Learning Promotes Subfield-Specific Synaptic Diversity in Hippocampal CA1 Neurons.

The hippocampus is functionally heterogeneous between the dorsal and ventral subfields with left-right asymmetry. To determine the possible location of contextual memory, we performed an inhibitory avoidance task to analyze synaptic plasticity using slice patch-clamp technique. The training bilaterally increased the AMPA/NMDA ratio at dorsal CA3-CA1 synapses, whereas the training did not affect the ratio at ventral CA3-CA1 synapses regardless of the hemisphere. Moreover, sequential recording of miniature excitatory postsynaptic currents and miniature inhibitory postsynaptic currents from the same CA1 neuron clearly showed learning-induced synaptic plasticity. In dorsal CA1 neurons, the training dramatically strengthened both excitatory and inhibitory postsynaptic responses in both hemispheres, whereas the training did not promote the plasticity in either hemisphere in ventral CA1 neurons. Nonstationary fluctuation analysis further revealed that the training bilaterally increased the number of AMPA or GABAA receptor channels at dorsal CA1 synapses, but not at ventral CA1 synapses, suggesting functional heterogeneity of learning-induced receptor mobility. Finally, the performance clearly impaired by the bilateral microinjection of plasticity blockers in dorsal, but not ventral CA1 subfields, suggesting a crucial role for contextual learning. The quantification of synaptic diversity in specified CA1 subfields may help us to diagnose and evaluate cognitive disorders at the information level.

Safer Vitrification of Mouse and Human Embryos Using the Novel Cryoroom Vitrification System for Assisted Reproductive Technology.

BACKGROUND: Vitrification is widely used for assisted reproductive technology (ART). Most vitrification devices require the skillful placement of embryos into the carrier and aspiration of excessive vitrification solution. OBJECTIVE: To evaluate the efficacy and safety of the Cryoroom as a vitrification device. MATERIALS AND METHODS: Mouse and human embryos were vitrified with Cryoroom or Cryotop, and the developmental potency was assessed in vitro. Mouse monozygotic twin blastocysts were vitrified with Cryoroom or Cryotop for microarray analysis. RESULTS AND DISCUSSION: In mouse and human embryos, there were no differences between the survival and developmental progress in each device. In silico, the Cryoroom device showed no changes, particularly in DNA methylation after vitrification compared with the Cryotop. These results showed that the form and function of the device may affect the gene expression levels in vitrified embryos. CONCLUSION: The Cryoroom represents a safe and potentially revolutionary vitrification device for ART.

In-process monitoring of a tissue-engineered oral mucosa fabricated on a micropatterned collagen scaffold: use of optical coherence tomography for quality control.

Background: We previously reported a novel technique for fabricating dermo-epidermal junction (DEJ)-like micropatterned collagen scaffolds to manufacture an ex vivo produced oral mucosa equivalent (EVPOME) for clinical translation; however, more biomimetic micropatterns are required to promote oral keratinocyte-based tissue engineering/regenerative medicine. In addition, in-process monitoring for quality control of tissue-engineered products is key to successful clinical outcomes. However, evaluating three-dimensional tissue-engineered constructs such as EVPOME is challenging. This study aimed to update our technique to fabricate a more biomimetic DEJ structure of oral mucosa and to investigate the efficacy of optical coherence tomography (OCT) in combination with deep learning for non-invasive EVPOME monitoring. Methods: A picosecond laser-textured microstructure mimicking DEJ on stainless steel was used as a negative mould to fabricate the micropatterned collagen scaffold. During EVPOME manufacturing, OCT was applied twice to monitor the EVPOME and evaluate its epithelial thickness. Findings: Our moulding system resulted in successful micropattern replication on the curved collagen scaffold. OCT imaging visualised the epithelial layer and the underlying micropatterned scaffold in EVPOME, enabling to non-invasively detect specific defects not found before the histological examination. Additionally, a gradual increase in epithelial thickness was observed over time. Conclusion: These findings demonstrate the feasibility of using a stainless-steel negative mould to create a more biomimetic micropattern on collagen scaffolds and the potential of OCT imaging for quality control in oral keratinocyte-based tissue engineering/regenerative medicine.

Symptomatic ossification of the anterior longitudinal ligament with stenosis of the cervical spine: a report of seven cases.

Seven men with a mean age of 63.9 years (59 to 67) developed dysphagia because of oesophageal compression with ossification of the anterior longitudinal ligament (OALL) and radiculomyelopathy due to associated stenosis of the cervical spine. The diagnosis of OALL was made by plain lateral radiography and classified into three types; segmental, continuous and mixed. Five patients had associated OALL in the thoracic and lumbar spine without ossification of the ligamentum flavum. All underwent removal of the OALL and six had simultaneous decompression by removal of ossification of the posterior longitudinal ligament or a bony spur. All had improvement of their dysphagia. Because symptomatic OALL may be associated with spinal stenosis, precise neurological examination is critical. A simultaneous microsurgical operation for patients with OALL and spinal stenosis gives good results without serious complications.

