Ontogenetic pattern of gyrification in fetuses of cynomolgus monkeys.

The ontogenetic pattern of gyrification and its relationship with cerebral cortical volume were examined in cynomolgus monkey fetuses. T(1)-weighted coronal magnetic resonance (MR) images at 7 T were acquired from the fixed cerebra of three male fetuses, each at embryonic days (EDs) 70 to 150, and the gyrification index (GI) of each slice was estimated. The mean GI was low (1.1-1.2) during EDs 70 to 90, and then increased dramatically on ED 100. The developmental profiles of the rostrocaudal GI distribution revealed that cortical convolution was more frequent in the parietooccipital region than in other regions during EDs 100 to 150, forming an adult-like pattern by ED 150. The mean GI was closely correlated with the volume of cortical gray matter (r=0.9877), and also with the volume of white matter/intermediate zone (r=0.8961). These findings suggest that cortical convolution is correlated with either the maturation of cortical gray matter or the development of white matter bundles. The characteristic GI distribution pattern of catarrhines was formed by ED 150 in correlation with the progressive sulcal infolding in the parietooccipital region of the cerebrum.

Development of cerebral sulci and gyri in fetuses of cynomolgus monkeys (Macaca fascicularis).

This study aimed to clarify the development of sulci and gyri on the external surface of the cerebrum of cynomolgus monkeys. Sulcus formation began with the appearance of the lateral fissure on embryonic day (ED) 70, followed by delineations of four cerebral lobes by the emergence of the parietooccipital sulcus, central sulcus, and preoccipital notch on EDs 80-90. The following primary sulci were then visible until ED 120: the superior temporal sulcus on ED 90; the intraparietal sulcus, lunate sulcus, inferior occipital sulcus, and arcuate sulcus on ED 100; and the principle sulcus on ED 110; the occipitotemporal sulcus, anterior middle temporal sulcus, and superior postcentral dimple on ED 120. These sulci demarcated the superior temporal gyrus on ED 90, the precentral gyrus, supramarginal gyrus, and angular gyrus on ED 100, and the inferior and middle temporal gyri, postocentral gyrus, superior parietal lobule, superior, middle and inferior frontal gyri, and inferior occipital gyrus on ED 120. Except for the intermediate and lateral orbitofrontal sulci, the sulci that appeared on ED 130 and thereafter were not related to the gyrus demarcations. Intriguingly, the brain markedly gained weight on EDs 100 and 120, corresponding to the embryonic ages when almost all gyri were visible. The results suggest that a rapid growth of the cerebrum involves convolutions of the gyri by a regular sequence of the sulcus formation in cynomolgus monkeys. This study further provides a standard of reference for normal development in the cerebral cortical morphology of cynomolgus monkeys.

Overview of studies on rat sperm motion analysis using a Hamilton-Thorne Sperm Analyzer--collaborative working study.

This collaborative study was conducted to determine the utility and sensitivity of nine sperm motion parameters generated by a Hamilton-Thorne Sperm Analyzer (HTM-IVOS) for detecting adverse effects of chemicals on sperm motion in rats. The efficacy of sperm motion parameters was investigated using nine reproductive toxicants: adriamycin, alpha-chlorohydrin (3 different studies were carried out), dinoseb, ethylene glycol monoethyl ether, 2,5-hexanedione, sulfasalazine, trimethyl phosphate, and ornidazole. The percentage of motile sperm (% motile sperm), the only parameter expressing the status of semen containing non-motile sperm, detected adverse effects on sperm motion in 9 out of 10 studies. However, weak effects on sperm motion were not detected by this parameter in 4 out of 7 studies in which sperm motion disorders were noted at medium or low dosages. The percentage of progressively motile sperm (% progressive sperm) and the sperm velocity parameters (average path velocity, straight line velocity, and curvilinear velocity) detected adverse effects on sperm motion in all studies. In 7 studies which noted sperm motion disorders at medium or low dosages, weak effects on sperm motion were detected by the % progressive sperm in 5 studies and by the sperm velocity parameters in 6 studies. In 10 studies, amplitude of lateral head displacement (ALH) did not detect adverse effects on sperm motion in 4 studies, and beat cross frequency (BCF) failed to detect adverse effects on sperm motion in 3 studies. Because ALH and BCF show the swimming pattern of spermatozoa as head movement, the characteristics of these parameters are different from the % progressive sperm and the sperm velocity parameters. Straightness (STR) and linearity (LIN), which are secondary parameters calculated from sperm velocity parameters, could not detect adverse effects on sperm motion when the sperm velocity parameters did not detect adverse effects. On the basis of these results, we concluded that the % progressive sperm and sperm velocity parameters are useful and sensitive indicators for detecting adverse effects on sperm motion. However, in the % progressive sperm, setting up a suitable threshold of VAP and/or STR is important to gain further sensitivity for detecting adverse effects on sperm motion. The % motile sperm is useful for assessment of sperm motion disorder, and ALH and BCF are useful for evaluating the swimming pattern of sperm. STR and LIN are not very useful for detecting adverse effects on sperm motion.

