Association between transforming growth factor-ß1 -509 C>T variants and hepatocellular carcinoma susceptibility: a meta-analysis.

The transcriptional activity of transforming growth factor-ß (TGF-ß) is increased in subjects with hepatocellular carcinoma (HCC). Recent studies have indicated that the -509C genotype in hepatitis B virus (HBV)-infected subjects and the -509T genotype in hepatitis C virus (HCV)-infected subjects can increase the transcriptional activity of the TGF-ß1 gene. We conducted a meta-analysis to clarify whether these two hepatitis viruses affect the association between TGF-ß1 C-509T variants and HCC susceptibility. Using data derived from 8 case-control studies available in the PubMed database (5 with Asian and 3 with Caucasian populations), including 1,427 cases and 3,735 controls [1,610 patients with chronic liver disease and 2,125 healthy controls], we calculated pooled odds ratios with corresponding 95% confidence intervals. We used dominant (TT + CT vs. CC), recessive (TT vs. CC + CT), and co-dominant (TT vs. CC and CT vs. CC) genetic models. An overall analysis showed no association between the TGF-ß1 C-509T variants and HCC susceptibility for all models. In contrast, a subgroup analysis, based on the infecting hepatitis viruses, provided the following results. Among the cases and controls with chronic liver disease, the TGF-ß1 C-509T variants were significantly associated with decreased HCC susceptibility for two models with HBV-infected subjects, whereas the variants were significantly associated with increased HCC susceptibility for one model with HCV-infected subjects. Among the cases and healthy controls, there was a significant association between the TGF-ß1 C-509T variants and increased HCC susceptibility for two models involving HCV-infected subjects. Among the cases and the entire control group, the same results were obtained for all genetic models with HCV-infected subjects. Although further data accumulation is required, our results suggest that these two hepatitis viruses affect the association between TGF-ß1 C-509T variants and HCC susceptibility in opposite manners.

Clinical and prognostic significance of bone marrow abnormalities in the appendicular skeleton detected by low-dose whole-body multidetector computed tomography in patients with multiple myeloma.

Clinical significance of medullary abnormalities in the appendicular skeleton (AS) detected by low-dose whole-body multidetector computed tomography (MDCT) in patients with multiple myeloma (MM) was investigated. A total of 172 patients with monoclonal gammopathy of undetermined significance (MGUS) (n=17), smoldering MM (n=47) and symptomatic MM (n=108) underwent low-dose MDCT. CT values (CTv) of medullary density of AS⩾0 Hounsfield unit (HU) was considered as abnormal. Percentage of medullary abnormalities and the mean CTv of AS in patients with MGUS, smoldering MM and symptomatic MM were 18, 55 and 62% and -44.5 , -20.3 and 11.2 HU, respectively (P<0.001 and P<0.001). Disease progression of MM was independently associated with high CTv on multivariate analysis. In symptomatic MM, the presence of abnormal medullary lesions was associated with increased incidence of high-risk cytogenetic abnormalities (34.4% vs 7.7%; P=0.002) and extramedullary disease (10.4% vs 0%; P=0.032). It was also an independent poor prognostic predictor (hazard ratio 3.546, P=0.04). This study showed that CTv of AS by MDCT is correlated with disease progression of MM, and the presence of abnormal medullary lesions is a predictor for poor survival.

Smooth pursuit eye movements and express saccades in schizophrenic patients.

Abnormalities of saccades such as disinhibition have been hypothesized as one cause of smooth pursuit eye movement (SPEM) dysfunctions in schizophrenia. Thus, we studied saccadic eye movements in schizophrenics with SPEM dysfunction. Subjects were divided into three groups: 10 normal control subjects, 10 schizophrenic subjects without SPEM dysfunction and 10 schizophrenic subjects with SPEM dysfunction characterized by a cogwheel appearance. Visually guided saccades in gap and overlap paradigms (Saslow, 1967) were examined and saccadic reaction times (SRTs) were measured in all subjects. Only schizophrenics with SPEM dysfunctions tended to manifest excessive reflexive saccades, named express saccades (Fischer, 1987), in the gap paradigm. Moreover, most of them were also found to have express saccades in the overlap paradigm, whereas normal subjects and schizophrenic subjects without SPEM dysfunction did not show such phenomena under the same conditions. In particular, most express saccades in the overlap paradigm in schizophrenics with SPEM dysfunction, were found in movements to the right.

