[Mitotic conditions in primary and metastatic nodes of breast and cervix cancer].

The results of the study on the mitotic regimen (mitotic activity ratios of mitosis phases and percent of pathological mitoses) in primary and metastatic nodes of the tumour by the example of mammary gland and cervical carcinoma are presented. A similarity in the mitotic regimen in primary and metastatic nodes of the tumour was observed which was manifested in a high level of mitotic activity predominance of metaphases over other phases of mitosis, the occurrence of similar pathological forms of mitosis. The difference between the mitotic regimen in the primary and metastatic nodes consisted in an increase in the latter of the number of pathological mitoses mostly at the expence of K-mitoses. Three-group metaphase typical of cervical carcinoma was found in all metastatic nodes of the squamous cell carcinoma of the cervix and may probably serve as a peculiar "marker" of tumours of this localization.


[Solitary plasmacytoma of the hypothalamus].

A rare case of intracranial extra osseal isolated plasmocytoma in a girl of 18 is presented. The tumour localized in the hypothalamus and extended into the intracranial parts of the optic nerves and chiasma opticum. It consisted of mature and immature plasma cells and contained paraamyloid depositions. The disease had a progredient course accompanied by the disorders of vision, endocrine-metabolic disturbances and hyperglobulinemia.


The variable natural history of subacute sclerosing panencephalitis: a study of 118 cases from the Middle East.

A variable natural history was found in a standardized follow-up study of 118 patients with subacute sclerosing panencephalitis (SSPE). Only 20% followed the sequence:behavior change, mental deterioration, periodic attacks, severe debility, and death within a year. Six stages were identified: 0, subtle psychointellectual symptoms; 1, obvious psychointellectual and neurological changes; 2, stereotyped attacks; 3, vegetative psychomotor condition; 4, improvement; 5, relapse. Illness began in stage 0 for 32%; 1, 36%; 2, 19%; 1 and 2 simultaneously, 13%. In early development, 77% were hyperactive, and 27% had psychointellectual difficulties one to five years prior to obvious illness. The average duration of each stage was as follows: stage 0, two years; 1, 2.5 months; 2, 7.5 months; 3, 5.5 months; 4, 3.5 years; 5, 1.5 years. Noteworthy improvements and plateaus occurred in more than half of the patients. In stage 4, improvement was long-term and substantial for 5% and modest for 18%. Survival followed an exponential curve with an average half-life of 1.8 years; 41% of the patients survived beyond two years. Half of the patients passed through neither stage 0 nor stage 4; their half-life was 0.7 years. The remainder had a half-life of 3.0 years.


Amyotrophic lateral sclerosis with ophthalmoplegia. A clinicopathologic study.

Ophthalmoplegia is rarely observed in patients with amyotrophic lateral sclerosis (ALS). We describe a patient with ALS in whom ophthalmoplegia, initially appearing midway in her course, progressed to total paralysis of extraocular movements by the time of death. In addition to the usual postmortem findings of ALS in the brain stem and spinal cord, there was extensive neuronal loss and gliosis involving the caudal portions of the dorsal and intermediate components of the oculomotor nuclei, the caudal part of the trochlear nuclei, and the abducens nuclei. This represents the first detailed report of the findings in the nuclei of cranial nerves III, IV, and VI in a patient with ALS and ophthalmoplegia.


Upward transtentorial herniation: seven cases and a literature review.

Seven cases of upward transtentorial herniation occurred. In each patient, coma with reactive, miotic pupils, asymmetrical or absent caloric responses, and decerebrate posture indicated brain-stem compression. In this setting, the development of unequal, then midposition, fixed pupils signaled midbrain failure from upward herniation. Vertebral angiography showed upward displacement of the superior cerebellar arteries. Results of autopsy confirmed the existence of grooving of the vermis by the tentorial margins and, in one case, of anterior displacement and distortion of the midbrain. In five of 45 reported cases of upward herniation, the conditions were diagnosed antemortem. Instances of cerebellar hematoma and tumor predominated. In at least seven patients, performance of ventriculography may have precipitated herniation. Clinical details were provided in only nine patients and did not separate upward herniation from brain-stem compression. Cerebellar ischemic infarct found in one of our patients is a rarely reported cause of upward herniation.


Administration of human somatotropin in levodopa-treated patients with Parkinsonism.

To investigate further the role of growth hormone (GH) on the cerebral effects of levodopa, human somatotropin (human growth hormone) was administered to four patients with parkinsonism with varying response to chronic levodopa therapy. The doses of somatotropin (5 IU) were administered on alternate days for four days, and the effects of this hormone on the patient's symptomatic control, dyskinesia, plasma GH, and dopa levels were evaluated and compared with those of patients receiving saline injections. We have demonstrated that administration of exogenous human somatotropin, even during marked and sustained elevations of plasma GH levels, does not alter the therapeutic or side effects of levodopa therapy. With one exception, plasma dopa levels after human somatotropin administration remained unchanged. We conclude that neither the endogenous increases of GH in response to levodopa nor those attained following human somatotropin administration modify in any consistent way the therapeutic and side effects of chronic levodopa therapy, and that the episodic releases of GH in response to levodopa occur independently of its cerebral effects.


Hypercapnic alteration of visual evoked responses in acute cerebral infarction.

To determine the effect of inhaled carbon dioxide on acute ischemic cerebral injury, we have compared occipital visual evoked responses (VER) at baseline and during hypercapnia in 20 patients with acute unilateral cerebral infarction (ten with and ten without homonymous hemianopsia) and in ten normal controls. Visual evoked responses were judged on the basis of interhemispheral symmetry. In eight of ten controls and six of 20 patients, baseline VERs were symmetrical and remained unchanged during hypercapnia. In 14 patients with asymmetrical baseline VERs, hypercapnia caused improvement of symmetry in five, worsening in three, and no change in six. Hypercapnic vasodilation may be either beneficial or deleterious to cerebral function in patients with acute cerebral infarction.


Computerized tomography in intracranial metastases.

Two-hundred consecutive patients with suspected metastatic carcinoma and signs of cerebral dysfunction were evaluated by computerized tomography (CT). In ten patients, CT defined a nonneoplastic disorder, whereas in 190, CT defined a metastatic neoplasm. In 70 of these patients, the lesion was solitary; in 120, the lesions were multiple. In 52 patients, plain scan showed a solitary lesion, but multiple lesions were seen after contrast scan. In nine patients, the abnormality was seen only on postcontrast scan. One hundred lesions were of low density and 87 showed enhancement; 81 were of high density, usually surrounded by a low-density rim, and 78 were enhanced. There were no characteristic CT patterns of specific systemic carcinomas, but epidermoid carcinoma frequently appeared as a low-density lesion with a thin peripheral enhancing rim, and adenocarcinoma appeared as a dense, homogeneous, round, enhancing nodule. After treatment, enhancement was the most reliable sign of residual or recurrent tumor.


Subacute necrotizing polioencephalopathy.

A previously healthy 20-year-old woman died of a progressive cerebral disease that involved the brain stem and the cerebral hemispheres successively. The illness ran its course in 80 days. Postmortem examination showed a multifocal necrotizing encephalopathy that chiefly affected gray matter structures and that was mainly located in the brain stem and cerebral cortex. The cause and pathogenesis remain unknown.


Devic's syndrome and systemic lupus erythematosus: a case report with necropsy.

Systemic lupus erythematosus (SLE) rarely occurs coincident with demyelinating disease and, to our knowledge, only one previous case of Devic's syndrome with SLE has been reported.


Neuropathy with susceptibility to compression aggravated by herniated disk. Early pathological and electrodiagnostic studies.

We describe a patient with a foot drop attributable to both herniated disk and peripheral neuropathy susceptible to external compression. Early electrodiagnostic studies and sural nerve biopsy indicated a role for myelin dysfunction in this disorder.


Successful treatment of narcolepsy with propranolol: a case report.

A patient with severe narcolepsy and cataplexy had been treated with a high dosage of methylphenidate hydrochloride, but the drug was not effective. To relieve the patient's cardiac arrhythmia, which was assumed to be secondary to drug therapy, we withdrew methylphenidate therapy and started propranolol hydrochloride therapy. When the dosage of propranolol was increased to a level consistent with maximum beta-adrenergic receptor blockade, the attacks were eliminated.


Subarachnoid dissemination of thoracic chordoma.

Chordoma at the T-9 level, originally manifested by lumbosacral radiculopathy, developed in a 50-year-old man. The patient underwent three operations and radiation therapy for this condition, but ten years later, thoracic myelopathy developed, followed by left facial weakness. On autopsy, extensive dissemination of chordoma was found along the base of the brain and in the leptomeninges of the spinal cord.


An atypical case of delayed radiation necrosis of the brain.

A patient had radiation necrosis of the brain after treatment for a chromophobe adenoma of the pituitary. Atypically, and in contrast to most previously reported cases, clinical symptoms and signs were few. The computerized tomographic findings are discussed with a review of the relevant literature.


Benign recurrent aseptic meningitis (Mollaret's meningitis): case report and clinical review.

Benign recurrent aseptic meningitis (Mollaret's meningitis) is rare. Only five cases have been reported in this country. This article reports another case and briefly reviews the characteristic manifestations of this disorder.


Visualization of basilar invagination by computerized tomography.

Computerized tomography was used to visualize bony masses in the posterior fossa in a patient with basilar invagination associated with symptoms of vertebrobasilar insufficiency.


Provocation and mechanism of angle-closure glaucoma after iridectomy.

Dark room tests and prone-position tests in a lighted room and in a dark room were carried out on 64 eyes in 32 normal patients and 37 eyes of 30 patients that had undergone complicated iridectomy. Among the iridectomized eyes, the dark room tests and the prone-position test in lighted room caused elevation of intraocular pressure of more than 8 mm Hg in only 2.7% and 16.2%, respectively. Nearly 60% of the eyes showed positive results when the prone-position test was performed in a dark room. Our findings may provide experimental support for the theory of direct lens block as an angle-closure mechanism.


The human corneal endothelium in keratoconus: A specular microscopic study.

The corneal endothelium in 12 cases of keratoconus was examined with the clinical specular microscope. There appeared to be an increase in cellular pleomorphism with many cells considerably smaller than normal distributed throughout the endothelial cell population. There were also many large, elongated cells whose long axis showed a definite tendency to assume a similar directional orientation. The long axis of these cells seemed oriented toward the apex of the cone, and the cells appeared to have been stretched by the ectatic process. Many endothelial cells contained dark intracellular structures. Their significance is unknown. The single cornea in this series with a history of acute hydrops contained a localized area in which the endothelial cells were seven to ten times larger than normal. This suggests that rupture of the endothelium and Descemet's membrane, responsible for the acute edematous process, occurs at this site, and that the adjacent cells enlarged to fill the defect.


