[Causes of death in lightning strokes (author's transl)].

On the basis of the literature and of their own investigations, including animal experimentation, the authors attempt to show the possible causes of death following lightning strokes. Animal experiments give evidence of the important role of cardiac arrhythmias, in particular of asystolia and ventricular fibrillation. Cardiac arrest, respiratory standstill, burns, fractures, mechanical lesions of internal organs and hemorrhages are stated as causes of death. Moreover, autopsy fails to reveal recognizable changes in some of the victims.


[Treatment of porphyria cutanea tarda with and without phlebotomy (author's transl)].

Extensive investigations form 1962 to 1973 on 23 patients with porphyria cutanea tarda are reported. Two collectives of patients with different treatments are compared. One collective was treated conventionally with "liver therapy, abstinence from alcohol, and rest in bed", the other collective with "phlebotomy, abstinence from alcohol, and rest in bed". Both collectives showed a nearly equal decrease of uroporphyrin excretion. The unfavourable effect of alcohol in this disease was confirmed. In the post-observation period, minimal excretion of uroporphyrin was found to be more frequent and to persist longer in the collective treated by phlebotomy. In this collective, abstinence from alcohol was more consistently adhered to.


[Restrictive bandages. Expert medical opinion (author's transl)].

The danger of pressure damage due to bandages is considerable. Plaster casts are incorrect immediately after accidents, repositioning of and operations on limbs. Complaints of circulatory disturbances and pains are to be taken very seriously. Pressure damage may occur not only after plaster casts, but also with elastic bandages. The urgent need to pay attention to undisturbed blood flow to the extremities after accidents and operations is emphasized with reference to 11 cases of various kinds.


Molecular analysis of spontaneous somatic mutants.

Eukaryotic structural gene mutations occurring spontaneously in a mouse myeloma cell line offer the opportunity to study somatic mutation in animal cells at the molecular level. Studies on the myeloma protein and on mRNA have enabled us to characterise four such mutants representing four different mutation mechanisms. The results may have some bearing on the origin of antibody diversity.


A fossil skull probably of the genus Homo from Sterkfontein, Transvaal.

A skull with numerous Homo features was discovered at Sterkfontein, near Krugersdorp, Transvaal, in August 1976. It stems from member 5 of the Sterkfontein Formation, with stone tools and with fauna pointing to an age of 2.0-1.5 Myr. The underlying member 4 contains Australopithecus africanus, no stone tools, and fauna dated 3.0-2.5 Myr. The new find supports the view that the Sterkfontein toolmaker was not the earlier A. africanus, but a later hominid related to Homo habilis. By a remarkable double coincidence, the first pieces of the new skull, Stw 53, were found on August 9, 1976, 40 years to the day after Robert Broom's first visit to Sterkfontein, while the last part came to light on August 17, the 40th anniversary of Broom's first discovery of a hominid cranium at Sterkfontein. Although most of the fragments were found in a decalcified pocket of cave earth, one large part of the calvaria was still present in the calcified wall of the pocket, thus establishing indisputably the provenance of the specimen.


Oral manifestations of secondary hyperparathyroidism related to long-term hemodialysis therapy.

Patients on long-term hemodialysis therapy may develop secondary hyperparathyroidism with oral symptoms. As the life expectancy of the dialysis patient increases, the dentist is seeing these manifestations with increasing frequency. A review of the subject is presented along with a case illustrating dramatic roentgenographic changes in a patient who was placed on hemodialysis when the technique was in its infancy.


The effect of a proteolytic enzyem mixture (Orenzyme-Forte) on experimentally induced pulpitis.

A proteolytic enzyme mixture, Orenzyme-Forte, containing trypsin, chymotrypsin, and ribonuclease was used to treat experimentally induced pulpitis in the teeth of three monkeys. Assessment by means of the criteria of Stanley showed that the enzyme mixture induced better healing than a zinc oxide--eugenol dressing. When the two were used simultaneously, a synergistic effect was seen. We suggest that this enzyme mixture may be useful in clinical practice in the treatment of pulpitis.


[Parenteral nutrition and nitrogen balances in low birth weight newborns in the adaptation period (author's transl)].

Nitrogen balance studies were performed in the course of parenteral nutrition in the first 5 days of life in three groups of low birth weight newborns (I. group = 12 premature, 27.--30. gestational week, b. w. M = 1298 g, II. group = a) 7 prematures, 27.--31.g.w.,b.w.M = 1295 g,b) 5 small for date prematures, 29.--32.g.w.,b.w.M = 1208 g, III. group = 10 prematures, 31.--36.g.w.,b.w. M = 1751 g). Losses of nitrogen via urine in extreme prematures during the adaptation period are higher than in full term or moderate prematures. Increased volume of parenteral nutrition (glucose, fat emulsion) and increased caloric quotient did not produce a significant restriction of N-losses via urine. No difference was found in N-losses between extreme prematures and small for date prematures of similar birth weight/group IIa): IIb)/. Aminoacids (cca 500 mg N/kg body weight/24 hrs) given on the second day of life were well retained; increased losses of N represented about 20% of N infused.


[Vaccination against hepatitis B in man].

The preparation of a vaccine against hepatitis B is described. The vaccine is prepared from the HB viral coat (HBs Ag) purified and formalin inactivated. The HBs Ag is isolated and purified from the blood of healthy HBs Ag positive donors by means of an immunoadsorbent technique. The inocuity and efficacy were tested on chimpanzees. Vaccination was then applied in an attempt to protect patients and ward staff in a high risk haemodialysis unit. The efficacy of the vaccine was assessed by humoral and cellular anti-HBs immune reactions. The study of HBs antigenaemia in vaccinated and non-vaccinated subjects indicate that this vaccine protects against hepatitis B. Many arguments are in favor of aetiological role of the hepatitis B virus in the genesis of primary liver cancer in tropical areas. Immunization against hepatitis B could be the first example of prevention of a potentially oncogenic viral infection.


[Use of demeclotetracycline in the treatment of hyponatremia in cirrhotic ascitis].

The activity of demeclotetracyclin, and ADH antagonist, is studied in 11 ethylic patients with cirrhosis of the liver, under a large hydric diet (1500 cm3). The prescription of the cyclin (600 mg daily) is always determined by a fall of the urinary osmolarity (-36%) and by a dramatic improvement of the free water clearance (+ 60%); consecutively, we observe an increase of natremia in 8 out of 9 cases. Associated with Spironolactone (200 mg daily) the anti-ADH activity persists (the free water clearance becomes positive in 5 out of 10 patients), in spite of the natriuretic activity of anti-aldosterone ; a minimal fall of the natremia is observed in only 2 cases. The indication of Demeclotetracyclin in the curative or preventive treatment of the hyponatremia of the liver cirrhosis is discussed.


Dysphagia and esophageal diverticula.

Normal swallowing depends on a highly integrated sequence of esophageal contractions and relaxations. When the upper or lower sphincter or the tubular esophagus in between fails to function properly, the abnormal pressures created may cause diverticula to form. Initial symptoms are mild and transitory, but severe obstruction and regurgitation may eventually occur, requiring surgery. Traction diverticula, resulting from an inflammatory process, occasionally develop, but their frequency has been overestimated.


Myeloma and other paraproteinemias.

The paraproteinemias, a large heterogeneous group of diseases, are best characterized by the type of immunoglobulin moiety (paraprotein) produced. For the most common disorder, myeloma, response to treatment with alkylating agents has been objectively shown. Waldenström's macroglobulinemia and heavy-chain disease are more closely related to lymphoma than to myeloma. Some patients with paraproteinemia have a benign course with a constant, abnormal, immunoglobulin level.


Nutritional management of the patient with advanced cancer.

Protein-calorie malnutrition, vitamin and other deficiencies, and weight loss frequently develop in cancer patients. Although there is no evidence that aggressive nutritional management prolongs survival, it may improve the quality of life. Efforts should be made to maintain adequate daily caloric intake with appropriate food selection and with control of complications interfering with nutrition. In selected patients, intravenous hyperalimentation can provide adequate nutrition during potentially effective chemotherapy or radiotherapy. Elemental diets also may be a source of complete or supplemental nutrition. Further experience with both approaches will help to clarify their role in the nutritional management of the patient with advanced cancer.


Inhibition of prostaglandin endoperoxide synthetase by thiol analogues of prostaglandin.

A variety of thiol compounds inhibited the enzymatic bis-oxygenation of 8,11,14-eicosatrienoic acid to prostaglandin G1, as examined with a purified preparation of prostaglandin endoperoxide synthetase (prostaglandin synthase; 8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase; EC 1.14.99.1) from bovine vesicular gland. The hydroperoxide cleavage of prostaglandin G1 producing prostaglandin H1 was not affected by these thiol compounds. Several prostaglandin analogues with a thiol group (9,11-dihydroxy-15S- or 15R-mercaptoprosta-5,13-dienoic acid, 1-mercapto-9,11,15-trihydroxyprosta-5,13-diene, and 1-mercapto-9-oxo-11,15-dihydroxyprosta-5,13-diene) were most potent inhibitors, showing almost complete inhibition at concentrations on the order of 1 muM. Other thiol compounds, such as 2,3-dimercaptopropanol, dithiotherreitol, and dihydrolipoic acid, were also inhibitory but were much less effective. The inhibition, as examined with 9,11-dihydroxy-15S-mercaptoprosta-5,13-dienoic acid and 2,3-dimercaptopropanol, was noncompetitive.


Partial inhibition of postreplication repair and enhanced frequency of chemical transformation in rat cells infected with leukemia virus.

Postreplication repair of DNA and chemical transformation with the carcinogen 4-nitroquinoline-1-oxide were studied in rat cell lines either uninfected or infected with Rauscher leukemia virus. The results indicate that equivalent amounts of carcinogen are bound to the DNA initially and removed during excision repair. However, the lines differ in that the infected line alone exhibits both sensitivity to nitroquinoline-oxide-induced transformation and a partial inhibition of the postreplication repair process after notroquinoline oxide or UV treatment.


Mechanism of a case of genetic coadaptation in populations of Drosophila melanogaster.

A cryptic polymorphism found in natrual populations of Drosophila melanogaster has been examined in an artificial population maintained for over 200 generations. The polymorphism is selected because it is insensitive to the segregation distorter phenomenon, and it thereby largely preserves the Mendelian rules of segregation. Segregation distorter chromosomes and the cryptic polymorphism form part of a coadapted complex which is associated with linkage disequilibrium in natrual populations.


Development of tumor cell resistance to syngeneic cell-mediated cytotoxicity during growth of ascitic mastocytoma P815Y.

