and feasible microsurgical procedure. Various suture materials have been tried experimentally and clinically. If the human iris forms scar tissue the ideal suture would be an absorbable, inert, proteinfree material causing no uveal reaction. It was the purpose of this study to evaluate the ocular tissue reaction to nylon, virgin-silk and polyglycolic acid (Dexon) after suturing of an experimental iridomy in 24 rabbit eyes. The tissue response was studied by biomicroscopy, iris fluorescein colour angiography, and histology. Nylon did not disintegrate and caused virtually no inflammatory reaction. Silk showed fragmentation and complete absorption after four to six months with moderate tissue response. Polyglycolic acid gave rise to a marked uveal reaction and depolymerised from the fifth to the sixth week. There was no wound dehiscence of the iris scar and the pupillary function remained intact. It is concluded that the non-absorbable materials are superior to the currently available absorbable sutures in iris surgery.


Intraocular reticulum cell sarcoma: a case report and literature review.

A 66-year-old white woman with a confusing spectrum of central nervous system signs and symptoms had a diagnostic enucleation of her blind left eye showing retinal infiltration. Histopathologic examination showed reticulum cell sarcoma involving the retina. The patient died one month later and autopsy revealed diffuse central nervous system reticulum cell sarcoma along with right eye and systemic involvement. A review of the literature indicates intraocular reticulum cell sarcoma to be an apparently uncommon occurrence, although ocular examination may be frequently overlooked.


Bilateral recurrence of granular corneal dystrophy in the grafts. A clinico-pathologic study.

Clinical, light- and electron-microscopic findings in two sisters with bilateral recurrence of granular corneal dystrophy in the grafts are presented. The clinical pictures and microscopic findings strongly suggest that granular dystrophy may primarily be an epithelial not a stromal disease.


[The anatomical and histological investigation of the pancreas in the 19th century and till the discovery of insulin (1921). 4. The pancreas-research after the discovery of pancreas-diabetes (1889) till the discovery of insulin].

In this study is the history of the pancreas-research between 1889 and 1921 described. In this period are any important discoverys detected: The islets have 2 cell types (TSCHASSOW-NIKOW 1900, 1906); the connection between diabetes mellitus and islet-alterations (OPIE 1900); the independence of islets on exocrine parenchyma (SCHULZE 1900); the discovery of internal secretion (BAYLISS, STARLING 1902) and the regeneration of islets in mammals and the man (KYRLE 1908; WEICHSELBAUM 1908 in independent publications.


[Investigations on the aging processes of the humerus by means of histomorphometry, regression and factor analysis (author's transl)].

Histomorphometric measurements were made on bone sections prepared from osseous material removed from the diaphysial center of 70 macerated humeri obtained from persons in their third to ninth decades of life. The diameters of osteons and Haversian canals, the densities of Haversian and Volkmann's canals and osteocytes, and the proportions by volume of special and interstitial lamellae were determined. The parameters were checked for age dependence and subjected, together with previously determined macroscopic dimensions of the same left humeri, to regression analyses. Influencing variables entering into the most suitable formula for age determination include the cross-sectional area of the medullary space in the diaphysial center as well as the smallest diameters of osteons and Haversian canals. Factor analysis of the complex structure of characteristics yielded 4 factors, namely, the age factor, size factor, structural factor, and nutritional factor. Also discussed are the processes of internal transformation of adult bones.


Effect of dexamethasone and testosterone propionate on LH response to gonadoliberin (LRH) in young post-pubertal bulls.

LH and testosterone responses to gonadoliberin (LRH) were studied after previous dexamethasone and testosterone propionate combined treatment (treated group) compared with a single dexamethasone previous treatment (control group) in 12 Montbéliarde bulls aged 15 months. This experiment was performed on two occaisions 6 months apart according to the same schedule. They included each time 6 bulls, treated with intramuscular injections of 400 mg testosterone propionate and 6 hours later 0.25 mg gonadoliberin together with the other 3 bulls. Testosterone propionate did not influence the mean LH response to gonadoliberin although mean testosterone levels before gonadoliberin injection was very low in the controls. These data suggest that (1) the previously reported depressing effect of dexamethasone on LH is not mediated by the low peripheral testosterone level and (2) under the conditions of this study, there is no short term effect of testosterone at the pituitary level.


Finishing of enamel surfaces after debonding of orthodontic attachments.

The finishing of enamel surfaces after removal of directly bonded attachments is essential. The following procedures are suggested: 1. The bonding of mesh-backed stainless steel brackets with a lightly filled resin system. 2. Debonding of attachments with a direct bonding bracket remover. 3. Removal of the bulk of the remaining resin with a 12-bladed tungsten carbide bur operated at high speed with adequate air cooling. 4. Finishing of the residual resin and underlying enamel with graded polishing discs or Ceramisté wheels used with light pressure and adequate air cooling. 5. Final finishing with a rubber cup and a water slurry of pumice.


Comparison of serum theophylline concentrations measured by high pressure liquid chromatography and quantitative enzyme-multiplied immunoassay technique.

Safe, effective theophylline therapy depends on the rapid determination of serum theophylline concentrations. Two rapid methods that require less than 0.1 ml of serum are high pressure liquid chromatography (HPLC) and quantitative enzyme-multiplied immunoassay technique (EMIT). A comparison of these two methods was carried out using 117 serum samples routinely collected from asthmatic patients in Charity Hospital of Louisiana at New Orleans. After determination by the EMIT method, specimens were analyzed by HPLC in a different laboratory. Mean serum theophylline concentrations in 100 specimens containing more than trace concentrations were 14.5 mcg/ml by the EMIT method, compared with 12.1 mcg/ml by HPLC. The paired t test showed this to be a highly significant difference (p less than 0.0005). Whichever method of determination of theophylline concentration is used, frequent validation of results by comparison with those of other laboratories seems indicated.


Diffference between mouth and esophageal occlusion pressure during CO2 rebreathing in chronic obstructive pulmonary disease.

During CO2 rebreathing, we measured the pressures generated at the mouth and in the esophagus during the first 0.1 sec of inspiratory effort against a closed airway in 6 normal subjects and 6 patients with chronic obstructive lung disease. Normal subjects showed similar reponses to CO2 in terms of both mouth pressure and esophageal pressure. Patients' responses at the mouth to CO2 were decreased compared to those of normal subjects, but the responses in the esophagus were not significantly different. The patients demonstrated a greater response of occlusion pressure measured in the esophagus than at the mouth. In patients with altered mechanical properties of the lung, the change in mouth occlusion pressure might be influenced by problems of equalization of pressure within the airways due to unequal time constants, by problems of regional differences in pressure gradients over the pleural surface, or both. Esophageal pressure during airway occlusion 100 msec after the onset of inspiration may be better measure of respiratory drive than mouth pressure in patients with intrinsic increase of airway resistance.


Uptake and degradation of Pneumocystis carinii by macrophages in vitro.

Pneumocystis carinii organisms, isolated from lungs of rats with glucocorticoid-induced pneumocystosis, were ingested and degraded in vitro by alveolar and peritoneal macrophages obtained from healthy rats and mice. Uptake of the organisms was inhibited at 4 degrees C and by treatment of macrophages with iodoacetate. Neither uptake nor degradation was inhibited by pretreatment of macrophages with hydrocortisone sodium phosphate in vitro. Although peritoneal macrophages of any age in vitro were capable of ingesting Pneumocystis, alveolar macrophages that had been cultivated in vitro for less than 2 days were incapable of phagocytosis of the organism, a functional defect that corrected itself spontaneously during cultivation in vitro.


Pulmonary vascular effects of endotoxin in leukopenic dogs.