Epidemiology of childhood burns in the critical care medical center of Kinki University Hospital in Osaka, Japan.

The objective of the present study was to describe the characteristics of pediatric burns in order to prepare a program for the prevention of severe burn injuries in children. We conducted a retrospective study of burn victims aged 15 years or younger who were hospitalized in our Critical Care Medical Center between 1982 and 1997. There were 73 children with burn injuries hospitalized in our center during the study period. The greatest number were children 1 year old. The average % body surface area burned was 21. 5+/-20.5%. The most important causes of pediatric burns were found to be hot bath water and other hot liquids. Hot bath scalds accounted for about half of the pediatric burns occurring in all age groups, and they were often extensive. Non-bath scalds accounted for about one-third of the pediatric burns and were most frequent in children 2 years and younger. All the injuries sustained at home occurred when a family member was in the house. Similar to many reports from overseas, non-bath scalds were one of the most common causes of burns in this study; however, hot bath scalds were the most important cause. These data are being used to develop a prevention program. We also consider it necessary to educate children and their family members about the dangers of burn injuries.

Spatio-temporal analyses of stimulus-evoked and spontaneous stochastic neural activity observed by optical imaging in guinea pig auditory cortex.

Stimulus-evoked response in the cortex involves random neural activity besides the deterministic responses reproducible to the stimulus. Recently, we have developed a new bright optical system that enables us to investigate the spatio-temporal patterns of such stochastic activity in the guinea pig auditory cortex without averaging. We show that (1) the stochastic neural activity is evoked by a tone-stimulus in addition to the deterministic response, and spontaneous stochastic activity is also observed in a similar manner; (2) our statistical estimation of optical responses such as variance showed that the evoked stochastic activity was increased by the sound stimulus compared to the spontaneous activity; (3) both types of stochastic activity mainly display oscillatory behavior, in the frequency range of 5-11 Hz; (4) there are no significant differences between the stimulus-induced and spontaneous stochastic neural activity in our statistical analyses using the PSD (power-spectrum density) and the spatial correlation function; (5) the spatial area of the evoked stochastic activity is not strongly correlated with the tonotopical area of the deterministic response that is mainly localized in the caudal area of field A of the guinea pig auditory cortex. Thus, the stochastic neural activity existing in the stimulus response and the spontaneous activity in the auditory cortex are possibly generated by a common neural mechanism. These results were confirmed statistically using 27 animals.

[Acute myelocytic leukemia and plasmacytoma secondary to chemotherapy and radiotherapy in a long-term survivor of small cell lung cancer].

A 68-year-old man was given a diagnosis of lung cancer of the right upper lobe (small cell carcinoma, T 4 N 2 M 0, stage IIIB) in February 1991. The tumor diminished after chemotherapy and radiotherapy. In February 1992, a partial resection of the lower lobe of the right lung was performed because of the appearance of a metastatic tumor. In September 1994, squamous cell carcinoma developed in the lower part of the esophagus, but disappeared after radiotherapy. In February 1998, a diagnosis of myelodysplastic syndrome was made. Two months later, the patient had an attack of acute myelocytic leukemia and died of cardiac tamponade. An autopsy determined that both the lung cancer and esophageal cancer had disappeared. Acute myelocytic leukemia and plasmacytoma of lymph nodes in the irradiated area were confirmed. These were regarded as secondary malignancies induced by chemotherapy and radiotherapy.

Characteristics of bath-related burns in Japan.