Epithelialization of the anterior chamber: clinical investigation with the specular microscope.

Four patients, each of whom had had an uncomplicated cataract extraction, were examined because of an apparent epithelialization of the anterior chamber. In each instance, the diagnosis was later verified histopathologically. The involved eye was photographed with the clinical specular microscope and the endothelial photomicrographs were analyzed. It was noted that considerable endothelial cell loss had occurred, as evidence by the larger size of the remaining cells. Endothelial cells were present but they were grossly abnormal well below the demarcation line visible with the slit-lamp biomicroscope. These in vivo observations support the thesis that damage to the corneal endothelium is a necessary factor for epithelial invasion of the anterior chamber.


The value of liver scintigraphy in choroidal melanoma.

Radionuclide liver scintigraphy was performed as part of the initial diagnostic evaluation in 35 patients with choroidal melanoma and no overt evidence of extraocular metastic diseases. The scans were normal in all but one patient in whom a solitary hepatic defect (due to an hemangioma) was found. The results of this study suggest that routine liver scans are not indicated in the initial staging evaluation of patients with choroidal melanoma, normal liver enzyme levels, and no other evidence of metastasis because of the low yield of scintigraphically detectable disease under these circumstances.


Latent, manifest latent, and congenital nystagmus.

Manifest latent nystagmus (MLN) was identified in 31 patients by accurate eye movement records. All the patients had horizontal tropias, and the nystagmus fast phases were always in the direction of viewing eye. The slow phases of MLN are decreasing-velocity exponentials while those of the jerk form of congenital nystagmus (CN) are increasing velocity exponentials. Several subjects who were believed to have latent nystagmus (LN) on clinical examination had small amplitude nystagmus evident by eye movement recording with both eyes open: these were actually cases of MLN. Many patients with MLN are misdiagnosed as having CN. An explanation for MLN and LN is provided based on confusion of egocentric directions between monocular and binocular viewing conditions.


Evaluation of Jensen procedures by saccades and diplopic fields.

A total of 15 eyes of 13 patients with lateral rectus palsies underwent Jensen procedures; one eye had a medial rectus recession and lateral rectus resection. It was arbitrarily decided to perform a Jensen procedure for patients with less than 40% normal abduction saccadic function. The patients' conditions were evaluated preoperatively and postoperatively by prism cover test. Versions, forced ductions, saccadic velocities, and diplopic field examinations were done. Postoperatively, all patients showed improved saccadic function; 12 of 13 patients acquired a functional range of diplopia-free vision; and 11 of 13 patients had aligned eyes with a good head position. By retrospective analysis we determined that the Jensen procedure gives good results for patients with severe lateral rectus palsy (less than 40% normal saccadic function).


Retinal wrinkling and macular heterotopia in diabetic retinopathy.

Retinal wrinkling of the posterior pole was studied in 40 eyes from 31 patients with diabetic retinopathy. Vitreoretinal traction was thought to produce the wrinkling in 32 of the eyes, in 13 of which macular heterotopia also developed, presumably from the same tractional forces. Epiretinal membrane formation was the apparent causal factor producing retinal wrinkling in six eyes and postphotocoagulation chorioretinal scarring in two eyes, in none of which macular heterotopia developed. Retinal wrinkling alone was associated with only mild or no visual acuity loss. Macular heterotopia was associated with more severe loss of visual acuity and with other visual symptoms. Displacement of retinal vessels was an important clue to the diagnosis of macular heterotopia.


Electro-oculogram testing in fundus flavimaculatus.

Electro-oculogram (EOG) measurements were obtained on seven patients with moderately extensive lesions of fundus flavimaculatus. Each patient was tested by two different methods of measuring EOG light-peak to dark-trough ratios. The results show that erroneously low ratios can be observed unless a diffusing sphere is employed in the determination of light-peak to dark-trough ratios in fundus flavimaculatus and presumably other diseases that affect primarily the posterior pole.


Vision threshold profiles in sector retinitis pigmentosa.

Absolute vision thresholds were measured along the horizontal and vertical meridians in four patients from one pedigree and one patient from a second pedigree with dominantly inherited sector retinitis pigmentosa. From these studies we find that (1) visual function is decreased for all parts of the retina, including the fovea, (2) rod and cone systems are affected to the same degree, and (3) the disease progression is confined to the inferior portion of the retina.


Aspiration cytodiagnosis of lid tumors.

In five patients, specimens of discrete, subepidermal lid tumors were successfully aspirated with 22- to 24-gauge spinal needles and dianosed cytologically. The simplicity, rapidity of diagnosis, and high accuracy of cytodiagnosis should make it a popular method for the evaluation of clinically puzzling subepidermal lid tumors.


Persistent pupillary membrane: successful medical management.

Persistent pupillary membranes usually undergo considerable atrophy during the first year of life. A minimum pupillary diameter of 1.5 mm is necessary for normal retinal image formation. Mydriatics, fixation pattern determination, and occlusion therapy as indicated can obviate the need for coreoplasty in patients with an extensive persistence of the pupillary membrane. We successfully treated a patient who had an almost total persistence of the pupillary membrane.


Laser iridotomy in closed-angle glaucoma.

An argon laser iridotomy was performed on 53 eyes of 34 patients with closed-angle glaucoma. Technically, all of the iridotomies were successful. Blue irides were more resistant to treatment than brown irides. The iridotomies were performed with high energy of 2 W and a very short exposure time of 0.01 to 0.04 s, thus minimizing thermal damage to adjacent tissues. Patients with narrow angles who underwent preventive laser irodotomy benefited most from the procedure, and all the eyes of this group maintained a normal intraocular pressure (IOP) after the iridotomy. Of the 20 eyes with acute angle-closure glaucoma, 17 maintained a normal IOP after iridotomy, and only three were resistant to this treatment, calling for filtering operations later. The IOP of eyes with chronic closed-angle glaucoma did not change after the procedure, and the iridocorneal angles remained practically the same. Argon laser iridotomy by this technique is highly recommended as the procedure of choice for eyes with acute angle-closure glaucoma and for preventive iridotomy in the fellow eye. The procedure is simple, is performed in the outpatient clinic, and engenders no major complications.


Lateral incomitancy in intermittent exotropia: cause and surgical therapy.

A hypothesis, previously proposed, of tight medial rectus muscles in conjunction with tight lateral rectus muscles associated with exodeviations as a cause of lateral incomitancy in intermittent exotropia is supported by clinical management. Three patients with these findings underwent bilateral medial rectus and lateral rectus recessions by means of the adjustable rectus recession technique. Primary position alignment was achieved, and rotations were balanced with the alleviation of the lateral incomitancy. The lateral rectus muscles were recessed an amount more than usual in order to compensate for the recession of the medial rectus muscles.


Influence of topically applied prazosin on the intraocular pressure of experimental animals.

Prazosin hydrochloride, an oral antihypertensive, is reported to inhibit phosphodiesterase and block postsynaptic alpha-adrenergic receptors, intraocular pressure (IOP) in rabbits was reduced in a dose-related manner following topical ocular application of concentrations of 0.0001% to 0.1%. The ocular hypotensive response lasted six to eight hours with a maximum effect at approximately two hours. The IOP of unilaterally sympathectomized rabbits treated in both eyes with prazosin decreased more in the normal eyes than in the sympathectomized eyes. Treatment of only the unsympathectomized eyes of these rabbits elicited a similar response. Normal rabbits elicited a similar response. Normal rabbits treated in only one eye also showed a slight response in the contralateral eye. Preliminary experiments did not support the hypothesis that these effects were due to a decrease of systemic blood pressure. No substantial ocular toxicity or pupillary changes were observed.


Dipivefrin and echothiophate: contraindications to combined use.

A study was undertaken to determine whether the antiesterase activity of echothiophate iodide would prevent the conversion of dipivefrin to epinephrine. Dipivefrin was administered singly and in combination with echothiophate to 24 adult rabbits. Administration of dipivefrin lowered the intraocular pressure (IOP) 8 +/- 1 mm Hg (P less than .001). When echothiophate was given before and concomitant with dipivefrin, there was no further decrease in IOP compared with that produced by echothiophate alone (5 +/- 1 mm Hg). Addition of epinephrine to eyes receiving dipivefrin plus echothiophate resulted in a significant additional decrease in IOP of 4 +/- 1 mm Hg (P less than .001). When echothiophate was given after dipivefrin had lowered the IOP and both drugs were continued, the IOP rose to baseline levels. These results fit the theory that the esterase converting dipivefrin to epinephrine is inactivated by cholinesterase inhibitors. The clinical use of cholinesterase inhibitors and dipivefrin may be contraindicated.


Kinetic vitreous fluorophotometry in experimental diabetes.

Kinetic vitreous fluorophotometry was used to measure dynamic alterations in blood-retinal barrier function. Normal hooded rats were compared with diabetic animals before and after insulin treatment. Rats with streptozocin-induced diabetes demonstrated significantly longer (P less than .001) half-periods of fluorescein loss from the vitreous when compared with controls, and insulin treatment significantly reduced (P less than .001) the mean half-period toward control values without normalization of serum glucose. These results suggest that kinetic vitreous fluorophotometry is a good indicator of blood-retinal barrier function and that sufficient amounts of insulin may be more important than normal blood glucose levels in recovery of altered barrier function in diabetes.


Tear film breakup time prolonged with unmedicated cellulose polymer inserts.

Unmedicated cellulose polymer (UCP) inserts exhibited marked superiority over six commercial artificial tear substitutes in enhancing and maintaining precorneal tear film stability as measured by tear film breakup time (BUT) in rabbits. The application of UCP inserts into one eye also resulted in an appreciable elevation of the BUT in the contralateral untreated eye. Sham inserts (polyethylene pieces) equal in size to our larger than UCP inserts lacked similar effects, which suggests that the latter actions of UCP inserts are most likely due to a slow release of polymer into the tear film rather than to induction of reflex responses associated with insertion of an inert foreign body into the cul-de-sac. The results indicate that UCP inserts, by virtue of their ability to maintain the integrity of the precorneal tear film over extended periods of time, may represent an important advance in the treatment of dry-eye diseases.


Dextran's effects on stressed lenses: water, electrolyte, and radioisotope studies.

