Milwaukee brace treatment of idiopathic scoliosis: late results. Forty-seven patients returned for examination, X-ray and statistical analysis of the results more than 5 years after Milwaukee braces had been discontinued. The mean curves showed a characteristic pattern of rapid improvement after the brace was applied and then gradual loss of correction during the follow-up. There was no statistically significant variation when the results were analyzed according to initial age, initial curve size, or curve pattern. One-third of the patients lost 5 degrees or less after their braces were discontinued at skeletal age 18. The other two-thirds progressed, with the loss of a degree or two a year until their improvement stabilized in the mid or late twenties. More flexible curves stabilized later and lost more correction. Although the mean overall improvement was only slightly more than 3 degrees there was a range from a gain of 40 degrees to a loss of 26 degrees. The 2 most important findings were the tremendous variation in the age at which stabilization or correction occurred and the variability of end results.


Psychological factors in failure to wear the Milwaukee brace for treatment of idiopathic scoliosis. Youngsters who fail to successfully adapt to a Milwaukee Brace displayed measurable psychological differences from those who do adapt satisfactorily to this treatment approach. The study did not encompass all conceivable variables which might affect orthotic wearing, however, use of logical and empirical approach to further delineate important variables seems feasible and desirable. In fact, one can hypothesize a predictive test battery which will detect high risk patients and thus afford the physician the option of alternative treatment modes, or intensified psychological intervention if the orthosis is preferred. The nature of such a psychological test battery, as well as the actions which would constitute effective intervention, will depend on future research. Based on our data, adolescent idiopathic scoliosis patients can be considered high risks for compliance with a Milwaukee Brace program if they display the following psychological characteristics: lower overall intelligence uith relative deficits in general information, reading recognition and reading comprehension skills; greater potential for acting-out/rebellious behavior; relatively lower sense of personal power or "potency", less tension associated with doctors; self reports of very active personal and family life styles.


Kyphosis in the paralytic spine.

Kyphosis in the paralytic spine. The paralytic spine without supplementary support is unstable and susceptible to axial collapse. The biomechanical factors responsible for spinal stability should be considered in any treatment regimen for paralytic spines. If posterior fusion is elected as the treatment, kyphosis must be corrected so that the eccentric loading and kyphotic bending moment is very small. When this is done, posterior fusion alone is adequate to give spinal stability and increased function to the individual.


Follow-up study of Milwaukee brace treatment in patients with idiopathic scoliosis. Milwaukee brace treatment for patients with idiopathic scoliosis very rarely accomplishes improvement approaching that of successful surgery. Prpgression of small and medium-sized curves (60 degrees or less) has been routinely halted. Few curves progress with adequate brace treatment. Occasionally, improvement in deformity and curve measurement is significant, but loss of improvement seems to be gradual and almost uniformly present to some degree after cessation of treatment. A much longer follow-up period will be necessary if the improvement seen with Milwaukee brace treatment can be considered "permanent." Milwaukee brace treatment is effective in skeletally immature patients with small, flexible and nondeforming curves. Corrective surgery is recommended for deforming curves in all patients for whom permanent improvement is the goal.


Anterior fibular strut grafting in the treatment of kyphosis. An intact segment of autologous fibula provides a strong, physiologic, anterior support in the surgical treatment of short segment kyphosis. In this series of 20 patients, only 3 had no signs of spinal cord injury. Correction averaged 20 degrees. At an average follow-up of 2.2 years, 9 degress of the previously obtained correction were maintained, including 3 patients with non-union and marked loss of correction. Twenty-four complications were noted in association with traction, surgery, and immobilization. The results suggest that attempts at correction should remain secondary to those of stabilization and relief or prevention of neurologic problems. Supplementary posterior spinal fusion is necessary to increase the strength of the stabilized segment as well as decrease the incidence of pseudoarthrosis and loss of correction.


The treatment of paralysis associated with kyphosis: role of anterior decompression. A multi-disciplinary team approach is essential to achieve good results and to reduce morbidity and mortality from anterior spinal cord compression due to kyphosis. There are several procedures for the individual patient management. The absolute indication is progressive neurological deficit. Preoperative investigations should include detailed neurological, neuro-urological, roentgenological and myelographic and pulmonary function measurements. Intraoperative management of patient positioning, exposure, ostectomy, hemostasis and replacement of blood loss require special attention. Postoperative and long term follow-up observations are necessary for good patient care.


Stress fractures of the calcaneus in women marine recruits. Stress fractures of the calcaneus constitute about 25% of all stress fractures seen during Marine recruit training, and are often bilateral. The incidence can be correlated with individual physical condition at the onset of training. There was no correlation with age, height, weight, or foot architecture. In 114 women Marine recruits the incidence was 10.5%. The principal factors involved in the occurrence of this fractur are: the types and mechanism of application of forces to the calcaneus, the musculo-skeletal architecture of the foot and ankle, and the initial physiologic condition of the individual.


The Boston brace system for the treatment of low thoracic and lumbar scoliosis by the use of a girdle without superstructure. A brace for the non-operative treatment of scoliosis constructed without a metal superstructure is preferred by teenage patients. Preliminary results show that a 50-60% correction can be achieved as measured on standing X-rays in the brace. Three quarters of these patients have no skin problems associated with brace wearing. In several years when these patients have reached skeletal maturity and have spent 1 year out of their braces, it will be possible to determine whether the short term results are comparable to the standard set by the Milwaukee Brace.


Osteoid osteoma of the cervical spine.

Osteoid osteoma of the cervical spine. Four cases of cervical osteoid osteoma occurred predominantly in the adolescent age group with either pain, pain with scoliosis, or radicular pain usually without neurological signs. The initial X-rays did not demonstrate the lesions but a high index of suspicion led to additional roentgenographic as well as tomography examinations and eventually an accurate diagnosis. The lesions were located in the posterior elements in all 4 cases. Treatment consisted of excision in 3 cases and excision and fusion in one case and resulted in cure with no recurrence.


Current status of anterior spine surgery for scoliosis. The greatest need for anterior spine surgery is for those cases that have neurological involvement with pressure or stress forces exerted on the spinal cord. With anterior decompression excising anomalous bone, shortening the spine with posterior osteomies, and correction with Harrington instrumentation, many of these cases were protected against neurological sequelae as well as correction of the deformity. Anterior spine reconstruction is a 2-stage procedure. The procedure protects against damage to the blood supply, untethers the spinal cord, corrects deformity, and stabilizes the spinal column. As more cases that can benefit from anterior spine correction of scoliosis are recognized, the expertise to deal with these lesions continues to grow.


Deltoid muscle abduction contracture.

Deltoid muscle abduction contracture. A child with an abduction contracture of the left shoulder secondary to diffuse fibrosis of the deltoid muscle was successfully treated by recession of the inserting muscle fibers proximally. Previously reported cases of deltoid muscle contracture were secondary to fibrous cords or nodules within the muscle. This patient's contracture may be related to either a brachial plexus birth injury or may be similar to the idiopathic fibrosis seen in the quadriceps muscle.


A modified brace (Prenyl) for scoliosis. Sixty-six skeletally immature patients with idiopathic scoliosis were treated with a Prenyl brace and their results were analyzed. Fifty-three patients (80%) showed a satisfactory response. The best results were obtained in patients with lumbar curves and thoracolumbar curves less than 40 degrees. Advantages of this brace are simplicity of fabrication and fitting, patient comfort, patient acceptance and relatively low cost. The disadvantages of this brace are that it is less effective in thoracic curves in the upper thoracic spine, double major curves and kyphosis. It probably causes more significant chest restriction than the Milwaukee brace.


Modern orthotics for spinal deformities. Four basic types of orthoses are now being used at the Twin Cities Scoliosis Center for the treatment of spinal curvatures. The Milwaukee Brace, either custom-made or using a prefabricated pelvic section is the orthosis of choice for thoracic scoliosis and kyphosis in the ambulatory child. For lumbar and thoracolumbar curves, the one-piece "TLSO" has proven the most effective design. For the collapsing spine of myelomeningocele, childhood paraplegia, and spinal muscular atrophy, the 2-piece bivalved polypropylene body jacket is excellent. For the severely involved cerebral palsy or Duchenne Dystrophy patient, the Chair Insert type Sitting Support Orthodosis is preferable.


Prevention of thromboembolic disease by external pneumatic compression in patients undergoing total hip arthroplasty. A prospective study was undertaken in order to test the efficacy of intermittent calf compression for prevention of thromboembolism in patients undergoing total hip arthroplasty. The patients were studied pre- and postoperatively by routine Doppler ultrasound examinations in addition to clinical assessment. Statistically significant evidence substantiates the view that intermittent calf compression decreased the incidence of thr thromboembolic problem.


Stainless steel fiber reinforcement of polymethylmethacrylate. The reinforcement of polymethylmethacrylate with small caliber stainless steel fibers can significantly improve its mechanical properties. While maintaining all the advantages of unreinforced polymethylmethacrylate, it can be demonstrated that compression, flexural tension, tension and impact parameters of cement reinforced with one quarter inch long steel fibers are dramatically enhanced. Careful cement preparation further improves these properties. The polymerizing composite is easily prepared within the operating room and the exothermic reaction is not as severe as the unreinforced material. Furthermore, the metal fiber reinforcement provides the potential for core heating, the capability of depolymerization to facilitate cement removal, and invites research on new prosthetic stem designs.


Occult injuries of the pelvic ring.

Occult injuries of the pelvic ring. With major trauma to the pelvis, injuries at more than one site within the pelvic ring are common. However, minor injuries seem to result in isolated fractures most frequently of the pubic rami. By means of the bone scan we have demonstrated in 6 consecutive cases that these apparent isolated injuries are associated with disruptions elsewhere within the ring, usually the acetabulum or sacroiliac joints. This finding may explain the complaints of pain in the sacral region or about the hip in some patients following isolated fractures of the pubic rami.


Internal derangement of the knee caused by a loose fragment of methylmethacrylate following uni-compartmental total knee arthroplasty: a case report. Internal derangement of the knee joint following uni-compartmental total knee arthroplasty was caused by a loose fragment of methylmethacrylate lodging in the normal compartment of the knee joint.


