Stylostome formation by Leptotrombidium mites (Acari: Trombiculidae). The modes of stylostome formation by larvae (chiggers) of Leptotrombidium intermedium, L. fletcheri, L. arenicola, and L. deliense in parasitized mouse skin were studied histologically in relation to their capacity to transmit Rickettsia tsutsugamushi. Three types of stylostome formation were recognized among the different species: the epidermal stylostome formed by the larva of L. intermedium; the mesenchymal stylostome formed by the larva of L. fletcheri; and, the mixed stylostome formed by the larva of both L. arenicola and L. deliense. Dermal inflammations related to the three types of stylostomes were histologically defined. The possible importance of stylostome characteristics to the transmission of rickettsial organisms is discussed.


Fine structural studies of radiation-resistant human squamous cell carcinomas. Squamous cell carcinomas of the oral cavity are relatively common lesions, and often can be controlled by radiation therapy. Recently, a series of these tumors has been encountered which did not respond positively to irradiation, necessitating subsequent extensive surgery. This report describes some fine structural changes which were observed in squamous cell carcinomas following exposure to x-irradiation. In addition to the common, keratin-forming differentiated cell, others which were observed were secretory-like, undifferentiated and phagocytic cells. Undifferentiated tumor cells occasionally became incorporated, at least temporarily, as a component of the blood vessel wall, perhaps reflecting metastatic potentiality. It is proposed that irradiation may either increase potential avenues of tumor cell differentiation or inactivate inhibitors thereof.


Histochemical study of labial salivary glands in Sjögren's syndrome. Human labial salivary gland biopsies of patients presenting connective tissue diseases associated with Sjögren's syndrome were submitted to a polysaccharide histochemistry study. The normal acinar secretion is an association of neutral polysaccharides with a sulphosialomucin. In Sjögren's syndrome, there is a great reduction in the secretory activity of the acinar cells, but no qualitative change was observed. The pathogenesis of this decreased production and its importance regarding the clinical manifestations of Sjögren's syndrome are discussed.


The effect of ultra-violet radiation and restricted diet on rat labial mucosa. The combined effect of ultra-violet radiation and a restricted diet on oral mucosa was investigated using the labial mucosa of pigmented rats. Twenty-four rats were divided so that 12 experimental animals received 50% of the average daily diet of the remaining 12 normal controls. After 1 month, the epithelium of the restricted group had thinned to 2/3 of that of the controls. Nine rats from each group were then subjected to daily ultra-violet irradiation of the labial mucosa, three animals in each group remaining as unirradiated controls. After 1, 4 and 8 weeks irradiation, three experimental and one unirradiated control from each group were sacrificed. Microscopic examination showed that the thickness of the epithelium and the mitotic index increased in both normal and restricted animals at 4 weeks. The increase in thickness was maintained at 8 weeks, but the mitotic index declined in the deficient animals at this time. Evidence of epithelial dysplasia was seen in the normal animals at 4 weeks, and this increased at 8 weeks; such changes were rarely seen in the restricted animals. It thus appears that the extent of ultra-violet induced dysplasia may be related to the mitotic index, a lower mitotic index implying less dysplasia.


A study of the mineral phase of cementifying fibroma. Physico-chemical study of a case of cementifying fibroma in the mandible of 78-year-old woman was carried out by X-ray diffraction analysis and thermogravimetric and differential-thermal analyses (TGA-DTA). The center of the tumor consisted of masses of acellular cementum-like tissues; while the periphery consisted of cementicle-like tissues. X-ray powder diffraction patterns showed that the mineral phase of these tissues was apatitic in nature. X-ray line broadening analysis revealed that the crystallinity of apatite of the cementum-like tissue was higher than that of apatite of cementicle-like tissue, and lower than that of bone apatite obtained from the same patient. Furthermore, TGA-DTA studies showed that the mineral (ash) value of cementum-like tissue was slightly higher than that of bone.


Scanning electron microscopic examination of root after apicoectomy. The scanning electron microscope was used to examine resected areas of eight roots of human teeth extracted after long intervals following surgical procedures. Some resorption lacunae were observed in the areas with protuberances of newly formed cementum. In the lacunae, honeycomb-like structures were found. On the resected surface, residues of ligaments and periodontal fibers, and in one of the specimens dentinal tubules with odontoblastic processes protruding above the surface were present.


A microagglutination test for Yersinia enterocolitica infection: recognition of multiple serotypes in experiments with stained suspensions of serotype O5,27. When suspensions of Yersinia enterocolitica were stained with triphenyl-tetrazolium chloride (TTC) their antigenic specificity, as determined by tube and microtitre-plate agglutination tests, was altered. Thus, a TTC-stained suspension of serotype O5,27 detected antibodies to nine O serotypes of Y. enterocolitica in sera from experimentally infected animals but did not cross-react with antisera to organisms of five other unrelated genera including Brucella. The same suspension did, however, cross-react weakly with antisera to four serotypes of Yersinia pseudotuberculosis. The value of this antigen preparation in detecting antibodies to the wide range of Y. enterocolitica serotypes likely to cause infection in man should now be assessed.


Signal to noise enhancement in a study of cell wall structure of Bacillus subtilis by interactive computation. This paper describes a technique for obtaining values of the width and variation in optical density of sectioned bacterial cell walls by interactive computational methods. Background 'noise' prevents accurate determination of cell wall boundaries from the data in a single scan line but the noise may be suppressed by averaging several consecutive scan lines. although application of the technique is explained for sectioned bacterial cell walls, it is equally valid for similar situations where single line scans of electron micrographs are inadequate for precise determination of measurement.


Hyperplastic foci in precancerous rat liver: light microscopic and electron microscopic study. 4-Dimethylaminoazobenzene was fed to Wistar-derived, male, albino rats after hepatic siderosis had been induced by including ferric citrate in the diet. Iron-free foci of hepatocytes developed and this characteristic enabled them to be recognized macroscopically in the brown parenchyma. Five such lesions, each 1 mm or less in diameter, were studied by light and electron microscopy. The cells in the foci were larger than those surrounding the foci and had a granular and moderately basophilic cytoplasm. Ultrastructurally, the cells closely resembled normal hepatocytes. They possessed well-developed rough endoplasmic reticulum, numerous free ribosomes, peroxisomes, bile canaliculi, and cytoplasmic junctional complexes, but only small stores of glycogen were observed. Occasional ferritin-laden lysosomes persisted in some cells. These foci were regarded as hyperplastic. Possibly, they evolved into hyperplastic nodules either of the basophilic or vacuolated type. These foci should be clearly distinguished from hyperbasophilic foci that consisted of very poorly differentiated cells.


Latent residual tumor following external radiotherapy for prostate adenocarcinoma. Fifty patients with adenocarcinoma of the prostate were treated by external supervoltage radiotherapy. Needle biopsies were obtained at timed intervals after completion of therapy. Six of 17 patients with stages A and B disease and 15 of 33 patients with stage C disease had positive biopsies. In patients biopsied more than 18 months after therapy 15 of 29 (52 per cent) had residual tumors. Of 17 patients biopsied 36 months or more after therapy 10 (59 per cent) had residual tumor. These results suggest that patients with residual tumor 18 months after therapy will not have resolution of the tumor at a future date and represent treatment failure.


Perihepatitis associated with salpingitis in adolescents. Perihepatitis, one manifestation of complicated gonorrhea, is infrequently diagnosed and reported. This study was undertaken to examine the incidence of gonococcal perihepatitis in adolescents as well as to study the effect, if any, of this condition on tests of liver function. Accordingly, the records of 137 adolescents with salpingitis were evaluated. Right upper quadrant tenderness or hepatic enlargement was noted in 27, while amino transferase level elevations were observed in 19 of the 59 in whom these tests were performed. All findings resolved promptly following initiation of intravenous penicillin therapy. The observation of hepatic dysfunction in 27% of these adolescents suggests that perihepatitis occurs more frequently than reported in adults and should be considered in the evaluation of the conditions of adolescents with salpingitis or upper abdominal tenderness.


Gonorrhea detection in posthysterectomy patients. A retrospective study of women examined at the Venereal Disease Clinic after hysterectomy was made to determine which culture site was most likely to show anogenital Neisseria gonorrhoeae infection when the cervix was absent. Seventeen of 104 such patients were culture positive for N gonorrhoeae. Rates of positivity for our culture sites were as follows: urethral, 17/17 (100%); vaginal, 7/17 (41%); and rectal, 2/17 (12%).


Geographic variation in physicians' fees. Payments to physicians under Medicare and Medicaid. To study geographic differences in physician fees recognized by the Medicare and Medicaid programs, we analyzed physician reimbursement rates at the national, regional, state, and county levels. The results indicate that nationally, Medicaid specialist fees are 77% of Medicare specialist fees. Meidcare specialist fees in metropolitan areas are 23% higher than those in nonmetropolitan areas, but there are no differences under Medicaid. State Medicare specialist fees varied from 73% to 132% of the national Medicare average, while Medicaid specialist fees ranged from 49% to 179% of the national Medicaid average. State Medicaid fees for specialists ranged from 39% to 100% of Medicare specialist fees. These results indicate that under national health insurance, fees set at national or statewide levels could have notable effects on physician remuneration in some localities.


Effects of enteral and parenteral nutrition on appetite in monkeys. Varied clinical observations of the presence of either hunger or anorexia during intragastric or intravenous alimentation have led to the current experiments. Nine rhesus monkeys (Macaca mulatta) were involved in studies of the long-term effects of enteral and parenteral nutrition on appetite as assessed by feeding behavior and gastric motility. The monkeys received either intragastric infusions of glucose or a complete liquid diet, or intravenous infusions of glucose or glucose/amino acid solutions. Oral intake was accurately adjusted to account for the calories administered by the intragastric route. Oral intake was also reduced in a calorically equivalent amount to account for the calories received during intravenous glucose. When glucose/amino acid solutions were administered parenterally, adjustments were less accurate, with resultant overeating and weight gain in some monkeys during parenteral nutrition, followed by prolonged suppression of appetite after cessation of the infusions. Further studies of the effects of varied compositions of parenteral nutrition, and varied methods of weaning from infusions, are indicated.