Smooth pursuit eye movements and voluntary control of saccades in the antisaccade task in schizophrenic patients.

It has been hypothesized that a saccade control dysfunction is one cause of a smooth pursuit eye movement (SPEM) dysfunction in schizophrenia. We studied the voluntary control of saccades in schizophrenic patients with the SPEM dysfunction using an antisaccade task. The mean error rate in the antisaccade task was significantly higher in the two schizophrenic groups with and without a SPEM dysfunction than in the normal control group. Furthermore, the schizophrenic group with the SPEM dysfunction showed significantly more errors than the schizophrenic group without the SPEM dysfunction. These findings seem to suggest a close relationship between the SPEM dysfunction and the appearance of errors which indicates an inability to inhibit reflexive saccades voluntarily in the antisaccade task. However, 4 of 10 subjects with the SPEM dysfunction showed an error rate less than the mean error rate of the schizophrenic group without the SPEM dysfunction. So, a voluntary control disorder of saccades as the main cause of the SPEM dysfunction appeared to be unlikely. An interesting finding of this study was that many schizophrenic subjects with the SPEM dysfunction showed errors with the latencies similar to those in express saccades, particularly in the rightward direction. This finding may suggest a close relationship between the SPEM dysfunction in schizophrenic patients and some pathological conditions of express saccades such as disinhibition of express saccades.

Smooth pursuit eye movement dysfunction as a biological marker for prediction of disease courses of schizophrenia: a preliminary report.

We investigated the relationship between a smooth pursuit eye movement (SPEM) dysfunction and long-term disease courses of schizophrenia. Many schizophrenic patients without the SPEM dysfunction tended to show an acute onset of illness, undulating courses and relatively good outcomes. On the other hand, patients with cogwheel-like SPEM dysfunction tended to show a chronic onset, simple courses, relatively severe outcomes and negative symptoms.

The influence of interfering input from the peroneal nerve on tibial-nerve somatosensory evoked potential.

Using a conditioning-test paradigm, we studied the recovery function of tibial nerve somatosensory evoked potentials (SEPs) conditioned by preceding peroneal nerve stimulation. The inter-stimulus intervals (ISIs) ranged from 0 to 400 msec, where 0 msec indicated simultaneous arrival of tibial and peroneal nerve volleys at the L1 spine. The recovery curve was W-shaped, showing two peaks of SEP suppression, maximum at 6 msec ISI (1st phase) and 50-75 ISI msec (2nd phase). In the 1st phase suppression, we found distinct differences in wave forms between 0-2 msec ISI and 4-6 msec ISI. At 0-2 msec ISI, P40-N50-P60 amplitude decreased and latencies shortened, while P31 and N35 were unchanged. At 4-6 msec ISI, all peaks, possibly excluding P31, were markedly depressed. We attribute the former change to an "occlusive effect" and the latter to an "inhibitory effect," each mediated via a central synaptic network between the two nerves. The attenuation of the 2nd but not the 1st phase suppression by peroneal nerve block distal to the stimulating electrodes provided evidence that the 2nd phase suppression resulted primarily from interfering afferent signals generated by peroneal nerve peripheral receptors, activated by foot movement.

Recovery functions of common peroneal, posterior tibial and sural nerve somatosensory evoked potentials.

We studied recovery functions of the somatosensory evoked potentials (SEPs) of common peroneal (CPN), posterior tibial (PTN) and sural nerves (SN) using a paired conditioning-test paradigm. The interstimulus interval (ISI) of paired stimuli ranged from 2 to 400 msec. In all SEPs with ISIs of 12-20 msec, the amplitude recovery was close to or beyond 100% of the control response, though their latencies and wave forms were not the same as the control. Further increases of the ISI resulted in significant depression of SEP (late phase suppression), most markedly in CPN, and less prominently in SN-SEP. With a longer than 50 msec ISI there was progressive recovery of SEP, but full recovery differed depending on the nerve stimulated; 400 msec ISI was required for CPN-, 250 msec for PTN- and 100 msec for SN-SEP. The peroneal nerve block by local anesthetic injected just distal to the stimulus electrodes abolished the late phase SEP suppression observed before the nerve block. These findings suggest that the late phase SEP suppression is attributable to the "secondary" afferents as a result of activation of peripheral receptors (muscle, joint and/or cutaneous) by the efferent volley initiated from the stimulus point. The greater and longer duration of peripheral receptor activation in CPN than in PTN or SN stimulation could explain the more pronounced and the longer duration of late phase suppression in CPN-SEP.

