Clinical outcome of surgical management of mild cervical compressive myelopathy based on minimum clinically important difference.

BACKGROUND CONTEXT: Cervical compressive myelopathy (CCM), caused by cervical spondylosis (cervical spondylotic myelopathy [CSM]) or ossification of the posterior longitudinal ligament (OPLL), is a common neurological disorder in the elderly. For moderate/severe CCM, surgical management has been the first-line therapeutic option. Recently, surgical management is also recommended for mild CCM, and a few studies have reported the surgical outcome for this clinical population. Nonetheless, the present knowledge is insufficient to determine the specific surgical outcome of mild CCM. PURPOSE: To examine the surgical outcomes of mild CCM while considering the minimum clinically important difference (MCID). STUDY DESIGN: Retrospective study. PATIENT SAMPLE: Patients who underwent subaxial cervical surgery for CCM caused by CSM and OPLL between 2013 and 2022 were enrolled. OUTCOME MEASURES: The Japanese Orthopedic Association score (JOA score) was employed as the clinical outcomes. Based on previous reports, the JOA score threshold to determine mild myelopathic symptoms was set at ≥14.5 points, and the MCID of the JOA score for mild CCM was set at 1 point. METHODS: The patients with a JOA score of ≥14.5 points at baseline were stratified into the mild CCM and were examined while considering the MCID. The mild CCM cohort was dichotomized into the improvement group, including the patients with an achieved MCID (JOA score ≥1 point) or with a JOA score of 17 points (full mark) at 1 year postoperatively, and the nonimprovement group, including the others. Demographics, symptomatology, radiographic findings, and surgical procedure were compared between the two groups and studied using the receiver operating characteristic (ROC) curve. RESULTS: Of 335 patients with CCM, 43 were stratified into the mild CCM cohort (mean age, 58.5 years; 62.8% male). Among them, 25 (58.1 %) patients were assigned to the improvement group and 18 (41.9 %) were assigned to the nonimprovement group. The improvement group was significantly younger than the nonimprovement group; however, other variables did not significantly differ. ROC curve analysis showed that the optimal cutoff point of the patient's age to discriminate between the improvement and nonimprovement groups was 58 years with an area under the curve of 0.702 (p=.015). CONCLUSIONS: In the present study, the majority of patients with mild CCM experienced improvement reaching the MCID of JOA score at 1 year postoperatively. The present study suggests that for younger patients with mild CCM, especially those aged below 58 years, subjective neurological recovery is more likely to be obtained. Meanwhile, the surgery takes on a more prophylactic significance to halt disease progression for older patients. The results of this study can help in the decision-making process for this clinical population.

Ultrasonographic Evaluation of Upper Esophageal Sphincter for Dysphagia During the Acute Postoperative Phase of Anterior Cervical Surgery.

STUDY DESIGN: A retrospective study. OBJECTIVE: To verify the pathophysiology of dysphagia during the acute postoperative phase of anterior cervical surgery and to identify its predictive features, using ultrasonographic (US) examination for upper esophageal sphincter (UES). SUMMARY OF BACKGROUND DATA: There are no clinical studies investigating dysphagia after anterior cervical surgery, using US examination for UES. MATERIALS AND METHODS: We enrolled patients who underwent anterior cervical spine surgery between August 2018 and March 2022. Dysphagia was evaluated using the Eating Assessment Tool-10 (EAT-10) questionnaires. The US examination was performed preoperatively and 2 weeks postoperatively. Three US parameters for morphologic measurements (outer diameter, inner diameter, and muscle thickness) and 4 for functional measurements (displacement, time to relax, passing duration, and time to contract) were assessed. To verify the pathophysiology of postoperative dysphagia, we examined the change in the ratios of US parameters (=US parameter 2 weeks postoperatively /US parameter at baseline ) and the existence of significant correlations with change in the EAT-10 score (=EAT-10 2 weeks postoperatively -EAT-10 at baseline ). To identify the predictive features, the baseline US parameters were compared between dysphagia (+) and dysphagia (-) groups. RESULTS: A total of 46 patients (mean age, 61.3 y; 78.3% male) were included for analysis. A greater increase of the EAT-10 score after surgery was positively correlated with change ratios of the muscle thickness and time to contract and negatively with change ratio of the inner diameter. The dysphagia (+) group exhibited significantly greater inner diameter and smaller muscle thickness at baseline than the dysphagia (-) group. CONCLUSION: Dysphagia during the acute postoperative phase of anterior cervical surgery is caused by the physical narrowing of the inner lumen due to muscle thickening of the UES and sphincter contractile dysfunction. In addition, a baseline UES morphology characterized by a greater inner diameter and a thinner muscle layer is predictive of postoperative dysphagia.

