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Biomedical subjects

Y Watahiki

Publications and source records attributed to Y Watahiki.

At least 19 recordsLinked to original sources

Cerebral oxygen and glucose metabolism and blood flow in mitochondrial encephalomyopathy: a PET study.

Cerebral blood flow (CBF), oxygen metabolism (CMRO2), and glucose metabolism (CMRGlc) were measured using positron emission tomography in five patients diagnosed as having mitochondrial encephalomyopathy. The molar ratio between the oxygen and glucose consumptions was reduced diffusely, as CMRO2 was markedly decreased and CMRGlc was slightly reduced. The CBF showed less changes. The CBF increase on hypercapnia was smaller than normal, though this was not significant. CBF with hypocapnia demonstrated a significant reduction compared with the normal. These results suggest that oxidative metabolism is impaired and anaerobic glycolysis relatively stimulated, due to a primary defect of mitochondrial function, and that mild lactic acidosis occurs in brain tissue because of impaired utilisation of pyruvate in the TCA cycle. As these findings appear to indicate directly a characteristic of this disease, such measurements may be a useful tool for assessment of the pathophysiology and for diagnosis of mitochondrial encephalomyopathy.

Acidosis, Lactic

Correlation of EEG activities between slow-wave sleep and wakefulness in patients with supra-tentorial stroke.

Using topographic EEG mapping, we studied the relationships between delta activity during slow-wave sleep (SWS) and the background EEG activity during wakefulness, in 11 normal subjects and 35 stroke patients with unilateral supra-tentorial lesions. Delta-1 power during SWS showed a significant positive correlation with alpha-1 power during wakefulness, in both hemispheres. Delta-1 and delta-2 power during SWS correlated positively not only with alpha-2 power, but also with delta-1 and delta-2 power during wakefulness in the affected hemisphere. these figures indicate that the amount of delta activity during SWS can be associated with that of alpha activity during wakefulness. A close negative correlation was observed between delta power during SWS and the age of the subjects in the patient group. The Barthel index showed no significant correlation with delta-1 or delta-2 power in either hemisphere in patient group. Our results suggest that delta activity during SWS may be associated with dysfunction of the cerebral cortex in stroke patients as well as in normal aged subjects.

Adult

Scalp topography of SEP late components in patients with supra-tentorial lesions.

Somatosensory evoked potentials (SEP) to simultaneous bilateral median nerve stimulation were recorded in 7 patients with unilateral brain lesions, 8 patients with degenerative dementia, and 5 normal volunteers. Right-left amplitude difference was compared from serial topographic images and the amplitude was compared at homologous electrodes. In patients with unilateral lesions, the amplitude from the frontopolar, frontal, anterior-temporal, and/or occipital electrodes was smaller on the affected side at 240 and 360 msec, regardless of whether the subjects showed sensory deficit or not. No significant laterality was seen in the primary sensorimotor areas. Distribution obtained from the patients with degenerative dementia was quite symmetrical. A significant right-left amplitude difference was seen at the anterior temporal site at 180 and 240 msec in normal controls, although an almost symmetrical distribution was obtained on the topographic images. The late components of SEP are not associated with the primary somatosensory function, but possibly with other cortical pathways.

Aged

[Outcomes of effective treatment of cases of metastatic liver tumors by intra-arterial infusion chemotherapy].

We studied the prognoses of unresectable liver tumors, including 31 colorectal cancers and 10 gastric cancers treated by intra-arterial infusion chemotherapy using an implantable reservoir. Adriamycin, epirubicin, or cisplatin were administered intermittently early on. Cisplatin and 5-FU combined therapy were given later. In nine with colorectal metastases and six with gastric metastases, metastatic lesions decreased, and in 4 patients with metastatic lesions could be resected. But in many patients, hepatic and other organ recurrences were observed. We need to try many other treatments.

Adenocarcinoma

Infratentorial infarction: correlation of MR findings with neurological and angiographical features.