The use of a peritoneal catheter for the irrigating system in arthroscopy: a better system for accurate diagnosis. The use of a peritoneal catheter enhances diagnosis using arthroscopy by affording a clear visibility of the knee joint. The accuracy in diagnosis is significantly enhanced using this method of irrigation. No better method of irrigation is available for cases of acute knee joint injuries.


A techinque for recording the results of knee surgery. A research form for recording clinical data relating to the arthritic knee is described. Data are recorded using a numerical code which facilitates transfer to a computer and provides an easily read record. Any form must be a compromise but the one described has been proven clinically by providing the data for a multi-center evaluation of hundreds of knees observed over a period of 5 years. A shorter form is described for routine follow-up purposes.


The presentation of the results of knee surgery. A method is described by which the detailed results of knee surgery may be presented in a compact, readily understood and easily analyzable fashion. The data can be analyzed and presented either manually or by a computer and if the latter is used no special print-out equipment is required. The success of the method has been proved over a 5-year period in the monitoring of the results of a multi-institutional investigation of total knee arthroplasty.


Bilateral compartment syndrome associated with androgen therapy: a case report. A patient being treated with androgens developed an acute bilateral compartment syndrome. Androgens are known to cause hypertrophy of muscle, which in a closed fascial compartment may predispose to a compartment syndrome. While an acute syndrome has not been reported previously, patients on androgen therapy frequently complain of cramps and leg pain, which may be manifestations of chronic compartment syndrome. The above case report does not establish a positive cause and effect relationship, but because this occurrence has not been documented before we believe the relationship should be considered. Patients on androgens should be examined for the possibility of compartment syndromes, either acute or chronic. The actual compartment pressures can be measured in suspected cases.


Congenital kyphosis.

Congenital kyphosis. Congenital kyphosis is an uncommon, but potentially devastating anomaly of the spine. Without treatment, the tendency is for severe, and sometimes catastrophic deformity. It is the most common etiology for spinal cord compression due to spine deformity, excluding tuberculosis. Few patients have nonprogressive benign lesions. Late treatment is difficult and dangerous. Braces and other forms of non-operative treatment do not work. The best treatment is early posterior fusion, before the curve reaches 50 degrees and before age 5 years. For curves over 60 degrees and over age 5, both posterior and anterior fusion are necessary. If cord compression exists, laminectomy is contraindicated. Anterior cord decompression and fusion are required.


A versatile surgical approach to the hip. A versatile surgical approach to the hip is presented which allows for total accessibility to the anterior, the lateral, or the posterior aspect of the hip through a single skin and fascial incision. The approach through an S-shaped incision is recommended for total hip replacement arthroplasty, femoral head replacement, hip nailings, fracture dislocations of the hip, and sciatic nerve explorations.


Changes in the calcar femoris in relation to cement technology in total hip replacement. Radiological changes in the calcar femoris after total hip replacement, in 97 hips where an extreme valgus position of the prosthesis had been achieved, were compared with 119 hips where the alignment of the prosthesis ranged from varus to only a moderate degree of valgus. In the series with extreme valgus there was a minimum of 1 cm of cement between the calcar femoris and the prosthesis, whereas in the other series the thickness of cement averaged 4.5 mm. In the series with thick cement destructive changes in the calcar were reduced by a factor of 10 and there were no examples of incipient subsidence of the femoral prosthesis. This comparison was based on a follow-up of only 2 years.


Arthrodesis for disabling hip pain in children and adolescents. A 9-year follow-up study of patients who had hip fusion for disabling hip pain in childhood suggests that arthrodesis for disabling hip pain in children is effective and well-tolerated. The patients had excellent functional results with return to normal childhood life styles, athletics, and later productive occupations. No patient wanted or needed conversion to a total hip replacement at follow-up. The fused hips adducted progressively until skeletal maturity. The surgeon should make allowances for future adduction in selecting the position of postoperative immobilization-fixation of a child's hip.


Osteoid osteoma and osteoblastoma. Similar histologic lesions with different natural histories. A study of 9 new cases of osteoid osteoma and 3 new cases of osteoblastoma demonstrated very similar histologic findings. Both lesions were extremely vascular and frequently showed areas with histologic features of an aneurysmal bone cyst. Differentiation between the 2 lesions often depended on their clinical features and radiographic appearances. A review of 851 osteoid osteomas and 181 osteoblastomas from the literature supported a difference, however, in the natural history of the 2 lesions with osteoid osteomas tending toward regression, and osteoblastomas tending toward progression and possible late malignant transformation. Osteoid osteomas were found to have a 4.5% recurrence rate compared with a 9.8% recurrence rate for osteoblastomas (p less than 0.01). No recurrence has ever been reported after complete en-bloc resection of either lesion and this must be considered the surgical treatment of choice for both lesions where possible. Despite apparent incomplete excisions, cures are achieved in many cases among both lesions.


Inorganic pyrophosphatase activity distinct from alkaline phosphatase in rat bone. The existence of a specific inorganic pyrophosphatase (PPi ase), distinct from alkaline phosphatase in bone has been suggested but is often regarded as questionable. In the present investigation, several features of PPi ase activity have been demonstrated, which suggest that it represents an enzyme protein different from those splitting phosphomonoesters and ATP. PPi ase was largely destroyed during extraction with n-butanol, which facilitated the solubilization of alkaline phosphatase and ATP splitting enzymes and only partially destroyed acid phosphatase. Two major groups of phosphate esters and pyrophosphates splitting enzymes were separated by gel filtration from homogenates of rat bones. The first pool contained high ATP-ase and phosphomonoesterase activities, but only low activity against inorganic pyrophosphate (PPi) in the presence of MgCl2. The second pool was most active against PPi at pH 7.5 in the presence of excess MgCl2 and only slightly hydrolyzed phosphomonoesters or ATP. Immunodiffusion showed that these 2 pools contained 2 distinct proteins. It was concluded that there exists a specific inorganic pyrophosphatase distinct from phosphomonoesterases and ATP-ases in bone tissue.


Experimental delayed union of the dog tibia and its use in assessing the effect of an electrical bone growth stimulator. A technique has been described for the consistent production of delayed bone healing of the tibia in an animal model. A controlled double blind trial, where independent observors did not know the coding of the stimulators and did not collaborate with each other, has evaluated the use of a direct current bone growth stimulator in such an animal model. The conclusion of the experiment is that this commercially available direct current stimulator does produce a significant acceleration of bone healing at 4 weeks in the experimental model used. There is no evidence of inflammatory or neoplastic changes. The eventual clinical role of electrical bone stimulation remains uncertain and many questions remain unanswered, but are promising enough to encourage a controlled clinical trial in situations of disturbed bone healing. Electrical stimulation is apparently safe and appears to significantly augment bone formation. A controlled clinical trial is now being carried out in major medical centers in Australia.


The effect of methylmethacrylate on complement activity. The effect of methylmethacrylate on the activity of the complement sequence has been investigated in vitro by standard hemolysis techniques. It was demonstrated that concentrations of methylmethacrylate monomer as low as .25% inhibit the reactions of the complement sequence by 50%. Methylmethacrylate concentrations of 2.5 to 5.0% abolished all complement activity. This effect is on the late-acting components of the complement sequence which are important for chemotaxis of polymorphonuclear leukocytes, immune adherence of bacteria to polymorphonuclear leukocytes, phagocytosos of bacteria by polymorphonuclear leukocytes, and bacteriolysis.


99Technetium bone scanning in experimental osteomyelitis. A rabbit model of experimental osteomyelitis was used in an attempt to clarify the natural history of bone infection associated with positive scintigraphic and negative radiological findings. In this model a pathogenic strain of Staphylococcus aureus is injected in the proximal metaphysis of the tibia of a rabbit, 15 minutes following the injection of a sclerosing agent. Scintigraphies were performed at 3, 5, 12, and 19 days following this procedure; 99m-Technetium phosphate compounds were used indifferently. On days 5, 12, and 19 a roentgenogram of the lower limbs was taken. Animals were sacrificed at random 6, 14, and 21 days following the procedure. Against expectations, the standard radiological procedure was more sensitive than the scintigraphic technique. The probability of finding a positive bone scintigrapy in the presence of osteomyelitis P(S+/O+) was 15/19 or 0.78. For the roentgenograms P(X+/O+) = 16/17 = 0.94. On pathological review the scintigraphic findings remained unexplained when fibrosis, periosteal reaction, granulocytic infiltration, and new bone formation were considered separately. In half of the cases the early scintigraphies revealed decreased uptake on the affected side, but this finding did not predict whether the final scintigraphy was positive. Finally, positivity was obvious in all cases, and a continuous range from negative to positive could not be documented. Present findings are a characteristic feature of the model. The physiological mechanism remains to be explained by independent measurements of relative bone blood flow made simultaneously with the scintigraphy and other bone tissue specific factors.


Acute elevation of intracranial pressure following transection of non-functional spinal cord. A spinal cord which is neurologically nonfunctional may be functioning as a conduit for CSF between the ventricular system and the spinal subarachnoid space. Interruption of this pathway can have catastrophic consequences unless there is an adequately functioning shunt.


Juvenile kyphosis.

Juvenile kyphosis. Scheuermann's disease is a common cause of kyphosis developing in the juvenile period. Untreated, the deformity may progress, producing significant pain and, rarely, neurologic signs and symptoms. Successful treatment is possible with the Milwaukee brace, provided that the child has not reached skeletal maturity. Bracing will produce a superior result in terms of correcting the deformity and reversing vertebral wedging. Surgery may occasionally be necessary for severe kyphosis, especially in the adult who presents with pain and/or neurologic problems. Combined anterior and posterior approach is the preferred surgical procedure.