We have demonstrated previously that in the dog, small doses of endotoxin abolish the pulmonary vasoconstrictor reponse to hypoxia, apparently by stimulating the production of a vasodilator prostaglandin. We previously ruled out platelets as mediators of this endotoxin effect. To evaluate leukocytes as possible mediators, we rendered dogs leukopenic by means of a leukocyte antiserum. However, this did not modify the inhibitory effect of endotoxin on hypoxic pulmonary vasoconstriction. Hence, neither leukocytes nor platelets appear to mediate the endotoxin effect. In the near absence of both platelets and leukocytes, the endotoxin effect can be prevented by inhibiting prostaglandin synthesis with meclofenamate. This suggests that endotoxin prevents hypoxic pulmonary vasoconstriction by acting on the systemic circulation or on the lung (possibly directly on the pulmonary blood vessels) to stimulate the production of a vasodilator prostaglandin.


Isolation of Eikenella corrodens from pulmonary infections.

Eikenella corrodens is a capnophilic gram-negative rod that is part of the normal human oral flora. We report the isolation of E. corrodens by transtracheal aspiration or percutaneous aspiration from 7 patients with pneumonia and/or lung abscess. Four of the 7 patients had an associated carcinoma of the lung. The susceptibilities of strains were tested to penicillin, dicloxacillin, clindamycin, and 10 cephalosporins. All strains were very susceptible to penicillin and cefoxitin and resistant to dicloxacillin and clindamycin. Susceptibilities of strains to the cephalosporins were variable. E. corrodens has been increasingly identified as a pathogen and should be recognized as an etiologic agent of pneumonia, especially in cases not responding to therapy with a penicillinase-resistant penicillin, clindamycin, or cephalosporin.


Morphometric analyses of tracheal gland secretion and hypertrophy in male and female rats after experimental exposure to tobacco smoke.

Quantitative morphologic analyses were performed by stereologic methods on the tracheal glands of male and female rats after exposure to tobacco smoke for 30 consecutive days. The female rats were evaluated at 2 stages of their estrous cycle. The upper segment of trachea from each animal was embedded in glycol methacrylate, sectioned, and stained with a combined Alcian blue and periodic acid-Schiff stain for glycoproteins. Exposure to tobacco smoke caused an increase in the relative proportion of gland cells in each sex when expressed in reference to the total tissue within the cartilage ring, and an increase in mucins in the gland by 50% in both sexes. Although the relative proportions of gland cells and lumina were equivalent between the sexes, male rats had a larger quantity of mucin. The volume proportion in the glands of Alcian blue-positive mucin was 80 to 84% greater in males, and periodic acid-Schiff-positive mucin was 18 to 19 per cent greater in males than in females, both in control animals and those exposed to tobacco smoke. This study demonstrated that sexual differences were present in the mucin composition of the tracheal glands of normal male and female rats, that the female glycoproteins varied during the estrous cycle, and that these differences were retained after exposure to tobacco smoke.


Rapid diagnosis of Legionnaires' disease by direct immunofluorescent staining.

A blind reading of direct immunofluorescent staining of sputum smears was positive in five of 21 patients with Legionnaires' disease and none of 47 control patients. Positive slides showed from eight organisms per smear (one slide) to 20 to 100 organisms per oil-immersion (magnification, 100) field (three slides). Two of the positive specimens were obtained through an endotracheal tube, one at bronchoscopy, and the other positive slides were from expectorated specimens. In addition, two open-lung biopsies and a bronchial lavage sediment from three confirmed cases of Legionnaires' disease were positive by direct immunofluorescent staining for Legionnaires' disease bacterium.


No initial therapy for stage III and IV non-Hodgkin's lymphomas of favorable histologic types.

The question of whether initial treatment is necessary in relatively asymptomatic patients with stage III and IV non-Hodgkin's lymphomas of favorable histologic types was studied by retrospective analysis. Two groups of patients were studied: [1] 44 nonprotocol patients, followed since 1963, in whom initial treatment was withheld until required to evaluate the pace of disease and the necessity of treatment; and [2] 112 previously untreated patients who have participated in prospectively randomized clinical trials since 1971. For all 44 "deferred" patients, the median time before requiring treatment was 31 months, and there have been 19 patients who have not yet required therapy for periods of 3 to 104 months. The median actuarial survival for all 44 patients was 121 months. At 4 years, the actuarial survival of the 44 patients with deferred treatment is 77.3%, compared with 83.2% for the 112 protocol patients (P = 0.60). Careful observation without initiation of therapy is an appropriate option in the management of patients with relatively asymptomatic advanced non-Hodgkin's lymphomas of favorable histologic types.


Probable transmission of Toxoplasma gondii by organ transplantation.

Two heart transplant recipients developed toxoplasmosis shortly after surgery. As neither recipient had serologic evidence of exposure to Toxoplasma gondii before transplantation, infection was acquired from an exogenous source. Of the possible modes of transmission of Toxoplasma to the recipients, infection by the oral route or through transfusion of blood or blood products seems remote. Since both heart donors had serologic evidence of recently acquired toxoplasma infection at the time of transplantation and the myocardium is known to be infected with the organism during acute infection, we considered these facts to be a strong implication that the donors' hearts were the most likely source of toxoplasma infection in the recipients.


[Primary hyperaldosteronism due to bilateral adrenal hyperplasia of the adrenals. Study based upon one case and a review of the literature (author's transl)].

The authors report the case of a 41-year-old man suffering from primary hyperaldosteronism due to bilateral adrenal hyperplasia, predominantly on the left. This condition is somewhat less common than Conn's adenoma and differs distinctly on the basis of a very poor response to surgical treatment. It can generally be diagnosed by non-invasive techniques, the most reliable of which are the postural test and adrenal isotope scan under inhibition with dexamethasone. These methods are nevertheless not always valuable in the presence of certain forms of hyperplasia which are less distinct from an anatomical standpoint, and must then be complemented by adrenal phlebography and estimation of aldosterone in adrenal venous blood or, if this proves impossible, in the inferior vena cava and renal veins.


[Cirrhogenic hepatitis due to perhexiline maleate: general review based upon one new case with ultrastructural study (author's transl)].

The authors describe a case of cirrhogenic hepatitis due to Pexid which was given for 8 months at 400 mg/day for a severe angina pectoris. We find here the anatomo-clinical profile of perhexiline maleate hepatiits already described in approximately 20 cases. There was a cirrhogenic evolution in our case as in 5 others : but here cirrhosis was revealing and seems stabilized since the treatment was stopped. The cirrhogenic evolution could be due to a cumulative effect of the drug and/or to an immuno-allergic mechanism as in alcoholic cirrhosis which is very similar, especially from an anatomical point of view. However cirrhogenic hepatitis differs by a characteristic lysosomal overload : brown pigment under microscopic observation and lipolysosomes with in some cases a lamellar structure under electron microscopic observation. The prescription of such a drug should be limited to cases of refractory angina pectoris and needed a regular clinical and biological survey.


Clinical pharmacology of narcotic antagonists.

Both naloxone and naltrexone are effective narcotic antagonists with minimal agonistic effects and a wide margin of safety. Naloxone is useful in the treatment of narcotic overdose and it is helpful in the quantification of physical dependence. Naltrexone is pharmacologically successful as an orally effective, long-acting antagonist but its clinical usefulness in the prevention of relapse is still being determined.


Advantages of interpositional long venous grafts in microvascular surgery.

Our clinical experience favors the use of long autologous venous micrografts any time excessive tension is noted along the anastomotic line or in case of a short pedicle in a free flap. The technical problems of harvesting and interposition of these long micrografts are presented.


Management of ulcers of the leg by muscle transposition.

Chronic stasis ulcers of the lower extremity can prove difficult to treat. In the event that conservative treatment fails, one approach is to excise the ulcer, ligate the incompetent perforating veins, and close the defect by muscle transposition, followed by application of skin grafts to the transposed muscles.