Spontaneous Cervical Epidural Hematoma Presenting with Respiratory Failure: A Case Report and Literature Review.

CASE: A 62-year-old woman who had an unremarkable medical history presented with sudden headache and neck pain. After the presentation, complete quadriplegia and respiratory arrest developed, and the patient was urgently intubated. Magnetic resonance imaging revealed an extensive epidural hematoma (EH), and emergency hematoma evacuation was performed. At the 1-year follow-up visit, the patient had no motor deficits. CONCLUSION: We reported a case of spontaneous cervical EH presenting with respiratory failure that was successfully treated with surgical management. Literature review has shown that the surgical outcome is very poor; nevertheless, prompt surgical decompression of the spinal cord can minimize neurological sequelae.

Studies in the Falls Efficacy Scale-International for patients with cervical compressive myelopathy: Reliability, validity, and minimum clinically important difference.

CONTEXT: Patients with cervical compressive myelopathy (CCM) often complain of body balance problems, such as fear of falling and bodily unsteadiness. However, no accepted patient-reported outcome measures (PROMs) for this symptomatology exist. The Falls Efficacy Scale-International (FES-I) is one of the most widely used PROMs for evaluating impaired body balance in various clinical fields. OBJECTIVE: To examine reliability, validity, and minimum clinically important difference (MCID) of the FES-I for the evaluation of impaired body balance in patients with CCM. METHODS: Patients who underwent surgery for CCM were retrospectively reviewed. The FES-I was administered preoperatively and at 1 year postoperatively. Further, cJOA-LE score (subscore for lower extremities in the Japanese Orthopaedic Association score for cervical myelopathy) and stabilometric data, obtained at the same time points of the FES-I administration, were analyzed. Reliability was examined through internal consistency with Cronbach's alpha. Convergent validity was studied using correlation analysis. The MCID was estimated using anchor- and distribution-based methods. RESULTS: Overall, 151 patients were included for analysis. Cronbach's alpha coefficient was the acceptable value of 0.97 at both baseline and 1 year postoperatively. As for convergent validity, the FES-I had significant correlations with the cJOA-LE score and stabilometric parameters both at baseline and 1 year postoperatively. The MCID calculated using anchor- and distribution-based methods was 5.5 and 10, respectively. CONCLUSION: FES-I is a reliable and valid PROM to evaluate body balance problems for the CCM population. The established thresholds of MCID can help clinicians recognize the clinical significance of changes in patient status.

Segmental cervical instability does not drive the loss of cervical lordosis after laminoplasty in patients with cervical spondylotic myelopathy.

