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Biomedical subjects

J M Griffith

Publications and source records attributed to J M Griffith.

At least 37 records · Page 2Linked to original sources
PubMed1995

Normalization of the auditory P50 gating deficit of schizophrenic patients after non-REM but not REM sleep.

Diminished suppression of the P50 response to repeated auditory stimuli is one example of a deficit in elementary sensory processing in schizophrenia. Normal subjects suppress the response to the second of two paired auditory stimuli. Although normal suppression is occasionally observed in schizophrenic patients, it generally disappears with subsequent testing. We have previously reported that slow wave sleep (SWS) transiently normalized suppression in schizophrenic patients and that the degree of suppression was positively correlated with the depth of SWS attained. We hypothesized that schizophrenic patients may have a defect that causes a neuronal mechanism to fail after brief use and that its activity can be restored by a transient period of inactivity. The present study examined whether this effect of sleep in schizophrenic patients is specific to SWS or is due to nonspecific factors involved in any period of unconsciousness. After baseline recordings, 10 schizophrenic subjects were allowed a period of sleep until they attained rapid-eye-movement (REM) sleep. They were awakened at the end of the REM period, and postsleep recordings were obtained. REM-stage sleep failed to normalize suppression in any of the schizophrenic subjects. P50 suppression was subsequently assessed after a period of non-REM (NREM) sleep. Subjects who reached stage-2 sleep did demonstrate a transient correction in auditory gating. These results replicate our previous findings and suggest that the sleep effect is specific to NREM sleep. A desensitized nicotinic receptor that is resensitized during cholinergic inactivity in NREM sleep is one possible mechanism for this effect.

Adult↗
PubMed1994

Fine motor performance in schizophrenia.

Peripheral and central aspects of motor dysfunction were assessed in 12 schizophrenic and 12 normal subjects, using a test of control of finger movement based on the widely used smooth pursuit eye movement task. This was performed in order to investigate the basis of neuromotor dysfunction in schizophrenia. In this task, subjects used finger movement to track a visual target. Simultaneously, an electromyogram of the extensor digitorum communis, the primary muscle utilized in the task, was recorded. Smooth pursuit eye movements were also assessed. Accuracy of finger-based and smooth-pursuit eye movement tracking was analyzed by fast Fourier transform and expressed as a log signal-to-noise ratio. The electromyograms were analyzed by motor unit potential discrimination and by interspike interval histography. Schizophrenics demonstrated significantly poorer finger tracking than did controls, with a mean score of 2.01 +/- 0.63 (SD) versus 2.81 +/- 0.42 (t = 3.52, d.f. = 21, p < 0.005). However, there was no evidence for motor-unit dysfunction. Schizophrenics also performed more poorly on smooth-pursuit eye movement, with a mean score of 2.06 +/- 0.62 versus 3.33 +/- 1.21 (t = 3.21, d.f. = 22, p < 0.005). Severity of extrapyramidal symptoms was correlated with poorer performance on the finger tracking task, but not smooth-pursuit eye movement. These findings support the hypothesis that schizophrenics' tracking abnormalities are due to central nervous system deficits rather than peripheral pathology.

Adult↗
PubMed1993

Normalization of auditory sensory gating in schizophrenic patients after a brief period for sleep.

Diminished suppression of the P50 component of the evoked potential following repeated auditory stimuli is one example of a deficit in elementary sensory processing in schizophrenia. Normal subjects suppress the P50 evoked potential to the second of two paired auditory stimuli. Although normal P50 suppression is occasionally observed in schizophrenic patients, it generally disappears with subsequent testing. The object of this experiment was to determine conditions for the reproducible normalization of P50 suppression in schizophrenic patients. After baseline recordings, 12 schizophrenic subjects were allowed to sleep for 10 minutes. The depth of sleep obtained was assessed by electroencephalography (EEG). Normalization of P50 suppression was observed for approximately 3 minutes in all subjects who entered slow wave sleep, but not in those whose EEG records remained desynchronized. Some change was even observed in subjects who had only persistent alpha waves. The amount of normalization was correlated with the deepest stage of sleep reached. Normal control subjects did not show this phenomenon but instead had a transient decrease in sensory gating after waking from sleep. The results suggest that schizophrenic patients may have a defect that causes a neuronal mechanism critical to sensory gating to fail after brief use, although its activity can be transiently restored by a short period of inactivity. A rapidly desensitized neurotransmitter receptor is one possible mechanism of such an effect.