To evaluate the beneficial effects of dextran 40 as an additive to infusion solutions, we studied an experimental model of lens stress with use of buffered, low calcium (Ca++)-containing solutions. Incubation in low Ca++ solutions (pCa = 10.7) for ten hours (stress period) resulted in lens swelling and electrolyte imbalances that were irreversible even with reincubation in physiologic, normal Ca++-containing media (pCa = 2.7) (recovery period). The addition of 6% or more of dextran to the media inhibited lens water gain during the stress period. It also rendered the resultant electrolyte imbalances reversible during the recovery period, thus exerting a protective effect. Radioisotope-tracer studies showed that dextran improved the ability of the lens to accumulate rubidium chloride Rb 86 and reduced its efflux during both the stress and recovery periods. Although dextran did not markedly decrease sodium chloride Na 22 uptake by lenses under stress, it did allow the lens to remove the 22Na during the recovery period.


Rhomboid flap in facial reconstruction. New concept of tension lines.

The rhomboid flap has become a popular reconstructive alternative for facial defects in recent years. Since the original description by Limberg, several modifications of the flap have been described, the most important of which was by Dufourmental. In the literature and at many soft-tissue courses, it has been taught that after rotation the maximum tension of the rhomboid flap is at the corner of the rhomboid most distant from the transposed flap. The author shows that the maximum tension of the flap is at the closure of the donor area. This phenomenon is amply illustrated with clinical cases. The Dufourmental modification is more satisfactory than the classical rhomboid flap in most cases because there is less tension on the closure. An understanding of these concepts is essential to the successful use of this important flap in order to avoid distortion of vital facial landmarks. I report a series of 30 consecutive rhomboid flaps.


The omocervical flap.

The omocervical flap is recommended for replacement of neck skin involved with malignancy or radioecrosis, carotid artery protection, or closure of pharyngostomes. The flap is very strong and reliable. It has a permanent pedicle and can be turned without delay. It will reach beyond the midline. By using appropriate lateral positioning of the patient, neck surgery and flap transfer can be accomplished with minimum difficulty. This flap is recommended as an excellent functional and cosmetic flap for neck reconstruction.


Synchronous multiple primary lesions of the upper aerodigestive system.

Multiple primary lesions were initially thought to be rare occurrences; however, recent numerous series show the incidence to vary from 1% to 11%. These reports generally refer to lesions that develop subsequently to diagnosis and treatment of the initial lesion, and the results of these studies reflect improved follow-up, treatment, and possibly a true increase in frequency. In the search for synchronously developing primary lesions, it was decided to perform panendoscopies on all cases of cancer of the upper aerodigestive tract, irrespective of size or situation or whether they were amenable to evaluation under local anesthesia. These panendoscopies were performed on 162 consecutive cases with a diagnosis of 15 synchronous second primary lesions, ie, an incidence of 9.2%. For this reason, as much time and effort as possible should be devoted to detecting the synchronous second primary lesion as the later developing lesion, and panendoscopy has proved invaluable in achieving this.


Revision of the endolymphatic subarachnoid shunt for Meniere's disease. Review of 59 cases.

Members of the Otologic Medical Group, Inc, Los Angeles, diagnose Meniere's disease in patients with fluctuating hearing loss, fluctuating tinnitus, episodic vertigo, and fluctuating pressure symptoms in the ear. Treatment is vasodilation. If medical treatment fails, an endolymphatic subarachnoid shunt operation is performed. If the shunt relieves symptoms for three or more months but symptoms then recur, revision of the shunt is recommended. If the revision surgery also fails, a destructive procedure is suggested.


A study of the practice of otorhinolaryngology in the United States. Initial findings.

Results of a national survey of nonfederal otorhinolaryngologist regarding their practices provide the following portrait of the typical physician who specializes in otorhinolaryngology: male, between 35 and 45 years old, engaged in solo practice in a metropolitan area in the southern part of the country. He works a 46-hour week, devoting most of his time to patient care. During a typical week, he sees 113 patients, mostly outside the hospital. Half of his patients are male; although their average age is 35, one fourth of his patients are under 15 years. Every third patient is new to him; every other patient has been referred. He spends almost 15 minutes with each patient, many of whom he is seeing on a continuous basis for a problem involving the ear. He prescribes medications in roughly half of all encounters; every tenth patient requires surgery. He rates the majority of the problems he encounters as chronic, and of minor to moderate severity and urgency--for which he provides services of limited complexity or less. He seldom refers his patients.


Noise and cochlear blood flow.

The effect of noise after unilateral transection of the cervical sympathetic trunk on cochlear blood flow was studied in anesthetized cats. The sound pressure level was 100 dB and the exposure time 6 min. Neither noise nor sympathectomy were found to affect the blood flow.


Acoustic trauma effects from doubling the exposure time.

Guinea pigs were exposed to 20 kHz for a period of 1 or 2 h, with and without an intermediate recovery period. Statistically smaller areas of damage were obtained after doubling the exposure time, especially without a recovery period. For a double exposure with a recovery period the areas of damage were the same as for the single exposures.


Auditory nerve activity and cochlear morphology after noise exposure.

Four chinchillas were exposed for 5 days to an octave band of noise centered at 4 kHz and having an SPL of 86 dB. After a recovery period of approximately 6 months, behavioral audiograms were obtained and auditory nerve fiber activity was recorded. The animals were killed and the cochleas embedded in plastic to obtain a surface preparation and 1 mu radial sections of the organ of Corti. Behavioral threshold shifts ranged from 5 to 20 dB at frequencies between 4 and 11 kHz. Auditory nerve fiber thresholds were elevated up to 70 dB for units with characteristic frequencies between 4 and 14 kHz. Units with higher and lower characteristic frequencies had normal thresholds. Cochleagrams showed narrow lesions of inner and/or outer hair cells over approximately a 1 mm distance. A comparison of the three realms of data revealed the following: (1) The greatest threshold shifts from the noise exposure were seen in the single nerve fiber thresholds while the smallest shifts were seen in the behavioral thresholds, (2) the greatest behavioral and neural threshold shifts and greatest cochlear damage occurred 1 octave above the center frequency of the noise exposure, and (3) based on the frequency-place map of the chinchilla cochlea, the range of fibers with elevated thresholds exceeded the extent of the OHC lesion. A number of anatomical changes were seen that effectively increased the extent of the damage found in the chochleagram. These changes included: distortions in the surface topography of the organ of Corti affecting the orientation of IHC; missing pillar cells in the presence of normal OHC and/or IHC and protrusion of the IHC cuticular plate into the subtectorial space.


Effects of acute noise traumata on whole-nerve and single-unit activity.

This paper gives some preliminary results of a research program on the effects of noise traumata on cochlear functioning. Measurements reported here include: the latency of the whole-nerve (compound) action potential (AP), the selectivity of frequency-tuning curves (e.g., the Q10-values) measured for the AP (with a forward-masking technique) and for single units in the antero-ventral cochlear nucleus (AVCN), the degree of phase-locking of the action potentials of these units to the stimulus waveform, and the phase of the stimulus waveform to which these potentials are locking. The noise traumata were induced during the experiments. After inducement of the traumata we found: an increase of AP latency, if a sinusoidal stimulas was presented at the same sound pressure level as before the trauma; no effect on AP latency (for most stimulus frequencies), if the latency values measured at the pre- and post-trauma thresholds were compared; a decrease of Q10-values of the AP frequency-tuning curves, (the pre-trauma Q10-values were small in comparison with single nerve fiber data); a decrease of the Q10-values of the single-unit frequency-tuning curves; no effect on the degree of phase-locking of the single-unit potentials to the stimulus waveform; an increase of cochlear response time calculated from the phase of the stimulus waveform to which the single-unit potentials are locking as a function of stimulus frequency.


Influence of thyroid state and improved hypoxia tolerance on noise-induced cochlea damage.

Guinea pigs were exposed to pure tone noise (2.7 kHz, 130 dB, 1 h) and cochlear microphonic potentials were measured 24 h after exposure. There is the possibility to modify the resulting noise-induced cochlea damage by regulating the function of the thyroid gland to alter the rate of metabolism. A hypofunction of the thyroid gland during sound exposure lessens, an over-function aggravates the damage. After gradual adaptation of the animals to a simulated 10,000 m altitude, the electrophysiologically demonstratable noise-induced damage was reduced. This might be explained by the greater hypoxia tolerance and perhaps additional better oxygen supply to the receptor cells.


Auditory function in guinea pigs treated with netilmicin and other aminoglycoside antibiotics.

The following aminoglycoside antibiotics netilmicin, sisomicin, gentamicin, and kanamycin were submitted to a comparative study of their ototoxicity using both reflexological (Preyer's pinnareflex) and electrophysiological (near and far field) methods. The daily s.c. administration of sisomicin, gentamicin, and kanamycin for 21 days provoked a dose-related impairment of the cochlear function, detected with all the employed techniques. On the other hand, a very low ototoxic effect of netilmicin was demonstrated with electrophysiological but not with the reflexological evaluation. The reliability of the methods used in these experiments is also compared.


Effects of modern loop diuretics on the inner ear a quantitative evaluation using computer technics.

The effects of some modern high ceiling loop diuretics on the guinea-pig's inner ear are tested. Short-time experiments are run registrating the cochlear microphonic potentials (CMP) before and after i.v. bolus injections of a diuretic. A 100-point matrix program is performed by automatic sampling of the CMPs after stimulating by five frequencies at 20 sound pressure levels each. Data can be plotted in different scales within 10 min after the end of a whole-day experiment. The data are on-line processed by a IBM 1800 computer.


Cell membrane alterations in the stria vascularis of the guinea pig after ethacrynic acid treatment studied by freeze-fracture.

A freeze-fracture examination of the stria vascularis during the first 2 h after injection of ethacrynic acid was performed. This showed a re-distribution of the particles on the membrane fracture faces of both marginal and intermediate cells. As oedematous spaces developed, particle-poor, vesicle-like structures were found associated with both cell types. The tight junctions at the apices of the marginal cells and around basal cells were unaffected.


The inner ear and the in vitro system.

The embryologic labyrinthine development of the CBA/CBA mouse occurs parallell in vivo and in vitro. Regarding post partum inner ears, either as cultured otocysts passing a corresponding time in vitro or inner ear explants of newborn/mature animals, the extracorporal system becomes unable to maintain specialized hair cell structures for more than a few days. The sensory cells themselves, however, survive for considerably longer time. Vestibular hair cells show sensory hair fusion. Cochlear hair cells loose their surface structures but the sensory hair rootlets penetrating into the cuticle are preserved. Post partum inner ears from the guinea pig reacted in a similar way in vitro as did labyrinths from the CBA/CBA mouse.


Localization of the marginal zone of the tectorial membrane in situ, unfixed, and with in vivo-like ionic milieu.