Kyphosis secondary to infectious disease. Infections of the spine usually involve the vertebral body and therefore by definition produce a kyphosis. Non-tuberculous infection usually staphylococcal and in the lumbar spine, is often diagnosed late and can involve the cord. Open exploration and stabilization with graft should therefore be considered. The destruction is usually less extensive and therefore the kyphosis less severe than in late neglected tuberculous infections. Tuberculous spinal infection accounts for 59% of all orthopedic tuberculosis. It invariably involves vertebral bodies and is progressive. Destruction of the bodies is by infection and avascular necrosis, kyphosis is inevitable and cord compression a common threat. While L-1 is the most commonly affected body T-10 is statistically the most commonly associated with cord compression. The treatment of spinal tuberculosis should be aimed at correcting 5 basic defects associated with the disease and the deformity: mechanical instability; chronic smoldering infection; spinal cord and nerve root compression; disturbance of spinal growth; depressed lung function. The cornerstone to effective treatment for spinal tuberculosis is drug therapy and the anterior fusion operation. For the established tuberculous kyphosis, which is always a fixed deformity, multiple staged operations and gradual correction used the Halo-pelvic apparatus is the best treatment available at present.


Kyphotic deformity of the spine in ankylosing spondylitis. Patients who present with apparent kyphotic deformity of the spine associated with ankylosing spondylitis may have their main deformity in the hip joints, in the lumbar spine, the thoracic spine, or it may be primarily cervical in situation. If any major correction is to be carried out, then the correction should be done in the area of the main deformity. Deformity in each of these areas is amenable to surgical correction, but this requires a very careful assessment, meticulous preoperative planning, and very precise attention to operative technique to allow reasonably consistent success without major risk to the patient.


Post-laminectomy kyphosis.

Post-laminectomy kyphosis. Post-laminectomy spinal deformity occurs in 50% of children undergoing laminectomies for cord tumors. Kyphosis is the most frequent deformity found. The integrity of the facet joints appears to be one of the most important factors in the development of this kyphosis. More children are surviving after treatment of these tumors and a pessimistic attitude is not warranted. Observation of a progressing deformity is not acceptable treatment. When kyphosis develops, early prompt bracing must be started. For a progressive or severe kyphosis, an anterior spine fusion is indicated. This is reinforced by a posterior fusion with Harrington instrumentation. Surgical reconstruction is indicated in children recovering from extensive laminectomies but with a good prognosis.


Wide-track polycentric total knee arthroplasty: one year follow-up study. The use of a peritoneal catheter enhances diagnosis using arthroscopy by affording a clear visibility of the knee joint. The accuracy in diagnosis is significantly enhanced using this method of irrigation. No better method of irrigation is available for cases of acute knee joint injuries.


Immunological aspects of the pathogenesis of pregnancy hypertension. Changes involving the immune system may be instigators of, or consequent upon, disorders in other systems in the natural history of gestosis. The extent of the immune 'disorder' may not correlate with the severity of the disease as manifest in either eclampsia or fetal death. A number of variables, e.g. hormonal and genetic, could affect any immunological trigger mechanism or any secondary altered immune response. Thus attempts to find an immunological factor in gestosis that operates in all cases may prove unrewarding. Certain matings, immunogenetic constitutions, or certain feto-maternal immune relationships may predispose to a particular pathology and directly or indirectly potentiate other pathological processes. Others may either have no effect or conceivably have even a homeostatic effect protecting the maternal host from pathological change. The picture of the role of immunological factors in the pathogenesis of pregnancy hypertension is no more, as yet, than a few hesitant, unrelated lines. However, the lines are getting more numerous and stronger.


A software system to record and analyze digitized cell images. This paper describes basic software for digitization and processing of microscopic cell images used at the Department of Clinical Cytology at Uppsala University Hospital. A family of programs running on a PDP-8 minicomputer which is connected to a Leitz Orthoplan microscope with two image scanners, one diode-array scanner and a moving-stage photometer, is used for data collection. The digitized image data is converted by converted by conversion program to IBM compatible format. The data structures for image processing and statistical evaluation on the IBM system are also described. Finally, some experiences from the use of the software in cytology automation are discussed.


Two-sample Kolmogorov-Smirnov test for truncated data. A nonparametric statistical test to compare two cumulative frequency distribution functions is presented that can be used even when both samples include censored data, as is often the case when comparing the survival of two groups of laboratory animals under conditions in which the experiment is terminated before all the animals die. (Such a design can produce considerable savings and is to be recommended.) The program calculates exact probabilities for both the one-sided and two-sided alternatives to the null hypothesis, applicable to the case of equal group size, as well as the corresponding general asymptotic values; a continuity correction is employed that markedly improves the asymptotic approximation. Expressions are stated in terms of two different but related statistics, and the one that utilizes more information in any particular set of data is selected for the probability calculations. All basic equations and definitions are provided.


The decomposition of a distribution into Gaussian components (Algol program. The paper attempts to give a practical solution to the problem of decomposition of a mixture of Gaussian components. The results of an earlier paper [1] have been used and the described algorithm has been revised and improved. A complete Algol program is given with all the necessary comments and descriptions and with results of testing examples.


Acquiring multichannel analyzer spectra with a mini computer. Spectra are produced on a multichannnel analyzer from biological samples with monochromatic fluorescent X-radiation. This mini-computer system is designed (1) to provide spectral data in a form immediately usable for computation, (2) to provide a great number of spectra stored on magnetic tape, (3) to examine the spectra in the laboratory before committing the spectra to tape and (4) facilitate the examining and manipulation of data in the laboratory. The spectra on the tape are used in high-level analyses. The mini-computer can examine parts of a spectrum, plot and print the values, identify and integrate peaks, all at the user's discretion.


A portable integer FFT in FORTRAN.

A portable integer FFT in FORTRAN. A radix 2 integer fast Fourier transform is organised for compatibility among small computer systems by simulating binary fraction multiplications and bit reversal as functions in basic FORTRAN. After installation the efficiency can be improved by machine code replacement of some parts.


Analysis of sudden deaths in a district of Bohemia in the period 1971--1973. A clinico-pathologico-anatomical analysis of 150 cases of sudden death in a district of Bohemia in the period 1971--1973 revealed coronary atherosclerosis as the most frequent cause of sudden death(87.3%); stenosing coronary atherosclerosis without postmortally detectable myocardial necrosis participated by 71.7% in the coronary group. Men, especially in younger age groups, were more frequent victims than women. Within one-hour duration of the terminal episode, 57.3% of the deaths occurred; 45.3% of the decreased succumbed to sudden death at their homes. With advancing age, severe findings in the coronary vascular bed and in the myocardium became more frequent. One half of the victims of sudden death in the coronary group had histories of ischaemic heart disease; 37 suddenly deceased persons (28.2%) had experienced myocardial infarction. In another 25 victims of sudden death scars after formerly asymptomatic myocardial infarcts were found.


A study of the catabolism of fibrinogen after myocardial infarction. The catabolism of fibrinogen was studied during the first week of acute myocardial infarction in twenty-three patients and in ten control patients. A trial was carried out using 125I-labelled fibrinogen. After myocardial infarction, the mean biological half-life of fibrinogen was 62.5 +/- 10.0 h and the mean plasma loss of fibrinogen per 24 hours was 34.1 +/- 6.9% of the intravascular fibrinogen pool. In the control group, respective values of 89.6 +/- 9.9 and 23.4 +/- 3.9% were obtained, which were in close agreement with published values for the normal catabolism of fibrinogen. The fractional catabolic rate of the intravascular fibrinogen pool was significantly increased in patients with myocardial infarction in contrast to the absolute plasma loss of fibrinogen which appeared to be the same as in subjects with normal plasma fibrinogen concentration. Possible explanations of the accelerated catabolism of fibrinogen after myocardial infarction are discussed.


Prognostic value of an abnormal P terminal force in lead V1 at onset of acute myocardial infarction. The presence of an abnormal P terminal force of the P wave in lead V1 (PTFV1) was demonstrated on the initial electrocardiograms in 69 of the 200 patients with transmural acute myocardial infarction. 61.5% of the total cases with a lethal outcome during hospitalization belonged to this group. The mortality of the patients who presented this ECG sign of left atrial hypertension at the onset was 53.7%, thus differing significantly from that in patients without the sign (22.1%). The PTFV1 anomaly has a prognostic value in patients without complications as well as in those with heart failure at the onset of the disease. The appearance during hospitalization of major arrhythmias and disturbances of conduction and of sudden death is significantly correlated to the presence of abnormal PTFV1 on the admission electrocardiograms.


Long-term prognosis of juvenile hypertension. A longitudinal study of juvenile hypertension made possible to investigate after 20 years 73% of a group of young hypertensives (original age 14--29 years, arterial blood pressure 170/100 and higher 20 years ago), which was originally investigated in 1952--1954. The surprising result was that 35.5% had a normal blood pressure without treatment in the interval, 40.2% showed the same level of hypertension, 5.7% showed higher blood pressure levels but without any new organic changes, 1.5% had the same blood pressure as 20 years earlier, but now required drug therapy as opposed to previously. Only 17.1% of the patients showed any convincing evidence of progression of the disease, i.e. the development of new organic changes. The prognosis of moderate hypertension at a young age is significantly correlated with: a) the occurence of hypertension in the parent; b) the life expectancy of the parents; and c) the initial values of blood pressure. There was no correlation between prognosis and over-weight, weight gain in the past 20 years, original or present heart rate, smoking, alcohol intake or physical activity, participation in sports or the living standard of the given individual.


Physical working capacity of young ice-hockey players. In 77 systematically training young ice-hockey players aged 11--13 years their physical working capacity was assessed by the bicycle ergometric test PWC-170, and their heart volume was measured teleroentgenometrically. The physical working capacity of young ice-hockey players considerably exceeded that of their non-training coevals and older children. A positive correlation was found between the magnitude of the physical working capacity and the heart volume: the greater the initial heart volume, the higher the physical working capacity.


Some aspects of potential new usages of Korotkov's method. Synchronous tracings of Korotkov's sounds, electrocardiogram, and pressure in sphygmomanometer cuff make possible to construct a curve whose shape is practically congruent with the ascending limb of the arterial pressure wave; the curve is usable for determining several haemodynamic indicators, namely, the maximal and minimal pulse, and mean pressures, pulse wave propagation velocity, and myocardial contraction capacity. When arterial sounds are objectively recorded with dur regard to the cuff dimensions and adherence to the "ipsilaterality principle", the error of pressure measurement does not exceed 4--5 mmHg.