John Davies Reese and the Reese dermatome.

John Davies Reese was a unique "loner" whose expertise lay in the field of bioengineering. This led to his development of the calibrated dermatome that bears his name. A bachelor, Reese devoted all his spare time to perfecting dermatape, glue, and the instrument itself.


A new polymer-iodine combination (iodoplex) for treatment of donor sites: a preliminary controlled study.

A recently introduced polymer preparation (Iodoplex) is described. It is based on a new type of hydrophilic polymeric carrier into which iodine can be incorporated to the extent of 50% or more. Its main feature is that the polymer and the petroleum jelly base are water-insoluble. The iodine is slowly released from the polymer by body fluids, which are rich in protein and dead cells. Iodine has been found to be useful in the treatment of donor sites; no pain or discomfort attends its use, and the dressing peels off easily from the healed epithelium. A controlled study comparing iodoplex-impregnated and scarlet red-impregnated gauze on donor sites was carried out, and the use of Iodoplex was found to have some real advantages over scarlet red.


Blast injury with particular reference to recent terrorist bombing incidents.

The aetiology of primary blast lung is discussed with reference to the biodynamics of blast injury, and the clinical and pathological features of the condition are described. An analysis of casualties from bomb blast incidents occurring in Northern Ireland leads to the following conclusions concerning the injuries found in persons exposed to explosions: (1) there is a predominance of head and neck trauma, including fractures, lacerations, burns, and eye and ear injuries; (2) fractures and traumatic amputations are common and often multiple; (3) penetrating trunk wounds carry a grave prognosis; and (4) primary blast lung is rare. A comparison of four bombing incidents in England in 1973 and 1974 shows how the type and severity of injury are related to the place in which the explosion occurs. The administrative and clinical aspects of the management of casualties resulting from terrorist bombing activities are discussed.


David Bayford. His syndrome and sign of dysphagia lusoria.

David Bayford (1739--90) was an unobtrusive medical worthy of the age of William and John Hunter, with each of whom there are documented links. From 1761, when he obtained the Membership of the Company of Surgeons, to 1782 he practised as a surgeon in London, though he was defeated by John Hunter in his bid for election to the staff of St George's Hospital in 1768. In 1782 he proceeded to the MD, granted by the Archbishop of Canterbury, when he removed to Lewes in East Sussex, where he practised as a physician. He later became disfranchised by the Company of Surgeons in order to obtain the Licentiate of the College of Physicians. In 1761, while still an apprentice surgeon, he made his discovery of the unique and bizarre cause--compression of the oesophagus by an aberrant right subclavian artery--of a fatal case of 'obstructed deglutition' for which he coined the term 'dysphagia lusoria' and for which he is eponymously remembered. This discovery remained unrecorded until 1787, when a paper describing the case was read on his behalf before the Medical Society of London.


Bupivacaine in spinal anaesthesia.

A study of 400 consecutive cases of bupivacaine spinal anaesthesia is presented. The anaesthesia was for surgery on the lower abdomen or on the lower limbs. The patients' ages ranged from 19--91 years with the majority (60%) being over 60 years old. The patients were graded according to the A.S.A. (American Society of Anaesthesiologists physical status grade and 43% of the patients were graded as III or more. The duration of surgery lasted up to 3 hours yet analgesia always outlasted the surgery. The quality of analgesia achieved was assessed and in 94% of patients this was either good or perfect. No serious complications was observed but a common sequela was hypotension which was easily controlled by etilefrine (Effortil). There were a few cases of post-spinal headache but this was never severe or long lasting.


Mitochondrial, nuclear and smooth-muscle antibodies in intrahepatic cholestasis of pregnancy.

Serum mitochondrial, nuclear and smooth-muscle antibodies were assayed by the immunofluorescence method in a series of 42 patients with intrahepatic cholestasis of pregnancy and a control series of 15 normal pregnant subjects. None of the subjects examined had mitochondrial antibodies, and nuclear antibodies were only found in one patient with intrahepatic cholestasis of pregnancy. Smooth-muscle antibodies were noted altogether in four patients with intrahepatic cholestasis of pregnancy, in three at a titre of 1 : 40 and in one at 1 : 80; in two controls at titres of 1 : 20, and in two at 1 : 40. In the differential diagnosis of intrahepatic cholestasis of pregnancy the smooth-muscle antibodies particularly may be helpful in differentiating viral hepatitis and intrahepatic cholestasis of pregnancy.


New rapid bioassay of gentamicin based on luciferase assay of extracellular ATP in bacterial cultures.

Bacterial ATP levels in Escherichia coli cultures were determined by luciferin/luciferase assay. Rapid effects of gentamicin on ATP levels in the cultures were studied, and a dose-dependent accumulation of extracellular ATP was demonstrated. This phenomenon was used to develop a rapid bioassay of gentamicin in clinical serum specimens. The accuracy of the assay, expressed as coefficient of variation over the range 16 to 1 mug/ml, varied between 1.8 and 6.5%, compared to 2.3 to 4.7% for an agar disk diffusion assay. Serum gentamicin concentrations were determined by both methods in 122 serum specimens from 43 patients receiving gentamicin alone or in combination with other antibiotics, and the results were compared (r = 0.942). Determination of gentamicin based on luciferase assay of extracellular ATP in bacterial cultures requires only 10 mul of serum, allowing for capillary sampling, and results are available within 2 h.


Assay of gentamicin and tobramycin in sera of patients by gas-liquid chromatography.

Therapeutic levels of gentamicin and tobramycin in the sera of patients were measured by gas-liquid chromatography. Concentration-response curves for both drugs were linear over an expected therapeutic range of 1.3 to 12.5 mug/ml (coefficient of determination was >0.97). Coefficients of variation for chromatographic response to gentamicin varied from 6.3 to 9.6%, and to tobramycin from 3.8 to 13.5%. Paired gas-liquid chromatography and microbiological assays for patient serum aminoglycoside levels were performed on 106 gentamicin and 40 tobramycin sera. At levels <2.0 mug/ml, the average difference of estimates between the two assay techniques for gentamicin and tobramycin were, respectively, 38 and 29%. At drug concentrations >2.0 mug/ml, the mean difference between paired estimates was near 20% for both aminoglycosides. The speed, precision, and accuracy of the gas-liquid chromatography assay indicate that it can be a useful alternative to the microbiological procedure for the determination of gentamicin and tobramycin levels in human serum.


Amikacin assay in serum by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the quantitative determination of amikacin in serum is described. The antibiotic was separated from serum by adsorption on silica gel. The adsorbed drug was then derivatized with o-phthalaldehyde and eluted with ethanol. The derivatized amikacin was separated by reverse-phase, high-performance liquid chromatography and quantitated by fluorometry. A linear response for serum samples containing amikacin ranging from 1.0 to 15 mug/ml was obtained. Other antibiotics including various aminoglycosides did not interfere with the amikacin assay. Comparison with a standard microbiological assay gave a correlation coefficient of 0.99. This chemical assay is sensitive and specific under the conditions tested and can be performed rapidly.


Origin of maltase and variations in infertile men.

A specific assay based on the spectrophotometric determination of the release of p-nitrophenol from p-nitrophenol-alpha-D-glucopyranoside by maltase has been used to measure the activity of the enzyme in seminal plasma and in homogenates of accessory reproductive organs. Specific activity of seminal plasma maltase was 467 muU/mg of proteins in 68 fertile men, decreased significantly in varicocele (296 muU/mg), in azoospermia (246 muU/mg) and in vasectomized patients (62 muU/mg). Application of ion exchange chromatography on DEAE-Sephadex A-50 columns led to the demonstration that maltase activity of seminal plasma and of cytosols from normal reproductive organs was recovered in three different fractions. Maltase activity is thus frequently decreased in infertility.