Using magnetic resonance imaging, we reviewed 141 infratentorial infarcts in 81 consecutive cases: 65 infarcts were seen in the paramedian pons, while 18 in the posterior inferior cerebellar artery (PICA) territory and 17 in the watershed area between PICA and superior cerebellar artery. No comparable sign or symptom was observed for 44 (31.2%) infarcts, whereas 66 (46.8%) infarcts appeared symptomatic and 31 (22.0%) infarcts were regarded as equivocal mainly due to the coexisting supratentorial lesions or non-localizing symptoms. The frequent coexistence of basal ganglionic small infarcts in those with infratentorial small (< 15 mm) infarcts implicated their common pathogenetic background. The fact that atrial fibrillation was seen in 33.3% of those with large (> 15 mm) infarcts whereas it was seen in only 6.5% of those with small infarcts may suggest a cardiogenic embolism as a possible cause of infratentorial large infarcts. Major artery occlusive lesion was seen in 15 of 22 cases with cerebellar infarction, whereas no occlusive lesion was seen in the majority of cases with pontine small infarcts. With MR imaging, infratentorial infarcts were detected more frequently than in the previous studies based on X-ray CT, and they can be considered as a benign condition.

Adult

Evolution of crossed cerebellar diaschisis in middle cerebral artery infarction.

To elucidate the evolution of crossed cerebellar diaschisis, cerebral oxygen metabolism was measured repeatedly by positron emission tomography (PET) in 35 consecutive patients with unilateral cerebral infarction within the territory of middle cerebral artery. The crossed cerebellar diaschisis was defined as significant when the laterality ratio of cerebral oxygen metabolism between the left and right cerebellar hemispheres exceeded the control range (mean +/- 2 standard deviations) as derived from 27 age-matched normal volunteers. Significant crossed cerebellar diaschisis was observed in 31 patients (89%) on the initial PET studies. Of these 31 patients, 23 with infarcts involving the frontal sensorimotor cortex persistently had crossed cerebellar diaschisis up to 5 years after onset, whereas the diaschisis disappeared in 8 patients with smaller infarcts mainly in the frontal or parietal lobe without recovery of oxygen metabolism in the infarcted areas. These present results suggest that crossed cerebellar diaschisis can exist persistently even in the late stage in those having a lesion involving the cortical pontine-cerebellar pathways.

Cerebellum

[A case of breast cancer with thrombosis during treatment of lung metastasis].

A 74-year-old female with lung metastasis of breast cancer was treated with chemo-endocrine therapy (intravenous administration of epirubicin at 30 mg/2w, oral administration of UFT at 400 mg/day, alternate oral administration of medroxyprogesterone acetate at 800 mg/day and tamoxifen at 40 mg/day) and immuno-therapy (intravenous administration of lentinan at 2 mg/w). Lung tumors decreased in size and number. At the same time, deep vein thrombosis of the lower extremities occurred, which caused multiple pulmonary embolization. In this case, several factors were suggested to cause thrombosis in the advanced or recurrent breast cancer patient.

Administration, Oral

Age-related decline of cerebral oxygen metabolism in normal population detected with positron emission tomography.

Using positron emission tomography (PET), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured in 32 healthy volunteers aged from 27 to 67 years. In bilateral putamen, left supratemporal, left infrafrontal and left parietal cortices, CMRO2 showed a significant decline during aging. The age-related decline of CBF was seen only at the left superior temporal cortex. The mean CMRO2 was significantly lower in the elder group (over 51 years old) than in the younger group (under 50 years old), whereas no significant difference in mean CBF between the two groups. The poor correlation of CBF to the age could be explained partly by the fact that CBF is easily influenced by the physiological, psychological and/or environmental factors. The age-related changes of CMRO2 were more marked in the association cortices of the left hemisphere than in that of the right hemisphere.

Adult

Potentiation by Lys-plasminogen of clot lysis by single or two chain urokinase-type plasminogen activator or tissue-type plasminogen activator.