Renin activity in the brain, the kidneys and the peripheral plasma or rats with different experimental models of hypertension. Renin activity (RA) in peripheral plasma, as well as in renal cortex and brain (cortex, stem and medulla) homogenates of rats with spontaneous, Goldblatt, NaCl, adrenal-regeneration and neurogenic hypertension was biologically assayed. The results suggest that RA exists not only in the brain of normotensive but of hypertensive rats as well. RA in the medulla is higher than in other brain areas and in the kidney, both in normotensive and in hypertensive rats with the exception of rats with adrenal regeneration and NaCl hypertension. In most of the experimental forms of hypertension (neurogenic, renal, spontaneous) in which RA in the medulla is increased, the role of the brain renin-angiotensin system seems to predominate, while in forms in which renal RA is elevated (adrenal regeneration) the kidney renin system most probably plays a more important role. A definite inverse interrelation between the brain and the kidney renin-angiotensin systems was established. The interrelation between the two renin systems in NaCl hypertension could not be evaluated, since exogenous factors (Na), which interfere with the kidney renin system, play a considerable role in the pathogenesis of NaCl hypertension.


Investigations of capillary network in the myocardium, skeletal muscles, and other organs by modified Gomori's method for determination of acid phosphatase activity. A modification of Gomori's sulfide method for the determination of acid phosphatase activity is presented, which visualizes the walls of all capillaries in the myocardium, skeletal muscles, synovial membranes, and some other organs (liver, kidney). Blocks of investigated organs (edge lengths 2--3 mm) are cold-fixed in acetone for 2--3 days. Fixed frozen tissues are cut to sections 90--120 micrometer thick and incubated for 2--3 days in an incubation mixture (1% lead/II) acetate, 90 ml; acetate buffer solution pH 6.2, 10 ml; 2% sodium beta-glycerophosphate 1 ml. The sections are then processed with 0.5% sodium sulfide solution for 10--15 min and embedded into glycerine-gelatin gel. In preparations processed in this way, acid phosphatase is visualized on the walls of all capillaries and precapillaries, makig visible the capillary network. In addition to the capillaries, the transverse striation of myofibrils is visualized as well. The described method is useful for investigating not only the cytochemistry of the vascular wall, but also the blood supply to the myocardium, skeletal muscles, and other organs in both normal and pathological states.


The effect of stimulation of the stellate ganglion on excitability of the heart. Stimulation of the stellate ganglion leads to a shortening of the effective refractory period of the heart, while the electrical systole duration decreases in normal heart condition only secondarily in consequence of the increase in heart rate. In myocardial focal ischaemia stellate ganglion stimulation leads to an increase in the electrical systole time, the refractory period of the heart significantly shortens and the repolarization of the heart becomes inhomogenous. Consequently, the arrhythmogenic effect of a sympathetic excitation manifests itself mainly in myocardial ischaemia.


Efficacy of monophasic electrical impulses with steep leading and trailing edges in cardiac defibrillation. Experiments on dogs were performed to investigate the efficacy of various defibrillation impulse waveforms. The results showed that the decisive factors for the effectiveness of the defibrillation impulse of certain shape are its relationship to the carciac tissue accomodation and the duration of the suprathreshold current flow. For cardiac defibrillation the most convenient impulse is therefore the impulse with the highest rate of rise of the leading edge as well as the trailing edge. The amplitude of the rear trailing edge of the defibrillation impulse should be either equal or higher than the amplitude of the front leading edge. That means that rectangular or trapezoidal impulses with an ascending slope may be most conveniently used for cardiac defibrillation. The biologically optimal duration of the trapezoidal impulse with an ascending slope proved to range from 7 to 14 msec. The authors emphasize the inevitability of additional characteristics of the defibrillation impulse by its peak current and total energy contents.


An equation illustrating the relationship between haemodynamic factors and renal sodium excretion. An equation is presented permitting to assess quantitatively the interrelationships between principal haemodynamic factors (mean blood pressure, renal venous pressure, filtration fraction, renal vascular resistance) and factors influencing the renal sodium excretion (glomerular filtration rate, fractional tubular sodium reabsorption).


Case report: coma due to oxytetracycline. An unusual case is reported of coma of gradual onset in a 67-year old woman being treated with oxytetracycline. Ten hours after the last dose, the patient regained consciousness but remained confused with hallucinations for another 24 hours. The possibility of side-effects should be borne in mind in any patient who develops coma whilst on oxytetracycline.


Gene dose effect: intraband mapping of the LDH A locus using cells from four individuals with different interstitial deletions of 11p. The quantitative expression of LDH A was studied in hemolysates from four patients with different but overlapping interstitial deletions of the short arm of chromosome 11. Deficiency of LDH A was demonstrated in one patient, and the LDH A locus has been assigned to that segment of 11p for which this patient alone was deficient, i.e., to band 11p12 (region 11p1203 leads to 11p1208).


Assignment of the gene for glyoxalase I to region p21 leads to pter of human chromosome 6. Using somatic cell hybrids between TK-deficient mouse cells and white blood cells derived from a patient with a translocation of the region p21 leads to pter of chromosome 17, we have assigned the gene for human GLO, to region p21 leads to pter of chromosome 6. Since the HLA region is only 10 cM distant from GLO, these results also confirm that the HLA region is located on the short arm of human chromosome 6.


Five early milestones in premature infants. The onset of five early milestones was studied in premature and full-term infants. The milestones are: recognition of mother's voice and face, 3-month smile, following through 180 degrees, and two hand-eye coordination. It was hypothesized that premature infants would show delay in acquiring milestones related to time separated from mother. Compared to full-term infants, the prematures had a significant difference in the means only for the onset of smiling, and no effect related to maternal separation.


Behavioral and neurological comparisons of neonates born to mothers of differing social environments. Sixty newborn infants, 30 born to parents of middle to upper-middle socioeconomic status and 30 born to parents of limited personal-social resources, were assessed on the Neonatal Behavioral Assessment Scale. Although no difference between groups was found in motor and neurological status, data from this study did indicate that the prenatal factors, having no obvious physiological base, associated with the parental social environment, may affect the newborn's behavioral outcome.


Milieu therapy under the primary caretaker system at the University of Michigan's Children's Psychiatric Hospital. The inpatient service at the University of Michigan's Children Psychiatric Hospital is a multidisciplined program whose purpose is to create a therapeutic milieu in which emotionally disturbed children can live while being effectively treated. The work of the primary staff as milieu therapist on the ward is a key factor in the success or failure of many cases. This paper describes the therapeutic milieu, the primary caretaker system of staffing, and the specific role of the primary staff as milieu therapist at the hospital.


Single-subject design and interaction analysis in the behavioral treatment of a child with a feeding problem. A research paradigm, including an AB1AB2 single-subject design was developed and used in conjunction with an adult-child interaction analysis methodology to evaluate the effectiveness of a behavioral treatment approach to a feeding problem in a 2 1/2-year-old male. The results indicate that after nine treatment sessions, the child's diet was appropriate and the undesirable mother-child interaction pattern was changed. In addition, the interaction analysis methodology was used to evaluate the therapist's behavior modification techniques so that these could be taught to the mother. This study continued the previous endeavors to delineate feeding problems in children and subsequently to treat these problems with a behavioral approach. This kind of systematic research, with functional analysis of presenting problems and specification of the therapist's treatment behavior, is offered as a clinically appropriate paradigm for psychotherapy and behavior modification research.


The attachment of a retarded child to an inanimate object: translation into clinical utility. This paper describes the relationship of a moderately retarded boy with autistic features to an inanimate object, relates this relationship to his emotional development, and suggests methods for utilizing observations of his behavior with the object for assessment of cognition. The authors suggest that the object differs only qualitatively from a transitional object. Implications for the evaluation of retarded children include the necessity for approaches identical to those used in evaluating intellectually normal children and interdisciplinary assessment with combinations of behavioral and dynamic techniques. Implications for parent counseling, institutional policies, therapeutic practice, psychological assessment, and personality theory are outlined.


Chromosome location of the ribosomal RNA genes in Triturus vulgaris meridionalis (Amphibia, Urodela). II. Intraspecific variability in number and position of the chromosome loci for 18S + 28S ribosomal RNA. Ribosomal genes have been localized on mitotic and lampbrush chromosomes of 20 specimens of Triturus vulgaris meridionalis by in situ hybridization with 3H 18S + 28S rRNA. The results may be summarized as follows: 1) each individual shows positive in situ hybridization at the nucleolus organizing region (NOR) on chromosome XI; 2) in addition, many specimens exhibit a positive reaction in chromosomal sites other than the NOR (additional ribosomal sites); 3) the chromosomal distribution of the additional sites appears to be identical in different tissues from the same specimen and to follow a specific individual pattern; 4) the additional ribosomal sites are preferentially found at the telomeric, centromeric or C-band regions of the chromosomes involved.


The effects of ageing on the meiotic chromosomes of male and female mice. The effects of age on the chiasma frequencies, chiasma position and numbers of univalents at MI in males and females of three strains of mouse were examined. Males showed a slight but non significant rise in chiasma frequency in age due to an increase in bivalents with two chiasmata at the expense of single chiasmata bivalents. In contrast, females exhibited a significant decrease in chiasma frequency with age due to the loss of two chiasma bivalents with a corresponding increase in single terminal chiasmata bivalents. In both males and females there was no significant increase in univalents with age in the strains studied. Of interest was the finding of a greater degree of contraction of the MI chromosomes in the oocytes of old relative to young females, a differential contraction that was independent of culture time. This finding is discussed with regard to the "production line theory" and non disjunction at Anaphase in other strains of mice.


The repetition frequency of DNA in Balbiani ring 2 of Chironomus thummi. The RNA of Balbiani ring BR2 of polytene chromosomes from Chironomus thummi salivary glands was microisolated and reassociated in the presence of an excess of total larval DNA. BR2 RNA reacts as a single component with a C0t 1/2 of 8.6. Ribosomal precursor RNA from microisolated nucleoli reassociates under identical conditions with a C0t 1/2 of 12.3. These C0t 1/2-values suggest repetition frequencies in the range of 35 and 50 for ribosomal DNA and Balbiani ring 2 DNA, respectively. The data presented here favour the view that the gene for BR2 RNA of C. thummi is internally repeated and contains only one type of DNA sequence.


