[Effect of thiol compounds on experimental liver damage (III). Effect of tiopronin (2-mercaptopropionylglycine) and glutathione on drug metabolizing activity (author's transl)].

In our previous papers, tiopronin (2-mercaptopropionylglycine) and glutathione were reported to suppress the liver damage induced by ethionine. In the damage induced by ethionine. In the present study, we evaluated such suppressive effect from the aspect of drug metabolizing activity. Aniline hydroxylating enzyme activity and aminopyrine N-demethylating enzyme activity of the liver microsome of rats 24 hr after administration of 1 g/kg ethionine were decreased to 53.2% and 61.7% respectively as compared with those of the normal rats. Administration of tiopronin or glutathione to the ethionine treated rats suppressed the decrease of both enzyme activities induced by ethionine. Ethionine did not influence NADH-cytochrome c reductase (fp1) but brought about increase of the activity of NADPH-cytochrome c reductase (fp2) and decrease of the cytochrome P-450 content. These thiol compounds did not influence fp1 and fp2 but tended to suppress the cytochrome P-450 content decreased by administration of ethionine. In particular, tiopronin suppressed the content significantly. Disappearance of aminopyrine, hexobarbital and pentobarbital from the blood was markedly delayed by ethionine administration. It was revealed, however, that such delay was recovered by tiopronin or glutathione. The sleeping time induced by hexobarbital and pentobarbital was also prolonged by ethionine, but this tended to be shortened by tiopronin or glutathione.


[Effects of diispropyl 1, 3-dithiol-2-ylidene malonate (NKK-105) on the drug-metabolizing enzymes and fine structure of rat liver (author's transl)].

The mechanism of liver enlargement and anti-fatty liver effect of NKK-105 in the rat were investigated by the mesurement of drug-metabolizing enzyme activities and morphological changes in liver tissue detected using electron microscopy. A single administration of NKK-105(250, 500, 1000 mg/kg, p.o.) induced an apparent increase in liver weight. The elevation of aminopyrine demethylase activity and slight increase in microsomal cytochrome b5 and cytochrome P-450 content were seen with the administration of NKK-105. NKK-105 inhibited lipid peroxide formation in mitochondrial and microsomal fractions. Total lipid content of liver decreased at 12 hr after the administration of NKK-105. Lipid peroxide formation in mitochondrial and microsomal fractions was markedly inhibited by the addition of NKK-105 (1 X 10(-3)M), in vitro. Disarrangement of rough endoplasmic reticulum and increase in smooth endoplasmic reticulum were observed by the administration of NKK-105. The decrease in drug-metabolizing enzymes caused by CCl4 or ethionine was protected in the combination with NKK-105. NKK-105 markedly inhibited the elevation of lipid peroxide formation caused by CCl4 or ethionine. Similar effects on lipid peroxide formation were also obtained in vitro. These results suggest that the enlargement induced by NKK-105 indicates a functional not a toxic response. The inhibition of lipid peroxide formation in mitochondrial and microsomal fractions may thus play an important role in the mechanism of anti-fatty liver effect of NKK-105 on the CCl4 or ethionine-induced fatty liver.


[Pharmacological studies of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101). (4). Enzyme induction (author's transl)].

The effect of M7310U, a new non-steroidal analgesic anti-inflammatory agent, on liver microsomal drug-metabolizing enzymes was investigated. Rats were treated orally with M73101 (100, 200, 500 mg/kg), henylbutazone (PZ, 200 mg/kg), aminopyrine (AM, 100 mg/kg) or phenobarbital sodium (PB, 100 mg/kg) once daily for 2 weeks and then were observed for 2 weeks during which treatment was not given. On treatment with M73101, PZ, AM and PB, the liver enlarged but was restored to normal 1 week after the last administration. The rate of increase in the case of M73101 was lower than that seen with the reference compounds. M73101 markedly increased the content of microsomal protein, cytochrome P-450 or b5 and NADPH cytochrome C reductase, aniline hydroxylase and AM demethylase activity, but these increments returned to the normal level 1 week after the last administration. The serum concentration of M73101 after repeated administration (200 mg/kg, p.o.) for 1 week was lower than that after a single administration. Furthermore, M73101 increased Vmax for both aniline hydroxylase and AM demethylase, whereas it increased Km only for aniline hydroxylase. M73101 did not enhance the lipid peroxidation. Our observations suggest that the enlargement of rat liver seen with M73101 was due to the induction of drug-metabolizing enzymes and that this agent can probably be classified as a phenobarbital-type inducer.


Visual capacities of the owl monkey (Aotus trivirgatus): temporal contrast sensitivity.

Aotus monkeys were tested in a forced-choice discrimination task to determine their ability to discriminate sinusoidally flickering lights varying in temporal frequency and luminance contrast. Under conditions of moderate light adaptation this primate is maximally sensitive to lights flickering at 10 Hz while the highest frequency they can discriminate is about 42 Hz. At very low light levels (10(-5) ft L) maximum sensitivity is for 2.2--5 Hz flicker. The highest flicker rate that could be discriminated under these conditons was about 29 Hz. In comparison to humans tested in the same situation. Aotus monkeys show relatively lower sensitivity to temporal flicker under conditions of light adaptation but relatively higher sensitivity at very low light levels.


Pregnancy diagnosis in the common marmoset (Callithrix jacchus jacchus).

Abdominal palpation of the uterus was carried out on 25 pregnant and 29 non-pregnant marmosets (Callithrix jacchus jacchus). 195 complete 24-hour urine specimens, collected between the first week of gestation and term (21 weeks), were tested with the Sub-Human Primate Tube (SHPT) test. No significant differences between the two methods in their ability to diagnose pregnancy were obtained between the first and 13th week of gestation. The SHPT test was seldom positive after the 13th week of pregnancy, whereas, with one exception, palpation always indicated pregnancy.


[Progress in the field of parenteral feeding].

A calorie sufficient intravenous nutrition for the severely ill is possible today with practically no limitations. Carbohydrates and fats are available as energy-donators. The maximum administration rate for glucose is 0.5 g/kg/h, however, in the postoperative phase it is only 0.25 g/kg/h. The dosage limit for fructose and sorbitol is likewise 0.25 g/kg/h and only 0.125 g/kg/h for xylitol. By taking advantage of the various metabolic pathways for the individual carbohydrates, a mixed-carbohydrate solution has been developed which is utilizable in a dosage of 0.5 g/kg/h. The fat emulsions which are commercially available today consist of soy bean oil with egg lecithin or phosphatides as emulsifiers. They are well tolerated and offer several advantages in contrast to high-percentage carbohydrate solutions. In newer developments, MCT fats are added as quickly utilizable substrates. Only L-amino acids should be used today in parenteral nutrition because of their specific utilization by the organism. In addition to the administration rate (0.1 g/kg/h), the relationship between essential and non-essential amino acids is decisive for utilization, whereby the so-called E/T ratio should be as high as possible. Improved substrate utilization can be achieved through the simultaneous administration of carbohydrates, protein and fat as well as minerals and vitamins, whereby the total daily requirement can be administered within 12 hours without metabolic dysfunction.


[Origin and biological role of lipid mediators during inflammation (author's transl)].

In chemical terms the mediators of inflammation can be divided in amines (histamine, serotonine), peptides (ECF-A, bradykinin), proteins (lysosomal enzymes), and lipids. They mainly act at three levels: 1.) They induce vascular reactions and are responsible for the classical symptoms of inflammation, 2.) they define and modulate the cellular response towards the inflammatory stimulus such as the morphology of the tissue infiltrate, 3.) they act on haemostasis by interaction with platelets. While in the past investigations on classical mediators have dominated research, recently the biological role of lipid mediators has been appreciated. They can be detected only in minute quantities; they often have a short half-life and are not preformed within the cells. The most common precursor of the lipid mediators is arachidonic acid. This unsaturated fatty acid is generated from phospholipids after phospholipase activation of cells and is transformed by the enzyme cycloxygenase to a series of compounds such as the prostaglandins. They induce the classical signs of inflammation such asvescular dilatation, increase in permeability, pain, hyperalgesia etc. By the same process, the thromboxanes and prostacycline are generated which mainly act on the coagulation system. Various products are obtained from arachidonic acid via lipoxygenase activation. To these belong a factor chemically not completely defined with classical SRS-A activity; there is strong evidence that PAF and ECF are formed on the same line. Experiments in recent years have supported the idea that neutrophils and mononuclear cells are by far the main producers of lipid mediators, thus indicating the cellular interdependence during the inflammatory process.


[Sarcosporidiosis (sarcocystis suihominis) in man (author's transl)].

Eleven medical students and six members of the Institute of Medical Parasitology, University of Bonn participated in a meal with raw pork of an experimentally Sarcocystis suihominis infected pig. During the first two days the test persons suffered from the same symptoms as a previous group (see Piekarski et al., 1978). The severity of the symptoms was related ito certain degree to the quantity of the pork comsumed, but the individual reaction varied considerably; one test person with a higher amount of meat remained healthy. Apparently, only excessively high quantities of infected meat lead to severe symptoms. Lower dosages cause a protracted course of the disease. In general, the Sarcosporidia infection produces a transitory disease which quickly disapprears without remaining after-effects.


[Hemolysis in ger test -- an alternative to hamagglutination inhibition test for search of antibodies against rubella virus (author's transl)].

640 sera of unknown immune status were tested in the rubella hemagglutination inhibition test (HI) as well as in hemolysis in gel test (HIG). The results have been analysed by statistical methods. The reproducibility of zones of hemolysis are 1.7 mm for the long term precision and 1.0 mm for the short term precision. Comparing the HIG and the HI tests we had a correlation of 97% = sensitivity (544 out of 561 sera) in positive reacting sera and of 87% = specifity (69 out of 79 sera) in the negative reactions. We consider a person to have antibodies against rubella if the zone of hemolysis had a diameter of 8 mm or above. In cases of diameters under 8 mm the results of IH and HIG-tests do not correlate. The reasons are not completely known and should be investigated.


Light chain heterogeneity of type lambda anti-streptococcal group A-variant polysaccharide antibodies in rabbits.

BASILEA rabbits lack the expression of chi-polypeptide chains and compensate for this lack with expression of lambda polypeptide light chains. These rabbits were immunized with streptococcal group A-variant vaccines. The heterogeneity of the lambda polypeptide chains of specific antibodies was analyzed and compared with that of chi light chains. No significant difference was found by SDS-PAGE and IEF in the number of light chain bands of high affinity antibody expressed. This suggests that in the rabbit the size of the variable region repertoire is similar for lambda and chi light chains.


