The significance of preoperative chemotherapy for early gastric carcinoma

In order to achieve a complete prognosis for early gastric carcinoma, a greater effort must be made to improve its present treatment, considering the small percentage of patients who still die from recurrence despite the prompt initiation of surgery. Over the past 9 years, 26 patients with early gastric carcinoma have undergone surgical resection after receiving preoperative chemotherapy in the form of oral 5-FU or 5-DFUR in our institute. The effectiveness of preoperative chemotherapy was evaluated by histopathological examination of the resected stomachs. Of a total of 24 patients with depressed type gastric cancer, 19 were histologically found to have a cancerless area within the cancerous lesion, 8 of whom were classified as being over Grade 1b. Gross changes were observed in 13 of these 24 patients. The frequency of multiple early gastric cancer occurring in patients who had not received chemotherapy was 11.6%, whereas in those who had received chemotherapy it was 3.8%. The findings of this study thus indicate that preoperative chemotherapy is useful for reducing minute cancer foci and microscopic metastatic lesions.     

Inhibitory effects of adhesion oligopeptides on the invasion of squamous carcinoma cells with special reference to implication of αv integrins

We studied invasion-related adhesion events in vitro using three squamous carcinoma cell lines (HSC-3, poorly differentiated type; OSC-19, well-differentiated type; and KB cells, undifferentiated type). An in vitro invasion assay through matrigel in the transwell chamber revealed that HSC-3 cells were most invasive, OSC-19 cells moderately invasive and KB cells least invasive. Inhibition assay of invasion using synthetic peptides RGD, RGDV, RGDS, RGDT, IKVAV and YIGSR, showed that invasion of the three cell lines was significantly inhibited by RGDV. There were other peptides that inhibited invasion significantly including IKVAV for HSC-3, and RGDS and YIGSR for OSC-19. HSC-3 cells and OSC-19 cells adhered to fibronectin, laminin, vitronectin, and type IV collagen, and KB cells did not adhere to laminin but did to fibronectin, vitronectin and collagen type IV. Pretreatment of cells with RGDV peptide in the attachment assay reduced the ability of these cells to bind to vitronectin and fibronectin more efficiently than pretreatment with RGDS. Anti-v antibodies inhibited adhesion of HSC-3, OSC-19 and KB cells to vitronectin, but anti-1 antibodies did not inhibit adhesion. Immunofluorescent microscopic examinations showed that all cell lines were positive for anti-5 and anti-v antibodies, and only HSC-3 cells were positive for anti-3 antibody. 51 was not clearly demonstrated in any of the cell lines. RGDV was the most effective inhibitor of squamous cell carcinoma invasion among the synthetic oligopeptides used in this experiment, and it is suggested that it affects v3-and/or v5-mediated carcinoma cell invasion.Abbreviations BSA bovine serum albumin - MEM Eagle's minimal essential medium - MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide - PBS phosphatebuffered saline - FITC fluorescein isothiocyanate This work supported in part by a grant from the Osaka Cancer Research Foundation     

Apoptotic cells associated with Wallerian degeneration after experimental spinal cord injury: a possible mechanism of oligodendroglial death.

We have investigated the temporal and spatial profiles of apoptotic cells in an experimental transection spinal cord injury by the terminal deoxynucleotidyl transferase-mediated biotin-16-2'-deoxyuridine-5'-triphosphate nick-end labeling (TUNEL) method. Twenty-four hours postinjury, a numerous TUNEL-positive cells appeared both rostrally and caudally to the transection site. Those positive cells, however, gradually diminished in number by several days postinjury. In contrast, other TUNEL-positive cells were found scattered within the white matter remote from the lesion by the third day postinjury. These cells were typically embedded in or among vacuolated fibers, where they were identified in close proximity to the vacuolated space enclosed by myelin basic protein (MBP)-positive structures confirmed by TUNEL-MBP double staining. Because of their linear arrangement, these TUNEL-positive cells were considered interfascicular oligodendrocytes, a fact that was confirmed by the finding that some TUNEL-positive cells were also stained with CCI, a cell marker for oligodendrocyte. Electron microscopic studies revealed that the cells expressing apoptotic morphology were invariably encased in a space formed by myelin splitting. Although the biological significance of apoptotic interfascicular oligodendrocytes in the process of wallerian degeneration is yet to be determined, the finding of such profiles localized within degenerating myelin structures suggests that; oligodendrocytes may be "trapped" within rapidly swollen and disintegrating myelin lamellae, which isolates and perhaps predisposes them to death.     

