Involvement of glutamatergic and GABAergic transmission in MK-801-increased gamma band oscillation power in rat cortical electroencephalograms.

Hypofunction of the N-methyl-D-aspartic acid receptor (NMDAr) has been considered to play a crucial role in the pathophysiology of schizophrenia. In rodent electroencephalogram (EEG) studies, non-competitive NMDAr antagonists have been reported to produce aberrant basal gamma band oscillation (GBO), as observed in schizophrenia. Aberrations in GBO power have attracted attention as a translational biomarker for the development of novel antipsychotic drugs. However, the neuronal mechanisms as well as the pharmacological significance of NMDAr antagonist-induced aberrant GBO power have not been fully investigated. In the present study, to address the above questions, we examined the pharmacological properties of MK-801 (0.1 mg/kg)-increased basal GBO power in rat cortical EEG. Riluzole (3-10 mg/kg), a glutamate release inhibitor, reduced the MK-801-increased basal GBO power. In contrast, L-838,417 (1-3 mg/kg), an α2/3/5 subunit-selective GABAA receptor-positive allosteric modulator, enhanced the GBO increase. Antipsychotics such as haloperidol (0.05-0.3 mg/kg) and clozapine (1-10 mg/kg) dose-dependently attenuated the MK-801-increased GBO power. Likewise, LY379268 (0.3-3 mg/kg), an metabotropic glutamate 2/3 receptor (mGlu2/3 receptor) agonist, reduced the GBO increase in a dose-dependent manner, which was antagonized by an mGlu2/3 receptor antagonist LY341495. These results suggest that an increase in cortical GBO power induced by NMDAr hypofunction can be attributed to the aberrant activities of both excitatory pyramidal neurons and inhibitory interneurons in local circuits. The aberrant cortical GBO power reflecting cortical network dysfunction observed in schizophrenia might be a useful biomarker for the discovery of novel antipsychotic drugs.

Effect of obesity and insulin on immunity in non-insulin-dependent diabetes mellitus.

OBJECTIVE: To understand the effect of obesity and insulin on immune functions in non-insulin-dependent diabetes mellitus (NIDDM). SUBJECT: Fourteen obese NIDDM (body mass index (BMI)=30.6+/-1.1), seven non-obese NIDDM (BMI=24.2+/-0.5) and five obese non-NIDDM (BMI=28.3+/-0.67). INTERVENTIONS: We first examined the influence of insulin on the proliferation of several human cell lines. Second, we compared several immune functions between obese and non-obese NIDDM, and obese non-NIDDM patients using peripheral blood mononuclear cells. RESULT: Insulin decreased proliferation of T-cell lines but not that of other types of cell lines. Furthermore, obesity augmented the production of IL-1beta which could have cytotoxity against islet beta cells in NIDDM. CONCLUSION: Our data suggested that the pathophysiology of NIDDM could be affected by the change of immunity due to obesity, and the treatment of obesity in NIDDM may be important from an immunological aspect.

[Emphysematous cystitis and neuropathy; a report of the case with diabetes mellitus].

A study was made of a 55 years old male, who suffered from emphysematous cystitis with diabetes mellitus. He had multiple complications due to diabetic neuropathy such as foot ulceration, oculomotor nerve palsy, peroneal nerve palsy and a neurogenic bladder. Klebsiella pneumoniae and Pseudomonous aeruginosa were cultured from urine specimens. There have been only 19 reported cases of emphysematous cystitis since 1962. Fourteen of these cases had diabetes mellitus.

Small angle X-ray scattering studies on local structure of tobacco mosaic virus RNA in solution.

Effects of temperature and ionic strength (S) on the local structure of tobacco mosaic virus RNA in phosphate buffer solution are studied by analyzing the small-angle X-ray scattering (SAXS) curves. The root-mean-square radius of a cross-section of RNA chain was kept at 0.845+/-0.005 nm over a wide range of S from 0.2 to 0.003 at 20 degrees C, whereas it gradually diminished from 0.85 to 0.61 nm when the temperature is raised from 20 to 50 degrees C at S = 0.2. Nevertheless, all of SAXS curves reflecting the backbone structures were equally mimicked by theoretical ones of freely hinged rod (FHR) models, i.e. several straight rods joined with freely hinged joints in the form of a combination of the letter Y, if the constituent rod lengths in the models are adjusted. From these facts, it is suggested that the local structure of the RNA chain in aqueous solution is characterized by an essential feature that unpaired bases in the partially double-stranded helix are constantly far isolated from each other along the helix and the rod-like structure of the helix is preserved over a range of helical contents. Such a characteristic local structure of the chain is entirely collapsed in the formamide solution at 50 degrees C.