Acoustic Stimulation↗
PubMed1990

31P NMR studies on the effect of phosphite on Phytophthora palmivora.

31P NMR spectra were obtained from perchloric acid (PCA) and KOH extracts of Phytophthora palmivora mycelium. Signals indicating the presence of large amounts of short-chain polyphosphate were observed in the spectra of PCA extracts of mycelia grown under both low (0.1 mM) and high (10 mM) phosphate conditions. The mean chain length of polyphosphate was calculated from the relative areas of signals arising from terminal and internal P nuclei in the polyphosphate chain. The small amount of polyphosphate evident in the KOH extract had an average chain length similar to PCA-soluble polyphosphate. 32P tracer studies indicated that phosphorus in the PCA fraction accounted for between 50 and 60% of total phosphorus, the bulk of the remainder being divided between the lipid and KOH extracts. The presence of the fungicide phosphorous acid markedly reduced the average chain length of acid-soluble polyphosphate. This reduction occurred both under low-phosphate conditions, in which treatment with phosphorous acid retards growth, and under high-phosphate conditions, in which no significant growth retardation is observed. Treatment with phosphorous acid perturbed phosphorus distribution and lipid composition under low-phosphate conditions.

Chytridiomycota↗
PubMed1989

Molecules relevant for T cell-target cell interaction are present in cytolytic granules of human T lymphocytes.

An ultrastructural analysis of human cytotoxic T lymphocyte-target cell (CTL-TC) interaction has been undertaken to enable a better understanding of the killing mechanism. Attention was focused on granules in the CTL, which are known to contain lethal compounds. Within the membrane-delimited cytotoxic granule an electron-dense core as well as numerous membrane vesicles were identified. In CTL-TC conjugates, specific membrane interactions take place, allowing the formation of intercellular clefts into which the granule cores and internal vesicles are released. T cell surface membrane molecules known to be involved in CTL-TC interaction (T cell receptor, CD3 and CD8) are present on the membranes of the granule cores and internal vesicles, facing outward. An explanation for this localization of the membrane may be found in the fact that the granule is connected with an endocytotic pathway. Moreover, the lumen of the granule is rich in the enzyme cathepsin D, which indicates an association with a lysosomal compartment. Exocytosed vesicles and cores are seen to adhere to the plasma membrane of the TC. Although the exact contents of the granule vesicles and core remain to be identified, we suggest that specific interaction of CTL membrane molecules on the cytolytic granule components with molecules on the plasma membrane of the TC may ensure the unidirectional delivery of the lethal hit.

Clone Cells↗
PubMed1989

Accelerated ion fluxes during differentiation in zoospores of Phytophthora palmivora.

Zoospores of Phytophthora palmivora show increased fluxes of Na+ and Ca2+ 3-5 min after they have been stimulated to differentiate with pectin. Both spontaneous and pectin-induced encystment are reduced below pH 6 and accelerated above pH 7. The ionophores monensin and A23187 induce slow differentiation when added together, but not when added separately. Ethanol (0.5%) also induces slow differentiation. Amiloride and verapamil inhibit pectin-induced differentiation and also reduce the onset of the Na+ and Ca2+ flux. A requirement for Ca2+ for differentiation is confirmed, but a requirement for Na+ could not be demonstrated.

Amiloride↗
PubMed1989

Relations between the intracellular pathways of the receptors for transferrin, asialoglycoprotein, and mannose 6-phosphate in human hepatoma cells.

