[Subdural hematoma following cardiac surgery].

We report 3 cases of subdural hematoma following open heart surgery under cardiopulmonary bypass. In 2 patients, emergency removal and drainage of a subdural hematoma was performed by neurosurgeons, and conservative management was performed in the remaining one. All patients belonged to a high risk group of bleeding due to anticoagulation therapy, and they had no episode of head trauma. Subdural hematomas may have been due to rapid alterations in cerebral volume, leading to a tearing of the dural bridging veins under cardiopulmonary bypass. Although early diagnosis and prompt treatment is very important, it is often difficult to examine neurological findings after cardiac surgery. We consider that patients who need long-term sedation under anticoagulation therapy must have their neurological status checked at least once in a few days.

An in vitro study of long-term potentiation in the carp (Cyprinus carpio L.) olfactory bulb.

Long-term potentiation (LTP) of synaptic transmission is considered a cellular mechanism for neural plasticity and memory formation. Previously, we showed that in the carp olfactory bulb, LTP occurs at the dendrodendritic mitral-to-granule cell synapse following tetanic electrical stimulation applied to the olfactory tract, and suggested that it is involved in the process of olfactory memory formation. As a first step towards understanding mechanisms underlying plasticity at this synapse, we examined the effects of various drugs (glutamate and GABA receptor agonists and antagonists, noradrenaline, and drugs affecting cAMP signaling) on dendrodendritic mitral-to-granule cell synaptic transmission in an in vitro preparation. Two forms of LTP are involved: a postsynaptic form (tetanus-evoked LTP) and a presynaptic form. The postsynaptic form is evoked at the granule cell dendrite following tetanic olfactory tract stimulation and is suppressed by the NMDA receptor antagonist, D-AP5, enhanced by noradrenaline, and occluded by the metabotropic glutamate receptor agonist, trans-ACPD. The presynaptic form occurs at the mitral cell dendrite following blockade of the GABA(A) receptor by picrotoxin and bicuculline, or via activation of cAMP signaling by forskolin and 8-Br-cAMP.

Long-term potentiation and olfactory memory formation in the carp (Cyprinus carpio L.) olfactory bulb.

Long-term potentiation of synaptic transmission is considered to be an elementary process underlying the cellular mechanism of memory formation. In the present study we aimed to examine whether or not the dendrodendritic mitral-to-granule cell synapses in the carp olfactory bulb show plastic changes after their repeated activation. It was found that: (1) the dendrodendritic mitral-to-granule cell synapses showed three types of plasticity after tetanic electrical stimulation applied to the olfactory tract-long-term potentiation (potentiation lasting >1 h), short-term potentiation (potentiation lasting <1 h) and post-tetanic potentiation (potentiation lasting <10 min); (2) Long-term potentiation was generally induced when both the dendrodendritic mitral-to-granule cell synapses and centrifugal fiber-to-granule cell synapses were repeatedly and simultaneously activated; (3) long-term enhancement (>1 h) of the odor-evoked bulbar response accompanied the electrically-induced LTP, and; (4) repeated olfactory stimulation enhanced dendrodendritic mitral-to-granule cell transmission. Based on these results, it was proposed that long-term potentiation (as well as olfactory memory) occurs at the dendrodendritic mitral-to-granule cell synapses after strong and long-lasting depolarization of granule cells, which follows repeated and simultaneous synaptic activation of both the peripheral and deep dendrites (or somata).

Lipid peroxidation end products-responded induction of a preneoplastic marker enzyme glutathione S-transferase P-form (GST-P) in rat liver on admistration via the portal vein.