Saralasin-induced renin release: its blockade by prostaglandin synthesis inhibitors in the conscious rat.

The angiotensin antagonist, saralasin, (10 and 30 mg/kg), increased serum renin activity (SRA) in normal, conscious rats from 2.7 +/- 0.4 to 16.2 +/- 3.7 and 22.5 +/- 2.4 ng/ml/hr (p less than 0.001), respectively, without markedly altering blood pressure or heart rate. Indomethacin, in a dose which inhibited the urinary excretion of prostaglandin E2 (PGE2) by 75%, and arachidonate-induced hypotension by 83%, failed to alter basal SRA but inhibited saralasin-induced renin release by 99% and 87% at the 10 and 30 mg/kg doses, respectively. Indomethacin failed to alter basal hemodynamics or the hemodynamic response to saralasin. Propranolol (1.5 mg/kg) inhibited saralasin-induced renin release by 93% and enhanced the suppressant effect of indomethacin from 79% to 100%. Meclofenamate, another prostaglandin synthesis inhibitor, also blocked saralasin-induced renin release by 99% and 72% at the 10 and 30 mg/kg doses, respectively (p less than 0.001). In sodium-depleted rats, saralasin (0.3 mg/kg) increased SRA from 12 +/- 2 to 119 +/- 6 ng/ml/hr (p less than 0.001) and decreased blood pressure by 6% (p less than 0.01). In these animals, indomethacin failed to alter basal SRA, but inhibited saralasin-induced renin release by 82%, urinary excretion of PGE2 by 79%, and arachidonate-induced hypotension by 81%. These findings suggest 1) that saralasin-induced renin release is mediated by renal prostaglandins, and 2) an interrelationship exists between the receptor controlling AII-mediated inhibition of renin release, which is blocked by saralasin, and the juxtaglomerular beta-adrenergic receptor.


[Clinical experiences with a variable balanced diet in a neurological intensive care station].

The variable balanced diet (Berodiät V) consisting of only a few requirement-adapted components can be used for longterm tube feeding in many patients of a neurological intensive care unit. This extraordinarily high energy supply necessary in this group of patients can be accomplished without difficulties, which makes it possible to dispense with longterm parenteral feeding. Preparation and administration are unproblematic. Cases of intolerance were observed only, if the rate of administration was too high.


[The problem of dosage and importance of fats in parenteral feeding].

Using human volunteers the metabolic effects of continuous infusions of fat emulsions (Intralipid and Lipofundin S) without and with addition of carbohydrates and amino acids were investigated. A steady state for triglyceride concentration was attained even at an infusion rate of 0.25 gm/kg BW for Lipofundin S. This fat emulsion was utilized during parenteral administration of 0.1 gm/kg BW almost without an increase in triglyceride concentration. In the case of parenteral administration of Intralipid, however, we did not find indications for the existence of a steady state for serum triglyceride concentration. Without the addition of carbohydrates the parenteral application of fat emulsions causes hyperlipacidemia and ketosis even in metabolically healthy volunteers. These metabolic effects are suppressed by the simultaneous administration of fructose or glucose. The concentration of inorganic phosphate is elevated merely during the highly dosed infusions of Lipofundin S and not by Intralipid. Liver functions were not altered even by highly dosed intravenous fat. According to the results of these investigations in human volunteers Intralipid is eliminated considerably slower than Lipofundin S. There should be qualitative differences also. Lipofundin S is obviously to a greater extent metabolized by the physiological intravasal fat metabolizing system. The small elimination capacity for Intralipid, however, demands caution in the uncontrolled application of this fat emulsion to severely ill patients. Even the better metabolized Lipofundin S should be infused principally with the addition of carbohydrates. By taking these precautions the undesirable metabolic effects of intravenous fat (i.e. lipacidemia and ketosis) are prevented.


[Loss of the serum iron diurnal rhythm during postoperative infusion therapy].

Iron-free parenteral nutrition following neurosurgery and vascular surgery leads to a loss of the known diurnal rhythm of the serum iron level. This fact is discussed in view to the post-operative pathophysiology and in view of the speculations on the reasons for this diurnal rhythm.


Rehabilitating children with temporomandibular joint ankylosis.

Although the probability of ankylosis following injury of the temporomandibular joint is small, patients, especially children with temporomandibular joint ankylosis, are greatly handicapped. Of the 42 cases of ankylosis seen in our clinic, six occurred in the adult, and 36 in children under 14 years of age. Treatment in all cases was surgical, and the results were beneficial, although the greatest difficulty in the treatment had been the early recurrence of ankylosis. Based on our experience, osteoarthrotomy for temporomandibular joint ankylosis in children has been advocated.


Surgical treatment of chronic hyperplastic sinusitis and maxillary sinus empyema of oral/dental origin.

Twelve patients with maxillary hyperplastic sinusitis or maxillary sinus empyema of oral/dental etiology have been treated according to a modified surgical technique. The treatment was initiated by several oro-nasal irrigations and drainage facilitated by an intact semilunar hiatus. This was followed by a surgical procedure including conservative curettage of inflamed sinus mucosa, adequate closure of the oro/antral communication, with establishment of a postoperative oral antrostomy. This antrostomy, through the canine fossa, was established by a vacuum drain, enabling continuous postoperative irrigation and aspiration. The rationale for this technique is discussed. A total of 12 patients operated according to this technique are described. Complete clinical and radiographic healing in all patients was observed over a postoperative period ranging from 6-12 months.


Anterior mandibular dentoalveolar advancement utilizing lyophilized bone.

Patients with low angle Class II malocclusions complicated by strong nasal and chin profiles, interarch width discrepancies, and an exaggerated mandibular curve of Spee present several diagnostic and treatment problems. Various treatment possibilities are discussed and anterior mandibular dentoalveolar advancement is suggested as a treatment for these patients. Lyophilized, homologous bone is recommended for placement into the defects created by segmental advancement to avoid root resorption and ankylosis caused by autologous bone grafts. Finally, a modified incision is presented that facilitates watertight closure of the surgical wound.


Effect of the addition of a vasoconstrictor to local anesthetic solution on operative and postoperative bleeding, analgesia and wound healing.

A clinical study of local anesthetic solutions with and without epinephrine was conducted involving 32 healthy adults requiring removal of bony impacted mandibular third molars. The time elapsing from the administration of the anesthetic solution until analgesia was obtained was significantly shorter in the vasoconstrictor group (P less than 0.001). Additional anesthetic was necessary in 44% of the patients in the control group. The blood loss in the vasoconstrictor group was significantly lower (P less than 0.001) than in the group receiving anesthetic solution without the vasoconstrictor. No statistically significant difference in operation time between the groups was found, although the profuse bleeding in the control group impeded to some extent the surgical procedure. A positive correlation coefficient between operation time and blood loss of r = 0.65 in the vasoconstrictor group (P less than 0.006) and r = 0.77 in the control group (P less than 0.001) was found. Hemorrhage occurring 24 h postoperatively was recorded in 37% of the subjects in the vasoconstrictor group, and of these 83% revealed a healing of the socket by second intention.


Usefulness of vascular examinations in diagnosis and treatment of the face-skull neoplasms.

Arteriography of external carotid artery and sporadically orbitophlebography were performed in 52 patients of both sexes, aged 10-74 years. Indications for arteriography and orbitography stemmed from cases in which routine clinical-radiological examinations failed to determine the extent of neoplastic changes. The technique of transdermic puncture of the common carotid artery of the supraorbital vein was applied in the studies. Uropolin 75% was used as control material. The studies confirmed usefulness of arteriography both in the diagnosis and surgical treatment of neoplasms of the jaws as well as the face facilitating the determination of topography of the tumor and the direction of growth.


Benign cementoblastoma.

A review of 44 patients with benign cementoblastomas is presented. An additional case is reported. This patient appears to be of particular interest due to radiographic records 18 months prior to admission. In this period the tumor appeared to grow very slowly.


Deep neck infections.

From January 1967 to August 1978, 65 patients with cervical abscesses were referred to the ENT Clinic of Turku University Hospital. The origin of these deep neck infections was odontogenic in 19, tonsillitis or tonsillectomy in 14, trauma in seven, salivary glands in five and branchiogenic cysts in five and other known causes in three cases. In 12 cases the origin was unknown. The cervical abscesses of odontogenic origin were located mostly in the submandibular space (11/19). The rest of the deep cervical infections were mostly found in the parapharyngeal space (25/46). Etiological factors and treatment of these severe infections are discussed.


Recurrence of the odontogenic keratocyst in relation to clinical and histological features. A 20-year follow-up study of 72 patients.

Seventy-two patients with 75 primary odontogenic keratocysts have been followed from 6 months to 20 years after the primary treatment. Patients with the nevoid basal cell carcinoma syndrome were not included in the material. Fifty-four patients with 57 primary cysts have been followed for 5 years or more, and 18 patients all having a single primary cyst for less. If the number of primary cysts later recurring was related to the number of primary cysts observed for more than 5 years, a recurrence rate of 51% was found. A diagnosis of recurrence was made in 37 cases within a period of 5 years postoperatively and in 10 cases from 5 to 12 years after the operation. Only two of these patients have been followed with regular intervals for the first 5 years postoperatively. The diagnosis of recurrence was in these two cases made 6 and 8 years after the primary treatment. A postoperative follow-up period of 10 years after the last operation is therefore advocated. The occurrence of microcysts and/or islands of odontogneic epithelium in the cyst membrane of 26 nonrecurring cysts, 25 recurring primary cysts and the last recurrence in 14 patients were compared. There were no statistical differences in occurrence of remnants of odontogenic epithelium in the cyst wall between the three groups.


Tranexamic acid in alveolar sockets in the prevention of alveolitis sicca dolorosa.

The effect of trans-4-amino-methyl-cyclohexane acid (AMCA) and a placebo preparation on the development of alveolitis sicca dolorosa (ASD) was investigated in a double-blind designed experiment. The preoperative registrations were age, sex, use of oral contraceptives, menstrual cycle, smoking, degree of impaction and operation time. The study included 120 healthy persons. Each person had bilateral impacted mandibular molars removed surgically at one session. AMCA (160 mg/extraction site) or placebor was applied in each socket after the operation. The postoperative course was evaluated on average 5 days later by the use of 13 different variables describing local and general discomfort. The incidence of ASD was 7.5% in the AMCA side and 5.0% in the placebo side. The result shows that a local inhibition of plasminogen activation by AMCA is insufficient to prevent the development of ASD. The occurrence of ASD and postoperative discomfort was not increased in women operated during the menstrual period. The usage of oral contraceptives is known to be associated with a high frequency of ASD. Women taking oral contraceptives may therefore postpone the operation to the withdrawal period of the pill, to reduce the risk of developing ASD. Postoperative pains and the consumption of analgetics were significantly increased in patients who were habitual smokers.