Specific IgG to gelatin in children with systemic immediate- and nonimmediate-type reactions to measles, mumps and rubella vaccines.

We examined anti-gelatin IgG in sera of children who suffered from systemic adverse reactions upon immunization with gelatin-containing live virus vaccines. In the group of 30 children who had immediate-type reactions and anti-gelatin IgE, 30 (100%) had anti-gelatin IgG and 29 (96%) had anti-gelatin IgG4. In another group of 75 children who had nonimmediate-type reactions and no anti-gelatin IgE, 22 (29%) had anti-gelatin IgG and six (8%) had IgG4. The IgG positivity well correlated with the lymphocyte proliferation assay positivity. In contrast, as a negative control, all 24 children who had no allergic reaction to live virus vaccines had no anti-gelatin IgG and IgG4. The results suggest that immune-response to gelatin may play a role in the pathogenesis of systemic nonimmediate-type reactions to the live virus vaccines.     

K+ loading, but not Na+ loading, and blockade of ATP-sensitive K+ channels augment renal kallikrein secretion

This study aimed to examine whether K+ loading or Na+ loading augments renal kallikrein (KK) secretion. It also investigated the effect of blockade of renal ATP-sensitive K+ channels on renal KK secretion. Rats were administered 50 mmol/kg body weight of KCl. Twelve-hour collected urine was measured for urinary excretion of K+ and Na+ and urinary activity of renal KK. Increases in urinary excretion of K+ and Na+ by K+ loading accompanied an increase in renal KK secretion. In another experiment, rats were infused intravenously with a solution of 75 mM K+ and 75 mM Na+, 150 mM Na+ or 300 mM Na+ for 150 min under anesthesia. Urinary KK activity was measured in urine collected every 30 min. Renal KK secretion began to increase within the 30 min infusion of K+ solution and persisted at more elevated levels during the infusion with K+ solution than with Na+ solutions. Furthermore, rats were given intravenous injection of ATP-sensitive K+ channel blocker, either PNU-37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl) at a concentration of 10 mg/kg or glibenclamide at 30 mg/kg. Renal KK secretion increased 30 min after administration of both PNU-37883A and glibenclamide. In conclusion, it may be that augmentation of renal KK secretion by K+ loading occurred through an increase in urinary K+ excretion followed by the inhibition of K+ transport from ATP-sensitive K+ channels.     

Isozyme selective induction of mouse pulmonary superoxide dismutase by the exposure to mercury vapor

Alterations in lung superoxide dismutase (SOD) isozymes after exposure of mice to mercury vapor were examined. Inhalation of mercury vapor (10 mg/m(3)) for 1 h by mice resulted in a higher accumulation of mercury in the kidney and lung compared to other organs, at 1 h after exposure. Under these conditions marked enhancement of protein content in bronchoalveolar fluid (BALF), attributed to lung injury, was observed. Exposure to mercury vapor caused a significant increase in the pulmonary Cu,Zn-SOD activity (1.32-fold at 48 h) whereas Mn-SOD activity was suppressed to 82% of the control level, suggesting different sensitivity to the metal inhalation. The selective induction of Cu,Zn-SOD protein (1.79-fold at 48 h) was confirmed by immunoblot analysis with polyclonal antibodies against these isozymes. These observations suggest that the selective induction of Cu,Zn-SOD at the translational level appears to occur as an initial defense against mercury-promoted oxidative stress.     

