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Biomedical subjects

S Funahashi

Publications and source records attributed to S Funahashi.

At least 73 records · Page 4Linked to original sources

Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex.

1. An oculomotor delayed-response task was used to examine the spatial memory functions of neurons in primate prefrontal cortex. Monkeys were trained to fixate a central spot during a brief presentation (0.5 s) of a peripheral cue and throughout a subsequent delay period (1-6 s), and then, upon the extinction of the fixation target, to make a saccadic eye movement to where the cue had been presented. Cues were usually presented in one of eight different locations separated by 45 degrees. This task thus requires monkeys to direct their gaze to the location of a remembered visual cue, controls the retinal coordinates of the visual cues, controls the monkey's oculomotor behavior during the delay period, and also allows precise measurement of the timing and direction of the relevant behavioral responses. 2. Recordings were obtained from 288 neurons in the prefrontal cortex within and surrounding the principal sulcus (PS) while monkeys performed this task. An additional 31 neurons in the frontal eye fields (FEF) region within and near the anterior bank of the arcuate sulcus were also studied. 3. Of the 288 PS neurons, 170 exhibited task-related activity during at least one phase of this task and, of these, 87 showed significant excitation or inhibition of activity during the delay period relative to activity during the intertrial interval. 4. Delay period activity was classified as directional for 79% of these 87 neurons in that significant responses only occurred following cues located over a certain range of visual field directions and were weak or absent for other cue directions. The remaining 21% were omnidirectional, i.e., showed comparable delay period activity for all visual field locations tested. Directional preferences, or lack thereof, were maintained across different delay intervals (1-6 s). 5. For 50 of the 87 PS neurons, activity during the delay period was significantly elevated above the neuron's spontaneous rate for at least one cue location; for the remaining 37 neurons only inhibitory delay period activity was seen. Nearly all (92%) neurons with excitatory delay period activity were directional and few (8%) were omnidirectional. Most (62%) neurons with purely inhibitory delay period activity were directional, but a substantial minority (38%) was omnidirectional. 6. Fifteen of the neurons with excitatory directional delay period activity also had significant inhibitory delay period activity for other cue directions. These inhibitory responses were usually strongest for, or centered about, cue directions roughly opposite those optimal for excitatory responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Development and clinical application of ICG clearance meter].

We have developed a finger-piece method that can indicates an accurate concentration of ICG based on the two wavelength spectrophotometry. Seventy-eight subjects were evaluated by this new method. The ICG clearance curve obtained from ICG clearance meter showed a rapid increase 20 or 40 seconds after the bolus injection. The curve decreased gradually, and increased again at 60 or 70 seconds. Plasma disappearance rate (PDR) by this method (XK ICG) was calculated by the at least square method from 600 data obtained from 5 to 15 minutes after the injection. There was a significant correlation between conventional PDR (KICG) and new method (XK ICG) also. We assume that this method have a possibility to discover new aspect of pharmacokinetics of ICG.

Adolescent↗

[A study on bacteria within stones in urolithiasis].

The bacteria in 37 stones obtained from 37 patients with urinary stone diseases, that is, 11 renal stones (containing 2 staghorn calculi), 21 ureteral stones, 4 bladder stones and 1 urethral stone, were studied, according to the Nemoy & Stamey's method. The stones were collected by partial nephrectomy (1 case), nephrolithotomy (1 case), pyelolithotomy (1 case), percutaneous nephrolithotripsy (PNL) (6 cases), 12 ureterolithotomies, transurethral ureterolithotripsy (2 cases), cystolithotripsies (4 cases) and spontaneous deliveries (10 cases). According to a stone analysis by infrared spectrophotometer revealed 30 were noninfection stones (81.1%) and 7 infection stones (18.9%). Of these 37 stones, 5 stones (13.5% of 11 stones) had bacteria within them. These stones consisted of 4 infection stones (57.1% of all infection stones) and 1 noninfection stone (3.3% of all noninfection stones). Out of 4 patients having bacteria within their stones, urine culture of whom were carried out before stones were collected, only one patient (25%) had the same species of bacterium (E. coli) both within the stone and in urine. The E. coli within the stone and that in urine, however, showed quite different reactions to some antibiotics. The fact that all organisms within stones cannot be detected by urine culture before collecting stones of the patients in our present study, suggests that patients undergoing endourological surgery, such as extracorporeal shock wave lithotripsy and PNL, may have a risk of complications, such as severe urinary tract infection and urosepsis, if the possibility of the presence of organisms within stones is not taken into consideration.