Influence of oral hygiene measures on the development of alveolitis sicca dolorosa after surgical removal of mandibular third molars.

This study was carried out in order to investigate the prophylactic effect of plaque control on the development of alveolitis sicca dolorosa (ASD). Sixty patients took part in the investigation. The patients in the test group had their teeth polished 5 days preoperatively and then used a 0.2% aqueous solution of chlorhexidine digluconate as a mouth rinse twice a day before the operation and during the postoperative week. No special oral hygiene measures were taken in the control group. Compared with the control group, the patients in the test group had significantly less plaque on their teeth on the day of operation (P less than or equal to 0.001). One patient in the test group developed ASD, while there were five cases of ASD in the control group. The results indicated that plaque control may be a possible way to decrease the incidence of ASD.


A model for evaluating the analgesic effect of a new fixed ratio combination analgesic in patients undergoing oral surgery.

A special model designed for evaluating the analgesic effect of oral analgesics was based on a short-time registration period of immediate postoperative pain. One-hour intervals in pain registration and a minimum of 2 h between the tablet intake allowed a good estimation of changes in pain levels. The patient material consisted of 112 patients and from each patient a lower impacted wisdom tooth was removed. The test model was used to compare two analgesic drugs with placebo. The two pharmacologically active preparations were Doleron (dextropropoxyphene, acetylsalicylic acid, phenazone, caffeine and Transergan) and Astra 2167 (dextropropoxyphene and acetylsalicylic acid). The trial was double blind and the tablets were administered according to a crossover design. There was no statistically significant difference in analgesic effect between Astra 2167 and Doleron, and both drugs were superior to placebo. Finally, the trial showed that a reduction of the number of components of a compound analgesic to some degree reduced the pain relieving effect on this particular postoperative pain. This observed reduction was however, not statistically significant.


Viral hepatitis in oral surgery and periodontics in Norway.

The incidence of viral hepatitis in general dental practitioners, oral surgeons and periodontists was analyzed by questionnaires. Viral hepatitis was found to be an occupational risk for oral surgeons with no significant professional risk for general practitioners or periodontists. The differences were due mainly to type of patients. The importance of preoperative risk evaluation and proper precautions is stressed.


Effect of irradiation-timing on the initial socket healing in rats.

The effect of a single dose of 1500 R on early postextraction socket healing was studied in jaws of rats. A severe delay in healing was found in animals irradiated 2 weeks prior to extraction. Retardation of healing to a lesser degree was demonstrated in sockets irradiated immediately after exodontia.


Photoelastic experiments on the implantation of a bone graft into the mandible with stable compression osteosynthesis.

The implantation of a bone graft into the mandible was simulated in photoelastic model tests. Problems posed by the lingual and alveolar areas untouched by the plate are discussed. The tests showed that in both problem areas enough interfragmentary pressure can be built up using a five-hold DC (dynamic compression) plate with a short implant and two four-hole DC plates with a long implant, whenever the metal plates have dynamic compression holes (DC), are prebent and the screws are in converging position. This is a prerequisite for a rapid revascularization of the implanted bone graft and primary bone healing. These tests and our clinical experience showed that with small implants using a five-hold plate and with long implants using two four-hole plates, and physiologically stressing the bone implant, the principles of stable compression osteosynthesis without intermaxillary immobilization have proved themselves.


Radiographic findings in 224Ra-caused dental resorptions.

Dental resorptions as a delayed effect of Thorium X (224Ra) were observed in four patients. The radiographic findings showed distinct and representative patterns. Apparently, the observed changes are typical for delayed alterations related to 224Ra-specific disturbances in the alveolar process. Degenerative and inflammatory reactions may also be involved in the pathogenesis.


Closed vertical subcondylar osteotomy (CVSO) of the mandible. A most versatile procedure.

The closed vertical subcondylar osteotomy (CVSO) of the mandible is accomplished with a wire saw. Through a systematic approach to anatomical landmark recognition and application of a very definite series of surgical maneuvers, the surgeon can achieve optimum results with little sequelae. Because the proximal segment resulting from this osteotomy is considerably larger than that produced in the closed subcondylar osteotomy, this procedure allows for a greater degree of movement (anterior, posterior and even rotational) of the distal segment. This added versatility permits the use of the CVSO in the treatment of aperthognathia, micrognathia, posterior open bite, and various combinations of these deformaties, as well as prognathia.


The Copenhagen spraymatic. A sterile spraymatic for oral surgery.

An apparatus is described which supplies sterile, air-free physiologic saline as coolant at the tip of the handpiece. The device is activated by the foot control of the dental engine and the bur is flooded with saline the very moment the rotations begin. In the same way is stops instantaneously without afterdrip and without suckback. The components are either disposable or autoclavable. Metallic components are stainless steel.


[Ten years experience with combination therapy for tonsillar malignancies (author's transl)].

From 1968 to 1978, 125 patients with cancer of the tonsil have been treated by the Departments of Radiology and Otolaryngology at the University Hospital, Homburg-Saar. Although all patients were unirradiated, many had previously undergone a surgical procedure. Most of the cancers when seen were in advanced stages. The three-year and five-year survival rates were 38.6 and 23.5% respectively. Reticulum cell sarcomas, Schmincke's tumors and non-keratinized squamous cell carcinomas had better prognoses than keratinized squamous cell carcinomas. Our findings indicate that the volume of large tumors should be reduced by surgical means before irradiation since irradiation alone resulted in a higher relapse rate in the advanced cancers. Various methods for radiotherapy either before or after surgery for different tumor stages are discussed. The combination of chemotherapy with radiation to make use of the so-called "partial synchronisation effect" in cases of inoperable extensive primary tumors or relapses is described.


Dissociation of adult mammalian heart into single cell suspension: an ultrastructural study.

Adult rat heart was dissociated into a single cell suspension by a perfusion technique which used 0.05% collagenase and 0.1% hyaluronidase in Krebs-Ringer phosphate buffer (KRP). The non-muscle cells of the suspension were separated from the myocytes by centrifugation through 3% Ficoll solution in KRP with 0.01 mM Ca2+. An approximately 90% pure suspension of isolated single muscle cells was obtained with this method. The effects of the successive steps in the dissociation procedure on the ultrastructure of the heart were studied by scanning and transmission electron microscopy. After 30 minutes of enzyme digestion, dissociation of the inner endothelial lining of the ventricle into single cells or small groups of cells became apparent. In addition, the underlying cardiac skeleton began to disintegrate and linear arrays of cardiac muscle cells were observed. After 45 minutes of enzyme digestion the number of released single cells was higher because of the separation of intercalated discs. The majority of non-muscle cells were by now dissociated from the surfaces of muscle cells. Widening of the lateral intercellular spaces between the myocardial cells was associated with separation of desmosomes. In some regions of the heart, intact desmosomes, fasciae adherentes and gap junctions were observed even though lateral intercellular spaces had widened greatly. The majority of myocardial cells had become separated from one another after 60 minutes of enzyme digestion. Separation of gap junctional sites took place in two ways: (1) by 'unzipping' them through enzyme action; (2) by tearing them mechanically. Gap junction remnants were sometimes observed in a vesiculated state within the cell. The dissociation of the heart was ineffective when perfused with media containing 1.0 or 2 mM Ca2+. Alcian blue treatment after 60 minutes of enzyme digestion revealed that the basement membrane, and its accompanying collagen fibrils, was still present on the plasma membrane of dissociated single cells. The isolated myocardial cells retained their normal morphological characteristics. This study has enabled us to understand in detail how dismantlement of highly ordered adult cardiac tissue into a single cell suspension takes place. Cell suspensions of this type should be invaluable in the study of metabolic and synthetic activities in adult myocardial cells.


In vitro microbiological evaluation of TEI-1194 and TEI-2012, novel antipseudomonal semisynthetic penicillins.

TEI-1194, sodium 6-[D-(-)-alpha-(coumarin-3-carboxamide)-phenylacetamide] penicillanate and TEI-2012, sodium 6[D-(-)alpha-(8-hydroxy-coumarin-3-carboxamide)-phenylacetamide] penicillanate are new semisynthetic penicillin derivatives both possessing a broad spectrum of in vitro antibacterial activities. Minimal inhibitory concentrations of both agents were compared with carbenicillin. TEI-1194 and TEI-2012 were clearly found to have more potent activities especially against Pseudomonas aeruginosa than carbenicillin. At a concentration at 6.25 micrograms/ml, 85 approximately 90% of a total of 50 strains of clinically isolated P. aeruginosa were inhibited by TEI-1194 and TEI-2012, whereas carbenicillin had no effect. Evaluation of the antibacterial activity against a series of mutants producing different levels of beta-lactamases and test of the susceptibilities to some beta-lactamases demonstrated that TEI-1194 and TEI-2012 had low susceptibility to various cephalosporinases. However, both compounds were susceptible to penicillinase from Klebsiella pneumoniae H-2 at a rate of about 15% of penicillin-G taking its absolute rate as 100.


New knowledge of the connective tissue diseases I.

This paper examines the extent to which understanding of six of the principle disorders of connective tissue: the glycosaminoglycan storage diseases, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, chondrocalcinosis, and osteoarthrosis, has progressed during the past ten years. The paper recalls the pioneer observations of PAUL KLEMPERER on the systemic diseases of collagen, and introduces a series of reviews in which advances in present understanding of some of the connective tissue diseases will be examined in greater detail.


Program evaluation research: an experimental cost-effectiveness analysis of an armed robbery intervention program.

An armed robbery alarm system was implemented in 48 different stores in two separate geographical areas for 6 months and 12 months, respectively. The alarms were placed in the two separate areas at different times and all alarms were eventually removed. Thus, multiple baseline and reversal strategies were used to evaluate program impact. A device planted in a cash drawer was triggered whenever "bait" money was removed from the drawer sending an alarm signal directly to police cars and headquarters. On-scene apprehensions of armed robbers within target stores were greatly increased even though the armed robbery systems did not deter robbery incidents nor influence the court disposition of the cases. There was also no crime deterrence, crime displacement, or increased apprehensions in either the immediate neighborhoods of target stores or on a city-wide basis. The cost effectiveness of the program was calculated to be poor even though the program is being maintained because of the absence of an alternative robbery apprehension technology.