The Studies of the Attacks of Abnormal Eye Movement in a Case of Infantile Spasms

We observed the attacks of nystagmus in a case of infantile spasms and carried out overnight sleep polygraphy. The following findings were obtained:

• 1 Awake time was prolonged to 56% of TIB, while sleep time was markedly shortened to 44% of TIB. Also REM sleep time was reduced to 20% of SPT and deep slow sleep (stage N3) was absent.
• 2 Attacks of nystagmus were observed only during wakefulness. At first, fast wave bursts appeared in the right occipital area, and were followed by left-upward deviations of eyeballs, and then the attacks of counterclockwise right-downward rotatory nystagmus. Also the fast wave bursts were succeeded by spreading of fast waves to adjacent areas. At the same time, EMG exhibited elevated muscle action potentials of mentalis and biceps fernoris. During the attacks of nystagmus, there was alteration of respiratory movements.

In NREM sleep, both fast wave bursts and the attacks of nystagmus were not observed. In REM sleep, the fast wave bursts and eye movements were observed but the attacks of nystagmus did not appear. During the fast wave bursts, alteration of respiratory movements were observed. From the results of this study, it was presumed that the brain lesions of this case were extended with severe degree of damage in the great parts of brain containing Cerebral cortex and brain stem.     

Problems related to dorsal root entry zone lesions

Summary Several clinical problems related to the dorsal root entry zone lesions (DREZLs) in 15 patients with chronic pain are presented and discussed in terms of ratings of pain relief following surgery, development of sensory or motor weakness and postmortem histologies. Subjective pain relief exceeding 70% was achieved at around 2 weeks after the operations in most patients (13/15), and then decreased in some to 30 from 70% in the follow-up observations. Our new objective pain relief score was tested in these patients. A significant positive correlation between subjective pain relief and our objective pain relief scale was found, but some discrepancies between them were also found during the follow-up. Sensory loss, motor weakness, paraesthesia and a new pain were found as complications in 12, 7, 4 and 6 patients, respectively. Postmortem histological findings of the spinal cord in two patients with systemic lupus erythematosus and uterine cancer, who received bilateral DREZLs twice and bilateral DREZLs plus commissural myelotomy, respectively, indicate that care should be taken to avoid extension of the coagulation beyond the dorsal horn.     

Diagnostic reliability and significance of irregular beta patterns.

We designated EEGs with marked and irregular beta waves in basic patterns as "irregular beta patterns" on the basis that these patterns are related with particular symptoms such as dysphoria, irritability and autonomic symptoms and they implicate choice of therapeutic agents. Because of good response to antiepileptic agents in patients with "irregular beta patterns" along with EEG characteristics, we hypothesized that the prevalence of "irregular beta patterns" is higher in epileptics than in other psychiatric patients. In the present study, we tested this hypothesis, investigating actual frequencies of these patterns among different diagnostic categories for all patients whose EEG were recorded in all the first-visit patients to the Outpatient Clinic, Department of Neuropsychiatry of the Tokyo University Hospital during one year period of 1986. Before starting this investigation, we checked the interrater reliability for these patterns. Therefore, two studies are reported here. In Study 1, five raters judged 98 EEG recordings blindly (43 epileptics and 55 healthy subjects). As a result, the generalized Kappa of 0.473 was obtained, indicating our agreement level was moderate or fair. This result lends support to our contention that irregular beta patterns are reliably judged. In Study 2, we judged the EEG recordings (137 schizophrenics, 62 affective disorders, 43 epileptics and 55 healthy controls) and calculated the prevalence rate of "irregular beta patterns" among the diagnostic categories. The results show that the prevalence rates of "irregular beta patterns" among psychiatric disorders and normal controls were 13% (18/137) in schizophrenics, 11% (7/62) in affective disorders, 14% (6/43) in epileptics and 4% (2/55) in healthy controls. These rates did not differ significantly among the three disorders. Thus, our hypothesis was not supported. The clinical significance of these patterns is discussed.