Studies on a protamine (galline) from fowl sperm. 3. The total amino acid sequence of intact galline molecule. Of the eight fractions (G-I-G-VIII) obtained from galline, a protamine from rooster sperm nuclei, the complete amino acid sequences of two fractions G-I and G-V have already been reported. Other fractions of galline purified repeatedly on the column of Bio-Gel CM-30 were submitted to structural analyses. The complete amino acid sequences of three (G-II, G-III and G-VII) of the fractions and the partial chemical structures of two (G-VI and G-VIII) of the fractions were established from the results of analyses of the tryptic and chymotryptic peptides together with those of end groups and terminal sequences. Remarkable similarities have so far been found in the sequences of these fractions. Combining these results with those complementarily explained in the following paper, it was finally confirmed that the intact galline molecule is composed of only one molecular species (G-VIII) and that fractions (G-I-G-VII) were derived from G-VIII by the action of an inherent protease in the preparation process. Consequently, the total amino acid sequence of the intact galline is concluded to be as follows: H-Ala-Arg-Tyr-Arg-Ser-Arg-Gly-Arg-Ser-Arg-Ser-Arg-Arg-Thr-Arg-Arg-Arg-Arg-Ser-Pro-Arg-Ser-Gly-Arg-Arg-Arg-Ser-Pro-Arg-Arg-Arg-Arg-Ser-Arg-Arg-Arg-Arg-Arg-Tyr-Gly-Ser-Ala-Arg-Arg-Ser-Arg-Arg-Ser-Gly-Gly-Val-Arg-Arg-Arg-Arg-Tyr-Gly-Ser-Arg-Arg-Arg-Arg-Arg-Arg-Tyr-OH.


Studies on a protamine (galline) from fowl sperm. 4. Degradation of galline by trypsin-like protease of fowl sperm heads. Galline, a protamine of domestic fowl, was obtained by two preparation procedures from the semen of a strain of White Plymouth Rock and submitted to fractionation by column chromatography on Bio-Gel CM-30. In the first procedure the specimen prepared from sperm heads was purified by the use of distilled water and dilute acetic acid and fractionated into almost eight fractions (G-I-G-VIII) in the same way as the specimen from a strain of New Hampshire (1,2). No difference could be found between galline specimens from the two different strains based on the amino acid and terminal analyses of each fraction. The specimen of galline from sperm heads purified with 1% citric acid (the second procedure) was composed of only one component, which was isolated as a single peak. The smaller fractions, G-I-G-VII, were found to be derived from G-VIII by the action of trypsin-like protease contained in the extract of sperm heads with 1% citric acid. This enzyme seems to originate in the acrosome of fowl spermatozoa. Consequently, it is concluded that intact galline is composed of only one molecular species and its total amino acid sequence is represented by the completed formula of G-VIII as shown in the preceding paper (4).


Separation of the two double-chain bovine intermediates of the proinsulin-insulin conversion I. Chemical, immunochemical, circular dichroism, and biological characterization. The intermediates of the proinsulin-insulin conversion were separated by cation exchange. The circular dichroism spectra of the intermediates showed less alpha-helix than insulin and proinsulin. It is suggested that the C-peptide interacts with the section of alpha-helix contained between residues 2 and 8 in the A-chain of the insulin moieties and unwinds the alpha-helix. The in vivo activities of the intermediates were found to be in the order of 50% relative to insulin. In the fat cell assay, the A-chain-substituted form is weaker (9%) than the B-chain-substituted form (19%). The C-peptide segments of the two forms reacted with C-peptide-specific antibodies as fully as the free C-peptide, on a molar basis. In contrast, the insulin segments were hindered from reacting with insulin-specific antibodies as fully as the insulin.


Tertiary structures of gastrin-like tetrapeptides. Tertiary structures of gastrin-like tetrapeptide Trp-Met-Asp-Phe-NH2 and those substituted by Leu, Val or Gly for Met are studied. The lowest energy conformations of the side chains when the back bone is fixed in alpha-helix are obtained by modified minimization algorithm. It is suggested that protein folding proceeds in the accessible conformation space as a self-organization process leading to minimum energy conformation in this space.


Application of the one-dimensional Ising model to the secondary structures in globular proteins. Prediction of beta-regions. An attempt has been made to predict the beta-regions in 16 globular proteins by applying the one-dimensional Ising model theory of Lifson & Roig (8). The parameters for the theory have been derived from the statistical data on globular proteins given by Chou & Fasman (5). Comparison of our results with the data available from the X-ray crystallographic studies indicates a prediction accuracy which is comparable to those of several other methods, especially in view of the limitations in our method for considering the other secondary structures. It is pointed out that not considering the long-range interactions in our and other methods based on short-range interactions would make these methods incomplete and incapable of being uniformly applicable to all proteins.


The Imbrication Model for the integration of social services in a community. An innovative model for organising social services in a community, the Imbrication Model, is contrasted with two traditional models, the Entrepreneurial and the Umbrella Agency. The structural characteristics and dynamics of the three models are illustrated with actual case histories. Imbrication Model calls for the interlocking of personnel from several agencies, with the purpose of redirecting the dysfunctional interagency rivalry prevalent in the traditional models. Imbrications at all organisational levels--Board of Directors, Administrators and Staff--facilitate adoption of the superordinate goal of providing clients with the best services available, regardless of which particular agency delivers the service. Few observers of the current social service scene would challenge the statement that needs for service are unlimited and resources limited. In the USA the imbalance between needs and resources persists despite a decade of massive governmental programmes intended to alleviate social ills. Recent substantial cutbacks in federal funds, moreover are not likely to improve the situation. The resource shortage involves more than a limitation of funds. Deliverers of service and competent programme administrators are also on critically short supply. These shortages are more often than not exacerbated by a chronic spirit of competition among agencies and programmes at the local level. Three organizational models for the delivery and administration of social services, two conventional and one of more recent date, are examined in this article. The innovative model, which has been named the Imbrication Model, explicitly calls for redirecting interagency rivalry and competition. Its ambitious goal is to integrate the efforts of those attempting to meet a community's social service needs.


Juvenile delinquency and the psychology of general deterrence. The study was concerned with the relevance of the judicial concept of general deterrence of juvenile delinquency. A comparison of attitudes of high-school boys, in areas of low and high delinquency, towards the likelihood of apprehension and the painfulness of punishment for criminal offences, and of the boys' factual knowledge of judicial punishment, did not support the hypothesis that potential juvenile offenders are deterred by fear of apprehension and punishment, or by having an objective knowledge of penal measures. The attitudes of the boys were found to vary with different combinations of socio-economic status and delinquency levels in their geographic areas. The findings were discussed in the light of the relevant literature. It was concluded that prevention of juvenile delinquency should be based on the acquisition of appropriate social values at home and in school, and not on fear of judicial retribution.


Halfway houses for alcoholics: a review, analysis and comparisons with other halfway house facilities. Eight halfway houses for alcoholics were surveyed and compared to other halfway houses for alcoholics, and halfway houses for the non-alcoholic mentally ill, as described in previous studies. The halfway houses for alcoholics surveyed in the present report may be separated into two principal groups: (a) a self-supporting profit-oriented type with an autonomous owner-operator, and (b) a board-controlled and supported type usually receiving group or institutional support. Regardless of group membership, however, none of the halfway houses for alcoholics in the present study matched the high standards set by halfway houses for the non-alcoholic mentally ill as described in other reports. Recent events indicate that halfway houses will be responsible for an increasing portion of persons requiring a structured, supportive or sheltered environment. This paper examines the ability of halfway houses for alcoholics to provide adequate residential care services. Additionally, disparities between alcoholism and non-alcoholism halfway houses regarding staffing, professionalised orientation, and adjunct services are scrutinised. The effectiveness of halfway houses is analysed, and suggestions for future utilisation of alcoholic halfway houses are advanced.


The methadone clinic: function and philosophy. Currently, methadone clinics are organised within two models, the metabolic and the psychotherapeutic. These models are seen to lack a completely successful opiate abuse therapy. A new model, the social psychiatric, is proposed to correct the deficiencies of these first two.


Some implications of variations in techniques of group therapy for social controls. Variations in techniques of group psychotherapy are related to the clients' ego strength. Clients with developmental or pathological ego deficit have different needs for social controls than those with good ego endowment. This paper illustrates differential use of such controls in three areas. 1. Constacy of the treatment milieu as a frame of reference: For patients with good ego endowment, time and place of group meetings should be kept constant to allow them to look inwards and permit experience of feelings hitherto avoided. A patient is described who, following a break-through of feelings in the group, attempted to disrupt the therapy by usurping control over time and place of sessions. Holding time and place of group meetings constant allows patients with ego deficit to anticipate events and helps them build additional controls over impulses. Responses of borderline patients to changes in the treatment milieu are described. 2. Control of group interactions: Matching group members for ego strength is considered essential. Clinical vignettes illustrate contrasts in group interactions considered therapeutic for patients with ego deficit and those with good ego endowment. Techniques for the first group include ritualising the group process, emphasis on reality rather than fantasy and dilution of inter-patient rapport; techniques that aid patients with good ego endowment to relinquish pathological controls include support of basic questions concerning the individual's identity, free flow of fantasy, tolerance of tension, silences or strong ventilation of affect and facilitating observations from patients concerning the process of interaction. 3. Relationship to the leader: For patients with developmental or pathological ego deficit, it is essential that the therapist be ready to set limits and lend defences when the patient's controls fail. Patients with good ego endowment often have too much control. It follows that the therapist will intervene, clarify and provide structure in the first group much more frequently than in groups for psychoneurotics. For patients with ego deficit the relation to the therapist may have to be moderated lest it further weaken ego boundaries. Such patients often need personal distance. Transference to the institution, to the treatment milieu and to the group as a concrete object provides these patients with a natural means of distancing relationships. The therapist should attempt to fit into this series. He should be highly visible in the benign exercise of his professional function. Rapport should be kept stable and primarily positive even after termination of treatment. In contrast, groups of patients with good ego endowment may relate to the therapist more intensively if he is less visible. These patients, unless they can move back and forth between positive and negative rapport, can hardly be said to be working. They will often attempt to control rapport with the therapist by splitting the transference...