The silent period produced by electrical stimulation of mixed peripheral nerves.

The electromyographic silent period (SP) produced by electrical stimulation of the median and ulnar nerve, before and after lidocaine block of the ulnar nerve at the elbow, was recorded in the voluntarily contracting abductor pollicis brevis (APB) muscle of 4 normal subjects. Prior to block, stimulation of the corresponding segment in either nerve (e.g., wrist and elbow) elicited SPs with similar end points. With more proximal stimulation, the SPs consistently ended earlier. Following the block, ulnar nerve stimulation below the elbow failed to elicit a SP in any subject, despite a mechanical twitch caused by the antagonistic contraction of adductor pollicis muscle. Ulnar nerve stimulation above the block elicited a SP in all subjects similar to the preblock SP. In all 4 subjects, submaximal median nerve stimulation at the wrist produced an H-reflex, followed by a SP in the absence of the direct M-response. This SP, due to selective activation of sensory fibers, lacked a collision component, but, was otherwise similar to the SP elicited by supramaximal wrist stimulation. These findings indicate that the ascending volley following electrical stimulation of a mixed peripheral nerve produces the SP without apparent contribution from the descending motor volley.

Saccadic eye movements in tracking, fixation, and rest in schizophrenic and normal subjects.

Horizontal eye movements were recorded electrooculographically during two different eye fixation tasks, during an eyes-closed waking state, and during eye tracking on a sinusoidally moving target in 16 chronic schizophrenics and in 12 normal subjects. The relationship between saccadic eye movements during tracking and in the other experimental situations was investigated. The intensities of eye fixation were successively decreased from Experiment I (eye fixation on a stationary target) through Experiment II (eye fixation on an imagined spot in the dark) to Experiment III (eyes closed in the dark, no cue for eye fixation), in that order. The frequency of saccades increased as the intensities of fixation decreased from Experiment I to Experiment III in both schizophrenic and normal groups. It was demonstrated that the frequency of saccades was higher in schizophrenics than in normal subjects in all of the experimental conditions. Some correlations were found between the increased frequency of saccades seen during eye tracking and the similar increases seen in eyes-fixated or eyes-closed states in schizophrenic subjects. It is suggested that the increased saccades seen during eye tracking and in other experimental conditions in schizophrenics are related to a deficit of nonvoluntary attention, due to a failure of an inhibitory mechanism.

Incidence of adult T-cell leukemia-lymphoma and its familial clustering.

The yearly incidence of ATLL in the Uwajima district is 6.6 patients per 100,000 inhabitants aged over 40. The yearly morbidity rate from ATLL of persons in this district who are positive for HTLV-antibody and older than 40 is 1 patient per 1,631. Familial occurrence was observed in 9/38 families available for pedigree analyses. Even in the endemic area, the existence of positive HTLV antibody is remarkably high in ATLL families, suggesting that HTLV has been transmitted from generation to generation mainly within these particular families.

Relative advance of eye movement to the target in the rightward tracking in schizophrenics.

Time relationship between the horizontal smooth pursuit eye movement (SPEM) and tracking target in the leftward or rightward tracking was investigated in 28 normal and 25 chronic schizophrenic subjects. Normal subjects were more liable to show a relative advance of SPEM in relation to the target in the leftward pursuit than in the rightward pursuit. These findings suggest that the spatial task such as SPEM depends more on the right hemispheric function in normal subjects. On the other hand, many of schizophrenic subjects showed a relative advance of SPEM to the target in the rightward pursuit. These findings suggest the dominance of the left hemispheric function in eye tracking tasks in schizophrenic subjects. The finding in the present study would support the hypothesis of the left hemispheric overactivation in the schizophrenic patients.

Model insomnia by methylphenidate and caffeine and use in the evaluation of temazepam.