The immune reactivity to tumor cells within a progressively growing tumor mass in the syngeneic host has been analyzed by studying the cell-mediated cytolytic response of DBA/2 mice to the ascitic mastocytoma P815Y. Peritoneal cells from P815Y tumor-bearing hosts were fractionated by velocity sedimentation at unit gravity. Cell-mediated cytotoxicity of fractionated and unfractionated cells was measured by 51Cr-release from tumor target cells. The cell separation procedure revealed significant levels of specific cell-mediated cytotoxicity to P815Y within peritoneal cell populations at 8-16 days after tumor cell inoculation. Tumor cells purified from the peritoneal cell populations of mice injected with 10(3) tumor cells 10 days previously were as susceptible to syngeneic and allogeneic cell-mediated cytotoxicity as P815Y grown in vitro. However, tumor cells obtained from mice 16 days after tumor inoculation were resistant to cytolysis by syngeneic, but not allogeneic, effector cells. In addition, day 16 tumor cells did not inhibit syngeneic cell-mediated cytotoxicity against P815Y grown in vitro. Immunoglobulin was not detected on day 16 tumor cells and no circulating antibody to P815Y was found in the ascitic fluid of day 16 tumor-bearing mice. These results indicate that tumor cells may escape immune attack by loss of expression of cell surface tumor-associated antigens in the absence of circulating antibody against tumor.


Multiple sclerosis: a social-psychological perspective.

Many patients with multiple sclerosis experience strong feelings of alienation due to the nature of a disease with unknown etiology and largely ineffective treatment procedures. The familial and societal involvement in the process of alienation is discussed and some issues relating particularly to the institutionalized patient are identified.


Median nerve compression and trigger finger in the mucopolysaccharidoses and related diseases.

Patients with Hurler's syndrome (MPS-1H), I-cell disease (ML-II) and pseudo-Hurler's  syndrome (ML-III) had median nerve compression and triggering of the fingers which limited finger extension. To our knowledge, this combination has not been reported previously in patients with mucopolysaccharidoses and related disorders. In all of our 3 cases the median nerve was compressed by thickened flexor tenosynovium. Synovectomy and resection of the volar carpal ligament improved the hand function in all, including the mentally retarded patient with Hurler's syndrome. Release of the fibroosseous tunnel in two patients was followed by an increased range of motion (but not full extension). A fourth patient, without a mucopolysaccharide storage disorder, also had the combination of trigger finger and carpal tunnel syndrome.


Fibrosing alveolitis in patients with neurofibromatosis.

Fibrosing alveolitis, or interstitial pulmonary fibrosis, is a common manifestation of neurofibromatosis, and was observed in 7 of 70 patients with the disease. Though neurofibromatosis is congenital, fibrosing alveolitis does not appear until adulthood, and occurs in 20% of patients with the disease who are over 30 years old. Characteristic radiographic findings include linear, interstitial density, and large upper lobe bullae; this combination limits the differential diagnosis. Pathological examination demonstrates alveolar wall thickening progressing to fibrosis and lung destruction. Pulmonary function tests can show obstructive or restrictive lung disease.


Massive subperiosteal hemorrhage in neurofibromatosis.

Neurofibromatosis is seen in association with elephantiasis neuromatosa and overgrowth of abnormal bones, but rarely with subperiosteal hemorrhage. This is a secondary finding after severe or minor trauma to the periosteum, which is abnormally loose from mesodermal dysplasia. The clinical, plain radiographic, and angiographic findings of 2 cases of massive subperiosteal hemorrhage are presented, and the literature reviewed.


Radiation therapy of thalamic, midbrain and brain stem gliomas.

The case histories of 40 patients with gliomas of the thalamus and midbrain (Group I) or caudal brain stem (Group II) were reviewed to determine the effect of radiation therapy on neurologic functional status and survival. Nine of 14 (64%) patients in Group I demonstrated an improvement in functional status following radiotherapy, as did 19 of 26 (73%) patients in Group II. Eight (57%) patients in Group I and 10 (38%) patients in Group II are alive with no evidence of disease after periods of 12 to 65 months following completion of treatment. Acturial survival data indicate a better survival rate in Group I patients. Based on our findings, an aggressive and potentially curative attempt with use of radiation therapy for gliomas of the thalamus, midbrain, and brain stem is justified.


[Elementary diet as an alternative to parenteral feeding in severe gastrointestinal diseases].

21 patients with gastroenterological disease and indication for the use of intravenous nutrition received an elemental diet (ED) for 5-44 days. In 6 out of 8 patients with exacerbation of Crohn's disease remissions were achieved, apart from 3 persistent fistulas. In 5 out of 9 cases with various primary diseases and postoperative intestinal fistulas, spontaneous healing was observed. Furthermore, 2 patients with ulcerative colitis, 1 with radiation enteritis and 1 with pancreatitis were treated with ED. On ED, hemoglobin increased from 11.3 +/- 0.4 (m +/- SEM) to 12.0 +/- 0.5 g% (p less than 0.01) and serum albumin from 2.7 +/- 0.1 to 3.4 +/- 0.1 g% (p less than 0.001). Nitrogen requirements were studied in 11 patients receiving various quantities of ED. Nitrogen balance was found to be in equilibrium or positive in 7 patients, and negative in 4. In one patient with severe ulcerative colitis, fecal nitrogen losses were higher than urinary nitrogen losses. The unpleasant taste of ED resulting from free amino acids limited the ED supply in 3 patients and led to premature ending of ED administration in 3 other patients. In such cases ED may be given by nasogastric tube feeding. From the results presented it appears that ED is indicated in Crohn's disease and intestinal fistulas. However, the results obtained require confirmation by further observations and comparison with an intravenously fed control group.


[Myasthenia gravis. New results on etiology, diagnosis and therapy].

Myasthenia gravis is discussed with reference to recent immunologic findings, improvements in diagnostic procedure, and therapy. Myasthenic reactions can be produced in animals by injection of receptor proteins. In addition, the injection of thymopoietin causes neuromuscular block. The majority of patients with myasthenia gravis have antibodies against acetylcholine receptors, and there is a markedly reduced number of bungarotoxin binding receptors at the endplates. Further, recent immunologic findings indicate that genetic factors may be involved in the etiology of myasthenia gravis. The recently developed single fiber electromyography is useful in the diagnosis of myasthenia gravis. New statistics demonstrate the value of thymectomy in the treatment of myasthenia gravis. Good results have been reported following treatment with corticosteroids and azathioprine.


[Waldenström's macroglobulinemia with immunocytoma of the lung].

A case of Waldenström's macroglobulinemia in a 63-year-old man is presented. The clinical course was complicated by pulmonary infiltration classified by biopsy as immunocytoma. The clinical findings and therapeutic possibilities in this rare case of Waldenström's macroglobulinemia with with pulmonary complications are discussed in the light of the literature.


Persistence of a specific pseudomonas infection in a large general hospital.

Of at least 37 strains of Pseudomonas aeruginosa distinguishable by their pyocine production, Type 10 is noteworthy for its relative rarity and its virulence to man. Opportunistic infections by this organism occurring in a single hospital over 8 years are described, and its ecology discussed with reference to its possible control.


Elemental analysis of a tumor from a nocturnal prosimian with special emphasis on bromine.

Few natrually occurring tumors have been reported in primates. A spherical mass was noticed on the medial aspect of the thigh and caudal abdomen of a 15-year old female Perodicticus potto. The mass was surgically removed and the recovery was uneventful. Histological examination provided the diagnosis of myeloliposarcoma. Thirty-two elements were detected by chemical analysis. These are Na, K, Rb, Cs, Li, Cu, Ag, Be, Mg, Ca, Sr, Zn, Cd, Hg, B, Al, Ga, Si, Sn, Ti, P, Bi, V, S, Se, Mo, F, Cl, Br, Fe, Co and Ni. It has been proposed by some that tumor tissue tends to be chemically similar to embryonic tissue. Bromine is unexpectedly high in the potto tumor, in other tumor analyses reported in the literature, as well as in the only available embryonic tissue from the female potto, a placenta. Data are presented that lend credence to the speculation that Br may have a hitherto unexpected function in reproduction.


Primate model for long-term study of intraventricularly or intrathecally administered drugs and intracranial pressure.

Meaningful pharmacokinetic investigations require animal systems which approximate the human situation. This report describes a primate model in which silicone catheters are placed into the fourth ventricle and the spinal subarachnoid space and connected to subcutaneous cerebrospinal fluid without tissue damage, prod, enables spinoventricular perfusion, and permits ventricular cerebrospinal fluid sampling over extended periods in unanethetized rhesus monkeys. This animal system may provide intraventricular pressure recordings and pharmacokinetic data similar to that obtained in man.


Basal ganglia cooling disables learned arm movements of monkeys in the absence of visual guidance.

Unilateral local cooling in the region of the globus pallidus of Cebus monkeys produced a severe breakdown in the performance of learned flexion-extension elbow movements when animals had no visual information about arm position but not when such information was displayed to them. This result indicates that visual information enables an animal to compensate to a large degree for the motor disorder produced by globus pallidus dysfunction, and it may explain why some previous workers have failed to see motor impairments in monkeys with lesions in the globus pallidus who were observed in their cages.


Membrane asymmetry.

The components of biological membranes are asymmetrically distributed between the membrane surfaces. Proteins are absolutely asymmetrical in that every copy of a polypeptide chain has the same orientation in the membrane, and lipids are nonabsolutely asymmetrical in that almost every type of lipid is present on both sides of the bilayer, but in different and highly variable amounts. Asymmetry is maintained by lack of transmembrane diffusion. Two types of membrane proteins, called ectoproteins and endoproteins, are distinguished. Biosynthetic pathways for both types of proteins and for membrane lipids are inferred from their topography and distribution in the formed cells. Note added in proof. A cell-free system has now been developed which permits the mechanisms of membrane protein assembly to be studied (108). The membrane glycoprotein of vesicular stomatitis virus has been synthesized by wheat germ ribosomes in the presence of rough endoplasmic reticulum from pancreas. The resulting polypeptide is incorporated into the membrane, spans the lipid bilayer asymmetrically, and is glycosylated (108). The amino terminal portion of this transmembrane protein is found inside the endoplasmic reticulum vesicle, while the carboxyl terminal portion is exposed on the outer surface of the vesicle. Furthermore, addition of the glycoprotein to membranes after protein synthesis does not result in incorporation of the protein into the membrane in the manner described above (108). Consequently, protein synthesis and incorporation into the membrane must be closely coupled. Indeed, using techniques to synchronize the growth of nascent polypeptides, it has been shown (109) that no more than one-fourth of the glycoprotein chain can be made in the absence of membranes and still cross the lipid bilayer when chains are subsequently completed in the presence of membranes. These findings demonstrate directly that the extracytoplasmic portion of an ectoprotein can cross the membrane only during biosynthesis, and not after.