The in vivo induction mechanism of a preneoplastic marker enzyme, glutathione S-transferase P-form (GST-P), by a number of carcinogens and some noncarcinogens such as anti-oxidants [Proc. Natl. Acad. Sci. U.S.A. 85 (1984) 3964] has remained to be solved. Among the various administration routes tested, GST-P became immunohistochemically demonstrable in the liver centrilobular zone 3 after 24-48h on administration of prostaglandin J2's, 15-deoxy-Delta(12,14)-PGJ2, PGJ2 and Delta(12)-PGJ2 to male rats via the portal vein, whereby the animals had been pretreated with Soya oil intraperitoneally to exhaust fatty acid binding proteins. Unsaturated aldehydes, 4-hydroxynonenal, crotonaldehyde and acrolein, given by the same route induced putatively preneoplastic single cells positive for GST-P. As these lipid peroxidation end products are the substrates as well as inducers of the enzyme, its physiological function could be their detoxication. These results indicate that GST-P expression can be mediated through lipid peroxidation possibly accounting for induction observed with a wide variety of carcinogens. In addition, present method may also be of use as a direct, simple, rapid, and sensitive in vivo test in examination of other biological responses.

Influence of age and comedication on steady-state clonazepam serum level-dose ratios in Japanese epileptic patients.

BACKGROUND: In antiepileptic drugs, the marked inter- and intrapatient variability of the level-dose ratio makes it difficult to predict serum concentrations from the administered per kg dose. It is therefore important to identify factors, such as age and comedication, that could contribute to this observed variability. OBJECTIVE: To investigate the effect of age and comedication on clonazepam (CZP) level-dose (L/D) ratios. METHOD: A retrospective evaluation of data from 137 epileptic patients who had received clonazepam. RESULTS: The CZP L/D ratio increased slowly with age up to 15 years in patients on monotherapy. Associated antiepileptic therapy affected the CZP L/D ratio, which was significantly reduced in patients on polytherapy as compared to patients on monotherapy. CONCLUSION: The study therefore suggests that routine monitoring of CZP serum levels is extremely useful, especially in the paediatric age group, and in patients who require associated antiepileptic medication.

[A survey on occupational health nursing activities and evaluation in TOHOKU area].

We did a mail survey in 1998 in Tohoku district. We sent questionnaires to approximately 300 Occupational Health (OH) nurses and got 132 replies. Occupations of respondents were 66 public health nurses and 57 nurses. More than 70% did not have a managerial position. About 40% were respondents without colleagues in nursing occupations. Full time occupational physicians were in 40% of companies, and semi-full time occupational physicians were in 60%. Respondents citing good coordination in the former were 60%, and in the latter were 80%. Of all business activities occupying OH nursing employees, persons who performed more than 90% of the tasks numbered more than 30%. Persons not satisfied with present employment positions were 80%. Reasons for dissatisfaction in declining order of incidence were work duties, contract conditions for employment, and personal relations. Planning and summary of OH nursing activities were carefully done highly. For the OH nursing activity evaluation, we examined guidelines for business locations by observing them from the OH nursing aspect and the OH nursing job itself. Guidelines considered for business locales from the OH nursing vantage point show numerically, for example, rates of examinees with abnormal findings, work absenteeism, etc, and expectations as to whether or not health conditions are conspicuously reflected in productivity. Conversely, from the OH nursing vantage point for guidelines on business locales, while receiving affirmative economic evaluation of occupational health and safety measures, progress (process) should also be included in the object of evaluation. Furthermore, guidelines should be mindful of the need to have qualitative and quantitative changes in health behavior of workers and perspectives on health.

The complete nucleotide sequence of a plant root-inducing (Ri) plasmid indicates its chimeric structure and evolutionary relationship between tumor-inducing (Ti) and symbiotic (Sym) plasmids in Rhizobiaceae.