A retrospective study of bath-related burn injuries was carried out at our institution. A total of 216 patients with burns were admitted between 1982 and 1996. Bath-related burns were identified in 58 patients (26.9%). The number of patients with bath-related burns increased throughout the study period. The percentage body surface area burned was 43.8 +/- 25.7% in the bath-related burn group and 27.3 +/- 28.3% in the bath-unrelated burn group. This difference was significant. There was no significant difference between the two groups with respect to mortality rate. The mechanism by which the patients sustained a bath-related burn clearly differed according to age. The percentage of burns which are bath-related and the severity of bath-related burns are higher in Japan than in any other country. This can be attributed to lifestyle, bathing systems, bathroom architecture, housing conditions and an increase in the elderly population. These burns can be prevented. Education based on this study will play a critical role in the prevention of the bath-related burn injuries.

Dendrite classification in rat hippocampal neurons according to signal propagation properties. Observation by multichannel optical recording in cultured neuronal networks.

Two-dimensional neuronal networks were formed using a dissociated culture of rat hippocampal neurons on glass plates. Neural activity in response to pulse stimuli applied to the neurons by whole-cell clamp electrodes was observed with a 128-channel optical recording apparatus using a voltage-sensitive dye, RH482. Dendrites emerging from the somata of single neurons were classified according to two signal-transmission properties, those with lower conduction velocities (0.12+/-0.034 m/s, n=24) and those with very fast conduction velocity (faster than 1.0 m/s), by evaluating the conduction velocities of pulse responses. The distinction between these two properties seemed to be related to the morphological differences in input connectivity with the axons of neighboring neurons.

Burns in a suicide attempt related to psychiatric side effects of interferon.

A 50-year-old woman was admitted to our critical care center after pouring lamp oil on herself and setting herself on fire. Diagnosed with chronic hepatitis, she had received interferon-alpha at another hospital. During interferon therapy she developed anxiety, irritability, sleeplessness, and depression. At our hospital she underwent fluid resuscitation according to the method of Baxter. After treatment with topical cream and ointment, she underwent skin grafting. Interferon was not given. After discharge, wound healing proved satisfactory. She was intelligent and insightful, and her mental condition remained stable with no apparent emotional problems. As she had no significant past medical or psychiatric history and no history of substance abuse, we believe that her depression was a side effect of interferon therapy. A number of reports have described depression and other psychiatric disorders associated with interferon, but none of these accounts have concerned burns sustained in suicide attempts. This case underscores the potential seriousness of adverse reactions to interferon characterized by emotional disturbance and also illustrates that physicians who treat burn patients need to have an understanding of affective disorders and unusual side effects of medication.

Estimated magnitude of behavioral effects of phenytoin in rats and its reproducibility: a collaborative behavioral teratology study in Japan.

A collaborative study was conducted by 30 laboratories that participated in the Behavioral Teratology Meeting in Japan. Pregnant Sprague-Dawley rats from four breeders were orally administrated 200 mg/kg of phenytoin each day from day 10 to day 14 of gestation. The offspring were tested for behavioral teratogenic effects at various ages. The effects were estimated in terms of common effect size, which should be very resistant to the variation inevitable in behavioral teratology results, and thus yield a different type of information from that reported in the usual behavioral teratology studies. The common effect size also gives information on the magnitude of the behavioral teratogenic effects that previous studies could not provide. A breeder difference in the effect of phenytoin for several measures was found in terms of common effect size. The estimated phenytoin effect was found to be large enough to be detected by using a sample size of 20 per group. As to reproducibility of results, estimation by standard deviation across laboratories disclosed that there was almost no difference in magnitude between behavioral and non-behavioral measures, indicating that much of the variation in behavioral teratology results of phenytoin might not be due to measurement error from behavioral tests but rather to the phenytoin effect itself administered via the mother. How seriously a single study is affected by uncontrollable variation of results was illustrated by plotting the respective laboratory results on a dimension. A standard practice in the interpretation of discrepancies among results obtained from single studies is criticized; it is pointed out that such interpretations rely on an optimistic assumption: that is, that results obtained from single studies would be free from the usual variation of results found in behavioral teratogenic research.

Multichannel optical recording of neuronal network activity and synaptic potentiation in dissociated cultures from rat hippocampus.

The activity of neuronal networks formed by dissociated rat hippocampal neurons was observed with a 128-channel optical recording apparatus using an absorptive voltage-sensitive dye, RH482. Two-dimensional patterns of neural electrical events along somata and neurites in the networks were visualized as the responses to pulse stimuli applied to the somata of the presynaptic neurons by patch-clamp electrodes. Synaptic delay was analyzed from propagation delay of the responses along the neurites. Synaptic potentiation was also observed in postsynaptic responses that were amplified by a factor of 1.24 after tetanization. In contrast, presynaptic components were unaffected by the procedure. In the light of the present results, multichannel optical recording promises to promote our understanding of neuronal interactions at cellular level.

