Cystic fibrosis with brain abscess.

A 21-year-old patient with cystic fibrosis developed bilateral brain abscesses due to anaerobic Streptococcus. This rare association presents an interesting etiologic study.


Congenital ocular motor apraxia. A possible disconnection syndrome.

In 1952, Cogan introduced the term "congenital ocular motor apraxia" (COA) to describe an abnormality of eye movements characterized by absent or defective voluntary horizontal gaze. Since his original description, there have been few subsequent reports of this disorder. A ten-year review of clinical records from the University of Wisconsin Hospitals disclosed eight patients with COA. In two patients subjected to neuroradiologic testing, agenesis of the corpus callosum was detected. Voluntary horizontal gaze appears to be a learned phenomenon, and defective interhemispheric transfer of visual information may be important in the pathogenesis of COA.


Parkinsonism with 'on-off' phenomena. Intravenous treatment with levodopa after major abdominal surgery.

Continuous intravenous infusion of levodopa was used for eight days to manage a parkinsonian patient with "on-off" fluctuations who underwent abdominoperineal resection for carcinoma of the rectum. Reasonable control of parkinsonism was obtained initially with small doses of levodopa, but more than 4 g daily were eventually required. No adverse effects on cardiac rhythm, blood pressure, or gastrointestinal function occurred. Frequent adjustment of levodopa dosage was necessary in view of continuing "on-off" fluctuations. Severe akinesia, which can cause dysphagia, respiratory complications, and venous stasis in the legs, can benefit from this method of management after major abdominal surgery in a patient with advanced parkinsonism.


Plexiform neurofibroma infiltrating the facial nerve.

A plexiform neurofibroma was unusual in that it extensively infiltrated the main trunk and branches of the left facial nerve without compromising function, rather than forming a circumscribed, compressive mass. Histologic sections showed diffuse involvement of even minute branches of the facial nerve. Electron microscopy disclosed Schwann cell and fibroblastic proliferation in a collagenous matrix. Collagen fibrogenesis by fibroblasts, but not by Schwann cells, was noted. Many of the Schwann cells were free of any association with nerve axons, which suggests that some release of the Schwann cell from its usually well-defined functions is involved in neurofibroma formation.


Computerized tomographic correlate of carbon monoxide poisoning.

A 44-year-old man was brought unconscious to the emergency room; he was believed to have suffered anoxic brain damage probably due to carbon monoxide poisoning. Computerized tomography with contrast enhancement helped establish the diagnosis and was correlated with the subsequent clinical improvement of the patient.


Metastatic intracranial seminoma.

A metastatic seminoma of the right temporal fossa, with facial pain, extraocular paresis, otitis, and abdominal symptoms, was found in a 34-year-old man one year after orchidectomy for a primary testicular tumor that had been treated by surgery and radiotherapy. This is an unusual intracranial metastatic tumor that merits active treatment.


The syndrome of painful ophthalmoplegia. A case with intraorbital mass and hypervascularity.

A patient diagnosed as having Tolosa-Hunt syndrome on clinical grounds was found by arteriography to have an intraorbital mass with hypervascularity. To our knowledge, this radiologic finding has not previously been reported in either Tolosa-Hunt syndrome or in the syndrome of orbital pseudotumor, and supports the proposition that these two conditions are anatomical variants of the same pathological process.


Self-induced pattern-sensitive epilepsy.

A case of self-induced pattern-sensitive epilepsy was observed in a 13-year-old girl. This case resembles those of patients who induce seizures in themselves by light stimulation. The close relationship between photosensitive and pattern-sensitive epilepsy is emphasized.


Neoplastic angioendotheliosis. The case of the missed primary?

Two patients are described, of whom one suffered from progressive dementia, the other with a picture suggestive of Guillain-Barré syndrome. Both were found at necropsy to have small vessels throughout the body clogged with malignant cells with resultant cerebral infarcts. The source in one case was a 1-cm tumor in the thyroid, in the other a microscopic focus in the pancreas. It is suggested that most cases described as neoplastic angioendotheliosis involving the brain represent vascular dissemination of an unrecognized primary carcinoma rather than a miraculously widespread malignant endothelial transformation.


Blinking to sudden illumination. A brain stem reflex present in neocortical death.

Further evidence that the blink reflex to light is a brain stem reflex was provided by a patient who continued to blink to sudden illumination despite anoxic neocortical death with electrocerebral silence and absent summated cortical visual evoked responses.


Neuropathologic findings in a patient with neuroblastoma and myoclonic encephalopathy.

The neuropathological basis for myoclonic encephalopathy associated with neuroblastoma has never been demonstrated. In our 6-year-old patient, the brain changes were restricted to the cerebellum and consisted of demyelination, gliosis, and loss of Purkinje's cells.


Pure memory loss with hippocampal lesions: a pneumoencephalographic study.

A case of pure memory loss occurred suddenly following inhalation anesthesia. Examination seven years after the onset of amnesia disclosed a profound and selective impairment of recent memory without concomitant deterioration of other higher functions or evidence of other neurologic abnormalities. Pneumoencephalotomography focused on the temporal horns showed severe atrophic changes confined to both hippocampi. This finding provides a radiologic counterpart of previously reported surgical and pathological observations of bilateral hippocampal lesions in cases with relatively pure loss of memory.


Basilar artery occlusion in childhood: report of a case.

Basilar artery occlusion occurred in a 13-year-old boy. Eighteen cases in children reported in the literature were also analyzed. Basilar artery occlusion is more common in males. The main clinical manifestations are disturbance in consciousness, hemiplegia or quadriplegia, and pupillary abnormalitites. The prognosis is better in children than in adults.


Intractable sneezing: case report and literature review.

Intractable sneezing is rare; the 12th case is reported here. Various causative factors have been identified in the literature; these include psychologic problems, cervical lymphadenitis, epilepsy, and allergy. The sneeze reflex consists of two phases, nasal and respiratory, which are mediated by cranial nerves V and VII and by brain-stem respiratory centers. Hypotheses that have been proposed to explain the multiple causation of sneezing are the concept of the trigeminal system as a central neuronal pool, optic-trigeminal summation, and parasympathetic generalization.


Prednisone use in concurrent autoimmune diseases.

A 40-year-old woman with clinical and laboratory features of myasthenia gravis, hyperthyroidism, and polymyositis responded to treatment with prednisone alone. Symptoms of myasthenia gravis appeared first followed by hyperthyroid symptoms. Triiodothyronine, thyroxine, and thyroid uptake were elevated as were serum levels of CPK, SGOT, SGPT, and LDH. Muscle biopsy specimen showed mild type II fiber atrophy and a small focus of inflammatory cells. Two weeks after initiation of prednisone, 100 mg every other day, the ESR declined from 44 to 12 mm/hr, serum enzyme values became normal, and the weakness improved. Over the ensuing four months, the thyroid function values returned to normal and the patient no longer needed any anticholinesterase drug. At present, she is functionally normal except for mild defects in eye movement and she takes no medication. Physicians should consider treating patients who have several concurrent autoimmune diseases with prednisone to see if all conditions can be brought under control with one simple therapy.


Skin wrinkling on immersion of hands: a test of sympathetic function.

Skin wrinkling of the fingers following immersion in warm water depends on intact sympathetic innervation. It is abolished by lesions affecting both central and peripheral sympathetic pathways. It affords a simple and reliable clinical test of sympathetic function.


Seasonal variation in the birth of left-handed schoolgirls.

The birth of left-handed girls in a school population displayed a seasonal trend, with a peak in November. No seasonal trend was seen in the birth of left-handed boys. The seasonal pattern of birth of left-handed girls is compatible with the hypothesis that nongenetic factors contribute to the occurrence of left-handedness.


Capsular infarcts: the underlying vascular lesions.

In ten patients, 11 infarcts involving mainly the internal capsule have been examined pathologically. Serial sections of the involved basal ganglia were studied in ten infarcts and only a gross dissection was made in the other. The implicated penetrating arteries were traced throughout their length and obstructive vascular lesions were found in nine instances. In two of the nine there was an atheromatous plaque with a superimposed thrombus, in four an atheromatous plaque had caused severe stenosis, in one a destructive arterial process lipohyalinosis had occurred, in one case the nature of the obstruction remained "uncertained," and in one the penetrating arteries were obstructed at their orifices by an atheroma in the superior division of the middle cerebral artery. In two cases the vessels were patent, suggesting embolism. The atheromas consisted almost exclusively of a conglomerate of fat-filled macrophages. The clinical correlate was a pure motor hemiplegia or hemiparesis involving the face, arm, and leg without sensory deficit, homonymous hemianopia, receptive aphasia, or apractognosia. Confusion was prominent in one patient.


Spirometry in amyotrophic lateral sclerosis.

Clinical evaluation and pulmonary function tests were performed in 218 patients with motor neuron disease, mainly amyotrophic lateral sclerosis (ALS). Serial studies were obtained in 103 patients, in 31 until death from ALS. Most patients, regardless of the pattern of motor neuron involvement, had characteristic abnormalities in pulmonary function, including reduced forced vital capacity (FVC) and maximum voluntary ventilation (MVV). Reductions in the FVC and MVV to as low as 50% were commonly missed by clinical evaluators. Spirometry is therefore of value in detecting early involvement of respiratory neurons. Progressively greater reductions in the FVC and MVV in all the fatal cases indicate that serial spirometry has prognostic value in ALS.


Brain stem auditory evoked responses: studies of waveform variations in 50 normal human subjects.

Brain stem auditory evoked responses (BAERs) were recorded in 50 normal adult subjects at various click rates. Attention was paid to absolute latencies, interwave latencies, interear interwave latencies, absolute amplitudes, and various amplitude ratios. The variability of waves VI and VII suggests that the clinical utility of these waves is restricted-their absence is not necessarily due to a CNS lesion. The wave IV-V complex appears with six different patterns. These variations must therefore be considered normal; none should be misconstrued as indicative of disease of the CNS. Repeated studies over a period of two to nine months showed no statistically significant changes in amplitude or latency measurements with the passage of time. Knowledge of these normal values and their variations, as a precondition for establishing criteria for abnormality, is essential to the interpretation of BAERs in clinical situations.


"Salla disease": a new lysosomal storage disorder.