Ethnic differences in family attitudes towards psychotic manifestations, with implications for treatment programmes. The tolerance of Irish-American and Jewish-American families towards psycho-social dysfunction in a psychotic family member was studied. As predicted, significantly more Irish families than Jewish families tolerated deviant thinking in a psychotic relative, while significantly more Jewish families than Irish families tolerated deviant verbal emotionality. These and other findings are discussed in terms of psycho-social and socio-cultural theory and lead to a consideration of the goals of treatment programmes. Differences in family attitudes have been shown to affect the decision to send relatives to a mental hospital, or accept them on discharge. Cultural factors are known to be related to attitudes on a variety of health-related issues, but studies have not focused generally on ethnic contributions to family differences in attitudes towards mentally disturbed family members. One reason for this neglect of cultural factors has been the emphasis on sociological phenomena, stimulated by investigations of social class and mental illness. Yet is has been shown that ethnic factors may be responsible for at least some of the correlations that have been found between community, social class and mental illness. Every social class, furthermore, can muster a variety of patterns for seeking professional assistance for psycho-social dysfunctions, and some of these patterns may be differentiated along cultural lines. The present study attempts such a differentiation. It deals with two ethnic groups and their family attitudes towards disturbing symptoms in relatives.


Mental health care by a family oriented general practice team. The mental health aspects of integrated comprehensive family care at a neighbourhood health centre in an underprivileged community include: (1) mental health promotion in high risk groups, (2) early intervention at stressful periods of the family cycle, including physical disease and reaching out to identify unfelt needs, (3) direct aid to patient and family through prevention, restoration or maintenance, depending on patient potential, and (4) attempts to isolate the patient's condition, at worst, and prevent harmful effects on the family environment. The medical team physician, medical worker and public health nurse achieved successful management of psychiatric problems through dynamic role division among its members with planned intervention of different modes and at various levels.


MHPG, amitriptyline and affective disorders. A longitudinal study. The daily urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) were studied longitudinally in five unipolar depressed patients. The patients were followed first during a pretreatment period, and then during a treatment period in which amitriptyline was administered. The data we have obtained suggest that: (1) there is a wide individual variability in MHPG pretreatment levels: (2) amitriptyline modifies MHPG levels in a way which seems to be related to the pretreatment MHPG; (3) amitriptyline may produce a sustained improvement in depressive symptoms, independent of the pretreatment MHPG values, and (4) the time course of modifications in MHPG excretion is shorter than the time course of improvement in depression. Some theoretical implication of these findings are discussed in terms of the catecholamine hypothesis of affective disorders.


Clinical and pharmacological spectral maps of the neuroleptics. The clinical and pharmacological activity spectra of the neuroleptics can be projected into a map where compounds with similar spectra, but with possibly different potencies, are grouped together. The spectral maps were devised for classification and for the prediction of therapeutic effects from pharmacological observations. Significant correlations are observed within and between pharmacological and clinical classifications (Spearman test, p less than 0.01). Pharmacological maps appear to be one-dimensional and resemble the Lambert incisive/sedative bipolar scale. The Liége clinical physiognomy of neuroleptics shows an additional component which may be related to antimanic/antiaustistic effects.


Lithium effects on magnesium, calcium, and phosphate metabolism in rats. Rats were treated with lithium chloride for 8 weeks. At the last day of lithium administration, the animals were given radioactive calcium, magnesium, and phosphate. Electrolyte content and radioactivity were determined in serum, bone, muscle, liver and brain. Lithium led to an increase of inorganic phosphate in muscle and a decrease in serum. Uptake of radioactive phosphate was increased in muscle and liver but reduced in bone. The amount of magnesium in muscle and serum was increased in the lithium-treated rats, whereas the uptake of radioactive magnesium into bone was decreased. Uptake of radioactive calcium into bone was reduced, and radioactive calcium in serum was increased after lithium.


Pilocarpine ocular inserts.

Pilocarpine ocular inserts. Pilocarpine was administered to a selected group of ocular hypertensive subjects in the form of a synthetic biosoluble matrix inserted into the conjunctival cul-de-sac. Satisfactory lowering of the intraocular pressure resulted, with a minimum of subject intolerance. The decreased pressure response was significant in some cases for greater than 24 hours. Drug delivery by soluble inserts offers promise as a convenient and effective mode of therapy.


Ascorbic acid prevents corneal ulceration and perforation following experimental alkali burns. Depressed aqueous humor glucose and ascorbic acid levels returned to control values within 14 days following a 20 sec, 6 mm. diameter, 1N sodium hydroxide burn of the rabbit cornea. These corneas did not ulcerate or perforate. After a 20 sec., 12 mm. diameter, 1N sodium hydroxide burn, aqueous humor glucose levels returned to normal values, but ascorbic acid levels remained significantly depressed for up to 30 days. These corneas became markedly ulcerated in about 60 per cent of animals and frequently perforated. Following 12 mm. alkali burns, rabbits treated daily with 1.5 Gm. of subcutaneous ascorbic acid rarely developed corneal ulcerations and the corneas did not perforate. It is suggested that exogenous maintenance of adequate aqueous humor levels of ascorbic acid overcomes the relatively scorbutic state of the anterior segment induced by a 12 mm. alkali burn, thereby impairing the development of corneal ulceration and perforation. Elevated aqueous humor levels of ascorbic acid had no influence on corneal epithelial cell migration patterns following alkali burns.


Calcium in tears, lacrimal gland fluid, and fluid from the other orbital glands. Abnormal tear calcium concentrations, which might be expected in ocular and systemic disorders,may be obscured if tear calcium concentration varies with flow rate. The results of the present study indicated that tear calcium concentration is independent of flow rate with rates faster than those which occur with stimulated overflow tearing (i.e., 2 mu1 per minute), but with slower flow rates such as would be encountered with basal, nonstimulated tear flow, tear calcium concentration increases as flow rate decreases. In addition, at given flow rates, tear calcium concentration is the same as that in at least two components of tears, i.e., lacrimal gland fluid, uncontaminated by fluid from the other orbital glands, and fluid from the other orbital glands, uncontaminated by lcarimal gland fluid. It is apparent that only if calcium concentration is correlated with fluid flow rate  will determination of calcium in tears and in the components of tears produce valid information not only about tear calcium levels in the presence of ocular and systemic diseases but also about the mechanism of secretion of calcium by the orbital glands.


Endothelial damage from intraocular lens insertion. Previous studies have shown that approximately 40 per cent of the corneal endothelial cells can be lost at the time of intraocular lens insertion. Momentary contact between the methacrylate surface and the endothelial cells causes an adhesion between these surfaces and results in extensive cell damage upon separation of the surfaces. This type of damage appears to be due to a biophysical interaction between these surfaces and may be avoidable by altering the surface of the lens.


A histochemical and morphologic study of postobstructive diuresis in the rat. Renal functional abnormalities constituting the syndrome of postobstructive diuresis imply both altered tubular and glomerular membrane properties. To determine the morphologic and ultrastructural correlates of this disorder a rat model was developed and 32 postobstructed kidneys were studied by light and electron microscopy at the midpoint of diuresis and compared to 22 controls. The abnormal morphology was: dilated distal tubules and collecting ducts, isolated proximal and distal tubule cells that allowed free access of luminal contents to the basement membrane, widened terminal bars and intercellular spaces, thickening of the glomerular basement membrane and, depending upon the portion of nephron, normal or reduced adenosine triphosphatase and acid phosphatase content. In order to confirm the functional nature of the nephrons studied as well as to assess glomerular and tubular permeability, horseradish peroxidase and cytochrome c were infused. These tracers, normally permeable to the glomerular basement membrane, were found in the intercellular spaces and to a lesser extent within cell organelles in the postobstructed diuretic animals whereas controls demonstrated a retarded filtration of horseradish peroxidase, no tracer in the intercellular spaces and large amounts of tracer contained within cell organelles. Absence of enzyme activity in the medulla and reduced dark to light cell ratios in the cortical collecting ducts correlated with prior observations made by others of diminished concentration and acidification processes, respectively. An increase in adenosine triphosphatase activity and renin granules within the juxtaglomerular cells indicated increased renin activity. These observations suggest that the renal functional abnormalities of postobstructive diuresis are attributable to altered glomerular and tubular permeabilities as well as with changes in metabolic activity.


The effect of intravesical formalin on the destruction and regeneration of the canine bladder. Instillation of cytotoxic compounds into the bladder elicits an effect that is based on contact of the agent with the mucosal cells. In the female dog, the distribution of this contact is characteristically in the lower portion of the bladder, and the dome of the bladder is almost invariably spared. Study with formalin indicates that the amount of mucosal contact is best increased by distention of the bladder to full capacity. These findings have significance in the use of topically active agents for the treatment of bladder cancer.


A new concept in vesical conduits.

A new concept in vesical conduits. To overcome the problems associated with cutaneous vesicostomies a new concept in vesical conduits was developed and performed in 13 dogs. The principle of the new conduit is the utilization of minimal bladder tissue to create a stoma analogous to that of the ileal conduit and to perform an antireflux vesicoureteral anastomosis. Preliminary results with the animal studies indicate that the vesicostomy's major faults have been successfully surmounted by this new procedure.


A technique for isolated in vivo renal perfusion. A new technique for in vivo renal perfusion is described which eliminates the need for autotransplantation. In short term ischemia studies using three solutions, Sacks' solution was found to provide the optimal renal ischemia protection.


A simple method for in situ preservation of the ischemic kidney during renal surgery. A simple method combining the advantages of intraluminal occlusion of the renal artery with hypothermic perfusion of the ischemic organ is presented. Using a double-lumen, balloon-tipped catheter, which is introduced from the periphery, the kidney can be rendered ischemic and can be perfused simultaneously. Initial, hypothermic perfusion and subsequent arrangement on the surface of the open wound effectively protected canine kidneys against ischemic injury over 2 hr of ischemia.


Hormonal control of seminiferous tubule contractions. A hypothesis of sperm transport from the testicle. The effects of steroids on the presence or absence and relative magnitude of rat seminiferous tubule contractions were evaluated microscopically. Both 10- and 30-mg implants of estradiol in vivo and concentrations of 10(-8) or 10(-9) M estradiol in vitro depressed the percentage of seminiferous tubules contracting without altering the magnitude of the contraction. Higher doses of both testosterone and dihydrotestosterone in vivo and in vitro maintained the tubular contractions at normal or above normal levels whereas lower doses of these compounds reduced both the percentage and magnitude of the tubules contracting. The results from these experiments suggest that rat seminiferous tubule contractions can be altered by steroids. Testosterone and dihydrotestosterone inhibit the contractions at lower doses and stimulate the contractions at higher doses and thus may regulate the transport of spermatozoa from the rat testicle.