A technique for evaluating sepsis in TPN patients. Sepsis continues to be one of the most feared complications of total parenteral nutrition. Many techniques have been advocated for dressing changes, solution preparation, and evaluation of patients with fever spikes. Our technique in evaluating such a patient with suspected sepsis is to remove the tubing and solution from the pumping mechanism and place the bottle below the patient, permitting approximately 10 cc of blood to flow into the tubing. The entire set-up of solution and tubing is then quickly replaced and the infusion resumed. The removed blood is transferred to a series of three standard blood culture bottles. The first bottle will be culturing blood; the second, a mixture of blood and infusate; the third, solution alone. When performed carefully, negative culture results appear to exclude TPN as a source of spesis. Positive results are obviously helpful, but must be interpreted with caution in that the blood, catheter, tubing, filter, or solution may be suspect.


Calcium requirements during total parenteral nutrition in well-nourished individuals. Eleven patients, receiving all nutrition intravenously, were given varying doses of calcium (0-20 mg/kg/day) to determine an optimal level for calcium administration during postoperative parenteral nutrition. During each study period, nitrogen, phosphorus, vitamin, and caloric intakes were constant. Negative calcium balance resulted when less than 2 mg Ca++/kg body weight was given daily. During excessive urinary calcium losses, serum calcium concentration remained in the normal range. Increasing calcium intake to approximately 5 mg/kg/day (500 mg/day) yielded an apparent retention of calcium, as did higher doses. Serum calcium did not rise at this time. Urinary calcium excretion was directly proportional to calcium intake. The preliminary data suggest that a minimum dose of 5 mgCa++/kg/day is necessary to attain equilibrium between intake and urinary output. This value is higher than recent suggestions for calcium replacement during intravenous feeding.


Recurring infection and "shunt nephritis" in home hyperalimentation. A patient on home hyperalimentation after a series of infections, developed a "shunt nephritis" not unlike the nephritis reported in patients with hydrocephalus undergoing ventriculoatriostomy. Permanent eradication of infection and reversal of kidney damage required removal of indwelling catheter.


Transplantation of preserved pancreatic islets into the portal vein of rats. Langerhans islets were isolated from the exocrine pancreata of Wistar rats by the improved collagenase-digestion method. The isolated islets were preserved in a tissue culture medium for seven days. Transplantation of these preserved islets into the portal vein of streptozotocin-induced diabetic rats resulted in a significant reduction of hyperglycemia, polyuria and glucosuria, and a restoration of weight gain. It was found that these effects could be maintained for 16 weeks. In order to normalize the K-values and plasma insulin levels, at least 600 islets had to be transplanted into each diabetic rat.


Postheparin-diamine oxidase (histaminase) in anaphylaxis. The level of plasma postheparin-diamine oxidase was determined in two patients three days after an anaphylactic shock and was controlled four weeks, and also six months later. A decrease of the enzyme levels to about 10% of a control group was found and a slow enzyme increase to about 40% observed six months later. It seems probable that in anaphylaxis a depletion of the enzyme in liver and small intestine occurs as could be shown in animals after heparin load.


Technique for transcervical intrauterine inoculation of the mouse. Suspensions of india ink or gonococci were inoculated into the murine uterus through the cervix with a simple plastic vaginal speculum and a 23 gauge blunted needle. The inoculated suspensions were distributed throughout both uterine horns, cervix, and vagina, but did not flow into the peritoneal cavity. This method avoided surgical stress as well as being simple, fast, and reproducible.


Observations on acute gastric dilatation in nonhuman primates. In the years 1967-1977 we diagnosed 23 cases of acute gastric dilatation in monkeys. Fourteen of these animals were Macaca mulatta, five Macaca fascicularis, and one each of Macaca nemestrina, Aotus trivirgatus, Saimiri sciureus, and Colobus guereza. Fourteen of the animals were males, nine were females, and all were adults or subadults. Mortality was 78% (18 of 23 animals). Thirteen of the animals had received on anesthetic, immobilizing, or tranquilizing drug 1-2 days before developing acute gastric dilatation; seven monkeys were overfed, and two had been transferred from one area to another the day prior to developing the disease. Two animals were found dead in their cages with no apparent cause for the gastric dilatation. Five Macaca mulatta and three Macaca fascicularis recovered following treatment, but two Macaca mulatta subsequently succumbed to another episode of acute gastric dilatation. Treatment consisted of evacuation of the stomach, correction of blood volume deficits and acid-base disturbances by administration of appropriate fluids, and supportive therapy for shock.


Experimental injury of the optic nerve with optic disc swelling. An ultrastructural study utilizing horseradish peroxidase was performed to determine the mechanism and consequences of leakage of vascular protein following injury of the optic nerve. Unilateral optic nerve injuries were produced in four rhesus monkeys by making a cautery lesion on the retrobulbar portion of the optic nerve. Optic disc changes were followed with stereo fundus photography and fluorescein angiography. Three to 14 days after injury horseradish peroxidase was given intravenously and the tissue was prepared for electron microscopy, including serial sections of selected tissue blocks. Fundus photography and fluorescein angiography showed edema of the optic disc in two animals. There was leakage of horseradish peroxidase into the optic nerve head from the optic nerve lesion and the peripapillary choriocapillaris. Although the pathway of horseradish peroxidase leakage in the injured optic nerve was not entirely clear, serial sections indicated intraendothelial channels as one possible route. Alterations of the optic nerve head were confined to the axon segments anterior to the injury, and included aggregation of mitochondria, disruption of neurotubules, and swelling. These findings suggest that optic nerve injury produces damming of axoplasmic flow and that swelling of the optic nerve head is the result of axon enlargement.


Fatigue-induced damage in glutaraldehyde-preserved heart valve tissue. Glutaraldehyde-preserved porcine mitral leaflet tissue has been subjected to extended accelerated fatigue loading in Ringer's solution containing 0.15% glutaraldehyde. Five tissue test pieces were subjected to cyclic tensile stresses of 50 and 200 Gm. per square millimeter and to 300 million to 800 million accumulated fatigue cycles. Tissue disruption occurred in each of the fatigued test pieces. Tensile loading, apart from reducing the acuteness of the collagen waveform and thereby decreasing tissue compliance, does not contribute significantly to the disruption process nor its rate of occurrence. Compressive flexure occurring during the unloading half of the fatigue cycle, however, does induce damage in the tissue. Mechanisms involved in the disruptive processes have been identified by conducting simultaneous morphologic and stress/strain observations on both the fatigued and unfatigued tissues in their wet functional condition. This vulnerability of the preserved tissue to compressive flexure could well affect the long-term durability of the glutaraldehyde-preserved heterograft valve, and this possibility is discussed in relation to the clinical use of these valves.


Motor disorder in pharyngoesophageal pouch. Patients with a pharyngoesophageal pouch studied by esophageal manometry were shown to have premature relaxation of the upper esophageal sphincter. Postrelaxation contraction of the sphincter was therefore already in progress while pharyngeal contraction was taking place. This motor disturbance creates a physiological obstruction at the upper esophageal sphincter so that high pressures are built up in the pharynx. These conditions are conductive to herniation of the pharyngeal mucosa through any weak area in the muscle wall of the pharynx.


Insulin treatment in diabetes.

Insulin treatment in diabetes. Efficacy of and indications for the use of purer forms of insulin have now been established, and arguments showing the relation of blood glucose control to the development and progression of complications have been strengthened.


Oral hypoglycemic agent update.

Oral hypoglycemic agent update. The treatment of diabetes is still a problem more than a half-century after the discovery of insulin. Patients are now living significantly longer but until the development of oral hypoglycemic agents, the only direct treatment modalities were exercise, diet, and insulin. Before evaluating the effectiveness of treatment, a therapeutic goal must be determined. While there are no absolutely "hard" facts proving that "good control" is beneficial in preventing chronic complications of diabetes, increasing accumulation of "soft" data strongly suggests that normal blood glucose levels are most desirable, when possible, but not at the cost of severe or disabling hypoglycemic reactions. The development of the oral agents was a great public health advance in that many persons with early diabetes, but fearful of insulin injections, had less dread of "the pills" and sought treatment. The oral agents simplified care but this very simplification process often undermined the need for proper diet and good fundamental care. This often led to mediocre diabetes care. While useful, the oral agents have marked limitations and in some are effective only temporarily. The presently available oral agents are sulfonylureas and require a viable beta-cell system for success. This limits the number of diabetics responsive to such treatment. The general indications for tolbutamide, chlorpropamide, acetohexamide and tolazamide are in maturity-onset diabetics, generally beyond the age of 40 with diabetes of less than 10 years. They are contraindicated in juvenile-onset diabetics, in pregnant women, and usually in patients undergoing major surgery, and can become ineffective during periods of extreme stress or during severe infection. They can lower blood glucose levels if used in proper doses in properly selected patients. Contrary to several decades of documentation, it has become popular to suggest that the oral agents are not effective. They can be effective but for many reasons apparently were not in their use by the U.G.D.P. researchers. This might not be the fault of the oral agent used. If ineffective, they should be discontinued. Many, but not all, patients may respond to diet therapy, which is then the treatment of choice. Obviously insulin, though difficult to use for many persons and in itself able to induce several severe reactions if not used properly, is the only treatment (with diet) for the severe diabetic. There is a large spectrum of patients inbetween in whom the oral agents may be useful. The use of phenformin (phenethyl-biguanide) has been effectively curtailed because of many reported cases of lactic acidosis, and while it is doubtful that phenformin alone, in the absence of complicating factors, is the causative factor, it is capable of being an augmenting influence when other conditions, such as decreased kidney function, prevail...


Proinsulin and C-peptide in diabetes.

Proinsulin and C-peptide in diabetes. The availability of C-peptide measurement continues to provide new and useful information about the state of beta cell secretory function and the natural history of diabetes. Measurement of proinsulin is of value in the diagnosis of insulin-secreting tumors.


[Total parenteral nutrition as primary therapy in Crohn's disease (author's transl)]. Total parenteral nutrition was given to 10 patients with acute regional enteritis for 3--12 weeks. The rationale of this therapy is elimination of potential food allergens and decrease of intestinal irritation. Complete remission of the disease could be achieved in 8 patients, thus surgical removal of the intestine involved could be avoided. One entero-cutaneous and two perinal fistulas healed spontaneously; two other perianal fistulas improved so much, that local surgical treatment  was sufficient. If well planned, total parenteral nutrition can be performed without disturbance of metabolism and septicemia caused by the catheter can be avoided. No final judgement about recurrence of regional enteritis after total parenteral nutrition is possible at present due to as yet limited experience.