Severe mental retardation, coarse facial features, clumsiness, and speech failure were common findings in three brothers and one female third-cousin of a family from northern Finland. All the patients had vacuolated lymphocytes in peripheral blood smears, and electron microscopy of fresh skin biopsy specimens showed abundant cytoplasmic inclusions in various types of cells of the skin. Eight lysosomal hydrolases were assayed in peripheral blood lymphocytes and cultured skin fibroblasts, but no enzyme deficiency was detected. Urinary excretion of mucopolysaccharides, amino acids, glycoasparagines, and oligosaccharides was normal. Clinical findings, course of the disease, and the presence of cytoplasmic inclusions, indicating lysosomal storage phenomenon, suggest that the patients suffer from a genetic lysosomal storage disorder not described earlier. The eponym "Salla disease" was introduced, referring to the geographically restricted area where the family resides.


Familial psychosis and diverse neurologic abnormalities in adult-onset Gaucher's disease.

A family is described in which adult-onset Gaucher's disease developed, followed years later by atypical psychotic disorders with neurologic and electroencephalographic abnormalities. A biochemical investigation of primary and secondary enzyme alterations in the index case was performed in an attempt to identify a pattern that might be specific to this clinical profile. The literature pertaining to CNS involvement in adult patients with Gaucher's disease is also reviewed. An etiologic link may exist between the inherited metabolic disorder and associated neuropsychiatric impairment. The biochemical basis of this hypothesized association remains unclear, however, and further enzymatic and pathologic investigations are warranted.


Ocular motility complications following intranasal surgery.

The ocular motility problem of two patients following intranasal surgery is examined. The patients were studied by eye movement records and ultrasonography. Surgery in both cases revealed a defect of the medial orbital wall with scar tissue incarcerated in the defect.


Medial rectus injury from intranasal surgery.

Severe medial rectus injury occurred in two cases following intranasal sinus surgery. In the first case a scarred medial rectus muscle was found at the time of corrective surgery. Reexamination of the surgical specimen in the second case confirmed our finding of medial rectus transection. Both patients had good cosmetic and functional improvement by means of vertical recti transposition to correct their large angle, fixed exotropias. A review of the literature indicates that this is, to our knowledge, a previously unreported complication of intranasal sinus surgery.


Congenital nystagmus surgery. A quantitative evaluation of the effects.

Nystagmus intensities at various gaze angles were studied both preoperatively and postoperatively, using accurate ocular motility recordings, in three cases of congenital nystagmus. In addition to shifting the nystagmus null, the surgery broadened the null region and resulted in an overall reduction in nystagmus intensity at all gaze angles. Surgical rotation also resulted in improved visual acuity in all cases. The postoperative acuity at 0 degrees was better than the preoperative acuity at both 0 degrees and the patient's preferred gaze angle (ie, the preoperative null angle). This was not only for the two patients who showed an improved preoperative acuity with their head turn but also for the patient whose preoperative acuity did not substantially improve with her preferred head turn. Eye movement recordings have made it possible to accurately determine the amount of surgery required and to predict acuity increases even when undetectable during the preoperative clinical examination.


Evaluation of soft contact lens disinfection in the home environment.

Recent reports of bacterial corneal ulcers in cosmetic soft contact lens wearers prompted an evaluation of one possible source of contamination, inadequate home disinfection of the lenses. Twenty-nine patients were asked to come for an early morning examination. They were told not to wear their lenses so their usual home disinfection procedure could be observed. On arrival, extensive bacterial and fungal cultures were taken of the solution in the previously unopened cases. Ten of the 29 patients (34.5%) had contaminated cases. Some patients did not follow the manufacturer's disinfection guidelines. The current disinfection procedure has repeatedly proven adequate in the laboratory. However, the practical fact is that a substantial percentage (34.5% in this study) of soft lens wearers are inadequately disinfecting their lenses. This serves as a possible source of contamination leading to bacterial corneal ulcers.


Changing concepts of failures after retinal detachment surgery.

One thousand eighty-eight consecutive operations for retinal detachment were analyzed to determine the influence of current methods of examination and treatment on failures following surgery. The majority of failures were produced by preretinal membranes formation (33%) and massive  preretinal retraction (27%). Other causes of failure included undetected retinal breaks (13%), inadequate scleral buckel (10%), new retinal breaks (8%), inadequate chorioretinal reaction (7%), and iatrogenic retinal breaks (2%). Primary operations yielded an initial cure rate of 76%. Successful reoperations raised the final cure rate to 89%. Reoperations were associated more frequently with preretinal membrane formation and chance of recognition and management of preretinal membrane formation. Except for new retinal tears and massive preretinal retraction, surgical failures can be avoided by improved utilization of current examination and operative techniques.


Orbitofacial angiomatosis.

Two patients with orbital vascular malformation ipsilateral facial nevus flammeus were studied. The literature contains one similar case that interestingly shares with our cases the lack of leptomeningeal angiomatosis. Orbitofacial angiomatosis seems to be a distinct entity from meningofacial angiomatosis because of its true vascular malformation of the orbit.


Ocular findings in thoracic-pelvic-phalangeal dystrophy.

Two unrelated patients with thoracic-pelvic-phalangeal dystrophy syndrome had retinal degeneration. A pathologic study of both eyes from one of the patients showed severe degeneration of the peripheral retina, with predominantly cone-type cells remaining.


Choroidal effusion during glaucoma surgery in patients with prominent episcleral vessels.

Rapid intraoperative choroidal effusion and flattening of the anterior chamber occurred during glaucoma filtering surgery in four young patients with prominent episcleral vessels, elevated episcleral venous pressure, and advanced open-angle glaucoma. Two of these four patients had Sturge-Weber syndrome. Intraoperative release of suprachoroidal fluid (SCF) through a posterior sclerotomy facilitated reformation of the anterior chamber and repositioning of the iris and ciliary body. Posterior sclerostomy performed prior to opening the anterior chamber minimized the above-mentioned untoward series of events. Analysis of SCF and serum demonstrated considerable differences in total protein and individual immunoglobulin levels; this appears to be a manifestation of molecular sieving at the level of the choriocapillaris. Choroidal detachment and postoperative serous retinal detachment are manifestation of this phenomenon.


Medial ectropion. A new technique.

Medial ectropion of the lower lid responds poorly to standard ectropion procedures. This region contains the initial parts of the nasolacrimal excretory system, which must be functionally reestablished. A new surgical approach to medial ectropion consists of a Z-plasty transposition skin flap from the upper to the lower lid, a plication of the lower crus of the medial canthal tendon, and a punctoplasty. The posterior and superior contraction forces in the transposition flap enhance and maintain the result. Seven lids have been successfully operated on with this technique from the functional and cosmetic point of view.


The basement membrane exfoliation syndrome.

Previous observations suggest that "pseudoexfoliation of the lens capsule" may be a disease in which cells produce abnormal basement membrane material. Electron microscopic studies indicate that exfoliative material can be produced by cells throughout the anterior segment of the eye. This report describes abundant exfoliative material on the ciliary and iridic epithelia but not on the surface of the lens whose epithelial cells were completely necrotic. Exfoliative material also was observed in the anterior iridic stroma close to a newly formed abnormal endothelial basement membrane, suggesting that exfoliative material may be produced locally within the iris. Furthermore, typical exfoliative material, best considered a filamentous, banded basement membrane with 500-A periodicity, in the wall of a short posterior ciliary artery in the orbit indicates that the exfoliative process is not solely limited to ocular tissues. The term "basement membrane exfoliation syndrome" is proposed for this entity.


Clindamycin in chronic toxoplasmosis. Effect of periocular injections on recoverability of organisms from healed lesions in the rabbit eye.

Bilateral toxoplasmic retinochoroiditic scars were induced in 21 rabbits. Eleven rabbits were treated with clindamycin phosphate and ten rabbits received parallel injections of normal saline solution. All injections were made into Tenon's space. Toxoplasma organisms could be recovered from tissue suspensions of retina and choroid of four (18%) of the clindamycin-treated eyes, compared with recovery from 12(60%) of the 20 control eyes. There were significantly fewer Toxoplasma cysts in the hematoxylin-eosin-stained sections of the treated eyes than in similar sections of the untreated control eyes.


Tretinoin and corneal epithelial wound healing.

The entire corneal epithelium of each of 16 rabbits was removed bilaterally. Tretinoin (vitamin A acid) ointment was applied topically twice daily to the eyes of one half of the experimental animals, and the ointment base alone was applied to the eyes of the other half (the controls). On days 1, 2, and 3 after the removal of the epithelium, the healing of the denuded corneas of the animals receiving tretinoin was significantly (P = .01, .01, and .05, respectively) more advanced than the healing of the corneas of the control animals.


The pneumatonograph. A laboratory study.

The scale reading of the pneumatonograph (PTG) is dependent on the force of application to the cornea. Since this force is relatively greater at low intraocular pressure, the scale is compressed, yielding an overestimate of intraocular pressure in physiologic range. When the PTG is held vertically, the weight of the plunger is added to the gas propulsion force and the compression of the scale is accentuated. When a 10-g plunger load is added, as is advocated for tonography, the scale compression is further accentuated. We conclude that the PTG scale is compressed, the PTG is position-sensitive, and that the PTG is totally unsuited to tonography. The PTG is not an applanation tonometer and should not be confused with applanation tonometers.


Variability of air calorics vs water. Statistical implications.

The increasing use of air as a medium for inducing caloric nystagmus has produced a wide variety of comment, much of which may be ignored by opponents or proponents of air. What cannot be ignored by the latter is the report of increased response variability with air irrigation. The effect of increased single-measure variability on the variability of the resultant measures of unilateral weakness (UW) was explored by (1) development of a theoretical equation for the variance of UW and (2) examination of results from normal and clinical subjects. The theoretical equation indicates that variability is a function of both mean responses and the correlation between responses from opposite sides, as well as the variability of single measures. Increases in single-measure variability are attenuated by the formula to a degree such that clinically important increases in the variability of measures of UW are unlikely. This conclusion was supported by results from 22 normal and 12 clinical subjects and reexamination of previous reports.


Maxillary chondrosarcoma.

Chondrosarcoma is a malignant tumor that arises from cartilage. In the maxillary area, the tumors spread locally but may also invade blood vessels and metastasize systemically. Initial surgical resection is the treatment of choice.


Function of the acoustic reflex in discrimination of intense speech.