Effect of pair-feeding of carcinogen on the incidence of bladder tumors in hamsters. Role of indole, age, and sex. The role of indole in 2-acetylaminofluorene (AAF) bladder tumorigenesis was critically evaluated in hamsters. To avoid the influence of a nutritional factor on the tumor incidence, the animals were pair-fed for 8, 10, and 12 months. Addition of indole to the AAF diet resulted in a higher incidence of bladder tumors in both males and females (P less than 0.05, P less than 0.05). Indole definitely increased the bladder tumor incidence at 8 months (P less than 0.05). Also significantly different was the tumor incidence between males and females irrespective of the diet administered (P less than 0.05). Indole did not alter the urinary output of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) in males.


Histogenesis of urinary bladder cancer induced in rats by bracken fern. Histologic examination of the urinary bladders of albino rats fed bracken fern (Pteris aqulinum) showed epithelial hyperplasia in all test animals after 3 weeks of feeding and nuclear abnormalities at 4 to 6 weeks. Epithelial tumors were present in animals surviving more than 12 weeks, and invasion of subepithelial tissue occurred in animals sacrificed after this time. Carcinoma in situ, comparable to that in man, was not observed before invasive carcinoma, but was noted later in the surface epithelium adjacent to invasive carcinoma. Transitional cell carcinomas originated from hyperplastic epithelium, squamous cell carcinomas from metaplastic squamous epithelium, and papillary carcinomas from papillomas. Papillomas were preceded by epithelial hyperplasia. The results suggest that hyperplasia precedes bladder carcinoma in rats fed bracken fern.


Spermatic granulomas of ischemic origin in the rat epididymis. The sequelae of the permanently reduced blood flow through the testes of rats, in which stenosis of the abdominal aorta had been produced by inserting an incomplete ligature between the two renal arteries, were studied. In a high proportion of animals, spermatic granulomas occurred unilaterally or bilaterally in the epididymides. Their development was proceded by an ischemic injury; the contents of the canaliculi penetrated into the interstitium, producing a marked macrophagic reaction, which developed after the 5th day. Simultaneously, ischemic lesions were observed in the testes.


The use of spermatic cord lymphatics in the relief of surgically created lower extremity edema. A preliminary report of experiments in dogs. When lower extremity lymphedema is not amenable to control by medical methods, attempts to ameliorate the problem surgically have generally been unsatisfactory. The intact testis and spermatic cord provide a potential bridge that may permit communication between the unobstructed lymphatics of the gonadal system and the obstructed lymphatics of the lower extremity. Preliminary experience in male dogs wherein lower extremity lymphedema is first induced surgically and is treated by testicular implantation into the edematous thigh shows that lympholymphatic communications between the lower extremity and the gonadal system may result.


Irradiation injury to the ureter and surgical tolerance. An experimental study. An attempt was made to produce damage to the ureter of the dog with external irradiation in the high therapeutic ranges in the absence of surgery or cancer. No significant changes were apparent on excretory urography and only minimal changes were seen on histologic study. In another series of dogs, one ureter was reimplanted before the administration of maximal irradiation and the other ureter was reimplanted after the irradiation. The reimplanted ureter tolerated later irradiation very well. The postirradiated ureter tolerated similar surgery very poorly.


Urodynamics of the upper urinary tract.

Urodynamics of the upper urinary tract. The control of ureteral peristaltic contractions by a pacemaker system is shown in a series of experimental observations on the anesthetized dog. Data are presented to illustrate the influence of pacemaker frequency on ureteral rate and bolus volume during oliguria and transient diuresis. Pacemaker frequency was determined from the pressure wave form of the renal pelvis and peristaltic rate was measured electrophysiologically. The bolus volume associated with each peristaltic contraction was recorded by a drop counter and correlated with pacemaker and ureteral activity. The results show that the pacemaker frequency remains constant over urine flow rates in the range of 0.3 to 15 ml per min. It is also shown that the pacemaker frequency is constant during transient increases in flow rate of more than one order of magnitude. During diuresis, the peristaltic rate changes in quantum steps determined by the fundamental frequency of the pacemaker, and at flow rates greater than 2 ml per min the ureter contracts at the pacemaker rate. Further increases in flow are accommodated by increasing the amount of urine transported by each bolus. The urologic importance of these observations on pacemaker function is discussed in terms of the unicalyceal and multicalyceal upper urinary tract.


Cryosurgery of the ureter in dogs.

Cryosurgery of the ureter in dogs. The effect of cryosurgery on the ureter has been studied in dogs. A single 1- or 2-min cryosurgical exposure produced stricture in two of eight animals. A tumoricidal cryosrugical dose consisting of three, 2-min exposures caused stricture in six of eight dogs. Histopathologic examination of the ureter after repetitive cryosurgery showed progressive, persistent loss of smooth muscle, fibrosis of the lamina propria, and early loss with subsequent regeneration of the transitional epithelium. Although there was no loss of ureteral integrity, the possibility of permanent ureteral damage should be considered with the use of cryosurgery.


Rapid formation of a staghorn calculus in the canine kidney. A surgical model. A model for immediate production of staghorn calculi in dogs is described. A paste made of gray investment is injected into the renal pelvis and allowed to solidify for 30 min. Calculi thus formed have a striking similarity to naturally occurring staghorn calculi and can be utilized by urology teaching programs to initiate residents in the technique of anatrophic nephrolithotomy.


Renal dialysis membrane leak detector.

Renal dialysis membrane leak detector. A leak developing in the membrane separating the blood from the dialysate in an artificial kidney machine requires immediate corrective action. The earliest possible action is desirable in order to minimize patient blood loss. This makes system sensitivity to hemoglobin concentration an important design criteria for blood leak detectors. The leak detector described in this paper matches the spectral properties of hemoglobin to those of the detector in order to achieve a maximum sensitivity while minimizing false alarms. The paper describes the instrumentation and circuitry as well as test results of simulated and clinical trials of the detection system.


Ultrasonic detection of cardiovascular flow disturbances. Blood flow that is disturbed or turbulent may have a significant effect on the development of cardiovascular disease. A method is presented here for detecting periods of disturbed flow using autocorrelograms of the audio signal from a pulsed ultrasound Doppler velocity meter (PUDVM). Autocorrelograms describe quantitatively how the form of a signal changes over time. We produced steady laminar and turbulent pipe flow in a hydraulic test tank, and computed autocorrelograms of the audio signal of the centerline velocity as detected by the PUDVM using fast Fourier transform techniques. We have shown that the autocorrelation coefficient averaged over a short length of time (64 ms) is significantly higher for laminar than for turbulent flow. We have also produced pulsatile flow in our hydraulic tank and computed the mean autocorrelation coefficient at different phases of the flow cycle. The regions of disturbed and undisturbed flow were predicted from the steady flow results. The disturbed flow first appears during the period of the highest forward velocities. These results indicate that the mean autocorrelation coefficient can serve as an indicator of the presence of flow disturbances.


A new design for an implantable hearing aid. There have been attempts to design a totally implantable hearing aid but, so far, the devices described in the literature have had various disadvantages. This paper describes a new type of hearing aid that is being implanted and tested in chinchillas. This device parallels the natural hearing mechanism and operates in conjunction with residual hearing, while providing amplified drive to the ossicular chain. Implantation procedures and results are described and discussed.


Development of telemetric techniques for use in studies of the electrical activity of the brain. A telemetry system has been designed to transmit two channels of wideband activity (0.2 Hz-2.5 KHz) recorded from high-impedance microelectrodes in the brains of free-moving cats. Thus, both unit activity and slow-wave field activity are accessible without disruption of the animals' behavior. In addition, circuitry is described that conditions the receiver signals, that dicriminates valid subcarrier signals from receiver noise and that automatically aborts data output in the absence of discriminable subcarrier. This receiver signal processing circuitry thus assures the fidelity of the decoded subcarrier, greatly facilitates further machine processing of the data and frees the experimenter from having to continuously monitor the receiver signals to subjectively edit out noisy data.


An isolated current monitor for iontophoresis. An inexpensive isolated current monitor has been developed as an effort to minimize stimulus artifact in experimental systems which include iontophoresis as the source of stimulus. The monitor becomes an element of the iontophoresis circuit, but provides an output voltage isolated from the iontophoresis current. The voltage is proportional to the iontophoresis current and will represent currents of 1/2 nA to 5 muA. It is this ability to detect minute currents that is valuable in iontophoresis measurements.


Separation and characterization of histones and acidic proteins from heart muscle and calf thymus. A method for the isolation of histones and acidic proteins extracted from rabbit heart and calf thymus chromatins has been studied. The histones present five major electrophoretic fractions in both tissues. Only lysine rich fraction in the heart splits into three peptides of different mobility. Amino acid composition of total histones shows values very similar in almost all components. The acidic proteins of rabbit heart and calf thymus have been characterized by sodium dodecyl sulphate polyacrylamide gel electrophoresis and by amino acid composition. The electrophoretic pattern reveals reproducible heterogeneous banding pattern from the two sources with different degree of phosphorylation. The amino acid composition of total acidic proteins is quite similar with the exception of serine content that in the heart is most elevated.


The relative effect of dietary fats and carbohydrates on lipid metabolism in the albino rat. This study is concerned with the effect of two carbohydrates, cane-sugar and corn starch, at four different levels in the presence of two dietary fats, on the serum and the tissue lipids (cholesterol, phospholipid and fatty acid patterns). Keeping the dietary fats (coconut safflower seed oil) at 20% level, diets containing (a) startch (54%) + cane sugar (0%), (b) starch (44%) + cane sugar 10%), (c) starch (10%) + cane sugar (44%) and (d) only cane sugar (54%) were administered to rats for 8 weeks. The lipid levels were determined at the end of the feeding period. The beneficial effect of the unsaturated fat in lowering the serum cholesterol level is nullified by an excess of cane sugar in the diet. In liver, there is an increase of 40-50% of cholesterol, as the cane sugar level in the diet is raised, irrespective of the type of dietary fat. The fatty acid pattern of the serum and tissue lipids is influenced by dietary fats as well as carbohydrates.