Selecting a cost-effective screening measure for the assessment of preschool social withdrawal.

The utility of teacher judgment (rankings, ratings) and peer judgment (sociometric ratings) were studied as screening variables for preschool social withdrawal/responsiveness. Observational measures of preschoolers' interaction were used as the validation criterion based upon theoretical, empirical, and practical considerations related to development of a multipurpose behavioral assessment system. Results indicated that teacher rankings of students' verbal interaction frequencies (1) were most highly correlated to interaction rate in two preschool settings, (2) had test-retest reliability consistently above Rho = .80, and (3) were useful in that 77% of teachers using this procedure could identify their least socially responsive student within five rankings. The peer nomination sociometric rating was the least reliable measure at retest (Rho = .35) and showed consistently the lowest correlation with observational indices of interaction partner preferences, e.g., reciprocal rate (Rho = .29 to .39). The tendency for relationships among screening measures and the criterion to increase at retest suggested a training effect on screening accuracy. The use of teacher rankings in combination with observational measures to confirm selection accuracy and for monitoring treatment progress is discussed as a cost-effective behavioral assessment procedure for preschool social withdrawal/responsiveness.


A calcium requirement for movement of cultured cells.

When calcium is removed from culture medium, motility of cultured cells is decreased. The effect is rapid, reversible and pronounced. Decreased motility is observed with normal mouse Balb/c 3T3 cells, mouse L929 cells, rat kidney fibroblasts and chick embryo fibroblasts. The calcium dependence of movement can be observed both with individual cells and with the movement of the margin of a monolayer into a wound. Magnesium will not substitute for calcium to maintain motility. Strontium will substitute, but is not as effective as calcium for maintaining cell movement. Low concentrations of the divalent cation ionophore A23187 (0.5-1 micron) partially reverse the reduced migration observed at low calcium concentrations. These results are consistent with the hypothesis that movement of non-muscle cells occurs through mechanisms similar to those important in the contraction of muscle.


Effects of depletion of K+, Na+, or Ca2+ on DNA synthesis and cell cation content in chick embryo fibroblasts.

Decreasing the K+ concentration of the medium from 5 mM to 0.59 mM decreased the K+ content of chick embryo fibroblasts to 22% of control values and increased the Na+ content to 820% of control values. The alteration of monovalent cation content occurred within two hours but had no effect on the rate of DNA synthesis, as measured by 3H-thymidine incorporation, for at least 16 hours. By decreasing the Na+ concentration in the medium, a 50% reduction in cellular Na+ could be obtained with no effect on thymidine incorporation. Since these changes in cellular Na+ or K+ are much larger than any known to occur under physiological conditions but have no effect on thymidine incorporation, we conclude that Na+ and K+ do not play a critical role in determining multiplication rate. Addition of 1.8 mEGTA to cells in media containing 1.7 mM Ca2+ and 0.8 mM Mg2+ inhibited thymidine incorporation and sharply decreased cellular K+ and increased cellular Na+ content. However, there was no reduction in total cellular Ca2+ levels. Likewise, decreasing the Ca2+ concentration of the medium below 0.01 mM inhibited thymidine incorporation, decreased cellular K+ and Mg2+, and increased cellular Na+ but did not affect total cellular Ca2+ levels. Inhibition of DNA synthesis, therefore, could not be correlated with changes in cellular Ca2+ levels.


The growth response of cells in medium made hyperosmolal with electrolytes or mannitol.

A comparison of the growth rates of established human lymphoid and tumor cell lines was performed in nutrient medium made hyperosmolal with mannitol, NaCl, or mixtures of NaCl and KCl at a constant Na/K ratio. It was found that considerably higher osmolalities were attained with mannitol than electrolytes before a reduction in the growth rate of the culture was observed. This suggests that mannitol and electrolytes affected the growth rate through different mechanisms. Mannitol uptake was studied with two of the cell lines and both cell lines were found to be permeable to mannitol. This eventually would have eliminated the osmolality gradient between the interior of the cell and the medium, and could explain why higher osmolalities were obtained with mannitol before the growth rate was effected. In addition, initial experiments showed that these cell lines may also be able to metabolize mannitol.


Determination of 6-mercaptopurine and azathioprine in plasma by high-performance liquid chromatography.

Using 1-ml plasma samples, levels of 6-mercaptopurine (6MP) as low as 5 ng/ml and azathioprine (AZA) as low as 40 ng/ml can be detected using a high-performance liquid chromatography reversed-phase column procedure following extraction. Both compounds were stable in frozen plasma for seven weeks. AZA stability in blood was temperature dependent; the half-lives of AZA breakdown to 6MP at 37 degrees were 28 and 46 min in blood drawn from two rhesus monkeys. Plasma levels of 6MP were measured in a rhesus monkey following 6MP (1.47 mg/kg) and AZA (3 mg/kg) intravenous administration. 6MP levels were also measured in three renal transplant patients on daily 50- and 100-mg AZA doses. Peak levels (45-75 ng/ml) were reached within an hour and 6MP levels were detected for up to 7 h.


Qualitative and quantitative analyses of polychlorinated biphenyls by gas-liquid chromatography.

A model is presented of the relationship between the relative responses of flame-ionization and electron-capture detectors and the structure of polychlorinated biphenyls (PCBs). The model permits the calculation of detector responses for all PCBs and opens the possibility of detailed structural analyses.


Separation of oligonucleotides on ion-exchange derivatives of Spheron.

Diphenylamine-formic acid hydrolyzate of Bacillus subtilis DNA (a mixture of pyrimidine oligodeoxyribonucleotides) was chromatographed using an ionic strength gradient on seven ion exchangers: five DEAE-Spherons 300 of various capacities, two types of BD-Spheron 300 and DEAE-Sephadex A-25. The suitability of ion-exchange derivatives of Spheron for the chromatography of oligonucleotides is discussed. The separation of mono- to undeca-deoxyribonucleotides was achieved.


Multiple of isolates of Pseudomonas aeruginosa with differing antimicrobial susceptibility patterns from patients with cystic fibrosis.

Clinical isolates of Pseudomonas aeruginosa from patients with cystic fibrosis were studied in an effort to determine the unique characteristics of the infecting strains and to elucidate the pattern of colonization. Of 413 patients studied, 81% were chronically infected with P. aeruginosa. Patients from whom P. aeruginosa was never or only occasionally isolated were in better clinical condition than the chronically infected patients. Isolates were classified into six morphologic varieties: classic, rough, mucoid, gelatinous, dwarf, and enterobacter. Most patients had two or more of these varieties. Such multiple varieties from the same individual were of the same serotype but often differed in antibiotic susceptibility as determined by both the disk and the minimal inhibitory concentration methods. These differences were apparent when mucoid strains were compared with nonmucoid strains and when nonmucoid strains were compared with one another. Studies of antibiotic susceptibility should be performed on each morphologically different type of P. aeruginosa obtained from patients with cystic fibrosis.


Comparison of antibiotic regimens for treatment of experimental pneumonia due to Pseudomonas.

The high mortality associated with pneumonia due to Pseudomonas aeruginosa prompted a comparative trial of several currently available antibiotic regimens for this infection in a guinea pig model. Normal guinea pigs receiving an intratracheal challenge of 10(8) colony-forming units of Pseudomonas routinely died within 3-48 hr when treated with saline injections. Treatment with carbenicillin or ticarcillin did not affect this uniformly fatal outcome. Groups of animals treated with gentamicin or tobramycin had survival rates of 39% and 67%, respectively. The addition of either carbenicillin or ticarcillin to an aminoglycoside failed to enhance further the survival rates or durations of survival after infection. These survival data were supported by studies showing superior clearance of viable Pseudomonas from lung tissues in aminoglycoside-treated animals chosen at random for sacrifice 3 hr after infection. Thus, in animals experimentally challenged with P. aeruginosa to cause pneumonia and in which only a single isolate of Pseudomonas was evaluated, protection from pulmonary infection was best provided by an aminoglycoside rather than by a beta-lactam antibiotic.


The role of antibody and complement in phagocytosis by rabbit alveolar macrophages.

The relative importance of antibody and complement in the phagocytosis of Staphylococcus aureus and Pseudomonas aeruginosa, two common bacterial pathogens, by alveolar macrophages from rabbits was studied. Normal rabbit serum was a satisfactory opsonin for the phagocytosis of S. aureus but not for P. aeruginosa. Normal rabbit serum opsonized S. aureus by both the classic and the alternative complement pathways; loss of both pathways destroyed opsonic activity. The presence of complement was not required for maximal phagocytosis when 10% staphylococcal immune serum was used. However, an intact alternative complement pathway enhanced phagocytosis when the concentration of staphlyococcal immune serum was lowered to 0.3%. Similarly, 10% pseudomonas immune serum opsonized P. aeruginosa without complement. When the concentration of pseudomonas immune serum was lowered to 1%, either the classic or the alternative complement pathway could significantly enhance phagocytosis of P. aeruginosa. Similar results were obtained with alveolar macrophages activated with bacille Calmette-Guérin. These studies demonstrate the importance of complement in enhancing phagocytosis by alveolar macrophages of bacterial pathogens when antibody concentration is the limiting factor.


Experimental syphilis in the rabbit: passive transfer of immunity with immunoglobulin G from immune serum.

A preparation of immunoglobulin G isolated from a pool of immune sera derived from rabbits with long-term syphilis was shown to possess a high degree of purity as judged by immunodiffusion and protein electrophoresis. The antitreponemal power of the preparation of immunoglobulin G and that of the immune serum pool from which it was derived were found to be equivalent in both the skin protection and the systemic protection test. The observation that neither normal serum nor a pool of serum derived from animals "immunized" with Salmonella typhi, Escherichia coli, Streptococcus pyogenes, or zymosan was protective indicates that the protective power of the immune serum studied was due to specific antibodies residing principally, if not entirely, in the immunoglobulin G fraction of the serum.


[Inhibin, a second testicular hormone (author's transl)].

Germinal epithelium secretes a peptide hormone, inhibin, that regulates FSH secretion. This substance originates inside the seminiferous tubules, from the Sertoli cells, and is transported towards the head of the epididymis where it is reabsorbed, and thus passes into the bloodstream. Inhibin blocks FSH pituitary secretion; its effect on the hypothalamus is debatable. Inhibin also exists in the female, in ovarian follicles and may have a role in follicular growth regulation.


Absorption test using latex particles as the indicator system for the species identification of bloodstains and muscles.

