[Knowledge and expectations of childbirth in primigravidas].

The primigravida's experience of childbirth is influenced by the knowledge and expectations she has of childbirth. Her expectations of childbirth are based on the information she got from the antenatal clinic, the nursing staff, her mother, friends and family. The purpose of this research was to determine the knowledge and expectations the primigravida has of childbirth. An exploratory, descriptive design was used within the context of an academic hospital in Johanneburg. The survey method was used. The method of research firstly consisted of a literature study of the primigravida's knowledge and expectations of childbirth. This was done in order to put the problem in perspective and also to serve as a theoretical framework for the study. Secondly, a structured questionnaire was used to make a survey of the primigravida's knowledge and expectations of childbirth. From this research it is clear that the respondents had insufficient knowledge of childbirth and the handling of pain during childbirth. This insufficient knowledge can mainly be attributed to the poor attendance of antenatal preparation classes, inadequate professional counselling and the mother of the primigravida as the primary source of information on childbirth. The respondents, however, had realistic expectations with regard to their handling of labour, as well as of the role of the midwife and the doctor. From this research it is clear that a large gap exists in the primigravida's preparation for childbirth. The group participating in this research is therefore not adequately prepared for childbirth to have realistic expectations. The group must rely on the support of the midwife in the labour ward.(ABSTRACT TRUNCATED AT 250 WORDS)


A model for clinical evaluation.

After grappling for years with the problems associated with clinical evaluation in nursing, and becoming increasingly aware of the importance of this aspect of the clinical teaching process, the researcher resolved to make an in-depth study of the state of clinical evaluation in nursing. The study was undertaken in the second semester of 1990. The most important findings of this research were discussed in a previous article (Mulder, M. and Viljoen, JJ. 1992. Die stand van kliniese evaluering aan Suider-Afrikaanse Universiteite. CURATIONIS, Vol. 15, No. 1, 29-41). The second aim of the study, i.e. the development of a proto-theoretical model for clinical evaluation, is discussed in this article. Since there was no existing model for Southern Africa which reflected the researcher's philosophy and view of clinical evaluation, she constructed one as an implicit part of the main recommendations of the research. This model is presented as the ideal for clinical evaluation. The model can be used by evaluators and researchers to assess, plan, implement, remedy and to solve problems of clinical evaluation. It can also be used to direct future research.


An evaluation of late attenders in labour in Alexandra.

To study why women present in late labour we interviewed 70 parturients in our labour room for a period of 8 days in March 1990. When presenting 19% were 8-10 cm dilated and 81% were 0-7 cm dilated. The group was stratified into those in early labour (0-7 cm of cervical dilatation) and in late labour (8 cm or more) and compared for all variables studied. Only a few differences were statistically significant. Early comers were less likely to have strong uterine contractions and more likely to have intact membranes at presentation. Late comers were more likely to report a number of delaying factors or to have financial worries. Twenty nine percent of Alexandra residents and only 6% of outsiders reported difficulty in finding transport to labour room after the onset of labour. Almost half of Alexandra residents did not have access to public transport, ambulance or own transport. The relative risk for late coming was: 9 for women reporting a number of delaying factors outside their control; 6 for those with financial worries or with ruptured membranes; 4 for unbooked cases or with current addresses in Alexandra; 3 for women with a normal past obstetric history or with a previous delivery outside the AHC; 2 for those worried with hospital referrals, with a previous rural address, for less than 1 year in Alexandra or with a normal current ANC. Women who came late in labour were more likely to need hospital referral or to have come to the labour unit walking.


[A model for qualitative research in nursing].

The aim of the research is to describe a model for research in Nursing from the Model of Botes (1989). Within a contextual, qualitative, descriptive design a model for research in Nursing is described through a literature study, script- analysis and intersubjective debate. The method of research went through five phases. The model for research in Nursing is described accordingly the assumptions of the model, a visual presentation, definition of the central concept and statements in the model. The model is evaluated and recommendations for implementation are given.


Commitment to patient care: an exploratory study among registered nurses in Bophutatswana.

In this second article on the commitment to patient care the methodology and results of the study are briefly described and discussed. The research method was a non-experimental qualitative survey, using several data-gathering methods such as semi-structured interviews with registered nurses and patients, the examination of nurses' and patients' records and non-participant observations. Although the responses of nurses and patients indicated that both groups considered commitment to be essential to patient care, the examination of patient records, nurses' evaluation reports and observations showed lack of commitment in practice. Various reasons for this are explored and recommendations made.


[Visual agnosia evolving to optic aphasia--a case study].

The underlying mechanism of visual agnosia and optic aphasia has not been fully elucidated, although a number of hypotheses have been proposed. Besides, the difference between these two conditions has been a matter of debate. We report here the result of neuropsychological evaluation in a case of associative visual agnosia evolving to optic aphasia. A 64-year-old right-handed patient was found to be disoriented and confused after undergoing the operation of gastrectomy. CT scan revealed a large infarction in the territory of left posterior cerebral artery. Since 3 weeks after onset, neuropsychological investigations were carried out during 5 months. He was alert and co-operative. Right homonymous hemianopia with macular sparing was noted, but his visual acuity was normal. There was neither a global deterioration of intellectual capacities nor aphasia. Most striking finding was his difficulty in identifying common objects and colours along with a profound alexia. Prosopagnosia was absent. Visual naming both for objects and line drawings was severely impaired. He was unable to describe or demonstrate the use of the objects which could not be named. Pointing to objects named by the examiner was also severely impaired. Although tactile naming was also impaired, both of auditory naming for environmental sounds and naming objects in response to verbal descriptions were preserved. While he was not able to copy the objects skillfully, matching of identical objects and matching objects to line drawings were normal. Clumsiness of coping was thought to be due to his constructional apraxia and visuomotor ataxia. Therefore, his deficit in visual domain was considered to be associative visual agnosia.(ABSTRACT TRUNCATED AT 250 WORDS)


[Magnetic resonance angiography in 12 patients with Wallenberg's syndrome].

Magnetic resonance angiography (MRA) was performed in 12 patients with Wallenberg's syndrome (WS) in chronic stage to investigate the lesion of the vertebral artery (VA). The laterality of infarction in the medulla oblongata was confirmed with MRI: the right in four patients and the left in eight. In this study, time-of-flight MRA was evaluated. Coronal and OM sections in MRA were examined, because the former is useful to observe asymmetry and curve of the cervical VA, and the latter is useful to observe asymmetry and stenosis of the intracranial VA. In nine out of 12 patients, the ipsilateral VA was rather hypoplastic compared to the contralateral VA, and the flow of the hypoplastic VA stopped before and after entering the intracranial region. The contralateral VA of the hypoplastic cases showed curve in the neck in five patients and stenosis in the intracranial portion in one patient. A comparative study was conducted between vertebral angiogram (VAG) and MRA in four patients. Both VAG and MRA were useful in detecting hypoplasia and stoppage of the flow. It was considered that VA hypoplasia is frequently responsible for WS, and that MRA is useful in screening the vascular lesion as a non-invasive procedure to reveal changes of the bilateral VA.


[A clinicopathological study on 13 cases of motor neuron disease with dementia].

Thirteen patients suffering from motor neuron disease with dementia were studied to analyze the clinicopathological spectrum. The diagnosis of the disease was made on the basis of a clinical history of progressive dementia and motor neuron involvement. The mean age at onset of 11 sporadic cases was 54.9 years (range, 43 to 69 years), with a mean duration of disease of 25 months (range, 11 to 47 months). The initial symptoms were dementia in 7 cases, motor neuron involvement in 2 cases, and both dementia and motor neuron involvement in 2 cases. The clinical picture of motor neuron disturbance in sporadic cases represented bulbar-type of amyotrophic lateral sclerosis (ALS). Bulbar palsy was the initial symptom in 7 sporadic cases and all 11 patients developed bulbar palsy with advancing course of illness. Muscular wasting and fasciculation were more predominant in the upper limbs, shoulder girdle and anterior chest. Fasciculation was more extensively and frequently observed in those portions than that of classical ALS. In contrast, muscle strength in the lower limbs was well preserved so that all patients could walk even when respiratory failure developed. Hyperreflexia including jaw jerk was found in all cases and positive Babinski sign in 7 cases. Parkinsonism appeared in the initial stage in one sporadic case and in two familial cases. The type of dementia with uninhibited behavior and personality change closely mimicked that of Pick's disease. The degree of dementia was mild or moderate in 8 cases and severe in 3 cases. Language disorder was characterized by progressive reduction of speech output, leading finally to mutism in 5 cases. Perseveration was observed in 10 cases. Visuospatial disorder was absent even in the advanced stage. Mild memory disturbance was noted in the early stage in 10 cases. Pathological examination was performed in 7 cases including one familial case, revealing frontal atrophy in 3 cases, frontotemporal atrophy in 2 cases and temporal atrophy in 2 cases. On microscopic examination there were mild neuronal loss, gliosis, mild spongy state of the cortical superficial layers and fibrous gliosis in the frontotemporal white matter. The scattered senile plaques in one case did not justify a diagnosis of Alzheimer's type dementia. Neither circumscribed atrophy nor Pick body was found in any case. The nucleus basalis of Meynert showed no neuronal loss. The substantia nigra showed a mild to severe loss of nerve cells without Lewy bodies in all cases.(ABSTRACT TRUNCATED AT 400 WORDS)


[Morphometry of the normal cadaveric cervical spinal cord].

We measured the cross-sectional area and diameters of the C7 segment in 80 cadaveric specimens obtained from patients without spinal cord lesions died at 60 to 79 years of age. We found considerable individual variation in the spinal cord size. The transverse area of the C7 segment varied from 33.3 mm2 to 67.7 mm2 (mean 48.4 +/- 6.9 mm2). The size of the cord had no correlation with body weight, and had some correlation with body height. But the individual variation in the cord size was considerably large even among the cases of the same height. This large variation in the cord size should be under consideration in morphometric analysis of the spinal cord. We showed the morphometric data based on the measurements of the cross-sectional area and diameters in each segment from C2 to Th1 in 14 cases. Although the size of the spinal cord varied markedly from case to case, the relative ratio of cross-sectional area in each segment to that of C3 was similar among the cases (C2; 1.01 +/- 0.04, C4; 1.02 +/- 0.03, C5; 1.09 +/- 0.04, C6; 1.09 +/- 0.06, C7; 1.07 +/- 0.06, C8; 0.98 +/- 0.05. Th1; 0.80 +/- 0.04). Based on our data, the proper cross-sectional area of each segment and of each individual may be calculable from measurement of a given single segment.