In order to determine the normal positional relationship between the tectorial membrane and the organ of Corti, a preparation method was developed which made it possible to study the unfixed tectorial membrane in its normal position in relation to the cochlea and with in vivo-like ionic conditions. With this method, post-mortem changes visible with the light microscope were detectable after 60 to 90 min instead of the normal 30 min. When endolymph of artifical endolymph are present in the scala media, the marginal zone lies in close contact with the surface of the organ of Corti. If the endolymph is replaced by artificial perilymph, first the marginal zone of the tectorial membrane, and later the whole membrane shrinks. At this stage, latex particles suspended in the perilymph are free to enter the subtectorial space.


Functions of different receptor systems in the reptilian labyrinth.

Different biopotentials, following a mechanical stimulus, were recorded from single hair cells of the reptilian labyrinth, with electronoptically circumscript localizations: 1. From the apical cell pole, the receptor potential, intracellular or from the ciliary surface, within the physiological range proportional to stimulus amplitude, frequency or phase, without delay, and with no real threshold of mechanosensitivity, as measured by ciliary displacement amplitude or velocity. 2. From the synaptic zone, in the basal region of the hair cell, or from contacting nerve endings, the synaptic potentials, local excitatory or inhibitory processes, respectively, with measurable latencies and with non-linear distortion. 3. From the (dendritic) endings of the first afferent neuron (or neurons), spike-shaped action potentials, synchronized by the (excitatory) synaptic potentials. Characteristic curves were plotted as a quantitative representation of the mechano-electric input-output relations of the different types of hair cells. For proceeding morphological and physiological system analysis, the comparison of the different submammalian inner-ear receptor systems gives us some new possibility of a closer correlation between ultrastructure and function.


Evidence of mechanical nonlinearity and frequency selective wave amplification in the cochlea.

A previously unsuspected mechanical response of the cochlear transduction mechanism has recently been discovered. It can be monitored outside the cochlear. Theorectical and experimental work leading to its discovery and identification are briefly reviewed. Its significance for models of the second filter and cochlear nonlinearity is discussed. An active wave amplification mechanism in the cochlea is proposed.


Local cochlear masking by frequency-modulated tone bursts.

Masking experiments are demonstrated for electrical frequency-modulated tone bursts from 1,000 to 10,000 cps and from 10,000 to 1,000 cps with superimposed clicks. The maximum of the masking was found at 3,700 cps ("narrow-band masking").


"Neural" responses to acoustic stimulation after destruction of cochlear hair cells.

Electrophysiological and histological observations in guinea pig's cochleas after amikacin treatment (14 X 450 mg/kg) confirm the results obtained in a former experiment: clear, short-latency, click-evoked responses were recorded in cochleas with only very few hair cells remaining at the extreme apex. Detailed analysis of these responses strongly indicates a neural origin and confirms their low-frequency sensitivity. Careful histological observations confirm the extensive hair cell loss and the preservation of nerve fibers in the remnants of the organ of Corti and of the vestibular sense organs. These results suggest that the acoustical vibrations either stimulate the vestibular receptors or act directly or through some kind of mechano-electrical transduction on the remaining cochlear nerve fibers.


Some aspects of temporal coding by single cochlear fibres from regions of cochlear hair cell degeneration in the guinea pig.

Some temporal coding properties of cochlear nerve fibers are investigated in kanamycin-treated guinea pigs (GPs) with various degrees of outer hair cell (OHC) degeneration. In particular, the phase locking ability of fibres from pathological cochleas, and also their adaptation properties are compared with the properties of normal cochlear fibres. No systematic effects of OHC loss on these properties have so far been found. These preliminary results therefore suggest (in so far as these animals can be regarded as models of sensorineural hearing loss of cochlear origin in man) that little deterioration should be expected in functions purely dependent upon faithful temporal coding of the stimulus waveform.


Grafting and electrical stimulation of the auditory nerve in cats.

The effect of implanting wire electrodes into the cochlea is limited by the deficit of nerve fibers in most diseases of the cochlea. Therefore, in a series of experiments it was tried, for the first time, to direct new outspreading nerve fibres into the afferent acoustic nerve by grafting a motor nerve to it. A second series of experiments should demonstrate the possibility of direct electrical stimulation of the eighs nerve by implanting wire electrodes via the transoccipital approach. The electrically evoked potentials, recorded at the auditory cortex, were compaired to potentials evoked by auditory stimulation. The answers to acoustic or electric stimulation showed no significant difference.


The permeability of 51Cr between cerebrospinal fluid and internal ear.

Radioactively labelled chromium was instilled in the cerebrospinal fluid of guinea pigs. After different intervals, the radioactivity of inner ear fluids was measured and compared with those of other regions. The results lead to kinetic information about the permeability of 51Cr between cerebrospinal and inner ear fluids.


Adenine nucleotides of the stria vascularis.

The levels of the adenine nucleotides ATP, ADP, and AMP in the stria vascularis were measured under normal conditions, and following various durations of ischemia. The concentrations of these compounds were used for the calculation of the adenylate energy charge, the energy status and the phosphorylation state of the stria. Following 10 min of ischemia the adenylate energy charge had decreased three fold, the energy status seven fold and the phosphorylation state 14 fold. To study the potential for recovery of strial function following various brief and prolonged ischemic intervals, a method for the perfusion of the ear via the anterior inferior cerebellar artery was developed. For various reasons it was found advantageous to use "artifical blood" as perfusate, relying upon fluorocarbons as oxygen carriers. The endolymphatic potential was used as electrical indicator of strial function. Recovery of the endolymphatic potential following brief periods of ischemia was paralleled by a corresponding increase of the ATP levels and a drastic decrease of the AMP levels of the stria vascularis. Preliminary results on the effects of substrate-free perfusion are presented.


Some vascular effects of noise exposure in the chinchilla cochlea.

Chinchillas were exposed to pink noise at levels ranging from 110 dB (for 8 h) to 125 dB (for 1/4 h). After a 3-week survival period, the animals were terminated without anesthesia and tissues were prepared using a soft-surface preparation technique [Axelsson et al., Acta Otolaryngol. 80, 362 (1975)]. Cochlear hair cell damage as well as vascular pathology was slight. On occasion, a vessel or vessel segment was obviously atypical, thus allowing noise-exposed animals to be differentiated from their non-noise-exposed controls. More often, however, differences between animals were more discrete and only evident through a computer analysis of the data. The specific effects of these particular noise-exposure parameters on the cochlear blood supply of the chinchilla will be discussed.


Assessment of peripheral arterial disease.

Atherosclerosis is epidemic in our community. Symptomatic peripheral arterial disease affects five to seven per cent of the population by retiring age. The major risk factors are smoking, high blood lipids and diabetes. A clinical history and examination of the peripheral pulses will precisely define the atherosclerotic occlusive lesions. Arteriography is only used as a preoperative measure in those patients requiring reconstructive vascular surgery.


Techniques of reconstruction for arterial insufficiency.

Arterial surgery has developed rapidly over the past thirty years, although the principles were well established at the start of the century. This article discusses the techniques currently used for arterial reconstruction of occlusive disease in the aorta, iliac and femoral arteries, and for embolectomy.


The management of intermittent claudication.

Many patients with intermittent claudication improve due to development of collateral vessels. Only a small proportion worsen, and few progress to severe ischaemia with the risk of amputation. Accordingly, most patients can be reassured and treated expectantly. Those patients have a reduced life expectancy compared with the population at large. Thus, surgical treatment should be reserved for patients who are severely restricted by claudication. The early technical results of arterial reconstruction for claudication are excellent. However, the late results are much worse in patients who continue to smoke. Nowadays, the complication rate from surgery is low.


Management of the severely ischaemic leg.

Ischaemic rest pain or tissue necrosis in the foot requires arterial reconstruction or lumbar sympathectomy if major amputation is to be avoided. Arterial reconstruction is preferred but if it is not possible, lumbar sympathectomy frequently is adequate. Conservative treatment is rarely successful. Arterial reconstruction is a relatively safe procedure, even in the elderly. The long-term survival rates are reasonably good, though appreciably less than for the general community. Many amputees have a short life expectancy and do not regain independence.


Unusual causes of arterial insufficiency.

Most patients with vascular insufficiency in the legs suffer from atherosclerosis. Thus, it is easy to miss the diagnosis in occasional patients with disease due to other causes. Mechanical and functional disorders which affect major arteries or arterioles are described.


Relationship of smoking to peripheral arterial disease.

Smoking is the most prevalent 'risk factor' causing atherosclerosis. The association is strongest for disease in arteries to the legs. Continued smoking worsens claudication, increases the risk of progression to gangrene, and decreases long-term patency rates of arterial reconstructions.


Prevalence of compound analgesic in Newcastle (NSW).

A household survey of analgesic use was carried out in two areas of different social advantage in Newcastle, New South Wales, during November 1977. The survey was preliminary to evaluating the proposed rescheduling of compound analgesics in the region. Approximately 16.5 per cent of the over 18-year-olds in the population claimed to use compound analgesics from time to time, and over 90 per cent used analgesics of some kind. Analgesic patterns varied between the two areas studied; of women living in the socially disadvantaged areas, about five per cent used compound analgesics daily. Rescheduling of compound analgesics may initially increase the workload of general practitioners, as up to one third of women who regularly use analgesics seek alternatives. A programme of public education and support is needed to assist compound analgesic users when rescheduling occurs.


First aid treatment of burns.

A burn refers to the damage caused to the skin, and sometimes deeper structures, by heat (flame, scald, contact, electricity), chemical agents or radiation. Methods of first-aid treatment of burns are varied, imprecise and sometimes harmful. This article deals with the major principles involved in first-aid, which when implemented will limit the damage created by the burn. The medical profession must be aware of what can be achieved and the necessary steps in the initial treatment of the burn. The profession is called upon to offer first-aid, to give advice and to lecture on accidents in our community, so it is necessary to have a clear plan of treatment.


The growth of medical manpower in New South Wales.

The postwar measures taken to increase medical manpower in New South Wales have been most successful, to the extent that the present number of medical practitioners available to the population exceeds the recommended level. These efforts have also been reasonably successful in providing more primary medical care in both country and some metropolitan areas. Calculations have been made to estimate how many doctors will be available to the year 1996 if; (a) present proposed training numbers are continued; (b) medical graduates are reduced by 100 per annum from 1985 (that is, 1980 student intakes); (c) medical graduates are reduced by 200 per annum from 1985. For the purpose of these calculations the immigration of doctors was neglected, which in the past has been responsible for a large percentage of the medical workforce. These conservative estimates show that with the 200 per annum reduction, there would still be an excess of doctors by 1991, but that the doctor/population ratio would be close to the recommended ratio by 1996.