Astigmatism of the mammalian cornea: evolutionary and perceptive significance. Astigmatism enables spatial, linear and directional discrimination. These faculties are demonstrated by astigmatic photographic experiments. Comparative anatomic deductions lead to the assumption that the eyes of early mammals were astigmatic. Thereby these animals, lacking binocularity and accommodation, could achieve visual spatial information. This assumption is supported by the fact that features of astigmatic refraction, specially straight linearity, have been adopted by various intra-ocular structures, and by the neuronal structuralisation of receptive fields in the visual cortex of mammals.


Usher's syndrome: electrophysiological tests of the visual and auditory systems. The symptoms of Usher's syndrome - congenital hearing impairment and tapetoretinal dystrophy - are difficult to detect in young children. The electroretinogram (ERG), visual evoked potential (VEP), auditory nerve and brain-stem responses as well as the cochlear microphonic potentials were used to evaluate the defects of the visual and auditory systems in 20 patients, 3-45 years of age. This study demonstrates the usefulness, reliability and convenience of the electrophysiological tests for early diagnosis and functional evaluation of Usher's syndrome.


Circannual variation in human erythrocyte adenosine aminohydrolase. In serially independent samples of blood from apparently healthy subjects controlled as to clock-hour of blood withdrawal but not as to any circannual changes in circadian state, human erythrocyte adenosine aminohydrolase undergoes a statistically significant circannual rhythm, which may or may not be aliased. This rhythm is also demonstrated in patients with a variety of neoplastic diseases and it occurs around a statistically significantly lower mesor in patients with a variety of malignant tumors investigated.


Visual phenomena following light coagulation in central serous retinopathy (CSR). A report on three patients with illustrations of their visual anomalies following light coagulation for their CSR disease is presented. The correspondence of the phenomena illustrated with the ophthalmoscopically visible fundus changes prove their objective origin.


[Pneumatosis cytoides coli. Conservative treatment with oxygen breathing (author's transl)]. Investigations in a 51-year old female patient suffering from severe tenesmus and therapy resistant diarrhoea led to a diagnosis of pneumatosis cystoides coli. After 4 days of treatment with continuous oxygen breathing there was dramatic clinical improvement and an incomplete radiological remission. This new method is an important step forward in the treatment of pneumatosis coli. The only potential side effect is pulmonary oxygen toxicity. Thus limitation of oxygen treatment to the shortest time necessary for abolishing symptoms is recommended. Oxygen breathing is a safe, simple and effective treatment of pneumatosis coli and may replace the currently performed surgical resection of the involved intestinal segments.


[Diagnosis of anticonvulsant osteomalacia in adults (author's transl)]. In 100 epileptic patients under treatment with long-term anti-convulsants, radiographs of the hands and feet, and estimations of serum 25-hydroxycholecalciferol, parathormone, alkaline phosphatase, calcium, and inorganic phosphate were done to detect a medication-induced osteomalacia. The correlation between the individual parameters was investigated. It was shown that the serum 25-hydroxycholecalciferol level and the skeletal radiograph were the most valuable in the early detection of osteomalacia. One of these investigations in addition to routine serum chemistry is recommended for the future at the yearly follow-up examinations of adult epileptics so that early and adequate treatment with vitamin D can be started.


[Determination of porphyrins in red blood cells. Comparison of two methods (author's transl)]. Two methods for measuring porphyrin concentrations in red blood cells were compared, one by Piomelli in which porphyrin is extracted from the RBCs and then measured fluorometrically, the other in which the blood-porphyrin content is measured direct with the hematofluorometer ZnP 400. Sample size is the same for both. Results in 59 patients exposed to lead were evaluated: the correlation coefficient between the two tests was 0.99.


[Hypercalcaemic crises in patients with chronic renal failure caused by ion-exchange resins, antacidotics and other calcium-containing drugs (author's transl)]. Between 1972 and 1976 15 patients with chronic renal failure of different aetiology and varying severity were observed who developed 23 hypercalcaemic phases during treatment with calcium-containing drugs. 12 instances of hypercalcaemia occurred during conservative treated during conservative treatment (serum creatinine 177-1061 mumol/l, equivalent to 20-120 mg/l) and 11 during chronic haemodialysis (serum creatinine 707-1061 mumol/l, equivalent to 80-120 mg/l). In 15 cases hypercalcaemia was caused by a hexacalciumhexasodium-heptacitratehydrate complex (Acetolyt), in 6 cases by the combined use of this drug with calcium ion-exchange resins on a calciumpolystyrolsulfonate base, and in two cases by the use of calcium tablets and calciumpolystyrolsulfonate, respectively. The daily doses of these drugs were in the usual therapeutic range in most cases. Deterioration of renal function was observed in two cases and coma in a further two cases. In 5 cases gastric ulcers were demonstrated. Three patients died. In no patient was there evidence of florid hyperparathyroidism. Treatment with calcium-containing drugs in patients with renal failure should only be carried out under regular control of calcium concentrations.


[Plasma levels of rifampicin and isoniazid and serum levels of aminotransferases in combined tuberculostatic treatment (author's transl)]. During treatment of active pulmonary tuberculosis with isoniazid, rifampicin and ethambutol in 15 patients transaminase activity increased in seven to levels of 60-340 U/l (group I). In the other eight the laboratory values remained within normal limits (group II). Rifampicin levels in group I were significantly raised at 2 and 5 hours after administration of 10 mg/kg body weight on proven fasting. There was no significant difference between the two groups for isoniazid. Estimated half-life of rifampicin was significantly longer in the first than the second group. If there is evidence of chronic liver disease (by history or by chemical tests) the rifampicin dose should be decreased to less than 10 mg/kg body weight.


[Lung functions and blood levels after parenteral administration of theophylline-ethylenediamine (author's transl)]. Theophylline-ethylenediamine (Euphyllin) was given to 45 patients with various degrees of obstructive airway disease, eight receiving 0.24 g i.v., 22 an infusion of 0.72 g over four hours, and 15 an i.m. injection of 0.36 g. Lung-functions, pulmonary artery pressures and - in several cases - theophylline blood levels were measured. The specific bronchial flow resistance was reduced in all patients, by 30% on average, without any significant correlation to the blood level. Ventilation rose by about 15%, while arterial pCO2 and mean pulmonary arterial pressure fell significantly. No effect on respiratory failure to the existing pulmonary hypertension was demonstrated in three patients with decompensated chronic cor pulmonale with 0.72 g by a four-hour infusion. After i.v. or i.m. injection of the same dose theophylline blood levels were at the lower range of effective concentration, which is thought to lie around 5-15 microgram/ml plasma. The results indicate that a specially effective and lasting therapy can be achieved with an initial dose of 0.24 g Euphyllin followed by continuous infusion of 0.72 g over 6-8 hours.


The effect of FSH on LH induced testosterone secretion in the immature hypophysectomized male rat. The effect of gonadotropin pretreatment of hypophysectomized male rats on LH stimulated serum testosterone concentrations was studied. A 5 day pretreatment period began 2 days after hypophysectomy at 21 or 24 days of age. On the day following the pretreatment period the animals received an intraperitoneal injection of saline or LH 60 min before blood collection. Animals pretreated with NIH-FSH-B1, or with doses of LH approximating the amount present in the NIH-FSH, had increased testosterone concentrations after LH stimulation compared to similarly stimulated saline pretreated animals. Pretreatment with more highly purified FSH Ex 199C at a lower dose than the minimum effective dose of NIH-FSH was also effective. There was no synergistic or additive effect when FSH Ex 199C and LH pretreatments were combined. FSH Ex 199C is more potent and contains appreciably less LH contamination than NIH-FSH-B1. The results obtained using FSH Ex 199C indicate that FSH, independent of LH contamination, can increase testes response to LH stimulation.


The effect of ether on formation and dissociation of rat uterine estradiol-receptor complex. The addition of 2% v/v ethyl ether to uterine cytosol incubation mixtures produced a 25% increase in the rat of association of 0 degrees with 3H-estradiol and almost a 3-fold increase in the rate of exchange of estradiol-receptor complex with 3H-estradiol at 20 degrees. Uterine cytosol saturated with non-radioactive estradiol required over 8 hours for complete exchange with 3H-estradiol at 20 degrees while in the presence of 2% ether exchange was complete in 2 hours and revealed about 15% more specific binding sites. The presence of ether in reaction mixtures had no effect on dextran coated charcoal separation on bound from free 3H-estradiol nor on the stability of the receptor on uterine cytosol.


Isolated prolactin and growth hormone granules from bovine pituitary: content and stability are seasonally dependent. Secretory granules containing prolactin (PRL) and growth hormone (GH) as essentially the only proteins were isolated by centrifugation. PRL and GH varied reciprocally in the granule preparations with the seasons. During winter PRL content was lowest (20%) and GH highest (80%); during summer the converse obtained: PRL, 70% and GH,, 30%. Both hormones were in almost equal proportion during the spring. The amount of either hormone released from granules and pituitary slices was directly related to its relative content in the gland. The pattern of PRL release from secretory granules and pituitary tissue in vitro was similar to that reported for blood levels in ruminants: low during winter and high during summer. It is concluded that seasonal factors affect primarily the synthesis and/or storage of PRL and GH, and there exists a direct relationship between intracellular stores and release.


Carboxypeptidase digestion of human chorionic gonadotropin. Native human chorionic gonadotropin (hCG) was resistant to carboxypeptidase digestion even in the presence of urea. Isolated alpha subunit of the hormone (hCG-alpha), though unreactive to enzyme treatment in the absence of denaturant, released up to four amino acid residues from the C-terminus on incubation with a mixture of carboxypeptidases A and B in urea. While an hCG-alpha product which lacked Ser-92 recombined completely with intact hCG-beta, hCG-alpha from which Ser-92 recombined completely with intact hCG-beta, hCG-alpha from which Ser-92 and Lys-91 were removed showed only partial recombination. The two recombinants were devoid of any in vivo biologic activity, but retained some of the immunologic activity of the native recombinant. These findings indicate that the integrity of the C-terminal residue of serine in hCG-alpha is essential for the expression of in vivo biologic activity of the native hormone.