It is known that the middle ear acoustic reflex (AR) alters the transmission characteristics of the auditory system; however, disagreement exists on how these changes may influence the ears; transfer of speech stimuli. In this study, speech with and without a competing message was delivered at supra-AR levels to cat ears that demonstrated an active and a pharmaceutically inactivated middle ear reflex mechanism. Resulting cochlear potentials were tape recorded and subsequently presented to 18 human subjects with normal hearing. Findings suggest word and sentence discrimination is enhanced in the presence of a functioning AR, with implications for hearing aid use and stapedectomy procedure.


The brow-lift 1978.

The direct brow-lift for correction of brow ptosis can be one of the most beneficial surgical procedures in cosmetic surgery. Careful preoperative evaluation and proper symmetrical marking of the correction are key elements for successful results. We discuss the surgical technique in detail.


Pharyngeal hypoplasia in Treacher Collins syndrome.

Examination of 11 patients with Treacher Collins syndrome (TCS), with the use of multiple-view videofluoroscopy and nasopharyngoscopy of the pharynx, disclosed marked narrowing of the airway. In several patients, the pharynx was less than 1 cm in width at its most narrow point. It is thought that reduced airway in TCS may help to explain the frequent reports of neonatal death associated with the syndrome. Pharyngeal narrowing was found throghout the entire vertical height of the pharynx in all 11 patients. Pharyngeal hypoplasia is probably responsible for reported difficulties in intubating patients with TCS for endotracheal anesthesia and for respiratory complications after palatoplasty and pharyngoplasty. Pharyngeal hypoplasia is considered to be a primary feature of the syndrome and may aid in its diagnosis.


Experience with a polyethylene total ossicular replacement prosthesis.

Surgical reconstruction of ossicular defects in chronic middle ear disease is a difficult problem. We have reviewed our results with the use of the Plastipore total ossicular replacement prosthesis (TORP). Of 29 procedures that were analyzed, nine were considered successful. None of our patients had a stapes superstructure, and 13 had no malleus. Placement of the TORP under the malleus handle and use of extra tissue between the prosthesis and the tympanic membrane provided better hearing results, but extrusion of the prothesis still occurred. Positioning of the prosthesis and contraction of the middle ear space, which causes extrusion of the prosthesis, remain problems in this type of reconstruction.


Effect of kanamycin sulfate on the endocochlear dc potential of guinea pigs.

The magnitudes of the endocochlear dc potential (EP) during adequate ventilation and during five minutes of anoxia were recorded in control guinea pigs and guinea pigs administered various dosages of kanamycin sulfate. The magnitudes of the EP after five minutes of anoxia were -44.6 +/- 5.9 mV in the controls and +26.6 +/- 9.9 mV in the guinea pigs that received kanamycin for seven or ten days. This change occurred after five or six days of administration of kanamycin. However, there was no significant change in the magnitude ot the EP with adequate ventilation with kanamycin intoxication. There is a significant correlation between the magnitude of the negative EP and the maximum output of the cochlear microphonics (r = -.770, P less than .001). These results suggest that the EP may not be the mathematical summation of the positive electrogenic potential and the negative diffusion potential. The mechanism for generating the negative EP during anoxia may have some relationship to hair cell integrity.


Surgical management of hypopharyngeal cancer. Particular reference to the gastric "pull-up" operation.

Between the years 1965 to 1977, 58 patients with advanced hypopharyngeal squamous carcinoma were treated by pharyngolaryngoesophagectomy and total thyroidectomy. Operative mortality for potentially curable cases was 8.6%, with a crude three-year survival rate of 29% for all cases. Mortality was 37% for patients with postcricoid tumors. Long-term management was uncomplicated except for calcium metabolism; two patients died from nephrocalcinosis secondary to return of circulating parathyroid hormone. I discuss the role of this operation in the successful treatment of hypopharyngeal cancer.


Effects of age and sex on static compliance.

The effects of age and sex on static compliance values were analyzed in 336 patients. Static compliance of the normal middle ear varies as a function of age and sex. In men and women, static compliance values are maximum between 31 and 40 years of age, and then decrease relatively systematically with increasing age. Under 30 years of age, static compliance values are slightly greater in female subjects. From 30 to 60 years of age, men show substantially greater static compliance measurements. Above 60 years of age, static compliance is comparable for both sexes. Comparison of normal vs otosclerotic ears showed that the age effect considerably reduces the clinical usefulness of the static compliance measure. The overall findings of this study support the concept of decreased compliance of the middle ear system with increasing age.


Clinical vs histopathologic staging in laryngeal cancer.

One hundred fourteen serially sectioned, nonirradiated, laryngeal specimens that were removed for cancer have been examined to determine the accuracy of preoperative staging. Characteristics of the primary lesion, which indicate invasion of the laryngeal framework, have been demonstrated for each region in the larynx. Pathologic findings, such as submucosal extension, growth into the preepiglottic space, infraglottic extension, and involvement of the laryngeal ventricle, have been correlated with clinical staging. The relationship between tumor size and accuracy of clinical staging has been evaluated. For multiregional lesions, the location that yielded the highest probability of metastasis was designated as the primary site. Our findings indicate inaccurate staging for 37% of glottic tumors, 38% of supraglottic tumors, 50% of transglottic tumors, and 13% of subglottic lesions. In 89% of the cases that were staged inaccurately, the error was one of underestimation. Depth of tumor invasion was the most difficult measurement to determine.


Treatment costs for patients with head and neck cancer.

A national health program is inevitable if medical care costs continue to soar as they have in recent years. Those of us treating patients with cancer of the head and neck are aware that the costs are high, but many are not aware of the actual figures involved. In this study, five typical head and neck cancer patients were selected, and the costs incurred by these patients were calcualted. Both direct and indirect medical expenses were considered and are presented. In addition, we report the representative costs of various treatment modalities. An awareness of medical care costs plus appropriate consideration of them in the planning and administration of treatment may help to reduce health care expenses. If we do not control these costs, the government undoubtedly will.


Morbidity experience of air traffic control personnel--1967--77.

The morbidity experience of 28,086 air traffic controllers has been examined from 1967--77 with particular emphasis to the potential effects of job demands on ATC health. The morbidity experience of air traffic controllers does not appear excessive, except for psychoneurotic disorders, compared with the experience of other outside groups studied. Additionally, a lack of association between disease occurrence and occupation is observed in the data correlating disease occurrence with length of service and age. While some isolated trends found in these data are supportive of an occupation/disease relationship, they are neither--as would be expected if the association were a strong one--impressive nor consistent. Although anticipated empirically, one of the more interesting results of the study was quantification of the substantial differences found to exist in the incidence of disease before and after the second-career legislation.


Stereological ultrastructural analysis of the axonal endings in the neuromuscular junction of rats after a flight on Biosputnik 782.

The study was aimed at quantitative and qualitative evaluation of the axonal endings of the neuromuscular junction in the quadriceps femoris muscle and the diaphragma in animals after a space flight. Quantitative morphometric studies at the ultrastructural level demonstrated a statistically significant diminution of the mean number of mitochondria and synaptic vesicles on the cross section of the axonal endings. Qualitative analysis of electronogrames revealed morphological changes indicating degeneration and various degrees of injury in some of the axonal endings of the neuromuscular junction.


Effect of alcohol and marijuana on eye movements.

The effects of alcohol and marijuana (tetrahydrocannabinol-THC) on saccades, smooth pursuit, and optokinetic nystagmus were quantitatively evaluated in 24 normal subjects using electro-oculographic recordings. Each subject was given an initial trial run and then tested three times (at weekly intervals) with either 0.0microgram THC or 100 microgram THC/kg bodyweight while at three different blood alcohol concentrations (0.0, 0.05 and 0.1%). A 2X3 factorial design was used. Saccades and smooth pursuit were induced by a dot of light moving in steps and ramps on a modified television set. Optokinetic nystagmus was induced by a cloth drum completely surrounding the subject and moving at a constant velocity of 30 degrees/s. Alcohol (0.05 and 0.1%) alone produced significant (p less than 0.05) impairment of saccade maximum velocity and reaction time, smooth pursuit velocity, and optokinetic slow-component velocity. The addition of THC caused performance to further deteriorate at each blood alcohol level but, in all but one instance, the added effect was not statistically significant ( greater than 0.05). At the THC and alcohol concentrations used in this study, the eye movement effects of alcohol over-shadowed those of marijuana.


Correlation of choice reaction time performance with biorhythmic criticality and cycle phase.

The biorhythm theory correlates behavior to physical, emotional, and intellectual cycles. It states that an individual's behavior is influenced by these three cycles which begin at the moment of birth and operate thereafter simultaneously. The theory is commonly tested when the occurrence of accidents is compared to the phase of the biorhythm cycles. If the theory is true, more accidents would occur on a critical day than would be expected by a random distribution. A second method to test the theory is used in this paper, where actual performance of a laboratory task is correlated with the phases of the cycle. Performance was measured in a choice reaction time (CRT) task with each task composed of 400 light flashes. The methods and results are presented and discussed. The conclusion reached from analyses of the data was that performance in the CRT task was no influenced by biorhythms.


Carbon monoxide and human time discrimination: failure to replicate Beard-Wertheim experiments.

Beard and Wertheium described a dose-related deficit in human time perception during low level CO exposure. Two other laboratories were unable to replicate this finding, although methodological differences could explain these failures. This study more precisely repeated the original experiment, but failed again to obtain any CO-related deficit. The bulk of evidence, therefore, does not indicate any adverse effect of low level CO exposure on time perception in healthy young adults.


Thermal sweat rate response to an acute short exposure at a simulated altitude of 4,600m.

An acute short exposure of human subjects to a simulated altitude of 4,600 m fails to induce any noticeable effect on the thermal evaporative response or on the central and cutaneous temperatures.


Emergency problems involving sinusitis.

The problems which the primary physician or flight surgeon might expect to encounter with regard to acute sinusitis are presented. The need for exact diagnosis, the goals of treatment, and the management of the progress of the disease processes are reviewed.


The understanding and teaching of reaction to pain.