[Big-toe localizing test--clinical study of proprioceptive localization].

Certain proprioceptive sense is utilized in localizing a part of the limb passively held in space. In the previous study (Hirayama, Fukutake, et al., 1986), we demonstrated that such kind of proprioception, which we called "proprioceptive localization", could be detected by making the patient pick up the thumb with the opposite fingers (the thumb localizing test, TLT). As a further development of the TLT, another test, named a big-toe localizing test (BTLT), was devised. In the BTLT, the patient, with eyes closed and a lower limb passively immobilized by the examiner (the fixed limb), is asked to point to the big toe with the index finger of one hand or the other (the reaching limb). Firstly, we assessed the unselected series of 33 patients with thoracic or lumbar myelopathy regarding their sensory impairment and obtained the following conclusions on the BTLT similar to those in our previous study on the TLT. (1) BTLT deficits results from perceptive impairment in the fixed limb. (2) The perceptual information involved in the proprioceptive localization is different from that of the test for the appreciation of passive movement and posture. (3) On the basis of the correlation to other symptomatology, it is suggested that BTLT deficits arise from lesions of the posterior column-medical lemniscal system. (4) The BTLT is more sensitive than the test for the appreciation of passive movement and posture. Secondly, we evaluated another unselected series of 63 patients with unilateral TLT deficits due to CNS lesions. Eight patterns of BTLT deficits were identified and classified into 3 following types.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cerebrovascular CO2 reactivity in patients with dementia due to multiple infarction in the territory of the perforating artery].

In order to clarify the pathophysiology of dementia due to multiple infarction in the territory of the perforating artery, the reactivity of cerebral vessels to increased carbon dioxide tension was examined in patients with multiple cerebral infarction with or without dementia. The subjects studied were 11 patients with multi-infarct dementia (MID) (age 57-82 years old, mean +/- S.D. 72 +/- 8) and 16 patients with multiple infarction without dementia (MI) (age 51-81 years old, mean +/- S.D. 69 +/- 9). The diagnosis of cerebral infarction was based on the clinical signs and symptoms and findings of magnetic resonance imaging (MRI). Only patients with cerebral infarction located in the perforator territories were included in this study. Dementia was diagnosed by DSM-IIIR criteria. The extent of periventricular high intensity area (PVH) on the T2-weighted image of MRI was classified into 3 subgroups by the criteria of Gerard et al with some modifications. Cerebral blood flow (CBF) was measured by the 133Xe intravenous injection method using a Cerbrograph (Novo), and gray matter flow (F1) and initial slope index (ISI) were calculated. The cerebrovascular reactivity to CO2 was estimated as the increase in F1 or ISI per unit increase in PaCO2 (delta F1/delta PaCO2 or delta ISI/delta PaCO2, respectively) during inhalation of 5% CO2 and as %increase in F1 or ISI per unit increase in PaCO2 (delta F1%/delta PaCO2 or delta ISI%/delta PaCO2, respectively) during inhalation of 5% CO2. 1. CO2 reactivity in both groups. delta F1/delta PaCO2 in the MI and MID groups were 3.2 +/- 1.4 ml/100 g/min/mmHg and 2.0 +/- 1.4, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


[Naming difficulties seen in a case of alexia with agraphia caused by a left postero-inferior temporal lesion].

A 71-year-old right-handed man presented writing and reading difficulties as well as naming difficulties. Neuropsychological examinations revealed mild fluent type aphasia accompanied by alexia and agraphia predominantly affecting kanji and also severe naming difficulties. Brain MRI showed cerebral subcortical hemorrhage extending from the anterior one-third of the left temporal lobe to the temporo-occipital junction involving the fusiform gyrus. The analysis of the several reported cases with severe alexia with agraphia for kanji including ours revealed a close correlation between the severity of kanji writing disturbances and that of naming difficulties. It was also shown that cases with severe naming difficulties had lesion extending anteriorly to the anterior middle temporal gyrus or medially to the parahippocampal gyrus, suggesting that the disconnection between the parahippocampal gyrus and other cortices including the temporal lobe was essential for production of naming difficulties.


[A case of B-cell lymphoma with clinical and histological features of malignant histiocytosis].

A case of B cell lymphoma with clinical and histological features of malignant histiocytosis was described. A 57-year-old male was admitted to Shinshu University Hospital because of transverse myelopathy. Five months before admission, he noticed urinary disturbance, which progressed to urinary obstruction. The following month, bilateral muscular weakness appeared in his legs. A few days later he could not stand up, and was admitted to a local hospital. Neurological examination revealed sensory disturbances below the level of Th12 in all modalities, and marked weakness and hyperreflexia in the lower limbs. A spinal tumor was suspected. However, myelography showed no abnormality. The patient's condition worsened and he became bed-ridden in February 1990. He was transferred to Shinshu University Hospital for further evaluation. On admission he was poorly nourished with fever, anemia, hepatomegaly, and bilateral pretibial pitting edema. No lymphadenopathy was observed. Neurological examination showed total sensory loss below the level of Th12, spastic paraplegia, hyperreflexia in the legs, and urinary obstruction. Laboratory findings revealed an elevated erythrocyte sedimentation rate, increased CRP, pancytopenia, and hypoalbuminemia. Serum level of IgG, IgA, IgM, LDH, ALP, GPT and total bilirubin were increased. CSF and MRI imaging of the spinal cord were normal. Proliferation of atypical histiocytes with marked erythrophagocytosis, which is a characteristic pathological feature of malignant histiocytosis, was observed in peripheral blood and aspirated bone marrow. Immunoenzyme staining of bone marrow using monoclonal antibody L-26, which is a B-cell marker, revealed B-cell lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)


[An autopsied case of Parkinson's disease manifesting Shy-Drager syndrome].

We report an autopsied case of Parkinson's disease manifesting Shy-Drager syndrome. At the age of 63 years, the patient noticed an onset of progressive orthostatic dizziness, which was followed by constipation, dysuria, and sexual impotence. When he was 66 years old, syncopal attack for a few minutes, tremor in the bilateral hands, and memory disturbance developed. On admission, his blood pressure was 142/72 mmHg in supine position, which fell to 58/42 mmHg on standing with appropriate increase of heart rate. Neurological examination revealed hallucination, memory disturbance, masked face, muscular rigidity, bradykinesia, mild postural tremor, and autonomic dysfunction including severe orthostatic hypotension, hypohydrosis, constipation, dysuria, and sexual impotence. Electroencephalogram showed diffuse slowing. Brain CT demonstrated absence of severe atrophy of the cerebellum, and brain stem. Pharmacological study revealed denervation hypersensitivity to the intravenously administrated noradrenaline. A diagnosis of Shy-Drager syndrome was made, and he was treated with anti parkinsonian drugs. However, no improvement was observed in his clinical symptoms. Seven months later, he died of pneumonia. Neuropathological examination revealed marked neuronal cell loss and gliosis in the substantia nigra and locus ceruleus. Lewy bodies were seen in those pigmented nuclei, dorsal vagal nucleus, hypothalamus and nucleus basalis of Meynert. No abnormality was found in the intermediolateral nucleus of the spinal cord. This is the first report on a Japanese patient who presented clinically Shy-Drager syndrome and pathologically typical Parkinson's disease. In this patient, from the pharmacological and pathological findings, sympathetic ganglia were supposed to be the responsible lesion for orthostatic hypotension.


[A case of periodic ataxia].

We report a sporadic case of periodic ataxia characterized by recurrent attacks of vertigo and ataxia. A 62-year-old male was known to have nystagmus at the age of 18. He has had recurrent episodes of vertigo and ataxia since the age of 48. During an attack remarkable downbeat nystagmus, limb ataxia predominant in the lower extremities and ataxic gait were present. MRI demonstrated an atrophy of the anterosuperior region of the cerebellar vermis. Vertical nystagmus, dysesthesia of gloves and stocking type and deep sensory disorder persisted during interictal intervals. There is no finding which supports this case to be vascular disorder, congenital anomaly, tumor, infection or demyelinating disease. We thought this case to be periodic ataxia and to belong to vestibulocerebellar ataxia reported by Farmer and his colleagues.


[A case of progressive supranuclear palsy presenting mouth opening difficulty with tonic contraction of the orbicularis oris muscle].

A 72-year-old man developed supranuclear ophthalmoplegia, bradykinesia, rigidity, unsteady gait, dementia, dysphagia, retrocollis, grasp reflex and apraxia of eyelid opening. These findings were compatible with progressive supranuclear palsy (PSP). At the age of 66, he presented a peculiar phenomenon characterized by simultaneous tonic contraction of the orbicularis oris muscle (OOM) and the palatal muscles elicited by pronouncing "pa", which resulted in difficulty of voluntary opening of the mouth and the rhinopharynx. Therefore, the respiration air reciprocated between the lung and the closed mouth. The expiratory pressure puffed out the cheeks, while the lips remained tightly closed. While the respiratory movements and the pressure increased by degree, the OOM contracted more strongly in proportion to the pressure. Sixty to ninety seconds after the elicitation, the pressure overcame the contraction of the OOM and the course of the phenomenon was completed. The electromyograms showed that the OOM activity was prolonged after initial voluntary contraction, remaining thus after a tracheostomy for pneumonia at the age of 72, and that it increased in response to the pressure. Apraxia of eyelid opening, one of the other symptoms, resembled this phenomenon in terms of the aspect of difficulty of voluntary mouth opening. The "holding" phase of grasp reflex, yet another symptom, resembled it in the recruitment of the OOM activity. The phenomenon is not common in patients with PSP. However, we concluded that it may be included among the symptoms of PSP because it has similar characteristics to apraxia of eyelid opening and grasp reflex, which are not uncommon in patients with PSP.


[Cerebellar infarction presenting erotic delusion and delusion of jealousy in the acute phase].

A 62-year-old female presented peduncular hallucinosis accompanied with outstanding manifestation of delusion of jealousy and erotic delusion in the acute phase of cerebellar infarction. The delusion seemed to appear as the swollen cerebellum was compressing the tegmentum of brainstem. CT scanning revealed the sequential images of the compression by the swollen cerebellum and deformity of the brainstem and their final recovery. The reason why the patient showed the outstanding delusion that is unusual in the ordinary peduncular hallucinosis is unclear. It might be brought about by the acute hydrocephalus induced by the occlusion of aqueduct.


[Multiple system atrophy with macro square wave jerks and pendular nystagmus].