We compared the intracellular pathways of the transferrin receptor (TfR) with those of the asialoglycoprotein receptor (ASGPR) and the cation-independent mannose 6-phosphate receptor (MPR)/insulin-like growth factor II receptor during endocytosis in Hep G2 cells. Cells were allowed to endocytose a conjugate of horseradish peroxidase and transferrin (Tf/HRP) via the TfR system. Postnuclear supernatants of homogenized cells were incubated with 3,3'-diaminobenzidine (DAB) and H2O2. Peroxidase-catalyzed oxidation of DAB within Tf/HRP-containing endosomes cross-linked their contents to DAB polymer. The cross-linking efficiency was dependent on the intravesicular Tf/HRP concentration. The loss of detectable receptors from samples of cell homogenates treated with DAB/H2O2 was used as a measure of colocalization with Tf/HRP. To compare the distribution of internalized plasma membrane receptors with Tf/HRP, cells were first surface-labeled with 125I at 0 degrees C. After uptake of surface 125I-labeled receptors at 37 degrees C in the presence of Tf/HRP, proteinase K was used at 0 degrees C to remove receptors remaining at the plasma membrane. Endocytosed receptors were isolated by means of immunoprecipitation. 125I-TfR and 125I-ASGPR were not sorted from endocytosed Tf/HRP. 125I-MPR initially also resided in Tf/HRP-containing compartments, however 70% was sorted from the Tf/HRP pathway between 20 and 45 min after uptake. To study the accessibility of total intracellular receptor pools to endocytosed Tf/HRP, nonlabeled cells were used, and the receptors were detected by means of Western blotting. The entire intracellular TfR population, but only 70 and 50% of ASGPR and MPR, respectively, were accessible to endocytosed Tf/HRP. These steady-state levels were reached by 10 min of continuous Tf/HRP uptake at 37 degrees C. We conclude that 30% of the intracellular ASGPR pool is not involved in endocytosis (i.e., is silent). Double-labeling immunoelectron microscopy on DAB-labeled cells showed a considerable pool of ASGPR in secretory albumin-positive, Tf/HRP-negative, trans-Golgi reticulum. We suggest that this pool represents the silent ASGPR that has been biochemically determined. A model of receptor transport routes is presented and discussed.

Asialoglycoprotein Receptor↗
PubMed1988

The pathways of endocytosed transferrin and secretory protein are connected in the trans-Golgi reticulum.

We used a conjugate of transferrin and horseradish peroxidase (Tf/HRP) to label the intracellular transferrin receptor route in the human hepatoma cell line HepG2. The recycling kinetics of [125I]Tf/HRP were similar to those of unmodified [125I]Tf, implying identical routes for both ligands. 3,3'Diaminobenzidine (DAB)-cytochemistry was performed on post-nuclear supernatants of homogenates of cells which were incubated with both Tf/HRP and [125I]Tf, and caused two different effects: (a) the equilibrium density of [125I]Tf containing microsomes in a Percoll density gradient was increased, and (b) the amount of immunoprecipitable [125I]Tf from density-shifted lysed microsomes was only 20% of that of nonDAB treated microsomes. The whole biosynthetic route of alpha 1-antitrypsin (AT), a typical secretory glycoprotein in HepG2 cells, was labeled during a 60-min incubation with [35S]methionine. DAB cytochemistry was performed on post-nuclear supernatants of homogenates of cells which were also incubated with Tf/HRP. DAB cytochemistry caused approximately 40% of microsome-associated "complex" glycosylated [35S]alpha 1-antitrypsin ([35S]c-AT) to shift in a Percoll density gradient. Only part of the density shifted [35S]c-AT could be recovered by immunoprecipitation. A maximum effect was measured already after 10 min of Tf/HRP uptake. The density distribution of the "high mannose" glycosylated form of 35S-alpha 1-anti-trypsin [( 35S]hm-AT) was not affected by Tf/HRP. If in addition to Tf/HRP also an excess of non-conjugated transferrin was present in the medium, [35S]c-AT was not accessible for Tf/HRP, showing the involvement of the transferrin receptor (TfR) in the process. Furthermore, we show that if Tf/HRP and [35S]c-AT were located in different vesicles, the density distribution of [35S]c-AT was not affected by DAB-cytochemistry. Pulse-labeling with [35S]methionine was used to show that [35S]c-AT became accessible to endocytosed Tf/HRP minutes after acquirement of the complex configuration. A common intracellular localization of endocytosed Tf/HRP and secretory protein could be confirmed by immuno-electron microscopy: cryosections labeled with anti-albumin (protein A-colloidal gold) as well as DAB reaction product showed double-labeling in the trans-Golgi reticulum.