BACKGROUND/CONTEXT: Kyphotic deformity after cervical laminoplasty (CLP) often leads to unfavorable neurological recovery due to insufficient indirect decompression of the spinal cord. Existing literature has described that segmental cervical instability is a contraindication for CLP because it is a potential risk factor for kyphotic changes after surgery; however, this has never been confirmed in any clinical studies. PURPOSE: To confirm whether segmental cervical instability was an independent risk factor for postoperative kyphotic change and to examine whether segmental cervical instability led to poor neurological outcomes after CLP for cervical spondylotic myelopathy (CSM). STUDY DESIGN/SETTING: A retrospective study PATIENT SAMPLE: Patients who underwent CLP for CSM between January 2013 and January 2021 with a follow-up period of ≥1 year were enrolled. OUTCOME MEASURES: Cervical radiographic measurements including C2-C7 lordosis (C2-7 angle), cervical sagittal vertical axis, C7 slope, flexion range of motion (fROM) and extension ROM (eROM) were assessed using neutral and flexion-extension views. Segmental cervical instability was classified into anterolisthesis (AL) of ≥2 mm displacement, retrolisthesis (RL) of ≥2 mm displacement, and translational instability (TI) of ≥3 mm translational motion. The amount of C2-7 angle loss at the follow-up period compared to the preoperative measurements was defined as cervical lordosis loss (CLL). Neurological outcomes were assessed using the recovery rate of the Japanese Orthopedic Association score (JOA-RR). METHODS: CLL was compared among patients with and without segmental cervical instability. Further, multiple linear regression model for CLL was built for the evaluation with adjustment of the reported risks, including cervical sagittal vertical axis, C7 slope, fROM, eROM, and patient age together with AL, RL, and TI, as independent variables. The JOA-RR was also compared between patients with and without segmental cervical instability. RESULTS: A total of 138 patients (mean age, 68.7 years; 65.9% male) were included in the analysis. AL, RL, and TI were found in 12 (8.7%), 33 (23.9%), and 16 (11.6%) patients, respectively. Comparisons among the groups showed that AL led to greater CLL; however, RL and TI did not. Multiple linear regression analysis revealed that greater CLL is significantly associated with greater fROM and smaller eROM (regression coefficient [ß]=0.328, 95% confidence interval: 0.178 to 0.478, p<.001; ß=-0.372, 95% confidence interval: -0.591 to -0.153, p=.001, respectively). However, there were no significant statistical associations in the AL, RL, and TI. Whereas, patients with AL tended to exhibit lower JOA-RR than those without AL (37.8% vs. 52.0%, p=.108). CONCLUSIONS: Segmental cervical instability is not the definitive driver for loss of cervical lordosis after CLP in patients with CSM; thus, is not a contraindication in and of itself. However, it is necessary to consider the indications for CLP, according to individual cases of patients with AL on baseline radiograph, which is a sign of poor neurological recovery.

Periodic quadriplegia during the acute postoperative phase of cervical laminoplasty: a case report and literature review.

The use of antibiotics can, in rare cases, induce neuromuscular blockade (NMB), resulting in paralytic symptoms. Although such antibiotic-induced NMB has been described in the anaesthesiology and infectious disease literature, it is an unfamiliar clinical entity in the fields of neurosurgery and spinal surgery. Herein, we report a case of periodic quadriplegia due to NMB induced by perioperative prophylactic antibiotic of cefazolin, resulting in highly confusing paralytic symptoms during the acute postoperative phase of cervical laminoplasty, together with a review of the relevant literature.

Decompression status of the spinal cord after cervical laminoplasty in various body positions and neck postures observed using percutaneous ultrasonography: Relationship with neurological recovery.