Evidence for interaction between granulosa cells and theca in early progesterone synthesis. The temporal characteristics of steroidogenesis in vitro by hamster preovulatory follicles, were compared to granulosa cells and theca incubated separately. Gonadotropin-stimulated intact follicles or recombined granulosa cells and theca synthesized increased amounts of progesterone by 30-120 minutes of incubation. The granulosa cells and theca, when incubated separately, did not begin to accumulate progesterone until 4 to 6 hours. The relatively rapid rise in follicular progesterone synthesis after in vitro gonadotropin stimulation follows the same time course as the rapid rise in vivo of hamster and rat preovulatory progesterone after the gonadotropin surge. The sharp differences in the temporal characteristics of progesterone synthesis between follicles and separated follicular cell types suggest an interaction between granulosa cells and theca in at least one phase of progesterone synthesis.


Environmental aspects of injury and disease: liver and bile ducts. Evolutionary processes have not yet developed specific and safe ways to detoxify all chemical species new to our environment. Indeed, some are transformed and/or conjugated by the liver into more toxic species. Environmental factors can modulate hepatic enzyme systems. Particularly responsive are the mixed function oxidases, which initiate the transformation of many xenobiotics to excretable species via reactions which generate electrophilic intermediates such as free radicals, epoxides and aldehydes. Unless these reactive metabolites are rapidly removed by subsequent detoxification reactions or by endogenous defense systems, destructive cytotoxic reactions can be triggered or cell constitutents "attacked" thereby causing either acute injury and/or more latent molecular injury to long chain biopolymers resulting in chromatin damage, or tumors. In vitro systems using purified, specialized cell fractions may be of considerable value in defining metabolic processes, but the results must be relevant to in vivo conditions. Although human liver is peculiarly resistant to tumorigenesis, liver microsomes (isolated endoplasmic reticulum) are extensively used as biological activators for in vitro mutagenicity test systems. The in vivo defense system of liver cells must be exceptionally efficient! Reactive metabolites generated in liver may be stable enough to migrate and cause injury to other tissues or organ systems. It is important to characterize metabolic pathways of toxic xenobiotics, subsequent molecular sites or modes of injury, and factors which depress or augment cellular defense systems including the biliary system responsible for the excretion of many xenobiotics. Only then can techniques or treatments be developed to screen individuals for risk to specific groups of xenobiotics, to protect those exposed, and to treat those injured.


Environmental factors and diseases of the pancreas. The five major diseases of the pancreas together make a significant contribution to morbidity and mortality among the people of the United States. These diseases are diabetes, cystic fibrosis, acute and chronic pancreatitis, and carcinoma of the exocrine pancreas. Four of these diseases can be modeled in laboratory animals by acute or chronic administration of chemical poisons or carcinogens. Human pancreatic diseases attributed to the effect of chemical agents including alcohol and drugs include many cases of chronic pancreatitis and some cases of acute pancreatitis. The cause is not known in many cases of human pancreatitis, including interstitial, acute, and chronic clinical forms. Epidemiologic studies suggest that the increasing incidence of carcinoma of the exocrine pancreas in the United States may reflect chemical carcinogenesis. On the basis of experimental observations, we know that pancreatic islet cells can be damaged directly by toxic chemicals, and that islet cell tumors can be chemically induced. Thus, there is adequate background data to conclude that several pancreatic diseases of obscure etiology may be due in part to hitherto unidentified toxic effects of chemical agents encountered in personal or general environments.


The respiratory tract and the environment. The primary determinants of pulmonary disease are environmental. The same thinness and delicacy of the air-blood barrier which allows rapid exchange of oxygen and carbon dioxide also reduce its effectiveness as a barrier to inhaled allergens, carcinogens, toxic particles, and noxious gases, and micro-organisms. Adults breath 10,000 to 20,000 liters of air daily. This volume of air contains potentially hazardous contaminating particles and gases. Future research should explore the diverse physiological mechanisms which prevent the accumulation and deleterious action of inhaled particles and gases. Since most pulmonary diseases are either initiated by or at least aggravated by the inhalagion of particles and gases, the role of environmental factors in the development of respiratory disease is an area worthy of continued support.


Hypothermia in the aged.

Hypothermia in the aged. Body temperature is maintained by a balance between heat production and heat loss. Temperature regulation consequent to exposure to a cold environment appears to be modified in elderly persons. An evaluation of the physiological adjustments made by older individuals is presented. It is apparent that hypothermia can develop in the older population as a consequence of modifications in both behavioral and physiological responses to cold exposure. With the growing awareness of an energy shortage with consequent lower ambient temperatures in homes, there is a need to obtain adequate information as to the physiological capabilities and adaptive potential of elderly individuals to a cold stress.


Biomagnetic effects: a consideration in fusion reactor development. Fusion reactors will utilize powerful magnetic fields for the confinement and heating of plasma and for the diversion of impurities. Large dipole fields generated by the plasma current and the divertor and transformer coils will radiate outward for several hundred meters, resulting in magnetic fields up to 450 gauss in working areas. Since occupational personnel could be exposed to substantial magnetic fields in a fusion power plant, an attempt has been made to assess the possible biological and health consequences of such exposure, using the existing literature. The available data indicate that magnetic fields can interact with biological material to produce effects, although the reported effects are usually small in magnitude and often unconfirmed. The existing data base is judged to be totally inadequate for assessment of potential health and environmental consequences of magnetic fields and for the establishment of appropriate standards. Requisite studies to provide an adequate data base are outlined.


Background information on high voltage fields. The increased demand for power has led to higher voltages for overhead transmission lines. Environmentalists, governmental agencies, and some members of the scientific community have questioned if past biological effects research and experience with lower voltage lines provide adequate bases for predicting the possible health and environmental effects of the higher voltage lines. Only a small amount of work has been done to explore the possible effects, especially long term effects, of the exposure of biological systems to electric fields from transmission lines. Research in Western Europe and the United States has not identified any prompt or acute effects other than spark and electric discharge and no permanent effects. Contrasted with this are the studies of workers in Soviet and Spanish high voltage switchyards that report effects, such as excitability, headaches, drowsiness, fatique, and nausea, that are not found in Soviet line maintenance workers. The results of current and planned research, supported by both U.S. Government agencies and the private sector, should resolve a number of the present uncertanties and provide answers for the many questions concerning potential effects.


Statistical methods for hazards and health. The objective of this article is to document the need for further development of statistical methodology, training of more statisticians and improved communication between statisticians and the many other disciplines engaged in environmental research. Discussion of adequacy of the current statistical methodology requires the use of examples, which will hopefully not be offensive to the authors. Reference is made to recent developments and areas of unsolved problems delineated in three broad areas: enumeration data and adjusted rates; time series; and multiple regression. A brief outline of the ideas behind current methods of analyzing discrete data is followed by a demonstration of their utility using an example of the effects of exposure, sex, and education on bronchitis rates. Examples are listed of the ubiquity of the time component when relating pollution effects to each other and to health effects. An artificial example is used to emphasize the effects of time-dependent autocorrelations, trends, and cycles. References are given to a variety of new developments in time-dependent autocorrelations, trends, and cycles. References are given to a variety of new developments in time-series analysis. Discussion of the pitfalls in multiple regression analysis, and possible alternative approaches is largely based on two recent reviews and includes references to recent developments of robust techniques.


Renal response to environmental toxins.

Renal response to environmental toxins. Several characteristics of normal renal function increase the risk to the kidney of damage by environmental toxins. Due to the magnitude of renal blood flow the total amount of noxious substance delivered may be disproportionately high. Furthermore, the capacity to concentrate substances within the kidney by processes of filtration, reabsorption and secretion has the potential to increase the toxicity of agents which would otherwise not lead to tissue injury. Unfortunately, there are few tests of renal function which are able to detect early functional abnormalities and which, at the same time, are suited for screening purposes by virtue of their simplicity, cost and safety. Furthermore, interpretation of the tests is complicated by adaptive changes in renal function which occur with aging and in response to other disease processes. Environmental agents produce a wide spectrum of renal dysfunction. Acute renal damage follows exposure to glycols, organic solvents, heavy metals, diagnostic and therapeutic agents and a variety of miscellaneous substances. Chronic renal disease may take the form of isolated tubular defects as seen with cadmium, interstitial nephritis due to the ingestion of lead, or vascular damage induced by external radiation. Some forms of glomerulonephritis may also be related to environmental toxins as are certain tumors of the urinary tract. In a somewhat different fashion, patients whose renal function is limited by the presence of pre-existing disease may manifest toxicity from substances ordinarily excreted in the urine. Particular problems exist with the patients on dialysis, as they are at considerable risk to alterations in the environment.


Mutagenesis testing program.

Mutagenesis testing program. Until recently, mutagenicity testing was done on preselected compounds in a manner in which the testing laboratories knew the identity of the substances under test and the "expected" results, i.e., positive for compounds selected because of their carcinogenicity and negative for food additives. There is no completed study in which substances were tested blind using a standardized protocol. Also, little attention has been placed on reproducibility and variability within and between laboratories. These aspects are currently under investigation in microbial systems by NCI but the results will not be available 1-2 years. In the NIEHS testing program a large number of substances will be tested in a blind study. At present we suggest use of a short-term testing system consisting of microbial tests plus mammalian activation systems (Tier 1), two different Drosophila systems (Tier 2) and four different whole animal systems (Tier 3). The compounds will initially be screened for mutagenicity in Tier 1, and the results obtained in Tier 1 together with what is known about the compound otherwise will dictate the decision whether to continue the test of the compound in Tier 2 and Tier 3.


Genetic and environmental factors affecting host response to drugs and other chemical compounds in our environment. Compared to laboratory animals, humans are extremely heterogenous with respect to the many factors that can influence the distribution and biological effects of toxic chemicals. This heterogeneity can prevent an accurate assessment of the impact of a particular toxic compound on the health of an individual subject. Some of the factors that can significantly modify the host response to certain drugs, which serve in this review as a model for environmental chemicals, are enumerated and discussed. Although the mechanisms by which many of these factors modify the biological effects of certain environmental chemicals and drugs have been determined in some cases, better definition of the nature of interactions between these factors and environmental chemicals in a particular individual is required at a biochemical and molecular level. Recommendations are offered for the further development of our knowledge concerning interactions between environmental chemicals and such factors in a particular individual.