Bone marrow imaging with 59Fe.

Commerically available collimators are not suitable for the visual demonstration of the kinetics of 59Fe, because of its physical properties. A locally designed collimator, that provides integral visual information of the whole body distribution of erythropoietic marrow, is discussed. Wholebody scans of 4 individuals are also included to demonstrate the capabilities of the collimator.


The effect of protein energy malnutrition on plasma renin and oedema in the pig.

Five litter-mate male pigs, aged 7 days and fed a standard Pig Industry Board diet containing 190 g/kg dry mass of digestible protein, were compared with 10 male pigs from two litters fed a protein-deficient diet (50 g/kg) for a period of 70 days. The 10 experimental animals developed oedema between the 42nd and 70th days of the study and 4 of them became lethargic. Although the 10 experimental animals showed the typical biochemical changes characteristic of protein energy malnutrition (PEM), including changes in muscle electrolytes, liver fat and plasma albumin, the 4 lethargic animals showed a significant increase in effective plasma renin activity (EPRA) only by the 70th day of the study. Since oedema preceded any increase in EPRA in some pigs and developed in others without any change in EPRA, it is suggested that the increased renin activity is not responsible for the initial fluid retention and oedema.


A study of the plasma free amino acids in infants of low birth weight, with a comparison of oral feeding with milk and total parenteral nutrition.

The plasma amino acid concentrations soon after birth, at 10 days and 1 month, were estimated in 25 infants of low birth weight (less than 1 500 g). Ten of these infants were fed with amino acids as casein hydrolysate, through the umbilical artery for the first 10 days. The normal range of plasma amino acid values for infants of low birth weight shows a wider range of concentrations than that of term infants. During total parenteral nutrition (TPN) the plasma amino acid values were generally elevated above those obtained in infants receiving conventional feeding with a "humanised" milk formula. In particular, the concentrations of aspartic acid, phenylalanine, cystine, leucine, isoleucine and glutamic acid were significantly higher. With the cessation of TPN, these levels returned to normal, so that no significant difference could be detected between the 2 groups after 1 month. The suitability of current amino acid solutions for paediatric use is discussed.


Effect of prolonged bacteremia on leukocyte bactericidal function.

Neutrophil bactericidal function (NBF) was studied in dogs during intravenous infusions of Pseudomonas aeruginosa. Administration of 10(6) bacteria per minute over 3 hours was associated with a bacteremia level of about 10(3) organisms per milliliter of blood without adverse effects on NBF. Infusion of 10(7) organisms per minute resulted in blood bacterial counts in the upper 10(4) range and significantly impaired NBF. To determine the relative contribution of the spleen in bacterial phagocytosis, splenectomies were performed in additional dogs immediately prior to 5 hour infusions of 10(6) Pseudomonas aeruginosa per minute. Results revealed that splenectomy did not influence the blood bacterial clearance. These experimental findings emphasize the dominant role of polymorphonuclear leukocytes in bacterial defense.


Isolation of drug-resistant bacteria from newborn infants.

The fetus is known to be bacteria-free and is contaminated with bacteria during birth. We examined drug-resistant bacteria in feces of new-born infants to know the distribution of drug-resistant bacteria in a hospital. Among 76 infants examined, we could isolate drug-resistant strains of bacteria from 65 infants (86%). We collected 110 drug-resistant strains of Escherichia coli, Klebisella pneumoniae, and Pseudomonas aeruginosa, and could isolate 53 strains (48%) carrying R plasmids; they being 33R (TC.CM.SM.SA.APC) and 20R (TC.CM.SM.SA) plasmids. The data indicated that R plasmids with the same resistance patterns were distributed in a hospital, and new-born infants were contaminated with bacteria carrying R plasmids, although the contamination rate of drug-resistant bacteria in the intestinal flora was very low.


[Consideration of inhomogeneities in irradiation planning. 2. Influence of inhomogeneities on the shape of the depth dose curve in water with 42 MeV X-rays (author's transl)].

With 42 MeV high-energy radiation, inhomogeneities such as bones, fat, plaster or palacos have no particular influence upon the depth dose curve in water because of the relatively insignificant differences of their atomic numbers, and there is no need to consider them in calculation of the focal dose. Metallic inhomogeneities, however, their effective atomic numbers being relatively high, show a different behaviour in 42 MeV X-ray bremsstrahlung: Just behing the metallic inhomogeneity an increase of the dose as compared to water is to be seen (e.g. directly behind a metallic plate, 4.5 mm thick, the augmentation of the dose amounts to 17%). This difference between 42 MeV X-ray bremsstrahlung and 60Co gamma rays (see part I of the present study) in the shape of the depth dose curve following permeation of metal by the radiations is due to enhanced pair formation within the high-energy radiation of 42 MeV photons.


Herpes simplex keratitis.

This article reviews the current concepts for the diagnosis and treatment of Herpes simplex keratitis and its complications, discussing characteristics of the virus, the prevalence of the disease, chemical and clinical differentiation between Types I and II Herpesvirus hominis, and the many clinical presentations of Type I disease. The antiviral agents commonly in use are reviewed, covering the historical development of the drugs, indications for their use and the associated toxic and untoward reactions. An outline for the medical treatment of the different forms of Herpes simplex keratitis is given, as well as the indications for surgical intervention in the treatment of the disease. The surgical complications and results following keratoplasty are discussed.


Slow virus infections.

Slow viruses produce diseases whose incubation periods range from several months to many years. Because of this long latency period, the lack of inflammation produced by these diseases and the lack of recoverable virus particles, it is only recently that the association has been made between the viruses and the diseases they cause. The detailed study of kuru, a neurologic affliction of a remote tribe of cannibals in New Guinea, was responsible for the synthesis of new and previously gathered information into a unified framework to explain not only kuru but other diseases as well. Since then, animal models, transmission experiments and histologic and biochemical studies have unveiled new links connecting viruses to previously obscure neurologic, neurophthalmic and ophthalmic entities.


Studies on the rosette inhibition assay. Results using monkey lymphocytes.

Results obtained using a modified rosette inhibition assay with human and monkey lymphocytes were compared. The monkey lymphocytes tended to yield lower titers against a series of antithymocyte globulin preparations. Titers or relative rosette inhibition activities obtained with monkey lymphocytes correlated more poorly with skin graft prolongation in monkeys than assays using human lymphocytes in previous studies.


Stability studies on horse antithymocyte globulin.

Two equine antithymocyte globulin preparations were studied with respect to their relative rosette inhibition activity after storage at 4 and 25 C. After storage at 4 C for 48 months no activity loss was observed; 25 C storage resulted in fragmentation and eventual loss of relative rosette inhibition activity. A third preparation was studied by monkey skin graft prolongation. During a 1-year period, there was no loss of immunosuppressive activity as measured by this method and the rosette inhibition assay.


Experimental regional cerebral ischemia in the middle cerebral artery territory in primates. Part 1: Angio-anatomy and description of an experimental model with selective embolization of the internal carotid artery bifurcation.

Selective embolization of the internal carotid artery bifurcation (ICA bifurcation) was performed in monkeys (Macaca mulatta) to study acute regional cerebral ischemia in the middle cerebral artery (MCA) territory with minimum surgical intervention in the neck under sedated conditions. The anthropomorphic similarity in angio-anatomy of the carotid system of monkeys and the use of silastic spheres, as artificial emboli, of the critical diameter of 1.2 to 1.4 mm resulted in the overall success rate of 87% in localizing the site of embolization to the ICA bifurcation, producing ischemia in the whole middle cerebral artery territory. All the animals with ICA-bifurcation embolization had contralateral deep motor weakness and conjugate eye deviation with nystagmus toward the site of embolization. Simultaneous EEG recording showed flattening of the basic background activities over the affected MCA area and cerebral arteriograms showed definite retrograde filling of the proximally occluded MCA. Clinical recovery was observed in a few animals within two to five hours of embolization. Gross ischemic swelling in the affected MCA territory, particularly in the gray matter, became obvious in six of eight animals which were exposed to four to five hours of ischemia. The angio-anatomical study of the carotid system of this experimental animal as a background for this MCA stroke model confirmed the previous observations of other investigators that the extremely abundant leptomeningeal anastomoses would be one of the major factors leading to the variability in the clinicopathological pictures seen in the models of proximal MCA occlusion. In addition, the pre-parenchymal anastomoses in the base of brain between the medial striate arteries from the proximal anterior cerebral (ACA) and lateral lenticulostriate arteries from the MCA were observed and described as a possible functional collateral to the basal ganglia in case of proximal MCA occlusion.


Experimental regional cerebral ischemia in the middle cerebral artery territory in primates. Part 2: Effects on brain water and electrolytes in the early phase of MCA stroke.

Acute regional cerebral ischemia was produced in the middle cerebral artery (MCA) territory in monkeys (Macaca mulatta) by selective embolization of the internal carotid (ICA) bifurcation with minimum surgical intervention in the neck under sedated conditions. Two of five hours after embolization, brain water (measurement of dry weight) and tissue concentration of sodium and potassium were determined in the tissues of the sylvian cortex, putamen and subcortical white matter in the affected MCA territory. As early as three hours, initial increase in brain water was detected in the samples of the putament without noticeable change in tissue electrolytes in two of three animals. Gross ischemic swelling of the gray matter, in both the sylvian cortex and putamen, became obvious in six of eight animals after four to five hours. This swollen gray matter showed marked increase in brain water (up to 36% swelling), increase in tissue sodium (up to 100% of the control value), and decrease in tissue potassium (down to 55%). On the other hand, edema in the white matter, if present at all, was minimal without detectable change in tissue electrolytes and was always accompanied by much greater ( greater than two to seven times) edema in the gray matter. Thus, the gray matter edema, in both the deep subcortical structures and the cortex, appeared to play the major role in the development of hemispheric swelling of the brain which may begin within hours of the onset of the MCA stroke in monkeys. Microscopically, the swollen gray matter which showed more than 10% swelling with a definite shift of tissue sodium and potassium content appeared to be dead tissue. However, early edema in the gray matter which showed less than 10% swelling without detectable change in electrolytes might be caused by simple diffusion of water through the dysfunctional capillary wall or cell membrane with or without a permeability gradient between the intravascular cerebrospinal fluid and cerebral tissue compartment and might possibly be reversible.