Photodecomposition of 1,2,3,4- and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in water-alcohol media on a solid support.

We used a hydrophobic solid support, octadecylsilylated silica gel (C18), packed in a quartz column as a reaction medium for the photolysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD). When we exposed the column to a 450 W UV lamp, the adsorbed 1,2,3,4-TCDD or 2,3,7,8-TCDD in 10% 2-propanol/water decomposed completely in 20 minutes and 5 minutes, respectively. The large estimated partition coefficient of 1,2,3,4-TCDD in 10% 2-propanol/water (> 1000) indicates that on the C18 stationary phase, both the saturated hydrocarbon chains and the absorbed 2-propanol may act as proton donors and accelerate the photolysis. In direct sunlight, the adsorbed 1,2,3,4-TCDD in 10% 2-propanol/water decomposed much faster than in a nonaqueous solvent (50% 2-propanol/methanol). This solvent effect is advantageous for the practical use of the C18 photolysis process in aqueous waste treatment. We have demonstrated that complete C18 trapping with continuous photodecomposition of TCDD contained in an aqueous alcohol waste is possible.

Patterns of thermoregulation associated with cold intolerance after digital replantation.

Twelve patients with complete thumb amputations were analyzed to determine the interrelations between thermoregulation for pain and cold intolerance and sensory nerve recovery. Patients were examined at 3 months, 6 months, 1 year, and after 2 years following replantation. Medical thermography was introduced to assess postoperative circulation following digital replantation, while vasomotor tone was assessed by cold-stress plethysmography testing. Postoperative circulation was divided into two different patterns based upon skin temperature, the transition of which over time correlated well with sensory nerve recovery. Patients with cold intolerance showed a persistent vasoconstriction pattern, the cold change of which was objectively detected by thermography.

Temporal coding in the guinea-pig auditory cortex as revealed by optical imaging and its pattern-time-series analysis.

The neural network structure of a guinea-pig's primary auditory cortex is estimated by applying pattern-time-series analysis to the auditory evoked responses. Spatiotemporal patterns in click-evoked responses, observed by optical recording with voltage-sensitive dye, are analyzed by time series analysis using a multivariable autoregressive (MAR) model. Oscillatory neural activities with a distribution of about 10 approximately 40 Hz in the click-induced evoked responses are found in the cortical response field. The cortical regions where the distributed neural oscillations are generated are identified by pattern-time-series analysis. In addition, two types of cortico-cortical connections, unilateral and bilateral connections between the cortical points, are speculated to be the causes of oscillatory neural activity transfer. It can be said that the so-called synchronized neural oscillation, in the sense of coherency or correlation between the two evoked responses at the oscillatory frequency, does not necessarily represent real cortico-cortical neural connections at the evoked response points.

The tonotopic representation in the auditory cortex of the guinea pig with optical recording.

We examined spatio-temporal characteristics of the tonotopic representation in the auditory cortex of the anesthetized guinea pig with a multichannel optical method using voltage-sensitive dye. The response latencies increased, and the response field in the cortex became small when the stimulus intensity levels were decreased. Low frequencies were represented rostrally and high frequencies caudally. The two fields responding to different frequencies at higher intensity levels gradually overlapped as time after stimulus onset increased, though these response field did not overlap at the beginning of the response. These findings indicate that tonotopic representation varies dynamically with time after stimulus onset.

Spatiotemporal observation of guinea pig auditory cortex with optical recording.

The spatiotemporal characteristics of neural activity in the guinea pig auditory cortex were studied in order to clarify neural processing and coding mechanisms of complex sounds. We used a multi-channel optical recording system for a voltage-sensitive dye: RH795. The experimental results showed that a boomerang-shaped moving pattern of optical response appeared on the cortical surface in response to complex sounds (clicks) stimulation, but a rather fixed pattern appeared in response to tone burst stimulation. The tonotopical organization observed using microelectrode was not directly visible, but a similar topographic pattern was evidenced by selecting regions of a strong response evoked by tone-bursts. The correlative functions of regionwide responses may indicate a parallel and serial neural processing structure.

Dynamic characteristics of the auditory cortex of guinea pigs observed with multichannel optical recording.