Epilepsy in the elderly.

PURPOSE: The aim of this study was to evaluate the clinical characteristics of elderly patients with epilepsy. METHODS: We retrospectively reviewed the clinical records of 190 patients (104 males and 86 females) aged 60 years or older at the time of study. RESULTS: Epilepsies were classified as generalized in 33 patients (17.4%), partial in 145 (76.3%), and undetermined in 12 (6.3%). Twenty-nine of 33 patients with generalized epilepsy were idiopathic, whereas all patients with partial epilepsy were symptomatic. Symptomatic partial epilepsy (SPE) began at all ages (2 to 81 years). Patients with early onset (< 20 years) showed the most unfavorable course in both seizure control and social adaptability. Patients with late onset (50 years or older) had no family history of epilepsy, and half of them had a past history of cerebrovascular disease or head injury as a presumed etiology. In patients with idiopathic generalized epilepsy (IGE), 25 of 29 had early onset, and a family history of epilepsy was found in 31%. Nineteen patients continued to have seizures after 50 years of age, albeit infrequently. Furthermore, 10 of them showed exacerbation around the age of 50. CONCLUSIONS: Most of the late onset epilepsies were SPE with a relatively good prognosis. General belief has held that seizure outcome in IGE is favorable, but some IGE patients show an increased seizure propensity in old age.

Surface roughness of cellulose hollow fiber dialysis membranes and platelet adhesion.

A great deal of research has been conducted focusing on membrane materials with reference to their blood compatibility, but blood compatibility is influenced both by the material used in membranes and their structure, and by the flow conditions at the membrane surface. Accordingly, the relationship between membrane surface roughness and hemocompatibility has been evaluated using five types of membranes of differing surface roughness by evaluating the inner surfaces of the hollow fibers by atomic force microscopy (AFM) and by measuring platelet adhesion ratios using bovine blood. The yield stress, which equates to flow characteristics, was also evaluated using a glycerol suspension of polymethylmethacrylate (PMMA), a Bingham fluid. It was found that membranes having rough surfaces had high platelet adhesion ratios and poor hemocompatibility, whereas those with smoother surfaces had lower platelet adhesion ratios and better hemocompatibility. Measurement of the yield stresses for these membranes revealed higher values for those with rough surfaces, and lower values for those with smoother polyethylene glycol (PEG) grafted surfaces. This suggests that flow conditions at the membrane surface differ according to its surface roughness, and that this difference in flow conditions also influences hemocompatibility.

Lung cancers treated with photodynamic therapy and surgery.

Laser endoscopic surgery, especially the effectiveness of photodynamic therapy (PDT) using Photofrin as a photosensitizer, has now achieved a status as effective treatment modality for lung cancer. Twenty-six lung cancer patients received the preoperative PDT for the purpose of either reducing the extent of resection or increasing operability. Bronchoscopical PDT is performed with topical anesthesia approximately 48 h after the intravenous injection of 2.0 mg/kg body weight of Photofrin. Operation was performed 2-9 weeks after initial PDT. The initial purpose of PDT, i.e. either to reduce the extent of resection or convert inoperable disease to operable status, was achieved in 22 out of 26 patients treated. The survival rate of T3 (main bronchus invasion) cases treated by surgery alone increased significantly from 50.9% to 60.0% with the application of preoperative PDT. This remarkable result may imply that this new option of PDT as preoperative laser irradiation may contribute to the management of advanced lung malignancy.

Peripheral non-small cell lung cancers 2.0 cm or less in diameter: proposed criteria for limited pulmonary resection based upon clinicopathological presentation.