Failure of prolonged hypocapnia, hypothermia, or hypertension to favorably alter acute stroke in primates.

The effects of induced hypocapnia, hypothermia, and hypertension were surveyed in a primate model of acute stroke during and following a 48-hour period of intensive care. The results were compared to a group of nine control animals previously studied. Hypocapnia (PaCO2=25 torr) was examined in five animals and did not appear to alter the expected mortality, degree of neurological deficit, or frequency of infarction. There was, however, a suggestion that the size of infarction may be reduced. Hypothermia (29 degrees C) in five animals had a detrimental effect in that no animals survived following the intensive care period and all had infarction with massive edema. We speculate that hypothermia caused a sufficient increase in blood viscosity as to compromise collateral flow, thereby accounting for this detrimental effect. Induced hypertension (to 20% above control levels) was abandoned after three animals because of severe systemic effects (cardiac failure and pulmonary edema) resulting in death during the period of intensive care.


[Thyroid function following thyroidectomy determined by the TRH-induced release of thyrotropin (author's transl)].

The response of hTSH to TRH (400 mug i.v.) was studied in 45 patients who underwent thyroid surgery for various reasons. Euthyroid values of T4 and ETI were observed in all but one patient. An increased response of hTSH to TRH (as compared with 15 control subjects) was observed in 12 out of 30 patients operated upon for non-toxic goitre, in one out of nine operated upon for toxic goitre and in three out of six patients who underwent thyroidectomy for thyroid carcinoma or proliferating adenoma of the thyroid. The necessity of specific replacement therapy in those individuals with increased release of hTSH upon TRH administration is discussed.


[Acute primary plasma cell leukemia (author's transl)].

The sudden onset of plasma cell leukemia with IgG-lambda-paraproteinaemia is reported in a 59-year-old patient. In the year before clinical manifestation of the disease the patient was examined and treated for a duodenal ulcer and a head injury on three separate occasions in different wards of the hospital without detection of any sign of disease of the haemopoetic system. The clinical features and course of the disease resembled those of acute leukaemia, the maximum percentage of plasma cells in the peripheral blood being 72 and in the bone marrow 98. Osteolytic bone lesions were not observed and there was no renal insufficiency. Therapy with mephelan-prednisolone and cyclophosphamide-prednisolone was not successful in influencing the fatal outcome of the disease.


[Epileptic manifestations following head injury (author's transl)].

An analysis is presented of the findings in a group of 300 patients with head injury, aged 15 years or over at the time of the accident, who subsequently developed epileptic manifestations. Early fits (including one case of immediate onset) were found in 33% of the cases (99 patients). In contrast to post-traumatic late epilepsy (PTE), which is a manifestation of a static process, early fits are triggered off by a dynamic process (brain oedema, haemorrhage) and are a sign of cerebral irritation, but do not represent a true form of epilepsy. Early fits are related to the acute traumatic state; the time limit is flexible, but lies in the region of 4 weeks following injury. Conversion of early fits to PTE (with or without a latent interval) occurred in 72% of the cases. This percentage is higher than the average incidence quoted in the literature and presumably arises partly from the selection criteria applied in this study. The time of appearance of early fits following injury is one factor which determines the prognosis. Fits appearing on the first day carry a relatively favourable prognosis and do not proceed to PTE in 41% of the cases, whereas this percentage shrinks to 15% in the case of fits appearing from the second week onwards. Early fits are an isolated occurrence in one third of the cases; progression to PTE is less frequent in these patients than following frequent, repeated convulsions. Furthermore, the incidence of early fits is dependent, to a large extent, on traumatological and clinical factors: the combination of unconsciousness of over three hours' duration, neurological signs referable to the central nervous system, persistent organic psychotic syndrome and intracranial bleeding leads to a significantly higher incidence of early fits than unconsciousness of less than three hours' duration and absence of neurological signs in patients who, moreover, do not display features of the psychotic syndrome, and shows a greater tendency to early fits even than the combination of depressed fracture of the skull with penetration of the dura. Should, however, early fits occur in spite of a favourable assessment of the traumatological factors involved, then progression to PTE occurs in a higher percentage of such cases than in patients displaying signs of a serious import following injury. The transition to PTE is markedly higher following diffuse cerebral contusion (75% of cases) than in cases displaying signs of local contusion....


[Effect of exchange transfusion on the plasma amino acid concentration in hepatic coma].

Exchange transfusion (ET) were made twice on a 22 year old patient with fulminant hepatitis and hepatic coma. The influence of the ET on the plasma amino acids (PAA) was examined. The 1. ET reduced the concentration of the total PAA from 10,023 to 7,152 mugmol/l (about 28.6%) and the 2. ET from 11,770 to 9,706 mugmol/l (about 17.5%). Three hours after the 1. ET the concentration of the total PAA has passed over the prevalue and after the 2. ET has nearly reached it. The influence of both ET on the concentration of the individual PAA was very different (- 47.9% to + 71.2% after the 1. ET and - 32.9% to + 41.8% after the 2. ET respectively). Therefor the ET seems to be not a suitable method to reduce the pathologic concentration of the PAA in the hepatic coma.


The relationship between expression of epithelial B-like blood group antigen, cell movement and cell proliferation.

Healing wounds in the oral mucosa of rhesus monkeys were examined by an immunofluorescence staining method to demonstrate the distribution of a blood group antigen cross reacting with human group B, and by labelling with tritiated thymidine to localize areas of cell proliferation. Within hours, blood group antigen reactivity was lost from epithelial cells adjacent to the wound margin. Reactivity was absent from the epithelial outgrowth into the wound, but returned with restoration of epithelial continuity. The zone of increased cell proliferation lay adjacent to, but outside of, the area of antigen loss. Antigen loss appeared to be associated with an area of increased cell movement, a finding of interest in relation to reports of antigen loss from epithelial tumors.


In vitro effects of prolactin and hydrocortisone on 7,12-DMBA-induced mammary tumour and virus-induced sarcoma in the rat.

The in vitro effect of prolactin and hydrocortisone, singly or in combination, on the DMBA-induced mammary tumour in the rat was investigated by organ cultures. Prolactin had a stimulating effect on the DNA synthesis in one out of five tumours. Hydrocortisone induced lobulo-alveolar differentiation but reduced the DNA synthesis or failed to affect it. The addition of prolactin to hydrocortisone did not alter this response. Virus induced rat sarcomas were studied as control tissue. Prolactin inhibited growth of one sarcoma. Hydrocortisone stimulated growth of sarcomas. The relevance of these findings in relation to similar in vitro experiments is discussed.


Renal anomalies and oligohydramnios in the cerebro-oculofacio-skeletal syndrome.

We describe two infants with the cerebro-oculofacio-skeletal syndrome in whom oligohydramnios is an additional finding. The oligohydramnios could be accounted for in one by renal agenesis but cannot in the other, who had a functioning and histologically normal kidney. The diagnosis of Potter syndrome was suspected in both patients. It is important in counseling to recognize the distinctive phenotype of this autosomal-recessive syndrome.


Chronic active hepatitis. Prolonged survival without treatment.

A case is presented of a patient with established HBsAg-positive chronic active hepatitis and cirrhosis of at least 14 years duration. The disease, although untreated, has caused the patient relatively little disability. The implications of the patient's prolonged illness are discussed with reference to current knowledge of chronic active hepatitis. It is concluded that corticosteroid therapy may not be a mandatory requirement for all patients with this disease.


Mucosal eosinophilic gastroenteritis with systemic involvement.

The unusual features in a 46 year old white woman with mucosal eosinophilic gastroenteritis are described. In addition to involvement of the gastrointestinal tract, she had eosinophilic splenitis and hepatitis. She responded to corticosteroid therapy, but not to an elimination diet or to cromolyn sodium therapy. The possible role of various factors chemotactic for eosinophilia in the patient are reviewed, and the place of the disorder among the hypereosinophilic syndromes is discussed.


Fulminant sepsis after the successful treatment of Hodgkin's disease.

Of 14 splenectomized patients with Hodgkin's disease who were treated with total nodal irradiation and combination chemotherapy (MOPP), fulminant sepsis developed in three (21.4 per cent) while they were in remission; two died within hours. Similar cases were not observed in a larger group of 146 patients with Hodgkin's disease (including 104 splenectomized patients who were treated less intensely). Our experience indicates the need for caution when asplenic persons are aggressively treated with both radiation and drugs.


A review of serologic problems caused by polyagglutinable red cells.

Polyagglutination is a condition in which the erythrocyte membrane has been altered so that the red cell becomes agglutinable with the majority of adult serums. In many instances, it can be shown that the red cell membrane alteration has resulted in activation of one (or more) latent antigens, i.e. T, Tk, or Tn. Adult serums normally contain IgM antibodies directed against these hidden antigens. When these latent receptors are exposed, the cells will be found to be polyagglutinable upon subsequent testing with these serums. This review describes the serologic procedures applicable for identification and resolution of the problems each type of polyagglutinable cell creates for the blood bank.


Maternal betamethasone and fetal growth and development in the monkey.

Bethamethasone was administered to pregnant rhesus monkeys of 134 to 150 days' gestation. At operative delivery, umbilical venous plasma cortisol concentrations were significantly lower in the treated group than in the control group, indicating that the agent crossed the placenta. In the treated group, accelerated differentiation was present in several fetal organs including lung, liver, kidney, and adrenal gland. Brain histologic changes suggestive of neuronal injury were found in some instances. There were no differences in the weights of these fetal organs except for liver. It was markedly increased in steroid-treated fetuses and this was accompanied by a fourfold rise in total hepatic glycogen content. These observations suggest that in the subhuman fetal primate, the differentiation of fetal organs in addition to lung is enhanced by short-term corticosteroid treatment while growth is not affected.


Effect of betamethasone on analysis of amniotic fluid in the rhesus-sensitized pregnancy.

Betamethasone was administered to six rhesus-sensitized pregnant women carrying seven fetuses in an attempt to accelerate fetal pulmonary maturation. A reduction in optical density of amniotic fluid at 450 mmu was observed in all cases following steroid therapy; however, only minimal changes were noted in the lecithin-sphingomyelin ratio. The implications of these findings for the management of rhesus-sensitized pregnancies are discussed.


Ocular abnormalities in the median cleft face syndrome.

An 8-month-old infant boy with median facial cleft syndrome had eyelid coloboma, symblepharon, and a cytic mass in the left upper eyelid. The mass proved to be an ectatic cornea containing a large cystic lens. Maldevelopment of the entire anterior segment of the eye was also present, although the posterior globe was well formed. We postulate that an area of localized abnormal mesodermal differentiation and fusion at the 17- to 20-mm stage of development served as a common mechanism for all the defects noted.