This paper reported the species identification of bloodstains and muscles by means of an absorption test in which antisera were absorbed by bloodstains or muscles and then the absorbed antibody capacity was titrated by using latex particles coated with corresponding serum proteins. This test method was proved to be simple, specific, and sensitive.


Variations in surface protein composition associated with virulence properties in opacity types of Neisseria gonorrhoeae.

The biological properties of a series of opacity variants of Neisseria gonorrhoeae P9 have been examined. A novel protein, designated protein IId* (mol. wt 28 850), was identified within the set of heat-modifiable surface proteins previously reported. All variants producing extra outer membrane proteins were less sensitive to the bactericidal action of serum than the prototype transparent strain, with protein IIa* (mol. wt 28 500) being associated with increased resistance. The production of a different protein, protein II* (mol. wt 29 000), was correlated with resistance to low molecular weight antimicrobial agents (penicillin, fusidic acid, Cu2+, Zn2+). Increased adhesion to human buccal epithelial cells was demonstrated in all variants that produced extra surface proteins. These variants did not show increased binding to hexyl- and phenyl-substituted Sepharose gels suggesting that hydrophobic interaction was not responsible for their cohesive properties. The prototype strain lacking additional proteins demonstrated the greatest binding to erythrocytes, indicating that adhesion to buccal cells and red blood cells is mediated by different mechanisms. One variant producing protein IIa* showed increased association with leukocytes, whereas another producing protein IIb* showed decreased association with leukocytes. These results show that the heat-modifiable surface proteins are important virulence attributes of the gonococcus: this must be considered in the selection of strains for vaccine trials.


Relationship of group P1 plasmids revealed by heteroduplex experiments: RP1, RP4, R68 and RK2 are identical.

The molecular relationships of the IncP1 plasmids RP1, RP4, R68 and RK2 were tested by electron microscopic examination of heteroduplexes. In several hybridization experiments molecules were detected which had a 7.8% portion of incomplete reannealing. This 'heterologous region' could be explained by the typical renaturation behaviour of the transposon Tn1. The identity of the Tn1 transposon present in RP1 and RP4 was proved by heteroduplex experiments with lambda phage DNA containing this transposon. These results indicated that the plasmids RP1 and RP4 are identical. Additional heteroduplex experiments between plasmids R68.45 and RP8 and between R68.45 and RK2 were performed. R68.45, a derivative of R68, has a small DNA insertion and RP8 can be regarded as a large insertion mutant of RP4; both insertions were used as single-stranded hybridization markers. From the hybrid molecules formed, it was deduced that R68 and RK2 are identical with RP1 and RP4 as far as molecular structure is revealed by the technique used.


Identification of different sites of expression for spo loci by transformation of Bacillus subtilis.

Asporogenous mutants of Bacillus subtilis were rendered capable of forming heat-resistant spores by transformation with wild-type (spo+) DNA at, or near, the start of sporulation. For several mutants up to about 50% of the colonies derived from heat-resistant spores, formed as a result of the transformation, remained genetically asporogenous (spo). This was thought to indicate that the genome of the mother cell, but not that of the forespore, was transformed to spo+ and that correct expression of the spo locus in the mother cell was sufficient for spore formation. At the end of the process the mother cell was destroyed, leaving a mature heat-resistant spore that was genetically asporogenous. It is concluded that the loci spoIIID, spIVA, spoVB and spoVE are expressed in the mother cell. For one mutant more than 99% of the colonies derived from heat-resistant spores were genetically spo+. It is concluded that the locus involved, spoVA, had to be expressed in the forespore. Thus different sporulation-specific loci are expressed in the mother cell and in the forespore. The loci expressed in the mother cell are expressed in one cell type so that another cell type, the forespore, can develop into a heat-resistant spore. Other unselected donor markers could be introduced into the recipient during transformation provided high concentrations of DNA were used. The frequency of congression was the same for spo survivors as for spo+ survivors. This implies that there was no correlation between the DNA strand into which the selected spo+ and the unselected donor markers integrated.


The growth and form of bacterial colonies.

A simple method is described for measuring the profile of bacterial colonies. Profiles were determined for colonies of Bacillus cereus, Escherichia coli and Staphylococcus albus of different ages. In spite of differences in cell morphology, the colony profiles had a common basic structure consisting of steeply rising leading edge connected by a ridge to an interior region where height also rose, though less steeply, to a flat or domed centre. The colony mass increased exponentially through part of the growth phase. It is suggested that net colony growth consists of a combination of leading edge growth, which is unrestricted and approaches the maximum specific growth rate of the organism, and diffusion-limited growth in the colony interior. Common elements of profiles from each species may be a consequence of such differences in growth rate.


Tetracycline-mediated photodynamic inactivation of animal viruses.

Demethylchlortetracycline (DMCT), doxycycline and, to a lesser extent, chlortetracycline were capable of mediating the in vitro photoinactivation of Venezuelan equine encephalitis (VEE) virus. Other tetracyclines tested were found to be inactive in this respect. However, no correlation between chemical structure and photosensitizing activity could be established. The photoinactivation of VEE virus by DMCT proceeds through a photodynamic mechanism as shown by the absolute requirement of O2 for the inactivation to take place. The photoinactivating effect of DMCT was also exerted upon other animal viruses tested, i.e. vesicular stomatitis virus, herpes simplex virus and poliovirus, even when, in the case of poliovirus, the capsid seems to be impermeable to the tetracycline. The fact that the two most effective photosensitizing tetracyclines for VEE virus are also the drugs more frequently associated with drug-induced phototoxicity in humans, suggests that virus photoinactivation could be used as a screening procedure for potentially phototoxic drugs developed for human application.


Heterogeneity of virus particles in measles virus.

A heterogeneous population of virions is generated by measles virus-infected cells. These particles are partially separable by sucrose density centrifugation into three peaks. Each population is stable and contains infectious particles. The particles of all three populations contain at least six polypeptide species that differ between particle populations only in quantity. All three populations contain a 50S RNA species, and the heaviest density peak also contains an additional species of 43S RNA. The difference between these results and previous studies with measles virions will be discussed.


Electron microscopy of the morphogenesis of Bacillus subtilis bacteriophage SP3.

The capsid of Bacillus subtilis bacteriophage SP3 is assembled via a prohead intermediate which subsequently encapsulates DNA and attaches a tail. The prohead contains a ring-like core structure. The spokes which extend from the core to the inner prohead surface are thought to form a scaffold for the polymerization of the prohead. Ninety percent of the proheads are assembled prior to the onset of DNA encapsulation. The first mature phage particles are observed at 45 min after infection; titres of intracellular phage demonstrate their infectivity. The core is visible in phage ghosts.


Characterization of a new avian influenza virus subtype and proposed designation of this haemagglutinin as Hav10.

The haemagglutinin of A/Dk/alb/60/76, an influenza A virus isolated from feral ducks in Canada, possesses no antigenic relatedness to any of the 16 reference haemagglutinin subtypes. Results of serological tests (HI and double immunodiffusion) with monospecific antisera to the haemagglutinin of this virus indicate that it represents a new avian haemagglutinin subtype. We propose that this haemagglutinin be designated as Hav10 under the current system of nomenclature.


The separation and analysis of hepatitis B e antigen.

A solid-phase radioimmunoassay has been used successfully for detecting hepatitis B e antigen in fractionated hepatitis B virus-containing serum. Ammonium sulphate precipitation followed by gel filtration through a column of Sepharose CL-6B resulted in two fractions of antigen-containing material with molecular weights of 220,000 and 130,000. The smaller of these two fractions was found to possess an average isoelectric point of 4.9 and consisted of two major polypeptide species with estimated molecular weights of 66,000 and 17,000 respectively. Affinity chromatography on Blue Sepharose showed that e antigen was not retained under conditions which bound serum albumin. These results are discussed in relation to the immunopathogenesis of hepatitis B.


Ultrastructure of supraspinal dorsal root projections in the toad. II. The cerebellar granular layer.

Following section of the left dorsal roots, degenerating fibres and boutons were observed in the granular layer of the ipsilateral cerebellum. The degenerating terminals were identified as large en passant varicosities of mossy fibres contacting the dendrites of presumptive granule cells. They contained round synaptic vesicles and neurofilaments and established Gray type I contacts. The terminals initially underwent filamentous degeneration with neurofilamentous hypertrophy, swollen mitochondria and loss of synaptic vesicles. At later survival times (6--30 days) they acquired an electron-dense appearance due to an increase and clumping of the filamentous component. After injection of horseradish peroxidase into the left cerebellum, all ipsilateral spinal ganglia showed a few (2--3%) labelled cells, indicating that a primary afferent contribution to this pathway originated from each segment of the spinal cord.


The mode of migration of neurons to the hippocampus: a Golgi and electron microscopic analysis in foetal rhesus monkey.

The mode of neuron migration from the site of their origin in the ventricular zone to area CA1 of the hippocampus was analysed with Golgi and electron microscopic methods during the first half of gestation in the foetal rhesus monkey. In the inner portion of the intermediate zone, the migrating cells have a bipolar form with one, or oaccasionally two, leading processes which do not reach the ammonic plate and with a single trailing process which usually ends within the intermediate zone. Both the nucleus and the cytoplasm of the migrating cells are relatively electron-dense and the latter contains organelles typical of young neurons as described in other brain regions. Analysis of electron micrographs from serial sections reveals that the length of the somata and of the leading and trailing processes of the migrating neurons is apposed to fascicles of radially oriented, electron-lucent, microtubule-filled fibres which are ultrastructurally similar to the radial glial fibres of the neocortex and to the Bergmann glial fibres of the cerebellum. The close (20 nm) apposition between the membranes of the migrating cell and the radial fibre is maintained even in areas where the fibres bend or curve tortuously. Migrating neurons situated at progressively more superficial levels of the intermediate zone become progressively more differentiated and complex. Thus, in the outer portion of the intermediate zone, the migrating cells acquire several additional cytoplasmic processes and occasionally a long thin axon-like process which courses into the incipient alveus. These cells have somewhat larger somata and less electron-dense nuclei and cytoplasm than the migrating neurons still situated in the inner part of the intermediate zone. Cells close to the ammonic plate usually have one to three cytoplasmic processes that enter the ammonic plate and terminate near their presumed final position. Migrating neurons situated at the lower border of the ammonic plate have a single large apical process which intermingles with neurons already in their final position and which sometimes traverses the ammonic plate. The apposition of the migrating neurons to the radial glial processes becomes less explicit as the cell soma enters the ammonic plate, reflecting the more complex three-dimensional intercellular relationships. However, the present analysis indicates that during the middle and late stages of neuronal migration to the hippocampus radial glial fibres may guide postmitotic young neurons across the intermediate zone to the ammonic plate in the same way that they guide neurons migrating to the superficial and middle layers of the neocortical plate.