Effect of starvation on hypothalamic-pituitary-thyroid function in the rat. Total starvation in the rat for 2 days did not alter the hypothalamic content of thyrotropin-releasing hormone (TRH), but did decrease both pituitary TSH content and serum TSH concentration. Five days starvation resulted in a significant decrease in serum TSH and a slightly enhanced serum TSH response to exogenous TRH, suggesting that the pituitary retains its sensitivity to TRH. Fasting for 5 days resulted in a decreased 1 and 4th, but an increased 24th thyroid 131I uptake. Other starvation-induced abnormalities of intrathyroid 131I metabolism were a consistent increase in the percent of organified 131I present as MIT and DIT and a decreased percent 131I labeled T4 AND T3. These alterations in the intrathyroid metabolism of 131I in the starved rat probably reflect both a decrease in serum TSH concentration and a decrease in urinary and fecal loss of administered 131I. The serum total and free T4 and total and free T3 concentrations were decreased following 2 and 5 days of starvation.


R plasmids among Gram-negative bacteria with multiple drug resistance isolated in a general hospital. The incidence of conjugative R plasmids in multiple drug-resistant strains of gram-negative bacteria isolated in 1973 from patients in a 700-bed general hospital in Tokyo and some properties of the R plasmids isolated are described. Conjugative R plasmids were found in 52 of the 96 strains (54%), from which 74 R plasmids were demonstrated. It is remarkable that the isolation frequency of R plasmids mediating quadruple- or five-drug resistance was rather low, and the complete pattern of multiple resistance of the original isolates was only rarely transferred by conjugation. These results revealed the existing state of the distribution of R plasmids among hospital strains with multiple drug-resistance.


Theoretical approach to laser trabeculotomy. Theoretical aspects of laser characteristics as well as the physics parameters involved in laser trabeculotomy in open-angle glaucoma are put forward. Outflow hydrodynamics and perforation mechanism as well as the required optical matching system are evaluated in detail.


Fast and thermal neutron profiles for a 25-MV x-ray beam. High-energy x-ray radiotherapy machines generate neutrons by photonuclear reactions in the target and the treatment head and expose the patient to a neutron flux. In order to evaluate the neutron exposure quantitatively, fast and thermal neutron profiles for 25-MV x-ray beams of the Sagittaire accelerator have been measured. An activation technique, using the reactions 31P(n, gamma)32P (thermal neutrons) and 31P(n, p)31Si (fast neutrons, E greater than 0.7 MeV), has been developed to measure fast- and thermal-neutron fluxes in an intense high-energy photon flux. The sensitivity of this activation detector to high-energy photons, which has plagued many previous neutron measurements, was carefully measured and found to be less than 4%. Neutron fluxes for various photon field sizes ranging from 5 X 5 cm to 30 X 30 cm have been measured. The fast-neutron profiles were observed to have rounded edges and the thermal fluxes were found to be relatively uniform. In the central part of the x-ray beam, the ratio of neutron dose equivalent to photon absorbed dose was found to be between 0.2% and 0.5%. Outside of the photon field, the ratio of neutron dose equivalent to the central-axis photon absorbed dose was 0.12%.


[Total parenteral nutrition].

[Total parenteral nutrition]. A short historical introduction is followed by an account of the indications and counter-indications for total parenteral feedings, together with its administration modalities, bearing in mind the importance this technique currently enjoys in the stomatological and maxillo-faccial field. The metabolic situation of average patients subjected to this form of treatment is described, along with the hydric, caloric, plastic and electrolytic aspects of a given method, and the way in which the success or failure of an adopted technique can be ascertained.


Influence of deficiency of the histone gene-containing 38B-40 region on X-chromosome template activity and the white gene position effect variegation in Drosophila melanogaster. The deficiency of the 38B-40 region containing histone genes in one of the 2nd chromosomes of D. melanogaster triploid intersexes increases the template activity of X-chromosomes both in vivo and in vitro without noticeably affecting autosome activity. This deficiency in the heterozygous state inhibits the variegated position effect of the white gene in the T(1;3)Wvco translocation in diploid females and males, but not affect their rate of development. The variegation suppressor Su(var)hg-1 not only suppress the gene position effect in diploid flies, but also increases the template activity of X-chromosomes in triploid intersexes. The results are discussed with respect to the dependence of gene activity on the structure of chromosomes (density of DNP packing).


[Combined polychemotherapy and radiotherapy in the treatment of carcinoma of the oral cavity]. A brief survey of the relevant literature is followed by an account of the method and techniques employed in combined radiotherapy and polychemotherapy of 32 cases of cancer of the mouth. The results are described, together with the indications and limitations associated with the method. It is suggested that this form of treatment is sound, though it is pointed out that follow-up of the series has not been long.


[Value of the use of a cement containing a combination of triamcinolone and tetracycline in cavity preparations]. Odontomix (reg'd) cement was used at the bottom of cavities prepared in healthy dog canines in a attempt to prevent pulp and dentine alterations caused by the preparation and filling of cavities. 24 dogs were used along with 24 controls. I.v. tetracycline was afterwards given 10 times at weekly intervals. Examination of tetracycline labelling under the cavities showed that the cement caused pulp and dentine changes in confined areas, though it has not yet been possible to determine whether these are due to the corticosteroid, the antibiotic, or the excipient employed in the preparation.


Molecular cloning of the gene region coding for the chloroplast rRNA of Euglena gracilis. E. gracilis chloroplast DNA Bam fragments E and D, coding for rRNA were cloned separately using the plasmid pBR 322 as vector and E. coli as host. The newly constructed recombinant plasmids EgcKS 8 and EgcKS 11 (containing the Bam HI fragments E and D respectively) were analysed and characterized by gel electrophoresis, electronmicroscopy and analytical ultracentrifugation.


Transfection with replicating DNA from the temperate Bacillus bacteriophage phi 105 and with T4-ligase treated phi105 DNA: the importance in transfection of being longer than genome-length. Replicating phage DNA extracted from Bacillus subtilis infected with phage phi 105 has a higher activity in transfection than mature DNA. By heteroduplex analysis it was shown that this DNA contains concatemeric molecules. Concatemers, constructed in vitro by treatment of mature DNA with T4-ligase also have an increased activity in transfection. DNA showing an increased activity in transfection does not have a requirement for more than one molecule per transfection event as is typically found for transfection with mature phi 105 DNA. An explanation is given for this difference suggesting that the structure of the ends of the transfecting molecules play an important role intransfection.


Evidence that F' lac replicates asynchronously during the cell cycle of Escherichia coli B/r. The replication of F' lac was studied in exponentially growing cultures of E. coli B/r. The cells were pulse induced for the synthesis of beta-galactosidase and their DNA pulse labelled with 3H thymidine. The cells were then separated into age classes by centrifugation through a sucrose gradient in a zonal rotor. Plasmide replication was measured in each age fraction by three methods: the rate at which beta-galactosidase could be induced, the amount of label incorporated into CCC plasmid DNA which had been separated from chromosomal DNA on agarose gels, and the amount of label incorporated into plasmid DNA which had been separated from chromosomal DNA by ultracentrifugation through CsCl-EtBr gradients. All these methods gave the same result, that replication of F' lac occurs in cells of all ages and is not confined to a part of the cell cycle.


Periodically interspersed repetitive sequences may govern higher-order DNA coiling in chromatin and chromosomes. The interspersed periodic arrangement of repetitive and unique sequences in eukaryotic DNAs is proposed as the underlying molecular basis for higher-order DNA coiling in chromatin and mitotic chromosomes. It is assumed that (i) two types of interspersed repetitive sequences are distributed strictly periodically throughout the genome, splitting the single copy DNA into short and long periods respectively in such a pattern that each long period is composed of a definite number of short periods and repeats, (ii) the short and long periods make the turn lengths of the solenoid and supersolenoid structures respectively determining their diameters; (iii) specific proteins interact with each type of repeats making cross ties between nearby repeats of each class helping to form, constrain, and stabilize the solenoid and the supersolenoid structures: (iv) the long period may be equated with the basic chromomere unit. The model predicts: (i) splitting of contiguous genes by inserted repetitive sequences; and (ii) two types of genomes differing in the hierarchy of DNA coiling.


Increased serum thyroid hormone binding and decreased free hormone in chronic active liver disease. To determine whether chronic inflammatory disease of the liver increases serum thyroid hormone binding, we measured tri-iodothyronine resin binding ratios in nine patient with primary biliary cirrhosis and in nine with chronic active hepatitis. In each group, the average binding ratio was about 50 per cent higher than in control subjects. Thyroxinebinding globulin, measured by immunoassay in three patients, was elevated. Although average total thyroxine and tri-iodothyronine were increased slightly, the corresponding free hormone concentrations were lower than controls, probably because of decreased thyroid function associated with the high incidence of autoimmune thyroiditis in nonalcoholic (autoimmune) liver disease. Thyroid autoantibodies were found in 13 patients. Impaired hepatic thyroxine-to -tri-iodothyronine conversion may have contributed to the low free tri-iodothyronine. Thyrotropin was elevated in four patients. Because of increased serum thyroid hormone binding in these patients total thyroxine and tri-iodothyronine concentration can be normal despite hypothyroidism.


Can the psro's be cost effective? A study of the effect of the Commonwealth Health Agencies monitoring program on the length of stay of Medicaid patients in Massachusetts. To analyze the effect of the Commonwealth Health Agencies Monitoring Program on the length of stay of a sample of Massachusetts Medicaid patients, we compared their experience with that of non-Medicaid patients. We found a consistently decreasing trend in the length of stay of Medicaid patients during the 2 1/2-year period studied. The average length of stay of Medicaid patients decreased by 11.9 per cent relative to the norm, whereas the non-Medicaid length of stay decreased by only 6.6 per  cent. We infer that the Program may be credited within the 5.3 per cent differential decrease. The consistency and reliability of the data suggest that similar results may be extrapolated to the hospitals not sampled. We conclude that Professional Standards Review Organizations, of which this program was a precursor, can be cost effective, given an expanded review mandate and the application of suibable evaluative processes.


[Distribution of repeating nucleotide sequences in the macronucleus DNA of Tetrahymena infusoria]. The genome of Tetrahymena pyriformis macronucleus contain less than 10% of repetitive sequences. About half of them consist of long, more than 2000 base pairs, moderately repeated sequences. Short repetitive sequences (200--300 base pairs) represent 4--5% of the genome. We assume, that the short repetitive sequences are interspersed with single copy sequences of about 1000 base pairs. In this case less than 15% of the Tetrahymena DNA should consist of interspersed repetitive and single copy sequences.