Undergraduate teaching in primary medical care.

There is considerable variation between medical schools both in the timing of undergraduate teaching of general practice and in the methods of teaching. In 1976, the Faculty of Medicine in the University of Melbourne determined that the period of exposure of students to teaching primary medical care would be two weeks in the fourth year, and an optional eight weeks in the sixth year. This paper describes the fourth year teaching programme and its assessment by the students. Essentially, it consists of a two week course of clinical general practice in which an attempt is made to integrate the knowledge and experience gained from both hospital and community medicine.


Growth, reproductive productivity and longevity of mice fed polyunsaturated ruminant-derived foodstuffs.

The effects on the well-being of mice of feeding linoleic acid-enriched foodstuffs derived from ruminants receiving protected polyunsaturated oil were determined. Growth, reproductive productivity and longevity were compared in mice fed freeze-dried human diets containing either these products or the corresponding conventional ruminant-derived foods. A laboratory mouse pellet diet was used as a standard for the comparison. Growth rates and life spans were found to be similar in all three groups. Although the reproductive productivity of the mice on the polyunsaturated diet was never significantly different from that of mice on the conventional human diet, productivities of both groups on human diets were usually significantly below those of mice eating pellets. By the third generation of the second reproduction study, productivities of both these groups of mice had returned to the same level as those of mice eating pellets. Possible reasons for the depression in reproductive productivity in mice on the human diets are discussed. It was concluded that the polyunsaturated human diet neither impaired nor improved the lives of the animals eating the diet relative to the lives of animals eating the conventional human diet.


Metabolism and defluorination of fluoroacetate in the brush-tailed possum (Trichosurus vulpecula).

The brush-tailed possum (T. vulpecula) from Western Australia was found to be nearly 150 times more resistant to fluoroacetate intoxication in vivo than the same species from South Australia. Acetone powder preparations from the liver of animals from both populations showed similar abilities to convert fluoroacetate into fluorocitrate. Aconitate hydratase activity in liver preparations from both Western Australian and South Australian animals was similarly and competitively inhibited by fluorocitrate. Both animals were capable of defluorinating fluoroacetate at similar rates by a glutathione-dependent enzymic mechanism resulting in the formation of free fluoride ion and S-carboxymethylcysteine. Glutathione was also capable of partial protection against the toxic effects of fluoroacetate in vitro by a further unelucidated mechanism.


Changes in body composition and efficiency of food utilization for growth in young adult female rats before, during and after a period of food restriction.

Changes in body composition were studied in three groups of young adult female rats; the treatments were (1) ad libitum food intake to obtain normal growth, (2) restricted food intake to cause body weight loss, and (3) restricted followed by ad libitum food intake to obtain recovery of lost body weight. In each of the three groups of rats the percentage body water was linearly and negatively correlated with the percentage body fat, the weight of body water was linearly and positively correlated with the weight of body protein, and the ratio of the weight of body protein to water was relatively constant at 1:3.20 +/- 0.02 (mean +/- standard error). The percentage body water in the fat-free body was linearly and negatively correlated with fat-free body weight during normal growth between 109 and 334 g body weight but positively correlated during body weight loss and recovery. During recovery of body weight rats laid down more fat and less protein than during normal growth through the same body weight range and the percentage of digestible energy retained as body tissue was increased.


Sulfur and methionine metabolism in sheep. I. First approximations of sulfur pools in and sulfur flows from the reticulo-rumen.

Sulfur pools in the rumen and sulfur flows from the rumen were investigated in two experiments with sheep on a diet containing equal parts of oaten and lucerne chaffs. The diet was fed at two levels, either chopped or pelleted, and with intraruminal DL-methionine supplements. Ruminal fluid volumes and fluid flows to the omasum were measured. None of the treatments influenced ruminal fluid volume. Fluid flow to the omasum, however, was increased by increasing dry matter intake (DMI), and was further enhanced by feeding chaffed hay rather than the same materials ground and pelleted; the DL-methionine supplement had no effect. First approximation of the ruminal sulfur pools and of sulfur flows to the omasum were derived from the concentration of sulfur in true digesta and the ruminal fluid volume or fluid flow. Increasing DMI from 500 to 1000 g/day resulted in larger ruminal pools of total (1096 v. 792 mg), neutral (1016 v. 731 mg) and protein (479 v. 419 mg) sulfur, but the reducible sulfur pools were not affected by the level of DMI. Infusions of DL-methionine increased the ruminal sulfide sulfur pool irrespective of level of DMI. The first approximation of total sulfur flow was increased by 1660 mg/day at the higher level of DMI, due mainly to increases of 710 mg S/day as protein sulfur and 859 mg S/day as non-protein neutral sulfur. Flows of inorganic sulfate and ester sulfate sulfur, although small in comparison with organic sulfur flows, increased with level of DMI. Sulfide sulfur flows were also increased at the higher level of DMI, and were almost doubled by intraruminal infusions of DL-methionine.


Sulfur and methionine metabolism in sheep. II. Quantitative estimates of sulfur metabolism in the sheep's stomach.

The metabolism of dietary and supplemental DL-methionine sulfur in the stomach of sheep was studied in two experiments. In both experiments sheep were fed a 50 : 50 oaten chaff: lucerne chaff ration at two levels of intake, and some animals received intraruminal infusions of DL-methionine. In experiment 2 increasing dry matter intake (DMI) increased first approximations of total, neutral, protein and reducible sulfur flows and also sulfide sulfur flow from the reticulo-rumen. Increased DMI (from 500 to 1000 g/day) also resulted in greater true flows of total (2207 v. 1104 mg/day), neutral (1867 v. 1043 mg/day) and protein (893 v. 482 mg/day) sulfur at the duodenum. Two flow diagrams of sulfur metabolism in the compartments of the ruminant stomach were developed from the data of experiment 2. Fluid flows of sulfur in experiment 1 were used to supplement the data of experiment 2 in developing the balance models. The two models represent the extremes of dietary and supplemental sulfur metabolism in the sheep's stomach under the conditions of experiment 2, and they are discussed in relation to previous research on sulfur metabolism in the stomach.


Ovarian response to exogenous hormones in six-week-old lambs.

Crossbred lambs 5--6 weeks old were treated with human chorionic gonadotrophin (hCG) (500 or 1500 i.u.) alone, hCG plus pregnant mare serum gonadotrophin (PMSG) (1000 or 2000 i.u.), 1000 i.u. PMSG alone, or were untreated. PMSG alone and PMSG + hCG increased ovarian weight and uterine weight. PMSG alone stimulated growth and luteinization of follicles but PMSG + hCG induced ovulations and formation of corpora lutea. hCG alone did not change any of the characteristics which were measured. PMSG had a significant effect on the number of vesicular follicles but none of the treatments affected the number of growing follicles.


Effect of treatment with azathioprine on the responses of rat lymphocytes to phytohaemagglutinin.

The proliferative responses of rat peripheral blood lymphocytes (PBL) and spleen cells to phytohaemagglutinin (PHA) were studied after single or multiple (daily for 4 days) injections of azathioprine (AZ). Lymphopenia developed within 4 h of a single dose (78 mg/kg) of AZ and persisted for at least 72 h. There was no lymphopenia 24 h after the last of 4 daily injections. In vitro, PBL were more sensitive than spleen cells to the inhibitory effect of AZ. Likewise, the responses of PBL were relatively more depressed than those of spleen cells after single or multiple injections of AZ. The degree of depression was less than was expected from the effect of AZ in vitro. Multiple small doses were more depressive than multiple large doses. Serum from treated rats, used at 20% concentration, was more depressive than normal. Thus, rat lymphocytes are quite sensitive to AZ in vitro, but appear to be relatively resistant in vivo, this resistance resembling the resistance of the primary antibody response to AZ treatment.


Serological responses of sheep and cattle exposed to natural Toxoplasma infection.

During a four and a half year period a group of cattle was grazed continuously with a group of sheep and observed for Toxoplasma antibodies. Initially, there were 25 cattle and 31 sheep, but these were reduced to 19 and 18, respectively, by the end of the observation. Only transient antibody responses were noted in 2 cattle, whereas persistent titres developed in 12 sheep. Interpreted in the light of available information, these results were taken to indicate that cattle do not readily acquire persistent T. gondii infections.


The kinetic behaviour of radiolabelled IgG1 derived from different sources in adult sheep and neonatal lambs.

The turnover rate and pool volume of radiolabelled autologous IgG1 was similar to homologous IgG1 in adult sheep. In neonatal lambs there was no significant difference for either of these parameters between homologous serum IgG1 and maternal colostrum IgG1. However, the pool volume for IgG1 expanded by approx. 30% over the experimental period in the lambs. When the turnover rates were corrected for this increase they were found to be similar to those observed for IgG1 in adult animals.


Cytotoxicity studies of human melanoma cells and fibroblasts.

In seven human melanoma cell lines and one human fibroblast strain some correlation of resistance to cell killing was found with two bifunctional alkylating agents (melphalan, chlorambucil) and three monofunctional agents (4(5)-(3,3-dimethyl-l-triazeno)imidazole-5(4)-carboxamide (DTIC), methylmethane sulphonate (MMS) and N-methyl-N1-nitro-N-nitrosoguanidine (MNNG), but little cross-resistance was found between these two groups of agents or with cytosine arabinoside (ara-C). In contrast to previous studies with rodent tumours, potentially synergistic (chloroquine, arginine) or antagonistic (ascorbic acid, leucine) compounds did not affect the toxicity of melphalan in a human melanoma cell line. In two melanoma lines DTIC induced patterns of DNA damage (inhibition of semi-conservative synthesis) and repair (strand breaks and repair synthesis) similar to, but not identical with, those induced by the methylating agent MMNG. These results suggest that a methylating species is derived from DTIC but has a different reactivity toward DNA compared with MNNG.


Oxalate excretion in rats injected with xylitol or glycollate: stimulation by phenobarbitone pre-treatment.

The hypothesis that the prior intake of barbiturates may predispose patients to form increased amounts of oxalate following the intravenous infusion of xylitol was investigated in the rat. Phenobarbitone pre-treatment resulted in a 2-3 fold increase in urinary  [14C] oxalate concentration following the intraperitoneal injection of [U-14C] xylitol or [l -14C] glycollate. The absence of any marked changes in urine volumes and creatinine excretion implied that this increase in urinary oxalate excretion was due to the enhanced synthesis of oxalate. The activities of key enzymes in hepatic oxalate synthesis, glycollate oxidase, lactate dehydrogenase, catalase and alanine aminotransferase were not altered by phenobarbitone pre-treatment. It is suggested that the increased activity of the microsomal mixed function oxidases, following phenobarbitone treatment, may facilitate the oxidation of glycollate and possibly xylitol. This communication leads experimental support to the concept that the prior intake of drugs, such as barbiturates, may predispose patients to form increased amounts of oxalate.