The Ri (root-inducing) plasmid in Agrobacterium rhizogenes and Ti (tumor-inducing) plasmid in Agrobacterium tumefaciens have provided the fundamental basis for the construction of plant vectors and transgenic plants. Recently, the determination of the first complete nucleotide sequence of the Ti plasmid (pTi-SAKURA) has been successful. To understand the general structure of these oncogenic T-DNA transfer plasmids, the whole nucleotide sequence of a mikimopine-type Ri plasmid, pRi1724, was analyzed. The plasmid is 217,594 bp in size, and has 173 open reading frames (ORFs) in total, which are asymmetrically distributed. Except for 27 ORFs, which are unknown, 173 ORFs were classified into 12 groups as follows: three for DNA replication, nine for plasmid modification, 22 for conjugation, 26 for virulence, 11 for T-DNA gene, 19 for mikimopine/mikimopine-lactam transport, ten for an unknown opine metabolism, seven for transcriptional regulator, five for sugar transport, five for glycerol metabolism, four for chemoreceptor and 32 for others. The elucidated chimeric structure of pRi1724 interestingly indicates that the evolution of Rhizobiaceae plasmids seems to have kept interactions among the plasmids; especially, the genes and elements for a conjugal transfer of pRi1724 had clearly closer kinship to those of a Sym (symbiotic) plasmid, pNGR234a in Rhizobium sp. than those of Ti plasmids. By using sequencing and Northern analysis, we examined the metabolic pathway and gene expression of mikimopine, which is probably an Ri-specific opine.

Genome analysis of Agrobacterium tumefaciens: linkage map and genetic features of the left region of the linear chromosome.

In addition to a unique tumor-inducing (Ti) plasmid, the plant pathogenic bacterium Agrobacterium tumefaciens has an unconventional chromosomal organization. Our previous studies on A. tumefaciens MAFF301001 revealed that it possesses a 2 Mb linear and a 2.8 Mb circular chromosome plus a 206.479 kbp Ti plasmid (pTi-SAKURA). In this study, a linkage map for the left half of its linear chromosome covering a 900 kbp region was constructed and the number of potential genes existing in the region was estimated. The linkage map consists of 31 BAC and 8 lambda phage recombinants without any gaps. It confirmed the size and all the structural landmarks indicated in the corresponding region of our previously constructed physical map for the linear chromosome. Sequencing analysis of the end-regions of each linking clone led to the identification of 6 genes and another 27 potential genes or ORFs, including genes and/or gene clusters responsible for homologous recombination (ruvB), trehalose/maltose sugar transport (thuR, thuG) and alanine catabolism (dadR). Two virulence-related gene homologues (attK and celB), previously reported in the circular chromosome of a different strain of A. tumefaciens were found in this region. These findings will provide a ready-to-use linkage map for further functional analysis of the linear chromosome.

Lordosis-inhibiting effect of progesterone in male and female rats with septal lesions.

The inhibitory role of progesterone (P) in regulating lordosis was investigated in male and female rats with septal lesions (SL). Male rats with SL showed lordosis quotients (LQ) as high as female rats with SL and female control rats without brain surgery after injection of 50 microg/kg estradiol benzoate (EB) followed by 0.5 mg P 44 h later. Even when primed with 5 mg P 1 h prior to the 50 microg EB-injection, the mean LQs were still high in all groups. When the dose of EB was decreased to 5 microg/kg, all rats showed high-score LQs. In contrast, all animals in both male and female in which 5 mg P was injected 1 h before 5 microg EB, showed low LQs. These results suggest that P is effective in suppressing lordosis enhanced by estrogen in either male rats or females. Furthermore, the high dose of estrogen overcomes the inhibitory action of P on lordosis in both sexes.

[A case of intracerebral and subarachnoid hemorrhage of unknown origin with preceding headache].

We report a case of a 31-year-old female with multiple intracerebral hemorrhage and subarachnoid hemorrhage. She presented with headache one week before hemorrhage, and a CT scan performed at that time showed no abnormal findings. Neurological examination on admission revealed mild disturbance of consciousness, papilledema, and mild left hemiparesis. CT scans demonstrated intracerebral hemorrhage in the right caudate head and left frontal subcortex, and diffuse subarachnoid hemorrhage. Cerebral angiogram and laboratory examination revealed no abnormal findings. Erythrocyte sedimentation rate, C reactive protein and antiphospholipid antibody were within normal ranges. The patient underwent removal of hematoma by craniotomy. One week after the operation, a subcutaneous hematoma in the area of the craniotomy was found. Cerebral angiography demonstrated an aneurysm of the right superficial temporal artery, which was remote from the craniotomy. This aneurysm was surgically removed and examined. Histopathological examination revealed the presence of a pseudoaneurysm but no inflammation. Although primary angitis of the central nervous system was suspected to be the cause of this disease, a definite diagnosis could not be obtained.