Experimental sleep disturbances (model insomnia) were produced by the administration of methylphenidate (MPD) 10 mg and caffeine (CAF) 150 mg. The effect of temazepam (TEM), 15 mg or 30 mg, on the model was investigated. All-night polysomnography was performed on 8 normal young male subjects under each of the following 9 conditions: baseline, MPD 10 mg, CAF 150 mg, TEM 15 mg, TEM 30 mg, MPD + TEM 15 mg, MPD + TEM 30 mg, CAF + TEM 15 mg, CAF + TEM 30 mg. A reduction in total sleep time and total amount of stage REM (S-REM) sleep and an increase in the sleep latency and wake time (S-W) were observed in both the MPD and CAF nights. The sleep latency was significantly longer in the CAF night than in the MPD night. Administration of TEM 15 mg or TEM 30 mg alone caused very few modifications in the sleep parameters. These drugs in combination with MPD or CAF resulted in almost complete recovery of the sleep disturbance induced by MPD or CAF. The results indicate that CAF and MPD produced similar models of insomnia except for a greater sleep latency for CAF than for MPD. Both models were useful in the evaluation of hypnotic drugs such as temazepam.

Smooth pursuit eye movements in epileptics under antiepileptic medication.

1) Smooth pursuit eye movements (SPEM) were recorded in 18 normal, 20 schizophrenic and 50 epileptic subjects. Most of the schizophrenic and epileptic subjects were under medication, antipsychotic drugs in the former and antiepileptic drugs in the latter. 2) In schizophrenics and epileptics, rate of the saccadic component in SPEM was higher than that of normal controls. The rate of large amplitude saccades was higher in epileptics than in schizophrenics. 3) Though small amplitude saccades were usually superimposed on SPEM in schizophrenic patients, both large and small amplitude saccades superimposed irregularly on the smooth tracking curve were observed in epileptics, and overshoots or undershoots were also seen frequently. 4) SPEM disorder in epileptics was observed in more than half of patients receiving antiepileptic medication, especially in patients with a long period of treatment. SPEM disorder in epileptics tended to occur frequently in patients who received phenytoin in doses higher than a certain level; i.e. approximately 150 mg per day for a long period of time. 5) It is conceivable that the SPEM disorder represents a latent or subclinical cerebellar dysfunction due to phenytoin medication. It is suggested that the SPEM measurement is a useful tool to find out subclinical side effects of antiepileptic drug in the treatment of epilepsy.

Flickering light spot as a tracking target for the study of smooth pursuit eye movements in schizophrenics--a new method.

Smooth pursuit eye movements (SPEM) were studied in 26 schizophrenics and 20 normal controls. A light spot on a screen of cathode ray oscilloscope was used as a tracking target. In order to induce SPEM disorder easily, the subjects were required to track a light spot which flickered in various frequencies. This new method devised by the authors has clearly demonstrated that the SPEM in schizophrenic was more profoundly disturbed by the flickering of the tracking target than that in the normal control subjects. It was supposed that poor tracking of a flickering light spot in schizophrenics may be due to the inadequate concentration of attention to visual stimuli, and/or inability to predict the movements of a tracking target.

The changing style of symptomatology of hysteria.

The symptomatology of 412 hysteric women was investigated and analyzed at the Neuropsychiatric Clinic, Tohoku University Hospital, from 1952 till 1973, according to the study stages, 1952-1957 and 1958-1973, and the patients' residence, both rural and urban. Withdrawal with taciturnity was seen in 27% of them and stubbornness with egocentricity in 14% as the frequent personality traits. Physical distress was significantly a frequent problem in the recent rural patients. Among symptoms insomnia and tinnitus have decreased. Mutism and deviated attitude were seen more frequently in the rural patients. Astasia-abasia and syncope have increased. Generally speaking, hysteric symptomatology seemed to have become of tranquil style recently and the rural patients showed more frequently nonverbal expression in terms of mutism and deviated attitude than the urban patients.

Pregnancy and delivery in penicillamine treated patients with Wilson's disease.

Pregnancy and delivery of two patients with Wilson's disease are reported. Case 1 was a 20-year-old housewife who had been taking D-penicillamine fore more than 10 years and had remained asymptomatic except an episode of dissociative reaction. She apparently survived longer than any of her three sisters who died of the same disease. She discontinued the use of D-penicillamine by herself when she was at the 22nd week of pregnancy. Case 2 was a 32-year-old housewife who developed an episode of mental disorder of short circuit reaction type with mild neurological symptoms and Kayser-Fleischer rings after the prolonged interval of medication since the first pregnancy and delivery. Three months after the complete recovery of neuropsychiatric symptoms she was at the 12th week of pregnancy and withheld penicillamine from herself. During the pregnancy they had not revealed any exacerbation in terms of clinical and laboratory findings. Each of them was delivered of a healthy baby. Although the pregnancy and delivery of both patients were successful, the authors recommended that they should not prolong the interval of medication to protect themselves against the onset or relapse of the illness.