Sensitivity of TSTA and species-specific cell membrane antigens of tumor cells to glutaraldehyde treatment. In vivo immunogenicity and in vitro species-specific membrane antigens in tumor cells treated or untreated with glutaraldehyde (GA) were studied. Two different syngeneic Syrian hamster transplantable tumor cell lines (spontaneous liver cancer and SV40-induced sarcoma) not only lost immunogenicity after GA treatment but were responsible for enhancement of test-tumor growth in immunized animals. In vitro mixed hemadsorption test used for determination of species-specific membrane antigens in Syrian hamster, green monkey and interspecies hybrid cells revealed drastic alteration of antigens on the membrane of cells treated with GA.


Accelerated atherosclerosis in chronic-dialysis patients--another look. Actuarial statistics of 53 dialysis patients treated between 1965 and 1976 are reviewed. It is suggested that dialysis did not accelerate atherosclerosis over the observed time period. It appears as though a fundamental change in the dialysis population has occurred and there are too few long-term dialysis patients available to establish whether dialysis does accelerate atherosclerosis.


Thyrotropin and prolactin secretory patterns during 24-hours infusion of thyrotropin-releasing hormone in calves. Plasma levels of thyrotropin (TSH), prolactin (Prl), growth hormone (GH), thyroxine (T4), and triiodothyronine (T3) were measured in response to continuous 24-h infusion of synthetic thyrotropin-releasing hormone (TRH) in normal and surgically thyroidectomized (THYX) calves in a series of 2 experiments. In the 1st experiment, the low dose of TRH (0.077 microgram/min) had no effect on any hormone levels measured. Plasma TSH concentration increased significantly (p less than 0.05) in response to TRH infusion (0.77 microgram/min) in both experiments, but plasma TSH levels plateaued and then declined in both cases despite continued TRH infusion and irrespective of the presence or absence of a thyroid gland. A similar pattern of secretion, though less markedly decreased over time, was observed for plasma Prl in both experiments. The higher dose (0.77 microgram/min) of TRH had no effect on plasma GH concentration in the 1st infusion, but did result in a significant (p less than 0.05) increase in overall mean concentration of GH in both normal and THYX calves in the 2nd experiment. Removal of the thyroid gland, thus removing the source of increasing T4 and T3 levels seen in normal calves infused with TRH, failed to alter the secretory patterns of TSH and Prl. These data suggest that feedback inhibition by increasing plasma thyroid hormone concentrations was not responsible for the failure of TSH and, to a lesser extent, Prl to maintain chronically elevated plasma levels in response to continuous 24-h TRH infusion. It is suggested that a depletion of pituitary TSH and Prl stores readily secretable in response to a constant dosage level of TRH may be responsible for the secretory patterns observed.


The effect of thyrotropin-releasing hormone (TRH) and somatostatin (GHRIH) on growth hormone and prolactin secretion in vitro and in vivo in the domestic fowl (Gallus domesticus). The effects of thyrotropin-releasing hormone (TRH) on growth hormone (GH) and prolactin (Prl) secretion have been investigated in vitro and in vivo in domestic fowl. In both conscious and anaesthetized immature chickens the administration (i.v.) of TRH (2.5 and 25 microgram/kg) significantly increased the concentration of plasma GH. The simultaneous administration of somatostatin (GHRIH), 2.5 microgram/kg, to conscious birds significantly reduced the magnitude of the GH response to TRH treatment, but had no effect on the basal levels of plasma GH. The repeated injection of TRH (10 microgram/kg) every 20 min over a 100-min period failed to maintain the concentration of plasma GH at a high level. Prl secretion was not stimulated in any of these experiments, and in anaesthetized birds TRH (2.5 and 25 microgram/kg) treatment was followed by a depression in the level of plasma Prl. The effects of TRH and GHRIH on GH secretion by an in vitro dispersed pituitary cell suspension system were very similar to the in vivo studies. TRH stimulated Prl release in vitro, in contrast to the in vivo studies, and the response was dose related. GHRIH had no effect on the basal release of Prl in vitro but significantly inhibited the response to TRH treatment.


Benign post-traumatic encephalopathy in young people and its relation to migraine. Thirteen children and adolescents between ages 4 and 19 years developed transient nonconvulsive neurological symptoms and signs within a few hours apparently trivial head injuries. Some became quite seriously ill, but all made rapid and complete recoveries. Some of these young people are known to have suffered from migraine before and/or after this episode, and in all but one of the others a family history of migraine was elicited. With these patients are compared five younger children who developed epileptic fits after equally slight trauma. A diagnosis of migraine should be considered in children who develop delayed impairment of consciousness after head trauma, with or without convulsive phenomena or focal neurological deficits, and in whom specialized investigations reveal no sign of a mass lesion or of intracranial hemorrhage.


Chronic ventricular cerebrospinal fluid sampling, drug injections, and pressure monitoring using subcutaneous reservoirs in monkeys. Animal models enabling reliable access to ventricular cerebrospinal fluid (CSF) are crucial to the study of neuropharmacological and neurotoxicological effects of cytotoxic agents used to treat central nervous system neoplasms. This investigation concludes that 4th ventricular catheterization using subcutaneous CSF reservoirs in rhesus monkeys: (a) provides chronic access to sterile CSF without chronic immobilization, (b) enables mixing of injected drugs with lateral ventricular CSF, (c) permits sensitive monitoring of intraventricular pressure and (d) does not produce tissue damage during cannula implantation or breakdown of the blood-brain barrier.


The effects of sodium nitroprusside and trimethaphan camsylate on cerebral blood flow in rhesus monkeys. Hemispheric cerebral blood flow was measured in the rhesus monkey before and after infusion of the hypotensive agents sodium nitroprusside and trimethaphan camsylate. The intracarotid injections of 133Xe was utilized, and flow was calculated by the "flow initial" technique. Cerebral blood flow did not change significantly with the administration of trimethaphan camsylate. However, with a small reduction in blood pressure (10.6%) during the administration of sodium nitroprusside, the cerebral blood flow fell significantly (15.4%).


Posttraumatic epilepsy and acute intermittent porphyria: effects of phenytoin, carbamazepine, and clonazepam. A patient with uncontrolled posttraumatic epilepsy and acute intermittent prophyria was subjected to successive therapeutic trials with phenytoin, carbamazepine, and clonazepam, while eating an adequate diet. Both phenytoin and carbamazepine treatments caused significant increases in porphobilinogen excretion and appeared to induce acute porphyric attacks. In contrast, treatment with clonazepam under rigid dietary control for 10 days caused no increase in porphilbinogen excretion. During the subsequent 7 months of treatment with clonazepam, neither seizures nor porphyric attacks recurred. These findings suggest that clonazepam may be a safe and effective treatment for chronic or severe generalized seizure disorders in patients with acute intermittent porphyria.


Validation of a new technique for measurement of intracranial pressure with a scintillation counter. Intracranial pressure sensors and subdural and subgaleal sensing tambours were used to measure the pressure difference between the intracranial and subgaleal spaces in two monkeys. The pressure differential was transmitted to fluid bathing a piston, to which an isotope source (145Pm) was attached. The radiation signal emanating through a fixed collimator was detected transcutaneously by a sodium iodide crystal contained within a photomultiplier tube connected to a scintillation counter. After in vitro testing of linearity, in vivo infusion studies were performed. Linearity between intracisternal pressure and radioactivity (r = 0.99; p less than 0.001) was established in the two experimental animals for an interval of 5 months and 1 year, respectively. Autopsy findings confirmed that the sensing tambours became encapsulated with a pseudomembrane that did not attenuate the pressure signal. The results of this investigation suggest that this method for measurement of intracranial pressure without transcutaneous connections may be suitable for long term monitoring of intracranial pressure.


Effect of intravenous sodium nitroprusside on cerebral blood flow and intracranial pressure. Local cerebral blood flow was measured with the hydrogen clearance technique during intravenous infusion of nitroprusside in monkeys. Concentrations of the drug required to reduce the mean arterial blood pressure by less than 40% resulted in no significant change or only a slight increase in regional cerebral blood flow. Larger doses, however, produced a loss of cerebral autoregulation, thereby inducing a drop in cerebral blood flow. Intracranial pressure rose proportionately to the nitroprusside dose during the infusion.


Diaphragm pacing in central von Recklinghausen's disease: a case report. A patient with central von Recklinghausen's disease with multiple lower cranial nerve tumors developed nocturnal central hypoventilation that was successfully treated with diaphragm pacing. An unusual postimplant complication requiring an increased amplitude of stimulation occurred and was later found to be due to a neurofibroma that had partially displaced the electrode cuff off the phrenic nerve.


Sinusoidal fetal heart rate pattern following intrauterine fetal transfusion. Two patients with severe rhesus isoimmunization had sinusoidal fetal heart rate patterns following intrauterine fetal transfusion. A consistent temporal relationship between fetal transfusion and sinusoidal fetal heart rate pattern was observed. Survival of a fetus who had a sinusoidal fetal heart rate pattern after each of three transfusions suggests that this pattern may not be ominous when observed transiently after fetal transfusion.


Alcoholic ketoacidosis in pregnancy.

Alcoholic ketoacidosis in pregnancy. The presence of severe ketoacidosis in the absence of hyperglycemia and glucosuria is reported in a young pregnant chronic alcohol abuser. The clinical presentation included an arterial pH of 7.15, a base deficit of 23 mEq/liter, a bicarbonate of less than 10 m Eq/liter, larger serum and urinary ketone levels, and hyperpnea with Kussmual-type respiration. Corrective therapy consisted of rapid fluid, electrolyte, bicarbonate, and glucose replacement with insulin supplementation. The ability of the fetus to tolerate the maternal metabolic derangements of "alcoholic ketoacidosis" as well as the stress of uterine contractions is discussed and contrasted with diabetic ketoacidosis.


The bacterial pathogenesis of acute pelvic inflammatory disease. To study the bacterial pathogenesis of acute pelvic inflammatory disease, peritoneal fluid was obtained by culdocentesis in 133 of 344 women with this disease. In 104 of the specimens bacteria were identified both in the gram-stained smear and culture. Neisseria gonorrhoeae was isolated from the lower genital tract in over half of these women, and there were 3 patterns of bacterial recovery from peritoneal fluid: N gonorrhoeae alone (22%), N gonorrhoeae and other organisms (32%), and nongonococcal organisms alone (46%). In women without cervical gonorrhea only nongonococcal organisms were identified from peritoneal fluid. In both groups of women a similar number of nongonococcal organisms were isolated. The results of this study supported those reported prior to availability of antimicrobials and suggest that N gonorrhoeae initiates most cases of pelvic inflammatory disease. A significant number of these women have superinfection with nongonococcal organisms which may preclude recovery of gonococci.