Methionine activating enzyme in various human platelet populations. Human platelets have been separated into four populations by a discontinuous sucrose gradient. MAE activity has been determined in the various platelet populations and significant differences were obtained with respect to platelet size, the large-heavy platelets showing a higher enzymatic activity than the small-light ones. These data suggest that higher MAE activity in the younger and large-heavy platelets may be responsible for a much higher biochemical and functional efficiency.


Correlation between the concentration of isoleucine transfer RNA and the isoleucine content of hemoglobin in rabbit and sheep reticulocytes. A correlation has been found between the concentration of isoleucine tRNA in reticulocytes and isoleucine content of rabbit and sheep hemoglobins: in rabbit reticulocytes, which synthesize a hemoglobin containing 8 residues of isoleucine per molecule, the isoleucine accepting activity is more than twice as high as in sheep reticulocytes, which produce a hemoglobin devoid of isoleucine.


Isolation and partial characterization of a kallikrein from mouse submaxillary glands. A simple procedure to obtain relatively large amounts of purified kallikrein from male mouse submaxillary gland is described. Some chemical and biological properties of this kallikrein have been investigated. The enzyme has a m.w. of 32,000 and shows strong BAEE-esterase activity, as well as kininogenase activity. It is partially inhibited by Aprotinin.


[Infantile papular acrodermatitis. Acrodermatitis papulosa and the infantile papulovesicular acrolocalized syndrome]. Papular acrodermatitis of childhood is an infectious disease characterized by a non-relapsing, non-itching, monomorphic erythemato-papular dermatitis limited to the face and limbs. It is always associated with anacute hepatitis, with hepatitis B antigen in the serum and with a reactive reticulohistiocytic lymphadenitis. In childhood other types of papular or papulovesicular acro-located eruptions, itching or non-itching, associated with reactive lymphadenitis, are observed, in the course of known diseases and with unknown cause. These acro-located cutaneous eruptions of unknown origin, which show varying features, should be classified as "papulovesicular acrolocated syndrome" until their ethiopathogenesis is known.


[Recent morphologic and experimental results on the normal and impaired function of cutaneous vascular organ]. The objective of this article is to briefly review our present knowledge of the pattern, the functional behaviour and the fine structure of the cutaneous papillary vessels and their alterations under various pathological conditions. The shape of these capillary loops varies within wide ranges dependant on the functional state of the covering epidermis. If the latter is hyperplastic the vessels are elongated, twisted and coiled. In case of epidermal atrophy the capillaries become shorter, decrease in number until their final complete absorption. At the level of the electron microscope the capillary wall clearly shows to consist of 2--3 or more endothelial cells of high electron density encircling an always narrow lumen. Both the inner and outer endothelial surfaces are irregular in outline and the cytoplasm is crowded with filaments of 50--70 A in diameter. In addition it is characterized by the occurrence of a larger number of vacuoles and Weibel-Palade bodies, the latter serving as an excellent marker for endothelial cells to e.g. clearly decide the morphogenesis of certain vascular tumors. Along their apex the capillary loops show a fenestrated endothelium particularly at their adepidermal sites. The basal lamina is multilayered and thereby giving a scroll-like appearance in cross sections. At the ultrastructural level endothelial cells are only provided with a limited repertoire of reactions to noxious stimuli. Among these are: (1) an increase in vesiculation and organelles, (2) the formation of cytoplasmic processes often accompanied by the development of interendothelial "gaps" and (3) alterations - mostly thickenings - of the basement membrane. These different fine structural changes were shown to also occur in various diseases of the skin including it's vascular tumors. In experimental research of the skin microvasculature the most spectacular technique was that of a human skin chamber as originated by Branemark. Thereby most of our older findings as to the functional behavior of the microcirculation in laboratory animals were shown to be valid and hence transferable to humans provided similar experimental approaches were used. Finally the vitalmicroscopy and ultrastructure of tumors (melanoma, hemangiopericytoma and neurilemmoma) transplanted into the hamster cheek pouch are briefly outlined.


[Vitiligo in an pair of enzygotic twins]. Investigations of twins can contribute in the investigation of hereditary factors participating in the etiopathogenesis of vitiligo. A 28-year-old pair of male twins are presented, whose monovularity was conclusively proved by a comparison of morphological and serological features. Vitiligo developed as a concordant feature at the age of 13 and 22 years respectively. It is noticeable that there was a good concordance of the localisation of the vitiligo in both brothers. This concordance is most probably explained by genetic fixation of the disease, leading to the manifestation of vitiligo. Multifactoral heredity with threshold is discussed.


[Influence of Palomo's varicocele operation on the spermiogram]. The anatomical condition and the pathomechanism of varicoceles are outlined. The results of the controls of 100 patients being operated by the technique according to Palomo are evaluated. A definite improvement is pointed out in the different parameters of the spermiogram. The differences are significant in follow-up periods up to two years. In the age group between 30-34 years the results are more satisfactory than at the age group 25-29 years and 35-39 years. Half a year after the operation the spermatozoal number generally resembles the norm (40 mill/ml). Catamnestic inquiries among ninetyfive cases showed that there were twentynine graviditis (= 30.5%), which led to a delivery at term in twentyfive cases (= 25.2%).


[Exogeneous hair damage caused by bleaching and cold waving. A case report with scanning electron microscope studies]. A case of exogeneous hair damage caused by bleaching and cold waving is reported. The clinical picture showed brittle, lustreless, fallow hair. The light microscope showed irregular spreading of the cuticular cells. The scanning electron microscope revealed loss of the regular cuticular pattern, breakage of the edges of the cuticular cells, and wave-like separations of the cuticular cells from the cortex. The hair shafts showed multiple longitudinal indentations like seen on a tree trunk.


Comparison of hospitals with regard to outcomes of surgery. Two overlapping studies of variation in postsurgical death and morbidity among short-term hospitals are reported. In one study, Professional Activity Study data were used to compute indirectly standardized mortality ratios for 314,000 patients in 14 surgical categories from 1,224 hospitals; in the second study, patient mix data were collected and ratios computed for 8,593 patients in 15 surgical categories from 17 hospitals. Comparison of results from the two methods in the 17 hospitals increases confidence in the methods and results. The results indicate that, for at least some types of surgery, substantial variation in outcome among hospitals does exist, independently of differences in patient mix. It is suggested that moderate expansion of routinely collected abstract data could provide a basis for continuing assessment of outcome to supplement local quality assurance programs.


Service unit management and nurses' satisfaction. Nurses' satisfaction was compared in 55 patient units, 32 with service unit management (SUM) and 23 without. Satisfaction of licensed practical nurses was unrelated to SUM, but intrinsic task satisfaction of registered nurses (and of head nurses, who were considered separately) was positively related to the presence of SUM. Transfer of nonprofessional tasks out of nursing and reduction of tension arising from reduced responsibility of nurses for coordinating activities with ancillary departments are possible explanations for the positive relation between the presence of SUM and professional nurses' satisfaction.


Indexes of severity: underlying concepts. Six severity indexes proposed in the health services research literature are shown to be special cases of a class of ordinal ranking functions called additive value functions. Deficiencies manifest in each of the severity indexes are discussed in relation to the properties that additive value functions must satisfy. In that severity indexes are a subset of health status indexes, the properties that imply and are implied by additive value formulations are relevant to the larger class of indexes as well.


Forecasting patient census: commonalities in time series models. Highly accurate patient census forecasting models are specified for five hospitals by use of a general equation for integrated autoregressive moving average (IARMA) forecasts. A general census forecasting model, based on features common to all five institution-specific models, is described and its forecasts are compared to those from the specific models.


Steroid dehydrogenases in the adrenal gland of four species of birds: a histochemical study. The presence of 5-3deltabeta-hydroxysteroid dehydrogenase, IIbeta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase and glucose-6-phosphate dehydrogenase has been demonstrated histochemically in the adrenal gland of the rain quail Coturnix coromendalica, barn owl Tyto alba, brown crake Amaurornis akool and painted partidge Francholinus pictus. All these enzymes occurred in the inter-renal cells. No activity was observed in the chromaffin cells. It is suggested that the inter-renal cells of these four species of birds are capable of synthesizing both corticosteroids and sex steroids.


Studies on the testis of the camel (Camelus dromedarius). III. Histochemical observations. The histochemical localization of carbohydrates and lipids and some oxidative, hydrolytic and steroid-linked enzymes has been studied in the testis of the camel with particular reference to the effect of the season on the distribution of these substances. PAS-positive, but diastase-resistant, material was seen mainly in the wall of blood vessels and in the boundary tissues of the seminiferous tubules, tubuli recti and rete testis. Clear cyclical changes were seen for glycogen in the lining epithelium of the seminiferous tubules. Glycogen was most abundant in early stages and very scanty or absent in the late stages of the cycle of the seminiferous epithelium. Numerous small lipid droplets were seen in the interstitial cells and towards the lumen of the seminiferous tubules that contain elongate spermatids or spermatozoa. Large lipid droplets were also demonstrable in the basal layer of the seminiferous epithelium and in the cytoplasmic debri. Alkaline phosphatase was demonstrated in the boundary tissues of the seminiferous tubules, tubuli recti and reti testis and in the cells bordering the lumen of the seminiferous tubules. Succinate and lactic dehydrogenases showed similar patterns of distribution in the interstitial elements and intratubularly. delta5-3beta hydroxysteroid dehydrogenase was exclusively demonstrated in the interstitial cells. 17beta-hydroxysteroid dehydrogenase could not be demonstrated. The season seems to have no effect on the distribution of all these substances. The possible significance of all these findings is discussed.


Identification of glycoproteins in goblet cells of epidermis and gill of plaice (Pleuronectes platessa L.), flounder (Platichthys flesus (L.)) and rainbow trout (Salmo gairdneri Richardson). A quantitative analysis has been made of the glycoproteins present in the goblet cells of the epidermis, gill filaments and gill lamellae of three species of teleost fish. The glycoproteins have been identified by a combination of techniques, including the use of the enzyme sialidase followed by Alcian Blue staining, at PH 2.6 or 1.0, in combination with periodic acid-Schiff. The selected fish were representative of species living in marine, freshwater and estuarine environments. The range of glycoproteins identified in these fish was similar to that found in mammalian tissue in that both neutral and acid glycoproteins were present, the latter included both sialomucins sensitive and resistant to sialidase, and sulphomucin. A single goblet cell contained either neutral or acid glycoproteins alone or in combination. Only the epidermis of the plaice and rainbow trout contained uniform cell populations producing acid glycoproteins, the former sulphomucin and the latter mainly sialomucin. At each site in the flounder and in the gill epithelia of the plaice and rainbow trout, the goblet cell population was mixed, with cells producing each type of glycoprotein. The number of goblet cells producing each type of glycoprotein varied at each tissue site.