A 51-year-old woman was admitted to our hospital because of gait disturbance and dysuria. Neurological examination revealed limb and truncal ataxia, orthostatic hypotension, cogwheel rigidity in all limbs, generalized hyperreflexia without pathological reflex, and horizontal gaze nystagmus. She became progressively worse and bedridden at age 52. Then she developed abnormal eye movements. Electrooculogram revealed vertical, horizontal or oblique macro square wave jerks and pendular nystagmus. Macro square wave jerks appeared during fixation and disappeared with eye closure or in the dark room. Macro square wave jerks were characterized by a duration of about 200 msec and an amplitude of 10 to 15 degrees. Pendular nystagmus with a duration of several seconds and amplitude of 5 to 15 degrees appeared when she changed her fixation or the point of fixation disappeared. Macro square wave jerks and pendular nystagmus were mildly suppressed after the intramuscular injection of 100 mg of phenobarbital, the oral intake of sodium valproate of 600 mg/day or baclofen of 60 mg/day. They were almost completely depressed after the intravenous injection of 3 mg of diazepam or the oral intake of clonazepam of 1.5 mg/day. We suggested that both macro square wave jerks and pendular nystagmus in this patient might be caused by the dysfunction of GABAergic system in the saccadic eye movement system.


[A case of acid maltase deficiency (juvenile type)--immunohistochemical and biochemical study].

A 22-year-old housewife was referred to us for review of progressive proximal muscle weakness which started at 15 years of age. A biopsy of left rectus femoris muscle showed acid phosphatase positive vacuoles partly filled with PAS-positive material. Acid maltase activity of the cultured fibroblasts was pathologically low at 0.4 nmol/mg protein considering 161.0 +/- 32.4 nmol/mg protein as a normal range. A diagnosis was made of acid maltase deficiency (juvenile type). Western blot using anti-acid maltase polyclonal antibody revealed 115 and 70 kDa bands in control muscles, where as only the 115 kDa band, a presumable precursor of the enzyme, was visualized in the patient. By immunohistochemistry using the same antibody the epitope was localized to the acid phosphatase positive vacuoles and immunoelectron microscopy demonstrated the acid maltase immunoreactivity within lysosomes. We concluded that the protein precursor unable to proceed into mature enzyme can access to lysosomes from endoplasmic reticulum through Golgi complex in the present case.


[Cervical root avulsion presenting proximal segmental muscular atrophy of unilateral upper extremity].

A 56-year-old woman noticed non-progressive weakness in the proximal part of the right upper extremity from her childhood. At the age of 37 years, she was diagnosed as "spinal muscular atrophy" by an orthopedic surgeon. At the age of 56, neurological examinations revealed muscular atrophy and weakness confined to the right deltoid, biceps brachii and brachioradialis together with minor sensory disturbance in the lateral side of the right shoulder and forearm without pyramidal sign in the lower extremities. The neurological features of this case differed from those of juvenile type of distal and segmental muscular atrophy of upper extremities in distribution of muscular atrophy, and simulated those of cervical spondylotic amyotrophy. Myelography demonstrated root avulsion of the right C5 and C6 roots. CT myelography revealed traumatic meningocele. Therefore a clinical diagnosis of cervical root avulsion resulting from unrecognized birth injury was made. The reason of motor dominant pictures of this case may be vulnerability of the anterior nerve roots to traction injury.


[A case of acute multiple sclerosis mimicking tumor on the neuro-imaging studies].

A 31-year-old woman with a history of suspected optic neuritis was admitted with weakness of right-sided extremities and confusion. On admission general physical examination revealed no abnormality. Neurological examination revealed central facial palsy, mild hemiparesis and hemisensory deficit on the right side. Cerebrospinal fluid analysis showed monocytosis of 29 cells, protein of 82 mg/dl, glucose of 62 mg/dl and myelin basic protein of 6.8 ng/ml. No oligoclonal bands were seen. X-ray computed tomographic (CT) scans showed multiple homogeneous contrast-enhancing lesions in the white matter of bilateral parietal lobes without distinct edema or mass effect. Follow-up CT scans showed ring-enhanced lesions. Magnetic resonance image (MRI) showed multiple Gadolinium-enhanced lesions. Additionally, 123I-IMP SPECT [Gamma view-SPCT 2000 H-20 (Hitachi Co.)] was performed at 30 minutes and 5 hours after intravenous administration of IMP (3 mCi). It showed high IMP uptake corresponding to the CT and MRI lesions. Cerebral angiography was considered to be normal. Other laboratory findings were within normal limits. A biopsy was performed. Histological examination showed spongiosis, gliosis and perivascular cuffing. The histological diagnosis was acute demyelinating disease. After therapy with methylprednisolone, she improved gradually. Enhanced lesions in CT and MRI may correspond to active demyelination at acute MS. High uptake of SPECT may also appear in acute stage, although it has not been reported. We should perform neuro-imaging studies including SPECT on acute MS.


[A case of cerebral infarction presenting as retrosplenial amnesia].

We report a 73-year-old right-handed female who presented with an acute amnesic syndrome. On November 18, 1991, she was admitted to a local hospital complaining of sudden-onset vertigo and nausea, but immediately after the admission she developed an amnesic syndrome. On November 27, she was transferred to our hospital for further assessment of her memory disturbance. Neurologically she was normal except for mild right hemianopsia and increased deep tendon reflexes in the extremities. Neuropsychological assessments were performed over 3 weeks. She was always alert, attentive, and cooperative. She had no confabulation. On the Wechsler Adult Intelligence Scale revised (WAIS-R), her total IQ was 110. Frontal, verbal, and perceptual functions and motor performance were normal. She had no signs of a callosal disconnection. Despite these preserved functions, her memory function was obviously disturbed. Several memory betteries showed that her recent memory for both verbal and visual modalities was impaired, while her immediate memory such as digit span was preserved. For remote memory her retrograde episodic memory concerning both personal and public events was almost intact, although she had a profound anterograde amnesia. In particular she recalled her personal information about just-premorbid events in detail. On the other hand, her semantic memory, for example understanding of proverbs, geography, and scientific law, was preserved. Taken together, her procedural memory on learning tasks, such as "Tower of Hanoi" and mirror drawing, was intact. Computed tomography demonstrated a low-density area medial to the trigon of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)


[Serial magnetic resonance imaging of spinal syrinx formation in a case of multiple sclerosis].

A 27-year-old woman had a subacute onset of back pain, dysesthesia and weakness of both arms. Neurological examination revealed bilateral pyramidal signs, paresthesia of both hands and arms, and hypalgesia below T-4. CSF showed no abnormal findings. T2-weighted MR images revealed linear high signal within the cervical and upper thoracic cord, but no syrinx. The signs and symptoms resolved substantially within three months, with the exception of paroxysmal itching localized to the right forearm. At age 30, she experienced an acute onset of back pain, and dysesthesia of both feet. She developed weakness of both legs and urinary retention two days after the onset. Neurological examination showed bilateral pyramidal signs in the lower extremities, hypalgesia below T-4, hypopallesthesia on both legs, but no abnormalities in the upper extremities. CSF contained 8 white cells/mm3, protein 17 mg/dl and glucose 44 mg/dl. Oligoclonal bands were not detected. T1-weighted, proton density, and T2-weighted MR images revealed a syrinx formation within the spinal cord, extending from the level of T-2 to T-5. There was no evidence of spinal tumor. MRI of the brain revealed multiple areas of high signal intensity on T2-weighted image, consistent with multiple sclerosis. The signs and symptoms resolved substantially within two months. The syrinx within the thoracic cord reduced in size after two months and disappeared after three months. Two months after the second episode of myelopathy, she experienced right optic neuritis, resolving substantially within three weeks. This case was diagnosed as definite multiple sclerosis based on the clinical and radiological findings.(ABSTRACT TRUNCATED AT 250 WORDS)


[A case of chronic multifocal myositis].

A 61-year-old civil engineer began to have slowly progressive muscle atrophy in the right shoulder and the left arm at 56 years of age. Muscle wasting became manifest in the left thigh at 59 years and in the right thigh at 60 years. He had mild difficulty in climbing and descending stairs. On examination, although he had notable muscle atrophy in the right trapezius and proximal muscles in the upper and lower extremities, his muscle strength was relatively well preserved. The muscle atrophy was asymmetrical; the right periscapular region and the left upper and lower extremities were more markedly atrophic. In addition, multiple foci of the striking muscle atrophy were noted in the upper trunk and the proximal limb muscles. Fasciculation was not present. Deep tendon reflexes were normal with no pathologic reflexes. Except for a moderately elevated serum creatine kinase level of 709 Ul/l (normal 40-170) and mildly elevated serum myoglobin level of 100 ng/ml (normal < 60), no laboratory tests showed abnormal values suggesting an inflammatory process. Motor and sensory nerve conduction velocities were within normal limits. Electromyography disclosed myopathic and neuropathic changes. Computed tomography (CT) of skeletal muscles showed asymmetrical muscle atrophy and patchy low-density foci. In biopsied left quadriceps and right gastrocnemius muscles which showed partially low density on CT, there was marked variation in muscle fiber size, with necrotic and regenerating fibers, an increased number of centrally placed nuclei, and interstitial fibrosis. There were numerous foci of mononuclear inflammatory cellular infiltration, especially around the blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)


[Neuron-specific enolase (NSE) and S-100b protein in cerebrospinal fluid of patients with cervical spondylosis--the relations with MRI findings and the changes of NSE and S-100b protein levels through Glisson's traction].

We have previously reported that NSE and S-100b protein (S-100) could be used as reliable markers to evaluate the damage of the spinal cord in cervical spondylosis (CS) and ossification of posterior longitudinal ligament (OPLL). In the present study we made MRI in 21 patients with CS. There was a positive correlation between the NSE level in CSF and the degree of the spinal cord compression shown by MRI. In 10 cases of CS we examined these specific protein levels in CSF before and after the Glisson's traction therapy for one month. In seven of them the NSE levels decreased with the clinical improvements. On the other hand, 2 cases showed the rise of NSE levels after the traction. One of them became clinically worse during the therapy, while in another case the NSE levels changed within the normal range. The level of NSE in the other case was unchanged. In 57-year-old patient with CS myelopathy we examined the NSE levels chronologically. The NSE level changed in parallel with his clinical features. We suggest that NSE level in CSF may be a useful marker to estimate the change of the degree of the spinal cord damage in CS.


[Esophageal manometry in patients with achalasia].

Fifty-eight patients with achalasia were evaluated by esophageal manometry. In the body of the esophagus, the resting pressure was elevated and the motor waves were typically of low amplitude and presented simultaneously. The LES was of normal or high tone with absent or reduced relaxation in response to deglutition. The authors noticed that the contraction pressure in the pharynx and the resting and closing pressures in the UES were markedly elevated. These features were not documented in the literature. Twenty-two patients were followed up by manometry 4 to 60 months after a Heller's myotomy. The resting pressures in the body of the esophagus and the LES were obviously reduced. We considered that esophageal manometry is an important method in the diagnosis of achalasia.