Identification of Rickettsia rickettsii in a guinea pig model by immunofluorescent and electron microscopic techniques.

Moribund guinea pigs infected with Richettsia rickettsii were examined by necropsy, histology, immunofluorescence, electron microscopy, and serology. Untreated animals died at 9 and 10 days after inoculation. Animals given saline subcutaneously survived from 1 to 4 days longer. Prolonged survival was accompanied by more severe lesions: scrotal necrosis; infarction of ears; and swollen, hemorrhagic footpads, epididymis, and cremaster muscle. Histopathologic examination demonstrated that acute, necrotizing vasculitis, perivascular hemorrhage, and focal necrosis were more extensive. Direct immunofluorescence indicated many more rickettsiae in endothelium and vascular wall of saline recipients. Ultrastructurally, typical rickettsiae were present focally in the cytoplasm of endothelial and vascular smooth muscle cells. Cytopathology in infected and adjacent cells included swelling, mitochondrial enlargement with decrease in matrix density and loss of cristae, and increased pinocytosis. In addition, treated animals had more cytonecrosis, thrombosis, extravascular fibrin deposition, prominent inflammatory cells with polymorphonuclear phagocytosis of rickettsiae, and antibody production.


Metric dental change in the European upper paleolithic and mesolithic.

Evolutionary trends for dental reduction are presented for European Upper Paleolithic and Mesolithic samples. The analysis demonstrates that the greatest decrease in tooth size occurs between the two divisions of the Upper Paleolithic, while little and insignificant change characterizes the Late Upper Paleolithic/Mesolithic transition. Trends for tooth size over this period indicate that (1) human evolution does not stop with the appearance of "anatomically modern Homo sapiens," (2) changes in tooth size fluctuate with increases in the efficiency and complexity of cultural systems, and (3) the Early Upper Paleolithic sample should be considered transitional between Wurm II European Neanderthals and later Upper Paleolithic and Mesolithic groups.


A gracile hominid cranium from upper member G of the Shungura formation, Ethiopia.

A fragmentary hominid cranium with teeth, specimen L.894-1, dating from 1.84 m.y. BP in the Shungura Formation at Omo, is described. From its dental and cranial morphology and because of similarities to Olduvai Hominids 24 and 13 and Sangiran 4, among others, it is concluded that the specimen represents a member of an early species of the genus Homo (Homo habilis or Homo modjokertensis). The specimen shows approximal grooving on the premolars, pre-mortem chipping of the molar enamel, foramina ovale and spinosum divided by the sphenosquamosal suture, limited pneumatization of the mastoid region, and a possible interparietal bone. Sedimentological, ostracod, pollen, macrofloral, and taphonomic data indicate that the paleo-environmental context was a savanna/grassland or savanna woodland on the margin of a saline lake.


Reorientation of myofilaments during contraction of a vertebrate smooth muscle.

The purpose of the investigation was to determine whether filaments within smooth muscle cells changed their orientation (with respect to the main axis of the cell) during contraction. The stomach muscle of Bufo marinus was used, since its cells may be easily isolated, enabling direct observation in living cells. In addition to still micrography, cinemicrography was used to record continuously during contraction. Polarization microscopy revealed a change in birefringence after contraction, with relaxed cells exhibiting uniform birefringence while contracted cells displayed a discontinuous pattern. Movies revealed a progressive change in orientation of birefringent elements from nearly parallel to the cell's main axis in relaxed cells to increasingly larger angles to the cell's axis as contraction progressed. Phase-contrast microscopy revealed a change in filamentous components, from being parallel to the cell's axis in relaxed cells to being in an undulating or helical pattern during concentration. Cell shape tended to follow the configuration of the filamentous component. Electron microscopy of muscle strips corroborated the observations of living cells and substantiated the conclusion that filaments change their orientation from parallel to oblique (with respect to the cell's axis) during shortening with an undulating or helical pattern of filaments in shortened muscles.


Effect of long-term parenteral feeding on gastric secretion in dogs.

Three dogs were surgically prepared with gastric fistulas and Heidenhain (vagally denervated) pouches. Acid and pepsin responses to pentagastrin and food were determined before, at the end of a 1-mo period of total parenteral feeding, and 1 mo after the resumption of a normal oral diet. Acid and pepsin output from the denervated pouch in response to pentagastrin and food decreased significantly (P less than 0.001) after parenteral feeding and returned to control levels after the dogs resumed a normal diet. Secretory outputs from the gastric fistula in response to pentagastrin remained unchanged throughout the experiment. Basal serum gastrin levels decreased 50% during the period of intravenous feeding and returned to levels approximately twice the control levels following resumption of normal oral food intake. Serum gastrin responses to a meal also decreased during intravenous alimentation and returned to higher than normal levels following a 1-mo period of oral intake. These studies indicate that the absence of oral food intake in the dog does not result in decreased acid secretion from the innervated stomach. Vagal innervation in some way is responsible for the preservation of normal secretion during the absence of food from the gastrointestinal tract of the dog.


Transient circadian internal desynchronization after light-dark phase shift in monkeys.

In four conscious chair-acclimatized squirrel monkeys (Saimiri sciureus) studied with lights on (600 lx) from 0800 to 2000 h daily (LD 12:12), prominent 24-h rhythms in feeding, drinking, activity, body temperature, and urinary potassium, sodium, and water excretion were seen. When the monkeys were subjected to 36 h of darkness followed by 36 h of light each variable demonstrated a circadian rhythm which was not passively dependent on the light-dark cycle. After the 24-h light-dark cycle was abruptly phase-delayed by 8 h, all the rhythms resynchronized with the new light-dark cycle phase, demonstrating that light-dark cycles are an effective zeitgeber. However, the resynchronization of the rhythms of feeding, drinking, activity, and body temperature was 90% complete within approximately 2 days while the 90% resynchronization of the urinary rhythms took approximately 5 days. These results suggest that the circadian timing system in S. sciureus may consist of several spontaneously oscillating units which can become transiently uncoupled during pertubations of environmental time cues.


Evaluation and measurement: some dilemmas for health education.

Seven dilemmas of evaluation and measurement posed by the nature of health education are presented, together with suggestions for their resolution. These include the dilemmas of : 1) rigor of experimental design vs significance or program adaptability; 2) internal validity or "true" effectiveness vs external validity or feasibility; 3) experimental vs placebo effectsl 4) effectiveness vs economy of scale; 5) risk vs payoff; 6) measurement of long-term vs short-term out-comon. Emphasis is placed on the need to develop a more cumulative data base through standardization of measures, replication of experiments in different settings, and better documentation, reporting, and diffusion of experiences in practice.


Effect of pentagastrin infusion on gastroesophageal manometry and reflux status before and after esophagogastrectomy.

The lower esophageal high pressure zone of eight Rhesus monkeys was characterized by manometry and reflux testing. It was found to respond characteristically to pentagastrin infusions. After excision of the lower esophageal segment and tis replacement by a stomach tube, an apparently normal, functional high pressure zone was demonstrable within the substitute.


Caloric requirements of the critically ill patient receiving intravneous hyperalimentation.

The caloric requirements of the critically ill patient was defined by body composition measurements performed in thirty-five patients before and after a course of total parenteral nutrition (TPN). A positive and statistically significant (p less than 0.001) correlation was observed between the number of kcal/kg/day infused and the mean daily change in Ke, which is a measure of the body cell mass. The intercept of the regression line was 46 kcal/kg/day indicating that balance is achieved when calories are infused at this rate. Fifteen of the thirty-five patients studied received less than 46 kcal/kg/day. In this group an average of 38.1 +/- 1.5 kcal/kg/day of TPN was infused for 13.3 +/- 1.2 days. The body composition of these patients was unchanged after TPN and was characteristic of malnutrition both before and after TPN. TPN was administered at a mean rate of 57.2 +/- 2.0 kcal/kg/day for 16.7 +/- 1.8 days in the twenty patients who all received more than 46 kcal/kg/day. The body composition of these patients before TPN was also characteristic of malnutrition. However, a marked improvement of body composition was observed after the course of TPN. In all the patients in both groups the amino acids were infused at a rate that exceeded the minimal amount required to achieve nitrogen balance. The data indicate that the average patient receiving TPN requires at least 46 kcal/kg/day for balance. In the depleted patient infusion of calories in excess of this amount results in a rebuilding of the body cell mass.


Comparison between glucose and a combination of glucose, fructose, and xylitol as carbohydrates for total parenteral nutrition of surgical intensive care patients.

The effects of four day periods of infusions of 600 gm/24 hours glucose and 600 gm/24 hours of a combination of glucose, fructose, and xylitol were compared. This study was performed during total parenteral nutrition of twelve postoperative patients with major complications. The mean plasma glucose level was significantly lower during the infusion of the combination of sugars (154.2+/-19.5 mg/100 ml versus 193.9+/-15.0 mg/100 ml[p is less than 0.005). Furthermore, the required dosage of exogenous insulin was significantly lower (18.9+/-12.3 units/day versus 43.7+/-19.7 units/day [p is less than 0.01). Mean renal carbohydrate losses were 0.85 per cent during glucose infusion and 1.7 per cent during infusion of the combination. The influence of both infusion regimes on values for pH, base excess, lactate, pyruvate, free fatty acids, insulin, sodium, potassium, chloride, magnesium, phosphorus, bilirubin, alkaline phosphatase, SGOT, and SGPT 0.85 has been investigated. No clinical side effects were observed. It is concluded that the administration of the investigated combination of glucose, fructose, and xylitol is justified in patients in whom hyperglycemia during infusion of glucose alone is difficult to control with insulin.


Fibers in monkey posterior articular nerves.

The distribution of axons in the posterior articular nerves in rhesus monkey has been studied in terms of ratio of myelinated to unmyelinated fibers, and size of myelinated fibers. Conduction velocity measurements were also made. The nerves contained 2,000 to 2,200 unmyelinated fibers of 0.2 to 1.2 mum diameter. They contained 399 to 478 myelinated fibers, varying in size from 1.4 to 12.3 mum. Thus 80 to 85% of fibers in these nerves were unmyelinated. The maximum conduction velocity of 70 to 80 meters per second corresponded to an initial small deflection, with most fibers conducting at slower rates. These results are compared to previous reports which severely underestimated the number of unmyelinated fibers because electron microscope counts were not utilized. It is suggested that pain fibers from the knee joint of monkey make up much of this large population of unmyelinated axons. An unknown number of post-ganglionic sympathetic fibers is also included in the unmyelinated fiber group.