Detection of large fetal--maternal transfusions. Two hundred consecutive Rh-negative women at risk of Rh sensitization were screened postpartum for large fetal--maternal transfusion by two acid elution techniques. The Nierhaus modification of the Betke-Kleihauer method and the Fetaldex test were compared. In 194 of 200 women, both procedures indicated the absence of significant fetal--maternal transfusion. In 6 women a large fetal--maternal hemorrhage was detected by the Betke-Kleihauer method and in 5 of these 6 by the Fetaldex test. The overall correlation between the two techniques was 99.5%. The Fetaldex test has advantages over the Betke-Kleihauer method and is well suited for routine use postpartum and for other situations where identification or quantitation of fetal cells is desirable.


Response of the living organism to dead and fixed dead, enclosed isologous tissue. Polyethylene tubes closed at both ends and with four perforations in the side walls were filled either with isologous muscle tissue or with formaldehyde-fixed or glutaraldehyde-fixed isologous tissue, and then implanted subcutaneously in rats. As controls, tubes with solutions of the fixatives were implanted. When cell reaction in the tissues surrounding the differently filled tubes was examined, the reaction to untreated necrotic tissue was found to be the least severe.


Reduced hepatic bilirubin uridine diphosphate glucuronyl transferase and uridine diphosphate glucose dehydrogenase activity in the human fetus. Hepatic bilirubin uridine diphosphate glucuronyl transferase (UDPG-T) activity was 0.14 and 0.22 units in two fetuses aged 17 and 22 weeks, respectively, and less than 0.1 unit in 15 fetuses, aged 8--19 weeks compared to 0.68--1.99 units in 21 normal adults. Hepatic uridine diphosphate glucose dehydrogenase (UDPG-D) activity in 14 fetuses, aged 8--18 weeks, ranged from 6.2--15.0 units (mean = 11.3 +/- 0.7) compared to 28.8--49.2 units (mean = 39.6 +/- 2.5) in eight normal adults (P less than 0.001). There was no correlation between UDPG-D activity and gestational age. The hepatic UDPG-D activity was 16.5 units in a 33-day-old full term, female infant, 42.4 and 24.3 units in two 2-year-old infants, respectively, and 24.3 units in a 5.5-year-old child. In three human fetuses, the apparent Km UDPG was 0.54 x 10(-4) M. Thus, both hepatic bilirubin UDPG-T and UDPG-D activity are markedly reduced in the human fetus during the second trimester of gestation. Retarded development of hepatic UDPG-D may extend beyond the first month of life.


Microbiology of the vagina in children: normal and potentially pathogenic organisms. Vaginal cultures from 100 healthy girls, 2 months to 15 years of age, were examined for the presence of normal and potentially pathogenic microorganisms. Corynebacterium vaginale, yeast species, and genital mycoplasmas were isolated from vaginal cultures from 13.5 %, 28%, and 28% of the girls examined, respectively. Colonization with these organisms was not associated with signs or symptoms of vaginitis. Neisseria gonorrhoeae was isolated from a 4-year-old with purulent vaginitis. Trichomonas vaginalis was recovered from two 13-year-olds, both of whom had an abnormal vaginal discharge. Vaginal antibody to Chlamydia trachomatis was found in two girls 4 and 13 years of age. In neither girl was the organism recovered from the vaginal culture. Chlamydia trachomatis was recovered from the vaginal culture of another 4-year-old who had no abnormal findings on examination. Cultures from 59 of the girls were examined for aerobic and facultatively anaerobic bacteria. Diphtheroids and Staphylococcus epidermidis were the most frequently isolated organisms. Lactobacilli were isolated most frequently from the older girls, whereas enteric organisms were isolated most frequently from the younger girls.


[Immuno-electro-diffusion on cellulose acetate membrane for serological testing in human malaria (author's transl)]. An immuno-electro-diffusion assay for human malaria, using cellulose acetate gel, is described. More than 3500 sera have been tested by this method, which proved very useful for epidemiology since 400 sera a day can be tested by one person, with simple equipment. Its sensitivity compared well to the IFA test, although the antibodies revealed are quite different. A constnat precipitin line appeared, against 56 degrees C labile antigens, in sera of subjects infected by P. falciparum, and up to 8 other precipitins per serum tested. The test may be useful in analyzing these multiple antibodies occurring in patients with malaria.


Effect of dopamine on renal blood flow of baboon in endotoxin shock. Renal vasodilation observed in canine endotoxemia did not occur during endotoxin shock in the baboon: in fact, renal artery blood flow was markedly reduced. Infusion of dopamine in the baboon restored the renal artery blood flow.


Phosphate transport in the proximal convolution of the rat kidney II. Effect of extracellular Ca2+ and application of the Ca2+ ionophore A 23187 in chronic PTX animals. Proximal inorganic phosphate (Pi) transport was evaluated using the standing droplet method with simultaneous microperfusion of the peritubular blood capillaries. In chronic parathyroidectomized (PTX) rats addition of 3 micron of the Ca2+ ionophore A 23187 to the luminal perfusate had  no effect on the Pi transport, although the isotonic fluid reabsorption was reduced by 20%. When the Ca2+ concentration in the perfusates was raised from 1.5mM to 3.0mM the the reabsorption did not change significantly. But when Ca2+ was omitted from the perfusates the Pi reabsorption dropped by 19%, and when 2mM EDTA were added to the perfusates Pi transport decreased by 35%. The influx of Pi from the interstitial space and from the cell into the phosphate-free luminal perfusate did not change, when the perfusates were Ca2+ -free, but it increased by 23% in the presence of 2mM EDTA. The data indicate that 1. a rise in intracellular Ca2+ above normal is not a factor which modifies "basal" Pi transport i.e. when Pi transport is independent of the action of parathyroid hormone. 2. A reduction of extracellular Ca2+ concentration from normal toward zero reduces Pi transport without changing the paracellular leak permeability for Pi. 3. With EDTA the the paracellular leak permeability for Pi is increased, thus causing an even greater reduction in net Pi transport than with Ca2+ -free solutions alone.


Studies on the occurrence of Peptococcus indolicus and Corynebacterium pyogenes in abscesses in swine, and on the occurrence of Pc. indolicus in apparently normal skin and mucous membranes of piglets. Pc. indolicus was isolated from 42.7% and Cb. pyogenes from 48.7% of 150 pus-samples from abscesses in pigs (slaughter-house material, Table I). In 41 specimens the two organisms were found together. Further, Pc. indolicus was demonstrated in 22.4% of 290 swabs from apparently normal skin and mucous membranes of piglets (autopsy material, Table II). By gel diffusion analysis the strains of Pc. indolicus were referred to the serotypes B, C, D, E, or F. The type distribution (Table III) possibly reflects a type-related variation in the invasive properties of Pc. indolicus.


[Nature of changes in glucagon secretion in diabetes mellitus]. Radioimmunological method was applied to the study of glucagon content in patients with diabetes mellitus of different severity and duration of the disease. Glucagon level on fasting stomach in patients with diabetes at the state of compensation failed to differ from that in healthy persons. But in decomensated disease with the ketoacidosis phenomena there was a sharp elevation of glucagon content with restoration to the normal after the compensation was reached. In patients with diabetes mellitus complicated by diabetic retinopathy blood glucagon content failed to correlate with the incidence of retinopathy. However, there was a direct relationship between the incidence of retinopathy and the duration of the disease. In adipose diabetic patients glucagon content was elevated, but this rise was insignificant in comparison with healthy persons.


Magnetic susceptibility studies of laccase and oxyhemocyanin. The magnetic susceptibility of Rhus vernicifera laccase has been remeasured over the temperature range 5-260 K. In contrast to our previous results [Solomon, E.I., Dooley, D. M., Wang R.-H., Gray, H.B., Cerdonio, M., Mogno, F. & Romani, G. L. (1975) J. Am. Chem. Soc. 98, 1029-1031] linear chi versus T-1 behavior was observed. The susceptibility of Limulus polyphemus oxyhemocyanin has also been measured in the range 5-260 K. Only weak paramagnetism, attributable to dissolved oxygen and a small amount of paramagnetic impurities, was observed. Analysis of the data establishes a lower limit of 550 cm-1 for J, consistent with our earlier work. The temperature dependence of the susceptibility of laccase is quantitatively accounted for by the presence of two paramagnetic copper ions (types 1 and 2) per enzyme molecule. Curie law behavior at low temperatures rules out significant interaction between the two coppper types, indicating that these redox centers are well separated (several angstroms) and are not connected by bridging ligands. Formulation of the type 3 site as binuclear Cu(II) requires J greater than or equal to 500 cm-1.


Use of T4 RNA ligase to construct model substrates for a ribosomal RNA maturation endonuclease. RNase M5 of Bacillus subtilis specifically cleaves a 179-nucleotide precursor 5S rRNA to yield mature 5S rRNA (116 nucleotides) and two fragments derived from the termini. Possible recognition elements for RNase M5 within the precursor structure include nucleotide sequences arranged with 2-fold rotational and translational symmetry about the substrate bonds. We have used bacteriophage T4 RNA ligase to construct, from synthetic oligonucleotides and mature or precursor 5S rRNA fragments, test substrates lacking these symmetry elements. The susceptibilities of the artificial substrates to RNase M5 demonstrate that the symmetrically arranged sequences are not used in the RNase M5 interaction with the precursor. Additionally, the synthetic protocols permitted the invention of an acid-soluble assay for RNase M5 and, potentially, other specific endoribonucleases.


Time of recombination in the Drosophila melanogaster oocyte: evidence from a temperature-sensitive recombination-deficient mutant. A temperature-sensitive recombination-deficient mutant, rec-126, has been isolated that permits high frequencies of recombination at the permissive temperature (25 degrees) but greatly decreases recombination at the restrictive temperature (31 degrees). The sensitive period for response of female germ cells carrying this mutant to the restrictive temperature has been defined. Sensitivity begins very close to the time the oocyte enters premeiotic interphase and initiates DNA synthesis; it continues for the duration of premeiotic-S; and it terminates with the completion of S. This time span precisely coincides with the sensitive period for enhancement of recombination by heat in the normal genome and is further characterized by the presence of the synaptonemal complex. These results provide compelling evidence for identifying premeiotic-S as the time of meiotic recombination.