A serological survey of Australian wildlife for antibodies to Leptospires of the Hebdomadis serogroup.

A serological survey for antibodies to Leptospira interrograns serovar hardjo was conducted on 574 serum samples from 10 native and 4 introduced wildlife species in south-eastern Australia. The microscopic agglutination (MA) test was used, and titres to hardjo antigen were detected in 33.5% of 352 brushtailed possums (Trichosurus vulpecula) sampled in several areas of Victoria. Prevalence of reactors ranged from 14 to 66% in 4 populations examined intensively. Serovar balcanica was isolated from possums with hardjo antibodies from two different areas. Of 20 wombats Vombatus ursinus) examined in Victoria, antibodies to hardjo were found in sera from 4 and titres to Pyrogenes and Pomona serogroups were detected in another. Hardjo antibodies were demonstrated in sera from 13 of 19 rusa deer (Cervus timorensis). Negative MA test results to hardjo antigens were recorded in 55 mountain possums (T. caninus), 63 macropods (Macropus spp.), 17 water rats (Hydrmys chrysogaster), 39 fallow deer (Dama dama), 2 hog deer (Axis porcinus) and 2 water buffalo (Bubalus bubalus). No MA antibodies to any of 16 leptospiral serogroups were detected in 17 water rats tested. Kidneys were examined from 330 of these animals and focal interstitial nephritis suggestive of leptospirosis was found in kidneys of 63 of 169 T. vulpecula, 3 of 55 T. caninus, 12 of 18 V. ursinus, 6 of 22 Macropus spp., 9 of 16 H. chrysogaster, 5 of 11 C. timorensis and 3 of 39 D. dama. A statistical association between focal interstitial nephritis and MA antibodies to hardjo was found in T. vulpecula.


A sero-epidemiological study of Leptospira interrogans serovar Balcanica in four brush-tailed possum populations in Victoria, Australia.

The microscopic agglutination (MA) test was utilised to study the prevalence of antibodies to Leptospira interrogans serovar hardjo in 4 populations of brush-tailed possums (Trichosurus vulpecula). The overall antibody prevalence varied from 14% to 66%; however, the age distribution of MA test titres was remarkably similar in all 4 populations. Antibody prevalence was similar in both males and females and demonstrable antibodies were limited to sexually mature animals. The greater prevalence of high titres (greater than or equal to 1:128) in the 18- to 24-month age group suggested that primary infections were acquired at this age. The findings suggested that infection was maintained in possum populations by direct transmission, probably associated with breeding. Focal interstitial nephritis was observed in kidneys of possums greater than 18 months of age and was associated with MA titres to hardjo (P less than 0.001). Serovar balcanica was isolated from possum kidneys from 2 of these populations, suggesting that balcanica infections were responsible for most of the hardjo titres. However, agglutinin-absorption tests indicated that some possums may be infected with a leptospire more closely related to hardjo than to balcanica.


Alteration in cell division, morphology and motility induced by the toxic principle of lupinosis.

A number of experiments are described in which the effect of the toxins causing lupinosis on cell morphology and motility is examined. The toxins arrested cells in metaphase leading to abnormal profiles, and inhibited leucocyte migration. Similar results were obtained with colchicine on cell division and, from the evidence obtained, it is suggested that the mechanism of action of the two agents is similar and that the same binding sites are probably involved.


Inhibition of Tamm-Horsfall glycoprotein induction of alkaline phosphatase in cystic fibrosis fibroblasts by medium conditioned by normal cells.

It is confirmed that the level of alkaline phosphatase in fibroblasts derived from cystic fibrosis patients can be induced many-fold by growing the cells in the presence of Tamm-Horsfall glycoprotein. It is further shown that normal fibroblasts produce a "CF corrective factor" which markedly inhibits this phenomenon. These observations support a previous hypothesis on the nature of the metabolic defect in cystic fibrosis.


Isolation and growth characteristics of psittacine viruses in chicken embryos.

Eight viruses were isolated in embryonating eggs, from psittacine birds comprising a cockatiel, a budgerigar, 3 parrots, a love bird, and 2 rosellas. Initial attempts at isolation used 3 routes of embryo inoculation: yolk sac, allantoic sac, and chorioallantoic membrane (CAM). The most sensitive route was determined for 6 of the isolates by making comparative titrations by yolk sac, allantoic sac, and CAM routes of inoculation. In growth-curve studies of 6 of the isolates, virus concentration was determined daily for 5-6 days postinoculation in the CAM, allantoamnionic fluid, and liver. Peak virus concentrations appeared in about 72 hours. The embryonic lesions observed are described. Only one of the isolates hemagglutinated fowl red blood cells.


Characterization of paramyxo-, herpes-, and orbiviruses isolated from psittacine birds.

Isolates of paramyxo-, herpes-, and orbiviruses from psittacine birds were characterized in the course of studies in cell cultures. The LBD-1 isolate, from a lovebird, was grown in chick kidney (CK) cells. It had the properties of a paramyxovirus but was found tobe serologically distinct from known avian paramyxoviruses. This virus was pathogenic for Japanese quail but not for young chickens or budgerigars. RSL-1 and -2, isolated from diseased rosellas, were propagated in chicken embryo fibroblasts and CK cells, and were found similar to other herpesviruses in physicochemical and morphological properties. They were immunologically related to the psittacine herpesvirus which causes Pacheco's parrot disease, and when inoculated into budgerigars produced clinical disease and death with hepatic lesions. The CKT-1 and PKT-1 isolates, from a cockatiel and a budgerigar, grew in fibroblastic cell cultures from several species. Their physicochemical properties suggested that they should be classified as members of the orbivirus group. They were mildly pathogenic for budgerigars.


Toxicity of endotoxin to chicks.

Large doses of purified lipopolysaccharide (LPS) purified from Escherichia coli induced clinical signs but no mortality in chicks. Five chicks survived a mean dose of 517 mg/kg. One individual that received LPS at 577 mg/kg recovered from clinical manifestations within two days. Attempts failed to produce a generalized Shwartzman-like reaction with two intravenous inoculations of LPS at about 24-hour intervals. Prior injection of uric acid did not protect chicks from LPS by intravenous exposure.


Isolation of an etiologic agent of acute respiratory disease (rhinotracheitis) of turkey poults.

A small gram-negative motile bacillus was isolated from laboratory poults affected by acute respiratory disease (rhinotracheitis) of turkeys. The bacterium was inoculated intranasally into susceptible day-old poults; the poults developed typical clinical signs of acute respiratory disease, and the bacterium was reisolated. This same bacterium was isolated from commercial poults with typical signs of acute respiratory disease but not from poults of similar age which were clinically normal. The bacterium has not been identified taxonomically. We conclude that it is a primary etiologic agent for acute respiratory disease of turkey poults.


Fungus species isolated from commercial hatcheries in Alabama.

Selected locations (incubators, incubator rooms, hatchers, hatcher rooms, chick pools, and egg rooms) in six commercial broiler hatcheries in Alabama were sampled for fungus species over a 12-month period (May 1977-April 1978) by open-plate techniques (cornmeal agar or Sabouraud's dextrose agar). Colonies at each location were counted at 24, 48, and 72-120 hours postexposure. Thirty-five species representing 21 genera were identified. The most prevalent genera were Cladosporium, Penicillium, Aspergillus, Geotrichum, and Fusarium. Aspergillus fumigatus was associated with clinical disease in the baby chick on several occasions, and Cladosporium cladosporioides was the most prevalent species isolated. In general, isolations increased in early spring and summer.


Hemolytic complement in specific-pathogen-free chickens: influence of age and sex.

Six groups of specific-pathogen-free (SPF) chickens of various ages were tested for hemolytic complement (C) activity with a radial hemolytic diffusion technique. The chickens tested were 2, 6, 7, and 8 weeks old. Chickens 2 weeks old were found to have little hemolytic activity compared with chickens 6 to 8 weeks old. Mean titers were similar in the older chickens. No significant differences were found in C titers between males and females, unlike reports for mice.


Vaccination of ring-necked pheasant for marble spleen disease.

Laboratory evidence indicates that a safe and effective procedure was developed for vaccinating pheasants against marble spleen disease. Field trials confirm the safety of the vaccine and suggest that vaccination will prevent marble spleen disease. Vaccination is by drinking-water administration of turkey-spleen-propagated turkey-origin live avirulent virus to pheasants 4 1/2 weeks old or older. The effect of field vaccination was studied in 39,000 pheasants in pens where recurrent annual mortality had been 5-15%.


Response of women mountaineers to maximal exercise during hypoxia.

Eight members of the American Women's Himalayan Expedition, ranging in age from 20-49, performed maximal exercise on a treadmill under normoxic and acute hypoxic (12.58% O2) conditions. Normoxic values for VO2 max were above average for all subjects and did not decline with age. The mean decrease in VO2 max (26.7%) during hypoxia was equivalent to that reported for younger males, which suggests that age was not a factor in response to hypoxia. Maximal heart rate, respiratory exchange ratio, oxygen pulse, and walk time were lower in hypoxia while ventilatory equivalent and blood lactate were higher. VEmax BTPS, was the same under both conditions. The combination of laboratory results and field observations by the Expedition physician suggest that women are capable of performing hard work at high altitude if they are in good condition and properly acclimatized.


Effects of vaccination for Marek's disease on growth of a Marek's-virus-induced transplantable lymphoma in syngeneic and allogeneic chickens.

A study was made of the effects of vaccination with turkey herpesvirus on the growth of tumors following inoculation of lymphoma cells induced by Marek's disease virus (MDV). The cells used were from a transplantable MDV-induced lymphoid tumor (MDT-198) maintained by passaging in syngeneic hosts. Vaccination did not prevent progressive tumor growth or alter subsequent mortality among syngeneic recipients of MDT-198 cells. With allogeneic recipients, however, vaccination had a significant protective effect in that progressive tumor growth and mortality were markedly lowered. Both development of visceral lymphomas and atrophy of thymus and bursa were found at necropsy in both syngeneic and allogeneic hosts when progressive tumor growth occurred at the site of inoculation. The results suggest that it is unlikely that the primary and effective component of turkey-herpesvirus-induced protection against Marek's disease is directed against Marek's-disease-tumor-specific antigens.