Ultramicrochemical determination of nucleic acids in individual cells using the Zeiss UMSP-I microspectrophotometer. Application to isolated rat hepatocytes of different ploidy classes. Edström's method for the ultramicrochemical determination of RNA and DNA in individual cells was modified for the measurement of extinction in u.v. light with the aid of the Zeiss scanning microspectrophotometer UMSP-I. With this new procedure, nucleic acids down to about 3 pg RNA or about 4 pg DNA can be measured with a very high accuracy. The method was applied to enzymatically isolated rat liver parenchymal cells. A mean DNA content of 6.52 pg was found for diploid cells. The DNA content of mononuclear cells of different ploidy levels and of binuclear cells showed a close proportionality with the nuclear ploidy and the number of nuclei per cell. The RNA content of mononuclear diploid cells amounted to 33.4 pg, yielding an RNA/DNA ratio of 5.12. The RNA/DNA ratio was similar for binuclear and mononuclear cells of the same ploidy level but decreased considerable with increasing nuclear ploidy.


Hydrolytic enzymes in the sebaceous glands of the domestic cat. The distribution and activities of some hydrolytic enzymes in various portions of the sebaceous glands of the domestic cat have been studeid. The results point to the outstanding importance of none-specific esterases and lipases for sebum production, which generally appears to be abundant in thickly-haired mammals. The activities of the lysosomal enzymes demonstrated were connected with autolytic processes during sebaceous gland cell differentiation. There was a strong aryl-sulphatase reaction in the sebum of the sebaceous gland excretory ducts.


Analytical ultrastructural studies on implanted dental amalgam in guinea-pigs. Implantation of amalgam induced a cellular reaction, and a rapid loss of copper and zinc and a more gradual loss of tin and mercury occurred. The silver remaining was generally associated with sulphur and was present either as a diffuse fuzz around remaining masses or in a finely particulate form.


Histochemical localization of adenylate cyclase in cultured sympathetic neurons. The catecholamine-stimulated adenylated cyclase activity was histochemically demonstrated at ultrastructural level in the cultured neurons of the sympathetic ganglia of the chick embryo. Adenylate cyclase activity was demonstrated in the axolemma of the axons and axon terminals, however not inside the axons. Heavy precipitates of the enzymatic reaction product was observed intracellularly in some cell processes identified as dendrites of the sympathetic neurons. In contrast to the extensive reaction in the neuropil, the reaction for the catecholamine-stimulated adenylate cyclase was scarse in the perikarya of the neurons. Only occasional spots of adenylate cyclase activity could be demonstrated in the plasmalemma of some neurons, and no reaction product was observed in the cytoplasm. No difference in the localization of the adenylate cyclase activity was observed when either dopamine or noradrenaline were used for stimulation. The possible roles of the catecholamine-stimulated adenylate cyclase in the function of the interneuronal connections between the aminergic neurons of the sympathetic ganglion are discussed.


The activity of non-specific esterase in the thyroid epithelial cells of the guinea pig as influenced by various inhibitors and activators. A histochemical study. The action of various inhibitors and activators upon esterase activity in the thyroid epithelial cells is demonstrated. The agents used were triorthocresylphosphate (TOCP), parachloromercuribenzoate (PCMB), Arsanillic acid, p-nitrophenyl dimethyl carbamate and bis p-nitrophenyl phosphate. TOCP was found to inhibit selectively the activity in the follicle cells proper when alpha naphthyl acetate was used as a substrate. Arsanillic acid (0,001 M) activated the follicle cells proper selectively, but if the concentration was raised to 0,01 M the effect was that of inhibition while the activity in the para-, inter- and intrafollicular cells was unchanged. The results obtained are related to previous biochemical and histochemical observations and the nature of esterases in the thyroid is discussed.


Alkaline Phosphatase distribution in the inferior vagal ganglion of the cat following vagotomy: a chronological study. The object of this study was to demonstrate sites of alkaline phosphatase activity within the cellular elements of the inferior vagal (nodosal) ganglion of the cat and chronologically observe and describe alterations in enzyme activity following vagotomy. In control tissues alkaline phosphatase activity was localized to the wall of perineuronal blood vessels and the satellite cell cytoplasm which envelops the neuronal perikarya. In the experimental tissues alkaline phosphatase activity was increased in the above locations during the first 20 days following vagotomy then gradually declined to approximate control levels by 60 days post-operatively. The functional significance of changes in alkaline phosphatase activity occurring within an altered metabolic environment induced by vagotomy is discussed.


Acid esterase in human arteries.

Acid esterase in human arteries. 150 human arterial segments of high or low susceptibility to develop atheromas were studied for differences in the amount of histochemically demonstrable acid esterase in them. An inverse relationship was found between intimal or medial enzyme content and susceptibility to atheroma formation.


An X-ray microanalytical azo dye technique for the localization of acid phosphatase activity. A new method is described for the histochemical localization of acid phosphatase. Naphthol AS BI, enzymatically released from naphthyl AS BI phosphoric acid, is coupled with diazotized 2,5-dibromoaniline to produce a fine insoluble red azo dye. The histochemical and cytochemical localization of this final reaction product in rat liver is described. In the electron microscope, sites of the azo dye can be detected by X-ray microanalysis of ultrathin cryosections of reactive tissue.


Electron cytochemical localization of gamma-aminobutyric acid catabolism in rat cerebellar cortex. An electron cytochemical technique is described for the localization of GABA-T, the enzyme which degrades the neurotransmitter GABA, in rat cerebellar cortex. The technique allows ultrastructural demonstration of GABA-T activity by the final deposition of an electron dense formazan precipitate at reaction sites, whilst maintaining adequate ultrastructural preservation for recognition of cellular and subcellular structures. Numerous electron dense precipitates are evident as discrete punctate deposits situated mainly in mitochondria of stellate cells, basket cells and astrocytic glial cells; they are also seen in axonal or dendritic profiles at some synaptic junctions. The technique enables the first cytochemical demonstration of the mitochondrial localization of GABA-T activity in nervous tissue to be presented. It establishes that GABA-T is present in supposed GABA neurones, in pre- or post-synaptic endings, or both, of presumed inhibitory synapses and in glial cells which may be associated with these synapses. From this seemingly ubiquitous distribution, functional aspects of GABA-T in these cells is considered.


The acridine dyes: their purification, physicochemical, and cytochemical properties. I. A purity test of some commercial acriflavine samples and the identification of their components. The present investigation was designed to allow a critical comparison of the dye purity of six commercial acriflavine samples. Thin layer chromatography, absorption-, IR- and NMR-spectroscopy were applied for the identification of dye components and impurities. Ambiguities regarding the purity of the acriflavine samples have been resolved, showing that: (a) The finding permits the conclusion, that all analyzed samples of the fluorochrome "acriflavine" are characterized by a two-component dye pattern (acriflavine II and proflavine III), and contain fluorescent impurities. (b) The dye component III was the main component of only one dye sample. The effectiveness of these experiments is concerned with making automated microfluorometric measurement of cells stained with pure dye fractions more quantitative and reproduceable.


[Comparison of different morphometric methods to estimate the surface of the rat intestinal mucosa. Their relationship to intestinal function (author's transl)]. In contrast to the human small intestine with predominantly fingerlike villi, trapezoid forms are encountered in the small bowel of the rat. For this reason, it is doubtful whether it is sufficient to measure the villus height alone as a representative parameter for the assessment of the villus surface. In this study, the method developed by Clarke is employed to calculate the villus surface per unit area of intestine. The data obtained by this method are compared with those estimated planimetrically. Correlations were then established between the absorptive capacity and enzymatic activity of the intestinal mucosa on the one hand, and the villus height or the villus area obtained by each method on the other hand. Under our experimental conditions--a hyperregenerative transformation of the intestinal mucosa caused by chronic exposure to glucagon--the results indicate that the calculated villus surface per unit area of small intestine correlates better than the villus height with the functional parameters of the intestinal mucosa.


SH groups in the alpha-naphthyl acetate esterase in the thyroid of the guinea-pig. A histochemical study. The alpha-naphthyl acetate esterase in both group I and group II thyroid cells is shown to contain SH groups since there is a decline in activity in both cell groups when certain sulfhydryl reagents [DTNB; 5,5'-Dithiobis-(2-nitrobenzoic acid)-AgNO3-Mersalyl-PCMB (parachloro mercuribenzoate) + urea] are added to the incubation media. Thus the inhibition is by far the greatest in group I cells, which also show the greatest activity after incubation in conventional media, when long fixation and storage times are used. In all cases the inhibiting effect was complete or almost completely reversed if cysteine was added to the incubation media in equivalent concentrations to the SH blocker. There were great differences among the sulfhydryl reagents used in their ability to bring about enzyme inhibition. The alkylating agents NEM (N-ethylmaleimide) and iodoacetamide had no or little effect while PCMB could only inhibit the activity of the alpha-naphthylacetate esterase if the enzyme was denaturated with 5 M urea. The maximal inhibitory effect of PCMB was only obtained when NaCl was added to the incubation media. The most effective inhibitor was AgNO3.