Environmental factors and the development of disease and injury in the alimentary tract. This review examines interactions between the alimentary tract and environmental agents. In these intera"ctions the alimentary tract is considered as an integrated organ system extending from mouth to anus. The alimentary tract shares with the skin and its appendages and the respiratory system the distinction of being a portal of entry into the human body for environmental agents as well as a target for their action. Food and water-borne environmental agents enter the body via the alimentary tract. By injurying the alimentary tract environmental agents after their portal of entry and thereby modulate their effects on the organism. Such modulation may enhance or depress effects of these agents. Interactions between environmental factors and the alimentary tract depend on (1) factors related to the alimentary tract that are determined by anatomic, physiologic, and biochemical considerations; (2) factors related to the environmental agents; and (3) individually determined factors. The role of these factors in development of disease and injury is considered. Environmental diseases of the alimentary tract and environmental agents acting on the gut are discussed and recommendations are made for future research.


Chemodynamics: transport and behavior of chemicals in the environment--a problem in environmental health. In the manufacture and use of the several thousand chemicals employed by technological societies, portions of these chemicals escape or are intentionally introduced into the environment. The behavior, fate, and to some extent the effects produced by these chemicals are a result of a complex interaction of the properties of the chemical with the various processes governing transport, degradation, sequestration, and uptake by organisms. In addition, such processes as adsorption, evaporation, partitioning, and degradation are influenced by ambient conditions of temperature, air movement, moisture, presence of other chemicals, and the concentration and properties of the subject chemicals. These influence the level and extent of exposure to these chemicals that man might receive. Study of the physiochemical properties and extent of exposure to these chem;cals that man might receive. Study of the physiochemical properties of compounds in relation to these various processes has provided a basis for better understanding of the quantitative behavior. Such information is useful in development of predictive models on behavior and fate of the chemicals in relation to human exposure. Beyond this, it provides information that could be used to devise procedures of manufacture, use, and disposal that would minimize environmental contamination. Some of the physical principles involved in chemodynamics are presented in this review.


Ethanol and development of disease and injury to tha alimentary tract. Effects of ethanol on the gastrointestinal tract are reviewed, and an overview of possible mechanisms of ethanol damage to the alimentary tract is presented. Ethanol toxicity most commonly results in metabsorption. Mechanisms contributing to ethanol-induced calcium malabsorption are considered in detail as a prototype for problems encountered in evaluating effects of toxicants on intestinal function. Effects at the local level in the intestine must be differentiated from systemic effects. The mechanism of suppression of calcium absorption by chronic ethanol ingestion differs from that produced by acute administration. Effects of acute administration appear to be due to local mucosal damage and are reversed in 18 hr. Such damage is not present with chronic administration, which affects only duodenal transport. Treatment with vitamin D and its metabolites does not reverse the inhibition of calcium transport. The overall findings suggest that ethanol inhibition of calcium transport is mediated at the intestinal level, probably affecting vitamid D independent mechanisms.


Environmental influences on the immune system and allergic reactions. Environmental interactions with the immune system may result in two types of adverse outcomes: immunodeficiency and immunopathology. Serious immunodeficiency most commonly results from ionizing radiation or as a recognized side effect of iatrogenic drug therapy, usually cancer chemotherapy. At present there is little basis for believing that biologically significant suppression of immune competence in man results from more subtle interactions with environmental agents. On the other hand, environmentally triggered immunopathology is a source of considerable morbidity and mortality. Additional research is needed in the following areas: (a) basic mechanisms of immunopathological reactions; (b) development of methods for accurately implicating or excluding immunological mechanisms in the etiology of hypersensitivity states; (c) development of methods for assessing in advance the potential immunogenicity of new industrial chemicals and occupational allergens; (d) identification of the risk factors which predispose to immunopathological outcomes when individuals are exposed to sensitizing chemicals or other "natural" allergens.


Exercise-induced changes in blood ammonia levels in humans. Five male and two female subjects each performed a maximal aerobic capacity (VO2 max) test, and two to four submaximal aerobic exercise bouts (requiring approximately 50 and 80% of the individual's measured VO2 max) on a motor-driven treadmill. Pre-exercise resting oxygen uptakes (VO2) and heart rates were determined and a venous blood sample drawn prior to each work session. These same measurements were repeated at 4, 15, 30, and 45 min of the resting recovery period that followed each exercise experiment. Additionally, at the 30th min of each 45-min submaximal exercise, another peripheral venous blood sample was drawn following determination of VO2 and heart rate. In all blood samples, the hematocrit and concentrations of ammonia, lactate, pyruvate, glucose, hemoglobin, and total plasma proteins were measured. A significant exponential relationship was observed betwen blood ammonia levels and VO2 for all sample periods (pre-exercise rest, exercise, and post-exercise recovery). Peripheral venous blood ammonia levels were significantly correlated with levels of pyruvate and lactate, as these latter substrates exhibited a similar exponential relationship with VO2 as was observed with ammonia.


[Temperature dependent alterations of the surface-EMG and ECG: an investigation of the electrical transfer characteristics of the human skin (author's transl)]. The influence of local heating of the skin on the integrated EMG (registered with surface and subcutaneous electrodes), the amplitude of the ECG, the skin blood flow, the electrode impedance, the electrode-to-skin impedance, and the tissue impedance is investigated. Except for the increasing skin blood flow each of the variables exhibits a significant reduction with an increase in skin temperature. From these results the existence of two mechanisms is deduced mediating thermal influence on bioelectric signals picked up by surface electrodes: 1. An alteration of the signal source. 2. An alteration of the electric transfer characteristics of the tissue between signal source and electrode. Especially in quantitative surface electromyography the temperature dependence of the signal can be a source of error.


Heart rate and perceptual response to exercise with different pedalling speed in normal subjects and patients. The perceived exertion rating (RPE) scale of Borg was used to investigate the relationship between perceived exertion and pedalling rate. Normal subjects and patients with chronic obstructive lung disease (Cold) were studied in repeated test series. Work load, applied in a random order, varied from 2.5 to 10 mkp/s (patients) and 5 to 20 mkp/s (normals). Pedalling rate varied from 2.5 to 10 mkp/s (patients) and 5 to 20 mkp/s (normals). Pedalling rate varied from 40 to 60, 80, 100 rpm. At constant work load, RPE decreases during increasing pedalling rate. With respect to validity, RPE, showing a closer relationship to work load than to heart rate, seems to reflect perception of physical stress rather than perception of physiological strain. In addition, the results raise the question of standardization of pedalling rate in bicycle ergometry.


Identity of DNA polymerase gamma from synaptosomal mitochondria and rat-brain nuclei. DNA polymerase gamma and mitochondrial DNA polymerase were isolated from brain nuclei and synaptosomes respectively. The presence of a single DNA polymerase in synaptosomal mitochondria was established by chromatography on DEAE-cellulose, phosphocellulose and DNA-cellulose, as well as by sedimentation analysis and isoelectric focusing. A great similarity between the purified nuclear DNA polymerase gamma and the mitochondrial enzyme was found by the following criteria: chromatographic behaviour in three column systems; essentially complete inhibition by N-ethyl-maleimide (2 mM); optimal requirements of Mn2+ (0.1 mM), Mg2+ (5 mM) and pH (8.0); template preferences, poly(A) - (dT)20-25 larger than activated DNA larger than poly(dA) - (dT)12-18; lack of activity on single-stranded polynucleotides and (dT)12-primed mRNA; molecular weight (180000), sedimentation (9.2 S) and isoelectric point (pI 5.4). We therefore conclude that brain nuclear DNA polymerase gamma and synaptosomal mitochondrial DNA polymerase are closely related and may even be identical.


Biosynthesis of triacylglycerols containing short-chain fatty acids in lactating cow mammary gland. Activity of diacylglycerol acyltransferase towards short-chain acyl-CoA esters. 1. Microsomal 1,2-diacylglycerol acyltransferase from lactating cow mammary gland incorporated equal molar amounts of microsomal-bound 1,2-dipalmitoyl [2-3H]glycerol and [1-14C]-butyrate, [1-14C]hexanoate or [1-14C]palmitate from their CoA esters into triacylglycerol. The enzyme could also utilize exogenous 1,2-diacylglycerols in the presence of ethanol. 2. The pH optimum of the enzyme was 6.1 and 6.4 with butyryl-CoA and hexanoyl-CoA respectively. Values of V were approximately the same (2.7 and 2.4 nmol-min-1-mg-1, respectively), but values of Km were different (34 and 10 muM, respectively) with these two substrates. Mg2+ was not required as cofactor. 3. The presence ofa Mg2+-dependent phosphatidate phosphatase in the microsomal fraction was demonstrated. 4. It is proposed that triacylglycerols containing butyric and hexanoic acid are biosynthesized in cow mammary gland by the glycerolphosphate pathway, in which long-chain 1,2-diacylglycerols derived from phosphatidic acid are acylated at the sn-3 position by short-chain acyl-CoA esters.


Joining of synthetic ribotrinucleotides with defined sequences catalyzed by T4 RNA ligase. RNA ligase catalyzed the joining of pC-C-Ap with C-A-A in the synthesis of C-A-A-C-C-Ap, which has the sequence of the Escherichia coli tRNAfMet 3'-end. pC-C-A was also shown to be joined to C-A-A without any undesired self-polymerization. Joining of pC-C-A to various synthetic ribotriplets, such as C-C-A, A-A-A, C-C-C, U-U-U, U-A-G, C-C-G and U-U-C, was performed as well as joining to the partially substituted trimers with a photolabile o-nitrobenzyl group, C-Anbzl-A and C-C-Anbzl. The yields were C-A-A-C-C-A (69%), C-C-A-C-C-A (38%), A-A-A-C-C-A (66%), C-C-C-C-C-A (71%), U-U-U-C-C-A (50%), U-A-G-C-C-A (23%), C-C-G-C-C-A (43%) and U-U-C-C-C-A (46%). C-Anbzl-A was a slightly poorer acceptor than C-A-A and C-C-Anbzl did not serve as an acceptor. Recognition of acceptor molecules by RNA ligase is discussed in terms of affinity of oligonucleotides for the enzyme.