Analysis of unique variable region of a plant root inducing plasmid, pRi1724, by the construction of its physical map and library.

Ri plasmids in Agrobacterium rhizogenes specifically induce the hairy root syndrome on various dicotyledonous plants. Its T-DNA transfer system as well as those of Ti plasmids have successfully provided the fundamental technique to introduce exogenous genes into plants. To study the Ri genome structure, we constructed a complete BamHI physical map and a lambda library of pRi1724 of A. rhizogenes strain 1724. By using these, we carried out the complete sequence of the 74-kb region between the right border of T-DNA and tra operon, which is the highly variable region (VAR) among Ri and Ti plasmids. As a result, we found three kinds of putative ABC-type transport operons, histidine utilization operon, glycerol utilization operon and two chemoreceptor genes. In addition, a virulence-related gene, tzs was located independently of the vir region.

Pharmacokinetic interactions among phenobarbital, carbamazepine, and valproic acid in pediatric Japanese patients: clinical considerations on steady-state serum concentration-dose ratios.

With antiepileptic drugs, the marked inter- and intrapatient variability of the concentration-dose ratio makes it difficult to predict serum concentrations from the dose administered per kilogram. The effects of comedication on steady-state serum concentration/dose ratios of antiepileptic drugs were evaluated retrospectively in 669 pediatric patients. To avoid complex pharmacokinetic interactions among multiple antiepileptic drugs, the data on serum concentrations in the current study were collected from patients who were co-administered only one additional antiepileptic drug (phenobarbital-carbamazepine, phenobarbital-valproic acid, or carbamazepine-valproic acid) or who received monotherapy. The concentration/dose ratio for the antiepileptic drugs increased significantly with body weight in children up to 15 years old. Associated therapy with antiepileptic drugs affected the concentration/dose ratio. Therefore, routine monitoring of serum concentrations of the antiepileptic drugs is extremely useful, particularly in children and in patients who require associated antiepileptic medication.

Inhibitory effect of microfibril wheat bran on azoxymethane-induced colon carcinogenesis in CF1 mice.

Microfibril wheat bran (MFW), a processed dietary fiber prepared by milling of coarse wheat bran (WB), is softer and has a more pleasant taste than WB. In this study, we examined the inhibitory effect of MFW on azoxymethane (AOM)-induced colon carcinogenesis in female CF1 mice and compared its effect with that of WB and cellulose (CL). The mice were fed a modified AIN 76 A diet supplemented with either MFW, WB, or CL at a final concentration of 20% (w/w). Six weekly s.c. injections of AOM (10 mg/kg body weight) were administered per mouse commencing 1 week after the start of the feeding period. Control mice were injected with saline only. Thirty-three weeks after the initial injection, the mice were sacrificed, examined for tumors, and the cecal contents were analyzed to determine the moisture content and the concentrations of short-chain fatty acids (SCFA). The average number of total tumors per mouse in the MFW (2.9 +/- 0.6, P = 0.017) and WB (5.3 +/- 1.3, P = 0.373) diet groups was lower than that of the CL diet group (7.5 +/- 1.3), though there was no significant difference in tumor incidence (94.7%, 90.0% and 94.7%, respectively) between the groups. More than 90% of the tumors in each group were adenocarcinomas. The incidence of adenoma and that of carcinoma in situ in the MFW diet group (5.3% and 0%, respectively) were also lower than those in the CL diet group (26.3 and 26.3%, respectively; P = 0.180 and P = 0.046, respectively). Analysis of the cecal contents revealed a significantly higher moisture content and significantly higher concentrations of SCFA, butyrate in particular, in the MFW and WB diet groups. The results of this study indicate that the source and texture of dietary fiber can influence tumor development in CF1 mice, and more specifically that MFW is a promising and useful dietary supplement with properties serving to protect against the development of colon cancer.