[Manometry indexes for evaluating esophageal function in patients with achalasia].

In 43 patients with achalasia (postoperative 18, post-dilatation 15, preoperative 10, and 10 normal people) esophageal manometry, esophageal emptying barium test and endoscopy were employed. The results showed that the esophageal emptying index EEI was 13.3 +/- 9.0 in the postoperative group, 4.7 +/- 7.6 in the post dilatation group, 50.0 +/- 17.4 in the normal group, 2.9 +/- 4.3 in the preoperative group. A linear relationship was seen between EEI and the lower esophageal barium retention area (So) (t = -5.00, P < 0.001). In patient with higher EEI and smaller So stronger esophageal emptying function was noted at swallowing. 80% of patients with less than 12 esophageal anti-reflux index (ARI) suffered from gastroesophageal reflux EEI and ARI can evaluate not only the esophageal motor functions but also the therapeutic effects of different treatment methods. The therapeutic effects are determined by esophageal peristalsis pressure and LES relaxation rate after LES is relaxed.


[Multiple organ failure following severe acute pancreatitis: its clinically patterns and pathogenetic factors].

To detect the clinical course and possible pathogenetic factors of multiple organ failure (MOF) after severe acute pancreatitis (SAP), we investigated retrospectively 70 consecutive patients with SAP for a 16-year period. Two different patterns of MOF were identified: rapid-single phase MOF developed early after SAP attack, and delayed tow-phase MOF developed progressively and sequentially with a lag phase. The clinical course of MOF was characterized by a severely systemic inflammatory response. Clinical variables associated with the evolution of MOF included early circulatory shock, pancreatic sepsis and severe pancreatic necrosis, which might be the leading one. It is suggested that the generalized inflammatory response triggered by the toxic focus seems to be the final common pathway linking SAP with MOF syndrome.


[Gait analysis in patients with injuries of spinal cord and nerve root].

In 102 normal subjects an IGI-3 gait analysis system was used to determine the normal level of walking. The results showed that the time of pressure appeared under foot and the sagittal joint movement of the lower extremities were similar to these reported previously. The forward and backward acceleration showed a single positive peak during swing phase, while the upward and downward acceleration showed two positive peaks. At heel contact of stance phase, the acceleration of all dimensions brought about a big negative peak. The variations in gait pattern were distinguished according to the curve characteristics and activity of muscles in the low extremities. The relations between the degrees of spinal cord injury and the gait characteristics were studied. The result indicated that the patterns of gait depend on the degree of injury. The more smooth acceleration curves, the better gait, and the abnormal gait is characterized by multiple peaks of pressure curves.


[Intravesical BCG, mitomycin-C and thiotepa in the prevention of bladder tumor recurrence after operation].

We observed the effects of intravesical irrigation with BCG (group B), Mitomycin-C (group M), and Thiotepa (group T) in prophylaxis of bladder tumor recurrence after surgical treatment. Follow-up for 1-10 years showed that the recurrence rate of bladder tumor was 12.5% (3/24) in group B, 46.9% (15/33) in group M, and 61.8% (21/34) in group T respectively. The effect of BCG was far better than that Mitomycin-C and Thiotepa (P < 0.01). In 5 cases, who failed to Thiotepa, also showed satisfactory results after use of intravesical BCG. Considering the side-effects of intravesical BCG, Thiotepa or Mitomycin-C should be used as the first choice of drugs in preventing the tumor recurrence.


[Atypical adrenopathy].

From 1985 to 1990, we treated 60 patients with adrenopathy, in which 4 (6.6%) had atypical adrenopathy. In the 4 patients, 1 showed Cushing's syndrome caused by an unilateral cortical adenoma and cortical hyperplasia on the contralateral side, 1 aldosteronism and pheochromocytomatic syndrome due to right cortical and medullary hyperplasia and a left cortical adenoma, 1 huge left nonfunctional cortical adenoma, and 1 pheochromocytomatic syndrome resulting from a cortical adenoma. The pathogenesis of the disease was discussed.


[Photodynamic treatment of bladder cancer. Report of 117 cases].

The clinical data on photodynamic treatment of bladder carcinoma in 117 patients confirmed that the treatment of bladder carcinoma of 1 cm to 2 cm in diameter may obtain better results. Carcinoma of 2-4 cm in diameter should be treated with increasing energy density and repeated exposure. If the carcinoma is larger than 4 cm in diameter or is involving the deep muscle and the cervix of the bladder, the treatment would be unsatisfactory. The tumor free rate in the 117 patients was 94%. The total recurrence rate was 30.1% after 8 years' follow-up. Finally, the indications for photodynamic treatment and the causes of recurrence were discussed.


[Microneurovascular free abductor hallucis muscle transplantation for resuscitation of facial paralysis in one stage].

After study of local anatomy in fresh cadaver the authors carried out free abductor hallucis muscle transplantation successfully in three patients with facial paralysis. In one patient the plantaris medialis vessels were anastomosed to the contralateral facial vessels and the plantaris medialis nerve was anastomosed to buccal branch of the contralateral facial nerve. In two patients the plantaris medialis vessels were anastomosed to the ipsilateral facial vessels and the plantaris medialis nerve was anastomosed to the myloidens branch from ipsilateral trigeminal nerve. The authors described the local anatomy and operative methods in details. The advantages of this operative method were also discussed.


[Median thoracic flap with cartilage for repair of large tracheal defect].

Large defect of the tracheal wall is very difficult to repair without support of cartilage. Two patients with large defect of the tracheal anterior wall (2.5-3.0 x 6.0 cm) were treated successfully. For the patients with much scar in neck a median thoracic flap (3.5 x 4.0 x 7.0 cm) was designed as follow: The flap was elevated, and 3 autocartilage bows (0.5 x 0.4 x 0.4 cm) were implanted into the separated tunnels just beneath the subdermal vascular plexus of the flap. The flap was sutured at the border of tracheal wall defect. The cartilage bows were fixed and covered with a combined cervico-thoracic and cervico-acromial bilobate flap. 13 cadavers showed that 1-2 stem vessels (n = 9) or 4-5 vascular branches (n = 4) developed in the flap.


[Early pericardiectomy of acute purulent pericarditis].

The results of early pericardiectomy in 15 cases of acute purulent pericarditis were reported. 13 cases were followed up from 2 to 8 years, none of them developed chronic constrictive pericarditis. The operation is simple and can shorten the time of hospitalization following thorough debridement of the infected foci.


[Analysis of factors influencing on the surgical results of arterial embolism in the lower extremities].

130 patients with arterial embolism in the lower extremities underwent surgical treatment. The curative rate was 66.9%, amputation rate-19.2% and the mortality rate-13.8%. Statistical study showed that sex, age and recurrent embolism had few effects on the surgical results (P < 0.05). One of the influencing factors was the ischemic time of the lower extremities. The mortality rate was 33.3% in the distal abdomen with aortic embolism and 8.7% in the lower extremities (P < 0.005). The mortality rate and amputation rate were significantly higher in embolic patients with atherosclerotic stenosis and occlusion (9% and 17%). The mortality rate and amputation rate were 2.3% and 3.4% in patients with good blood flow and were 42.1% and 57.9% in patients without good blood flow uspectively. Reembolectomies showed no satisfactory effect. The results indicated that embolectomy combined with other necessary operations did not increase the mortality rate and amputation rate (P < 0.05). Postoperative anticoagulation therapy is extremely important.


[Undesirable effects of drying on articular cartilage].

Knee joints of mature rabbit were exposed to room air (room temperature 23 degrees C, humidity 63.5%) for a period ranging from 30 minutes to hours to imitate the human situation in operating room. The morphological findings indicated that the articular cartilage of the femur trochlea was moderately degenerated after 30 minutes of drying and obvious degeneration occurred two hours after operation. The articular cartilage of the patella also degenerated after two-hour drying. No necrosis was noted in the cartilage of the femoro-tibial joint as that part could not be exposed thoroughly. It was possible to reduce the degenerative changes of articular cartilage if the joint was irrigated with Ringer's solution every 5 minutes. The results indicated that drying, a physical factor, can induce the degeneration of the articular cartilage. The longer the drying time, the more obvious the degenerative changes of cartilage; Ringer's solution is useful to prevent the degenerative changes. Clinically, the following points are worth considering: (1) Operating under arthroscope is much better than arthrotomy in avoiding the degenerative change of the cartilage; (2) The operating time should be as short as possible; (3) It is useful to irrigate the joint with some liquid to keep the joint surface moist; and (4) The consequence of exposure of the joint cartilage in cases of open injury of the joint must be seriously considered.


[A study on knee joint geometry in Chinese: significance to prosthesis design].

This study for the first time provided the geometric parameters of knee joints in Chinese, which are indispensable for the design of domestic knee prosthesis. Thirty five items, including linear, radial and angular measurements, were taken from 105 cadaver knees and knee X-ray films of 100 subjects. The method and calculation for proper correction of the X-ray image magnification and joint cartilage space was established. Correlation between the X-ray correction coefficients and the body weight was found to exist, and it formed the basis for individualized correction of X ray measurements. Statistical analysis revealed that most of the linear and radial measurements were highly related while the angular measurements were independent of others. Principal component analysis showed that the width of femoral condyle might be taken as the leading index in determining the dimension of the knee, and regression functions were established. Multivariate discriminate functions could aid the selection of knee prosthesis.


The in vitro and in vivo biotransformation of N-deacetyl-N-formylcolchicine.

The major pathway of metabolic transformation of N-deacetyl-N-formylcolchicine is the oxidative cytochrome P450 dependent O-demethylation of substituents in the aromatic ring A and tropolone ring C. It was found that O-demethylation (both, in vitro and in vivo) takes place predominantly in the aromatic ring, especially at position 2.


Hemodynamic effects on hepatic blood flow of a selective beta 2-adrenoceptor agonist, clenbuterol, in rat.

Acute clenbuterol administration (50 micrograms/kg, i.v.) to anesthetized normotensive rats, produce a marked reduction in the mean blood pressure, (MBP), about 58 mm Hg. Indocyanine Green clearance analysis (control, 1.83 +/- 0.15: clenbuterol, 1.10 +/- 0.20 ml/min/100 g, P < 0.05) showed that the action in the hepatic vascular bed is opposite to its systemic vasodilator effects. The hepatic blood flow (HBF) appears significantly reduced (control, 8.24 +/- 0.35: clenbuterol, 3.83 +/- 0.71 ml/min/100 g, P < 0.05) whereas the hepatic uptake and excretion proceedings were apparently not affected (control hepatic extraction coefficient, 0.225 +/- 0.024: clenbuterol, 0.300 +/- 0.04, NS). These findings show that a marked reduction in HBF follows systemic vasodilator effects produced by clenbuterol.