Pain is both the commonest and one of the most enigmatic symptoms in medicine. Its subjective nature renders management difficult and its conceptualization is complex. Reaction to pain cannot be easily generalized; group differences are postulated, based on sex, age, culture, psychiatric diagnosis and personality variables. Early developmental aspects of pain and discussed in animal studies and case reports but little systematic data exist. Experimental findings show the influence on pain response of cognitive and emotional factors. Clinically, the variables determining perception, reporting and reaction to pain are numerous and harder to study scientifically. Acute and chronic pain should be distinguished: the latter is more complicated, leading of ten to diagnostic problems and management stalemates. Discovering the relationship of pain to emotional phenomena, as cause or effect, is difficult, though essential to effective treatment. Various frames of reference apply: e.g., individual medical, familial, and "workmen's compensation" models. Reaction by family, lawyer, or work commission involves potential secondary gain and may reinforce or discourage pathological responses by the patient. The potential of pain for symbolic meaning and its acceptance as a "legitimate" medical symptom renders it ideal for both expression and masquerading of intrapsychic and interpersonal conflicts involving anger, punishment, control and dependency. Teaching about pain and its significance is best done in clinical settings such as obstetrical units and multidisciplinary pain clinics. Videotaped modular presentations with discussion provide a satisfactory though less desirable alternative.


The teaching of liaison psychiatry in the hemodialysis center.

The hemodialysis unit is usually a uniquely desirable place for liaison teaching because of the importance and variety of behavioral problems seen there. The trainee may be educated at these units about the syndrome of delirium because of the potential for his seeing in a given patient the presentation and resolution of the syndrome before and after each run. Because of the abject dependency of these patients, issues surrounding patient dependency "needs" and frustration of their independence are common with patient "uncooperativeness", an important area in which the professional staff need education and patients need intervention. Depression, common among these patients because of their many losses, is among the host of psychological problems to be potentially diagnosed and treated by the liaison trainee and/or teacher. The theme of life setting conductive to medical illness and the setting of realistic rehabiliation goals are also important areas of liaison training, particularly suitable for demonstration there. Therefore, hemodialysis centers offer usual wide variety and often untapped resources for liaison education.


Teaching and training of the psychosomatic approach.

In the United States, teaching and training of the psychosomatic approach relies upon (1) the application of psychosomatic concepts, such as reaction to stress, life change and illness, and neuroendocrine influences on disease process to the delivery of mental health services to the sick and dying through liaison programs, and (2) the focussing upon relevant methodology of psychological care in the context of American medicine with its growing knowledge of social implications of health care. Such methodology includes the teaching of data collection, substantive psychiatric disorders in the medically ill, supportive therapy and crisis intervention, psychopharmacology, emotional reaction to illness, and management of obstacles to a psychosocial approach. The resistance of nonpsychiatrist personnel to psychological factors and of psychiatric personnel to medical factors are obstacles which require particular emphasis in graduate and postgraduate training in this clinical area.


Rehabilitation in the elderly.

The prerequisites for effective rehabilitation programmes in elderly patients are described, taking into account the specific social, physiological and psychological changes associated with senescence. The special problems facing elderly patients admitted to hospital are discussed and how their needs can be met. The importance of dementia as a factor influencing rehabilitation is considered and the various forms of residential and non-residential care described. Similarly, the paramount importance of accurate diagnosis of the causes of confusional states is emphasized and principles of management described. The fruitfulness of effective liaison between the psychiatrist and geriatrician is underlined and various ways by which this can be achieved, including the place of psychogeriatric assessment unit, and the role of the acute geriatric ward and geriatric rehabilitation unit. The principles of management of the elderly mentally ill in hospital are outlined. As specific examples of the principles and problems of rehabilitation programmes for disorders in the elderly, a detailed description is presented of the rehabilitation of the patient with myocardial infarction and the patient who has developed a hemiplegia following a cerebrovascular accident.


Psychiatric consultation for the geriatric population in the general hospital.

The first part of this paper is based on a study by the author in 1975--1976. The conclusions were that liaison psychiatry with geriatric patients differs from that with other age groups in the following ways: (1) referrals occur primarily when behavior becomes disturbing; (2) organic causes are often overrated but psychological and social causes and functional disorders are underestimated; (3) psychopharmaceutical agents and vasodilators are overused, while psychotherapy and other forms of treatment are underutilized. Attitudes towards consultations among these patients, their families and consultees do not differ from those of younger groups. Liaison psychiatry with a situation-oriented approach is well suited to the needs of all concerned. Review of the psychosomatic parameters of aging is summarized as a basis of the proposed psychosomatic differential model for management.


Teaching liaison psychiatry and clinical practice of psychosomatic medicine in the general hospital.

One of the recent trends in the general hospital is the increase of psychiatric units and the number of psychiatrists working therein. Thus the psychiatrist has had greater opportunities to participate as a member of a clinical team in the care of patients of other units. Accordingly, daily cooperation with other specialties casts him into new roles which transcend those of the traditional psychiatric consultant. The role of liasion psychiatrist involves the complex relations of doctor--nurse--patient--family, interdepartmental relations, communications and so on. By improving these relationships he tries to bring about a more holistic approach in the general hospital.


Training in anger: how not to communicate with one's medical seniors.

Meyer and Mendelson (2) have identified four critical situations which influence the interaction of consultant and consultee, namely, (1) inappropriate setting; (2) threat through disease and death; (3) character disorders; (4) family and social pathology. Feeling states of hopelessness, pessimism and despair are induced in both consultant and consultee and may lead to a breakdown of their working alliance. It is postulated that the breakdown is programmed by the physicians' basic attitudes towards coping with dependency needs are ignored by the faculty of not being patient-oriented (5). Covert or open hostility towards the faculty is manifested (10). Basic professional needs are not discussed with one's medical seniors who are seen in anger. If liaison medicine is to become effective, its proponents have to direct their attention towards attitudinal learning during undergraduate study. This will require supervised exposure to patients needs, assuming increasing responsibility, individual and faculty feedback.


Skin thickness and collagen content in progressive systemic sclerosis and localized scleroderma.

Skin biopsies of uniform location and surface area (7 mm diameter) were obtained from the extensor aspect of the forearm of 147 patients with progressive systemic sclerosis (PSS) (107 with diffuse scleroderma, 40 with the CREST syndrome variant) and 58 individuals with normal skin. After careful removal of all subcutaneous fatty tissue, the skin cores were weighed and their water and hydroxyproline content determined. Despite recent claims to the contrary, it was found that there is a marked and highly significant increase in the thickness of the skin during the indurative phase of PSS, and that this is associated with a proportionate increase in total dermal collagen content. A similar degree of thickening was found in the skin of patients with eosinophilic fasciitis and acromegaly. A close correlation was observed between clinical estimation of the degree of skin thickening and the weight of the skin biopsy cores. Change in the weight of skin cores was observed during the course of illness of the patients with PSS and may serve as a useful measurement of alteration in the degree of skin thickening.


Cartilage proteoglycan alterations in an experimentally induced model of rabbit osteoarthritis.

Size distribution of cartilage proteoglycans (PG) extracted from control and osteoarthritic rabbit knees after partial meniscectomy was analyzed. In normal control knees, about 30% of PG molecules were in aggregate form and average sedimentation constant was 60S. No aggregates were found in osteoarthritic cartilage, whether ulcer, rim about ulcer, or distant normal-appearing cartilage was examined. Weight average sedimentation constants for PG subunits were similar to controls, 15S. Up to 70% of guanidinium-extractable PG could be extracted from osteoarthritic cartilage by using 0.5M guanidine HC1 (GuHCl); sedimentation characteristics of extracted PG were similar to those using 4.0M GuHCl. Absence of aggregates is consistent with a disorder of link protein, hyaluronic acid, or PG subunit hyaluronic acid binding sites. Absence of subunit degradation was an enexpected finding. The demonstrated ability of 0.5 M GuHCl to extract large amounts of PG from osteoarthritic cartilage will allow study of cartilage proteoglycans in their native nondissociated state.


Increased toxoplasma antibodies in idiopathic inflammatory muscle disease. A case-controlled study.

Antibodies to Toxoplasma gondii were measured in sera from 69 patients with polymyositis, dermatomyositis, and myositis associated with other connective tissue diseases and compared to 69 age-, race-, and sex-matched controls with unrelated diseases. Complement fixation toxoplasma antibodies were significantly more frequent in polymyositis and correlated with high IgM levels. Other distinguishing clinical or laboratory features of these patients were not found. The high toxoplasma antibodies were not associated with generally hyperactive humoral immunity. The serologic data suggested that inflammatory muscle disease was associated with recent active toxoplasma infection in certain patients. The pathogenetic role of the microorganism remains uncertain.


Connective tissue activation. XIV. Composition and actions of a human platelet autacoid mediator.

Connective tissue activating peptide-III (CTAP-III) isolated from human platelets is a potent mitogen for human connective tissue cells in culture in addition to stimulating glycosaminoglycan synthesis, glucose consumption, and lactate formation. The amino acid composition of apparently homogeneous CTAP-III was determined, confirming the presence of two disulfide links and providing a calculated molecular weight of 11,633 daltons. Comparison of the mitogenic activity of serum and plasma-serum suggests that CTAP-III is a major mitogenic component of human serum. Seventeen strains of human connective tissue cells (synovial, cartilage, dermal and thyroid) incorporated [3H]-thymidine at up to 30 times control at levels under the influence of microgram quantities of CTAP-III and caused detectable increases in thymidine incorporation at levels as low as 10-29 ng/ml. Prostaglandin E1 (0.01 microgram/ml) and dibutyryl cyclic AMP (25 microgram/ml) potentiated the glycosaminoglycan stimulating effect of CTAP-III, but not its mitogenic effect. Cycloheximide and actinomycin D blocked the biologic actions of CTAP-III. Cortisol and penicillamine had little effect on the mitogenic activity of CTAP-III, whereas antirheumatic agents such as acetylsalicylic acid and phenylbutazone opposed the mitogenic activity when added to cultures at clinically relevant concentrations. A weak antiheparin factor secreted by platelets, low affinity platelet factor 4 (LA-PF4), was shown to be similar to CTAP-III in biologic actions, electrophoretic mobility, amino acid composition, and antigenic determinants.


Unusual electromyographic findings in a patient with polymyalgia rheumatica.

A case of polymyalgia rheumatica (PMR) with biopsy-proven giant cell arteritis (GCA) is described in which there were marked abnormalities noted on electromyography (EMG). Spike potentials, positive waves, and fibrillation potentials were seen in the proximal musculature of the upper and lower extremities as well as in the erector spinae muscles. Investigation failed to reveal abnormalities in either creatinine phosphokinase (CPK), aldolase, or muscle obtained at biopsy. The presence of these EMG findings in the PMR-GCA syndrome is unusual. Response to therapy with systemic corticosteroids and normalization of the EMG are documented.


Apparent acute renal failure associated with therapeutic aspirin and ibuprofen administration.