Effect of direct application of estrogen aimed at lateral septum or dorsal raphe nucleus on lordosis behavior: regional and sexual differences in rats.

The role of estrogen in lordosis-inhibiting systems in the lateral septum or the dorsal raphe nucleus was investigated in female and male rats. Ovariectomized rats received implantation of 22-gauge guide cannulae to the bilateral or right side of the lateral septum (LS and rLS, respectively), the dorsal raphe nucleus (DRN) or bilateral cortex (CX). In castrated male rats, bilateral implantations of the cannulae to the LS were carried out (mLS). Three behavioral tests in total were performed at 2-week intervals. In the first test, all animals were subcutaneously injected with 1.5 microg/kg estradiol benzoate (EB). Forty-four hours after EB, 0.5 mg progesterone (P) was injected and a behavioral test was started 4 h after P. These hormonal regimes were used in all tests. In the second test, 2 h before EB injection, 27-gauge cannulae filled with estradiol (E2) were inserted into the DRN, LS or CX through the guide cannulae and were kept there for 4 h. In the third test, cholesterol was implanted instead of E2 into these areas. In the first test, most females showed low levels of lordosis quotient (LQ) and most males showed no lordosis. In the second test, mean LQs in the LS or rLS groups of females increased but not in the DRN and CX groups. In the mLS group no increase of LQ was observed. When cholesterol was implanted in the third test, mean LQs in all groups were as low as in the first test. These results suggest the possibility that estrogen releases the inhibition when it acts on the LS, but not on the DRN female rats. On the other hand, inhibition in the male LS may not be released by the direct action of estrogen.

[Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients. 4. Actual status of the management of tuberculosis patients in a university hospital without isolation wards for infectious diseases].

We retrospectively evaluated clinical findings and the actual status of management of 69 tuberculosis patients admitted to the Fujita Health University Hospital, a hospital without isolation wards for infectious diseases, between 1991 and 1994. Forty-nine patients were smear-positive and 22 patients were smear-negative and culture-positive. Twenty-five cases (36.2%) were classified as type II (cavitary) and 29 cases (42.0%) as type III (non-cavitary) according to the GAKKAI classification of findings on chest X-ray films for pulmonary tuberculosis. Physicians in charge did not diagnose twenty-four patients (34.8%) as tuberculosis on admission. Physicians in charge tended not to suspect smear-negative patients of tuberculosis. Most of the patients with cavities on their chest X-ray films were strongly suspected of tuberculosis on admission, but in some of them, tuberculosis was not considered at all. Smear-positive patients with strongly suspected tuberculosis were diagnosed with the disease within three hospital days, while it took about three weeks in patients who were not considered as tuberculosis on admission to be diagnosed as tuberculosis. In the case of smear-negative patients, it took about one month and two months respectively to diagnose the case as tuberculosis. About half (51.1%) of the smear-positive patients were admitted and treated in single-bed rooms while 44.7% were attended in multiple-bed rooms for 11 days before they were transferred to single-bed rooms. When acid-fast bacilli were detected, 57.4% of the smear-positive patients were transferred to hospitals with isolation wards for infectious diseases, while the remaining smear-positive patients were treated in single-bed rooms at the university hospital. About one-third (31.7%) of the smear-negative patients had already left the hospital when specimens were found to be culture positive for tubercle bacilli. In conclusion, it is utmost important for physicians to suspect to tuberculosis for the early diagnosis of the disease.

Treatment of large complex cranial bone defects by using hydroxyapatite ceramic implants.