Efficacy double-blind, crossover study of sodium cromoglycate in patients with seasonal allergic rhinitis.

In a double-blind, crossover, placebo-controlled study, consisting of 100 clinical trials, the active drug (sodium cromoglycate) was effective in 83.2%, while in 11.6% the placebo was judged more effective (p less than 0.0001). Four patients suffered minor side effects. No deleterious effect on the nasal mucosa was noticed and no one complained that the drug produced sedation.


Experimental infection of cats with the liver fluke Platynosomum concinnum,.

The severity of Platynosomum concinnum infection in cats experimentally infected with 125 flukes (small dose) and 1,000 flukes (large dose) was determined by monitoring clinical signs and hematologic, serum biochemical, and pathologic changes during the infection. All cats (8/8) with a small fluke burden and 3 of 8 cats with a large burden remained clinically asymptomatic, whereas 60% of the cats given large doses had mild signs of inappetence and lethargy. Eosinophilia, peaking 4 to 5 months after infection, was present in all parasitized cats. During the early stages of platynosomiasis, a transient but substantial increase in aspartate aminotransferase and alanine aminotransferase activities was observed in cats given small and large doses. These observations agreed with gross and histopathologic observations, which included enlargement of the gallbladder and biliary ducts, with leukocyte infiltration, adenomatous hyperplasia, and fibrosis of the ductal areas.


Preventing infection in intravenous therapy.

Any part of an infusion system--not just the cannula, its most distal portion--may be at fault when sepsis complicates IV therapy. Detailed here are both intrinsic and extrinsic meachanisms by which contamination may occur; recommendations such as more widespread use of steel scalp needles and early termination of infusions are given. The special requirements of total parenteral nutrition systems are defined.


Persistence of Mycobacterium tuberculosis in sputum without chest roentgenographic evidence of active disease.

Mycobacterium tuberculosis has been isolated consistently from sputum over an 11-year period in an asymptomatic 64-year-old man whose chest radiographs show evidence of healed primary tuberculosis (Ranke complex) but no evidence of parenchymal disease. A lymph node-bronchial fistula associated with the Ranke complex is the likely site of active tuberculosis; however, repeated examinations of the upper and lower respiratory tract have been normal. We attribute the persistence of infection in our patient to erratic usage of antituberculous drugs.


Bacillus cereus pneumonia. Survival in a patient with cavitary disease treated with gentamicin.

Cavitary pneumonitis due to Bacillus cereus occurred in a patient with acute lymphoblastic leukemia. Pneumonia due to this organism is uncommon and recovery has not been previously reported. The present report is the first description of cavitary pneumonia due to B. cereus with a successful outcome. Recovery was attributed to appropriate antimicrobial therapy and induction of leukemic remission with chemotherapy.


Labyrinthitis ossificans.

Three cases with postinflammatory inner ear sequelae are presented to illustrate unusual histopathologic changes. Endolymphatic hydrops without changes in the perilymphatic system was present in one ear following "influenza" meningitis and labyrinthitis ossificans in the contralateral ear. The characteristic histopathological changes of the temporal bones with hematogenic bacterial infection were an extensive labyrinthine ossification associated with a generalized sclerotic change of the whole periotic bone. Bony fixation of the stapedial footplate occurred with the generalized inflammatory process of the otic capsule. Severe and diffuse labyrinthitis ossificans occurred in one case due to tympanogenic inflammation spreading through the round window membrane in the course of suppurative otitis media. A general immunosuppression leading to fatal termination was the apparent factor predisposing to the inner ear complication.


In vitro activity of netilmicin, gentamicin, and amikacin.

The in vitro activity of netilmicin (Sch 20569), a new semisynthetic derivative of gentamicin, was compared with that of gentamicin and amikacin. One hundred and ninety-two clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus were tested using both agar and broth dilution techniques. Netilmicin was comparable to gentamicin, with the following exceptions: (i) for Serratia marcescens and P. aeruginosa, gentamicin was more active than netilmicin; (ii) all strains of Escherichia coli, Klebsiella, Enterobacter, Proteus mirabilis, and Citrobacter freundii, which were resistant to gentamicin, were susceptible to netilmicin; (iii) some strains of S. marcescens, indole-positive Proteus, and Providencia, which were resistant to gentamicin, were susceptible to netilmicin. Netilmicin was more active than amikacin for all Enterobacteriaceae and S. aureus and equal to amikacin in activity against gentamicin-susceptible strains of P. aeruginosa. All strains of P. aeruginosa, resistant to gentamicin, were also resistant to netilmicin but were susceptible to amikacin. Minimal inhibitory concentrations (MICs) obtained with broth and agar showed no significant differences except for P. mirabilis, where broth MICs were twofold greater than agar MICs, and for P. aeruginosa, where agar MICs were twofold higher than broth MICs. The minimal bactericidal concentration (MBC) was either identical to or within one twofold dilution of the MIC for the strains tested. A 100-fold increase in inoculum size produced less increase in MIC and MBC with netilmicin than with gentamicin or amikacin.


Stability of cephalosporins in horse serum.

The antibiotic activity of cephalothin, cephaloridine, cephalexin, cephaloglycin, cefazolin, and cefamandole was determined after storage for up to 30 days in horse serum at -10 and 4 degrees C. Cephalothin, cefamandole, cefazolin, and cephalexin were stable for at least 30 days at -10 degrees C, whereas cephaloridine lost 29% of its initial activity and cephaloglycin lost more than 50%. Cefamandole, cefazolin, and cephalexin could only be stored for 3 days at 4 degrees C without significant loss in activity, whereas cephalothin, cephaloridine, and cephaloglycin could be stored for only 1 day. Repeated freezing and thawing had a detrimental effect on the stability of cephaloridine.


Production of megacins C and Cx: presumptive evidence extrachromosomal control.

Exposure of growing cultures of Bacillus megaterium C4A(-) to ethidium bromide or an elevated growth temperature was found to eliminate megacin C production. Ethidium bromide resulted in a cure rate of up to 13%. Growth at 43 degrees C gave a cure rate of up to 99%. Megacin C production was lost spontaneously at a rate of 4% or less. There was a greater rate of spontaneous loss of megacin Cx production by B. megaterium 337, up to 14%. Growth at 43 degrees C resulted in a cure rate of up to 24% in this organism. Reversion to the Meg(+) state by cured clones has never been demonstrated. These observations support the hypothesis that production of megacins C and Cx is plasmid mediated. Meg(-) clones adsorbed more megacin than either parent strain and were more susceptible to megacin action.


Interferon induction in cynomolgus and rhesus monkey after repeated doses of a modified polyriboinosinic-polyribocytidylic acid complex.

Serum interferon activity was determined in 12 cynomolgus and 12 rhesus monkeys injected intravenously once daily for 10 days with from 0.1 to 6.0 mg of a stabilized polyriboinosinic acid . polyribocytidylic acid complex per kg, composed of polyriboinosinic acid . polyribocytidylic acid, poly-1-lysine, and carboxymethylcellulose [poly(ICLC)]. Interferon activity was detected 2 h after the first injection, with maximum activity occurring 8 h after the second injection. A period of hyporesponsiveness occurred after the third injection of poly(ICLC) in all monkeys and lasted until the sixth injection in the rhesus monkeys, when interferon activity again became more elevated. The delayed rebound was not as apparent in cynomolgus monkeys. Rhesus monkeys injected with 6 mg/kg did not exhibit serious side effects.


Purification and specificity of bacteriolytic enzyme I from Hartmannella glebae.

A soil amoeba (Hartmannella glebae), when grown in conjunction with Enterobacter aerogenes and Alcaligenes faecalis, produced two enzymes. Enzyme I was purified by gel filtration on Sephadex G-100 and chromatography on diethylaminoethyl-cellulose. It is a basic protein. The analysis of the enzymic digest of the cell walls of Micrococcus lysodeikticus after reduction and acid hydrolysis showed that the enzyme cleaved the glycosidic bond between acetylmuramic acid and acetylglucosamine of the peptidoglycan moiety of the cell walls. The enzyme is identified as endo-beta-N-acetylmuramidase.


Hydrogen production by nitrogen-starved cultures of Anabaena cylindrica.

Nitrogen-starved cultures of the alga Anabaena cylindrica 629 produced hydrogen and oxygen continuously for 7 to 19 days. Hydrogen production attained a maximum level after 1 to 2 days of starvation and was followed by a slow decline. The maximum rates were 30 ml of H2 evolved per liter of culture per h or 32 mul of H2 per mg of dry weight per h. In 5 to 7 days the rate of H2 evolution by the more productive cultures fell to one-half its maximum value. The addition of 10(-4) to 5 X 10(-4) M ammonium increased the rate of oxygen evolution and the total hydrogen production of the cultures. H2-O2 ratios were 4:1 under conditions of complete nitrogen starvation and about 1.7:1 after the addition of ammonium. Thus, oxygen evolution was affected by the extent of the nitrogen starvation. Thermodynamic efficiencies of converting incident light energy to free energy of hydrogen via algal photosynthesis were 0.4%. Possible factors limiting hydrogen production were decline of reductant supply and filament breakage. Hydrogen production by filamentous, heterocystous blue-green algae could be used for development of a biophotolysis system.


Incidence and properties of temperate bacteriophages induced from lactic streptococci.

Sixty-three strains of lactic streptococci isolated from commercial lactic streptococcal starter cultures were examined for lysogeny by treatment with ultraviolet light or mitomycin C. After treatment with the inducing agent, all strains, whether or not they lysed, were examined for evidence of phage release by electron microscopy. Thirty-eight strains yielded intact phages or phage particles of varying morphology. All the temperate phages had isometric heads and noncontractile tails; some had collars and structurally distinctive baseplates. Indicator host strains were found for phages induced from seven different strains. Three strains that released phages spontaneously yielded titers of 10(3) to 10(4) plaque-forming units per ml. When strains that spontaneously released phages were grown in mixed culture with indicator strains, increased phage titers of 10(6) to 10(7) plaque-forming units per ml were observed. These findings indicate that lysogenic lactic streptococcal strains may serve as a reservoir for phages that attack sensitive strains in mixed- or multiple-strain lactic starter cultures.


Mutant of Aspergillus flavus producing more aflatoxin B2 than B1.

A mutant of Aspergillus flavus having a high and relatively stable aflatoxin B2/B1 ratio was recovered after treatment with nitrosoguanidine.


Production of cyclopiazonic acid by Aspergillus flavus Link.