Autoradiographic and ultrastructural study of Cucurbita pepo root cells during their growth and differentiation. Cortex cells of the root meristem of Cucurbita pepo (0.0-0.5 mm from the cap junction), in the 3-4, 5-6 and 7-8 mm segments above the root tip, and the cells of the first three layers of lateral part of root cap were the object of the present study. The volume of cortex cells increases more than 20 times in the 7-8 mm segment as compared with meristematic cells, and the volume of cytoplasm about sevenfold. The largest increment of the cytoplasmic volume occurs between 0.5-6.0 mm. In consecutive root segments the sustained increase of the volume of nuclei takes place. By applying autoradiography the following processess have been investigated: DNA synthesis (3H thymidine uptake), template activity of DNA (3H actinomycin D(3H AMD)-binding), RNA synthesis (3H uridine incorporation), and protein synthesis (3H leucine). In the root cap cells and in segments where meristematic activity is over, DNA is replicated by endomitosis. On the basis of nuclear labelling it appears that nuclei in the 3-4 mm segment reach 4C ploidy state, but in the 7-8 mm segment half of the nuclei reach the 8C ploidy state. Most of the root cap cells are 4C, the remaining cells are 8C. Considering the uptake of 3H thymidine into nucleoli one may suppose that in the root cap cells nucleolar DNA is underreplicated, and to a lesser degree in 5-6 and 7-8 mm segments, while in 3-4 mm segment DNA is overreplicated as compared to meristem cells. Measurements of nucleolar volume, 3H uridine uptake, 3H AMD binding and quantity of granular component, indicate that the most noticeable nucleolar activity takes place in meristematic zone and in root parts showing the highest increase of cytoplasmic volume (3-4 and 5-6 mm segments). 3H leucine is still incorporated intensely into 7-8 mm segment, in which the concentration of ribosomes is low, however they are present in the form of polysomes. Comparison of 3H thymidine uptake into nuclear DNA with 3H AMD binding and 3H uridine incorporation into nuclei indicates that endomitotic DNA replication results in an increase of DNA template activity in root cap cells as well as in 3-4 and 5-6 mm segments; in the 7-8 mm segment binding of 3H AMD slightly decreases, while 3H uridine incorporation is considerably reduced. Divergence between the ploidy state, 3H AMD binding and 3H uridine incorporation can be due to the increment of the condensed chromatin area in differentiated cells. Plastids and mitochondria reach full maturity in 3-4 mm segment. The increasing volume density of ER and diminishing volume density of Golgi structures is accompanied by differentiation of cortex cells.


A method for studying glyoxylic acid induced fluorescence and ultrastructure of monoamine neurons. Inasmuch as precise correlations of light- and electronmicroscopy are crucial for understanding biostructure, it seemed necessary to bring together the advantages of the glyoxylic acid (GA) method (for inducing monoamine fluorescence) and electron microscopy. A combined fluorescence and electron microscope method using GA is introduced. The brain is perfused by 2% GA in Krebs-Ringer bicarbonate buffer (pH 7.0) and this solution is followed by 4% paraformaldehyde containing 0.5% glutaraldehyde in Sorensen's phosphate buffer (pH 7.4). Sections are cut by cryostat or by vitratome and incubated in 2% GA in phosphate buffer (pH 7.0). Using fluorescence microscopy, features of interest are sketched and/or photographed. Afterwards, the same or subsequent section is processed for electron microscopy. Since axons of catecholamine-containing neurons (as well as their perikarya and terminals) are visualized by GA, the recommended procedure expands the range of studies concerning monoamine neurons that can now be carried out effectively.


Changes of acid phosphatase activity of fast and slow rat muscles during ontogenetic development. 1. The activity of acid phosphatase (AP) were studied both bio- and histochemically in fast and slow muscles of the rat during postnatal development. 2. Both biochemical and histochemical methods show at birth a similar, high AP activity in both, fast and slow muscles. From 20 days onward AP activity is higher in the slow soleus than in the fast extensor digitorum longus (EDL) muscle. 3. Fibres with high AP activity have also higher activities of oxidative enzymes and of non-specific esterase (NSE). This property is not coupled to degree of ATP-ase activity; fibres with high or low ATP-ase activity reveal similar activities with respect to AP. 4. There is a "two-phase" developmental change in the degree of enzyme activity in both the fast EDL and slow soleus muscles. AP activity is high at birth, decreases during later postnatal development and increases again in senescent muscles.


[Histochemical and biochemical investigation of alpha-glucosidases by means of 2-naphthyl-alpha-D-glucoside (author's transl)]. Histochemical and biochemical studies yield the following method of choice for the in situ detection of neutral (microvillous) and acid (lysosomal) alpha-glucosidases: 12 mg 2-naphthyl-alpha-D-glucoside (dissolved in 0.5 ml N,N-dimethylformamide) and 0.6--0.8 ml hexazonium-p-rosaniline in 10 ml 0.1 M citric acid phosphate buffer for aqueous or 5 ml buffer mixed with equal parts of 2% agar for incubation with semipermeable membranes, pH 5 or 6.5. With this method neutral alpha-glucosidases can be exactly demonstrated in the brush border of the small intestine (glycoamylase, sucrase-isomaltase) and kidney of mammals, birds,fishes, amphibia and reptiles; localization of acid alpha-glucosidases is achieved at the cellular level in many organs and tissues. Fluorometric and photometric measurements prove that 2-naphthyl-alpha-D-glucoside is superior to 6-brom-2-naphthyl-alpha-D-glucoside for the demonstration of alpha-glucosidases in situ due to the lower Michaelis constant and higher maximal reaction velocity of the naphthol derivative.--Among the coupling reagents tested neutral alpha-glucosidases can be localized correctly with hexazotized p-rosaniline (with and without semipermeable membranes) for simultaneous coupling. Fast Blue B delivers false positive results in the suczedaneous and simultaneous coupling procedure using aqueous incubation media; in combination with the membrane technique azo dye can not be observed in the sections. Hexazonium-p-rosaniline inhibits neutral and acid alpha-glucosidases to nearly the same extent as Fast Blue B. Fixation of blocks of tissue in formaldehyde and glutaraldehyde suppresses alpha-glucosidases in the intestine and epididymis. The inhibition rates amount to 50 and 70% respectively. Washing in sugar solution rises enzyme activity to 65 and 50%. Species and organ dependent activity differences of neutral and acid alpha-glucosidases and changes of enzyme activity in the intestine and kidney after castration as well as in the course of pregnancy can be detected by means of biochemistry but not with the histochemical assay including minimal incubation. In comparison with p-nitrophenyl-alpha-D-glucoside the 2-naphthyl derivative is also the substrate of choice for the biochemical determination of alpha-glucosidases.--Agar gel electrophoresis reveals one band in the neutral and acid pH range.


The histochemical demonstration of choline acetyltransferase by semipermeable membrane technique. The application of the semipermeable membrane technique in light microscopical demonstration of choline acetyltransferase is described. The method founds upon earlier developed lead salt techniques. Use of semipermeable membranes fully prevents any loss of enzyme by dissolvement or inactivation during fixation. Addition of NaCl to the incubation medium markedly increases the activity of choline acetyltransferase.


Remarkable electron-microscopic localization of thiamine diphosphate phosphohydrolase (TDPase) in the tanycytes of the rat. The electron-microscopic localization of TDPase in the tanycytes of rat brain was studied. The reaction product was demonstrated in the membranes, but not in the Golgi apparatus of this cell type. Possible functional aspects of these findings were discussed.


Influence of fasting and stimulation on the rat gastric endocrine cells. Histochemical and ultrastructural study. The ultrastructure and certain cytochemical parameters of endocrine cells of the rat gastric mucosa during 168 h of fasting were investigated. To some of the fasting animals peroral food or alcohol was administered before decapitation. The EC (enterochromaffin cells) the ECL (enterochromaffin-like cells), D1 cells, AL (A-like cells) and G cells were identified by means of electron microscopy. Only the EC, ECL, and G cells could be identified by means of light microscopy by an adequate histochemical technique. The ultrastructural picture of the ECL and of the EC cells did not change markedly during the fasting. In the D1 cells there occurred an agglomeration of secretory granules. Some of them disintegrated and disappeared. In the AL cells an agglomeration of granules during the fasting was also observed. Granules engulfed in lysosomes were often found. The participation of lysosomes in the degradation of granules during the fasting was more marked in the AL cells than in the G cells. The participation of lysosomes was questionable in the EC and D1 cells, and in the ECL cells no lysosomes were observed. In contradistinction to the G cells of the non-fasting animals, where more than one half of the gastrin granules were "empty", the G cells during the fasting were filled with agglomerated dense granules and contained lysosomes with fragments of engulfed secretory granules. Following the administration of food (Larsen's diet) 3 h before sacrificing the dissolution of the content of granules with well preserved membranes was observed (emiocytosis did not take place). The administration of food did not lead to changes in the ultrastructural appearance of the EC cells. The peroral administration of alcohol did not lead to any changes in the ultrastructural appearance of the AL and G cells.


Histochemical findings in the rat gastric mucosa during starvation. The influence of starving on the activity of enzymes of the rat gastric mucosa was investigated by selected histochemical methods. Beside the conventional methods of enzymatic histochemistry the technique of semipermeable membranes was used in the proof of lysosomal enzymes. Dehydrogenases were proved in aqueous and also in gel media with PMS. During the starvation in the parietal cells a marked increase took place in the activity of acid phosphatase, E-600 resistant esterase, less in beta-glucuronidase. High activity of the lysosomal enzymes in macrophages did not change during starvation. Nor did any changes took place in the activity of alkaline phosphatase in the endothelium of the capillaries. The chief cells in the control and starving animals, in contrast to the human gastric mucosa, did not contain any non-specific esterase. Concerning dehydrogenases, parietal cells with a different activity of these enzymes were observed both in starved and control animals. In the rat gastric mucosa starving induced changes in the activity of the enzymes which mark important organelles of the cells. Thus it is possible to consider the observed histochemical changes as a functional manifestation of morphological damage of cellular structures which are affected during starvation.


Histochemistry of some acid hydrolases in striated muscles of the rat. The distribution of acid phosphatase, beta-N-acetylglucosaminidase, beta-glucuronidase, and acid beta-galactosidase was studied in mm. extensor digitorum longus, soleus, and diaphragm of rats. Using the technic of semipermeable membranes activities of these enzymes were demonstrated beside cells of the interstitial tissue in muscle fibers themselves as well. Acid phosphatase displayed the highest activity which appeared in many small dots dispersed in the fiber. The activity of acid phosphatase was about 1.2 X higher in the m. soleus than in the m. extensor digitorum longus. In the latter muscle a somewhat higher activity was often found in muscle fibers displaying a higher staining for NADH tetrazolium reductase. The activity of beta-N-acetylglucosaminidase was slightly lower, that of beta-glucuronidase very weak but still discernible. The activity of acid beta-galactosidase was not ascertained in the majority of fibers. The ratio of activities measured in an area of the same size in cells of the interstitial tissue and in muscle fibers amounted in average to 2.6:1 in the case of acid phosphatase, 2.5:1 in the case of beta-N-acetylglucosaminidase, 5.7:1 in the case of beta-glucuronidase, and 44.3:1 in the case of acid beta-galactosidase. The importance of the histochemical technic in studies concerned with acid hydrolases in striated muscle fibers in normal and pathological conditions is pointed out.