Effect of cockpit temperature gradients on the validity of single-point measurements.

Dry bulb temperature was measured at six sites throughout seven sorties in F4E aircraft in a study of vertical and lateral cockpit temperature gradients designed to determine the validity of single-point measurements. The results show that both vertical and lateral gradients exist in F4E aircraft and that single-point measurements of Tdb close to the right shoulder show a bias of up to 4 degrees C in relation to mean cockpit dry bulb temperature derived from measurements at five sites. This bias may be removed by using the predictive relationships developed in this study. The relationship between black globe and dry bulb temperatures is also given for F4E aircraft flown in warm, sunny conditions.


A streptomycin-dependent live pasteurella multocida type-3 vaccine for the prevention of fowl cholera in turkeys.

A live streptomycin-dependent Pasteurella multocida (Serotype 3) vaccine was found to protect turkeys orally and parenterally against homologous challenge.


Experimental Newcastle disease virus infections in three species of wild birds.

Three species of wild birds--the red-winged blackbird (Agelaius phoeniceus), an African weaver finch (Quelea quelea), and the sandhill crane (Grus canadensis)--were exposed to Newcastle disease virus (NDV) to determine susceptibility and host response. The NDV used were a vaccine strain (LaSota) and a viscerotropic velogenic strain (New York Parrot). Host response was monitored by virus isolation, signs of disease, and serologic response. Both the red-winged blackbirds and the quelea shed little virus and developed low antibody titers. A low mortality in the blackbirds did not appear to be due to ND alone. Vaccinated cranes were well protected against velogenic challenge, whereas unvaccinated cranes shed the velogenic virus from the cloaca for weeks. The ramifications of the low antibody titers produced in birds of two species are discussed, as well as the potential involvement of each species in transmission of the virus.


Influence of body temperature on nitrogen transport and decompression sickness in fish.

Incidence of lethal bends and intravascular bubbles has been studied in the eel (Anguilla anguila L.) submitted to hyperbaric air decompressions at temperatures of 17 and 27 degrees C. The fish was an accurate model to seek the nature of the inert gas transport limiting process (diffusion or perfusion) because an increase in temperature considerably influences the rate of perfusion whereas the properties of gases vary in relatively lower proportions. Qualitative and quantitative analysis of the results are consistent with the hypothesis of a diffusion limited nitrogen transport through the tissues of the decompressed eel.


Separation of the effects of raised skin and core temperature on performance of a pursuit rotor task.

Performance of a pursuit rotor task was studied during induced cycles of core temperature between limits of 37.9 degrees C and 38.5 degrees C. At each level of core temperature tested (37.9 degrees C, 38.5 degrees C, and 38.5 degrees C) performance was significantly worse during heating, when skin temperatures were high, than during cooling. The observed decrements were 13.6% at 37.9 degrees C, 16.0% at 38.2 degrees C and 18.1% at 38.5 degrees C. While it may be true that the performance changes were caused by changes in the level of skin temperature, the direction and rate of change of both core and skin temperatures may be important determinants of performance. The results are discussed in relation to current arousal theory.


Prevention of egg transmission of Mycoplasma meleagridis by antibiotic treatment of naturally and experimentally infected turkey eggs.

Turkey eggs infected naturally and experimentally and treated with 1 mg of tylosin or gentamicin before incubation produced progeny with less infection with Mycoplasma meleagridis than did infected but untreated eggs. Higher doses of gentamicin eliminated infection, as indicated by an absence of M. meleagridis antibodies in poults tested at 3 weeks and retested at 5 weeks of age. The rate of reduction or elimination of egg transmission was correlated negatively with the incidence of M. meleagridis infection in untreated controls. Hatchability was reduced by gentamicin, especially at doses of 1.75 and 2 mg, whereas tylosin at 1 mg/egg improved hatchability.


Psychophysical assessment of angular vibration: comparison of vertical and roll vibrations.

A psychophysical matching experiment was conducted to compare the perceived intensity of roll vibration with the perceived intensity of Z-axis translational vibration. Seated subjects matched their perceptions of the intensity of Z-axis vibrations by adjusting the intensity of roll vibrations of the same frequency. The Z-axis stimuli were administered at seven frequencies (from 2.5 to 10 Hz) at each of three intensity levels: the 25-min Fatigue-Decreased Proficiency (FDP) level, the 1-hr FDP level, and the 2.5-hr FDP level, as defined in ISO Standard 2631-1974. The results showed that the acceleration of the roll matching response increased significantly as a function of both the intensity and the frequency of the stimulus vibrations. Since the stimuli were chosen from existing Z-axis equal intensity contours, the mean matching responses define equivalent contours of equal intensity for roll vibration. These results provide information on the relationship between Z-axis vibrations measured in translational acceleration units of G and roll vibrations measured in angular acceleration units of rad/s2. The determination of such relationships is essential for the development of improved vibration exposure criteria applicable to complex vibration environments.


Temperature changes during exercise measured by thermography.

The present study explores the dynamic changes of surface temperatures associated with peripheral vascular shifts during and following hand gripping, one-legged ergometric, and running exercise. An AGA 680 thermovision system, incorporating a Bolex 16-mm camera and displaying 10-colored isotherms on a slave monitor, generated synchronous infrared (IR) movies at 16 frame/s. Incremental increases in surface skin temperatures (Ts) were observed while gripping at 20, 50, and 80% of maximum with a peak rise of 1.7 degrees C. Thermographic recorded Ts changes during dynamic one-legged exercise were higher in the exercising leg than the resting leg. Surface temperatures dropped in both limbs following exercise. The advantages of the use of thermography during transient thermal states, as produced by dynamic exercise, is supported by comparative Ts data taken from thermograms and thermistors.


Effect of physical training at moderate altitude (1850 m) on hypoxic tolerance.

Effect of systematic physical training at moderate altitude (1850 m) on hypoxic tolerance was estimated on a group of young soldiers, by determining the Time of Useful Consciousness (TUC) at a simulated altitude of 7620 m in a hypobaric chamber together with the Critical Flicker Frequency (CFF) test. The subjects, after initial testing at Delhi (near sea level) were taken to an altitude of 1850 m and divided into two groups. One group was given systematic endurance physical training for 8 weeks, while the other group served as control. The subjects were then taken to an altitude of 3500 m and kept at that altitude for 4 weeks, after which they were brought back to Delhi and TUC was estimated again within 2 d. The results indicate that endurance physical training at moderate altitude improved hypoxic tolerance and the central nervous system activity under hypoxia.


Hyperventilation in aircrew: a review.

The causes and effects of hyperventilation, relevant to the flight environment, have been reviewed and one case history is presented. Methods of investigating in-flight hyperventilation are discussed.


Epileptic-type convulsions and magnesium deficiency.

Immediately following 4 h of continuous exercise at +/- 45% Vo2max in heat, a 23-year-old, well-trained man displayed epileptic-type convulsions. One week preceeding this incident, he completed an identical work test successfully under room temperature conditions. An assessment of his physiological and biochemical results indicated only one abnormality: during exercise in heat, an abnormally low serum magnesium concentration prevailed for most of the test. Treatment with phenobarb and magnesium chloride enteric tablets ("Slow Mag", 2 x 535 mg/d) reversed the biochemical abnormality. After checking his resting serum magnesium, the subject subsequently heat acclimatized and repeated similar treadmill tests as before without any ill effects.


Measuring instrument for the determination of the oxygen consumption of scuba divers in open waters.

An apparatus is described for the estimation of incremental oxygen consumption and carbon-dioxide production of SCUBA divers working in the field. Air is supplied to the diver in discrete volumes, and aliquots of respired air collected from each discrete time interval.


Inheritance of isozyme variation and heterozygosity in Pinus ponderosa.

Techniques are presented to detect 23 isozyme loci in the long-lived perennial plant, ponderosa pine. Meiotically derived megagametophyte from seeds is used to examine directly the segregation of allelic variants. Approximately seven seeds were initially examined for 12 enzymes from each of 47 trees from ten stands throughout the northern Rocky Mountain region. Additional seeds were also examined from selected families to confirm the inheritance of observed electrophoretic variants at 13 polymorphic loci and to estimate linkage relationship. Significant norandom segregation was consistently detected for three pairs of loci: ADH-1:AAT-2, ADH-1:PGI-1, and LAP-2:6PG-1. Preliminary estimates of population parameters reveal a relatively high average heterozygosity (H = 0.123). This is partitioned into a high amont of genetic variation within local stands, with only approximately 12% of the total heterozygosity resulting from genic difference between stands.


Genetic polymorphism of the major parotid salivary glycoprotein (Gl) with linkage to the genes for Pr, Db, and Pa.

Genetic polymorphism of the major glycoprotein (Gl) found in parotid saliva is determined by autosomal inheritance of one unexpressed and four expressed alleles. This hypothesis is supported by studies in 41 white families including 146 children. For 143 randomly collected salivas from whites and 82 randomly collected salivas from blacks, maximum likelihood estimates of the gene frequencies are as follows: for whites, Gl1 = 0.742, Gl2 = 0.040, Gl3 = 0.155, Gl4 = 0.017, Gl0 = 0.46; for blacks, Gl1 = 0.459, Gl2 = 0.050, Gl3 = 0.337, Gl4 = 0.044, Gl0 = 0.110. There is strong evidence for linkage of Gl/Pr (seven families, lod score at theta = 0 is 5.24) and G1/Db (eight families, lod score at theta = 0 is 4.45). The allelic products of Gl show evidence for linkage disequilibrium with the products of the Pr, Db, and Pa loci (P less than 0.0005). On the basis of varying degrees of linkage disequilibrium, Gl may be closer to Db than to Pr or Pa and on the "outside" of Db with respect to Pr or Pa. Amino acid analyses of Gl 1 and Gl 4 proteins show strong resemblances in composition to the major basic glycoprotein and the acidic proline-rich proteins of parotid saliva described by other workers. The polymorphic forms of the Gl proteins show microheterogeneity due to variability in charge and molecular weight. The electrophoretic polymorphism appears to be determined by apparent differences in molecular weights between the Gl proteins.


Distinguishing allozymes and isozymes of phosphoglucoisomerases by electrophoretic comparisons of pollen and somatic tissues.