Clinical features of peripheral non-small cell lung cancer 2.0 cm or less were retrospectively analyzed. Nodal status and prognosis in relation to tumor diameter and histologic type were investigated in 171 consecutive patients with peripheral clinical T1N0M0 non-small cell lung carcinomas 2 cm or less in diameter and who had undergone surgical resection between 1976 and 1997. Of the 171 patients, 136 had adenocarcinoma, 27 had squamous cell carcinoma, four had large cell carcinoma, three had carcinoid and one had adeno-squamous carcinoma. There was no statistically significant difference in the incidence of stage I cases between adenocarcinoma and squamous cell carcinoma. Lymph node involvement was recognized in 30 (17.5%) patients: ten (5.8%) at N1 nodes and 20 (11.7%) at N2 nodes. Lymph node metastasis was significantly more common in tumors 1.5-2.0 cm in diameter (22%) than in those 1.5 cm or less in diameter (14.0%, P = 0.0490). There was no lymph node metastasis in tumors 1.0 cm or less in diameter. The 5-year survival rates cases with or without lymph node involvement were 63.3 and 75.3%, respectively, showing significant difference (P = 0.0338). The result of the present study suggested that systematic mediastinal and hilar lymph node dissection is necessary even for cases with tumor diameter less than 2 cm. However, if the tumor is within 1.0 cm in diameter, mediastinal lymph node dissection might be dispensable; therefore, these cases are good candidates for video-assisted lobectomy.

Platelet adhesion, contact phase coagulation activation, and C5a generation of polyethylene glycol acid-grafted high flux cellulosic membrane with varieties of grafting amounts.

Grafting of polyethylene glycol chains onto cellulosic membrane can be expected to reduce the interaction between blood (plasma protein and cells) and the membrane surface. Alkylether carboxylic acid (PEG acid) grafted high flux cellulosic membranes for hemodialysis, in which the polyethylene glycol chain bears an alkyl group at one side and a carboxyl group at the other side, have been developed and evaluated. PEG acid-grafted high flux cellulosic membranes with various grafting amounts have been compared with respect to platelet adhesion, the contact phase of blood coagulation, and complement activation in vitro. A new method of quantitating platelet adhesion on hollow-fiber membrane surfaces has been developed, which is based on the determination of lactate dehydrogenase (LDH) activity after lysis of the adhered platelets. PEG acid-grafted high flux cellulosic membranes showed reduced platelet adhesion and complement activation effects in grafting amounts of 200 ppm or higher without detecting adverse effects up to grafting amounts of 850 ppm. The platelet adhesion of a PEG acid-grafted cellulosic membrane depends on both the flux and grafting amounts of the membrane. It is concluded that the grafting of PEG acid onto a cellulosic membrane improves its biocompatibility as evaluated in terms of platelet adhesion, complement activation, and thrombogenicity.

[Focal cortical dysplasia and epilepsy surgery].

We conducted corticectomy in twenty-five patients with intractable partial epilepsy due to focal cortical dysplasia (FCD). MRI could not detect FCDs in three patients, interictal SPECT, however, revealed hypoperfusion corresponding to FCDs in two of these patients, while the FCD in one remaining patient was histologically identified in a resected specimen. The location of FCDs was as follows: the frontal lobe in sixteen patients, the temporal in five, the occipital in two, fronto-parietal in one, and the temporo-parietal in one. Prior to the surgery, twenty-one patients underwent invasive long-term intracranial EEG/CCTV monitoring. Of the fourteen patients who were tracked for longer than 2 years following surgery, eleven belonged to Class I according to Engel's criteria, two to Class II, and one to Class III. We compared intracranial EEG findings (interictal and ictal) between these twenty-one patients and eight patients with frontal lobe epilepsy resulting from different lesions. The results of this comparison, together with the seizure outcome following surgery, indicated that FCD is intrinsically epileptogenic. The invasive long-term monitoring should, as a rule, be performed in all patients with FCDs prior to the corticectomy.

Recommendation of early surgery from the viewpoint of daily quality of life.

We surveyed pre- and postoperative levels of satisfaction with a range of the daily quality-of-life (QOL) domains in 132 sets of epilepsy surgery patients and their families. All patients underwent resective surgery for temporal lobe epilepsy and were monitored for > 2 years. Patient and family assessments showed patients' overall QOL markedly improves after surgery, depending on freedom from seizures. However, factors such as social contacts, family relations, or financial status improved little. Some families and patients were not satisfied with the postsurgical status, despite freedom from seizures. Patients who had surgery at a later age were not so satisfied with their postsurgical status as were patients who had surgery at a younger age, particularly on the QOL domains of role activities, memory function, leisure activities, or emotional well-being. This lower satisfaction level in older patients likely results from a variety of problems affecting patients during the long-lasting epileptic process; social handicaps, psychologic conflicts, and deterioration of cognitive/behavioral functions. Based on each case, we recommend that investigations start at an early stage of the illness, so that surgical intervention may be considered as early as possible.