Production of cyclopiazonic acid by Aspergillus flavus is reported for the first time. A procedure for its production by agitated solid substrate fermentation on red wheat is described along with the isolation procedure and physical and chemical properties of this indole derivative. The compound has been found to exert antibacterial activity.


Thermal resistance of Bacillus subtilis var. niger in a closed system.

The heat resistance of Bacillus subtilis var. niger has been measured from 85 to 125 degrees C using moisture levels of percent relative humidity (%RH) less than or equal to 0.001 to 100 in a closed system. Five curves have been presented to characterize the thermal destruction, using thermal death times defined as F values at a given combination of three moisture and temperature conditions. Reductions of 99.99% (4-log10 cycles) of the initial population were estimated for the three moisture conditions. At 110 degrees C, the expected time for a 4-log10 reduction was 1.1 h at %RH = 100, 3.1 h at %RH less than or equal to 0.1 and 54 h at %RH = 10.7. Goodness-of-fit tests to examine the adequacy of three polynomial models failed to indicate a trend. The linear model (from which estimates of D are obtained) was satisfactory for estimating the thermal death times (%RH less than or equal to 0.1) in the plate count range. The estimates based on observed thermal death times and D values for the %RH = 100 diverged so that D values generally gave a more conservative estimate over the temperature range 90 to 125 degrees C. Estimates of ZF and ZL ranged from 32.1 to 58.3 degrees C for the %RH less than or equal to 0.1 and 100. A ZD value of 30.0 was obtained for data observed at %RH less than or equal to 0.1. The ZF results were obtained from plotting observed log times to achieve a 99.99% reduction in the initial population versus temperature. Estimates of ZL and ZD were obtained by using linear estimates of L100 approximately equal to 4D and D values in a similar plot.


Glutaraldehyde (pentanedial) allergic contact dermatitis. Usage test on sole and antecubital fossa: regional variations in response.

Glutaraldehyde (pentanedial) is an effective topical therapeutic agent for patients with hyperhidrosis of the soles. A usage test was performed on the soles and antecubital fossae of six previously documented glutaraldehyde-sensitive subjects. All had negative usage test reactions to 25% glutaraldehyde on the soles. But when tested on the antecubital fossae with 2.5% glutaraldehyde, they developed a severe dermatitis within 48 hours. These data demonstrate a striking variation by which glutaraldehyde-sensitive patients tolerate or react to its use in two diverse anatomic sites.


Pyogenic meningitis in chronic gastroenteritis and marasmus.

Pyogenic meningitis occurred in 6 infants in the course of chronic gastroenteritis, in 5 of whom a normal CSF had been recorded earlier in the illness. Clinical signs of meningitis were often absent. The problems of diagnosis and management and of possible predisposition to pneumococcal meningitis in children suffering from chronic gastroenteritis are discussed.


Vitiliginous achromia with malignant melanoma. Tyrosinase activity and ultrastructural study of achromic and normal skin.

Vitiliginous achromia with malignant melanoma shows some discrepancies with vitiligo. In both achromic and normal skin, four bands A, B, C, D of tyrosinase activity are observed; in vitiligo only bands A and B appear. Ultrastructural findings in achromic skin are similar in both conditions. But in achromia with malignant melanoma, melanocyte abnormalities are also present in normal skin and the role of immunological factors is discussed.


Intraluminal duodenal diverticulum in the adult.

Four patients with intraluminal diverticulum of the duodenum are presented and compared with those reported previously. This lesion is a rare congenital disorder that usually becomes symptomatic in adult life. It is located in the second portion of the duodenum within the lumen, extending distally. It has the appearance of a "thumb of a glove" and it is lined by mucosa on both surfaces. It develops betweeen the fourth and eighth week of the embryo's life, but it increases in size during adult life. It usually presents with typical or atypical symptoms of peptic ulcer disease, but sometimes manifestations such as gastrointestinal bleeding, duodenal obstructions or pancreatitis may predominate and may be severe and life-threatening. The diagnosis is best made with hypotonic duodenography, which demonstrates the lesion as a barium coated pouch within the air filled duodenal lumen. The treatment of choice is duodenotomy and excision of the lesion. Proper identification of the papilla of the ampulla of Vater is important since this structure is often adjacent to the diverticulum. No recurrences have been noted in the three patients operated upon.


Evaluation of a new amino acid source for use in parenteral nutrition.

Ninety-two patients, ranging from two days to 92 years of age, received parenteral nutrition using a new synthetic amino acid solution designed to provide optimal nitrogen retention and obviate metabolic complications. Weight gain and positive nitrogen balance were produced in the majority of patients. Hyperchloremic acidosis and hypophosphatemia did not occur. Hyperammonemia in infants was avoided with the exception of occasional, transient, asymptomatic elevations of blood ammonia in low birth weight infants. It was suspected that an inadequate nonprotein calorie/gram of nitrogen ratio may have been employed in these infants. Blood ammonia levels declined from initial levels in 80% of adult patient. Nitrogen retention was directly proportional to the supply of nonprotein calories.


Effect of 50% distal small bowel resection on gastric emptying in Rhesus monkeys.

The effect of bowel resection, sufficient to cause gastric secretory changes, on gastric emptying is unknown. Gastric evacuation was characterized in 8 Rhesus monkeys by a modification of George's double sampling test meal. Fifty per cent distal small bowel resection was then performed. Gastric emptying was again studied at 6 weeks and 6 months. The rate constant fell from -0.00289 +/- 0.000467 (+/-1 SEM) to -0.00232 +/- 0.00106 during the early phase, but role to -0.00308 +/- 0.00186 by 6 months, neither value being statistically different from the preoperative values. T1/2 rose from 125.2 +/- 19.2 mins to 367 +/- 173.4 mins by 6 weeks and to 380.9 +/- 161.6 mins by the end of the experiments. Corresponding values for T were: control period 425.8 +/- 63.2 mins, early phase 1223 +/- 589 mins and late phase 1245.9 +/- 529.6 mins. None of these changes were statistically significant. Alterations in emptying time within each animal were consistent at the two postoperative phases. Although the two animals showing acceleration of evacuation were those with least change in secretion, compensation for the observed increase in output of gastric juice did not materially alter the results.


Synchronization of Anacystis nidulans. Oxygen evolution during the cell cycle.

A new technique of short alternating light-dark periods was successfully used to synchronize the blue-green alga Anacystis nidulans. Oxygen evolution during the cell cycle is characterized by a maximum in the middle of the cycle and by a minimum at the time of division, a pattern very similar to that found in synchronized green algae.


Sporulation in the filamentous cyanobacterium Anabaena cylindrica. The course of spore formation.

Sporulation in the filamentous cyanobacterium Anabaena cylindrica involves the transformation of a vegetative cell into a thick-walled resistant structure. Because this process occurs at predictable loci in each filament and involves a significant increase in cell size, the course of sporulation in a culture can be quantitatively determined. Sporulation occurs during the late logarithmic phase of a culture, a time of slow but unbalanced growth. Under the conditions employed here, sporulation is not a synchronous event either between or within filaments. The information in this paper provides as estimate of the rate of spore differentiation and supports the previous notion that in the formation of strings of more than one spore, a gradient of spore maturation exists.


Nervous system effects of cardiac arrest in monkeys. Preservation of vision.

Thirteen juvenile monkeys were taught two visual discrimination tasks. After 12 to 24 hours of food deprivation, ten underwent 14-minute episodes of cardiac arrest. Three served as controls. Five of the ten arrested animals survived and were tested in the discrimination box. All continued to perform color and pattern discrimination tasks with one to eight days' delay. All appeared neurologically intact, while brain pathologic examination after 11 to 64 days' survival showed either intact brains or injury restricted to nuclear structures in the brain stem, cerebellar Purkinje cells, and hippocampus. Five animals died 4 to 36 hours after they were resuscitated. Two required prolonged cardiac massage and, despite return of adequate cardiovascular function, died early. A third animal dislodged its arterial catheter and exsanguinated. The remaining two animals, who received infusions of glucose just prior to arrest, developed widespread fasciculations and myoclonic seizures. They became decerebrate and opisthotonic and were killed after 10 and 36 hours. Their brains showed mild edema and widespread necrosis of cortex and basal ganglia. Thus, food-deprived monkeys tolerate 14 minutes of circulatory arrest well and show minimal neurologic and pathologic changes, while administration of glucose just before arrest markedly augments the severity of brain injury and alters its distribution.


Persistent hyperplastic primary vitreous: roto-extraction and other surgical experience.

We discuss nine cases of persistent hyperplastic primary vitreous seen recently, including mode of presentation, management and postsurgical follow-up. Emphasis is placed on early operative intervention in order to preserve the globe, as well as to prevent irremedial stimulus deprivation amblyopia. The advantages of roto-extraction in the surgical approach to this entity are considered, and the difficulties of postoperative visual rehabilitation are also discussed.


Soluble artifical tear inserts.

This article reports a new concept in the treatment of tear film abnormalities. Solubilization of an artifical tear insert provides a continuous flow of polymer into the tear film in place of intermittent drop therapy. The physiochemical properties of succinylated collagen were studied in vitro and compared favorably with presently available tear substitutes. The use of this polymer as a solid solubilizable insert was evaluated in normal patients. It was found to be comfortable, resulted in no blurring of vision, and prolonged the tear film breakup time.


Cyclocryotherapy: a light and electron microscopic study.

Previous anatomic studies of the effects of cyclocryotherapy have produced confusing results because of variations in technique and instrumentation. Five eyes from three patients treated by a standard technique were compared to the eyes of rhesus monkeys that received identical treatment. The monkeys were given horseradish peroxidase intravenously 30 minutes before enucleation. Hemorrhage, edema, and epithelial disruption were characteristic of the acute lesions. Later, the nonpigmented ciliary epithelium disappeared, but by two months, normal morphology was restored. Normal peroxidase flow reappeared at a similar time. Anatomic changes in the human and monkey eyes were similar.


Relation of etidocaine and bupivacaine toxicity to rate of infusion in rhesus monkeys.

The relationship between infusion rate of etidocaine and bupivacaine and central nervous system toxicity was studied in three rhesus monkeys. Increasing the infusion rate from 0.5 to 2.0 mg/kg.min-1 decreased the seizure dosage of etidocaine but had no effect on that of bupivacaine. Arterial plasma concentrations of etidocaine and bupivacaine that induced electrical seizure activity increased as the infusion rate was increased from 0.5 to 1.0 mg/kg. min-1. A plasma decay study in a fourth animal demonstrated that etidocaine decayed more rapidly than did bupivacaine. These results suggest that the rate of administration of these agents is important in determining central nervous system toxicity.