Hydroxyapatite ceramic implants were used in the reconstruction of very large and complex-form cranial bone defects in nine patients. The bone defects were the result of craniectomy after infections and other complications such as severe brain edema, after neurosurgery, and as a result of trauma, subdural hemorrhage, and surgery for brain tumor. The size, shape, and curvature of the hydroxyapatite ceramic implants were determined based on high-precision, full-scale models fabricated through a laser lithographic molding method by using computed tomographic data. The use of this method allowed the fabrication of hydroxyapatite ceramic implants of shapes that accurately matched the area of bone defect, allowing for a minimum of adjustment during the operation even with a complex-form implantation. Not only were good cranial contour reconstructed and aesthetically satisfactory results obtained in the cases treated by incorporating this series of techniques, but neurologic conditions present in some cases were also improved to some extent. The postoperative course has been steady for all nine patients, with no blood transfusions required during or after the operations and no implants requiring removal because of infection or other postoperative complications. The average length of postoperative hospitalization for the nine cases was 11.7 days, remarkably short considering the clinical conditions.

A newly designed underwater antenna and its application to underwater radio-telemetry for measuring electroencephalographic activity from the rainbow trout freely swimming in natural environments.

A novel underwater antenna (which we named an 'aquaerial') for telemetering the biological signals from freely swimming fish in freshwater natural environments is presented. It is designed for receiving a 90-100 MHz carrier wave and consists of plural unit receiving antennas (UAs). The plural UAs are placed underwater to cover the area where the target fish carrying the transmitter is swimming. The UAs are equally spaced and have a directional coupling amplifier to supply the signals received to the coaxial cable. The optimal length of the UA was found to be 16.5 cm (a half wavelength in water) and optimal spacing was 2 m (one wavelength along coaxial cable) when 95 MHz was used as the carrier frequency. Using this 'aquaerial', long-term monitoring of EEG signals from the olfactory bulb of the rainbow trout (Oncorhynchus mykiss) swimming freely in natural environments was achieved.

Genome structure of Ri plasmid (2). Sequencing analysis of T-DNA and its flanking regions of pRi1724 in Japanese Agrobacterium rhizogenes.

We sequenced 42.6 kb including T-DNA and its flanking regions which corresponds to about 1/5 of entire length of a mikimopine-type Ri plasmid, pRi1724 in A. rhizogenes. We identified 37 ORFs (Open Reading Frames) including genes in total. Among them, 20 ORFs are probably new genes. Those ORFs have similarity with those in Agrobacterium and 9 ORFs of them was newly found on Ri plasmids.

Clinical evaluation of the peroral cholangioscopy using a new videoscope.

Peroral cholangioscopy (PCS) has been performed in 22 cases using XCHF-B200 (Olympus Optical Co.) since June 1995 and in 77 cases using CHF-B20 (Olympus Optical Co.) after EST from Jan. 1989. XCHF-B200 has a longer rigid portion of distal end and a smaller channel diameter than CHF-B20. The successful rate of PCS using XCHF-B200 (82%) was lower than that of CHF-B20 (89%). The vascular pattern and fine vertical groove of the bile duct mucosa were shown more clearly on the photographs obtained with XCHF-B200 than those obtained with CHF-B20. However, not enough biopsy specimens could be obtained because the channel diameter of XCHF-B200 was rather small.If the length of rigid portion and biopsy channel of XCHF-B200 are improved, PCS using XCHF-B200 will be more useful for the diagnosis of bile duct disorders.

Inhibitory effect of progesterone on androgen-induced lordosis in ovariectomized rats.

Androgen has a potency to induce female sexual behavior in ovariectomized rats. This study investigated the inhibitory effect of progesterone (P) on lordosis behavior facilitated by androgen. Ovariectomized female rats were given 100 to 800 micrograms/kg testosterone propionate (TP) or 5 micrograms/kg estradiol benzoate (EB). Forty-four hours after administration of the TP or the EB, all females received 0.5 mg P, and the first behavioral test was carried out four hours later. TP-treated animals showed lordosis responses in a dose dependent manner. Two weeks after the first test, the animals were retested by using the same hormonal regime as in the first test, except that an additional 5 mg P was administered 1 h prior to the TP or the EB. As a result, significant reductions in sexual receptivity were observed in the TP-treated as well as in the EB-treated females. These results indicate that progesterone can inhibit androgen-induced lordosis behavior in female rats.