Biological Transport↗
PubMed1984

Calcium efflux associated with encystment of Phytophthora palmivora zoospores.

Zoospores of the fungus Phytophthora palmivora, pre-labeled with 45Ca, excreted up to 30% of their total 45Ca when stimulated to encyst. Excretion was essentially completed within 90 sec of the application of the stimulus. Encystment of the population was completed within 5 min. Four different stimuli were used: pectin addition (420 micrograms ml-1), Sr2+ addition (5 mM), cyclic AMP addition (6.7 mM) and mechanical agitation. The kinetics and amount of Ca excretion were essentially the same in each case. The calcium ionophore A23187 increased the rate of 45Ca uptake by motile zoospores, incubated in 100 microM CaCl2, but did not induce encystment under these conditions. The ionophore did not induce 45Ca efflux from pre-labeled zoospores. Incubation in EGTA and in K+ failed to induce either encystment or 45Ca excretion. We conclude that rapid excretion of a significant proportion of the zoospore calcium is linked to the early stage of stimulus-induced encystment, and that this comes from an intracellularly located, non-cytoplasmic source, such as the peripheral vesicles, but that changes in cellular Ca2+ are not necessarily the single controlling factor in the induction of encystment.

Adenine Nucleotides↗
PubMed1984

Hyperadrenalism in childhood and adolescence.

Hyperadrenalism in childhood and adolescence has unique features that influence diagnosis and management. We reviewed our experience with 18 patients, ranging in age from 18 months to 18 years. Nine had bilateral adrenal hyperplasia, eight had adrenal neoplasms, and one had micronodular hyperplasia. Patients with congenital adrenal hyperplasia and hyperaldosteronism were excluded. Six patients with Cushing's disease diagnosed in earlier years were treated by total adrenalectomy and recently two patients underwent transsphenoidal removal of pituitary tumors. Bilateral adrenalectomy was carried out in one patient with micronodular hyperplasia and in a second because of elevated adrenocorticotrophic hormone (ACTH) levels from an undefined source. Eight patients had adrenal neoplasms, including five adenomas and three carcinomas. We found no reliable criteria to differentiate before surgery between adrenal adenomas and adrenal carcinomas. The most recognizable characteristic of malignancy was tumor size, specifically weight greater than 75 gms. Of the three patients with adrenal carcinoma, one expired 20 months after adrenalectomy and 8 months after receiving palliative partial hepatectomy for liver metastasis. Two patients are well with normal growth and development at 11 and 20 years following adrenalectomy. With the exception of one patient who died 6 years after surgery from a glioblastoma multiforme, all patients with adrenal adenomas are well. Eight patients underwent bilateral adrenalectomy for hypercortisolism. Five of the six who have reached their adult stature are significantly stunted. Four of six patients with Cushing's disease, treated by total adrenalectomy, have developed Nelson's syndrome at 2, 6, 10, and 12 years after surgery. Of the two patients undergoing transsphenoidal surgery, one had recurrent disease at 2 years and was treated by pituitary irradiation with recovery. The patients undergoing adrenalectomy for micronodular hyperplasia and ectopic ACTH are well at 2 and 4 years, respectively. Cushing's disease in children and adolescents is best treated by transsphenoidal removal of the pituitary adenoma. Adrenalectomy, once the most accepted approach, plays a secondary role and is indicated primarily in micronodular adrenal hyperplasia, in patients with ectopic ACTH production of an undefined source, and in recurrent Cushing's disease following prior pituitary irradiation. The high incidence of Nelson's syndrome in children treated by adrenalectomy mandates that patients at risk be monitored lifelong for the progression of a pituitary tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗
PubMed1978

An ultrasound system for combined cardiac imaging and Doppler blood flow measurement in man.

An ultrasound instrument has been developed that combines a real-time cross-sectional imaging system and a spectrum analyzer-based Doppler velocimeter. This combination allows the Doppler sample volume to be superimposed on the cross-sectional image of the heart so that the sample volume can be located accurately. The same 2.2 MHz transducer utilized for cross-sectional imaging is stopped mechanically and quickly switched to transmit and receive the Doppler ultrasound signal. Preliminary experience in 20 young and adult normal subjects indicates that it is possible to place the Doppler sample volume in the proximal main pulmonary artery at a point where the sound beam and blood flow stream are parallel. Measurement of the distance from transducer to the sample volume and the peak blood flow velocities in the main pulmonary artery of normal subjects indicates that these quantities are within the measurement capabilities of the system. The ultimate goal of this device is to make measurements of volume blood flow in man noninvasively.