Stereochemistry of olefinic bond formation in defensive steroids of Acilius sulcatus (Dytiscidae). The defensive secretion of Acilius sulcatus contains a number of pregnane derivates: cortexone, 20alpha-hydroxy-4-pregnen-3-one, together with the unusual delta4,6 dienes, 6,7-dehydrocortexone, 20alpha-hydroxy-4,6-pregnadien-3-one and 4,6-pregnadien-3,20-dione. The synthesis of all these steroids except cortexone is described. Complete separation of the steroids of Acilius can be achieved by high-performance liquid chromatography on the reversed-phase column system. During biosynthesis of the Acilius steroids from cholesterol, introduction of the delta4 and delta6 bonds involves elimination of the 4beta and 7beta hydrogens, respectively. Possible mechanisms of formation of the delta4,6 steroids are discussed.


The denaturation-renaturation of chicken-muscle triosephosphate isomerase in guanidinium chloride. 1. The process of denaturation of the chicken muscle dimeric enzyme triosephosphate isomerase on addition of guanidinium chloride has been studied at pH 7.6, the pH at which the recovery of activity is optimal (100%) on removal of denaturant. Determinations of the sedimentation coefficient, intrinsic viscosity, molecular weight (by sedimentation equilibrium studies) and the absorption coefficient at 280 nm in various concentrations of guanidinium chloride concurred in showing a single, sharp transition at about 0.7 M guanidinium chloride at a protein concentration 1-5 mg/ml from the native enzyme to the dissociated, unfolded chains of the monomer. Relative fluorescent intensity measurements revealed a single transition at about 0.4 M guanidinium chloride at enzyme concentrations of about 0.05 mg/ml. 2. The process of denaturation in different guanidinium chloride concentrations was first order with respect to enzyme and about sixth order with respect to denaturant. 3. The rate of attainment of equilibrium during the renaturation obeyed second-order/first-order reversible kinetics. It was concluded that the rate-determining step in renaturation at pH 7.6 must be the association of two subunits.


Conformational features of bradykinin. A circular dichroism study of the aromatic side-chains. The circular dichroism (CD) of the peptide hormone bradykinin and its analogues, [Phe(H4)5]-bradykinin, [Phe(H4)8]bradykinin, [Phe(H4)5,8]bradykinin, [TyrOMe5]bradykinin, [TyrOMe8]bradykinin and [TyrOMe5.8]bradykinin, is described. The comparison of the CD spectra of these analogues with each other, recorded under a variety of conditions (pH, solvent, temperature), allows the monitoring of the behaviour of the aromatic side-chains (phenylalanine, tyrosine) and an estimation of their respective spectral contributions in both spectral regions (320-250 nm, 250-190 nm) with good precision. Conformational non-equivalence of the residues Phe-5 and Phe-8 together with some overall conformational features of bradykinin are thus established.


Studies on DNA unwinding. Proton and phosphorus nuclear-magnetic-resonance studies of gene V protein from bacteriophage M13, interacting with d(pC-G-C-G). The interaction of gene V protein from bacteriophage M13 with the self-complementary tetranucleotide d(pC-G-C-G) was studied by 1H and 31P nuclear magnetic resonance. It is shown, using the hydrogen-bonded proton resonances of the Watson-Crick base pairs as a probe, that the protein is able to unwind the small double-helical fragment even at 0 degrees C. Binding of the tetranucleotide causes changes in the aromatic part of the 1H NMR spectrum of the complex, suggesting that aromatic residues, most likely tyrosines, take part in the protein.nucleic-acid interaction. From the 31P NMR spectra of the protein.nucleic-acid complex it follows that the pK value of the 5'-terminal phosphate is lower than for the free nucleic acid species. Moreover, it could be shown that the exchange of the protein between nucleic acid substrates is fast. Combination of these measurements has led us to derive a mechanism of unwinding on the tetranucleotide level. To a large extent the unwinding is determined by fluctuations in the double-helical DNA structure.


Hydrodynamic properties of 2-mercaptoethanol-modified glycogen. Treatment of glycogen with 2-mercaptoethanol and iodoacetamide gives rise to a modified glycogen which resembles the original glycogen in its hydrodynamic behaviour but has a pronounced tendency to aggregate. The modified glycogen can be distinguished easily, by its diffusion coefficient, from glycogen degraded by more traditional methods of extraction. The 'fundamental' glycogen particle appears to be composed of two or three glycogen beta-particles linked by a single protein chain.


Studies on the role and mode of operation of the very-lysine-rich histones in eukaryote chromatin. Effect of A and B site phosphorylation on the conformation and interaction of histone H1. 270-MHz proton magnetic resonance has been used to study the effect of phosphorylation of histone H1 in vitro on the structure of isolated H1 molecules and on the interaction of H1 with DNA. Phosphorylation at serine-105, which is located in the globular region of H1, was found to reduce the enthalpy of structure formation from 24 +/- 2 kcal mol-1 (100 +/- 8 kJ mol-1) to 13 +/- 2 kcal mol-1 (55 +/- 8 kJ mol-1). Phosphorylation at either or both of serine-37 and serine-105 was found to reduce the strength of binding of the histone to DNA considerably at some ionic strengths.


Determination of the solution conformation of dephospho coenzyme A by nuclear-magnetic-resonance spectroscopy with lanthanide probes. A method for analysis when more than one complex species is present. The aqueous solution conformation of the 1 : 1 complex of dephospho CoA bound to a lanthanide ion has been determined by examination of the dipolar shift and induced relaxation at pH 6.4. The experimental data are shown to arise from the presence of both 1 : 1 and 1 : 2 metal : ligand complexes and a graphical method is described to divide the experimental data into information corresponding to each of the two species. The formation constants are also derived. For the 1 : 1 complex the ribose is found in a 2E conformation with the adenine base predominantly anti. A small contribution from a syn conformation is evident. The pantoinic acid fragment of the chain is folded back towards the pyrophosphate while the remainder of the chain is extended.


Enzymatic incorporation of ATP and CTP analogues into the 3' end of tRNA. Structural analogues of adenosine 5'-triphosphate and cytidine 5'-triphosphate were investigated as substrates for ATP(CTP):tRNA nucleotidyl transferase. Eight out of 26 ATP analogues and six out of nine CTP analogues were incorporated into the 3' terminus of tRNA. In general, for the recognition of the substrates the modification of the cytidine is less critical than is the modification of adenosine. An isosteric substitution on the ribose residue is possible in both CTP and ATP. The free hydroxyls of these triphosphates can be replaced by an amino group or hydrogen atom without loss of substrate properties. Modifications of positions 1, 2, 6, and 8 on the adenine ring of ATP are not allowed whereas modification on positions 2, 4 and 5 on the cytosine ring of CTP are tolerated by the enzyme. No differences can be observed in the substrate properties of ATP(CTP):tRNA nucleotidyl transferase isolated from different sources. Methods for preparation of tRNA species, which are shortened at their 3' end by one or more nucleotides, and analytical procedures for characterisation of these modified tRNAs are described.


Regulation of synthesis of a brain-specific protein in monolayer cultures of clonal rat glial cells. C6 cells were grown in monolayer culture under conditions permitting continued exponential cell division after attainment of a density at which extensive intercellular contacts were formed. An increase in the relative synthesis of S100 protein coincided with the time of formation of extensive intercellular contacts and preceded the onset of the stationary phase of growth by three generations. These observations suggested that the induction of S100 protein synthesis was mediated by cell contact and not by an arrest of cellular growth. The mechanism of this induction was first studied in a homologous non-initiating cell-free protein-synthesizing system from C6 cells, using fixed amounts of free amino acids or fully charged rat liver aminoacyl-tRNA as a source of precursors for protein synthesis. Real synthesis of total soluble proteins decreased as the cells progressed from logarithmic to stationary growth while synthesis of S100 protein increased during this period. The capacity of poly(A)+ RNA from logarithmic and stationary cultures to direct the synthesis of S100 protein was estimated in a cell-free protein-synthesizing system derived from wheat embryos. Increased synthesis of S100 protein in stationary cultures was directly correlated with an increase in translatable S100 protein mRNA.


Covalent structure of collagen: amino-acid sequence of chymotryptic peptides from the carboxyl-terminal region of alpha2-CB3 of chick-skin collagen. The amino acid sequence of chymotryptic peptides C4 and C5 which together make up 206 COOH-terminal residues of alpha2-CB3 of chick skin collagen is described. This in combination with the sequence of 132 residues from the amino-terminal region published earlier [Dixit, Seyer, and Kang (1977) Eur. J. Biochem. 73, 213-221] completes the total amino acid sequence of the large CNBr peptide, alpha2-CB3 of chick skin collagen. The amino acid sequence was determined by automated Edman degradation of intact peptides C4 and C5 and their respective tryptic and maleylated tryptic peptides, and thermolytic peptides of C4. The comparison of the sequence with the homologous segment of alpha1(I) chain showed striking variance of over 51% within the same species.


Heterogeneity in the kinetics of oxygen binding to partially reduced human methemoglobin. A pulse-radiolysis study of oxygenated solutions of methemoglobin. The pulse-radiolysis technique has been introduced because it permits a rapid reduction (in a few microseconds) of one heme group of the methemoglobin tetramer by hydrated electrons. The kinetics of the binding of oxygen to this particular valence intermediate (Hb3+) with one reduced alpha or beta subunit has been studied. It appears that the hydrated electrons preferentially reduce one type of subunit of methemoglobin at acid and neutral pH-values as is shown by the biphasic behaviour of Hb3+ on oxygenation. The second-order on-rate constants measured for the binding of oxygen to Hb3+ are 14 +/- 3 mM-1 ms-1 and 56 +/- 9 mM-1 ms-1, respectively. The relative contribution of the faster fraction is about 0.63 +/- 0.08 of the total oxygenation process. A comparison of the kinetic absorbance difference spectrum for the reduction of methemoglobin with the static difference spectrum of deoxyhemoglobin and methemoglobin in the Soret-region revealed a decreased absorbance of the unliganded subunit of Hb3+ at 430 nm. This fact suggests that Hb3+ is in the relaxed quaternary conformation, which is in agreement with the observed on-rate constants.