BACKGROUND: Percutaneous ultrasonography (PUS) is used to evaluate the status of the spinal cord after cervical laminoplasty (CLP). This technique helps assess real-time movements of the spinal cord and provides immediate information regarding the decompression status. Additionally, it can also be utilized to evaluate the status of the spinal cord in various body positions and neck postures. This study aimed to examine changes in the decompression status of the spinal cord after CLP for cervical spondylotic myelopathy (CSM) in different body positions and neck postures using PUS and to assess whether these decompression statuses are related to clinical outcomes at each time point. METHODS: The study included 66 consecutive participants with CSM who underwent double-door CLP with suture anchors. PUS was performed postoperatively at 2 weeks, 3 months, 6 months, and 1 year in sitting [neck flexion (Flexion), neutral (Neutral), and extension (Extension)] and supine (Supine) positions. The decompression status was classified into grade I (noncontact), grade II (contact and apart), and grade III (contact). Clinical outcomes were evaluated using Japanese Orthopaedic Association (JOA) scores. RESULTS: The decompression status improved until 3 months postoperatively in all body positions and neck postures and was stable onwards. It changed depending on body positions and neck postures and was worse in Flexion and better in Supine at all postoperative time points. Participants with grade I decompression status in Supine had a significantly better recovery rate of JOA scores after 3 months, 6 months, and 1 year postoperatively than those with grade II + III decompression status. However, this significant relationship was not observed in each sitting position. CONCLUSIONS: The spinal cord after CLP is most decompressed in Supine. Sufficient and continuous restoration of the anterior subarachnoid space in supine position may indicate positive clinical outcomes after CLP.

Usefulness of Percutaneous Ultrasonography for Deciding the Need of Surgical Evacuation of Epidural Hematoma After Cervical Double-door Laminoplasty.

STUDY DESIGN: This was a retrospective study. OBJECTIVE: The objective of this study was to investigate the diagnostic utility of percutaneous ultrasonography (PUS) for postoperative epidural hematoma (EH) as a postoperative complication. SUMMARY OF BACKGROUND DATA: We investigated the usefulness of PUS for determining the need of surgical evacuation of postoperative EH by comparing the postoperative magnetic resonance imaging (MRI) and PUS of the spinal cord. MATERIALS AND METHODS: This study included patients who underwent cervical laminoplasty using suture anchors. Regular MRI and PUS were performed 1 week postoperatively. Whenever the patients exhibited neurological deterioration, MRI and PUS were performed. The spinal cord decompression status was classified into 3 grades using MRI and PUS. The existence of spinal pulsation was determined by PUS. RESULTS: One hundred thirty-one patients were investigated. The decompression status by MRI and PUS, and the pulsation status by PUS showed a correlation with neurological deterioration (P<0.001). Four cases showed postoperative neurological deterioration and required revision surgery. The decompression status in these cases was classified as "poor" by both MRI and PUS, and as "no-pulsation" by PUS pulsation. The sensitivity and specificity for neurological deterioration was 100% and 95.1% in MRI decompression, 100% and 92.9% in PUS decompression, and 100% and 99.2% in PUS pulsation, respectively. CONCLUSIONS: This is the first report that the disappearance of spinal pulsation was associated with neurological deterioration. PUS was useful in determining the need of surgical evacuation for postoperative EH. PUS should be the first choice of examination in the event of postoperative neurological deterioration following a cervical laminoplasty. When the disappearance of pulsation is confirmed, an additional hematoma evacuation surgery should be considered immediately without undertaking MRI. LEVEL OF EVIDENCE: Level III.

Impact of morphological restoration of the spinal cord from the preoperative to early postoperative periods on C5 palsy development.