Reactivity of F(ab)2 fragments of sperm antibodies in agglutination, immobilization and immunofluorescence tests.

The reactivity of F(ab)2 fragments of sperm antibodies was studied in agglutination, immobilization and immunofluorescence tests. Pepsin digestion of full serum was an easy and effective procedure for preparing F(ab)2 fragments. Compared to the reactions with serum, F(ab)2 preparations revealed only a moderate decrease in agglutination titres but a complete loss of immobilizing activity. In immunofluorescence tests, nonspecific background staining was strongly reduced by using F(ab)2 fragments, thereby offering a more reliable basis for the reading of reactions. Even though the titres obtained with serum and F(ab)2 preparations did not differ essentially, it is suggested that the use of F(ab)2 fragments in IF-tests on spermatozoa may help to provide a higher degree of reproducibility.


On myths and countermyths: more on Szaszian fallacies.

There has never been a single set of criteria for the ascription of disease. The pathoanatomic view ascribed to Virchow and propounded by Thomas Szasz has coexisted with the patient-centered or phenomenologic view for millenia. Schizophrenia, as well as such entities as idiopathic epilepsy and migraine, may be considered a disease because it entails suffering and incapacity, albeit in the absence of any obvious lesion. The Szaszian view of disease neither appreciates the nuances of Virchow's own position nor acknowledges the fluidity of current medical nosology.


The effects of methylphenidate on the mother-child interactions of hyperactive children.

Twenty hyperactive boys were observed while interacting with their mothers during a free play and task period on each of three occasions (no drug, drug, placebo). A triple-blind, drug-placebo crossover design was used to study the effects of methylphenidate on these interactions. A complex objective coding system was used to score the children's responses to various maternal behaviors as well as the mother's responses to a variety of children's behaviors. Results indicated that these children were more compliant with maternal commands during drug treatment. In response, mothers displayed increased attention to compliance while reducing their directiveness toward the boys. However, the hyperactive boys receiving methylphenidate initiated fewer social interactions and tended to show greater nonresponding. Thus, methylphenidate may improve the compliance of hyperactive children but tends to decrease their sociability.


Improvement of schizophrenic patients treated with [des-Tyr1]-gamma-endorphin (DTgammaE).

It was postulated from animal experiments that gamma-endorphin and, in particular, the nonopiate-like peptide [des-Tyr1]-gamma-endorphin (DTgammaE, beta-lipotropin [beta-LPH]62-77) have neurolepic-like activity. To test this, 14 patients with long-lasting, relapsing schizophrenic or schizoaffective psychosis resistant to conventional neuroleptics were treated with DTgammaE. An open design was used first for six patients (study 1) and a double-blind, crossover design for the other eight (study 2). In study 1, all neuroleptic medication was discontinued and 1 mg of DTgammaE zinc phosphate was given daily intramuscularly for about seven days. In study 2, six patients were maintained with neuroleptic therapy and two patients were drug free; all eight received daily intramuscular injections of 1 mg of nonlasting DTgammaE in saline and solution for eight days. There was transient or semipermanent improvement in both studies in which the psychotic symptoms diminished or even disappeared. In study 2, there was a slight but significant improvement with the first treatment. Improvement continued and by day 4, the psychotic symptoms had almost disappeared. No toxic side effects were noted. These effects of DTgammaE may be a consequence of the normalization of beta-endorphin homeostasis in the brain.


Combination of lithium carbonate and haloperidol in schizo-affective disorder: a controlled study.

Lithium carbonate alone has been shown to be inferior to neuroleptics alone in the treatment of excited schizo-affective illness. However, in clinical practice, lithium carbonate and neuroleptics are often combined in this disorder. We report a double-blind five-week controlled trial of lithium carbonate plus haloperidol vs placebo plus haloperidol in the treatment of excited schizo-affective patients. Eighteen patients were studied in each treatment group. Modest but statistically significant differences in favor of lithium carbonate plus haloperidol were found by week 5, using the Brief Psychiatric Rating Scale. Lithium carbonate plus haloperidol was favored both for affective schizo-affectives and for schizophrenic schizo-affectives. Lithium carbonate benefit did not seem to be restricted to affective symptoms only. In the clinical treatment of acute schizo-affective illness, the modest benefits of added lithium carbonate must be weighed against the risks of the drug's toxicity.


New therapies and new pathologies: end-stage--dialysis kidneys.

End-stage kidneys in patients who are receiving long-term intermittent treatment with hemodialysis are metabolic structures that participate in many body processes and that themselves develop and change despite severe excretory deficiencies. Nephron loss is severe. Other lesions in such kidneys include the following: smooth muscle nodules that arise in necrotic arteries and arterioles; embryonal hyperplasia of Bowman's capsular epithelium; remodeling of the arteries and veins; tubular atrophy; dilation and cyst formation (acquired cystic disease); arteriolar granular cell hyperplasia and hypertension; deposits of oxalate, calcium, and immune complexes; interstitial fibrosis with collagen and smooth muscle; mucoid change; and cellular infiltration. This list does not include all pathologic conditions found in the end-stage--dialysis kidney. The necessity of and the criteria for an experimental model of human long-term intermittent hemodialysis for end-stage renal disease, presently lacking, are indicated.


Draw-A-Person Test: implications for gender identification.

Human figure drawings were collected from 50 gender dysphoric adults and compared with the drawings of 84 adult evening-school students and college sophomores. The gender dysphoric males drew a person of the opposite sex first more often than the control group males (p less than 0.001). The gender dysphoric females drew a person of the opposite sex first more often than the control group females (p less than 0.05). Results are discussed in light of existing literature of the DAP and gender identity formation.


Treatments of premature ejaculation and psychogenic impotence: a critical review of the literature.

Research on the treatments of premature ejaculation and psychogenic impotence is reviewed. Problems with the existing definitions of these disorders are discussed. The studies are reviewed under seven major headings: depth therapies, behavior therapies, hypnosis, drug therapy, mechanotherapy, reeducative and supportive therapies, and extensive retraining programs. Most of the studies were case reports. Considerable methodological weaknesses were found, most notably the failure to specify subject and treatment variables, the confounding of treatment methods, inadequate or nonexistent control groups, limited, if any, follow-up assessments of treatment effects, and a failure to obtain partner validation of subjects' progress. The studies which used systematic desensitization and the studies which assessed the extensive retraining programs reported the most consistently positive results, although better-controlled replications are needed. Among other issues, it was suggested that future investigators examine the impact of treatment of homogeneous samples and conduct controlled comparisons of different treatment methods.


[Changes in the hypothalamo-hyophyseal neurosceretory system of mammals following pituitary stalk transection and hypophysectomy].

Hypophysectomy and pituitary stalk section result in dramatic morpho-functional changes in all parts of mammalian hypothalamo-hypophyseal neurosecretory system. Reorganization of the hypophyseal stalk consists of several interconnected but differing in time processes. Simultaneously with the developing traumatic changes (degeneration of the sectioned neurosecretory fibers, secretory disorders) proliferation of pituicytes with characteristic phagocytic activity is observed. A little bit later, intensive mitotic division of endothelial cells and capillary formation piercing the stalk periphery begins. At the same time, a new way for blood outflow from the capillaries of the primary portal plexus into the synuses of the brain pias is restored. Degenerated neurosecretory fibers are gradually substituted by regenerating fibers forming a dense network in heavily vascularizated stalk parts. As differentiation of endothelial cells and regeneration of neurosecretory fibers procede, axovasal contacts are gradually forming. At that time the hypophyseal stalk begins functioning as a neurohumoral organ but morpho-functionally less perfect than the posterior hypophyseal lobule. In the median eminence of the operated animals, unlike the intact ones, neurosecrete is accumulating around the capillaries of the portal plexus. Mechanical damage of neurosecretory fibers during the operation results in degeneration of a greater number of neurosecretory cells in the supraoptical and paraventricular nuclei. Preserved cells have an increased functional activity because of neurohormonal deficiency in the organism. As a result of the structural changes mentioned, diabetes mellitus develops, subsiding gradually with time course.