Location of the genes for human heavy chain immunoglobulin to chromosome 6. Immunoglobulin synthesis was examined in 31 man-mouse hybrid clones produced by fusing RAG mouse cells with human lymphoid cells. Cells were grown in serum-free medium containing [(14)C]leucine and a (14)C-labeled amino acid mixture. Spent medium was dialyzed, concentrated, and subjected to radioimmunoelectrophoresis. Eighteen clones were found to produce material that gave a radiolabeled precipitin line with anti-human IgG (gamma-chain specific). Production of material which was indistinguishable on radioimmunoelectrophoresis from human Ig gamma heavy chain, was dependent on the presence in hybrid clones of human chromosome 6. The material was found to have the ion-exchange elution characteristics of human IgG. When radiolabeled spent medium from human lymphoid lines and from chromosome 6-positive hybrid clones was exposed to protein A-Sepharose and bound material eluted with 8 M urea was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis, three radiolabeled peaks occurred with molecular weights of approximately 55,000 (coinciding with that of Ig gamma heavy chain), 40,000 and 25,000 (coinciding with that of Ig light chains). No similar peaks were detected in experiments where spent medium from RAG cells was treated identically. These studies lead us to conclude that certain RAG-human lymphoid hybrid clones produce human IgG and that the structural genes for gamma heavy chains are located on human chromosome 6. These results also imply that the locus coding for human alpha,-antitrypsin (Pi) is located on chromosome 6.


Induced cell aggregation and mating in Streptococcus faecalis: evidence for a bacterial sex pheromone. Recipient strains of Streptococcus faecalis produce a trypsin sensitive, heat resistant, nuclease resistant factor, designated clumping-inducing agent (CIA) which causes strains carrying certain conjugative plasmids to aggregate. RNA and protein synthesis but not DNA synthesis are required for aggregation to occur. Recipient filtrates that contain CIA activity also induce donors to mate at high frequencies. Introduction of a transferable plasmid into strains producing CIA dramatically reduces the amount of CIA activity produced by the strain but allows the strain to respond to exogenously added CIA. Our data suggest that CIA represents a bacterial sex hormone (pheromone).


Contraction of detergent-treated smooth muscle. After exposure of segments of rabbit taenia coli to the nonionic detergent Triton X-100, tension could be induced by increasing the [Ca2+] in the micromolar range. In the presence of a saturating [Ca2+], this preparation developed nearly 100% of the control tetanus tension recorded from the intact muscle prior to the detergent treatment. In addition, tension could be induced by increasing the [Mg2+], in the virtual absence of Ca2+. Mg2+ seems to inhibit the Ca2+-induced tension in a predominantly competitive manner.


High speed liquid chromatography, 14C-radioassay and spectrophotometry for measuring antipyrine plasma half-life in rhesus monkeys (Macaca mulatta). 6 male rhesus monkeys (Macaca mulatta) were treated with 14CH3-N-antipyrine (15 mg/kg, i.v.). Antipyrine plasma half-lives (APH) were determined using HSLC, radiometric, and spectrophotometric methods. APHs obtained by HSLC analysis of plasma extracts were lower than radiometric and spectrophotometric determinations. The three procedures were investigated to determine if coextraction of metabolites might be responsible for differences in APH. All three solvent systems extract significant quantities of antipyrine metabolites. N-desmethylantipyrine and 3-hydroxymethylantipyrine may interfere with spectrophotometric determination of antipyrine. While all three methods are capable of detecting changes in hepatic oxidative metabolism, HSLC permits direct measurement of antipyrine concentrations and APH.


Changes in locomotor activity and naloxone-induced jumping in mice produced by WIN 35, 197-2 (ethylketazocine) and morphine. Acute i.p. administration of morphine or cocaine produced increase in locomotor activity in Swiss-Webster female mice that were maximal at 32-100 mg/kg for morphine and at 32 mg/kg for cocaine. WIN 35, 197-2 produced dose-dependent decreases in locomotor activity from 3.2-32 mg/kg. Chronic administration of WIN 35, 197-2 led to a 6-10 fold shift to the right in the locomotor activity decreasing effect of the drug, but WIN 35, 197-2-tolerant mice retained their sensitivity to the locomotor stimulant effects of morphine and cocaine. Acute administration of WIN 35, 197-2 failed to sensitize mice to naloxone-induced jumping, although morphine did so. Chronic administration of WIN 35, 197-2 did lead to sensitization to naloxone, but WIN 35, 197-2 was much less efficacious in this regard than morphine. These behavioral effects of WIN 35, 197-2 may be helpful in the classification of modes of action of different narcotic agonists.


The effect of chronic administration and withdrawal of amphetamine on cerebral dopamine receptor sensitivity. Mice with a 6-hydroxydopamine induced unilateral nigro-striatal lesion received (+)-amphetamine sulphate (2.5-20 mg/kg) over a 3-month period by daily incorporation into the drinking water. Druing this period the circling response to apomorphine hydrochloride (0.01-0.5 mg/kg, s.c.) was increasingly suppressed in comparison to control animals, while spontaneous locomotor activity increased. Following drug withdrawal the circling response to apomorphine remained suppressed two months later. However, spontaneous locomotor activity was also reduced up to 1 month following drug removal. The dopamine content of the lesioned side of the forebrain was 25% of the intact side in control animals and was not further reduced by amphetamine administration. The dopamine content of the intact forebrain was reduced by 43% during amphetamine administration and remained 18% depressed 1 month following drug withdrawal. No changes in 5-hydroxytryptamine or noradrenaline concentrations were observed in either the intact or lesioned side. This data, while showing that chronic amphetamine treatment can induce persistent changes in dopamine receptor sensitivity, can be interpreted in terms of increased striatal receptor sensitivity or as a decreased response of dopamine receptors in the nucleus accumbens.


Modification of the 5-hydroxytryptophan-induced head-twitch response by exogenous endocrine agents. Estrogens both alone and in combination with progestagens, gonadotrophins, gonadotrophin-releasing factor, corticosteroids, and corticotrophin antagonise the head-twitch response produced by 5-hydroxytryptophan in mice. In contrast, a potentiation was seen following thyroid hormones, thyrotrophin, and thyrotrophin-releasing hormone. Pre-treatment with androgens had no significant effect. Possible mechanisms for these interactions are discussed.


Methodological problems in the measurement of drug-induced rotational behaviour: continuous recording reveals time-course differences undetected by previous techniques. Rats were lesioned unilaterally in the medial forebrain bundle with either the catecholamine neurotoxin 6-hydroxydopamine or the indoleamine neurotoxin 5,6-dihydroxytryptamine. Their rotational responses in automated rotameters to a challenge with the dopamine-receptor agonist apomorphine were compared using four different techniques in current use, and by assessment of complete rotation curves using both conventional statistical procedures and elementary computer-derived elements of curvature. The rotational responses of the two groups, characterized neurochemically by identical depletions of striatal dopamine but with a greater depletion of striatal 5-hydroxytryptamine in 5,6-dihydroxytryptamine-lesioned animals, were indistinguishable using each of the four current techniques. Assessment of rotation curves by both methods revealed significant differences between the two groups, characterised by faster onset and offset of the rotational response in 5,6-dihydroxytryptamine-lesioned animals. Some current techniques may implicitly exclude the detection of such time-course differences in rotational behaviour. Assessment of complete rotation curves may best allow valid comparisons between experimental groups.


Behavioural effects of methylphenidate in 6-hydroxydopamine-treated neonatal rats. Neonatal rats treated at 7 days of age with 6-hydroxydopamine show normal levels of activity during maturation, but less hyperactivity than normals do when additionally treated with methylphenidate hydrochloride between 14 and 22 days of age. Comparison of these results with those of other workers suggests that several experimental variables must be controlled precisely if reproducible results analogous to the disturbed behaviour of children with minimal brain dysfunction (MBD) are to be obtained.


Swimming capacity of mice after prolonged treatment with psychostimulants. I. Effects of caffeine on swimming performance and cold stress. A comparative study of the effects of a single dose of caffeine (50 microgram/g s.c.) and of 6-weeks treatment with 150 microgram/g p.o. caffeine/day on swimming capacity and resistance to cold exposure was performed in mice. In contrast to acute treatment, chronic treatment with caffeine greatly reduced the swimming capacity and diminished the ability of the animals to withstand cold stress. It could be shown by indirect means that the detrimental effect of the prolonged treatment with caffeine was not due to an accumulation of toxic levels of caffeine. Motor coordination was unaffected. There was no deficiency of metabolic substrates, since glycogen, and fat stores, and blood glucose, and fatty acid levels were not lower than in control animals. It is proposed that caffeine may interfere with the animals' ability to mobilize and spend metabolic substrates for energy requirements of skeletal muscle.


Differential tolerance to pentobarbital in rats bred for differences in alcohol sensitivity. Two lines of rats bred for differences in motor impairment following alcohol treatment were also found to be differentially affected by sodium pentobarbital in three experiments. The most affected (MA) animals, bred for sensitivity to alcohol, showed a decrement in stabilimeter activity at doses of 8 mg and 16 mg pentobarbital per kg body weight. The least affected (LA) animals, bred for insensivity to alcohol, were affected only by the higher dose, at which the resulting impairment was still less than that of the MA group. This finding was partially replicated in a second study designed to test the possibility of an activating effect of pentobarbital on LA animals at 8 mg/kg. In a final study, MA animals were more likely to lose their righting reflex than LA animals at a dose of 18 mg/kg, and 'slept' longer following this dose. These results indicate that the differential sensitivity shown by these animals is not specific to alcohol, but can be generalized to another depressant.


Open-field and Lashley III maze behaviour of the offspring of amphetamine-treated rats. Albino rats of our colony were administered 0.5 mg/kg of d,l-amphetamine sulphate or saline once daily throughout gestation beginning on day 1 of pregnancy. After delivery no other treatment was received by offspring. When adults, the pups of amphetamine-treated mothers had a higher motor activity in the open-field test measured as locomotion and rearing. In the Lashley III maze the treated group made more errors than controls in the first 4 days. After day 4 there seems to be habituation because no difference was observed in either the number of errors or the running time between the groups. These results are discussed in terms of brain catecholamines metabolism.