Use of anaesthesia with ketamine HCl in assessing the emetic activity of staphylococcal enterotoxin B in the rhesus monkey (Macacca mulatta).

Anaesthesia of rhesus monkeys with ketamine HCl which facilitated feeding them with staphylococcal enterotoxin B solutions was shown not to affect the ED50 of this toxin. Adoption of this anaesthetic procedure was found to make feeding studies with enterotoxins easier and safer.


Protein-energy malnutrition in infant non-human primates (Macaca nemestrina). I. Correlation of biochemical changes with fine structural alterations in the liver.

Male infant pigtail monkeys (Macaca nemestrina) aged 6-9 months and born in captivity were fed restricted amount of either an adequate protein diet (20% casein) or a protein-deficient diet (2% casein). After 3-5 months of receiving the low protein containing diet, ultrastructural evaluation of hepatic parenchymal cells revealed extensive fatty metamorphosis, marked fragmentation and vesiculation of the rough endoplasmic reticulum, some evidence of distension of the nuclear membrane, variable degree of mitochondrial polymorphism and gigantism, increased intracytoplasmic accumulation of glycogen particles and enhanced prominence of collagen fibres in the intercellular and perisinusoidal spaces. Biochemical studies indicated severe distortion in the plasma profile of free amino acids by Week 10 of malnutrition, with a prominent decrease in valine/glycine ratio (9% in the malnourished animals compared to a ratio of 55-63% in the control group). While plasma concentration of glycine was elevated above baseline value throughout the period of malnutrition, the level of alanine showed an initial rise followed by a significant drop (-58% at Week 20). Although showing wide individual variation, plasma level of corticosteroid in general tended to increase with duration of protein malnutrition, an observation consistent with the accumulation of glycogen and enlargement of mitochondria in the hepatic cells.


Interactions of platinum complexes with the essential and nonessential sulfhydryl groups of thymidylate synthetate.

Thymidylate synthetase (methylenetetrahydrofolate:deoxyuridylate C-methyltransferase) from Lactobacillus casei was progressively inactivated when incubated at 25 degrees C, pH 6.8, in the presence of trans-Pt(NH3)2Cl2. The inhibition appeared to be irreversible, and the rate ofa ctivity loss was dependent on the inhibitor concentration. The corresponding cis isomer was incapable of inhibiting the enzyme under the same conditions. The presence of 2-mercaptoethanol protected the enzyme from inhibition, but did not reactivate enzyme preparations which had been inhibited prior to the addition of the thiol. The interactions of cis- and trans-Pt(NH3)2Cl2 with the enzyme's sulfhydryl (-SH) groups were inferred from the results of spectrophotometric titrations of the enzyme with 5,5'-dithiobis(2-nitrobenzoic acid) and p-hydroxymercuribenzoate. The results suggested that the cis isomer reacted with an average of 1.3 of the enzyme's 4-SH groups and that these were not essential for catalysis. The trans isomer reacted with a total of approximately 2.5 -SH groups, 1.2 of which are essential for catalysis. Neither the trans isomer nor a combination of both isomers was able to react with 1.2 of the 4 -SH groups. Further evidence that the Pt complexes are interacting with enzyme's -SH groups was obtained by reversibly blocking the -SH groups of thymidylate synthetase, and demonstrating the resistance of these preparations to inhibition by the trans Pt complex. Possible explanations for the preferential inhibition of thymidylate synthetase by only one of the two geometric isomers of Pt(NH3)2Cl2 are considered.


Envelope glycoproteins of Rauscher murine leukemia virus: isolation and chemical characterization.

The envelope glycoproteins (designated gp70 and gp45) of the Rauscher strain of murine leukemia virus were solubilized by osmotic shock and freeze-thawing in chaotropic solutions. The viral glycoproteins were then purified by phosphocellulose chromatography and gel permeation chromatography on Bio-Gel A-1.5m. Yields by this procedure were 6.2% for gp70 and 1.3% for gp45 on a protein input basis. The apparent molecular weights were respectively 67 500 and 47 500 with a polypeptide chain molecular weight of approximately 45 000 for both glycoproteins. Amino acid analysis showed a high degree of similarity for both components, with some differences subject to further evaluation. The total carbohydrate content was approximately 32% for gp70 and 6-9% for gp45. In keeping with the amino acid compositional similarity suggesting relationships, alanine was found to ba the amino-terminal amino acid of both glycoproteins, and cross-reactivity was demonstrated by immunologic tests. The data suggest that the chief difference between gp70 and gp45 lies in the carbohydrate content.


Expression of the chloroplast ribosomal RNA genes of Euglena gracilis during chloroplast development.

The cellular content and transcription program of the chloroplast ribosomal RNA genes of Euglena gracilis Z have been determined during the light-induced development of chloroplasts by hybridization of total cell DNA or RNA to purified 3H-labeled chloroplast ribosomal DNA ([3H]ctrDNA). Pancreatic DNase activated, partially purified chloroplast rDNA was enzymatically labeled in vitro by E. coli DNA polymerase I with [3H]TTP as a substrate. The [3H] DNA was denatured and hybridized with a vast excess of purified chloroplast 16 and 23S rRNA. The rRNA-[3H]ct rCNA hybrid was isolated by chromatography on hydroxylapatite. The [3H]ct rDNA was purified and characterized by the kinetics of its renaturation with chloroplast DNA and rRNA, and by the thermal stability of [3H]DNA-DNA and [3H]DNA-RNA hybrids. [3H]ct rDNA was hybridized in trace amounts to cellular RNA or DNA isolated from Euglena cells 0,4,8,12,24,48, and 72 h after the onset of chloroplast development. From a comparison of the kinetics of hybridization with hybridization of standards of known kinetic complexity quantitative estimates of the cellular rRNA and rDNA gene content were made. Chloroplast rRNA increases from 2 to 26% of the cellular RNA during development, while the percentage of cellular DNA represented by ct rDNA increases two- to threefold. Correcting for the change in cellular RNA and DNA content during development, the number of copies of the rRNA gene increases less than twofold, while the number of copies of rRNA per cell increases sixfold. The results are consistent with either a transcriptional activation of the ribosomal genes or an increased rRNA stability during developmental.


Cellular content of chloroplast DNA and chloroplast ribosomal RNA genes in Euglena gracilis during chloroplast development.

The cellular content of chloroplast DNA in Euglena gracilis has been quantitatively determined. DNA was extracted from Euglena cells at various stages of chloroplast development and renatured in the presence of trace amounts of 3H-labeled chloroplast DNA. From the kinetics of renaturation of the 3H-labeled chloroplast DNA, compared with the kinetics of renaturation of excess nonradioactive chloroplast DNA, the fraction of cellular DNA represented by chloroplast DNA was calculated. The content of chloroplast DNA was found to increase from 4.9 to 14.6% of cellular DNA during light-induced chloroplast development. Correcting for the change in DNA mass per cell, the number of copies of chloroplast DNA is found to vary from 1400 to 2900 per cell. During this developmental transition, the cellular content of the chloroplast ribosomal RNA genes varies from 1900 to 5200 copies per cell. The ratio of the number of copies of rRNA genes to chloroplast genomes per cell remains in the range of 1-2 throughout chloroplast development, ruling out selective amplification of chloroplast rRNA genes as a means of regulation of rRNA gene expression. Direct measurement of the number of rRNA cistrons per 9.2 X 10(7) dalton genome yields a value of 1 or 2.


The photochemical and fluorescence properties of whole cells, spheroplasts and spheroplast particles from the blue-green alga Phormidium luridum.

The photochemical activities and fluorescence properties of cells, spheroplasts and spheroplast particles from the blue-green alga Phormidium luridum were compared. The photochemical activities were measured in a whole range of wavelengths and expressed as quantum yield spectra (quantum yield vs. wavelength). The following reactions were measured. Photosynthesis (O2 evolution) in whole cells; Hill reaction (O2 evolution) with Fe(CN)63- and NADP as electron acceptors (Photosystem II and photosystem II + Photosystem I reactions); electron transfer from reduced 2,6-dichlorophenolindophenol to diquat (Photosystem I reaction). The fluorescence properties were emission spectra, quantum yield spectra and the induction pattern. On the basis of comparison between the quantum yield spectra and the pigments compositions the relative contribution of each pigment to each photosystem was estimated. In normal cells and spheroplasts it was found that Photosystem I (Photosystem II) contains about 90% (10%) of the chlorophyll a, 90% (10%) of the carotenoids and 15% (85%) of the phycocyanin. In spheroplast particles there is a reorganization of the pigments; they loose a certain fraction (about half) of the phycocyanin but the remaining phycocyanin attaches itself exclusively to Photosystem I (!). This is reflected by the loss of Photosystem II activity, a flat quantum yield vs. wavelength dependence and a loss of the fluorescence induction. The fluorescence quantum yield spectra conform qualitatively to the above conclusion. More quantitative estimation shows that only a fraction (20--40%) of the chlorophyll of Photosystem II is fluorescent. Total emission spectrum and the ratio of variable to constant fluorescence are in agreement with this conclusion. The fluorescence emission spectrum shows characteristic differences between the constant and variable components. The variable fluorescence comes exclusively from chlorophyll a; the constant fluorescence is contributed, in addition to chlorophyll a, by phycocyanine and an unidentified long wavelength component. The variable fluorescence does not change in the transition from whole cells to spheroplasts. However, the constant fluorescence increases considerably. This indicates the release of a small fraction of pigments from the photosynthetic photochemical apparatus which then become fluorescent.


Sodium transport and oxygen consumption in toad bladder. A thermodynamic approach.

The relationship between active sodium transport and oxygen consumption was investigated in toad urinary bladder exposed to identical sodium-Ringer's solution at each surface, while controlling the transepithelial electrical potential difference delta phi. Rates of sodium transport and oxygen consumption were measured simultaneously, both in the short-circuited state (delta phi = 0) and when delta phi was varied. Under short-circuit conditions, when the rates of active sodium transport changed spontaneously or were depressed with amiloride, the ratio of active sodium transport to the estimated suprabasal oxygen consumption Na/O2 was constant for each tissue, but varied among different tissues. Only when delta phi was varied did the ratio Na+/O2 change with the rate of active sodium transport; under these circumstances dNa+/dO2 was constant but exceeded the ratio measured at short-circuit [(Na+/O2)delta phi = 0[. This suggests that coupling between transport and metabolism is incomplete. The results are analyzed according to the principles of nonequilibrium thermodynamics, and intepreted in terms of a simple model of the transepithelial sodium transport system.