Spectrophotometric quantification of astemizole and its demethylated metabolite in urine after TLC separation.

The coupling of TLC and UV measurement for determination of astemizole and its main metabolite, O-demethylated derivative, in urine has been investigated. The metabolite like the drug absorbs maximally at almost the same wavelengths, which makes their simultaneous UV determination in biological fluids quite inapplicable. TLC separation on silica gel F254 utilizing chloroform/methanol (85:15, v/v) achieved the best fractionation of the two compounds from the matrix-components of urine. Concentration levels of 0.5-140 micrograms/ml (ppm) in worked-up sample could be reached by adopting the spectrophotometric measurements at 286 nm for ethanolic extracts of the silica layers carrying each individual compound against a blank silica. Varying levels of the intact drug and its phenolic primary metabolite could be accurately traced in urine samples following a 10 mg single oral dose (approximately 12.5 micrograms/kg) after different time intervals up to 12 h. Synthetic preparation of the metabolite by demethylating astemizole is mentioned and its physicochemical characterization is briefly discussed.


The effects of Danshen (Salvia miltiorrhiza) on pharmacokinetics and pharmacodynamics of warfarin in rats.

Danshen is a Chinese folk medicine commonly used in the Chinese population. The effects of Danshen on the pharmacokinetics and pharmacodynamics of warfarin were studied in rats. In the pharmacokinetic study, single oral doses of warfarin were administered to rats or after 3 days treatment with Danshen intraperitoneally twice daily. Plasma warfarin concentrations were measured for 48 after each of two warfarin doses by high performance liquid chromatography (HPLC). In the pharmacodynamic study, the treatments were similar to the pharmacokinetic study, the prothrombin time (PT) was measured daily both in the Danshen treatment period and after the warfarin doses for 4 days. The absorption rate (Ka), volume of distribution (Vd) and elimination half-life (T1/2) of warfarin were significantly decreased while Cmax and Tmax were significantly increased after treatment with Danshen. There was no significant change in PT during the Danshen treatment period while the PTs were increased significantly in the first two days after warfarin doses. Our results suggested that Danshen can increase the initial bioavailability of warfarin and also affect the elimination of warfarin. It can also increase the PT further after the warfarin doses. The pharmacokinetic and pharmacodynamic interactions observed in this study indicate a clinically important interaction between Danshen and warfarin if these two agents are taken together.


The effect of felodipine on bile flow in pentobarbital anaesthetized rats and conscious rats receiving bile salt supplementation.

Felodipine, a vasoselective dihydropyridine calcium antagonist, has been given i.v. (0.2 mumol/kg) to anaesthetized and conscious male rats. There was no effect of pentobarbital anaesthesia on bile flow over a 6 h observation period. Felodipine increased the 6 h recovery of bile by approximately 25% in the conscious rat but in the anaesthetized rat there was a 20% decrease in bile flow following i.v. felodipine. A positive effect of Na-taurocholate infusion (1 mumol/min/100 g body weight) on bile flow in conscious rats was reinforced by concomitant felodipine dosing. Accumulated 6 h recoveries were 2.32 +/- 0.80 g/100 g body weight (control), 3.09 +/- 0.91 g/100 g body weight (taurocholate) and 5.00 +/- 0.80 g/100 g body weight. (taurocholate plus felodipine). The excretion of felodipine in the bile was significantly reduced during anaesthesia and during infusion of 2% bovine serum albumin (0.01 ml/min/100 g body weight) to conscious rats.


Pharmacokinetics of diltiazem and a new analogue, LR-A/113, in the conscious rat.

Pharmacokinetics and metabolism of diltiazem and a new analogue, LR-A/113, have been studied in the rat. Conscious rats, with the jugular vein cannulated, received the compounds by intravenous (3 mg/kg body weight) or oral (50 mg/kg body weight) route. Parent compounds and their N-demethyl and N-deacetyl metabolites were assayed at serial times in blood. Half-life of elimination of diltiazem was significantly shorter than that of LR-A/113, both after oral (37 +/- 9 vs 59 +/- 26 min) and intravenous (29 +/- 12 vs 57 +/- 16 min) administration. N-deacetyl-diltiazem concentrations after oral administration were higher than the parent compound and N-demethyldiltiazem; LR-A/113 blood concentrations were higher than those of its two metabolites. Metabolites were measurable only in traces after intravenous administration. Oral bioavailability was very low, 3.5% for diltiazem and 4.2% for LR-A/113. In conclusion, the substitution of a methyl by an isopropyl group appears to slow in vivo elimination of the analogue of diltiazem, LR-A/113.


Pharmacokinetics of mefloquine in children aged 6 to 24 months.

The study was carried out in 12 children aged 6 months to 2 years, with uncomplicated falciparum malaria admitted to the Hospital for Tropical Diseases, Bangkok. They were treated with mefloquine in the form of MSP (mefloquine 250 mg+sulfadoxine 500 mg+pyrimethamine 25 mg) at a single dose of 25 mg mefloquine base/kg body weight. All of them were cured (28 days follow-up) with minimal side effects. Pharmacokinetic parameter determination was carried out in 9 cases. The results revealed that MRT, t1/2 and tmax in this study (children 6-24 months old) are comparable to the values in children aged 5-12 years, but shorter than in adult patients. Cmax and AUC in children 6-24 months old are comparable to those in children of 5-12 years, but much higher than in adult patients. Vz/f values in this study are comparable to those in children 5-12 years old, but lower than in adult patients.


Pharmacokinetics, hydrolysis and aromatisation of norethisterone-3-oxime in female cynomolgus monkey.

Norethisterone-3-oxime (NETO) was administered to 3 female cynomolgus monkeys intragastrically and, after a wash-out period of 2-5 weeks, intravenously at a dose of 1 mg/kg. The radioactive dose of tritiated NETO was 20 microCi/kg for both treatments. For i.v. injection, a 30% propylene glycol/water solution and for i.g. administration an aqueous microcrystalline suspension was used. Excretion of radiolabel in urine and feces was followed for 5 days and plasma samples were obtained up to 2 days after administrations. In all samples (urine, feces and plasma) radioactivity was determined. Extracts from plasma samples were subjected to HPLC separation of drug and metabolites, as well as NETO and NET (metabolite of NETO after hydrolysis of the oxime group) levels were determined. In addition, EE2 (ethinylestradiol, A-ring aromatised metabolite of NET) levels were estimated using a specifically designed HPLC system for separation. Quantification of EE2 was achieved by radioimmunoassay (RIA) of specific eluate fractions. The results demonstrate that [3H]-NETO was absorbed completely at a dose level of 1 mg/kg, and excreted predominantly via the kidneys. A urinary to fecal excretion ratio of 1.5 (i.v.) or 1.0 (i.g.) was found. Renal excretion of total radiolabel proceeded with a half-life of about 0.8 (i.v.) or 1.1 (i.g.) days. Balances were incomplete, probably due to technical reasons. Orally administered NETO was highly bioavailable (84.0 +/- 16.9% of dose) but rapidly cleared from plasma (total clearance corresponded to 97% of plasma liver flow). The clearance from plasma is equivalent to the metabolic clearance because almost no unchanged NETO is excreted. Extensive metabolism of the parent drug was observed leading to at least two pharmacologically active metabolites (NET, EE2). The main progestogenic metabolite was NET reaching similar high plasma levels as NETO. EE2 turned out to be a metabolite of NETO and a conversion rate of below 0.5% of dose was estimated. However, due to its high estrogenic potency EE2 might contribute to the overall pharmacological pattern of NETO in the cynomolgus monkey.


Electrical properties of neurons in the mediolateral part of the lateral septum: intracellular recordings from guinea-pig brain slices.

Membrane properties of 174 neurons were studied in the mediolateral part of the lateral septum (LSml) using an in vitro slice preparation of guinea-pig brain. Intracellular recordings were correlated with morphological data obtained from 34 neurons intracellularly stained with horseradish peroxidase (HRP). Neurons were divided into three classes according to their electrical responses. Class A and B neurons displayed the common property of an overshooting of spikes in response to the direct application of weak depolarizing current pulses. Class A neurons (59.2% of the total) generated tetrodotoxin-insensitive, high-threshold Ca2+ spikes in a control medium. Class B neurons (20.7% of the total) generated high-threshold Ca2+ spikes only if tetraethylammonium was used to block delayed rectifying K+ current. Features common to class A and B neurons included the inactivation of Na+ conductance, the participation of high-threshold Ca2+ conductance in the generation of spikes--when repetitive discharges were elicited by strong depolarizing current pulses--and Cs(+)-sensitive, Ba(2+)-insensitive anomalous rectification. Class C neurons (20.1% of the total) displayed discharges comprising small-amplitude Na+ spikes followed by slow and large Ca2+ spikes, suggesting a locus of impalement which was not the soma. HRP-filled class B neurons (n = 5) were characterized by small to medium perikarya with spindly dendrites. The majority of HRP-filled class A (15/21) and all class C (n = 8) neurons showed large perikarya with thick primary dendrites and spiny dendritic branches. Thus, class A and C neurons typify the guinea-pig LSml in their morphological characteristics and in their ability to generate high-threshold Ca2+ spikes in a control medium.


Pharmacokinetics of etodolac enantiomers in the rat after administration of phenobarbital or cimetidine.

The influences of phenobarbital and cimetidine on the pharmacokinetics of etodolac enantiomers were studied in male Sprague-Dawley rats. Phenobarbital caused significant reductions in the AUC of both the active S-enantiomer (24%) and the inactive R-enantiomer of etodolac (26%), and an increase in the urinary excretion of glucuronidated S-etodolac. In bile duct-cannulated rats the initial biliary recoveries of the acyl-glucuronidated etodolac enantiomers were not affected by phenobarbital. In vitro, phenobarbital caused no changes in the hepatic microsomal net glucuronidation of etodolac enantiomers after phenobarbital, although it did result in significant increases in the apparent oxidative metabolism of both enantiomers. Therefore, phenobarbital seems to cause an enhanced CL of etodolac by induction of hepatic non-conjugative metabolism. Cimetidine had no discernible effect on the pharmacokinetics of etodolac enantiomers.