OBJECTIVE: C5 palsy (C5P) is a known complication of cervical decompression surgery. The tethering effect of the C5 nerve root following the posterior shift of the spinal cord is the most accepted pathologic mechanism for C5P development; however, this mechanism cannot fully explain C5P by itself in clinical practice. Separately, some studies have suggested that preoperative severe spinal cord compression and postoperative morphological changes in the spinal cord affect C5P development; however, no previous study has quantitatively addressed these possibilities. The aim of this study was to examine whether spinal cord morphology and morphological restoration after surgery affect C5P development. METHODS: The authors reviewed consecutive patients with degenerative cervical myelopathy who underwent laminoplasty including the C3-4 and C4-5 intervertebral disc levels. All participants underwent MRI both preoperatively and within 4 weeks postoperatively. To assess the severity of spinal cord compression, the compression ratio (CR; spinal cord sagittal diameter/transverse diameter) was calculated. As an index of morphological changes in the spinal cord during the early postoperative period, the change rate of CR (CrCR, %) was calculated as CRwithin 4 weeks postoperatively/CRpreoperatively × 100. These measurements were performed at both the C3-4 and C4-5 intervertebral disc levels. The study cohort was divided into C5P and non-C5P (NC5P) groups; then, CR and CrCR, in addition to other radiographic variables associated with C5P development, were compared between the groups. RESULTS: A total of 114 patients (mean age 67.6 years, 58.8% men) were included in the study, with 5 and 109 patients in the C5P and NC5P groups, respectively. Preoperative CR at both the C3-4 and C4-5 levels was significantly lower in the C5P group than in the NC5P group (0.35 vs 0.44, p = 0.042 and 0.27 vs 0.39, p = 0.021, respectively). Patients with C5P exhibited significantly higher CrCR at the C3-4 level than those without (139.3% vs 119.0%, p = 0.046), but the same finding was not noted for CrCR at the C4-5 level. There were no significant differences in other variables between the groups. CONCLUSIONS: This study reveals that severe compression of the spinal cord and its greater morphological restoration during the early postoperative period affect C5P development. These findings could support the involvement of segmental cord disorder theory, characterized as the reperfusion phenomenon, in the pathomechanism of C5P, in addition to the tethering effect.

Hidden coexisting pathology diagnosed after cervical surgery in patients with degenerative cervical myelopathy or myeloradiculopathy: A case series report.

Many neurological disorders can present similar symptomatology to degenerative cervical myelopathy (DCM) or myeloradiculopathy (DCMR). Therefore, to avoid misdiagnosis, it is important to recognise the differential diagnosis, which has been well described in previous literature. Additionally, DCM or DCMR can also coexist with other diseases that overlap some of its clinical manifestations, which may be overlooked before cervical surgery. Nevertheless, few studies have addressed this clinical situation. In clinical practice, the diagnosis of coexisting disease with DCM or DCMR would be typically made when some symptoms persist without improvement after cervical surgery. To inform the patients of this possibility preoperatively and arrive at the early diagnosis during the postoperative period, some knowledge of the possible coexisting diseases would be necessary. In this report, we reviewed 230 patients who underwent surgery for DCM or DCMR in an academic centre to examine the prevalence and kind of underlying disease that was overlooked preoperatively. The coexisting diseases relevant to their baseline symptoms were diagnosed only after cervical surgery in three patients (1.3%) and included amyotrophic lateral sclerosis, lung cancer and polymyalgia rheumatica. The overlapping symptoms were gait difficulty, scapular pain and neck pain, respectively. Surgeons should recognise that the coexisting disease with DCM or DCMR may be overlooked before cervical surgery because of overlapping symptomatology, although its prevalence is not certainly high. Further, when the specific symptom persisted without improvement after surgery for DCM or DCMR, the patient should be comprehensively examined, considering diverse pathological conditions, not only neurological disorders.

Biologic Agents Preserve the C-2 Pedicle in Patients with Rheumatoid Arthritis: A Comparative Imaging Study Using Three-Dimensional Computed Tomography.

OBJECTIVE: To investigate whether biologic agents (BAs) reduce a narrow C-2 pedicle screw trajectory, which is often a key stabilizer in surgical treatment, in patients with rheumatoid arthritis (RA). METHODS: A total of 100 patients with RA treated with and without BAs (BA [+] group [n = 50] and BA [-] group [n = 50]), respectively, were included in the present study. Computed tomography (CT) images of their cervical spine, including C-2, were analyzed. The maximum screw diameter at C-2 that could be inserted without breaching the cortex, measured on 3-dimensional images using a CT-based navigation system, was compared between the groups with and without BA administration. Furthermore, the destruction of the atlantoaxial joint was examined using CT images. The risk factors for a narrow C-2 pedicle were elucidated among the patients treated with BAs. RESULTS: The pedicle in the BA (+) group had a significantly larger C-2 maximum screw diameter than the BA (-) group (6.00 mm vs. 5.13 mm, P < 0.001), with less destruction of the atlantoaxial joint. Among the BA (+) group, a longer period until the initial administration of BAs and RA disease duration were associated with a narrow C-2 pedicle. CONCLUSIONS: This study suggests that BAs can maintain the trajectory for C-2 pedicle screws, which acts as a key stabilizer in surgical management for the rheumatoid cervical spine, by halting the destruction of the atlantoaxial joint. Early introduction of BAs can be especially important to prevent the narrowing of the C-2 pedicle.