A radiometric microbiologic assay for the biologically active forms at niacin.

A radiometric microbiologic assay has been developed for the determination of niacin in biologic fluids. Lactobacillus plantarum produced 14CO2 from L-[U-14C] hr malic acid in quantities proportional to the amount of niacin present. The assay is specific for the biologically active forms of niacin in humans. Thirty normal hemolysates were analyzed and the values ranged from 13.0 to 17.8 micrograms niacin/ml RBC (mean = 15.27 +/- 1.33 s.d.). Good recovery and reproducibility studies were obtained with this assay. On thirty blood samples, correlation was excellent between the radiometric and the conventional turbidimetric assays.


Gallium-68 labeling of albumin and albumin microspheres.

Because of the high stability constant of gallium transferrin, the formation of a protein that will be stable in vivo and labeled with gallium-68 (a positron emitter) requires preliminary coupling of a strong chelating group to the protein. In the present study, we have used a reaction developed by Krejcarek and Tucker, in which DTPA is coupled to proteins by the formation of an amide bond. Using human serum albumin (HSA) as a model, we have studied the efficiency of the reaction of HSA with the mixed acid anhydride of the quarternary triethyl ammonium salt of DTPA and butyl formate, as a function of the ratio of albumin to DTPA. After purification of the DTPA-labeled HSA, it is possible to prepare Ga-68-labeled albumin in high yield by chelation of the Ga-68 with the DTPA-labeled protein. In vitro and in vivo stability studies showed that the labeled protein was stable over a period of several hours. The same type of bifunctional chelate has been used to attach Ga-68 to HSA microspheres.


Radiolabeled liposomes as metabolic and scanning tracers in mice. II. In-111 oxine compared with Tc-99m DTPA, entrapped in multilamellar lipid vesicles.

We describe the organ distribution of positively and negatively charged multilamellar lipid vesicles (MLV) labeled with Tc-99m DTPA or In-111 oxine in mice. The organ distribution of MLV (In-111 oxine) is fairly constant throughout 72 hr, indicating that the radiotracer remains associated with cellular structures at the site of MLV uptake. In animals injected with MLV (Tc-99m DTPA), on the other hand, there is continuous leakage of radioactivity from the involved organs. This can be explained by the release of the radiotracer following MLV destruction in the organs. MLV (IN-111 oxine) may be used to study MLV uptake by different organs, whereas MLV (Tc-99m DTPA) may be a good indicator of the destruction rate of lipid vesicles. Various conditions bearing on liposome kinetics merit further study in order to assess the potentialities of these vectors as diagnostic or therapeutic agents.


Indium-111-labeled human polymorphonuclear leukocytes: viability, random migration, chemotaxis, bacterial capacity, and ultrastructure.

Human polymorphonuclear leukocytes (PMNs) were labeled with indium-111 oxine in ethanol, and the effects of the labeling procedure, radioactivity, and concentrations of oxine and ethanol on PMN function and structure were studied in vitro. The standard labeling procedure did not alter the viability, random migration, chemotaxis, bactericidal capacity, or the ultrastructure of PMNs. Exposure to higher doses of radioactivity, or to higher concentrations of ethanol, had no appreciable effects on random migration and chemotaxis of PMNs. A dose-dependent reduction in their random migration and chemotaxis was observed when higher concentrations of oxine were used. These results indicate that In-111-labeled PMNs are structurally intact and have normal in vitro locomotion and bactericidal activity. Indium-111-labeled PMNs should be suitable for studying the kinetics and distribution of these cells in health and disease.


Technetium-99m-labeled methylene diphosphonate and hydroxyethylidine diphosphonate--biologic and clinical comparison: concise communication.

The biologic and imaging characteristics of Tc-99m MDP and Tc-99m HEDP were compared in ten patients: Tc-99m MDP exhibited lower blood activity, lower 4-hr urinary excretion, and higher normal bone-to-background ratio. Assessment of overall image quality also favored Tc-99m MDP, indicating that the normal skeleton is better visualized with this agent. The total number of lesions seen (18) was not large enough to allow critical comparison of relative lesion-detecting efficacy. However, discrepancies between the two agents were observed, suggesting additional evaluation of the relative lesion-detecting efficacy of these two bone agents.


A new electrophoretic method for determining ligand: technetium stoichiometry in carrier free 99mTc-radiopharmaceuticals.

An electrophoretic procedure is outlined for the determination of the number of ligands bound to technetium-99m radiopharmaceuticals. The approach involves use of ligands that will complex technetium in a similar fashion but that differ in charge. This approach was applied experimentally to dimercapto ligands in which the ligating sulfur atoms are separated by a flexible three-carbon chain (1,3-dimercapto compounds). Two such ligands studied are 1,3-dimercaptopropane (DMP) and dihydrothioctic acid (DHTA). The Tc compound of DHTA migrates much farther on electrophoresis than the Tc complex of DMP. However, when TcO4- is reduced by SnCl2 or NaBH4 in the presence of equimolar quantities of DHTA and DMP, a new compound is formed being twice as abundant as either the TcDMP or the TcDHTA compound and migrating an intermediate distance. The formation of this new complex and the 1:2:1 distribution indicates that two 1,3-dimercapto compounds are attached to the Tc-center in all three compounds.


Vitamin B2 activity of 7,8-dimethyl-10-(2,3,4-trihydroxy-4-formylbutyl)isoalloxazine in Lactobacillus casei.

The microbial activities of vitamin B2-aldehyde and vitamin B2-acid, produced by Schizophyllum commune, a Basidiomycete, were studied. Lactobacillus casei ATCC No. 7469 was used as a test microorganism. B2-aldehyde exhibited a good response curve in the growth of L. casei. B2-acid had neither a stimulatory nor an inhibitory effect on the growth. When B2-aldehyde was incubated with the homogenate of L. casei, it was converted to riboflavin. The flavin formed from B2-aldehyde by the homogenate not only exhibited an equivalent response curve to authentic riboflavin in the growth of L. casei, but also showed the same Rf value as authentic riboflavin in any paper chromatogram, as far as tested. Hence, the microbial activity of B2-aldehyde for L. casei seems to be ascribable to riboflavin which is a reduction product of B2-aldehyde.


Effect of low protein diets on free amino acids in plasma of young men: effect of wheat gluten diet.

Studies were made on alterations in plasma amino acids in young men fed a diet containing graded levels of wheat gluten. After one week on a standard diet containing 200 mgN/kg of mixed protein (animal protein content 45%), 38 young men were given a wheat gluten diet containing 170, 100, 60, 30, 15 or zero mgN/kg for 2 weeks. Blood samples measuring plasma free amino acids were taken before breakfast at the end of the periods on a standard diet and an experimental diet. In subjects on diets containing 170 to 30 mgN/kg the plasma concentrations of threonine, valine, methionine, leucine, tyrosine, phenylalanine, serine, histidine and arginine fell significantly with decrease in protein intake, but the concentration of alanine increased significantly. On the other hand, in subjects on diets containing 15 or zero mgN/kg, the plasma concentrations of the essential amino acids did not decrease, but increased to slightly more than in subjects on a diet containing 30 mgN/kg, and the alanine and glycine concentrations increased steadily. Values for plasma lysine varied from 146 +/- 22 to 194 +/- 31 mumoles/liter with gluten intakes of 170 to zero mgN/kg, but were comparable with that of 186 +/- 33 mumules/liter in subjects on a standard diet, showing that the plasma lysine concentration did not clearly reflect the dietary concentration of lysine in young men on a wheat gluten diet.


Effect of an amino acid imbalance on intestinal sucrase and leucine aminopeptidase activities in rats.

In order to investigate the relationship between dietary amino acids and protein, as well as the activities of intestinal sucrase and leucine aminopeptidase in rats, the effects of an amino acid imbalance on these enzyme activities were studied. The amino acid imbalance was created by adding 8% of an indispensable amino acid mixture lacking threonine to a 6% casein diet supplemented with 0.3% methionine. The food intake and growth of rats fed the imbalanced diet ad libitum were depressed, and the segmental weights of the small intestine and its sucrase activity were clearly lower than those of rats fed the basal diet. The effect of the imbalanced diet under pair-feeding condition on the sucrase activity was similar to that under an ad libitum feeding condition. The food intake and segmental sucrase activity, that is, sucrase activity per length of the small intestine, of rats injected with cortisol (1 mg/day) and fed the imbalanced diet were not depressed, although administration of insulin (1.5 U/day) had no effect on the food intake or segmental sucrase activity. Force-feeding stimulated growth of rats receiving the imbalanced diet, as well as increasing their segmental sucrase activities. The effects of these different conditions on the leucine aminopeptidase activity of rats receiving the imbalanced diet were obscure. These results suggest that changes in segmental sucrase activity might be mediated by stimulating factors in food intake affected by the composition of ingested amino acids and protein together with sucrose in the gastrointestinal lumen.


Tumorous conditions of the fibula, supraorbital area and mandible.

Our patient's initial biopsy of the right fibula was diagnosed as Ewing's sarcoma and surgical amputation was suggested as the treatment of choice. After he refused, he was treated with chemotherapy and radiotherapy. The patient refused to continue this type of therapy after a 6 weeks' regimen. The supraorbital swelling occurred 3 years later and the biopsy of it also revealed Ewing's sarcoma, as did the mandibular specimen. The patient, again, refused any further treatment.


Fine structure of cell types in an ameloblastoma.

An unusually large and old ameloblastoma, which revealed a diverse histological appearance, was studied by light and electron microscopy. In the tumor, the epithelial component formed several patterns in the collagenous stroma. The epithelial islands, consisting of tall columnar cells surrounding the inner core of stellate cells, mimicked the cells of the inner enamel epithelium and stellate reticulum, respectively, of the normal enamel organ. The ultrastructural appearances of the columnar cells, however, were only similar to those which are seen in undifferentiated preameloblasts. Areas of squamous metaplasia were present, and these squamous cells were structurally similar to the cells at the base of the oral epithelium. Some epithelial cells containing numerous lipid granules and mitochondria formed a network of cords. The connective tissue stroma was made up of fibroblast-like cells which appear to be metabolically active. In addition, multinucleated giant cells were present in the connective tissue stroma near the epithelial component.


Effects of isoproterenol on chemical carcinogenesis with DMBA in mouse salivary glands.