The effect of housing and gender on morphine self-administration in rats. To determine the effect of housing conditions on morphine self-administration, rats isolated in standard laboratory cages and rats living socially in a large open box (8.8 m2) were given morphine in solution (0.5 mg/ml) as their only source of fluid for 57 days. They were then exposed to a series of 3-day cycles previously shown by Nichols et al. (1956) to increase self-administration of morphine in caged rats. On morphine/water choice days late in the period of forced consumption, between the Nichols cycles, and during a subsequent period of abstinence, the isolated rats drank significantly more morphine solution than the social rats, and the females drank significantly more morphine solution than the males. During the four choice days in the Nichols Cycle Period the isolated rats increased their consumption, but the socially housed animals decreased theirs.


Cannabis interferes with nest-building behavior in mice. Nest-building, a behavioral model shown to be disrupted by hallucinogens, has never been used to answer questions concerning the psychotomimetic effects of delta9-THC. Several fractions of cannabis and tobacco pyrolysis products were tested consecutively in the same procedure. The following drugs were injected i.p. under a saline-drug-saline schedule: d-amphetamine (6 mg/kg), pentobarbital (25 mg/kg), delta9-THC (10 mg/kg, 5 mg/kg, 2.5 mg/kg), the cannabis fractions designated Is (water soluble products), IIs (nonsoluble, nonvolatile products, IIIs (it comprises what is inhaled by a common hashish smoker), and analogous fractions of tobacco pyrolysis products designated IIIB (what is inhaled by a common tobacco smoker), IIB and IB. The effects of delta9-THC (10 mg/kg), IIs, and IIIs were quite similar as far as the disruption of the normal behavioral pattern is concerned. d-Amphetamine, delta9-THC (5 mg/kg), and IIB disrupted the normal behavioral pattern as well. The similarity of the effects of IIs and IIIs was unexpected in view of the different contents of cannabinoids in these fractions. Also unexpected was the similarity of the effects of delta9-THC (10 mg/kg) and IIIs (40 mg/kg containing 7% delta9-THC) as well as the activity of fraction IIIB.


Effects of d-amphetamine on temporal and spatial discrimination in rats. Rats were trained to lever-press for food reinforcers on a multiple schedule that had a fixed-interval (FI) and a differential reinforcement of low rate (DRL) component. Illumination of a stimulus light above the right-hand lever indicated that responses on this lever would be reinforced according to a FI 60-s schedule while responses on the left-hand lever were without programmed consequences. However, when the light above the left-hand lever was illuminated only responses on this lever were reinforced according to a DRL 15-s schedule. When the behaviour of the subjects had been brought under schedule control so that characteristic patterns of FI and DRL responding were emitted and there were relatively few responses on the incorrect levers, the effects of several doses of d-amphetamine (0.25, 0.5, 1.0, and 2.0 mg/kg) were assessed. The drug increased preference for responding on the right-hand lever. Thus, as dosage increased performance tended towards a constant high rate of responding on the right-hand lever throughout a session, with a much lower response rate on the left-hand lever. This result emphasises that the behavioural effects of drugs depend not only on patterns of ongoing behaviour but also on the context in which this behaviour occurs.


Drug-modulated behavioural responses to environmental enrichment. The home-cage activity of mice housed in either social or enriched sensory environments was continuously recorded for 23 days. During this period the mice were given daily injections of either strychnine, chlorpromazine, or saline. Both chlorpromazine and social rearing depressed home-cage activity. Strychnine also depressed activity, but only in the social group.


Tardive dyskinesia: age and sex differences in hospitalized schizophrenics. An examination of the severity of tardive dyskinesia in psychiatric inpatients using the Abnormal Involuntary Movement Scale (AIMS) indicates differing trends with age for each sex. Females show a significant linear increase with age, while males display a significant curvilinear relationship. Reliable differences between males and females are found only for the 70-79 and greater than or equal to 80 year age groups. The differences between the sexes cannot be accounted for by differences in length of current hospitalization or by current level of neuroleptic medication. Possible reasons for the results are discussed.


Pupillary abnormalities in schizophrenic patients during long-term administration of psychotropic drugs: dissociation between light and near vision reactions. Pupillographic studies were made of the reactions to light and near vision in 12 schizophrenic patients under long-term administration of psychotropic drugs. The results showed a significant reduction in the light reaction, while the near vision reaction was preserved. The pupillographic study revealed not only reduction in amplitude of the light reaction but also changes in dynamic aspects of the reaction, i.e., prolonged latency time, shortened constriction time, and half redilatation time after the light stimulus. The mechanisms underlying the dissociation between light reaction and near vision reaction induced by long-term administration of psychotropic drugs are obscure, but both the peripheral and central actions of these drugs may be involved.


Effects of morphine and chlorpromazine on the detection of shock. A discrete-trial, two-choice, 'yes-no' procedure was used to determine the extent to which the perceptual effects of compounds such as morphine and chlorpromazine (CPZ) can be attributed to drug-induced changes in ability to detect shock stimuli (sensitivity). Both morphine (4.0, 5.0, and 6.0 mg/kg) and CPZ (0.25, 0.50, and 1.0 mg/kg) significantly reduced accuracy and increased the times (i.e., lowered the speeds) to initiate trials and to make choice responses. The effects of morphine appeared to be somewhat greater than those of CPZ, particularly at the lowest shock intensity (0.05 mA). When compared to appropriate saline control days, morphine, but not CPZ, significantly reduced accuracy of discrimination on trials when shocks were presented, whereas CPZ, but not morphine, reduced accuracy on no-shock trials. The effects of morphine, but not of CPZ, on accuracy (both overall and on shock trials) decreased as shock intensity increased. The effects of shock intensity were generally inversely related to the effects of morphine and directly related to the effects of CPZ.


Changes of sensitivity to the cuing properties of narcotic drugs as evidenced by generalization and cross-generalization experiments. With a discrete-trial, food-reward, two-lever procedure, rats were trained to discriminate 0.04 mg/kg fentanyl from saline. Individual threshold doses for generalization of fentanyl and for cross-generalization of morphine were determined repeatedly during a 17-week posttraining period. Threshold doses of both drugs almost continuously shifted in both the up- and downward direction. Shifts of fentanyl threshold doses covaried with those of morphine threshold doses. These shifts can best be described by a sustained oscillation, the mean amplitude of which amounts to a factor 3.65 of the dose-range for fentanyl, and to a factor 1.85 for morphine. The upper and lower limits of oscillation were symmetrical with respect to baseline. The oscillation can be described by a function expressing that the more distant a point along the function is from the baseline, the more it is susceptible to (positive/negative) acceleration along the intensity (i.e., dose) axis.


Effects of chronic lead exposure on levels of acetylcholine and choline and on acetylcholine turnover rate in rat brain areas in vivo. Rats were exposed to lead acetate from birth, and were killed at the age of 44--51 days for analysis of levels and turnover rates of acetylcholine (ACh). Steady-state levels of ACh were not altered in midbrain, cortex, hippocampus, or striatum of lead-exposed rats. Similarly, no changes in choline (Ch) concentrations were found in cortex, hippocampus, or striatum. In the midbrain, however, a 30% reduction in Ch levels was observed. Changes in specific activity of Ch and ACh were measured as a function of time in selected brain areas of rats infused with a radio-labeled precursor of Ch. Specific activities of ACh were not altered. Ch specific activities were, however, significantly elevated in all brain areas examined, as compared with age-matched control rats. The in vivo ACh turnover rate in cortex, hippocampus, and striatum was diminished by 35%, 54%, 51%, and 33%, respectively. These findings provide direct evidence for an inhibitory effect of lead exposure from birth on central cholinergic function in vivo. Since a significant reduction of body weight was found in those animals treated with lead acetate, the alteration of central cholinergic function may partially be attributed to malnutrition observed in the lead-exposed animals.


Morphine as a discriminative cue in gerbils: drug generalization and antagonism. Gerbils were trained in an electrified, T-shaped maze to discriminate between one of the three training doses of morphine (8, 16, or 32 mg/kg) and the nondrug condition. The rate of acquisition of the morphine discriminations was a function of dose, the high dose being the most rapidly discriminable condition. Dose generalization tests with morphine showed that the higher the training dose, the higher the ED50 value in producing 50% morphine-appropriate responding. Antagonism of the discriminable effects of morphine by naltrexone (dose range tested: 0.025-0.40 mg/kg) also was related to the training dose of morphine; i.e., the higher the training dose of morphine, the higher the corresponding ED50 value for blockade by naltrexone. A stereoisomeric requirement for morphine discrimination was evident since levorphanol, but not the analgesically inactive dextrophan, yielded morphine-appropriate responses when tested by substitution.


Effects of Met-enkephalin on body temperature of normal and morphine-tolerant rats. The endogenous opioid met-enkephalin intraventricularly adminstered to the rat at the dose of 100 microgram raised rectal temperature, whereas 400 microgram of the pentapeptide caused a diphasic effect, i.e., hypothermia followed by hyperthermia. Met-enkephalin was ineffective when administered i.p. The effects on temperature were substantially similar to those elicited, for both routes of administration, by morphine, which may either raise or lower rat temperature depending on the dose. More naloxone was required to antagonize thermic effects of met-enkephalin than morphine. Finally, there was a lack of effects on temperature for met-enkephalin centrally administered to morphine-tolerant animals, thus providing further evidence, in vivo, of cross tolerance between opiates and naturally occurring ligands of opiate receptors.


Influence of catecholamines on dexamphetamine-induced changes in locomotor activity. In the mouse, central noradrenaline receptor stimulation by clonidine, or intracerebroventricular injection of noradrenaline or alpha-methylnoradrenaline, caused marked enhancement of the locomotor stimulant effects of dexamphetamine in doses that were without effect when given alone. A minimally locomotor-stimulant dose of apomorphine reduced the effect of dexamphetamine. Pimozide and phenoxybenzamine each virtually abolished locomotor stimulation after dexamphetamine, while FLA63 caused significant reduction. Phenoxybenzamine also abolished the enhancement by clonidine. The intensity of the dexamphetamine effect was dose-related, while in the case of apomorphine the duration rather than the intensity was related to the dose administered. Clonidine potentiated apomorphine locomotor stimulation; following this drug combination, the nature of the movements more closely resembled those seen after dexamphetamine. The results suggest the involvement of both noradrenaline and dopamine in the dexamphetamine response.