Aspirin and ibuprofen may cause a decrease in renal function which, although statistically significant, is usually small. We report a patient with active systemic lupus erythematosus and apparent acute renal failure associated with the administration of these drugs. Renal biopsy revealed no light microscopic evidence of drug nephrotoxicity although patchy nonspecific ultrastructural changes in the tubular epithelium were seen. The renal failure reversed rapidly when the drugs were withdrawn.


Acute monocytic arthritis.

Five patients with the triad of fever, skin rash, and acute polyarthritis were studied with regard to synovial fluid analysis. All cases revealed inflammatory effusions with a predominant monocytosis. Skin biopsies from two cases and synovial membrane biopsy from one case revealed a nonnecrotizing vasculitis. Although the etiology of this syndrome was not ascertained, it bears striking similarities to certain viral arthritides. It also deserves consideration as a form of acute hypersensitivity angiitis.


Hereditary stomatocytosis: association of low 2,3-diphosphoglycerate with increased cation pumping by the red cell.

The levels of glycolytic intermediates have been measured in red cells from patients with both overhydrated and dehydrated varieties of the hereditary stomatocytosis syndrome. Red cell 2,3-diphosphoglycerate was reduced by 33% below normal in all patients with either stomatocyte or target cell morphologies (i.e. over or under hydrated varieties respectively). The relative decrement in 2,3-diphosphoglycerate was even greater when abnormal cells were compared with control cells with similar reticulocytosis. Red cell ADP concentrations in stomatocytosis were significantly increased above normal but ATP concentrations were not significantly changed. Whole blood oxygen affinity in stomatocytosis was increased in proportion to the lowered content of diphosphoglycerate. Some new parameters of membrane transport in hereditary stomatocytosis have been measured. Platelet K+ and Na+ concentrations and platelet K+ permeability were normal in stomatocytosis. The number of 3H-uridine transport sites in stomatocytes were increased by 9-39% above normal and this increment was the same as the increment in red cell lipids (0-38%). Hereditary stomatocytes contain 2-10-fold more cation pumps than normal and the increased active cation pumping may explain the high ADP, the low 2,3-diphosphoglycerate concentration and the increased oxygen affinity in this syndrome.


Association of IgA multiple myeloma with pre-existing disease.

A retrospective analysis of 153 patients with multiple myeloma was performed for evaluation of the possible significance of pre-existing disease. 37% of the group had no significant antecedent disorder. The most common prior illnesses were peptic ulcer disease and gallbladder disease. Of 12 patients in the group who had prior biliary tract disease and for whom immunoelectrophoretic studies were available, eight (66.7%) had IgA paraproteins. This figure is statistically higher (P less than 0.01) than the 14.1% prevalence of IgA paraproteins in those myeloma patients without biliary disease. Of 20 individuals with IgA myeloma, only two had no significant antecedent disease. The rest had primarily chronic biliary, peptic ulcer, other gastrointestinal or respiratory tract inflammatory diseases. We conclude that prior inflammatory gastrointestinal, pulmonary, and, particularly, biliary disease may be implicated in the pathogenesis of the IgA subset of multiple myeloma.


The effect of desferrioxamine on fibroblasts and collagen formation in cell cultures.

Iron is essential for the activity of proline hydroxylase and is an important co-factor in collagen synthesis. Fibroblast cultures exposed to desferrioxamine show impairment of DNA synthesis and reduced collagen formation, as measured by hydroxyproline synthesis and the deposition of hydroxyproline in the cell mat. In patients with transfusional iron overload long-term treatment with desferrioxamine is said to result in the inhibition of hepatic fibrosis. It is suggested that this may be a direct effect on collagen synthesis rather than an effect of reduced iron stores.


Comparison of sickle cell-beta0 thalassaemia with homozygous sickle cell disease.

Clinical and haematological features in 41 patients with sickle cell-beta0 thalassaemia (Sbeta0 thalassemia) and in 123 age--sex matched controls with homozygous sickle cell (SS) disease were compared. Persistence of splenomegaly was more common and fetal loss less common in Sbeta0 thalassemia but other clinical features were similar in the two genotypes. Total haemoglobin, Hb A2, PCV, CCV, and red cell count were significantly higher and MCV, MCH, MCHC, and ISC counts significantly lower in Sbeta0 thalassaemia. Proportional reticulocyte counts were significantly lower in Sbeta0 thalassaemia but there was no difference in absolute reticulocyte counts. Persistence of splenomegaly and low ISC counts are compatible with decreased intravascular sickling which may result from the lower mean cell haemoglobin S concentration in Sbeta0 thalassaemia. If beneficial effects of a low MCHC can be confirmed then a carefully monitored trial of iron deficiency in SS disease may be a logical experimental procedure.


'Prolymphocytoid' transformation of chronic lymphocytic leukaemia.

We report clinical, morphological and surface marker studies on seven patients with the common type of chronic lymphocytic leukaemia (CLL) whose disease underwent an insidious though progressive change in character with increasing refractoriness to treatment. This transformation was accompanied by the appearance of a population of immature-appearing cells in the peripheral blood which resembled prolymphocytes, both at light and electron microscopy. The characteristic morphological feature was the presence of two distinct populations of cells, the typical CLL lymphocytes and the 'prolymphocytoid' cells. These cells retained the surface characteristics of CLL, i.e. the information of mouse RBC rosettes and sparse surface-bound immunoglobulin. This transformation can be distinguished by morphological and surface marker criteria from acute leukaemia occurring in CCL, Richter's syndrome and prolymphocytic leukaemia. The recognition of this group of CLL patients may add a new prognostic index to CLL and may help plan subsequent trials for the treatment of the disease.


Serial changes in coagulation and viscosity during sickle-cell crisis.

Coagulation activity and whole-blood viscosity were measured in the steady state, and serially during painful crisis, in eight patients with sickle-cell anaemia. Platelet and coagulation activation occurred in the steady state and became more pronounced early in crisis. Whole-blood viscosity increased during crisis in parallel with plasma fibrinogen. Similar changes were found in a parallel study of 20 patients with localized bacterial or viral infection who did not have sickle-cell anaemia. Reports of platelet activation, hypercoagulability, and hyperviscosity during painful crisis therefore reflect secondary changes arising from vascular stasis, precipitating infection, and an acute-phase protein reaction. Although secondary, these changes may contribute to vascular occlusion by an additive effect in vessels already partially occluded by sickled cells.


Dietary restriction and the development of atherosclerosis.

1. White Carneau pigeons develop genetic atherosclerosis. The aorta shows intimal cushions at birth, cholesterol accumulation at 9 months of age and definite atherosclerotic lesions by 3 years of age. To determine whether these age-related arterial changes can be prevented by dietary restriction started early in life, 3-month-old pigeons were subjected to dietary restriction (40% of ad lib. diet). 2. Plasma cholesterol levels, cholesterol excretion and aortic cholesterol concentrations were compared with those of pigeons on the ad lib. diet. The pigeons on dietary restriction showed a decrease of 30% in weight. The plasma cholesterol levels of these pigeons decreased 20% when compared with those of ad lib. group. In the dietary-restricted group, both the faecal excretion of bile acids (P less than 0.01) and the aortic cholesterol level (P less than 0.02) were significantly reduced, with changes in the free and in the esterified sterol fraction. 3. This study shows, for the first time, that age-related accumulation of aortic cholesterol can be prevented or at least delayed by dietary restriction started early in life.


The effect of varying the quality of dietary protein and energy on food intake and growth in the Zucker rat.

1. Food intake and rates of protein, lipid and energy deposition were measured for lean and obese (fatty) Zucker rats offered to appetite from 34 d of age to slaughter at 66 d of age, one of sixteen semi-synthetic diets. Measurements were also made of the digestibility of dietary protein and the metabolizability of dietary energy. Total carcasses were analysed for protein and lipid, and body energy was calculated thereby. Changes in body constituents were calculated by the comparative-slaughter technique. 2. In Expt 1, four rats of each phenotype and sex were offered one of four diets, each of which contained either 150 or 300 g casein (150 C and 300 C respectively)/kg and either 150 or 300 g cellulose (150 cell and either 150 or 300 g casein (150 C and 300 C respectively)/kg and either 150 or 300 g cellulose (150 CELL and 300 CELL respectively)/kg (diets 150 C/150 CELL, 150 C/300 CELL, 300 C/150 CELL and 300 C/300 CELL. As expected, males ate more and had higher rates of protein deposition than female animals of the same phenotype on all diets. These sex differences were greater for the lean phenotype. The results for animals in this experiment are presented with, and discussed in relation to, those obtained previously for animals of both sexes fed on cellulose-free diets having these two levels of casein. 3. In Expt 2, four female animals of each phenotype were fed one of twelve semi-synthetic diets, each of which contained casein, gluten or zein at one of the following levels (g crude protein (nitrogen x 6.25)/kg diet): 93, 132, 267 or 627. On all diets containing zein both fatty and lean rats had similar, low food intakes and failed to grow. Fatty rats fed on diets containing casein or gluten had higher rates of food intake, weight gain, lipid and energy deposition than lean rats, but similar rates of protein deposition. Rats fed on diets having the two lower levels of casein ate more and grew better than animals of the same phenotype fed on the two corresponding diets containing gluten but at higher protein levels differences in food intake and growth attributable to differences in protein quality disappeared and furthermore, the rate of protein deposition became similar and maximal for both phenotypes. 4. The results from both experiments are discussed in relation to previous work on appetite control in the Zucker rat. It appears that fatty and lean rats eat during growth to attain the maximal rate of protein deposition of which they are capable. The rate of lipid deposition would appear to be of no importance in the food intake regulation of animals depositing protein maximally. 5. Rats given diets that fail to support maximal rates of protein deposition appear to regulate their intake of digestible energy rather than that of digestible protein. They do not overeat protein-deficient diets in order to acquire sufficient protein for maximal growth although the factors that induce satiety in these animals are unknown.


Some effects of sulphur intake on molybdenum metabolism in sheep.