Peculiarities of inhibition in cat auditory cortex neurons evoked by tonal stimuli of various durations.

The extra- and intracellular responses of 262 neurons in A1 to tones of best frequency with durations ranging from 10 ms to 1.2 min were studied acute experiments on ketamine-anesthetized cats. Following the generation of action potentials in response to the tone stimulus, inhibition of both the background and the auditory stimulus-evoked spike activity were observed in 91% of the investigated neurons. The duration of this inhibition corresponded to the stimulus duration. For the remaining neurons (9%) an inhibition of the stimulus-evoked spike activity alone was seen, also corresponding to the stimulus duration. Maximal inhibition of the spike activity occurred for the first 100-200 ms of the inhibitory response (the period which equalled the time of development of an IPSP in a cell). During this period of IPSP development, the membrane resistance of the neuron was reduced to 60-90% of its initial value. Varying the duration of the acoustic signal within a range of 10-200 ms was accompanied by a change in the IPSP duration and inhibition of the spike activity of the neuron. Whenever the tone lasted more than 200 ms, the membrane potential of the neuron was restored to the resting potential. However, during this period, the responsiveness of the neuron was lower than that initially observed. Measurement of the membrane resistance during the inhibitory pause that was not accompanied by hyperpolarization produced an index with an average 17% lower than the initial value for 87% of the neurons.(ABSTRACT TRUNCATED AT 250 WORDS)


Pharmacokinetics of nefazodone in the dog following single oral administration.

The pharmacokinetics of nefazodone (NEF) and two of its pharmacologically active metabolites viz hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were determined following single oral administration of 100, 200 and 400 mg NEF to 6 beagle dogs in a three-way crossover study. Blood samples were collected for 48 h and plasma was analyzed for NEF, HO-NEF and mCPP by a validated HPLC assay. NEF was rapidly absorbed after oral administration. Cmax values for all three compounds and AUCinf values for HO-NEF and mCPP were dose-proportional; AUCinf values for NEF were dose-linear but not dose-proportional. The T1/2 values for NEF and HO-NEF following the 400 mg dose were significantly greater than those for the 100 mg dose. No differences in mCPP T1/2 were observed among the doses. The Cmax and AUCinf ratios for metabolite:NEF were about 2-fold lower for the 200 and 400 mg doses than those observed for the 100 mg dose. However, due to extensive variability, the ratios for three doses were not significantly different based on statistical analysis. Overall, these data suggest the pharmacokinetics of NEF are dose-dependent in the beagle dog. Statistical significance for dose-dependency for many of the pharmacokinetic parameters could not be demonstrated due to high variability associated with the plasma concentration vs time profiles.


Pharmacokinetics of nefazodone following multiple escalating oral doses in the dog.

The single and multiple dose pharmacokinetics of nefazodone (NEF) were investigated in a dose-escalating study in which 4 beagle dogs (weighing approximately 10 kg) were orally administered 100 mg nefazodone hydrochloride on days 1-7, 500 mg on days 8-14 and 1000 mg on days 15-20 once daily. Serial blood samples were collected over a 24 h period following administration of the first (day 1) and last (day 7) doses for the 100 mg/day dose and the last dose for the 500 (day 14) and 1000 mg/day (day 20) doses. Blood samples were also collected for trough level (Cmin) determination on the morning of the 5th, 6th and 7th day of 100 and 500 mg/day dosing regimens and the 3rd, 5th and 6th day of 1000 mg/day regimen. Plasma was analyzed for NEF and 3 metabolites [hydroxynefazodone (HO-NEF), m-chlorophenylpiperazine (mCPP) and p-hydroxynefazodone (p-HO-NEF)] by a validated HPLC assay. There were no significant differences between the 100 mg single and 100 mg/day multiple dose pharmacokinetic parameters for NEF, HO-NEF and mCPP. However, for p-HO-NEF, single dose elimination half life (T1/2) and area under the plasma concentration-time curve (AUC) extended to infinity were significantly smaller (P < or = 0.05) than the multiple dose T1/2 and AUCTAU, respectively. Based on Cmin data, steady state was reached by the 5th day of 500 mg/day and 1000 mg/day multiple dosing. Mean multiple dose AUCTAU values for NEF increased in a 1:9:26 ratio for a 1:5:10 increase in dose. Due to extensive variability and small number of animals used in the study, the statistical analysis indicated that AUCTAU values were dose-proportional. However, metabolite formation decreased significantly with increasing dose as indicated by AUCTAU ratios for metabolite:NEF. These data suggest that NEF exhibits nonlinear pharmacokinetics within 100-1000 mg/kg dose range in dogs.


Brain stem projections of rat lumbar dorsal root ganglia studied with choleragenoid conjugated horseradish peroxidase.

Brain stem projections from each of the L1-L6 lumbar dorsal root ganglia (DRGs) were investigated in adult rats following DRG injections of choleragenoid-horseradish peroxidase. All these DRGs projected throughout the rostrocaudal extent of the gracile nucleus (Gr). Labeling from L1-L6 DRGs was transported to successively more dorsomedial areas of Gr. Investigation of the Gr projections from the DRGs revealed a somatotopic organization which was most prominent in the middle part of Gr. The cuneate nucleus showed smaller projections from all investigated DRGs. Minor projections to the internal basilar nucleus, external cuneate nucleus, medial vestibular nucleus, ventral cochlear nucleus and trigeminal sensory nuclei were also found from some of the DRGs.


The influence of head position and head reorientation on the axis of eye rotation and the vestibular time constant during postrotatory nystagmus.

Reorienting the head with respect to gravity during the postrotatory period alters the time course of postrotatory nystagmus (PRN), hastening its decline and thereby reducing the calculated vestibular time constant. One explanation for this phenomenon is that the head reorientation results in a corresponding reorientation of the axis of eye rotation with respect to head coordinates. This possibility was investigated in 10 human subjects whose eye movements were monitored with a three-dimensional magnetic field - search - coil technique using a variety of head reorientation paradigms in a randomized order during PRN following the termination of a 90 degrees/s rotation about earth vertical. Average eye velocities were calculated over two time intervals: from 1 s to 2 s and from 7 s to 8 s after cessation of head rotation. The time constant was estimated as one third of the duration of PRN. For most conditions, a reorientation of the head with respect to gravity 2 s after the rotation had stopped did not significantly alter the direction of the eye velocity vector of PRN with respect to head coordinates. This strongly indicates that, in humans, PRN is mainly stabilized in head coordinates and not in space coordinates, even if the otolith input changes. This finding invalidates the notion that the shortening of PRN due to reorientation of the head could be due to a change of the eye velocity vector towards a direction (torsion), which is not detectable with the eye recording methods (electrooculography) used in earlier studies.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of practice on final position reproduction.

Three subjects practiced fast, accurate 36 degrees elbow flexion movements to a 2.5 degrees target for 14 sessions of 100 trials (total, 1400 trials). Subjects then returned for a 15th experimental session in which they were asked to perform 15 movements under identical conditions to the practice condition. They were then tested under three experimental conditions without visual feedback: (1) identical to the practice conditions, (2) with small shifts in starting position (+/- 3 degrees of the practiced starting position), that were insufficient for subjective discrimination and, therefore, subjects were instructed to repeat the practiced movements; and (3) with a large shift in starting position (range, +/- 15 degrees of the practiced starting position), under the instruction to move to the same target. Experimental conditions 2 and 3 demonstrated that shifts in starting position were partially correlated with shifts in final position. These results are interpreted from the point of view of the equilibrium-point hypothesis of motor control.


Viewing-distance invariance of movement detection.

Since visual movement information is often presented in electronic displays or films it is amazing that there is a paucity of research on the influence of viewing distance on motion detection in cinematograms. We report a relatively high degree of detection constancy with changing viewing distance for coherent motion in random-pixel cinematograms. A constant performance irrespective of viewing-distance is called 'distance-invariance' and for motion detection it proves to hold reasonably well for a relatively wide range of viewing distances both for foveal and eccentric vision. The limits of this viewing-distance invariance are explored as a function of screen velocity. Detection performance is quantified by a threshold signal-to-noise-ratio (SNR-) value, S, which is determined as a function of velocity for a range of viewing distances from 53 to 13,476 mm for foveal vision and from 60 to 1925 mm at 24 degrees eccentricity on the nasal horizontal meridian of the right eye's retina. The data can be explained, at least qualitatively, by a model in which a spatial-resolution stack has a stack of velocity-tuned motion detectors at every resolution layer. Such a 'stack-of-stacks' model is in line with proposals for contrast-detection stack-models, but it suggests that the usual hypothesis that motion perception is based on the activity of two separate systems, the short-range and the long-range system, might be superfluous. This two-systems distinction was largely based on the different performance found for moving random dot patterns and moving form-defined stimuli. A moving random pixel array viewed at very close range (e.g. 6 cm) presents the subject with relatively large almost square 'blobs', which are less dissimilar from the phi-stimuli used in classic motion perception studies than random dot stimuli at the usual medium to large viewing distances. It leads to maximum displacement threshold (Dm-) values that are not untypical of the 'long-range' system, but by gradually increasing the viewing-distance and thus decreasing the pixel-size a continuous change is found from typical long-range to typical short-range values of Dm. The two-systems distinction for motion detection appears to refer to the stimulus rather than to the visual system: The motion-detection system might be forced into a local or a global 'mode of operation' by the choice of stimulus.


Control strategies in directing the hand to moving targets.

We have evaluated the use of visual information about the movement of a target in two tasks--tracking and interceptions--involving multi-joint reaching movements with the arm. Target velocity was either varied in a pseudorandom order (random condition) or was kept constant (predictable condition) across trials. Response latency decreased as target velocity increased in each condition. A simple model that assumes that latency is the sum of two components--the time taken for target motion to be detected, and a fixed processing time--provides a good fit to the data. Results from a step-ramp experiment, in which the target stepped a small distance immediately preceding the onset of the ramp motion, were consistent with this model. The characteristics of the first 100 ms of the response depended on the amount of information about target motion available to the subject. In the tracking task with randomly varied target velocities, the initial changes in hand velocity were largely independent of target velocity. In contrast, when the velocity was predictable the initial hand velocity depended on target velocity. Analogously, the initial changes in the direction of hand motion in the interception task were independent of target velocity in the random condition, but depended on target velocity in the predictable condition. The time course for development of response dependence was estimated by controlling the amount of visual information about target velocity available to the subject before the onset of limb movement. The results suggest that when target velocity was random, hand movement started before visual motion processing was complete. The response was subsequently adjusted after target velocity was computed. Subjects displayed idiosyncratic strategies during the catch-up phase in the tracking task. The peak hand velocity depended on target velocity and was similar for all subjects. The time at which the peak occurred, in contrast, varied substantially among subjects. In the interception task the hand paths were straighter in the predictable than in the random condition. This appeared to be the result of making adjustments in movement direction in the former condition to correct for initially inappropriate responses.