[History of Arkhiv patologii].

In connection with the completion of the 40th volume of the journal "Archive of Pathology", the author, a member of the editorial board and chief secretary of the journal at the time of its foundation in 1935, deals with the first period of the work of the journal until the interruption caused by the Great Patriotic war. He characterizes the contents of the journal reflecting both the research activity of pathologists of that period and most important events of the social and scientific life. Of special interest are the materials of discussions on the important problems of science, teaching, the subjects of scientific and pedagogical literature as well as the materials dealing with the practical work of pathologists and its organization.


Partial artificial heart (ALVAD) use with subsequent cardiac and renal allografting in a patient with stone heart syndrome.

The abdominal left ventricular assist device (ALVAD) is an order of magnitude more effective than conventional intra-aortic balloon pumping (IABP) in unloading and providing circulatory support to the failing left ventricle. This is a report of a unique case which demonstrates that in the absence of pulmonary vascular obstruction or constriction, the ALVAD can substitute for both left and right heart function. A 21-year-old patient with a congenital bicuspid aortic valve developed acute valvular endocarditis which rapidly progressed to congestive heart failure. An operation was undertaken, the mitral and aortic valves were excised and replaced by porcine heterografts, and a fistula from the right sinus of Valsalva to the right ventricle was closed. When coronary circulation was restored, irreversible ischemic contracture of the left ventricle, or "stone heart" syndrome, developed and emergency ALVAD or partial artificial heart implantation was effected. This device functioned as a total artificial heart for nearly six days, while a donor heart was sought. The patient then underwent removal of the ALVAD and cardiac and renal allografting. The transplanted heart functioned well, but the patient expired fifteen days later from gram-negative sepsis.


Postanoxic action myoclonus (Lance-Adams syndrome) responding to valproate.

A patient with postanoxic action myoclonus (Lance-Adams syndrome) was severely disabled with this movement disorder. Valproate sodium was administered orally, with complete resolution of the myoclonus. This favorable response has been maintained for two years. Excessive yawning, the only side effect encountered, was dose related and was abolished with the addition of pimozide to the drug regimen.


HLA antigens in ocular cicatricial pemphigoid.

HLA antigen frequencies were studied in 45 patients with ocular cicatricial pemphigoid. HLA-B12 was found to have an increased frequency of 44.4% in patients with ocular cicatricial pemphigoid, which was statistically significant when compared with a frequency of 19.6% in the control population (P less than .001 or P less than .031 when corrected for the number of antigens tested). The results of this study suggest that there is an immunogenetic susceptibility to the development of ocular cicatricial pemphigoid.


Magnetodontics. The use of magnetic forces in dentistry.

A recently discovered alloy of cobalt and samarium (CO5Sm) has exceptional magnetic properties. A laboratory evaluation was made of the grip force of samples of this alloy of a size suitable for dental use. A review of both dental and general literature points to the need for establishing, prior to widespread usage, that magnetic fields are harmless to surrounding tissues.


Parallel pin retention for anterior bridge retainers.

Various methods of preparing anterior fixed bridges are described. Retention is gained by the use of slots, three-quarter crowns and suitably placed wrought or cast pins. The use of a number of paralleling devices is described.


Re-establishing natural tooth position in the endentulous environment.

The routine prosthetic arrangement of teeth set according to arbitrary criteria frequently results in adaptive problems, tissue damage, poor aesthetics, lack of stability and functional disabilities. A phonetic technique, based on the "S" position of the mandible, in the majority of cases provides a useful aid in achieving natural tooth positions and the occlusal vertical dimension. This technique can enhance the quality of prosthodontic service especially for patients having difficulties with full dentures.


Hormonal profile, blood sugar control and HLA patterns in long-term insulin dependent diabetes with and without vascular disease.

Nineteen insulin dependent diabetics with onset at 30 years of age or less and duration of diabetes of greater than 25 years were divided into two groups on the basis of the presence or absence of clinically evident vascular disease. The patients without vascular disease were characterised by a later mean age of onset, lower fasting growth hormone concentration, and a lower frequency of the unusual HLA pattern B8 without A1 compared to the diabetics with vascular complications. The level of blood glucose control assessed over the last 15 years, insulin antibody titres, plasma glucagon levels and plasma cholesterol did not differ between the two groups. Residual beta cell activity was found in only one of the 19 patients. Although this study does not exclude an effect of the degree of blood glucose control or persistence of beta cell function in the early stages of diabetes on the subsequent development of vascular disease, it suggests that genetic factors, age of onset and plasma growth hormone levels may be more important.


Radionuclide quantitation of left-to-right cardiac shunts in children.

In order to evaluate the clinical usefulness of radionuclide methods measuring the magnitude of left-to-right cardiac shunts, a comparison has been made of the results obtained using these procedures with those estimated by cardiac catheterization. Seventy children in whom the presence or absence of a shunt had been established, were studied. Two methods for radionuclide shunt quantitation, the pulmonary to systemic blood flow ratio (Qp/Qs) of Maltz and Treves and their modified C2/C1, were evaluated. The former was found to be superior and showed a high correlation of shunt size with the catheter results. With attention to the performance of the investigation and in the data analysis, good discrimination can be achieved between normal patients and those with shunts. Because of the atraumatic nature of the investigation, it is concluded that the procedure is of value in the diagnosis of a cardiac murmur, the assessment of postoperative patients and the follow-up of patients known to have a small shunt.


Plasma gonadotrophins and LHRH infusions in anorexia nervosa.

Nine female patients with anorexia nervosa were studied, three of them at different stages of weight gain. Basal plasma LH (luteinising hormone) was depressed in emaciated patients, but basal plasma FSH (follicle stimulating hormone) was normal. LH was significantly lower in patients who had been amenorrhoeic for less than 24 months than in those whose amenorrhoea was of longer duration. LH and FSH levels were stimulated by LHRH (luteinizing hormone releasing hormone), infused at a rate of 0.5 microgram/min for four hours. One patient, tested at 60% of standard weight, had no LH response. In all other patients below 70% of standard, the maximal LH response occurred within the first hour of infusion. In patients at higher weights, the LH response was biphasic, and the maximal level was reached during the last hour of the infusion. The FSH response, similarly, approached maximal during the first hour in patients below 70% of standard, but continued to rise throughout the infusion in patients at higher weights. Body weight expressed as a percentage of standard correlated significantly with both phases of the LH response, but not with the FSH response. Most previous authors have found an association between low body weight and depressed pituitary gonadotrophins in anorexia nervosa. The present findings further elucidate this relationship.


Transient global amnesia--a review of 213 cases from the literature.

TGA is a clearly recognisable clinical syndrome with many and varied aetiologies, the most ubiquitous being transient cerebral ischaemia. This entity is probably much more common than the literature suggests, many patients not coming to the attention of a physician due to the transient nature of the isolated memory defect and the risk of recurrence being low, it is of interest that many of the original patients described tended to be the more prominent members of the community, e.g. physicians and relatives of physicians, perhaps suggesting that the occurrence of TGA in such a person is less likely to pass unnoticed. In the differential diagnosis one should include the following: transient cerebral ischaemia, epilepsy, migraine, temporal lobe encephalitis, psychogenic fugues, post-traumatic, and rarely cerebral neoplasms.


Obstetrics: education and practice in Sydney, 1870-1939: part 1.