Adult↗

Cloning and characterization of the gene encoding the major protein of the A-type inclusion body of cowpox virus.

We have mapped and determined the nucleotide sequence of the cowpox virus (CPV) gene coding for the protein of A-type inclusion bodies (ATI). The ATI gene was mapped to the central part of the largest HindIII restriction fragment of the CPV genome. Vaccinia virus (VV) also contained a similar sequence at the equivalent position in its genome, which even under stringent conditions hybridized with the CPV ATI gene. Nucleotide sequence analysis revealed that the upstream region of the coding frame contained a sequence closely resembling the VV late promoter consensus sequence and that the gene encoded a protein of Mr 150,000.

Amino Acid Sequence↗

Factor VII activity and antigen in a patient with abnormal factor VII.

A patient with abnormal factor VII, which showed different activity when thromboplastin from different sources was used, is reported. The propositus, who was first seen at routine health examination 1 month after delivery, was a girl with no complaints of bleeding. The coagulation pattern was characterized by an abnormal clotting time using Normotest reagent which did not respond to the administration of vitamin K. Factor VII activity was decreased when measured using rabbit brain and lung thromboplastin, mildly decreased using human brain or human placenta thromboplastin and within the normal range using ox brain thromboplastin. The level of factor VII antigen was normal and revealed a normal mobility on immunoelectrophoresis. The molecular weight of this factor VII was not different from normal factor VII when analysed using autoradiography after sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). It seems probable that the propositus had an abnormality similar to the factor VII Padua 1 described previously.

Antigens↗

[Comparison of chemical and immunological methods in fecal occult blood testing].

Conventional occult blood testing using the chemical method has been compared with newly developed immunological testing methods; the Hemoccult slide II (HEM II) test has been widely accepted as a guaiac test but such recent tests as the Latex agglutination test (Latex) and the Enzyme Immunoassay method (EIA) have also come to be employed. Thirty colorectal cancer patients, 30 gastric cancer patients and 30 healthy persons were subjected the three above described tests during 3 consecutive days while under no restricted diet. False positive rates during this three-day testing period were 26.7% in HEM II, 93.3 in Late and 8.3% in EIA. Although the immunological testing method has the advantage of reducing the false positive rate without the need for a restricted diet it is time-consuming and expensive. Considering these results as well as our previous knowledge accrued from a mass survey, it is suggested that a new flow-chart may be found necessary, in which an initial screening is given by the chemical method and then followed by a secondary screening by the immunological method. This new flow-chart, if routinely employed, would greatly facilitate the mass screening of colorectal cancer.

Hemoglobins↗

Chromosome walking shows a highly homologous repetitive sequence present in all the centromere regions of fission yeast.

By cloning centromere-linked genes followed by partial overlapping hybridization, we constructed a 210-kb map encompassing the centromere in chromosome II and a 60-kp map near the centromere of chromosome I in the fission yeast Schizosaccharomyces pombe which has three chromosomes. Integration of the cloned sequences into the chromosome and subsequent analyses of tetrads and dyads revealed an approximately 50 kb long domain located in the middle of the 210-kb map, tightly linked to the centromere and greatly reduced in meiotic recombination. This domain contained at least two classes of repetitive sequences. One, designated yn1, was specifically present in a particular chromosome and repeated three times in the 210-kb map of chromosome II. The other, designated dg, was located in all the centromere regions of three chromosomes. One (dgI) and two (dgIIa, dgIIb) copies of the dg were found in the maps of chromosomes I and II, respectively. The dgIIa and dgIIb were arranged with a 20-kb interval within the repetitive domain. In the centric region of chromosome II, 3-4 copies of the dg appeared to exist. By determining the nucleotide sequences of dgI and dgIIa, the dg was identified to be 3.8 kb long. The sequence homology was 99% between dgI and dgIIa. These extraordinarily homologous sequences seemed not to be transcribed into RNA nor to be encoding any protein. The larger part of the dg sequence was internally non-repetitious, a 600-bp region existed which consisted of stretches of several short repeating units. The structures in or surrounding the centromeres of S. pombe appear to be much more complex than those of the budding yeast Saccharomyces cerevisiae.

Base Sequence↗

Isolation and characterization of Schizosaccharomyces pombe cutmutants that block nuclear division but not cytokinesis.