The Effect of Military Load Carriage on Postural Sway, Forward Trunk Lean, and Pelvic Girdle Motion.

Musculoskeletal injuries are a common occurrence in military service members. It is believed that the load carried by the service member impedes stability and alters back and pelvis kinematics, increasing their susceptibility to musculoskeletal injuries, specifically in the lower extremities. The purpose of this study was to examine the effects of two different loads on postural sway, forward trunk lean, and pelvic girdle motion in United States Army Cadets. Twenty male Army Reserve Officers' Training Corps Cadets participated in this study. Each participant performed the Modified Clinical Testing of Sensory Interaction (mCTSIB) Protocol and the Unilateral Stance (ULS) Protocol under three different rucksack load conditions (unloaded, 16.0 kg, and 20.5 kg loads). Mean postural sway velocity was recorded along with 2-D kinematics of the trunk in the sagittal plane and the pelvis in the frontal and sagittal planes. External loads of 16.0 kg (p < 0.001) and 20.5 kg (p ≤ 0.003) significantly increased mean sway velocity by 16% to 52% depending on stance and visual condition, but did not produce significant changes in trunk and pelvic kinematics.

Low-dose pravastatin and age-related differences in risk factors for cardiovascular disease in hypercholesterolaemic Japanese: analysis of the management of elevated cholesterol in the primary prevention group of adult Japanese (MEGA study).

BACKGROUND: Limited data are available regarding the relationship between age and the effect of HMG-CoA reductase inhibitor (statin) treatment. OBJECTIVE: The aim of the present analysis was to evaluate the relationships between age, baseline patient characteristics, and pravastatin treatment with respect to the development of cardiovascular disease (CVD) in the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study, a large-scale clinical study conducted in Japanese patients with mild or moderate hyperlipidaemia to evaluate the primary preventive effect of pravastatin against coronary heart disease. METHODS: To compare the prevalence of CVD risk factors, the incidence of CVD in relation to each risk factor, and final values and changes in lipid parameters, the 7832 patients were classified into six age groups: <45, 45-49, 50-54, 55-59, 60-64 and ≥65 years. The relationship between pravastatin (10-20 mg/day) treatment efficacy and aging and the incidence of events in relation to the age groups were compared using the multivariable Cox proportional hazards model. RESULTS: The prevalences of diabetes mellitus and hypertension were higher in older men than in younger men, while the prevalences of smoking and obesity were higher in younger men. However, a similar difference in risk factors was not seen in women. High-density lipoprotein cholesterol was higher in women than in men across all age groups. Triglycerides were higher in younger men than in older men and all groups of women. The mean follow-up levels of total cholesterol and low-density lipoprotein cholesterol were lower in older patients than in younger patients. Pravastatin (10-20 mg/day) reduced the risk of CVD by about 30-40% across all age groups, and there was no difference between men and women. Of particular note in this analysis, CVD risk was markedly reduced in older women compared with younger women (53% vs 30% in women aged ≥65 vs ≥45 years). CONCLUSION: A similar satisfactory risk reduction for CVD was achieved with low-dose pravastatin in all men and in older women in particular, despite differences in the prevalence of risk factors. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00211705.

Novel endoscope system with plasma flushing for off-pump cardiac surgery.