1. To investigate the effects of sulphur intake on molybdenum metabolism in sheep, ewes were given intakes of 0.3 or 3.5 mg Mo and 0.98, 1.33, 1.73 or 3.23 g S/d in a 2x4 factorial experiment with two replicates lasting 35 d. 99Mo with 0.1 mg carrier Mo was infused intravenously for the last 14 d and, when 99Mo concentrations in urine and faeces had attained plateaux (days 11-14), stable Mo and 99Mo balance trails were conducted; samples of blood and rumen contents were taken principally for studies of Mo distribution. 2. Increases in S intake caused the following changes in Mo metabolism; absorption decreased, urinary and faecal endogenous excretion decreased and retention increased; Mo concentrations in rumen contents decreased but the predominant association with the solid phase was unaffected; Mo concentrations in plasma decreased, but a higher proportion was associated with the protein fraction; Mo in protein-free plasma became apparently less ultrafiltrable at the glomerulus. 3. The pattern of response to S for each factor was generally curvilinear, the first increment in S intake having by far the greatest effect. The effect of S was generally greatest at the higher Mo intake. 4. It is suggested that the manifold effects of S on Mo metabolism are related to a common interaction in the rumen leading to the formation of Mo-complexes, possibly thiomolybdates, which are poorly absorbed but even more poorly excreted.


Studies on digestion and absorption in the intestines of growing pigs. 5. Measurements of the flow of nitrogen.

1. Digesta were collected from twenty-three pigs, initially of 30 kg live weight, and fitted with single Ash re-entrant cannulas in either the duodenum, jejunum or ileum. A further twenty-four pigs were used in a conventional digestibility trial. 2. Three approximately isonitrogenous diets were used; they contained: barley, fine wheat ofal, white fish meal, minerals and vitamins (diet BWF), starch, sucrose, maize oil, cellulose, minerals, vitamins and either groundnut (diet SSG) or casein (diet SSC). 3. The flow-rates of nitrogen (N), liquid-fraction N (LN) and non-protein liquid-fraction N (NPLN) were measured hourly in the duodenum and every 6 h in the ileum during 24 h collection periods. Faeces were collected during 5 d periods. 4. Marked increases in flow of N, LN and NPLN were seen in the duodenum and jejunum after feeding each diet, but not in the ileum. 5. Values for, N output: intake from the duodenal, jejunal or ideal cannulas and in faeces in 24 h periods were respectively: 0.98, 0.88, 0.25 and 0.21 for diet BWF; 1.00, 0.97, 0.22 and 0.24 for diet SSG; 0.98, 0.73, 0.09 and 0.03 for diet SSC. The corresponding values for LN in the duodenum, jejunum and ileum respectively were: 0.53, 0.53 and 0.12 for diet BWF; 0.46, 0.60 AND 0.13 FOR DIet SSG' 0.57, 0.50 and 0.06 for diet SSC. The corresponding values for NPLN in the duodenum, jejunum and ileum respectively were: 0.41, 0.38 and 0.09 for diet BWF; 0.35, 0.36 AND 0.08 FOR DIET SSG; 0.46, 0.38 AND 0.04 for diet SSC. 6. The results are discussed in relation to similar studies, particularly in pigs with duodenal cannulas, in which widely different observations were made.


Studies on digestion and absorption in the intestines of growing pigs. 6. Measurements of the flow of amino acids.

1. Digesta were collected from seventeen pigs initially of 30 kg live weight fitted with single re-entrant cannulas in either the duodenum, jejunum or ileum. A further twenty-four pigs were used in a conventional digestibility trial. 2. The pigs received three types of diet containing: barley, fine wheat offal, white fish meal, minerals and vitamins (diet BWF); starch, sucrose, maize, oil, cellulose, minerals and vitamins and either groundnut (diet SSG) or casein (diet SSC). 3. Amino acids were measured in samples representative of the digesta flow in 24 h periods and in the faeces collected in 5 d periods. 4. For each diet the total flow in 24 h periods in the duodenum for aspartic acid, threonine, serine and glycine exceeded  or equalled intake, while the amounts of the other amino acids were usually rather less than intake. 5. For each diet in the jejunum, the amounts of glycine and cystine exceeded intake in 24 h periods, while methionine, arginine and tyrosine were the most rapidly absorbed amino acids anterior to the cannula site. On average 0.22, 0.25 and 0.31 of the dietary amino acids were absorbed anterior to the cannula site for diets BWF, SSG and SSC, respectively. 6. For each diet in the ileum, the least apparently absorbed dietary amino acids were glycine and cystine. On average 0.81, 0.83 and 0.95 of the dietary amino acids were absorbed anterior to the cannula site for diets BWF, SSG and SSC, respectively. 7. There was net disappearance of most amino acids in the large intestine, but some net accumulation occurred in this region. 8. The results are discussed in relation to the amino acid composition of endogenous secretions (particularly glycine in bile), protease and peptidase specificity, free amino acid absorption and the role of the microflora in the large intestine.


Ntau-methylhistidine in human skeletal and smooth muscle proteins.

1. Fifteen pieces of rectus abdominus muscle and fifteen pieces of taenia muscle were removed from patients undergoing various surgical procedures. 2. The muscles were extracted, hydrolysed and the content of Ntau-methylhistidine was measured. 3. The rectus muscles contained 3.13 +/- 0.7 mumols Ntau-methylhistidine/g fat-free dry solid and the taenia muscles 2.4 +/- 0.6 mumols/g fat-free dry solid. There was a statistically significant difference (P less than 0.05) between these values using the Student's unpaired tau test, although this could have been due to contamination of the taenia muscles with connective tissue. 4. The muscle content of Ntau-methylhistidine was at least 40% higher than the only other reported value and therefore the method of calculating muscle protein breakdown based on Ntau-methylhistidine excretion requires revision.


Carotid or jugular amino acid infusions and food intake in the cockerel.

1. Infusions of histidine into the carotid arteries of cockerels receiving a histidine-limiting, imbalanced diet caused an increase in food intake, whereas similar infusions into the jugular veins did not. 2. Infusions of lysine into the carotid arteries or jugular veins of young cockerels receiving a balanced, low-protein diet caused decreases in food intake. There was evidence of a more marked effect of carotid infusion. 3. The mechanisms of food intake regulation by amino acids in mammals are applicable to birds and excesses of single amino acids do seem to affect food intake directly.


The nutritional value and quality of squid (Illex illecebrosus) meal as source of dietary protein for broiler chicken.

1. Squid meal (SqM), produced by grinding and drying the whole squid (Illex illecebrosus) common to the northeast Atlantic and Mediterranean, contained 645 g protein/kg and appeared limiting with respect to lysine, methionine and cystine. 2. Although a comparison of the essential amino acid profiles of SqM with other protein concentrates indicated that SqM was higher than fish meal and soya-bean meal but lower than casein or whole-egg protein, these teported for evaluating protein quality of SqM. It was based on the direct chromatographic determination, of its collagen content, from the amounts of 5-hydroxylysine or 5-hydroxyproline present, and elastin, from the amounts of desmosine or iso-desmosine present. This method can also be routinely used to assess the connective tissue content and protein quality of animal protein supplements such as fish, meat-and-bone meals. 4. A nutritional evaluation of SqM as a source of protein for poultry was carried out using 320 male and 320 female Cobb chicks fed from 1-d-old to 48 d, a control diet containing 50 g/kg fish meal or test diets containing 50 g, 100 g or 150 g SqM/kg. 5. Feeding of SqM at a rate of up to 100 g/kg diet resulted in optimum biological response and monetary returns.


Seasonal variation in the effect of dietary RNA on criteria of energy homoeostasis in the rat.

1. RNA was administered to rats as part of a meal while standardizing food intake and minimizing the effects of psychological stress and diurnal metabolic rhythms. It was demonstrated that circulating levels of glucose and free fatty acids (FFA) in the animals, which were deprived of food for 48 h, were responsive to orally administered caffeine. 2. Inclusion of RNA in the diet slightly but consistently reduced the normal postprandial hyperglycaemia. Its effect on plasma FFA was variable although statistically significant in some experiments. The differences between RNA-and control-fed animals were not attributable to differences in the rate of passage of digesta along the gastrointestinal tract. 3. Evidence was obtained that the variability in the FFA response was related to a seasonally-dependent change in the state of animals. The synchronizer ('Zeitgeber') responsible for this change was not identified and no satisfactory way of suppressing its effect was found. 4. The present findings, taken in conjunction with those of previous workers, suggest that there is a seasonal influence on the sympathetic nervous system manifesting itself as a variable susceptibility to arousal or excitation.


Effect of varying energy and protein intake on nitrogen balance in adults engaged in heavy manual labour.

1. The effect of varying energy and protein intake on nitrogen balance in adult men engaged in heavy manual labour was investigated. 2. Low protein and energy levels resulted in negative N balance and urea index (Waterlow, 1963) was decreased. 3. Urinary excretion of hydroxyproline was found to be sensitive to dietary protein level, but not to energy.


The origin of nitrogen incorporated into compounds in the rumen bacteria of steers given protein- and urea-containing diets.

1. Two young Friesian steers fitted with rumen cannulas were each given three different isonitrogenous and isoenergetic diets for successive periods of 2-3 weeks. The diets consisted mainly of straw and tapioca, with the nitrogen supplied mainly as decorticated groundnut meal(DCGM; diet A), in approximately equal amounts of DCGM and urea (diet B), or entirely as urea (diet C). 2. At the end of each period on a given diet, part of the dietary urea of a morning feed was replaced by a solution of [15N]urea which was infused into the rumen. Samples of rumen contents were removed just before giving the 15N dose and at 1,3,5,7 and 24 h afterwards, concentrations of ammonia and its 15N enrichment were determined and samples of mixed bacteria were prepared. Amino acids, ammonia derived mainly from amide groups, and hexosamines were prepared by ion-exchange chromatography of acid-hydrolysates of the bacteria and analysed for 15N. 3. Approximate estimates of net bacterial N synthesis were made from turnover data for rumen fluid and 15N enrichments in rumen fractions. From the determined efficiency of incorporation of urea-N into bacteria recovered at the duodenum, it was calculated that on diets A, B and C respectively 82%, 37% and 0% of the bacterial N was derived from dietary protein or other non-urea sources. 4. [15N]urea was converted rapidly to ammonia and the 15N then incorporated into bacterial amide-N; it appeared at a slower rate in total bacterial non-amide-N. Rates of incorporation into non-amide-N were highest for glutamic acid, aspartic acid and alanine, and generally lowest for proline (pro), histidine (his), phenylalanine(phe), arginine(arg), methionine(met) and galactosamine. A similar ranking was also generally observed for relative 15N abundances (15N atoms % excess in N component divided by 15N atoms % excess in total bacterial N) achieved after several hours. Relative 15N abundances in his, arg and pro increased with decreasing protein (DCGM) in the diet but those in the other protein amino acids, including the poorly labelled met, phe (and its derivative tyrosine) did not. 5. It was concluded that different extents of labelling of the amino acids (at least those present mainly in protein) indicated that different amounts of preformed units (amino acids or peptides) were used. When an adequate supply of such units was available (particularly on diet A) pro, arg, his, met and phe were derived in this way to a greater extent than the other amino acids, but whereas synthesis of pro, arg and his increased on the low-protein diet C, that of met and phe did not. Thus met and phe may be limiting for bacterial growth on diets low in protein and high in non-protein-N. 6. Differences in the extent of labelling of other bacterial N components may be due to different turnover rates.