The development of obstetric education in Sydney, 1870-1939. is presented in two parts: part 1 looks at the education of nurses and part 2 looks at the education of doctors and their practice of midwifery. Maternal mortality remained stubbornly high until the late 1930's. Reformers urged better education as the solution to the "problem" of maternal mortality. It is suggested that the established maternity care system very probably limited such benefits as came from better education.


The effects on sexual response and mood after sterilization of women taking long-term oral contraception: results of a double-blind cross-over study.

Twenty women using oral contraception for a minimum of 2 years with no side effects volunteered to take part in this experiment which commenced after they had undergone laparoscopic sterilization. In a double-blind cross-over design, patients were administered either 1.0 mg ethynodiol diacetate + 0.1 mg mestranol ("Ovulen") each day for 21 days or an identical-looking placebo for the same number of days. The following month the alternative (cross-over) tablet was given. On days 12 and 25 of each cycle the women completed a modified form of Pitt's Depression Index and a short Sexual Response Score. The result indicated that the active pill ("Ovulen") was associated with a decreased sexual response, but with no increase in the depression index (relative to placebo). The significance of these findings is discussed in relation to previous work, the methodology of the study and hormone-behaviour experiments.


Early psychiatry in Western Australia: Dr. Nicholas Langley--a born loser.

Dr. Nicholas Langley was the first recorded "psychiatric" patient in Western Australia. His story provides an insight into the difficulty experienced in managing cases of violent behaviour in a small, isolated group without facilities or expertise. Langley recovered from his symptoms, and was accepted into the local community without undue stigma. He practised as a surgeon in Fremantle, and died at the age of 35, from what was apparently a cerebrovascular accident.


Teaching medical students psychosomatic medicine: of substances and approaches.

The author describes a curriculum in which the emphasis is on teaching of medical students a general systems approach to health and illness from the first year of medical school through the fourth year. In the first year, a three-part course in behavioral science includes: Introduction to the Patient; Social and Ethical Issues in Medicine; Exercises in Decision-Making; and a didactic lecture series, Determinants of Behavior. This is followed in the second year by a course in psychopathology taught from environmental, psychological and social perspectives. The third-year clerkship emphasizes a liaison approach where students return to the medical and surgical services to work-up patients from a broad multidimensional perspective. The formal program in psychiatry and behavioral science is supported by more than 40 electives in human development, biological, social and psychological psychiatry, including behavior. During these phases the student has experience in working as a member of a team. She/he approaches the health of an individual in terms of the life phase of the individual, the present life of the individual, his/her past experiences, previous personality, reaction to the current illness phenomenon while following the illness through the hospital phase of the present illness, studying coping and adaptational processes.


Characterization of an Escherichia coli K12 mutant that is sensitive to chlorate when grown aerobically.

Escherichia coli can normally grow aerobically in the presence of chlorate; however, mutants can be isolated that can no longer grow under these conditions. We present here the biochemical characterization of one such mutant and show that the primary genetic lesion occurs in the ubiquinone-8-biosynthetic pathway. As a consequence of this, under aerobic growth conditions the mutant is apparently unable to synthesize formate dehydrogenase, but can synthesize a Benzyl Viologen-dependent nitrate reductase activity. The nature of this activity is discussed.


Opposite effects of starvation on oxidation of [14C]adenosine and adenosine-induced insulin release by isolated mouse pancreatic islets.

To test further the hypothesis that ribonucleosides stimulate insulin secretion and biosynthesis by producing metabolic signals, the effects of starvation on adenosine-stimulated insulin production and the oxidation of adenosine by isolated mouse pancreatic islets were examined. No direct correlation was found between the metabolic flux and insulin secretion, since the starvation-induced impairment of the adenosine-stimulated insulin secretion was accompanied by an increased rate of adenosine oxidation. Adenosine-stimulated insulin biosynthesis was, however, unaffected by starvation.


Joint effusions after kidney transplantation.

Thirty-seven consecutive renal transplant recipients were studied prospectively for joint disease. Six developed arthralgias while corticosteroid doses were being lowered. Eleven patients (30%) developed knee effusions at a mean interval of 10 days following transplantation. Synovial fluids were colorless or very pale yellow, with few leukocytes (mean, 28/mm3). These benign transudative effusions did not correlate with immunologic abnormalities, transplant rejection, crystal deposition, or avascular necrosis and may have been due to high dose oral corticosteroid therapy.


Synovitis in secondary syphilis. Clinical, light, and electron microscopic studies.

Polyarthritis and tenosynovitis were seen as the presenting complaints in 7 patients with secondary syphilis. Synovial needle biopsy was obtained in 3 cases and showed mild synovitis with infiltration by lymphocytes, plasma cells, and polymorphonuclear leukocytes; vascular congestion; and slightly increased synovial lining cells. In addition, electron microscopy in these synovial membranes showed many necrotic polymorphonuclear leukocytes, much interstitial debris and fibrin, and in 2 patients, bodies suggestive of Treponema pallidum in the interstitium and in vessel lumens.


The natural history of antitumour immunity in human breast cancer assayed by tube leucocyte adherence inhibition.

The specificity of the tube LAI in breast cancer was examined in a study with coded samples of PBL. In addition, 64 patients with breast cancer had their LAI reactivity monitored and correlated with their clinical status for up to 3 years after mastectomy. When patients were assayed by tube LAI, 83, 72, and 29% with Stage I, and II and III breast cancer respectively were positive. In Stage IV brest cancer, 88% of those with local recurrence and 15% of those with disseminated cancer were positive. By contrast, 3% of control subjects were LAI+. A select group of patients admitted to hospital with suspicious breast lumps that histopathologically proved to be benign breast disease (BBD) had a higher incidence of LAI+ (12%), whereas of outpatients with BBD only 2% were LAI+. Most breast cancer patients LAI reactivity became negative 2--4 months after mastectomy, even when some harboured micrometastases. LAI reactivity remained absent in those patients who remained clinically "cancer-free". In the follow-up patients, LAI activity returned about 4 months before local recurrence. LAI reactivity was observed in 7/8 patients in the coded study and 14/15 patients in the follow-up study preceding and/or at the time of local recurrence. A few patients (15%) progressed to widespread cancer without preceding positive LAI activity. The results suggest that tumour-specific immunity rapidly fades after surgery and may play no role in the rejection of micrometastases by 6 months after surgery. In addition, the present study has shown that the human hose manifests tumour-specific immunity when the cancer is small, and suggests that the early detection of human cancer would depend upon reliable methods to measure the tumour-specific immune response.


A study of false positive and negative responses in the tube leucocyte adherence inhibition (tube LAI) assay.

A panel of 5 different breast-cancer and 2 other cancer extracts was used to clarify the false-negative responses in patients with Stage I and II breast cancer and the false-positive responses in control subjects. Most patients with Stage I and II breast cancer who had an initially negative LAI response were positive when tested against the panel. The false negatives occurred because of (1) the experimental errors of the assay; (2) changes in the antigenic strength of the extracts; (3) antigenic heterogeneity of a few tumours and (4) lack of tumour-specific reactivity of the host. 3% of control subjects had a false-positive LAI response. The leucocytes from most of these positive patients did not react to the panel of antigens, and hence the false positives appeared to result from experimental error. In-hospital patients with benign breast disease had a 12% positivity rate when initially assayed, and 63% of these patients reacted to the panel of breast-cancer antigens. Those patients with benign breast disease who reacted to the panel of breast-cancer antigens had cytophilic anti-breast-cancer antibody in their serum; their leucocyte LAI reactivity was blocked in an immunologically specific manner by serum from advanced Stage IV breast-cancer patients; their leucocytes reacted to extracts of breast cancer and not fibrocystic breast tissue; their leucocyte reactivity was blocked by isolated breast-cancer TSA that was linked to beta 2 microglobulin, but not by normal breast-tissue proteins; and the kinetics of the LAI response after excision of the breast mass was identical to that observed with breast-cancer patients after mastectomy. In these patients, the breast tissue within the breast lump expressed breast TSA similar to unequivocal breast cancer.