The purpose of this study is to develop a new endoscope for performing simple surgical tasks inside a cardiac atrium/chamber filled with blood, i.e., for performing "off-pump" cardiac surgeries. In general, it is very difficult to observe the inner wall of the vessels containing circulating blood because the light from the endoscope is scattered by the red blood cells. "Plasma flushing" performed using the separator system is developed to observe the inner side of the heart filled with blood and to remove blood cells from the front of the endoscope tip. The system was used in in vitro quantitative measurement of the device performance and in vivo experiments on a swine. In these experiments, we successfully obtained high-resolution images of the interior of the heart during off-pump surgery.

Aquaporin NIP2;1 is mainly localized to the ER membrane and shows root-specific accumulation in Arabidopsis thaliana.

We investigated a nodulin 26-like protein NIP2;1, which belongs to the third subgroup of Arabidopsis aquaporins. Histochemical analysis of a promoter-beta-glucuronidase fusion revealed the root-specific expression of NIP2;1. The NIP2;1 protein was detected in young roots, but not in leaves, stems, flowers or siliques. The transient expression of NIP2;1 linked with green fluorescent protein in Arabidopsis cultured cells showed its putative endoplasmic reticulum (ER) localization. NIP2;1 expressed in yeast cells had low water channel activity in the membranes. NIP2;1 may function as a water channel and/or ER channel for other small molecules or ions.

Immunochemical analysis of aquaporin isoforms in Arabidopsis suspension-cultured cells.

Aquaporins mediate the movement of water across biomembranes. Arabidopsis thaliana contains 35 aquaporins that belong to four subfamilies (PIP, TIP, SIP, and NIP). We investigated their expression profiles immunochemically in suspension-cultured Arabidopsis thaliana cells during growth and in response to salt and osmotic stresses. Protein amounts of all aquaporins were much lower in cultured cells than in the plant tissues. This is consistent with the low water permeability of protoplasts from cultured cells. After treatment with NaCl, the protein amounts of PIP2;1, PIP2;2, and PIP2;3 in the cells increased several-fold, and those of TIP1;1 and TIP1;2, 15- and 3-fold respectively. PIP1 did not change under the stress. Cell death began after 19 d in culture, accompanied by marked accumulation of PIPs and TIPs and a gradual decrease in SIPs. Our results suggest the followings: (i) Accumulation of aquaporin isoforms was individually regulated at low levels in single cells. (ii) At least PIP2;2, PIP2;3, TIP1;1, and TIP1;2 are stress-responsive aquaporins in suspension cells. (iii) A sudden increment of several members of PIP2 and TIP1 subfamilies might be related to cell death.

Effects of Antimutagens on the Teratogenicity of N-Methyl-N'-Nitro-N-Nitrosoguanidine in Mice.

We examined whether vanillin (VA) and CoCl2 ∙6H2 O(CoCl2 ), antimutagens, which have mutation suppressing effect, i.e., promotion of cellular repair function in vitro, can modify the teratogenicity in mice caused by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting monofunctional alkylating agent. ICR mice were treated with MNNG alone (single IP dose of 40 or 60 mg/kg) or in combination with the antimutagen on day 11 of gestation. Embryotoxicity and teratogenicity were examined at term. The incidence of MNNG-induced syndactyly in the fore- and hindlimbs was significantly decreased by VA (50 mg/kg, IP) or CoCl2 (10 mg/kg, IV) and a tendency to decrease in the incidence of oligodactyly was noted as well. On the other hand, the incidence of MNNG-induced brachydactyly was increased by VA or CoCl2 . Though the mechanism of the modifying effects of both VA and CoCl2 on MNNG-induced malformations could not be delineated in the present study, the results indicate that the antimutagens which stimulate DNA recombination repair in vitro modify the manifestation of malformations caused by teratogens that attack the fetal DNA in the initial teratogenic mechanism.