Amphetamine- type reinforcement by dopaminergic agonists in the rat. Intravenous self-administration of d-amphetamine (0.25 mg/kg/injection) decreased in a dose-related fashion after injections of the dopaminergic agonists apomorphine and piribedil. The dopaminergic agonists appear to suppress amphetamine intake in the same way as do 'free' amphetamine injections, by extending drug satiation in a given interresponse period. Clonidine, an alpha noradrenergic agonist, did not have similar effects. Apomorphine and piribedil did not increase 14C-amphetamine levels in rat brains, nor did they retard disappearance of 14C-amphetamine; thus their amphetamine-like effects are not due to alterations of amphetamine metabolism. Rats responding for amphetamine continued to respond for apomorphine or peribedil when the latter drugs were substituted for the former. Rats experienced in amphetamine self-administration readily initiated and maintained responding for apomorphine and piribedil. The dopaminergic blocker (+)-butaclamol disrupted responding for apomorphine and piribedil, although it produced no marked increase in responding for the dopaminergic agonists, as it does for amphetamine. These data add to the evidence that actions in the dopaminergic synapse account for amphetamine's reinforcing properties.


Marijuana: effect on nonverbal free recall as a function of field dependence. The effect of marijuana on the free recall of nonverbal memory was evaluated by presenting 22 male volunteers with line drawings of geometric figures for ten acquisition trials. Each subject served as his own drug control. The study was performed over two sessions with drug condition and list of stimulus materials counterbalanced. Recall varied with drug condition and scores obtained on the Embedded Figures Test. Marijuana reduced recall mainly in those subjects making two or more errors on the Embedded Figures Test, but had little effect on subjects making one or no errors. Intrusion errors were also elevated following marijuana intoxication, but this effect was unrelated to embedded-figures performance . These results are discussed with reference to degree of field dependence and cognitive style.


Can cigarette size and nicotine content influence smoking and puffing rates? The stimuli controlling the rate at which people smoke cigarettes have not been clearly defined. On the hypothesis that smoking is basically nicotine-seeking behavior, nicotine available to the subject was experimentally manipulated through controlling cigarette size and nicotine content. In Experiment I, subjects given their won cigarettes in whole, half, quarter, and eighth lengths, increased the number of cigarettes smoked and number of puffs to compensate for reductions in size. Satisfaction was directly related to cigarette length. In Experiment II, subjects given special cigarettes delivering 0.2 or 2.0 mg nicotine/cigarette smoked significantly more of the low than of the high nicotine cigarettes and took significantly more puffs. As in Experiment I, significantly more quarter length than full length cigarettes were smoked, but total number of puffs did not differ. These results support the hypothesis that nicotine controls smoking behavior.


The effects of d-amphetamine and scopolamine on drinking induced by a multiple schedule. Three food-deprived rats obtained food pellets on a multiple fixed-interval fixed-time schedule. During fixed-interval components a 45 mg pellet was made available for a lever-press every minute (FI 1 min). When the fixed-time component was in operation the lever was retracted and a pellet was delivered every minute (FT 1 min) independent of behaviour. A water bottle was available to each subject and similar levels of schedule-induced drinking developed during the two schedule components. The effects of several doses (0.25, 0.5, 1.0, 2.0 mg/kg) of d-amphetamine and scopolamine were assessed on lever-pressing and drinking maintained by this procedure. Both drugs increased rates of lever-pressing at lower doses and reduced levels of licking and water intake at all doses. The patterning of fixed-interval lever pressing was altered by both drugs increasing the proportion of responses emitted during early parts of the intervals. d-Amphetamine also increased the proportion of licks that occurred during early segments of the interfood intervals, while scopolamine had variable effects on patterns of licking. There were no consistent differences in the effects of the drugs on licking induced by the two schedules.


Lithium effects on rat brain glucose metabolism in long-term lithium-treated rats studied in vivo. The time course of lithium effects on several brain energy metabolites has been investigated in rats. The rats were injected once daily with lithium chloride and killed by freezing in liquid nitrogen 1--8 h after the last injection. The effect of lithium was most marked in the period in which the brain lithium concentration was increasing, whereas the effect was wearing off when the brain lithium concentration had stabilized, even though the lithium concentration was higher. These results led to the hypothesis that the effect of lithium on several parameters depends on the increase in lithium concentration following the administration of lithium, rather than on the absolute concentration of lithium.


An alternate approach to hospital cost control: the Rochester project. The rapid escalation in health care costs has demonstrated a need to control costs in general and hospital costs in particular. In New York State, efforts at control have followed one of several paths, including reduction of Medicaid program expenditures, elimination of hospital beds, and prospective reimbursement of hospital costs. Although some success has been achieved in each of these areas, hospital costs containment has not been as successful as had been hoped. A new project called MAXICAP, being developed in the Rochester region, seeks to link payment with regional hospital planning. MAXICAP represents a voluntary attempt by hospitals, third party payers, planners, consumers, and governmental agencies to devise a prospective hospital payment system. Under this system community hospital plans in the Rochester region would be integrated and a cap imposed on both revenues and expenses for acute hospital care. The principal advantage of the MAXICAP is that it offers a mechanism for linking hospital planning with payment functions on a regional basis. The principal disadvantage is that the success of the MAXICAP depends upon the  voluntary cooperation of the vast majority of the acute care hospitals in the area--hospitals that may be scattered throughout a relatively large region.


[Production of alkaline protease from acid cheese whey]. The use of acid cheese whey as an essential substrate for the production of alkaline protease was studied by growing Bacillus subtilis NRRL 3411 on different conditions of aereation. The maximum enzymatic activity of 17 000 proteolytic units was obtained in the following conditions: 200 RPM, air flow of 1 v/v minutes (KLa 37 h-1), separate sterilization of the medium components and periodical additions of peptone.


Differentiation of mycobacteria by "in vivo" and "in vitro" delayed hypersensitivity reactions. Guinea pigs were sensitized with heat killed M. tuberculosis, M. kansasii, M. scrofulaceum, and M. avium-intracellulare. Purified Protein Derivatives (PPDs) prepared from each of these organisms were tested for delayed type hypersensitivity by lymphocyte transformation, macrophage migration, and mantoux type skin sensitivity tests. The homologous reactions were consistently more intense than heterologous reactions in all three procedures. The skin test procedure was more sensitive than either in vitro method. Positive  skin test reactions were elicited with 2 times and 50 times less antigen than, respectively, the lymphocyte transformation and the macrophage migration tests.


[Immunodiffusion serologic study of equine infectious anemia in the Province of Buenos Aires, Argentina]. Twenty seven per cent of 238 serum samples obtained from horses with clinical diagnosis were positive for the immunodifusion test, while 17% of the 452 sera obtained from asintomatic horses were positive. Twenty one per cent of the 870 sera studied were positive.


New peroxides and their antimicrobial activity. Antimicrobial activity of hydroperoxides and cyclic peroxides has been studied. 2,4-Dihydroperoxy-2,4-dimethylpentane (1) and 2,5-dihydroperoxy-2,5-dimethylhexane (2) were active against microorganism, but 1 showed a large specially against C. albicans, M. luteus and B. subtilis with a MIC value of 31.5 mcg/ml.


Clinical and histological study to assess changes in the nasal mucosa in patients with chronic perennial rhinitis comparing sodium cromoglycate and placebo. A controlled trial comparing sodium cromoglycate 2% nasal solution against placebo has demonstrated that in patients with severe perennial rhinitis sodium cromoglycate is clinically effective and also that gross histological changes in the nasal mucosa are reversed following treatment for eight weeks with this therapy.


[The value of the immunodiffusion test in the diagnosis of animal histoplasmosis]. A serological study which involved the agar gel immunodiffusion test of 11316 animal serum samples (porcine, bovine, equine and ovine cattles) was made in the Havana province in an attempt to detect precipitation bands for Histoplasma capsulatum. 135 porcine serum samples and 4 bovine serum samples were positive.


Normal values for free light chains in serum different age groups. The concentration of free light chains from the immunoglobulins was measured in twelve paired sera from mothers and newborns and from 149 sera from normal individuals in various age groups. Variations in concentration during life are correlated to the variations in the concentration of 'regular' immunoglobulins. A concentration of light chains in cord blood of 35% of mean normal adult level (MNA) together with a rapid passage of light chains across the placenta is interpreted as indicating catabolization of maternal light chains in the fetus. This is further supported by the finding of a lower concentration of light chains in maternal serum than in normal adult serum. The investigation shows that the concentration of light chains falls rapidly from 35 to 24% of MNA during the first few days of life. From the first week of life the concentration of light chains increases and low normal adult values are attained by one year of age. Except for difference in concentration, the elution pattern for light chains from Sephadex G-100 columns was similar for normal, adult and cord blood. The relationship between kappa and lambda chains--the K/L ratio--is 1.2 for normal and maternal serum and 1.0 for cord serum.


Effect of storage conditions of serum lipoproteins on electrophoretic mobility in agarose gel and on lipid composition. The effect of conditions of storage of sera and lipoprotein fractions on electrophoretic mobility in argarose gel and on lipid composition has been assessed. It was found that sera or lipoprotein fractions may be stored at 4 degrees C in the presence of ethylene diamine tetra-acetate for up to 5 days before electrophoresis or up to 8 days before estimation of cholesterol and triglycerides. Addition of mercurothiolate of p-chloromercuriphenyl sulphonate offerred no further advantage.


[A case of GM-Gangliosidosis (atypical form of the AB variant)]. A case of GM-gangliosidosis, variant AB, with some atypical feautres is reported in a male child, who died at the age of 4 years and 3 months. When he was 2 and a half years old, he showed signs of progressive cerebral disease with increasing motor and mental impairment. The clinical signs suggested a form of neurolipidosis; however the data of the enzymatic activities of the peripheral blood leucocytes did not show any deficit related to these forms. More specifically the values of the exosaminides A and B were normal, although the component A was near the lowest limit of the range. The anatomical, histological, histochemical, ultrastructural and chemical studies showed that it was a form of GM-gangliosidosis with visceral involvement. In the crude lipid extracts of various organs there was not only GM-ganglioside, but also a compound not previously demonstrated in these forms of neurolipidosis. Chemically this compound may be considered a phosphoglyco-lipid-and protein complex. From the enzymatic data in the peripheral blood leucocytes, the case may be a variant AB of the Sandhoff and al. classification (1971). However some clinical signs make our case closer to the 3th type of the O'Brien and al, classification while some histopathological aspects are similar to Tay-Sachs disease (i.e. to the variant B of the Sandhoff et al. classification; i.e. to the 1th type of the O'Brien et al. classification). These data, and the presence of an 'unknown compound', not yet demonstrated in the known forms of GM-gangliosidosis, support the hypothesis that our case may be considered as an 'atypical' form of the variant AB of the gangliosidosis GM and that further studies are necessary to reach a final nosography of these entities.