The fluorescent demonstration of tissue aldehydes with dansylhydrazine. Dansylhydrazine, previously introduced in a selective fluorescent cytochemical method for the demonstration of sialic acid residues of cellular glycoconjungates, may be broadly applied as a specific, covalently bonded fluorochrome of aldehyde residues, both those naturally occurring as in elastin or those generated through PAS or Feulgen-type procedures.


[Surgery of inner ear diseases (author's transl)]. In the treatment of Menière's disease, surgical procedures are available when conservative measures have failed. The most distressing symptom of vertigo can frequently be arrested, tinnitus reduced and hearing improved. Sudden deafness due to round window rupture is treatable. The most important disorder with labyrinthe symptoms is the acoustic neuroma, the smaller ones of which can be operated on by otologists in collaboration with neurosurgeons using the transtemporal or translabyrinthine approach with preservation of the facial nerve.


[Tuberculosis of peripheral lymph nodes (author's transl)]. The diagnosis and therapy of tuberculosis involving peripheral lymph nodes is discussed in a series of thirthy patients. Diagnosis is best made by both bacteriological and histologic study. Therapy is best effected by combining medical tuberculostatics with operative intervention. Epithelioid cell or proliferative forms of lymph node tuberculosis best respond to medical management.


[The pathogenesis and management of cervical vertigo (author's transl)]. A case of labyrinthine failure due to trauma to the cervical vertebrae and its successful chiropractic management is reported. Various pathogenic theories are discussed, and the chiropractic theory explained.


[The Göttingen audiometric speech test for children. I. Speech audiometry of the young and retarded child by a picture-test (author's transl)]. The Göttingen audiometric speech test was developed for testing 3 to 4-years-old and retarded children. The test presents the following advantages: 1. The child is tested by one-syllable nouns. Thus more information by speech-rhythm is prevented. 2. For each word there are given four different pictures, which present words containing the same vowel, therefore a) the possibility of choice remains constant, b) the child won't be overtaxed by too many pictures, c) the possibility of understanding the test-word by hearing the vowel alone is avoided. The test was applied to 122 3 to 6-years-old children in order to get normal values.


[Aggravation of hearing loss (author's transl)]. Functional hearing loss is defined as a syndrome in which audiologic responses are found lacking. Such phenomena are related to capacities of the auditory system which are not fully understood (and include constant functional threshold levels as well as decreasing functional overlay with steeper discrimination scores). Examples are given for symptoms which characterize functional hearing losses, and variable timing for degrees of functional hearing loss described. In addition, etiologic factors are tabulated from a literature survey.


[Metastatic melanoma of the parotid gland (author's transl)]. The finding of metastatic melanoma simulating a parotid gland tumour and following the unknown excision of a primary tumour in 7 patients prompted assessment of lymph drainage to the parotid region. It is possible to define 4 areas of the scalp. The more posterior the primary, the lower the cervical node involvement.


[Prematurity, incubator noise and hearing disturbances (author's transl)]. 1. An audiologic follow-up study was done on 62 children, ages 10-11 years. All children had been pre-term infants, with a gestational age between 29 and 35 weeks. They had been maintained in an incubator for a period of 21-61 days. The children had frequently received ototoxic antibiotics in the newborn period, and had been subject to many perinatal risk factors with a high "non-optimal score." 2. 44 children (71%) were found to be audiologically normal, whereas 8 (13%) had minor auditory defects and 10 (16%) had major hearing defects. 3. There was a significant correlation between hearing defects and the "non-optimal score": children with the most difficult perinatal course were more likely to develop hearing difficulties. 4. This study was unable to support the assumption that the hearing loss found was due to high incubator noise levels: (a) The incubator noise level was slightly below the probably dangerous limit for noise exposure. (b) There was no correlation between the hearing impairment and the length of incubator stay. (c) The type of hearing defect was not generally consistent with that associated with noise pollution.


[Presentation and treatment of stapes dislocation and subluxation (author's transl)]. The symptomatology, especially vestibular, and the surgical findings in traumatic dislocation of the stapes into the oval window are described in 2 patients, one of whom seen 1 3/4 h after the accident and the other after 12 days. The main indication for exploratory tympanotomy was change of the spontaneous nystagmus from an irritative to a paretic type. Special attention should be given to positional nystagmus, which increases on turning onto the affected side, the mechanism for which is apparently similar to the positional vertigo of labyrinthine fistulae. Hearing was preserved in both patients. In one patient, vestibular function recovered considerably whilst in the other, there remained considerable impaired function.


[The Göttingen audiometric speech test for children. II. Speech audiometry of the pre-school child with a monosyllabic picture-test (author's transl)]. The Göttingen audiometric speech test was originally developed for testing three to four-year old children as well as retarded children. A refinement of this test supplements the original test in order to test five and six-year old children. This latter test follows the same advantages by using one-syllable nouns in combination with four different pictures. These pictures present words containing the same vowel but in contrast to the earlier test, the word list is expanded from twenty to 100 words. Standardization of the test was obtained by testing 62 five and six-year old normal children.


[Experiences with a new bone drill for surgery of the ear and nose (author's transl)]. Surgical drilling similar to that developed by Kaltenbach and Voigt for bone work on the ear, nose, maxilla, hand and vertebrae can be used at up to 80,000 rev/min without undesirable heat production. Drill-bits with the normal shaft length of 45 mm remain steady at 80,000 rev/min, but drill-bits of 70 mm length sometimes vibrate. The size of drill head and rate of revolution in this respect are related proportionately especially with cutting as opposed to diamond drill-heads. In ear surgery this method is only suitable on certain conditions. In nasal surgery it is useful for the transverse osteotomy with a 45 mm long circular saw.


[An emergency tracheal cannula and alarm for the laryngectomee (author's transl)]. An emergency tracheal cannula and a sound and light alarm for the laryngectomised patient are described. Both instruments, which are inexpensive and simple, were developed at patient request.


Sorbistin, a new aminoglycoside antibiotic complex of bacterial origin. I. Production, isolation and properties. A strain of a new Pseudomonas species produced the aminoglycoside antibiotic complex, sorbistin, which was separated by ion-exchange chromatography into three bio-active components A1, A2 and B, and two bio-inactive components C and D. Sorbistins A1, A2 and B showed moderate intrinsic activity against a wide range of bacterial species and inhibited most of the aminoglycoside-resistant organisms. Sorbistin A1 exhibited the highest activity among the three bio-active components. Sorbistins showed low order of acute toxicity in mice.


Sorbistin, a new aminoglycoside antibiotic complex of bacterial origin. II. Isolation and taxonomy of sorbistin-producing organism. The sorbistin-producing organism Pseudomonas sorbicinii nov. sp. has been isolated from a soil sample by psychrophilic pre-incubation technique. The organism resembles P. fluorescens in many respects but differs in some of the important physiological characteristics such as oxidase production, media specificity for the production of fluorescent pigment, and carbohydrate utilization pattern. The type strain No. D946-B83, has been deposited under the numbers ATCC 31086 and FERM-P 3328.


Sorbistin, a new aminoglycoside antibiotic complex of bacterial origin. III. Structure determination. The structures of sorbistins A1, A2, B, C and D have been determined including stereo-chemistry. Sorbistins A1, A2 and B are composed of a 4-acyl-amino-4-deoxy-D-glucose and 1,4-diamino-1,4-dideoxy-D-sorbitol, the latter compound being hitherto undescribed in literature. Sorbistins C and D have the same aglycone of 1,4-diamino-1,4-dideoxy-D-sorbitol, which is linked with D-glucose and 4-amino-4-deoxy-D-glucose, respectively, through a glycosidic bond.


Studies on juvenimicin, a new antibiotic. I. Taxonomy, fermentation and antimicrobial properties. An actinomycete, strain No. T-1124, was found to produce new macrolide antibiotics, juvenimicins. Based on the results of taxonomic studies, the strain was considered to be a new variety of micromonospora chalcea and the name Micromonospora chalcea var. izumensis is proposed. This strain also produced everninomicin. The production of juvenimicins was stimulated by addition of ferrous sulfate and magnesium sulfate in the fermentation medium. Among juvenimicins, juvenimicin A3 exhibited the most potent antimicrobial activities against gram-positive bacteria and furthermore was active against gram-negative bacteria.


Studies on juvenimicin, a new antibiotic. II. Isolation, chemical characterization and structures. A series of new macrolide antibiotics was isolated from the culture filtrate of Micromonospora chalcea var, izumensis. The fat-soluble basic complex consisted of eight components which were named juvenimicin A1 approximately A4 and B1 approximately B4. Juvenimicin A3 was found to be identical with rosamicin and the structures of four of the other components (JVM A2, A4, B1 and B3) have been elucidated. Juvenimicin A2 has a methyl group at position 6 instead of the formylmethyl group of juvenimicin A3. Juvenimicin A4, B1 and B3 possess a hydroxyethyl group at position 6. Juvenimicin A4 and B1 differ from each other in the nature of the chromophore. Juvenimicin B3 differs from juvenimicin B1 in that a hydroxymethyl  group is present at position 14 in the former.


The description and antibiotic production of Streptomyces hygroscopicus var. Geldanus. A new variety of Streptomyces hygroscopicus was isolated from a Kalamazoo soil. This isolate is described and identified as var. geldanus. When fermented in preferential media it produces geldanamycin, nigericin, nocardamine, and a libanamycin-like activity. Fermentation conditions, chromatographic separation, and antimicrobial spectra of the antibiotics are given.


Biological glycosidation of macrolide aglycones. I. Isolation and characterization of 5-O-mycaminosyl narbonolide and 9-dihydro-5-O-mycaminosyl narbonolide. Glycosidation of narbonolide with mycaminose was attempted by feeding narbonolide during the fermentation of a parent or a mutant strain of Streptomyces platensis, a producer of 16-membered macrolide antibiotics, platenomycins. As a result, two new compounds I and II were isolated from the fermentation broth and identified as 5-O-mycaminosyl narbonolide (I) and 9-dihydro-5-O-mycaminosyl narbonolide (II), respectively. Physicochemical and antimicrobial properties of I and II are also referred to.