Studies on the body composition, fat distribution and fat cell size and number of 'Ad', a new obese mutant mouse.

1. Studies have been performed on the body composition, the fat distribution, the fat cell size, and the 'observable' fat cell number of a new obese mutant, the Adipose (Ad) mouse. The serum glucose and insulin concentrations have also been investigated. All studies were undertaken with animals aged 6 months. 2. The obese animals weighed over 50% more than the lean, but there was no difference in the body or tail lengths. 3. The obese animals had an increase in the weight of the liver, but the increase was only proportional to the increase in the total body-weight. 4. The carcasses of the obese mice contained more water as well as more fat than those of the lean. In the males the fat content was 3.9 times greater, while in the females it was increased by 5.5 times. 5. The nitrogen content of the defatted dry carcass was the same in both lean and obese animals but the total body protein was higher in the obese. 6. Fat was dissected from four major depots, gonadal, abdominal, hind subcutaneous and interscapular subcutaneous (including brown adipose tissue), and each was substantially larger in the obese animals. This indicated that the additional fat of the Ad mouse was not localized to any particular site. 7. In Ad males there was no over-all increase in the observed number of adipocytes, all the extra fat being accommodated by an increase in fat cell size (3.8 times). However, in Ad females there was a 3.3 fold increase in the number of observable fat cells as well as a 2.2-fold increase in fat cell size. 8. Non-fasted obese animals were not hyperglycaemic, but there was a 5.3-fold increase in the concentration of serum insulin. Hyperinsulinemia in the presence of normoglycaemia suggested that the obese animals were insulin resistant.


Estimates of maintenance requirement of growing lambs.

1. Total body energy retention (ER) and metabolizable energy intake (MEI) values from experiments with 231 lambs (Suffolk male x (Border Leicester male x Cheviot female) female) housed indoors and given thirteen forage diets were used to estimate the metabolizable energy (ME) required for maintenance. 2. ER was measured using the comparative slaughter technique, and the lambs were fed at several planes of nutrition above maintenance between 2 and 5 months of age. 3. The daily ER and MEI results were scaled to live weight (kg0.75) and linear regression lines fitted to the values for individual diets. Extrapolation of the fitted lines to zero ER gave estimates of maintenance requirement ranging from 141 to 466 kJ ME/kg0.75 per d and values for the efficiency of utilization of ME for growth and fattening (Kf) of 0.25-0.53 (mean 0.39). 4. An alternative analysis constrained the estimated maintenance requirement to be the same for all diets. An iterative search procedure indicated minimal residual variation at 339 kJ/kg0.75 per d. This common value of ME for maintenance gave Kf values ranging from 0.30 to 0.54 (mean 0.39). 5. The implications of the technique were considered together with some discussion of the variability of the estimate. Allowing the minimum RSD to vary by 10% gave a maintenance requirement of between 231 and 408 kJ/kg0.75 per d.


Vitamin B-complex deficiency and visual acuity.

1. A study was carried out on 973 school children to find out any relationship between vitamin B-complex deficiency signs and defective vision, and the effect of supplementation of B-complex vitamins on visual acuity. 2. The results of the study showed a significant association between presence of clinical signs of vitamin B-complex deficiency and defective vision. 3. Supplementation with vitamin B-complex was found to have a beneficial effect in improving the visual-acuity status of defective children and in preventing visual defects from developing. 4. It is concluded, therefore, that from the present study it appears that the relationship between vitamin B-complex deficiency and visual defects could be one of 'cause and effect'.


Nutritional effects of field bean (Vicia faba L.) proteinase inhibitors fed to rats.

1. Weanling rats were fed on purified-casein diets containing active and inactive (autoclaved) field bean (Vicia faba L.) proteinase inhibitors (PI) at levels of 1.25, 2.5, 5.0 and 10 g/kg. Diets containing raw- and autoclaved-field-bean meal (FBM) were also given. The body-weight gain, protein efficiency ratio (PER); i.e. the ratio of the live weight gain in g/g of protein consumed and apparent nitrogen digestibility were determined 7, 14 and 21 d after the start of the trial. 2. Significant growth depression (P less than 0.001) was observed in rats given diets containing 2.5 g/kg PI (27--35%). In rats fed on raw FBM growth depression was severe after 7 d (57%). 3. Food intake was depressed at PI inclusion levels of 5 g/kg and higher between 14 and 21 d. 4. PER was depressed significanlty (33-44%) in rats given diets containing the active PI at all levels after 7 d. The protein utilization of all casein diets was higher than that of the FBM diets. 5. Apparent N digestibility was depressed in rats fed on diets containing 10 g/kg PI by 9 and 7% at 14 and 21 d respectively. The N digestibility of both raw and heated FBM was similar at approximately 84%. 6. It was concluded that the PI are not the main factors responsible for the growth depression observed when raw FBM is fed to rats.


Absorption of lactulose from mammalian gastrointestinal tract.

1. The disaccharide lactulose (galactosyl-beta-1,4-fructose) was poorly absorbed from rat small intestine in vitro and human mouth in vivo. 2. These results confirm indirect clinical evidence of poor absorption from the intestine. 3. The presence of calcium ions, or absence of sodium ions, had no effect on lactulose absorption from buccal cavity. 4. The presence of ouabain, or absence of Na+, did not increase the absorption of lactulose from small intestine. 5. It is thought that the mode of transport, in both instances, is by passive diffusion with the concentration gradient.


A method of presenting longitudinal growth data.

1. Longitudinal growth profiles contain much information but are difficult to incorporate into mathematical and statistical analyses. 2. A growth function, which is a weighted average of growth achievement at different ages, is proposed. 3. This function is a non-dimensional number with defined statistical properties, and emphasizes growth achievement in early life. It can be used to compare the growth of individuals and populations.


Toxicity of shoti (Indian arrowroot: Curcuma zedoaria) for rats and chicks.

1. A flour was prepared from rhizomes of shoti(Curcuma zedoaria) in such a way that most of the protein was retained. The crude protein (nitrogen x 6.25) content in this product was 155 g/kg, compared with approximately 10 g/kg in commercial shoti flour. 2. The high-protein flour proved highly toxic to 5-week-old rats and caused 100% mortality within 6 d when given at 320 g/kg diet. 3. Fresh rhizomes were minced and dried, and the resulting meal was given to weanling rats at 400 g/kg diet. All the animals lost weight rapidly, and two of the five rats died within 4 d. 4. This same shoti meal was given to 1-d-old chicks at 100 and 200 g/kg diet. All the chicks survived the test period (20 d), but body-weight, food intake and efficiency of food conversion decreased with increase in the level of shoti meal in the diet. 5. The traditional method of preparing shoti involves prolonged washing in changes of water, which removes most of the protein and other water-soluble nutrients and, presumably, a toxic constituent. Further investigation is needed to identify the toxic principle, and to discover a less wasteful procedure for removing it.


47Ca turnover in endemic fluorosis and endemic genu valgum.

1. Calcium turnover was determined after intravenous injection of radioactive 47Ca in patients with fluorosis and endemic genu valgum and in age-matched controls. Total Ca turnover in the body, loss of Ca from the body in urine, faeces and sweat (external turnover) and bone mineralization rate were calculated from whole-body retention of 47Ca and specific activity of 47Ca in serum. 2. Total Ca turnover was significantly higher in younger subjects than in older subjects. 3. Total Ca turnover was significantly higher in patients with fluorosis and in those with endemic genu valgum than in age-matched controls, but the external turnover of Ca was lower in both groups of patients than in controls. 4. Bone mineralization rate was significantly higher in patients with fluorosis and in those with genu valgum as compared to age-matched controls. 5. Total body Ca turnover and bone mineralization rates were significantly higher in patients with endemic genu valgum than in those with fluorosis. The differences persited even after adjusting for differences in age between patients with fluorosis and those with genu valgum.


The relationship between hormonal balance and growth in malnourished children and rats.

Plasma concentrations of insulin, cortisol and growth hormone, and growth velocities have been measured in a group of Gambian village children up to 3 years of age. All three hormones showed changes in concentration with age, as did rates of growth. 2. Plasma insulin concentrations in the children were directly correlated with velocity of growth in height and weight, whereas cortisol concentrations showed inverse relationships. The values for insulin:cortisol concentration correlated more closely with growth velocity than did either hormone individually. Growth hormone values in plasma exhibited only marginal correlations with growth in height or weight, and these were negative. 3. Similar relationships between these hormones and growth were obtained from an animal experiment in which the rates of growth of rats were altered by restricting dietary intake of protein or energy or both. 4. Possible mechanisms for these observations are discussed in the light of recent knowledge concerning the hormonal control of growth rates.


Antithrombin reactions with alpha- and gamma-thrombins.

Human alpha-thrombin with high clotting activity and its proteolyzed derivative gamma-thrombin with virtually no clotting activity reacted in an essentially identical manner with antithrombin. The two enzyme forms bound proflavin with similar constants and showed identical behavior with small substrates. No significant differences were found for the antithrombin reactions (measured by proflavin displacement or active site titration) with respect to kinetics, extent of reaction, or effect of added heparin. The enzyme--antithrombin complexes could not be dissociated with sodium dodecyl sulfate (NaDodSO4) but the NaDodSO4-denatured complexes were dissociated by hydroxylamine treatment. The gamma-thrombin-antithrombin complex has an approximate molecular weight of 75 000 by disc gel electrophoresis as compared with 100 000 for the alpha-complex, consistent with the polypeptide structures of the two proteins. The gamma-thrombin--antithrombin complex did not inhibit clotting catalyzed by alpha-thrombin. In addition, fibrinogen did not affect the reaction of gamma-thrombin with antithrombin or antithrombin--heparin. Thus, the antithrombin and antithrombin--heparin reactions do not involve the fibrinogen recognition sites which are destroyed by proteolytic conversion of alpha-thrombin to the noncoagulant gamma form.