[Resection of recurrent lung cancer].

The resected recurrent lung cancer cases were evaluated retrospectively. Out of 1,060 cases who received an operation due to primary lung cancer, 21 (1.8%) had recurrent lung cancer which were resected subsequently. Stage I adenocarcinoma cases were found to be most frequent at the first operation (76%). Out of 21 cases, 7 received completion pneumonectomy, 5 had lobectomy and 8 had limited operation, respectively. The 5-year survival rate after the second operation was 36.6% in all the cases. There was no statistical difference in survival rate between the lobectomy group (including completion pneumonectomy) and the limited operation group. There was statistical difference in survival rate between cases who received a second operation in a time span of 2 or more years after the first operation and the cases who received it in less than 2 years. Good prognosis can be expected after the resection of recurrent lung cancer, but further analysis would be required in evaluation of respiratory function as well as biological malignancy of the tumor.

Improvement of quality-of-life following resective surgery for temporal lobe epilepsy: results of patient and family assessments.

In order to evaluate the quality-of-life (QOL) of epilepsy surgery patients, we surveyed patients' degree of life satisfaction and their families' degree of satisfaction with patient's status in a range of domains both pre- and post-operatively. Of 100 patient-family sets of surveys that were mailed out, 93 were completed and returned from patients and 91 from their families. All patients surveyed had temporal lobe epilepsy and had been followed for longer than 2 years after resective surgery. Patients and their families rated overall QOL as having markedly improved following surgery. However, they rated social domains of QOL, including role activities, financial status, and social and family relationships as having improved relatively little. Despite freedom from seizures, a few patients' families were dissatisfied with the patients' post-operative status, primarily for psychosocial reasons. Patients operated on at a later age reported little gains in life satisfaction following surgery. This study supports the conclusion that surgical intervention should occur before patients are subjected to the psychological conflicts and social handicaps associated with chronic intractable epilepsy.

[Significance of lymph nodes dissection of lung cancer treatment].

From 1950 to 1991, 1,221 lung cancer cases were treated with surgery in Tokyo Medical College Hospital. The 5-year survival rate was achieved in 70.1% for stage I, 49.5% for stage II, 17.0% for stage III A, 0% for stage III B and 8.3% for stage IV respectively. Considering for the survival rate with pN factor in 753 resected cases, the 5-year survival rate of N0, N1, N2 and N3 cases was 65.8%, 38.1%, 16.3% and 0% respectively. In these pN2 group, the 5-year survival rate of single mediastinal lymph node metastasis cases was 35.5%, while that of multiple mediastinal lymph node metastasized cases was 6.9%. The relationship between lymph node metastasis and DNA ploidy pattern was also discussed. The most of N0 cases showed diploid pattern, while N2 cases indicated aneuploid pattern. A mediastinal lymph node dissection of pN2 lung cancer cases may be effective to improve the prognosis of a kind of cases showing biologically low malignant lung cancer.

Localizing value of seizure manifestations of temporal lobe epilepsies and the consequence of analyzing their sequential appearance.

We investigated the localizing and lateralizing value of principal seizure manifestations in temporal lobe epilepsies (signal symptoms, oroalimentary automatisms, somatomotor manifestations, unilateral dystonic posturing, ictal speech, motionless stare) of 223 complex partial seizures in 50 patients. All the patients had invasive long-term monitoring with the combined implantation of intracerebral electrodes in and subdural electrodes on the bilateral temporal lobes. Postoperative freedom from seizures was ascertained for longer than one year. We found that 35 patients had amygdalohippocampal seizures and 15 had lateral temporal seizures. The value of the manifestations was established in relation to the site and side of seizure origin and to the progression of seizure discharges within the unilateral temporal lobe or to the contralateral cerebral hemisphere. Several signs among the manifestations were found to be reliable in predicting the site or side of the temporal lobe seizure focus. We emphasized the importance of investigating sequential changes of seizure manifestations in relation to ictal EEG findings by means of simultaneous recording.