Mass spectrometry of platenolides and their derivatives in connection with structure elucidation. Mass spectra of platenolides--biosynthetic precursors of the 16-membered macrolide antibiotics, platenomycins--and their derivatives are discussed in detail especially in connection with structure elucidation. Mass spectrometry was of great use in establishing the structures for platenolides I (1) and II (2).


7-(2-aminomethylphenylacetamido)-3-(1-carboxymethyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid. The synthesis of 7-(2-aminomethylphenylacetamido)-(1-carboxymethyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (BL-S786) is described and the antimicrobial activities are compared with cefazolin and cefamandole. The compound exhibits broad antimicrobial spectrum, produces high intramuscular blood levels in mice and demonstrates a high degree of therapeutic efficacy in experimental bacterial infections in rodents.


Studies on bactericidal activities of beta-lactam antibiotics on agar plates: the correlation with the antibacterial activities determined by the conventional methods. A simplified method to determine minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of beta-lactam antibiotics on agar plates is described. MIC values were determined on agar plates for benzylpenicillin, methicillin and cephalothin using Staphylococcus aureus and Klebsiella pneumoniae. A beta-lactamase solution was then sprayed onto the plates to inactivate the drug(s). After further incubation at 37 degrees C overnight, the minimal concentration at which no test bacteria were visible on the plates was defined as MBC. Both MIC and MBC values decreased with decreased inoculum size. The two values were almost coincidental when high dilutions were used as the inocula. These values were compared with those obtained by the conventional broth dilution method. In this study, MIC as well as MBC values determined by the simplified method were generally smaller than the values determined by the broth dilution technique.


Rancinamycins, metabolites produced by Streptomyces lincolnensis in sulfur-depleted media. Rancinamycins I, II, III, and IV are secondary metabolites produced by Streptomyces lincolnensis in a sulfur-depleted culture medium. Rancinamycins I, and II, the main components of the mixture, show broad spectrum antibiotic activity in vitro. Subcutaneously injected or orally administered antibiotic afforded no protection for experimentally infected mice against lethal challenges of Staphylococcus aureus. Radioactive tracer studies failed to demonstrate that the rancinamycin were precursors in the biosynthesis of lincomycin.


Rancinamycins I, II, III and IV structural studies. Rancinamycins are secondary metabolites produced by Streptomyces lincolnensis in a sulfur-depleted culture medium. The structures (except stereochemistry) of the main components of the rancinamycin-complex were determined by the use of IR, UV, PMR, and CMR spectra.


Production of quinoline-2-methanol and quinoline-2-methanol acetate by a new species of Kitasatoa Kitasato griseophaeus. Two metabolites have been isolated from the fermentation broth of a new species of Kitasatoa, Kitasatoa griseophaeus. These alkaloids have been identified as quinoline-2-methanol and quinoline-2-methanol acetate. The former exhibits hypoglycemic activity in the rat.


Deisovalerylblastmycin produced by Streptomyces SP. A new antifungal antibiotic was isolated from the fermentation broth of Streptomyces sp. 5140-A1. Degradation studies of the crystalline antibiotic, m.p. 186 approximately 188 degrees C, C21H28O8N2, suggested Piricularia oryzae and less toxicity against killfish than antimycin A--blastmycin antibiotics.


Isolation of a new peptide antibiotic, 339-29 (studies on antibiotics from the genus Bacillus. XIV). A new antibiotic named 339-29, active against Gram-positive bacteria was isolated from a strain of Bacillys pumilus. The hydrochloride is soluble in water and aqueous alcohols. The antibiotic is a basic peptide containing valine (3), isoleucine (1), Leucine (2), tyrosine (1), lysine (3) and a fatty acid.


Isolation of a new peptide antibiotic complex, B-43 (studies on antibiotics from the genus Bacillus. XV). A new peptide antibiotic complex B-43, active against Gram-positive and Gram-negative bacteria, was isolated from a strain of Bacillus circulans. This antibiotic contains aspartic acid, valine, isoleucine, leucine, phenylalanine and 2,4-diaminobutyric acid. It seems to be related to polypeptin and antibiotic complex 4205, but differs in that it contains aspartic acid residue.


1-methylpseudouridine, a metabolite of Streptomyces platensis. 1-Methylpseudouridine is a new metabolite isolated from culture filtrates of Streptomyces platensis. The structure of this compound was determined from its physical and spectral properties.


Microbial transformation of antibiotics II. Additional transformation products of maridomycin III. Streptomyces sp. strain No. K-245 was found to transform maridomycin III into four derivatives (A1, A2, A3 and A4) in addition to the transformation products reported previously. Isolation of the main product A1 was carried out by column chromatography on silica gel developed with CHCl3-MeOH (19:1). From the partial investigation of the structure of A1, it proved to have a C-18-aldehyde group and C 4''-propionyl group but no antimicrobial activity. The relationships between A group's derivatives and known derivatives of maridomycin III are also discussed.


Protective effect of D-glucaro-delta-lactam against amino-glycoside-induced nephrotoxicity in rats. The nephrotoxicity of rats caused by dibekacin (3',4'-dideoxykanamycin B) or kanamycin with or without dextran was effectively reduced by D-glucaro-delta-lactam potassium salt, as evidenced by lower levels of blood urea nitrogen and kidney edema rate, better excretion of antibiotics,and less morphological damage. Protection was dosage related, and potentiated with increasing doses, but only when the two drugs were given simultaneously. Among three alkali-metal salts examined, the potassium salt was almost equal to the lithium salt, but surpassed the sodium salt in effectiveness. Inorganic salts, in particular potassium chloride were found to be effective for the protection of normal rats, but their effect decreased for the dehydrated rats, especially in the presence of dextran.


Herbicidins A and B, two new antibiotics with herbicidal activity. I. Producing organism and biological activities. Herbicidins A and B, two new antibiotics with selective and contact herbicidal activity, were produced by a new species of Streptomyces designated as S. sagononensis. Among tested microorganisms, herbicidins indicated some activity against fungi in vitro and Xanthomonas oryzae in vivo. Their characteristic features were brought into relief by their selective and contact killing effect on many dicotyledonous plant as well as their inhibition of germination of the plant seeds, such as Chinese cabbage.


Herbicidins A and B, two new antibiotics with herbicidal activity II. Fermentation, isolation and physico-chemical characterization. Herbicidins were produced in submerged fermentation by Streptomyces sagonomensis. Isolation of the antibiotics from the culture broth was performed by adsorption on resinous adsorbent followed by elution with aqueous acetone. Herbicidins A and B were separated from each other by counter-current distribution on a Ronor column or by silica gel chromatography. Physico-chemical characterization revealed that herbicidins are new antibiotics having an adenine nucleoside moiety in their structures.


A new antibiotic,, asukamycin, produced by Streptomyces. Asukamycin, a new antibiotic, has been isolated from the culture broth of a streptomycete designated as Streptomyces nodosus subsp. asukaensis. The antibiotic inhibits the growth of Gram-positive bacteria including Nocardia asteroides. The empirical formula of antibiotic asukamycin has been proposed as C29H22N2O9 (M.W. 542). An acute toxicity of the antibiotic in mice is LD50 48.5 mg/kg by intraperitoneal injection and it has no effect on mice when it was administered by 450 mg/kg per os.


Nocardicin A, a new monocyclic beta-lactam antibiotic II. Structure determination of nocardicins A and B. The structures of nocardicins A and B, novel monocyclic beta-lactam antibiotics produced by a strain of Nocardia, have been established as 1 and 2, respectively, on the basis of spectroscopic and chemical evidence. They are the first examples of monocyclic beta-lactam antibiotics possessing relatively high antimicrobial activity, and are stereochemically and biologically related to penicillins and cephalosporins.


New pleuromutilin derivatives with enhanced antimicrobial activity. I. Synthesis. A series of new derivatives of the antibiotic pleuromutilin, produced by some Basidiomycetes, was synthesized by chemical modification of natural pleuromutilin. Most of them contain basic functional groups in the side chain at C14 of the mutilin skeleton. The monotosylate of pleuromutilin was used as a versatile intermediate for displacement by N-, O- and S-nucleophiles.


New pleuromutilin derivatives with enhanced antimicrobial activity.II.Structure-activity correlations. Structural modification of the antibiotic pleuromutilin has afforded several derivatives with considerably enhanced activity against bacteria and mycoplasmas, and has permitted conclusions to be reached about structure-activity relationships. The carbonyl group in the five-membered ring and the hydroxyl group at C11 seem to be essential for activity. The vinyl group can be hydrogenated without loss of activity. Chemical modification at C14 offers the most possibilities for achieving the best activity and solubility properties. Mutilin, and other compounds with a free OH at C14, are inactive. It was shown that mutilin esters of substituted thioglycolic acids had distinctly superior MIC values, especially in combination with a tertiary amino group in the side chain, the latter group of derivatives having MIC values better than pleuromutilin by a factor of more than 10. Further variation within this group led to the development of 14-deoxy-14-[(2-diethylaminoethyl) thioacetoxy]-mutilin hydrogen fumarate (81.723 hfu, tiamulin) for extensive investigation of its chemotherapeutic potential.


Semisynthetic beta-lactam antibiotics. 8 Structure-activity relationships of alpha-sulfocephalosporins. Synthesis and in vitro activity of a number of cephalosporins having alpha-sulfoacyl- or other acyl groups, e.g., alpha-carboxyacyl- and alpha-sulfoaminoacyl- at the 7-position and bearing a variety of heterocyclic thioether or pyridinium moieties at the 3-position are described.


Preventive effect of D-glucarate against renal damage induced by kanamycin. Kanamycin-induced renal impairment in dehydrated rats was spared by the administration of sodium D-glucaro-1,4-lactone. In the plasma elimination and urinary excretion studies, D-glucarate-treated rats showed quick removal of the antibiotic from the body as compared with non-treated rats. Organ distribution study clearly demonstrated the potent nephrotoxicity of kanamycin and the reduction effect of D-glucarate against the nephrotoxicity. The drug level in the kidney in non-treated rats was more than two orders of magnitude higher than those in other organs such as the liver, lung and spleen, and remained high for 48 hours after antibiotic administration. In D-glucarate-treated rats the kidney content of the drug was diminished as compared with non-treated rats just after the antibiotic administration, followed by a gradual decline with time.