Study has been made of the influence of addition of human NH2 terminal glutamic acid plasminogen (Glu-Plg) or human NH2 terminal lysine plasminogen (Lys-Plg) to normal citrated plasma upon the rate of lysis of fully crosslinked plasma clots in the presence of single or two chain urokinase type plasminogen activator (scu-PA/tcu-PA) or tissue plasminogen activator (t-PA). The specificity of any thrombolytic property was evaluated by measurement of plasma fibrinogen levels. Lys-Plg added to a concentration of 20% of normal plasma plasminogen caused 5 to 6 fold increase in the extent of lysis observed at 6 hours by 100 units/ml of scu-PA and with a small increase in fibrinogenolysis. Glu-Plg added at 20% of normal level had no influence on thrombolysis but at 50% of normal caused increased thrombolysis with rapid depletion of plasma fibrinogen. An apparently synergistic effect of addition of tcu-PA on scu-PA activity was increased by addition of plasminogen (e.g. addition of 20% Lys-Plg increased the lysis rate 4 to 5 fold over the first hour equivalent to an increase of potency of approximately three to four fold). Addition of plasminogen up to double the normal plasma concentration was observed to have no influence on clot lysis in the presence of t-PA. Plasminogen potentiated the rate of lysis by scu-PA/t-PA synergic mixtures with an approximately 1.5 to 1.9 fold increase in potency. Potentiation occurred without increase in the depletion of plasma fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Tests

Activation of pro-urokinase by plasmin: non-Michaelian kinetics indicates a mechanism of negative cooperativity.

Enzyme kinetic plots relating the initial rate of activation of pro-urokinase to urokinase by plasmin, according to the concentration of substrate, were smooth downward curves and indicated that an apparent decrease in binding affinity occurred with increase in the concentration of pro-urokinase. Such nonlinear plots were obtained with plasmin 1 and also plasmin 2. Over sections of each curve it was possible to estimate apparent kinetic constants. At the uppermost concentrations of substrate tested, these were Km 2.9 microM and kcat 35.5 min-1 for plasmin 1, and at the lowermost concentrations, Km 9.5 nM and kcat 2.0 min-1. Linear plots were obtained when the single proteolytic cleavage was made by K5-plasmin or undegraded plasmin in the presence of 1.0 mM 6-aminohexanoic acid (6-AHa). Constants were estimated for catalysis of this reaction by K5 plasmin to be Km 6.0 microM and kcat 38 min-1 (r = 0.987). The catalytic efficiency of plasmin, at the lowermost concentrations of pro-urokinase tested, was therefore 33-fold higher than that of K5-plasmin. Plotting of data for the cleavage of pro-urokinase by plasmin 1 (in the absence of 6-AHa) according to the model of Hill, gave a slope of 0.5 at the lowermost concentrations of pro-urokinase increasing to 1.0 at higher concentrations (greater than 0.3 microM); such a profile is characteristic of negative cooperativity. The rates of formation of plasmin and urokinase in a mixture containing a low concentration of plasminogen and pro-urokinase were measured and compared to those predicted by a computer program designed to calculate theoretical rates using available kinetic data. The observed rates of generation of both plasmin and urokinase coincided to those predicted from the negative cooperativity model. The mechanism of the negative cooperativity may reside in a conformational change induced by binding of pro-urokinase to the kringle structure of plasmin. This property may be of significance in controlling the fibrinolytic properties of the urokinase-type plasminogen activator system.

Allosteric Regulation

Sympathetic skin response in diabetic neuropathy.

Sympathetic function test was undertaken using the sympathetic skin response (SSR), a technique for assessment of sudomotor activity, in 67 diabetics, and the results were compared with those from 45 age-matched normal subjects. The SSR was readily elicitable in normal subjects, but absent in six patients with diabetes. In 28 patients, the SSR was preserved, but their amplitude was below the normal range. The decrease in the SSR amplitude correlated well with a fall in motor and sensory conduction velocity. The SSR magnitude correlated well to the impaired R-R interval variation during deep breathing and the heart rate increase and the blood pressure change on standing, indicating a close correlation between the disturbance of sudomotor function and that of other sympathetic and parasympathetic functions. Most of the patients with clinical evidence of dysautonomia and with insulin treatment revealed diminished or absent SSR.

Adolescent

[Chronic demyelinating polyradiculoneuropathy associated with malignant histiocytosis].