Does limb proprioception drift?

The hypothesis that proprioceptively perceived limb position drifts during visual occlusion was re-examined by combining some of the protocols used in previous experiments. Sixteen adult subjects made judgements of static limb position during visual occlusion lasting up to 2 min. In addition, the effect of brief 250 ms "glimpses" of the limb, occasional proprioceptive stimulation and directed attention were examined. Despite, conflicting evidence from earlier experiments, there was clear evidence of a drift in perceived limb position, towards the body, during visual occlusion. This drift was halted if brief glimpses of the limb were provided, or minor re-positioning (without vision) was allowed. In neither case, however, did the supplementary cues reset limb position to its originally perceived position. Drift was amplified when subjects attempted to attend to limb position rather than perform a secondary tracking task. The results are not easily accounted for if drift is considered purely as an effect of peripheral sensor adaptation. A notion of central-drift between visual and proprioceptive maps is suggested as an alternative hypothesis.


Differences between steady-state and transient post-synaptic potentials elicited by stimulation of the sural nerve.

In cat medial gastrocnemius motoneurons, single stimuli to the cutaneous sural nerve evoke a post-synaptic potential with a mixture of depolarization and hyperpolarization, depolarization being dominant in type F cells and hyperpolarization in type S cells. This pattern is consistent with previous reports showing that activation of the sural nerve can sometimes reverse the normal order of motor unit recruitment by inhibiting S motor units while simultaneously exciting F motor units. However, during repetitive stimulation for 1-2 s, we found that the hyperpolarizing component of the sural input to medial gastrocnemius motoneurons was not persistent, but instead gave way to depolarization after the first 30 ms. The net steady-state response after 0.5-1.0 s of stimulation was depolarization in all cells, regardless of motor unit type. This suggests that tonic sural input may be incapable of producing prolonged recruitment reversals.


A mammalian model of optic-flow utilization in the control of locomotion.

Gibson (1966, 1979) and Lee (1976) have described the potential usefulness of optic-flow information for the control of locomotion. One variable that might be particularly important for an animal approaching a target is time-to-collision, which Lee argues is most efficiently specified by the tau margin (the inverse of the relative rate of expansion of the target image on the retina). In humans, most empirical studies of optic flow have required perceptual judgements or have examined catching/intercepting behaviours. In animals, most studies have been strictly observational. This is particularly true for mammals, where there has been no experimental work of any kind looking at the control of locomotion. The present experiment demonstrates that the Mongolian gerbil (Meriones unguiculatus) uses time-to-collision information to control deceleration as it runs towards a target. The development of this animal model will aid investigation of the neural circuitry underlying optic flow utilization in motor control.


Understanding motor events: a neurophysiological study.

Neurons of the rostral part of inferior premotor cortex of the monkey discharge during goal-directed hand movements such as grasping, holding, and tearing. We report here that many of these neurons become active also when the monkey observes specific, meaningful hand movements performed by the experimenters. The effective experimenters' movements include among others placing or retrieving a piece of food from a table, grasping food from another experimenter's hand, and manipulating objects. There is always a clear link between the effective observed movement and that executed by the monkey and, often, only movements of the experimenter identical to those controlled by a given neuron are able to activate it. These findings indicate that premotor neurons can retrieve movements not only on the basis of stimulus characteristics, as previously described, but also on the basis of the meaning of the observed actions.


Effects of neonatal removal of superior cervical ganglion on serotonin and thyrotropin-releasing hormone immunoreactivity in the intermediolateral cell column of the rat spinal cord.

In this study, we investigated the effects of the neonatal removal of the right superior cervical ganglion on the serotonin-like and thyrotropin-releasing-hormone-like immunoreactivities (5-HT-LI and TRH-LI) in the intermediolateral cell column (IML) of the spinal cord by quantitative image analysis. Two weeks after the lesion, we observed a 60% reduction in 5-HT-LI, while TRH-LI was not significantly reduced, in the right IML (lesioned side) at T1-2 levels. One month after the lesion, 5-HT-LI and TRH-LI were significantly reduced by 60% in the right IML at T1-2 levels. After 3 months, this decrease persisted at this level. In addition, we observed a 30% loss of the 5-HT-LI in the right IML at T3-4 levels, whereas TRH-LI did not decrease significantly at T3-4 levels. These findings are discussed and compared with those of other experimental studies on serotonergic reorganization in the rat spinal cord.


Collateral reinnervation and expansive regenerative reinnervation by sensory axons into "foreign" denervated skin: an immunohistochemical study in the rat.

Immunohistochemistry has been used to study, the capacity of different types of sensory axons in the saphenous nerve to extend into denervated glabrous skin territory after a chronic sciatic nerve lesion. In this study, the extension of the intact or regenerating thin peptidergic and coarse saphenous nerve fibres in adult and neonatal rats was determined. Substance P (SP) and calcitonin gene-related peptide (CGRP) antibodies were used as markers for thin axons and neurofilament (NF) antibodies for coarse axons. In addition, S-100 protein (S-100) antibodies, which primarily stain Schwann cells associated with myelinated axons, as well as innervated lamellated cells of Meissner corpuscles, were used. After a chronic sciatic nerve lesion in adult rats, thin dermal and epidermal SP-immunoreactive (IR) and CGRP-IR saphenous nerve fibres were present in an area lateral to that normally innervated by the saphenous nerve in the foot sole. In neonatally lesioned animals, thin dermal and epidermal SP-IR and CGRP-IR, as well as coarse dermal NF-IR fibres and S-100-IR cells, all of which derived from the saphenous nerve, were found in the sciatic nerve territory. In addition, some dermal SP-IR and CGRP-IR fibres were transiently present in the lateral part of the foot sole. After chronic sciatic nerve lesion and a concomitant crush injury of the saphenous nerve in adults or neonatals, thin dermal and epidermal SP-IR and CGRP-IR fibres, as well as coarse dermal NF-IR fibres and S-100-IR cells, were found in the innervation area normally occupied by the sciatic nerve. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in adult rats, the SP-IR and CGRP-IR fibres, as well as the NF-IR fibres and S-100-IR cells were restricted to the medial part of this area. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in neonatal rats, a few thin dermal SP-IR and CGRP-IR fibres were found in the lateral part of the foot sole as well. The findings of the present study together with those of previous morphological studies indicate that intact thin axons from the saphenous nerve, including those exhibiting peptide immunoreactivity, but not coarse saphenous axons, are capable of extending into "foreign" denervated glabrous skin after chronic sciatic nerve injuries. In neonatally sciatic-nerve-injured animals, both groups of axons spread from the intact saphenous nerve into the sciatic nerve territory.(ABSTRACT TRUNCATED AT 400 WORDS)


The fascicular organisation of the cat optic nerve.

Mammalian optic nerve axons are organised within a fascicular framework. This pattern changes between the eye and the chiasm. For most of the length of the nerve fascicular patterns are apparent, but close to the chiasm, in a region of major fibre rearrangement, the fascicular configuration is lost. It is not known how this change occurs, or whether there are less obvious systematic changes in the number of fascicles or their geometry along the length of the nerve. In this study these questions have been addressed at successive locations along the length of the cat optic nerve. The number of fascicles varied depending upon the location examined. A relatively high number were found behind the eye. The number declined in the mid-orbital portion before increasing again in the region of the optic canal. Further caudally there was a progressive change in the pattern of fasciculation, with a loss of fascicular structure medially. The remaining fascicles became concentrated around the inferotemporal periphery of the nerve. There was no fascicular organisation at the point at which the two nerves fused at the chiasm. Although the number of fascicles varied along the length of the nerve their geometric pattern did not change.


Patterns of projections from area 2 of the sensory cortex to area 3a and to the motor cortex in cats.

Peripheral information reaches the motor cortex partly through corticocortical pathways that arise from two functional subdivisions, area 2 and area 3a, of the sensory cortex. These sensory areas are synaptically linked with one another. The patterns of connectivity and the different submodality input that each area receives suggest that they send different efferent signals to the motor cortex. The projections from area 2 to area 3a and to the motor cortex were studied with retrogradely transported fluorescent tracers. The pattern and distribution of neuronal labeling in area 2 was determined following injections of different tracers into the forelimb regions of area 3a and the motor cortex. The results showed that the projections from area 2 to the two target regions were topographically and somatotopically related. Multiple clusters of motor cortex projection neurons were found in area 2, and these clusters overlapped extensively with clusters of area 3a projection neurons. Although cells labeled with one of the dyes were often in close proximity to cells labeled with the other dye, no double-labeled cells were found. Two different laminar patterns were seen for the two populations of neurons. The projection to area 3a originated from cells located in layers II-III and layers V-VI. The projection to the motor cortex originated from cells spread throughout layers II-IV, but predominantly in layer III. Differences in laminar arrangement of the two populations of cells suggest a directional flow of information processing in the sensorimotor cortex.(ABSTRACT TRUNCATED AT 250 WORDS)


Differences in FM response correlate with morphology of neurons in the rat inferior colliculus.

The response characteristics to linear frequency sweeps were studied in two groups of FM (frequency modulation) sensitive neurons in the rat inferior colliculus. 'FM specialized' cells responded to frequency sweeps but not to pure tones. 'Mixed' cells responded to both frequency sweeps and pure tones. FM specialized cells preferred faster and broader sweeps of higher intensity than did mixed cells and were more directionally selective. In addition, FM specialized cells were more sharply tuned to FM velocity and FM range and had longer response latencies. Physiologically identified FM cells stained intracellularly with horseradish peroxidase revealed differences in morphology correlating with the differences in their responses to tones. FM specialized cells had larger dendritic fields, more dendritic branching and more dendritic spines than did mixed cells. The findings are taken as evidence that the two groups of inferior colliculus neurons are both functionally and morphologically distinct.


Rapid increase in relaxin gene expression in early pregnancy in the pig.

Relaxin mRNA concentrations in porcine corpora lutea were examined during the peri-implantation period and throughout pregnancy using Northern and slot blot analysis. Total RNA was extracted from corpora lutea obtained from pigs of known breeding dates and pregnancy was confirmed by embryo recovery. A 32P-labelled porcine relaxin cDNA probe identified the 1.0 kilobase relaxin transcript. Slot blots were subsequently used to quantify relaxin mRNA concentrations. Relaxin mRNA was detectable in the corpus luteum of the regular cycle and was also present at similar low levels in corpora lutea of days 10, 11 and 12 of pregnancy. In corpora lutea from day 16 of pregnancy onwards 100-fold greater quantities of relaxin mRNA were observed. The intensity remained similar in samples between days 16 and 102 of pregnancy. These studies indicate that elevated relaxin gene expression commences very early in pregnancy and is first detectable in the peri-implantation period.