Histopathological studies were conducted on experimental carcinogenesis in mouse salivary glands using D L-isoproterenol hydochloride (isoproterenol) and 9 10-dimethyl-1 2-benzanthracene (DMBA). DMBA was administered once at 1 mg/0.02 ml in olive oil to the salivary glands, and isoproterenol was injected intraperitoneally at 1 mg/0.05 ml saline solution three times a week for 2 weeks at different periods during the oncogenic process. Salivary glands treated with carcinogen showed a relatively constant sequence of changes and developed epithelial and mesenchymal tumors irrespective of isoproterenol administration. Isoproterenol did not influence the development of another type of tumor; however, it did retard the oncogenic processes.


Acatalasia in two Peruvian siblings.

The oral findings in two Peruvian brothers, 10- and 11-years-old, with acatalasia are presented. Gingival necrosis and severe alveolar bone destruction were the main oral manifestations. Otherwise the patients were in good health. Thirteen hypocatalasemic individuals, including both parents, were found among 29 relatives of the probands examined from four generations. No other acatalasemic individuals were found. Hypocatalectic relatives of the probands did not have oral lesions, and no other abnormalities were detected. The parents of the affected children were not known to be related; however, both parents and their families come from the same small rural community. The inheritance pattern in the kindred was compatible with an autosomal recessive disorder. It is postulated that the gingival lesions resulted from damage to tissue from hydrogen peroxide generated by organisms in gingival plaque. The hydrogen peroxide cannot be degraded by gingival tissue or by leukocytes genetically lacking the enzyme catalase.


Pathways of inflammatory cellular exudate through radicular cyst epithelium: a light and scanning electron microscope study.

A feature of radicular cyst histology is the observation that polymorphonuclear leucocytes infiltrate the epithelium whereas chronic inflammatory cells do not and accumulate in the subepithelial connective tissue. Material for the study of this phenomenon consisted of radicular cysts fixed in formol saline. Observation under the SEM indicated that the lumenal surface of the radicular cyst is characterized by numerous interepithelial spaces through which polymorphonuclear cells reach the cyst cavity. The cells on the lumenal surface are associated with interepithelial spaces. Observations of the cut surface indicate that channels occur between epithelial cells through which the polymorphonuclear leucocytes migrate. The channels may also be a pathway for exudates from capillaries to reach the cyst cavity and provide a means for radicular cyst enlargement. Erosions of epithelial cells and features of necrosis of superficial cells were observed. Thus it appears that polymorphonuclear leucocytes migrate through definite channels between epithelial cells in the radicular cyst lining, the chemotactic stimulus being degeneration and breakdown of the superficial epithelial cells.


Bge snail cell-line antigens: ineffectiveness as antischistosomal vaccine in mice.

Mice and rabbits were immunized with antigens derived from Bge cells, Biomphalaria glabrata hemolymph, or Schistosoma mansoni. Antisera from mice given molluscan antigens did not form immunoprecipitates with soluble antigen from adult worms, but their binding to surfaces of sporocysts, cercariae, and schistosomules suggests the presence of cross-reacting determinants. In vitro, cell-mediated immune responses to Bge antigens were not demonstrable in infected nor in immunized mice. Mice immunized with Bge cell-line antigens and challenged with S. mansoni cercariae showed no reduction in worm burden when compared with control mice.


Infectivity of Plasmodium simium to Aotus trivirgatus monkeys and different anophelines.

Infections of Plasmodium simium were induced in splenectomized and intact Aotus trivirgatus griseimembra monkeys by parasitized blood and by sporozoites from Anopheles freeborni mosquitoes. Eleven of 13 monkeys developed infection after sporozoite inoculation; prepatent periods ranged from 11 to 25 days (mean 15.8 days). Comparative infectivity studies indicated that An, freeborni mosquitoes were the most susceptible followed by An. stephensi, An. Balabacensis balabacensis, An. maculatus, An. quadrimaculatus, An. culicifacies, and An. albimanus. Studies with 3 pupal phenotypes of An. freeborni indicated that lines containing the green and nonstriped pupal phenotypes were more susceptible than the base colony; the striped phenotype was slightly less susceptible.


Sarcocystis transmitted by blood transfusion.

Merozoites were found in blood smears from calves, lambs, and pigs exhibiting signs of acute sarcocystosis after oral infection with sporocysts of Sarcocystis bovicanis, Sarcocystis ovicanis, and Sarcocystis suihominis. In each of 3 experiments, whole blood containing merozoites was transfused from an infected host to 2 uninfected recipients of the same species; 2 additional animals of the same species served as uninfected nontransfused controls. The bovine, ovine, and porcine donors all died of acute sarcocystosis. Clinical signs of sarcocystosis were not seen in any transfusion recipients or controls. All recipients and controls were killed and histologic specimens of esophagus, diaphragm, heart, skeletal muscle, and tongue were examined microscopically. Large numbers of intramuscular cysts were present in transfusion recipients, whereas few or no cysts were present in controls, indicating that S. bovicanis, S. ovicanis, and S. suihominis had been transmitted between intermediate hosts of the same species by blood transfusion.


Tetrapetalonema (T.) panamensis (McCoy, 1936) comb. n. (Filarioidea: Onchocercidae) in Colombian primates, with a description of the adults.

Microfilaria panamensis McCoy, 1936 was identified in the blood of Cebus apella, C. capucinus, C. albifrous, and Saguinus oedipus from various regions in Colombia. Adult worms, recovered from the subcutaneous connective tissues of C. apella and S. oedipus, were identified with this microfilaria and are described as Tetrapetalonema (T.) panamensis (McCoy, 1936) comb. n. This nematode is smaller configuration of the female tail and in the appearance of the spicules, and T. barbascalensis which differs in the placement of the vulva relative to the base of the esophagus and in the structure of the right spicule. The spicular ratio of T. panamensis (1.6 to 2.1) is lower than that of any other member of the subgenus (2.6 to 10.8). The host induced and/or geographic variation of microfilariae and adults of T. panamensis is discussed.


Conduction velocity of the ulnar nerve, length of the forearm and body weight as correlates of gestational age in the infant pigtail macaque.

The conduction velocity of peripheral nerves is an indication of their growth. Ulnar nerve conduction velocity, forearm length, postpartum age and weight were measured in 25 monkeys (Macaca nemestrina) to determine the best way to estimate gestational age. Correlation analysis showed that while conduction velocity is strongly correlated with gestational age (r = 0.68), both forearm length (r = 0.91) and weight (r = 0.94) are more strongly correlated. Of the three simple measurements made, weight provides the best estimate of gestational age.


Supernumerary epiphyses in the macaque (Macaca nemestrina).

The frequency, age distribution and development of supernumerary epiphyses in the hand and foot were radiographically documented in 98 macaque fetuses and infants. Extra epiphyses were observed only on distal metacarpal 1 and metatarsal 1, and were present in 15% of a cross-sectional sample and 20% of a longitudinal sample. They appeared coincidentally with the ossification of other secondary epiphyses of the hand and foot. Development of extra epiphyses in this species seems to be a normal phenomenon.


Estrogen and luteinizing hormone secretion in diverse primate species from simplified urinary analysis.

A practical approach for monitoring urinary estrogen and luteinizing hormone (LH) in various primate species is described. Total immunoreactive estrogen (Et) levels, measured without chromatography, provided a convenient estimation of estrone, estradiol and estriol as the sum of their separated parts. Bioactive LH in urine was measured by the rat interstitial cell testosterone (RICT) in vitro bioassay. Correction for urinary creatinine content allowed for the comparison of hormone production from small volumes of urine collected from single daily voidings. Using these methods, urinary Et and LH profiles through the reproductive cycles of a human, gorilla, chimpanzee and capuchin monkey have been determined.


Selection and pairing of 'normal' rhesus monkeys (Macaca mulatta) for research: procedures, techniques, and observations.

A selection process has been developed by the authors to insure investigators that animal subjects used in their experiments will accurately reflect biological changes associated with the project design. The procedure involved the following: complete physical examination; complete hemogram, serum electrolytes, serum biochemistry, body weight; and anthropometric determinations; aging by dentition; electrocardiography; total-body radiography; fecal culture; fecal ova, and parasite examinations; and examination of other conditions. Arithmetic means and standard deviations were calculated and used to eliminate monkeys whose values varied from the mean by more than two standard deviations.


Weights and heights of stump-tailed macaques (Macaca arctoides) living in colony groups.

Weights and heights of adults, week-old infants, and animals of intermediate ages were obtained from colony groups of stump-tailed macaques and are compared with similar measurements of rhesus, Japanese macaques, and other stump-tailed monkeys.


A prolonged hematopoietic disturbance associated with aortic aneurism and splenomegaly in a squirrel monkey (Saimiri sciureus). A case report.

In a squirrel monkey (Saimiri sciureus), monitored clinically for five years, histopathological review revealed diffuse lymphoblastic lymphocytes infiltrating the thyroid, kidney, liver, pancreas, adrenal medulla, internal fat, extramedullary hematopoietic foci in the spleen and liver, and a mild chronic peritonitis.


Infective substructures of measles virus from acutely and persistently infected cells.

Ribonucleoprotein from cells acutely or persistently infected with measles virus were shown to be infectious by the calcium phosphate technique. Very little or no infectivity was obtained when calcium phosphate precipitation was omitted. Electron microscopy showed that the majority of ribonucleoprotein structures isolated from acutely infected cells were folded, whereas those from persistently infected cells were linear in appearance.


Common protective antigen between Pseudomanas aeruginosa and Vibrio cholerae.

Immunization with a common antigen (OEP) of Pseudomonas aeruginosa produced a high level of protection in mice against Vibrio cholerae infection. The average OEP-HA titer in mice sera of immune group was 1,600 HA titer. However, vibriocidal titer and agglutinin titer against V. cholerae were not observed in sera of mice immunized with OEP. By passive administration of anti-OEP rabbit serum, mice were also protected against challenge with V. cholerae. In order to confirm the presence of the common antigen of P. aeruginosa in V. cholerae, IF-30 (common antigen of V. cholerae) was provided. Antibodies were found by the OEP-passive hemagglutination test to cross-react with the common antigen (OEP) of P. aeruginosa in sera of rabbits immunized with IF-30. The titer of OEP antibody formation in rabbits immunized with IF-30 was almost the same as that of P. aeruginosa. When mice were immunized with IF-30 and challenged with each of 7 kinds of Fisher's immunotype of P. aeruginosa, protection was observed in all the mice vaccinated against the challenge with each of the 7 kinds of strains. Furthermore, it was also confirmed that there was significant protection in mice injected with anti-IF-30 rabbit serum against all strains of Fisher's immunotype of P. aeruginosa.