The different electrophoretic patterns of dimeric phosphoglucoisomerases extracted from haploid pollen and diploid somatic tissues of plants may be used to distinguish allozymes and isozymes. The analysis depends on the presence of two alleles at each locus in somatic tissues but only one or the other allele in pollen grains. Consequently, in heterozygotes, heterodimeric allozymes can be identified because they are formed in stems and leaves but not in pollen. The procedure is described in enzymes extracted from the diploid annual plant Clarkia dudleyana, which possesses three gene loci for PGI subunits. Comparison of the electrophoretic patterns of stem and pollen extracts makes it possible in many cases to identify allelic state without breeding tests. The technique also is likely to be useful in the interpretation of zymograms of other multimeric enzymes coded by more than one gene locus.


DNA of Akodon (Rodentia, Cricetidae). I. Biophysical characterization.

Buoyant density in CsCl, melting temperature, and G + C base content of the DNA from four species of Akodon (Rodentia, Cricetidae) were determined. The buoyant density values of 1.699-1.701 g/cm3 were in accordance with the data reported for other cricetids. No satellite bands were seen in neutral CsCl. The Tm values determined in 1 x SSC ranged from 86.2 to 87.0 C, which corresponds to G + C contents of 41.2-43.2%. There was good agreement in DNA base composition of the four species, although values were slightly higher in A. obscurus, suggesting a certain degree of interspecies variability.


Biochemical characterization of "LAP," a polymorphic aminopeptidase from the blue mussel, Mytilus edulis.

A genetically variable naphthylamidase enzyme, previously described as "leucine aminopeptidase," was purified approximately fiftyfold, and its biochemical properties were investigated. The enzyme was renamed "aminopeptidase I." Substrate affinities demonstrate that it is an alpha-aminoacyl peptide hydrolase (E.C. 3.4.11.-). Aminopeptidase I had a monomer molecular weight of 65--68,000, average of pI of pH 4.88, and broad pH optima between 6.5 and 8.0. The enzyme was inactivated rapidly between 40 and 50 C. Antibodies from purified enzyme did not cross-react with other naphthylamidases, but aminopeptidase I activity was inhibited by immune serum. The enzyme exhibited highest naphthylamidase activity for aromatic and hydrophobic aminoacyl naphthylamides. Aminopeptidase activity was highest for aromatic and hydrophobic N-terminal residues of tripeptides. Certain divalent metal cations, p-OH-mercuribenzoate, and N-ethylmaleimide were strongly inhibitory while chelating agents activated the enzyme.


Expression of PGK-A in the Australian brush-tailed possum, Trichosurus vulpecula (Kerr), consistent with paternal X inactivation.

An extensive survey of erythrocytes of marsupials other than kangaroos for electrophoretic variation if X-linked enzymes revealed two rare PGK-A phenotypes in the phalangerid Trichosurus vupecula and one in Trichosurus caninus. Four putatively heterozygous females expressed only the variant allelic isozyme in some tissues but expressed a trace of the normal isozyme in others. A putatively hemizygous male expressed only the variant isozyme in all tissues. The phenotypic patterns were consistent with those observed in kangaroos known to exhibit partial or complete parternal X inactivation in cells of females. Tow of the T. vulpecula were a mother and her female pouch young, further suggesting that paternal X inactivation occurs in T. vulpecula. This peculiar mechanism of dosage compensation may not be restricted to kangaroos.


Evolution of fraction 1 protein in the genus Lycopersicon.

The large- and small-subunit polypeptide composition of fraction 1 protein contained in seven species of Lycopersicon and Solanum pennellii was determined by electrofocusing. The eight species of protein had large subunits composed of three polypeptides separated by about 0.05 pH unit, but there was no difference in the isoelectric points of the clusters of three polypeptides. By this criterion, no surviving mutations have appeared in the extranuclear DNA coding for the cluster of large-subunit polypeptides during a period of evolution which generated the eight species of plants. The genus Lycopersicon appears to be much younger than its sister genus Nicotiana in the family Solanaceae, where four types of polypeptide clusters have evolved. Three different small-subunit polypeptides whose isoelectric points are coded by nuclear DNA have arisen among the seven Lycopersicon species, and L. hirsutum and S. pennellii have proteins containing single polypeptides and are therefore considered older than L. chilense, L. chimielewskii, and L. parviflorum, whose proteins contain two polypeptides. L. cheesemanii, L. pimpinellifolium, and L. esculentum (and probably L. peruvianum) seem to be the most recently evolved species since their fraction 1 proteins have small subunits composed of three polypeptides.


Segregation of the isozymes of flax genotrophs.

The segregation of isozymes of peroxidase and acid phosphatase in progenies of crosses between large (L) and small (S and L6) flax genotrophs has been determined. The peroxidase isozymes segregated as expected on a simple Mendelian model with a dominant and a recessive allele and with the L genotroph being a homozygous dominant. All the peroxidase isozymes which differed segregated together, so the isozymes are controlled by either a single locus or closely linked loci. The acid phosphatase isozymes in the F1 were all L type, but the segregations observed in the F2 were not always consistent with a simple Mendelian model.


Labelling of the intramembranous region of the major sialoglycoprotein of human erythrocytes with a photosensitive hydrophobic probe.

Human erythrocyte membranes were incubated with the photosensitive hydrophobic reagent 1-azido-r-iodo[3H]benzene and the mixture was irradiated. The major sialoglycoprotein was then isolated and the labelled polypeptide subjected to proteolytic dissection. Characterization of the purified tryptic and chymotryptic peptides show that the probe is covalently attached only to the transmembrane region of the protein. This labelling pattern is discussed in relation to the use of such reagents for the identification of segments of membrane proteins exposed to the hydrophobic millieu of the membrane.


Studies on horseradish peroxidase in dimethyl sulphoxide/water mixtures. The activation of hydrogen peroxide and the binding of fluoride.

We studied the variation in spectra and in reactivity towards H2O2 of solutions of horseradish peroxidase in dimethyl sulphoxide/water mixtures, obtained by diluting stock solutions of the enzyme in either water or dimethyl sulphoxide, and assayed the enzyme activity and studied the binding of F- by the peroxidase in 65% (v/v) dimethyl sulphoxide. A broadly similar pattern of changes is observed whether one starts from water or from dimethyl sulphoxide; the changes are essentially reversible, though hysteresis is observed. When the dimethyl sulphoxide content of the solvent mixture is increased, the peroxidase retains its ability to activate H2O2 up to 74% (v/v) dimethyl sulphoxide. The peroxidase in 65% (v/v) dimethyl sulphoxide binds F- together with a proton (or the equivalent loss of HO-), as already established for aqueous solutions. We point out that the occurrence in such solutions of both the ability to activate H2O2 and the inability to bind F- without taking up H+ or losing HO- supports the proposed mechanism for activating H202, whereby the protein binds the substrate in the form of the much more reactive HO2-.


Use of photosensitive hydrophobic probes to label the membrane of the human erythrocyte.

Two photosensitive hydrophobic probes, azido [3H]benzene and 1-azido-4-iodo[3H]-benzene, have been compared for their effectiveness in labelling, selectively, the intramembranous domains of lipid and proteins. Both partition preferentially into the lipid bilayer and, upon irradiation, covalently attach to both phospholipids and membrane proteins; the more extrinsic polypeptides have a significantly lower specific radioactivity than that of the intrinsic species. Proteolytic experiments also reveal higher labelling of intramembranous regions of the proteins. Consistently, the iodinated form of the probe showed the greater preference for the non-polar phase and a higher degree of selectivity for labelling hydrophobic regions. The results also suggest that penetration through the annulus of tightly bound lipid surrounding integral proteins occurs readily.


Studies on haemin in dimethyl sulphoxide/water mixtures.

The nature of the complexes and equilibria shown by solutions of protohaemin in dimethyl sulphoxide/water mixtures and in the presence of acid and base were studied by u.v.-visible spectrophotometry. In neutral solutions containing from 40 to 100% dimethyl sulphoxide, haemin is present as a monomeric complex in which the Cl-ion is not coordinated. Only a single pH-dependent equilibrium pK12 is observed over the range 40-80% dimethylsulphoxide, corresponding to formation of the mu-oxo dimer. As the dimethyl sulphoxide content is lowered below 35%, so the single equilibrium (pK12) is replaced by two equilibria (pK1 and pK2); with solutions of 5 microM-haemin, pK1 decreases (from pK12 7.55 in 65% dimethyl sulphoxide to pK1 approx. 1.5 in 0.01% dimethyl sulphoxide), whereas pK2 hardly changes (from pK12 7.55 in 65% to pK2 approx. 7.5 in 0.01%).


The variation with age of the structure of chromatin in three cell types from rat liver.

The organization of chromatin in three rat liver nuclear populations, namely diploid stromal, diploid parenchymal, and tetraploid parenchymal nuclei, which were separated by zonal centrifugation, was studied by digestion with micrococcal nuclease and pancreatic deoxyribonuclease in 3-week-old rats in which the parenchymal cells contain diploid nuclei and in 2-and 4-month-old rats with a high proportion of tetraploid nuclei. Digestion by micrococcal nuclease allowed the estimation of DNA-repeat length in chromatin. Parenchymal nuclei have shorter repeat length than stromal nuclei and DNA-repeat length increases with the age in all three nuclei populations. The kinetics of digestion by micrococcal nuclease showed that nuclei with shorter repeat length are more sensitive to micrococcal nuclease and that the sensitivity of chromatin decreases with age for all the types of nuclei in this study. The kinetics of digestion by pancreatic deoxyribonuclease showed that sensitivity of chromatin is related to the repeat length and that the sensitivity decreases with the ages.


The relationship of detergent-solubilization plasma-membrane components of rabbit alveolar macrophages to an isolated inhibitor of phagocytosis.

1. A plasma-membrane fraction prepared from rabbit alveolar macrophages by hyposmotic borate lysis is described. 2. Rabbit lung lavages, containing a glycoprotein inhibitor of phagocytosis, may be fractionated by preparative isoelectric focusing in the presence of Triton X-100. 3. Chemical analysis indicates that the glycoproteins of the lung lavage contain sialic acid, fucose, mannose, galactose, hexosamine and appreciable quantities of glucose. 4. The relationship of macrophage membrane glycoproteins, solubilized with Triton X-100 in the presence of borate, to the lung lavage glycoproteins is demonstrated immunoelectrophoretically.


Localization and verification by synthesis of five antigenic sites of bovine serum albumin.

Recently we have shown that the major antigenic sites of bovine serum albumin exhibit functional equivalence progessively increasing with the time at which antibodies are obtained after the first immunization. Analysis of our recent immunochemical findings and the known covalent structure of bovine serum albumin have enabled us to predict the locations of five antigenic sites of bovine serum albumin. The predicted locations were synthesized, and immunochemical studies with late-course antisera showed them to constitute antigenic sites of native bovine serum albumin.