A case of malignant histiocytosis (MH) presenting with peripheral nerve involvement is described. A 67-year-old man initially noted left facial weakness on July 20, 1986. The symptom was improved within a week, however, two weeks later he noticed numbness in his fingers and a burning pain in his legs, which was followed by double vision and progressive weakness in all four limbs. On examination, he was found to have total ophthalmoparesis of the right eye and a trace of the left facial palsy. There was severe weakness of the leg muscles, as well as mild weakness of the arms. This was accompanied by wasting of his limbs. All tendon reflexes were absent. Planter responses were flexor. Although cutaneous sensation was intact, vibratory sense was markedly impaired in the legs below the knees. The sphincter function was mildly disturbed. The sedimentation rate was 32 mm/hr. The hemoglobin was 11.9 g/dl and the leukocyte count was 5,700/mm3. The platelet count fell to 60,000/mm3. Results of routine biochemical and radiological studies were unremarkable. The cerebrospinal fluid protein level was 129 mg/dl with a normal cell count. Motor nerve conduction study revealed marked reduction in amplitude of the compound muscle action potential, slow motor nerve conduction velocities and multifocal conduction blocks along the nerve trunks (the left ulnar nerve in the forearm, the bilateral tibial nerve in the lower leg). F-wave was absent or elicited with prolonged latency and with increased chrono-dispersion. Sensory nerve had normal or nearly normal conduction. EMG sampling showed an impaired interference pattern during voluntary contraction and a few denervation potentials at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Kinetic analyses of the activation of Glu-plasminogen by urokinase in the presence of fibrin, fibrinogen or its degradation products.

The kinetics of the activation of Glu-plasminogen (Glu-plg) and Lys-plasminogen (Lys-plg) by urokinase (UK) were studied in purified systems. The activation of plasminogen by UK in the purified systems followed Michaelis-Menten kinetics with a Michaelis constant (Km) of 1.45 microM and a catalytic rate constant (kcat) of 0.93/sec for Glu-plg as compared to 0.25 microM (Km) and 0.82/sec (kcat) for Lys-plg. In the presence of fibrin and fibrinogen or its plasmin degradation products (fragment D and fragment E), Km for Glu-plg hardly changed, whereas kcat for Glu-plg increased. Effect on increase in kcat was in the order of fibrin greater than fibrinogen greater than D greater than E. Fibrin, fibrinogen, D and E did not influence the activation of Lys-plg by UK. These results indicate that Glu-plg bound to fibrin, fibrinogen, D or E becomes easily activatable by UK. The activation of Lys-plg, however, is not influenced in the presence of fibrin, fibrinogen, D or E.

Enzyme Activation

[Akinetic mutism from recurrent hydrocephalus: successful treatment with levodopa, bromocriptine and trihexyphenidyl].

A case of akinetic mutism was reported with reference to a marked improvement by levodopa, bromocriptine and trihexyphenidyl. A 39-year-old male, first seen on February 2, 1981, had an occipitalgia, accompanied by nausea and vomiting. For several months before this consultation, the patient had suffered from asthenopia. Brain CT scan and cerebral angiogram demonstrated internal hydrocephalus due to aqueduct stenosis of unknown etiology. After a ventriculoperitoneal shunt operation on February 20, 1981, he completely recovered. Two years and a half after the shunt insertion he had no difficulty in his daily life. He reentered the hospital on December 21, 1983, because of personality change, mental deterioration and bradykinesia. Brain CT scan showed recurrent hydrocephalus resulting from shunt blockage. Following the shunt revision, hydrocephalus was resolved. Nevertheless, the patient did not return to his previous state. And he became bed-ridden, incontinent of urine, and unable to take fluids or foods, following which he went into a state of akinetic mutism. Other neurological findings were as follows: upward gaze palsy, impaired convergence, convergence nystagmus, plastic rigidity of neck and all four limbs, and diffuse hyperreflexia with right Babinski's sign. Abnormal involuntary movement was not seen. On March 27, 1984, levodopa therapy was instituted and on April 2, trihexyphenidyl was combined with levodopa. Shortly after administration of levodopa and trihexyphenidyl, akinetic mutism began to improve, but upward gaze palsy was not affected. He began to speak and could walk unassisted by the end of July.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult