Occurrence of the spinal reflex due to skin pressure in sudomotor and cutaneous vasoconstrictor nerve system of humans

The effects of skin pressure applied to one side of the waist on sudomotor and vasoconstrictor nerve activity were compared with the effects on sweating and cutaneous blood flow in humans. The sweat rate and cutaneous blood flow were measured on left and right dorsal feet. Skin sympathetic nerve activity (SSNA) was recorded by microneurography from a microelectrode inserted in left and right peroneal nerves. Skin pressure was applied in a supine position to the area over the left or right anterior superior iliac spine under warm (T(a): 30-36 degrees C) and cool (T(a): 19-23 degrees C) conditions. Sudomotor and vasoconstrictor bursts were identified for quantitative analysis. The skin pressure increased the contralateral/ipsilateral ratio of the sweat rate. It also increased the contralateral/ipsilateral ratio of the cutaneous blood flow and the contralateral/ipsilateral ratio of the sudomotor burst amplitude. However, skin pressure did not induce any significant changes in the contralateral/ipsilateral ratio of the vasoconstrictor burst amplitude. The results indicate that an asymmetrical reflex effect of skin pressure on vasoconstrictor nerve activity was absent, suggesting that, whereas the ipsilateral suppression of sweating elicited by skin pressure was mediated by the sudomotor nerve system, the ipsilateral suppression of cutaneous blood flow was not mediated by the vasoconstrictor nerve system. Thus, the occurrence of the spinal reflex due to skin pressure is not uniform between the sudomotor and the vasoconstrictor nerve systems, which represent different organizations at the level of spinal cord.     

Radiographic pulmonary and pleural changes after carbon ion irradiation

PURPOSE: For the treatment of Stage I non-small-cell lung cancers, a Phase I/II study of carbon ion irradiation was undertaken. In the present study, we focus on posttreatment radiographic lung damage: specifically, its timing, features, and relation to dose-volume factors. MATERIALS AND METHODS: Forty-three patients with 44 Stage I non-small-cell lung cancers were treated with carbon ion irradiation ranging from 59.4 to 95.4 photon Gy equivalent dose (GyE) in 18 fractions over 6 weeks, according to our dose escalation protocols. Primary lesions were irradiated by 2-4 portals. Follow-up evaluation with computed tomography (CT) was sequentially performed to assess changes in the lung. CT findings were classified into two categories: pulmonary reaction and pleural reaction. A dose-volume histogram for each patient was calculated, using a three-dimensional CT planning system. Statistical analysis was conducted using Spearman's rank test. RESULTS: The median appearance period of pulmonary reactions was 3 months after the start of carbon ion irradiation, whereas the maximum period was 6 months. The severity of pulmonary reactions statistically correlated with lung volumes irradiated no less than 20 GyE (vol. 20) and 40 GyE (vol. 40) (p = 0.017 and p = 0.0089). Geometrically unique findings in the irradiated fields were observed in 7 patients (16%). The median appearance period of pleural reactions was 4 months after the start of carbon ion irradiation. The occurrence of pleural reactions significantly correlated with planning target volume (p = 0.000098), vol. 20 (p = 0.00011), and vol. 40 (p = 0.00097). CONCLUSIONS: Lung damage after carbon ion irradiation was observed in the parenchyma and in the pleura. The severity of pulmonary reactions was correlated with dose-volume factors. These findings might provide useful information in the planning and management of carbon ion irradiation.     

No major difference in inhibitory susceptibility between CYP2C9.1 and CYP2C9.3

OBJECTIVE: CYP2C9 is a polymorphic enzyme, and CYP2C9*3 is associated with decreased metabolic activity. In addition to the impaired metabolism, we investigated whether the CYP2C9*3 exhibited altered inhibitory susceptibility compared with CYP2C9*1. METHOD: In the present study, CYP2C9.1 and CYP2C9.3 were expressed in yeast. Using typical CYP2C9 substrates (diclofenac, tolbutamide and S-warfarin) and a potent CYP2C9 inhibitor (nicardipine), the Ki values for nicardipine on the three metabolisms in CYP2C9*1 and CYP2C9*3 were determined. RESULT: The ratios of Ki(CYP2C9*3)/Ki(CYP2C9*1) on tolbutamide, diclofenac and S-warfarin metabolisms were 1.2, 3.1 and 0.8, respectively. CONCLUSION: In conclusion, there are no significant differences in the inhibitory susceptibility between the two CYP2C9 enzymes.     

Frequent occurrence of CCND1 deregulation in patients with early stages of plasma cell dyscrasia

Chromosomal translocations involving the immunoglobulin heavy chain gene ( IgH ) and nonrandom protooncogene loci are the hallmark of genetic alterations found not only in multiple myeloma (MM), but also in premalignant stages of MM, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM). We studied the frequency of IgH (14q32) rearrangements and their partner chromosomes in 16 Japanese patients with MGUS (13 cases), and SMM (3 cases) by means of interphase double-color fluorescence in situ hybridization (DCFISH) applied to purified plasma cells and using CD138-bead selection. IgH rearrangement was recognized in nine of the patients (56.3%). Protooncogene loci juxtaposed to IgH were identified in seven cases including CCND1 (11q13) in six cases and FGFR3 (4p16) in one. Four out of the six t(11;14)-positive cases showed nuclear staining of the cyclin D1 protein, whereas none of the seven t(11;14)-negative cases did. Moreover, neither MUM1 (6p25)- IgH nor MAFB (20q11)- IgH fusion signals were observed. This suggests to us that cyclin D1 deregulation due to the presence of t(11;14) is involved in the early development of plasma cell neoplasms, and that this event alone is not enough for the development of symptomatic myeloma. (Cancer Sci 2003; 94: 350-354)     

Time-locked perceptual fading induced by visual transients

After prolonged fixation, a stationary object placed in the peripheral visual field fades and disappears from our visual awareness, especially at low luminance contrast (the Troxler effect). Here, we report that similar fading can be triggered by visual transients, such as additional visual stimuli flashed near the object, apparent motion, or a brief removal of the object itself (blinking). The fading occurs even without prolonged adaptation and is time-locked to the presentation of the visual transients. Experiments show that the effect of a flashed object decreased monotonically as a function of the distance from the target object. Consistent with this result, when apparent motion, consisting of a sequence of flashes was presented between stationary disks, these target disks perceptually disappeared as if erased by the moving object. Blinking the target disk, instead of flashing an additional visual object, turned out to be sufficient to induce the fading. The effect of blinking peaked around a blink duration of 80 msec. Our findings reveal a unique mechanism that controls the visibility of visual objects in a spatially selective and time-locked manner in response to transient visual inputs. Possible mechanisms underlying this phenomenon will be discussed.     

Adenovirus-mediated gene transfer of ICOSIg fusion protein ameliorates ongoing experimental autoimmune myocarditis

Experimental autoimmune myocarditis (EAM) has been used as a model for human myocarditis. We previously demonstrated that blockade of B7/CD28 or CD40/CD40 ligand (CD40L) had a potential preventive effect on EAM, but less therapeutic effect on ongoing EAM. Thus, we searched for the involvement of other costimulatory molecules in EAM. We demonstrated the expression of inducible costimulator (ICOS)/ICOSL molecules in the lymph nodes, spleen, and heart in the EAM rat. We constructed adenovirus vectors containing ICOSIg (Adex1CAICOSIg) to achieve effective inhibition of ICOS/ICOSL interaction, and examined the effects of Adex1CAICOSIg on EAM. Adex1CAICOSIg treatment shortly after the immunization did not inhibit the onset and severity of EAM compared to control rats. On the other hand, delayed treatment with Adex1CAICOSIg significantly inhibited ongoing EAM. The survival rate in rats treated with Adex1CAICOSIg was significantly higher than that of the control group. Furthermore, the affected area ratio of the Adex1CAICOSIg treatment group was significantly lower than that of the control group. This study indicates that ICOS/ICOSL costimulation makes an important contribution to the progression of EAM and that the blockade of this pathway by gene transfer has therapeutic potential for ongoing autoimmune myocarditis.     

Do P1 and N1 evoked by the ERP task reflect primary visual processing in Parkinson's disease?

To evaluate whether P1 and N1 evoked by ERP tasks could appropriatelyreflect primary visual processing in Parkinson's disease (PD). Methods: We recorded ERPs in 13 PD patients with duration of illness less than 5 years and 18 age-matched normal control subjects. P1 and N1 from Oz were evoked by a visual oddball and a delayed matching S1-S2 task. The effect of different events on P1 and N1 was studied. All patients were given an ECD-SPECT examination, and the SPECT images were overlaid on the 3D-MRI. The correlation of P1 or N1 to the regional cerebral blood flow (rCBF) was studied. Results: P1 was not influenced by different events. There was no significant P1 differences between the PD and the normal group. N1 was significantly shorter and smaller in the patients than that in the normal group. N1 amplitude after the waveform subtraction (target-frequent) in the PD group did not show significant difference with that in the normal controls, nor with the N1 before the subtraction. Nd, the subcomponent of N1 after the subtraction in the patients was significantlyearlier and smaller than that in the normal controls. P1 only weakly correlated with the rCBF in the occipital lobe. N1 was correlated with the rCBF in a global region. Conclusions: The results provided some evidence that P1 might reflect the primary visual processing, and N1 might be involved in both primary and cognitive visual processing. The altered N1 in the PD patients might be due to the deformed Nd.     

Secretory granules of pituitary adenomas: quantitative study of hormonal antigenicity

Ultrastructurally, the antigenicity of major pituitary hormones in secretory granules was quantitatively investigated in five growth hormone (GH)-secreting adenomas, five prolactin (PRL)-secreting adenomas and eight clinically non-functioning (CN-F) adenomas. Sparsely granulated cells with a few or several small secretory granules (60–100 nm) exhibiting little or only weak antigenicity of various biochemically unrelated hormones were commonly observed in CN-F adenomas and occasionally in GH- and PRL-secreting adenomas. GH- or PRL-secreting adenomas consisted of many densely granulated cells with medium-sized (200–250 nm) or large (over 250 nm) secretory granules and a few or several sparsely granulated cells with small secretory granules. The densely granulated cells showed intense GH or PRL antigenicity and slight to moderate antigenicity for other hormones in large secretory granules and little or only weak antigenicity for various hormones including GH or PRL in small secretory granules. Their secretory granules larger than 160 nm or 140 nm significantly exhibited intense GH or PRL antigenicity (Fisher’s exact test; P < 0.05 and < 0.01, respectively). Two CN-F adenomas showed sparsely and densely granulated cells as well as intermediate cells. The densely granulated cells closely resembled GH-secreting cells. The intermediate cells simultaneously included small and medium-sized or large secretory granules exhibiting little/slight and intense GH-antigenicity, respectively. This study indicates that sparsely granulated cells of different categories showing slight antigenicity for various hormones, antigenically share the same origin, and that their hormonality, single or multiple, may be selectively activated in the developmental course of secretory granules. Received: 21 January 1999 / Revised, accepted: 13 July 1999     

Manifestation of scotomas created by transcranial magnetic stimulation of human visual cortex.

Reduced visual performance under transcranial magnetic stimulation (TMS) of human visual cortex demonstrates suppression whose spatial extent is not directly visible. We created an artificial scotoma (region missing from a visual pattern) to directly visualize the location, size and shape of the TMS-induced suppression by following a large-field, patterned, visual stimulus with a magnetic pulse. The scotoma shifted with coil position according to known topography of visual cortex. Visual suppression resulted in pattern-dependent distortion, and the scotoma was filled in with temporally adjacent stimuli, suggesting spatial and temporal completion mechanisms. Thus, perceptual measurements of TMS-induced suppression may provide information about cortical processing via neuronal connections and temporal interactions of neural signals.     

Short‐ and long‐term outcomes following redo valvular surgery

Aim

We reviewed our experience in redo valvular surgery to evaluate trends in short‐ and long‐term outcomes.

Methods

We reviewed 414 patients (mean age, 62.8 ± 13.6 years) who underwent redo valvular surgery in the past 25 years. A total of 301 patients (54.2%) underwent first‐time redo valvular surgeries; 178 (32.1%) were second redos, 60 (10.8%) were third redos, and 16 were fourth redos (2.9%). The mean follow‐up period was 6.8 ± 6.3 years.

Results

Hospital mortality was 5.8%. New York Heart Association (NYHA) class III/IV (P = 0.0007, odds ratio = 4.403) and hemodialysis (P = 0.0383, odds ratio = 7.196) were risk factors for hospital death. Long‐term survival rates at 15 and 20 years were 64.7% ± 4.3% and 59.1% ± 5.0%, respectively. Predictors of late death were first time redo (P = 0.0076, hazard ratio = 0.422) and age younger than 61 years (P = 0.0005, hazard ratio = 0.229). There were significant differences in long‐term survival between NYHA classes I/II and III/IV (log‐rank test, P = 0.0419) and between the time from redo surgery (log‐rank test, P = 0.0189) and age (log‐rank test, P = 0.0001).

Conclusions

The hospital mortality rate for redo valve surgery has improved. Early referral for redo surgery can contribute to improving early and late outcomes.