Investigations on polysaccharide components of cells of Herpetomonas samuelpessoai grown on various media.

Herpetomonas samuelpessoai, when cultured in various media, forms a linear beta-D-(1 leads to 2)-mannopyranan and a branched-chain glucuronoxylan containing D-glucopyranosyluronic acid nonreducing end units connected with alpha- and beta-linked D-xylopyranose units, as depicted in fragmental structures I, II, and III. Traces of amylose and alpha-linked mannopyranose moieties are also present. Mannose-containing materials predominate over glucuronoxylan in cells grown with proline as the carbon source (medium C). In a medium with sucrose as the carbon source and complex supplements (medium A) the proportion of glucuronoxylan is greater, and when the supplements were all chemically defined (medium B), a galactose-containing component is also formed. Glucuronoxylan is liberated from cells with hot aqueous alkali and it could be freed from lower molecular weight mannan by fractional precipitation. Mannan was obtained as the only polymeric component, with lower molecular weight homologues, by extraction of cells with hot water. In terms of ratios of component xylose, mannose, and galactose, the flagella resemble whole cells. However, flagella contain polysaccharide with alpha-D-linked mannopyranose side chains rather than beta-linked linear forms. These data are considered from standpoints of immunochemistry and electron microscopy.


Melting-profile analysis of thermal stability of thermolysin. A formulation of temperature-scanning kinetics.

The melting-profile method consists of a continuous observation of a structural parameter while the temperature of the sample is raised at a constant rate [Fugita, S. C., & Imahori, K. (1974) IN Peptides, Polypeptides and Proteins (Blout, E. R., Bovey, F. A., Goodman, M., & Lotan, N., Eds.) p 217, Wiley, New York, N.Y.]. An analytical solution to the melting profile was formulated for the two-state irreversible process and called temperature-scanning kinetics. The theory was tested with thermolysin with consistent results, and the thermodynamic parameters of thermal denaturation were calculated: deltaH identical to = 80.3 kcal/mol, deltaS identical to = 153 eu. These values agreed with the corresponding values obtained from the classical constant-temperature relaxation kinetics. The possibilities of temperature-scanning kinetics are discussed.


Conformations of an ion-binding cyclic peptide analogue of valinomycin, cyclo(L-Val-Gly-Gly-L-Pro)3.

A 270-MHz 1H nuclear magnetic resonance investigation of an ion-binding cyclic peptide analogue of valinomycin, cyclo(L-Val-Gly-Gly-L-Pro)3, and its cation complexes is reported. In CD2Cl2 and CDCl3, the peptide is proposed to occur in a C3-symmetric conformer with the N--H's of all six glycine residues intramolecularly hydrogen bonded. This conformation is different from the familiar valinomycin bracelet structure and lacks any "cavity". Cations do not bind, or bind only weakly, to the peptide in these solvents. Uncomplexed cyclo(L-Val-Gly-Gly-L-Pro)3 in acetonitrile appears to be averaging among several conformations with no evidence found for any preferred intramolecular hydrogen bonds. The strong 1:1 complexes of cyclo(L-Val-Gly-Gly-L-Pro)3 with K+ ANd Ba2+ in acetonitrile are structurally analogous to the bracelet conformation of valinomycin and involve the N--H's of the Val residues and of the Gly's preceding Pro in intramolecular hydrogen bonding. Tl+ was also found to form strong 1:1 complexes with the dodecapeptide.


Amino acid sequence of the beta chain of human fibrinogen.

The beta chain of human fibrinogen contains 461 amino acid residues, 15 of which are methionines. The calculated molecular weight, independent of a single carbohydrate cluster, is 52 230. In this regard, we have isolated and characterized all 16 cyanogen bromide fragments. In one case (CNI), we have concentrated on a disputed portion of a previously reported fragment. The arrangement of the cyanogen bromide peptides was deduced by the use of overlap fragments obtained from the tryptic digestion of modified and unmodified beta-chains and from digestions with staphylococcal protease, as well as by considerations involving the plasmic digestion products of fibrinogen. In one case two adjacent fragments were aligned by homology with the corresponding segments of the gamma chain. The homology of the beta chain with the gamma chain is especially strong over the course of the carboxy-terminal two-thirds of the sequence. Neither of these chains appears to be homologous with the alpha chain in these regions. With a few minor exceptions, the sequence reported in this article is in agreement with data reported by other groups in Stockholm and Munich.


Characterization of the genome of the free-living nematode Panagrellus silusiae: absence of short period interspersion.

The complexity of the DNA of the free-living nematode Panagrellus silusiae has been examined. Reassociation kinetics of pressure-sheared fragments (approximately 290 nucleotides) in 0.18 M Na+ at 60 degrees C showed the presence of foldback, repetitive, and unique DNA sequence elements. The three classes comprise 9.3%, 26.1%, and 61.3% of the total DNA, respectively. The mean length of the foldback duplex DNA after digestion with S1 nuclease is about 185 nucleotides. There are about 1.8 x10(4) inverted repeats per genome. Sequence arrangement was deduced from (1) renaturation kinetic profiles of long and short fragments on hydroxylapatite; (2) the pattern of renaturation of tracer DNA, labeled in vitro with 125I, of various sizes after incubation with excess short fragments; and (3) thermal denaturation behavior of DNA that had been reassociated to various C0t values. It was found that DNA fragments of the repetitive fraction that are, at least, 2000 nucleotides in length are virtually free of unique sequences. Moreover, it is estimated that the repeated segments in this species could extend for 10,000 nucleotide pairs. Thus, Panagrellus DNA lacks the pattern of extensive short period interspersion that is typified by the DNA of Xenopus.


Modulation of erythrocyte membrane proteins by membrane cholesterol and lipid fluidity.

Human erythrocyte membranes were enriched or depleted of cholesterol and effects on membrane proteins assessed with a membrane-impermeant sulfhydryl reagent, [35S]glutathione-maleimide. Reaction of the probe with intact cells quantifies exofacial sulfhydryl groups and reaction with leaky ghost membranes permits quantification of endofacial sulfhydryl groups. The mean endofacial sulfhydryl titer of cholesterol-enriched membranes exceeded that of cholesterol-depleted membrane by approximately 45 nmol/mg of protein or 64%. The corresponding exofacial titer of cholesterol-enriched cells was less than that of cholesterol-depleted cells by approximately 0.4 nmol/mg of protein, or 14%. Labeled membranes were examined by autoradiography of sodium dodecyl sulfate-polyacrylamide gel electropherograms to determine the labeling patterns of individual protein bands. Cholesterol enrichment enhanced the surface labeling of Coomassie brilliant blue stained bands 1,2,3, and 5, decreased the labeling of band 6, and did not change significantly that of band 4. The results demonstrate that changes in membrane cholesterol which influence lipid fluidity can alter the surface labeling of both intrinsic and extrinsic membrane proteins.


Interaction of divalent antibody with cell surface antigens.

This paper presents a thermodynamic description of the interaction between divalent protein in solution and monovalent ligand attached to a cell membrane, but freely mobile therein. The intrinsic differences between this system and interaction which takes place in a uniform bulk solution are discussed. Specific problems which are addressed include the determination of the number of ligand sites on a specific cell system, comparison of several cell systems in terms of common antigenic components, comparison of different antibody preparations, and attempts to study solubilized cell-surface antigens using established serological methodology.


Comparison of the subunits of Torpedo californica acetylcholine receptor by peptide mapping.

The acetylcholine receptor from Torpedo californica electroplax was purified approximately 100-fold by affinity chromatography on alpha-neurotoxin-Sepharose 6B. Four putative subunits (alpha, beta, gamma, delta) of apparent molecular weights of 43,000, 52,000, 58,000, and 63,000 were found when the purified material was analyzed by sodium dodecyl sulfate (NaDodSO4) gel electrophoresis. In some preparations, however, the amount of the gamma polypeptide was small. The presence of N-ethylmaleimide throughout the purification procedure greatly enhanced the amount of the gamma chain. To investigate the possibility that the putative subunits may be structurally related, they were isolated by preparative NaDodSO4 gel electrophoresis and subjected to peptide mapping analyses. The patterns of fragments generated by Staphylococcus aureus V8 protease, papain, or chymotrypsin were different for each of the polypeptides. Thus, it is unlikely that they are derivatives of each other.


Effect of concanavalin A on the kinetics of ecto-5'-adenosine monophosphatase (5'-adenosine monophosphate phosphohydrolase) in the outer surface of intact neural cells in culture.

Oncogenic cultured rat C6 astroblastoma cells display strikingly high ecto-5'-adenosine monophosphatase (ecto-5'-AMPase) activity, 4.23 +/- 20 mumol of Pi liberated by intact cells from 3 mM extracellular 5'-AMP (mg of protein-1 h-1, as compared with 0.15 +/- 0.01 for nononcogenic cultured hamster astroblasts. A further rise in C6 cell ecto-5'-AMPase activity occurs with increase in cell density during growth. Less than 2 pg of the lectin, concanavalin A (Con A), bound per cell reversibly inhibits most of the cellular ecto-5'-AMPase activity. Inhibition by Con A binding is independent of cellular temperature. Con A binding suppresses phosphohydrolase activity of a pK=7.4 functional group on the cell surface. A direct proportionality is observed between quantity of Con A bound to the cell surface and simultaneous relative decreases both in Michaelis constant and maximum velocity of ecto-5'-AMPase in the intact cell. The findings suggest that a major consequence of the specific high affinity binding of Con A to the C6 cell surface is the inactivation of the enzyme--substrate complex of ecto-5'-AMPase.


Catalytic action of L-methionine gamma-lyase on selenomethionine and selenols.

We examined the catalytic action of L-methionine gamma-lyase (EC 4.4.1.11) on selenomethionine (2-amino-4-(methylseleno)butyric acid), methaneselenol, l-hexaneselenol, and benzeneselenol. The enzyme catalyzes alpha, gamma-elimination of selenomethionine to yield alpha-letobutyrate, ammonia, and methaneselenol, and also its gamma-replacement reaction with various thiols to produce S-substituted homocysteines. Selenomethionine is an even better substrate than methionine in alpha, gamma-elimination but is less effective in gamma-replacement. In addition, L-methionine gamma-lyase catalyzes gamma-replacement reaction of methionine and its derivatives with selenols to form the corresponding Se-substituted selenohomocysteines, although selenols are less efficient substituent donors than thiols. This is the first proven mechanism for the incorporation of selenium atom into amino acids.