By examining cytological phenotypes of 587 temperature-sensitive mutants of the fission yeast Schizosaccharomyces pombe, we obtained 18 mutants which cause cell division in the absence of nuclear division. By genetic analyses, these novel nuclear division arrest mutants can be classified into nine complementation groups (designated cut1 - cut9). The cytological phenotype of cut mutants is similar but not identical to that of DNA topoisomerase II mutants (top2). The cut1 gene was cloned by transformation and shown to complement cut2 as well as cut1, indicating a functional relationship between the two genes. The cut genes are required for nuclear division, but their mutant phenotypes differ from most of the previously identified mutants which block nuclear division and also the subsequent cytokinesis. Fluorescence microscopy indicates that the mitotic chromosomes formed in cut mutant cells are abnormal and fail to separate properly. We suggest that cut mutations, like top2, block mitotic chromosome formation and concomitantly nuclear division, but that cytokinesis proceeds independently of the defects in nuclear division, demonstrating uncoordinated mitotic pathways. A novel mutant nuc1 is also described which shows a cytological phenotype similar to the double mutant of DNA topoisomerases I and II but contains normal levels of both DNA topoisomerase activities.

Journal Article↗

[Hereditary angioneurotic edema: pathophysiology and therapy].

The hereditary angioneurotic edema (HANE), owing to its characteristic clinical symptom, episodic formation of localized edema, has been the subject to be discussed in relation to the problems of the mechanism for the edema formation. On the other hand, when HANE is considered from the point of view on the abnormality in the plasma proteinase systems, it has been thought to be a suitable hereditary defect which enables to investigate into the interactions of the plasma proteinase systems. However, when the clinical course of the disease is correlated with the changes in the plasma proteinase systems, it appears very likely to state that HANE is a very unique model disease, in which edema attacks are elicited by the interactions between plasma proteinase systems and vascular system of the microcirculation, that are triggered by the exogenous stimuli under the influence of the control functions of the endocrine systems.

Angioedema↗

Studies of four Japanese families with hereditary angioneurotic edema: simultaneous activation of plasma protease systems and exogenous triggering stimuli.

Forty-five relatives of 4 families with hereditary angioneurotic edema (HANE) were studied. Twenty-five, including 11 asymptomatic kindreds with the disposition, showed typical changes in complement system compatible with HANE. Follow-up study of HANE patients showed that, even in remission period, complement, coagulation and fibrinolytic systems can be activated. During edema attacks, moderate haemoconcentration and neutrophilia were encountered and kallikrein-kinin system was found to be also activated. Replacement therapy with C 1-inhibitor preparation for an edema attack revealed that clinical improvement paralleled the increase in blood levels of high molecular weight kininogen. Thus, HANE attack is considered to be elicited in kindreds with the hereditary disposition by activation of plasma protease systems, particularly by that of kallikrein-kinin system. On the other hand, exogenous triggers that can initiate activation of the protease systems can be classified into 2, neuro-humoral (sympathetic nerve response) and physico-chemical, categories. Hence, the edema attack of kindreds with the hereditary disposition can at least be modified by the biosynthesis of plasma factors and the individual susceptibility to the liberated catecholamines. These two different reaction processes are considered to be linked by the release of plasminogen activator and/or Hageman factor activating enzyme.

Angioedema↗

Responses of monkey prefrontal neurons during a visual tracking task reinforced by substantia innominata self-stimulation.

The role of the substantia innominata (SI) in the generation of a behavior mediated by the prefrontal (PF) cortex was examined in two Japanese monkeys. PF neuronal activities related to a visual tracking task by wrist movement were recorded and neural responses to SI stimulation were analyzed. Sixty-six neurons showed task-related activity and were classified into 3 types. Type 1 (n = 31) showed transient activation during the movement. Type 2 (n = 26) showed gradually increasing activity before the reward presentation. Type 3 (n = 9) showed tonic activation from the GO signal to the reward presentation. Antidromic and orthodromic responses to SI stimulation were observed in every type. In Type 1, the percentage of antidromically activated neurons (26%) was similar to that of orthodromically activated ones (16%), but in Type 2, 83% of responding neurons showed antidromic responses, and 56% of Type 3 showed orthodromic responses. These results show that the different types of PF neurons have different anatomical relations to SI. Although orthodromically activated neurons were fewer than antidromically activated neurons, many orthodromically activated neurons showed movement-related activity. This suggests that ICSS at SI facilitates the generation of the behavior through the afferent pathway to PF.

Animals↗