Isolation of an insulin-like growth factor II cDNA from guinea pig liver: expression and developmental regulation.

Insulin-like growth factor II (IGF-II) cDNA was isolated from adult guinea pig liver by polymerase chain reaction (PCR) screening. A cDNA sequence was obtained corresponding to part of the preproIGF-II, including the signal peptide, the mature IGF-II and 37 amino acids of the acid carboxy-terminal E-domain. Amino acid sequence prediction, based on the cDNA clone, showed that mature guinea pig IGF-II has a high homology with both human and rat IGF-II, 100 and 94% identity, respectively. Levels of IGF-II mRNA in guinea pigs of different ages were analyzed by solution hybridization/RNase protection assay using part of the isolated IGF-II cDNA as a probe. There is a marked developmental regulation of IGF-II after birth. IGF-II mRNA levels were high in fetal livers, and decreased 15- to 30-fold in adults. As in man, but in contrast to rats, adult guinea pigs have significant levels of IGF-II mRNA in the liver. In fetal guinea pigs, the expression of IGF-II mRNA was 5-, 2- and 70-fold lower in kidney, skeletal muscle and brain cortex, respectively, than in liver. IGF-II mRNA levels in kidney and skeletal muscle of fetal guinea pigs were 5- and 4-fold higher, respectively, compared with adults. Similar sizes of IGF-II mRNA transcripts could be observed on Northern blots in newborn rats and in fetal guinea pigs. Our conclusions are that the mature IGF-II peptide in the guinea pig is 100% identical to the mature peptide in the human.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of cold acclimation on the expression of glucose transporter Glut 4.

Glucose uptake by brown adipose tissue, measured following deoxyglucose injection in vivo, was increased by 6- and 11-fold following 2 and 14 days of cold exposure, respectively. To look for the possible mechanism of these modifications, the glucose transporter Glut 4 has been characterized at the protein and mRNA levels in brown adipose tissue, skeletal muscle and white adipose tissue following cold acclimation. Crude membranes were prepared from those tissues, and Glut 4 was studied by Western blot analysis. In brown adipose tissue, the total Glut 4 amount was increased by 52 +/- 7% and by 104 +/- 12% following 2 and 14 days of cold exposure, respectively. By contrast, in white adipose tissue of 14-day-cold-exposed mice the total Glut 4 content was decreased by 42 +/- 5%. However, Glut 4 concentration, expressed per mg of membrane protein, was unchanged in both brown and white adipose tissues following cold exposure, since the membrane protein content increased in brown but decreased in white adipose tissue. No modification in Glut 4 content was observed in skeletal muscle from cold-exposed mice. Total RNA were prepared and analyzed for Glut 4, glyceraldehyde phosphate dehydrogenase (GAPDH) and actin. Glut 4 and GAPDH mRNA were increased 2-fold in brown adipose tissue from cold-exposed mice, while actin mRNA content was unmodified. Glut 4 mRNA content was not changed in white adipose tissue and skeletal muscle from cold-exposed mice. Our results suggest that Glut 4 expression is differently modulated in the three insulin-responsive tissues during cold acclimation.


Basal and gonadotrophin-releasing hormone-induced biosynthesis and release of luteinizing hormone: effect of calcium deprivation.

The present study examines the basal and gonadotrophin-releasing hormone (GnRH)-stimulated biosynthesis and release of luteinizing hormone (LH) by pituitary cells in primary culture, and the effect of extracellular calcium deprivation on these events. Pituitaries from ovariectomized adult rats were enzymatically dispersed and cultured for 96 h. The cells were then incubated for 5 h (Expts. 1 and 3) or for different time intervals between 0 and 5 h (Expt. 2), in medium containing [14C]leucine ([14C]leu) and [3H]glucosamine ([3H]gln), with or without GnRH. Total immunoreactive LH (iLH) was measured in the medium and the cell extract by radioimmunoassay. LH translation (as estimated by [14C]leu incorporation into LH; [14C]LH) and LH glycosylation (as estimated by [3H]gln incorporation into LH; [3H]LH) were measured by immunoprecipitation with specific LH beta antiserum in both medium and cell extract. Treating the cells with GnRH caused both time- and dose-dependent increases of iLH in the medium as well as in total (cells plus medium) content, with an approximate ED50 of 0.7 nM. GnRH also stimulated LH biosynthesis by increasing both LH polypeptide chain synthesis and LH glycosylation. The effect of GnRH on LH glycosylation was detected earlier than that on translation, the [3H]LH rates of production and release being higher than those of [14C]LH. These findings suggest that GnRH-induced translation and glycosylation of LH are independently regulated. Removal of extracellular calcium resulted in the loss of cellular responsiveness to GnRH, preventing not only the stimulatory effects of GnRH on total and released iLH but also the GnRH-induced incorporation of both [14C]leu and [3H]gln into newly synthesized LH. These observations suggest that GnRH-stimulated LH glycosylation and LH translation involve calcium-dependent mechanisms. Neither the uptake of radiolabeled precursors nor their incorporation into total protein were affected by GnRH or Ca(2+)-deficient (no added calcium) medium. The results also suggest that the release of newly synthesized LH is regulated differently from previously synthesized stored hormone.


The cloning of the human follicle stimulating hormone receptor and its expression in COS-7, CHO, and Y-1 cells.

Follicle stimulating hormone (FSH) receptor clones were isolated from a human testis cDNA library. Characterization of the cDNA clones showed that the DNA and predicted amino acid sequences of the long open reading frame differed from a previously published human ovarian FSH receptor sequence (Minegish et al. (1991) Biochem. Biophys. Res. Commun. 175, 1125-1130) by seven nucleotides and five amino acids. A human FSH receptor splice variant was also identified and characterized. A full-length human FSH receptor cDNA was engineered for expression in COS-7, CHO, and Y-1 cells. In transient transfections of COS-7 cells and stable transfections of Y-1 cells, efficient FSH receptor mRNA accumulation and isolation of FSH-responsive cell lines occurred only when an intron was included in the 5' untranslated region of the FSH receptor transcription unit. Y-1 cells stably transfected with the FSH receptor responded to FSH treatment by rounding up and by synthesizing increased amounts of progesterone. Stably transfected CHO cell lines, which responded to FSH by synthesizing increased amounts of cAMP, were isolated irrespective of the presence of the heterologous intron. The FSH-responsive CHO and Y-1 cell lines may be suitable for the development of better in vitro FSH bioassays. These cells also constitute a convenient source of human FSH receptor protein for use in radioreceptor assays and in studies of receptor-ligand interactions.


Mouse submandibular glands express an androgen-regulated transcript encoding an acidic epididymal glycoprotein-like molecule.

Acidic epididymal glycoprotein (AEG) is an androgen-regulated, epididymal secretory protein assumed to be involved in sperm maturation. In the present study, we show that the mouse submandibular gland (SMG) expresses two genes designated Aeg-1 and Aeg-2. The nucleotide sequence of Aeg-1 cDNA clones was identical to that of epididymis-expressed Aeg cDNA clones, indicating that Aeg-1 is expressed in both epididymides and SMGs. The second, more abundant transcript, Aeg-2, had a sequence similar to, but distinct from, that of Aeg-1, and was not detectable in the epididymis. The level of Aeg-1 and Aeg-2 transcripts in the SMG was androgen-regulated and showed sexual dimorphism. In situ hybridization of SMG sections showed that Aeg-1 and Aeg-2 transcripts are produced by the cells of granular convoluted tubules. The C-terminal cysteine-rich region of the mouse AEG-2 molecule appears to have diverged faster than that of the mouse AEG-1 molecule, consistent with the idea that this region may play a role unique to the protein of the male reproductive system.


Vasopressin biosynthesis in rodent Leydig cells.

Local biosynthesis of the peptide hormone vasopressin is demonstrated in vitro in Leydig cells derived from rat and mouse testis. Cycloheximide-sensitive production of the nonapeptide was shown for rat Leydig cells in primary culture. A polymerase chain reaction technique demonstrated the presence of functionally constituted vasopressin mRNA in rat and mouse testis, primary mouse Leydig cells and in rat and mouse Leydig tumour cell lines (MA10, R2C). Stimulation of cells with gonadotropins, however, had no effect either on peptide production or on levels of specific mRNA. Similarly, treatment of the MA10 cell line with a phorbol ester, or with rat atriopeptin, which activate other second messenger pathways, had no influence on vasopressin mRNA levels. The results are discussed in terms of an autocrine regulatory system which would provide the cell with information about its microenvironment.


Regulation of the epididymal glutathione peroxidase-like protein in the mouse: dependence upon androgens and testicular factors.

The protein MEP24 was previously described as a glutathione peroxidase-like molecule specifically secreted by the mouse caput epididymidis. Recently, its binding to the head of spermatozoa was demonstrated. Here, the regulation of MEP24 expression was studied by analyzing transcriptional and translational activities in the epididymis (1) of adult mice castrated on day 60 and given various substitutive testosterone (T) treatments from day 90 and (2) of hemicastrated adult animals. In castrated mice, T treatment induced a significant rise in plasma T and 5 alpha-dihydrotestosterone (DHT) concentrations that greatly exceeded the control values. Owing to efficient regulation, however, the epididymal T and DHT levels were never higher than those of the controls. The restoration of MEP24 mRNA accumulation was complete when the epididymal DHT content returned to its normal value. However, when estimated in a cell-free system, the in vitro translatable MEP24 mRNA level never exceeded 70% of control values, even though the DHT and accumulated mRNAs were restored by 100% or more. In hemicastrates, the T content was normal on the castrated side, while the DHT content exhibited a significant decrease (47%). In this case, the MEP24 mRNA accumulation reached 88% of the normal value, but the translation rate, both in vitro and in vivo, was only about 50%. Ultrastructural studies showed that the normal rough endoplasmic reticulum organization in segment I cells is dependent upon the presence of testicular fluid in the epididymal duct lumen. Thus, this report shows that the MEP24 mRNA steady-state level is completely recovered in the presence of a normal epididymal DHT content, while restoration of the regulation of translation is just partial. This could be related to the cell organization but seems mainly dependent upon the presence of specific mRNA-associated factors which are probably under the control of androgens and/or molecules carried by the testicular fluid.