Serological response to intracaecal injections of antigenic mouse tumour cells.

Immunofluorescence studies of sera from mice with induced enhancement of tumour growth demonstrated that these sera contained factors ("interfering factors") which in an apparently competitive manner interfered with the subsequent binding of specific antibodies to antigenic sites on the tumour-cell membrane. The factors were tumour-specific but lacked some of the immunoglobulin determinants. They could not be detected by polyvalent FITC-antimouse gamma-globulin. Interfering factors did not seem to be related to IgA or IgE. They were demonstrable in sera from tumour-free animals without growing tumours, thus differing from the tumour-specific "blocking factors".


BCG treatment of human tumour xenografts in athymic nude mice.

Xenografts of 3 human malignant cell lines in congenitally athymic nude mice have been examined for susceptibility to BCG. Growth of all 3 tumours, a bladder carcinoma, a melanoma and a colon carcinoma, was suppressed when cells were injected in admixture with BCG. Distant injection of BCG was ineffective. Mice with progressive growths had no detectable anti-human antibody, and rejection of cells and BCG failed to confer protection against subsequent tumour challenge. These studies indicate that human malignant cells are susceptible to local BCG-activated host responses, and that athymic mouse xenografts may be a useful model for assessing the response of human tumours to such agents.


Size of cancer clinical trials and stopping rules.

A recent international survey on the size of clinical trials in cancer showed the frequent problem of slow patient accrual, which remains a major hindrance to progress. The survey also revealed that, although the design of most trials specified a fixed number of patients, subsequent experience revealed a much more flexible approach, with analysis of results, say, every 4--6 months. Conventional sequential methods are hardly ever used and unfortunately most trials proceed without any predetermined stopping rules. Some trial organizers use repeated significance tests on accumulating data as a guide to the detection of treatment differences, an approach that can be adapted to a more rigorous statistical framework as a "group sequential design". The major statistical principle involved is that the more often one analyses the data the greater is the probability of achieving a statistically significant result, even when the two treatments are equally effective. Group sequential designs require the adoption of a more stringent significance level to allow for repeated testing. If one intends up to 10 repeated analyses of the data, only a treatment difference significant at the 1% level would merit a decision to stop the trial. For any trial to implement a stopping rule successfully there must also be prompt feedback and processing of response and survival data ready for up-to-date analysis. Such efficiency is often lacking. The repeated presentation of interim results of a trial to participating investigators can seriously affect their future reaction, especially if there are interesting but non-significant differences. Thus, some secrecy about ongoing results is advisable if trials are to achieve an unbiased conclusion.


Lactose carrier protein of Escherichia coli. Transport and binding of 2'-(N-dansyl)aminoethyl beta-D-thiogalactopyranoside and p-nitrophenyl alpha-d-galactopyranoside.

The elevated level of lactose carrier protein present in cytoplasmic membranes derived from Escherichia coli strain T31RT, which carries the Y gene of the lac operon on a plasmid vector (Teather, R. M., et al. (1978) Mol. Gen. Genet. 159, 239--248), has allowed the detection of a complex between the carrier and the fluorescent substrate 2'-(N-dansyl)-aminoethyl beta-D-thiogalactopyranoside (Dns2-S-Gal). Binding is accompanied by a 50-nm blue shift in the emission maximum of the dansyl residue. The complex (dissociation constant, KD = 30 micron) rapidly dissociates upon addition of competing substrates such as beta-D-galactopyranosyl 1-thio-beta-D-galactopyranoside or upon reaction with the thiol reagent p-chloromercuribenzenesulfonate. Binding of both Dns2-S-Gal and p-nitrophenyl alpha-D-galactopyranoside (alpha-NPG) occurs spontaneously in the absence of an electrochemical potential gradient across the membrane. Comparison of equilibrium binding experiments using Dns2-S-Gal or alpha-NPG and differential labeling of the carrier with radioactive amino acids shows that the carrier binds 1 mol of substrate per mol of polypeptide (molecular weight 30 000). In addition to specific binding to the lactose carrier, Dns2-S-gal binds unspecifically to lipid vesicles or membranes, as described by a partition coefficient, K = 60, resulting in a 25-nm blue shift in the emission maximum of the dansyl group. Both Dns2-S-Gal and alpha-NPG are not only bound by the lactose carrier but also transported across the membrane by this transport protein in cells and membrane vesicles. The fluorescence changes observed with dansylated galactosides in membrane vesicles in the presence of an electrochemical gradient (Schuldiner et al. (1975) J. Biol. Chem. 250, 1361--1370)) are interpreted as an increase in unspecific binding after translocation.


Yeast mitochondrial deoxyribonuclease stimulated by ethidium bromide. 2. Mechanism of enzyme activation.

An endonuclease (EtdBr DNase), which is more active in the presence of EtdBr, has been purified from yeast mitochondrial membrane (Jacquemin-Sablon, H., et al. (1979) Biochemistry 18 (preceding paper in this issue)). This paper deals with the analysis of the mechanism of this activation. Determination of the enzyme activity in the presence of intercalating and nonintercalating agents showed that the enzyme does not recognize the DNA structure modifiction provoked by drug intercalation. Studies carried out with a series of phenanthridinium derivatives led to the following model. The EtdBr DNase activation would result from the formation of a ternary complex, DNA--drug--Triton X-100. The activation capacity of a drug depends on its ability to bind simultaneoulsy to the DNA (not necessarily by intercalation) and the detergent. When this complex is formed, the DNA molecule is surrounded with Triton X-100 molecules which constitute an hydrophobic environment and make the substrate more prone to interaction with the enzyme. The implications of this model are discussed.


Triphasic concentration effects of gentamicin on activity and misreading in protein synthesis.

Gentamicin is shown to exert a triphasic concentration effect on peptide synthesis in vitro with natural messengers. Low concentrations (up to 2 micron) caused slowing and a decrease in total synthesis, but little misreading (assayed with extracts lacking Glu-tRNA); the inhibition was greater with an initiating system (with phage RNA as messenger) than with pure chain elongation on purified endogenous polysomes of Escherichia coli. Moderate concentrations (up to 100 micron) slowed synthesis less, markedly increased its duration in the noninitiating system, and strongly stimulated misreading; at optimal concentrations total synthesis was even greater than normal. Moreover, with phage RNA these concentrations increased the synthesis of large polypeptides. We conclude that binding of gentamicin to its first site causes inhibition but little misreading; binding to additional site(s) partly reverses the inhibition by first-site binding and markedly stimulates misreading, and the misreading appears to favor "readthrough" of termination codons. In the third phase (greater than 100 micron) synthesis is slowed again but the pattern of misreading does not appear to be altered; this effect need not involve a specific further action on the ribosome.


Rapid purification of biologically active individual histone messenger RNAs by hybridization to cloned DNA linked to cellulose.

We describe a rapid and simple method for the purification of biologically active messenger RNAs. The method allows the isolation in a few hours of specific mRNAs from either whole cell or polysomal RNA even if the RNA represents less than 1% of the starting molecules. We used, as a model, cloned sea urchin (Strongylocentrotus purpuratus) histone gene fragments linked to cellulose by the method of B. E. Noyes & G. R. Stark (1975) Cell 5, 301--310) as hybridization probes to isolate specific histone mRNAs from whole cell and polysomal RNA extracts. RNAs isolated in this manner maintain their biological activity, serving as templates for histone proteins in a wheat-germ, cell-free protein translation system. In addition, radiolabeled histone-specific RNA purified from cleavage stage sea urchin embryos, pulse labeled for short periods of time and analyzed on denaturing polyacrylamide gels, was the same size as mature histone mRNA's.