The spatiotemporal characteristics of neural activity in the guinea pig auditory cortex are investigated to determine their importance in neural processing and coding of the complex sounds. A multi-channel optical recording system has been developed for observing the cortical field of the mammalian brain in vivo. Using the voltage-sensitive dye: RH795, optical imaging was used to visualize neural activity in the guinea pig auditory cortex. Experimental results reveal a boomerang-shaped pattern of movement of activated neural cell regions for the evoked response to click as complex sounds. Parallel and sequential neural processing structure was observed. Although the exact frequency selectivities of single cells and tonotopical organization observed using microelectrode were not visible, the similar feature to the microelectrode evidences was imaged by extracting the strongly response field from the optical data.

Use of fibrin glue to minimize bleeding of microvascular repairs in hypertensive rats.

The purpose of this study is to describe our technique of applying fibrin glue at the microvascular anastomotic site and to evaluate the effect of fibrin glue on anastomotic hemostasis and patency under various high pressure states using dopamine-induced acute hypertension in rats. A total of 72 male Wistar Kyoto rats, 10 weeks old, were used in this study. Under urethane anesthesia, end-to-end anastomosis of the left femoral artery was performed using 10-0 nylon suture by the standard interrupted suture technique. Pasteurized fibrin glue was then topically applied upon the suture line of the anastomosis. Thirty-six normotensive rats were divided into three groups based on the number of sutures (4, 6, or 8) used to complete the anastomosis. Groups were subdivided, half receiving fibrin glue application and half without. Thirty-six dopamine-induced acutely hypertensive rats were divided into three groups based on the blood pressure levels of 150, 200, and 250 mmHg, respectively. These groups were again subdivided, with half receiving glue applications. Microvascular anastomosis was performed using 6 nylon sutures. Patency rates and anastomotic bleeding were evaluated. The results revealed that successful anastomoses could be performed with fewer sutures when fibrin glue was used as a reinforcement at the anastomosis. Fibrin glue was also effective at the maximum blood pressure (250 mmHg) with no anastomotic leakage and no decrease in postoperative patency rate. These results suggest that conventional microsurgical suturing technique combined with fibrin glue would be effective in the prevention of leakage in microsurgical repairs, even under conditions of high blood pressure.

[Effects of superoxide dismutase on liver regeneration in rats].

This study was performed to clarify the effects of superoxide dismutase (SOD) on liver regeneration in rats. After about 70% hepatectomy, changes of lipid peroxides (LPO) in the remaining liver tissue, regeneration rate, mitotic index, serum transaminases and ketone body ratio (KBR) were measured under the treatment with and without SOD. The maximal value of LPO of the control group was 14.87 +/- 2.28 nmol/mg protein on the first postoperative day. In contrast, the value in the SOD-treated group was 12.14 +/- 2.38, which was significantly lower than that of the control group. The regeneration rate in the SOD-treated group had been significantly higher than that of the control group from the 4th postoperative day until 4 weeks after the operation when the experiment ended. The mitotic index of the SOD-treated group was also higher than that of the control group on the 2nd postoperative day. Although there was no significant difference in the values of KBR between two groups, the levels of transaminases in the SOD-treated group were significantly lower than those in the control group. These results indicate that SOD treatment suppresses the lipid peroxidation which cause cellular damage after hepatectomy, and hence the mitosis of the liver cell and the liver regeneration can be enhanced.

[A case of prolonged jaundice after surgical treatment of obstructive jaundice caused by a carcinoma of the head of the pancreas relieved with dibutyryl cyclic AMP].

Recently, we experienced a case of obstructive jaundice caused by a carcinoma of the head of the pancreas which could not be relieved by reduction surgery. The operation performed was a cholecystectomy and supraduodenal choledochotomy with T-tube insertion. Glucagon and insulin were, therefore, administered with the aim towards the recovery of the liver function to be induced by the enhancement of the liver regeneration. The treatment, however, was not effective. Then, dibutyryl cyclic AMP was administered to the case by intravenous drip infusions at the rate of 5 micrograms/kg/min. Thereafter, the value of serum total bilirubin was reduced remarkably. A prolonged and intense obstructive jaundice is generally accompanied by damage to the liver function, and the condition carries a high risk of postoperative complication. In this paper, the effectiveness of dibutyryl cyclic AMP on liver cell damage caused by prolonged obstructive jaundice are reported.