Coronary Circulation↗
PubMed1977

Cross-sectional echocardiography in the diagnosis of congenital heart disease. Identification of the relation of the ventricles and great arteries.

Using a mechanical sector-scanner, two-dimensional echocardiograms were obtained from 28 normal subjects, 15 patients with tetralogy of Fallot, 11 patients with complete transposition of the great arteries and six patients with double outlet right ventricle. The image obtained perpendicular to the long axis of the left ventricle at the base of the venticular septum was superimposed on the image obtained perpendicular to the long axis at the origin of the great arteries. In normal subjects, these superimposed images demonstrated that the aorta originated posterior and to the left of the ventricular septum. In patients with tetralogy of Fallot, the aorta was displaced anterior and to the right resulting in the aorta over-riding the ventricular septum. In patients with double outlet right ventricle both great arteries originated anterior to the ventricular septum (i.e., from the right ventricle). In patients with complete transposition, the aorta originated anterior and the pulmonary artery posterior to the ventricular septum. Thus, cross-sectional echocardiography permits noninvasive identification of the relation of the ventricles and great arteries and, therefore, provides important information for the diagnosis of patients with congenital heart disease.

Adolescent↗
PubMed1976

Regional contractility. Selective depression of ischemic myocardium by verapamil.

The effects of verapamil (0.02-0.2 mg/kg) on contractility in normal and partially ischemic myocardium were compared with the changes following propranolol (0.01-1.0 mg/kg). Regional contractile function was studied in open-chest dogs with ultrasonic crystals and ischemia was controlled by graded occlusion of a carotid-to-coronary artery shunt. Reduction in shunt perfusion pressure (40-55 mm Hg) resulted in hypokinesia. Verapamil depressed contractility in ischemic myocardium in 5/5 dogs, but did not alter the maximum velocity of shortening (max V) or end-diastolic segment length in normal myocardium. Propranolol in doses sufficient to depress ischemic myocardium also depressed contractile function in normal myocardium. In two dogs without coronary occlusion, verapamil (up to 1.0 mg/kg) increased end-diastolic segment length but did not reduce max V. We conclude that verapamil selectively depresses ischemic myocardium, a finding that may have clinical implication since ischemic injury can be decreased by reducing contractility (and thereby MVO2).

Animals↗
PubMed1975

Mechanism of left ventricular outlfow obstruction in patients with obstructive asymmetric septal hypertrophy (idiopathic hypertrophic subaortic stenosis).

Left ventricular outflow obstruction in patients with idiopathic hypertrophic subaortic stenosis or obstructive asymmetric septal hypertrophy is due to abnormal forward motion during systole of the anterior mitral leaflet. To determine why some patients with this disease hav left ventricular outflow obstruction whereas others do not, we studied a large number of patiens with assymetric septal hypertrophy using both one- and two-dimensional echocardiography. In 100 patients with asymmetric septal hypertrophy and 22 normal subjects, mitral valve position at the onset of systole was quantitated by measuring the distance from the ventricular septum to the mitral valve and the distance from the mitral valve to the posterior left ventricular wall. None of the normal subjects and only 3 (6 percent) of 51 patients with nonobstructive asymmetric septal hypertrophy had a septal-mitral valve distance of less than 20 mm compared with 23 (66 percent) of 35 patients with obstructive asymmetric septal hypertrophy. Moreover, the mitral valve at the onset of systole was actually positioned forward in the left ventricular activity. Two-dimensional studies in 11 patients with obstructive asymmetric septal hypertrophy revealed that contraction of the malaligned papillary muscles did not cause the abnormal forward mitral valve motion. We propose that the left ventricular outflow obstruction in patients with obstructive asymmetric septal hypertrophy occurs as a result of two factors: (1) narrowing of the left ventricular outflow tract at the onset of systole, and (2) hydrodynamic forces generated by contraction on the left ventricle.

Aortic Stenosis, Subvalvular↗