S1 nuclease as a probe for the conformation of a dimeric tRNA precursor.

We have employed S1 nuclease to probe the structure of an intermediate in tRNA biosynthesis available only in radiochemical purity. The dimeric precursor to tRNAGln and tRNALeu from bacteriophage T4 was digested with the single-strand specific nuclease, and the products of the reaction were compared with the S1 digestion products of the mature cognate tRNA'S. Quantitation and sequence analysis of the products revealed that the location and accessibility of S1 cleavage sites in the precursor were substantially identical with those in the mature forms. Based on these conclusions, it is argued that the dimer is comprised of two domains in which the specific features of both secondary and tertiary conformation closely resemble those found in the mature molecules; at the same time we noted small but apparently significant differences in certain regions of the molecule which may reflect signals for various maturation events. Finally, we have determined that the sites of precursor cleavage by RNase P, the endonuclease which generates the mature 5' termini of these tRNAs, were completely inaccessible to S1 digestion.


Yeast hexokinase in solution exhibits a large conformational change upon binding glucose or glucose 6-phosphate.

Using small-angle X-ray scattering from solutions of yeast hexokinase, we have measured the radii of gyration of the monomeric B isozyme and its complexes with sugar substrates. We find that the radius of gyration decreases by 0.95 +/- 0.24 A upon binding glucose and 1.25 +/- 0.28 A upon binding glucose 6-phosphate. This observed reduction in radius of gyration in the presence of glucose is the same as that calculated from the coordinates of the high-resolution crystal structures of native hexokinase B and a glucose complex with hexokinase A. Thus, these measurements suggest that the dramatic closing of the slit between the two lobes of hexokinase observed in the crystal structures (Bennett, W.S., & Steitz, T.A. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 4848--4852) occurs in solution when either glucose or glucose 6-phosphate is bound.


T7 RNA polymerase: promoter structure and polymerase binding.

The sequences of two promoters recognized by the phage-specificied T7 RNA polymerase are presented. The two are identical in sequence but for one base pair from the initiation point (as determined by the 5' sequence of the transcripts), denoted +1, to position -15. The common : formula: (see text),  sequence also includes a region of hyphenated twofold symmetry indicated by the boxes, with the twofold axis as the center of the six base-pair box. The heavy line indicates the extent of homology. The first promoter (A) is demonstrated to lie within gene 1, the gene for the polymerase itself, and 40 bases into the message transcribed from this promoter is found the R Nase III site separating genes 1 and 1.1. Binding of T7 RNA polymerase to these promoters is associated with a hyperchromic blue shift of the base chromophores consistent with partial melting of the base pairs at the promoter. Binding of T7 RNA polymerase to these promoters disappears at low pH and low temperature and is accompanied by a consequent loss of polymerase activity. The pH dependence of the binding step is adequately described by a single pK of 7.0. Polymerase catalytic activity, but not promoter binding, requires a single free sulfhydryl group of the enzyme with a pKa of approximately 7.8.


Photocross-linking analysis of the contact surface of tRNA Met in complexes with Escherichia coli methionine:tRNA ligase.

Photoinduced covalent cross-linking has been used to identify a common surface of four methionine-accepting tRNAs which interact specifically with the Escherichia coli methionine:tRNA ligase (EC 6.1.1.10). tRNA--ligase mixtures were irradiated, and the covalently linked complexes were isolated and digested with T1 RNase (Schimmel & Budzik, 1977). The fragments lost from the elution profile of the T1 RNase digest were considered to have been cross-linked to the protein and therefore in intimate contact with the enzyme. Only specific cognate tRNA--ligase pairs produce covalently linked complexes. The four substrate tRNAs used in this study have substantially different sequences, but all showed a common cross-linking pattern, supporting the view that the sites cross-linked to the enzyme reflect the functionally common contact surface rather than particularly photoreactivity regions of tRNA. The cross-linked contact surface is comprised of three regions: (1) the narrow groove of the anticodon stem and its extension into the anticodon loop; (2) the 3' terminal residues; and (3) the 3' side of the "T arm". Unlike previous studies with other tRNAs, the D arm is not involved and significant radiation damage is suffered by the tRNA which must be taken into account in the analysis. The results are consistent with and complement chemical modification studies [Schulman, L. H., & Pelka, H. (1977) Biochemistry 16, 4256].


Ionic selectivity of pores formed by the matrix protein (porin) of Escherichia coli.

Incorporation of the matrix protein (porin) from the outer membrane of Escherichia coli into black lipid films results in the formation of ion-permeable pores with a single-pore conductance of the order of 2 nS (in 1 M KCl). Information on the structure of this pore has been obtained by determining the selectivity for various species differing in charge and size. From the permeability of the pore for large organic ions (Tris+, glucosamine+, Hepes-) a minimum pore diameter of 0.8 nm is estimated. At neutral pH the pore is two to four times more permeable for alkali ions than for chloride. On the basis of the observed pH dependence of permeability, this cationic selectivity is explained by the assumption that the pore contains fixed negative charges.


Specificity and functions of guanine methylase of Shigella sonnei DDVI phage.

DNA methylase methylating adenine with formation of 6-methylaminopurine has been identified in Shigella sonnei 1188 cells which are the natural host of DDVI phage. At the same time, in DNA of DDVI phage replicating both in Sh. sonnei 1188 cells and in Escherichia coli B cells 7-methylguanine was found as the only minor base in amounts of 0.25 and 0.27 mol per 100 mol of nucleotides, respectively. The extract of the infected cells was found to contain both kinds of DNA methylases: virus-specific guanine methylase and cellular adenine methylase. The lack of 6-methylaminopurine in DNA of this phage is explained by reversible inhibition of the cell enzyme in the infected cells. The amount of methyl groups transferred by DDVI-specific methylase on DNA does not depend on the species of the infected cells and is similar in the case of unmodified SD phage DNA and DNA of T2 phage methylated by E. coli B enzyme. Guanine methylase has been shown to be a DDVI-induced modification enzyme and to protect against restriction of B-type. It methylates double-stranded DNAs only and is inhibited by S-adenosylhomocysteine.


The effects of temperature and ethidium bromide on the banding of heat-denatured DNA in gradients of NaI.

The effects of temperature and ethidium bromide on the banding of heat-denatured DNA was studied during equilibrium centrifugation in density gradients of NaI. Centrifugation at 10 degrees C prevents the partial renaturation of Escherichia coli DNA and Clostridium perfringens DNA that occurs at 20 degrees C. A centrifugation temperature of --5 degrees C is required to prevent renaturation of T7 phage DNA. Ethidium bromide decreases renaturation of Escherichia coli DNA during centrifugation at 20 degrees C and causes a small shift in the buoyant density of both denatured and native DNA. Equilibrium centrifugation at lower temperatures prevents DNA renaturation and permits increased utilization of the large buoyant density difference between native and heat-denatured DNA in gradients of NaI.


An essential arginyl residue in yeast hexokinase.

The inactivation of yeast hexokinase A (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) by phenylglyoxal obeys pseudo first-order kinetics. Formation of a reversible enzyme-reagent complex prior to modification is suggested by the observed saturation kinetics. Loss of activity correlates with the incorporation of 1 mol of [14C]phenylglyoxal per mol 50 000 dalton subunit. No significant conformational change occurs concomitantly. Inactivation is attributable to modification of an arginyl residue. The pattern of protection by substrates and analogs favors an interaction of this essential residue with the terminal phosphoryl group of ATP or glucose 6-phosphate.