Experimental Rickettsia tsutsugamushi infections in dogs.

Dogs were infected intravenously and intradermally with the Gilliam and Karp strains of R. tsutsugamushi. Although the development of clinical signs was related to the dose of the organism, Gilliam-infected dogs developed severer infections than those infected with Karp. Specific antibodies were demonstrated in sera of experimentally infected dogs.


Persistence and reactivation of Rickettsia tsutsugamushi infections in laboratory mice.

The persistence of R. tsutsugamushi in tissues of experimentally infected mice for 565 days was demonstrated. Reactivation of apparently dormant infections was accomplished by inoculating the mice with a heterologous strain of the organism or treatment with cyclophosphamide.


A kinetic measurement of red cell deformability: a modified micropipette aspiration technique.

A kinetic measurement of the red cell deformability is developed, modifying the micropipette aspiration technique of BRAASCH (1971). The sedimented human red cells on a slide-glass are individually aspirated into a micropipette by negative pressure (delta P), and the decreasing "velocity (v)" of the applied electric current, due to the aspirating cell, is taken as a measure of the "easiness" of the cell to enter into the small orifice of the micropipette (inner diameter, 2 R congruent to 3 micrometer). An empirical relation, v infinity (pi r2) . (delta P) . ("deformability"), is obtained. In order to test the validity of the method, some factors influencing the deformability are studied: i.e., the "velocity" decreases as lowering temperature; the "velocity" of the glutaraldehyde-pretreated cells and of both in vivo and in vitro aged cells decreases. Therefore, the parameter, "velocity (v)," reflects the deformability well. In addition, if a few assumptions could be allowed, v would be related to the Young's modulus of the membrane.


Elevation of visual pattern discrimination limen in monkeys with total removal of inferotemporal cortex.

Attempts were made to test the validity of the general view that inferotemporal lesions in monkeys do not result in a visual acuity disorder. It was found in the first experiment that monkeys with total removal of the inferotemporal visual area (TIT monkeys) showed a significant elevation of the discrimination limen for visual patterns of reduced sizes even when compared to monkeys with removal of lateral striate cortex (LS monkeys); yet in a food-morsel (raisin) detection test the TIT monkeys performed as well as normal monkeys, although the LS monkeys showed significant deficits. A second experiment was conducted, in which the same subjects were tested with the same patterns as in the first experiment but with the stimulus background changed from the square used earlier to an enlarged disc. While both normal and LS monkeys performed this task easily, the TIT monkeys could not learn the discrimination within the training limit of 1,200 trials. The results suggest that such a marked elevation of the discrimination limen in the TIT monkeys as found in the first experiment is not attributable to a visual acuity disorder, but is explained as due to an impairment of the pattern perception mechanism.


A quantitative evaluation for peripheral respiratory chemosensitivities by the withdrawal test in man.

Ten healthy subjects were tested for their peripheral respiratory chemosensitivities by the withdrawal technique two times on separate days. Hypoxic hypercapnia of PET, O2 75, 65 AND 55 mmHg with PET, CO2, 5 mmHg higher than the control level was replaced by 100% O2 two times with spontaneous respiration. Then, breath-by-breath depression calculated in minute ventilation (delta V) was observed during the period 5-20 sec after the first O2 inhalation. The results were analyzed by the linear relationship between PET, O2 and 1n delta V, and PaO2 and 1n delta V. Delta V at P02 50 mmHg, delta V50, was 9.09 +/- 6.81 liters/min (mean +/- SD) in PET, O2-1n delta V analysis and 9.22 +/- 7.46 liters/min in PaO2-1n delta V analysis, respectively. The averaged day to day variation of delta V50 expressed by SE in % was 5.3% in PET, O2-1n delta V analysis and 11.5% in PaO2-1n delta V analysis, respectively.


Stimulation of microsomal drug oxidation activities by incorporation into microsomes of purified NADPH-cytochrome c (P-450) reductase.

The effects of addition of purified NADPH-cytochrome c (P-450) reductase on microsomal activities of aniline hydroxylation, p-phenetidine O-deethylation and ethylmorphine and aminopyrine N-demethylations were investigated utilizing microsomes from untreated, phenobarbital-treated and 3-methylcholanthrene-treated rats. The purified reductase was incorporated into microsomes. The drug oxidation activities were increased by the fortification of microsomes with the reductase while the extent of increase in the activities varied with the substrate and microsomes employed. The most pronounced enhancement was seen in p-phenetidine O-deethylation, followed by aniline hydroxylation and aminopyrine and ethylmorphine N-demethylations. The enhancement was more remarkable in microsomes from rats treated with 3-methylcholanthrene or phenobarbital. alpha-Naphthoflavone inhibited p-phenetidine O-deethylation activity markedly when the reductase was incorporated into microsomes, indicating that a larger amount of a species of cytochrome P-450 sensitive to the inhibitor was capable of participating in the oxidation of this substrate in the presence of the added reductase. One of the two Km values seen with higher concentrations of aniline or aminopyrine was altered by the fortification of microsomes with the purified NADPH cytochrome c (P-450) reductase. From these results, we propose that NADPH-cytochrome c (P-450) reductase transfers electrons to the selected one or two of multiple species of cytochrome P-450 more preferentially depending upon the substrate and the concentration of the substrate in microsomal membranes.


[Autotransplantation of Langerhans' islets in a case of total duodenopancreatectomy (author's transl)].

A 36-year-old man suffering from chronic pancreatitis involving the whole organ had total duodenopancreatectomy. The Langerhans' islets were isolated from the extirpated organ and transplanted into the liver via portal artery. Insulin substitution could be lowered from 50 I.U. to 12 I.U. by the 5th post operative day. Repeatedly, raised insulin levels could be verified in response to high blood sugar loads. C-peptide and glucagon were also found. 7 months after transplantation the islets still seem to be functioning.


Patterns of reversion to bobbed condition of magnified bobbed loci in D. melanogaster.

The number of genes coding for the ribosomal RNA (rDNA) can increase in D. melanogaster by means of a process called magnification. In this way, a partial deletion in this locus, termed bobbed, can reach a wild type condition. A newly magnified locus, in turn, reverts to a deficient bobbed condition if it is kept in a phenotypically wild type genotype for several generations. We studied bobbed loci at different magnification steps, analysing their behaviour through the reversion process and the way they carry out a second round of magnification. Results based on the analysis of the reversion process led to the conclusion that magnification consists of a progressive integration into the bobbed locus of free rDNA copies. Moreover, evidence is supplied that the extent of this integration affects the way a reverted locus goes through a second magnification cycle. The extensive characterization of reverted bobbed loci lends substantial support to the extra copies model of rDNA magnification.


E. coli ribosomal proteins are cross reactive with antibody prepared against Chlamydomonas reinhardi chloroplast ribosomal subunit.

Antisera prepared against purified Chlamydomonas reinhardi small chloroplast ribosomal subunit, judged homogenous by sucrose gradient velocity sedimentation and RNA gel electrophoresis was immunologically cross reactive with E. coli ribosomal proteins. The results of three different experimental approaches, namely Ouchterlony double diffusion, sucrose gradient velocity sedimentation and two dimensional crossed immunoelectrophoresis indicate that both E. coli ribosomal subunits and the chloroplast large ribosomal subunit contain proteins which show antigenic similarity to the chloroplast small ribosomal subunit proteins. However, cytoplasmic ribosomal subunits did not contain proteins which were cross reactive with immune antisera.


Biological activity of an antibiotic produced by Myxococcus coralloides.

A strain of Myxococcus coralloides was isolated which produced an antibiotic active against Gram-positive bacteria and also against Neisseria sp at high levels of antibiotic. The antibiotic was bactericidal on sensitive growing bacteria. It was inactive on non-growing cells and also on cells whose growth has been stopped by addition of chloramphenicol. Strains of S. aureus resistant to several antibiotics, including penicillin and ampicillin, were also sensitive to this antibiotic.


[Quantitative determination of the vascular volume of the cat carotid body under normoxia, hyperoxia, hypoxia and hypercapnia (author's transl)].

The ratio vascular volume to total volume was quantitatively analyzed in the cat's carotid body in dependence on the oxygen content of respired air and arterial pO2, respectively. Under hypoxia the vascular volume was 50% higher than under hyperoxia. This connection was ascertained after both perfusion fixation and immersion fixation.


In vitro studies on bacterial colonization. The effects of beta-lactam antibiotics on the growth of Escherichia coli and Pseudomonas aeruginosa in mixed culture.

Many cases of Pseudomonas aeruginosa infection are considered to be secondary superinfections, resulting from bacterial colonization. Such cases of superinfection with P. aeruginosa developing after administration of cephalosporin or penicillin are offering serious clinical problems. To make a fundamental analysis of the development of such superinfections, attempts were made to compare the growth patterns of Escherichia coli and P. aeruginosa in pure and mixed cultures and to determine the effects of cephalothin, cefazolin, cephalexin, and ampicillin on the growth patterns. In mixed cultures, the growth of P. aeruginosa was markedly inhibited by E. coli. The higher the concentration of each of the cephalosporins and ampicillin added to the mixed culture, the smaller the population of E. coli sensitive to these agents. When the population of E. coli became smaller than that of P. aeruginosa, which is resistant to these agents, the latter was restored to the same population level as that in pure cultures. Experimental bacterial colonization, by which the predominant population of E. coli was replaced by that of P. aeruginosa in mixed culture, was brought about more efficiently with the cephalosporins than with ampicillin. This might be accounted for by the difference in minimal inhibitory concentration for P. aeruginosa between ampicillin and the other three agents.


Cell wall-bridge maintaining three dimensional structure of cell packets formed by the localized suppression of cell separation of a Micrococcus lysodeikticus (luteus) mutant.

Cell packets of Micrococcus lysodeikticus (luteus) mutant strain MT grown in medium supplemented with trypsin consisted of a tetrad as the unit structure. An interstice was observed between the unit-tetrads, and a three dimensional structure of cell packets was maintained by the cell wall-bridge along the rim of the cell packets which linked each unit-tetrad. This unique structure of strain MT cell packets seemed to occur when the cell separation was suppressed locally, i.e., when the cross wall inside the initial site of cell separation was cut off, while the wall outside the initial site of separation was not cut off but remained as a joint of the daughter cells. The mechanism of cell wall-bridge formation is discussed in connection with cell separation.