An integrated service digital network (ISDN)-based international telecommunication between Samsung Medical Center and Hokkaido University using telecommunication helped radiotherapy planning and information system (THERAPIS).

This study introduces the integrated service digital network (ISDN)-based international teleradiotherapy system (THERAPIS) in radiation oncology between hospitals in Seoul, South Korea and in Sapporo, Japan. THERAPIS has the following functions: (1) exchange of patient's image data, (2) real-time teleconference, and (3) communication of the treatment planning, dose calculation and distribution, and of portal verification images between the remote hospitals. Our preliminary results of applications on eight patients demonstrated that the international telecommunication using THERAPIS was clinically useful and satisfactory with sufficient bandwidth for the transfer of patient data for clinical use in radiation oncology.

Analysis of hypertrophy of the posterior longitudinal ligament of the cervical spine, on the basis of clinical and experimental studies.

OBJECTIVE: The goal of this study was to elucidate the pathophysiological features and treatment of hypertrophy of the posterior longitudinal ligament (HPLL) of the cervical spine. HPLL is defined as a pathological thickening of the posterior longitudinal ligament (PLL), causing spinal cord compression. Incomplete decompression via removal of only coexisting herniated intervertebral discs or spondylotic spurs might be performed, resulting in unsatisfactory surgical outcomes, when the PLL becomes abnormally thickened and contributes to myelopathy. METHODS: Patients with HPLL who underwent cervical decompression surgery were selected. Medical records and radiographs were retrospectively reviewed, to obtain data on the pre- and postoperative clinical conditions of the patients. Autopsy cases with HPLL proven by low-energy x-ray examinations were chosen for assessment of the pathological characteristics. RESULTS: Seventeen men and three women with HPLL underwent treatment via an anterior approach, with direct removal of HPLL. Nineteen patients developed myelopathy, whereas one patient developed radiculopathy. Radiologically, all HPLL cases exhibited coexisting herniated intervertebral discs and 10 exhibited small segmental ossifications of the PLL. Magnetic resonance imaging or computed tomographic myelography revealed extensive cord compression across the vertebral endplate level. The average preoperative Benzel modified Japanese Orthopaedic Association score was 10.8, and the average postoperative score was 13.2. Histological examinations revealed thickening of the PLL with proliferation of chondrocytes, together with various degenerative changes. CONCLUSION: Patients with HPLL can benefit from an anterior approach with direct removal of the HPLL and associated herniated intervertebral discs or ossification of the PLL. Cervical polytomography, computed tomography, and magnetic resonance imaging are useful in establishing a diagnosis of HPLL.

Isolated histiocytosis X of the pituitary gland: case report.

The authors describe a case of a granuloma of histiocytosis X localized in the pituitary gland. The patient presented with diabetes insipidus and hyperprolactinemia. The diagnosis was established by surgical removal of the pituitary lesion through a transsphenoidal approach. The clinical and pathological aspects of the case are discussed.

Pituitary tumors composed of adenohypophysial adenoma and Rathke's cleft cyst elements: a clinicopathological study.

Nine cases of pituitary tumors composed of mixed tissue elements of adenohypophysial adenoma and Rathke's cleft cyst are reported. All cases were associated with hyperprolactinemia and were managed by transsphenoidal adenomectomy with good results. The clinical and pathological features are presented, and embryological pathogenesis for the occurrence of this unique association is discussed in connection with the high incidence of immunoreactive S-100 protein cells identified in tumor tissues. Patients with this kind of pituitary tumor can be managed in the same fashion as patients with other types of pituitary adenoma.

Ganglioglioma of the cerebellum: case report.

The authors report a rare case of a cerebellar ganglioglioma. A review of 12 previously reported cases and our case suggest that surgical removal of this neoplasm carries a good prognosis.

Management of prolactinomas associated with very high serum prolactin levels.

The authors have reviewed the results of transsphenoidal microsurgical management in 69 patients with prolactin-secreting pituitary adenomas who had preoperative serum prolactin levels over 200 ng/ml. The patients were divided into three groups based on their preoperative serum prolactin levels: over 200 to 500 ng/ml (Group A); over 500 to 1000 ng/ml (Group B); and over 1000 ng/ml (Group C). The percentage of successful treatment ("control rate") was 68%, 30%, and 14%, respectively, in these three groups of patients. Based on these results, the authors offer guidelines for the management of patients with prolactin-secreting pituitary adenomas associated with exceptionally high serum prolactin levels. The surgical control rate of 68% in Group A seems to justify surgery for these patients, while primary medical care with bromocriptine is recommended for most patients with serum prolactin levels over 500 ng/ml.

Pathology of spinal cord lesions caused by ossification of the posterior longitudinal ligament, with special reference to reversibility of the spinal cord lesion.

This report describes pathological findings of the spinal cord damage, with ossification of the posterior longitudinal ligament (OPLL), with special reference to reversibility of such lesions. Twenty-five autopsy cases associated with OPLL were examined, and the spinal cord damage was pathologically classified into four categories based on degree of destruction (stage 0-3). In stage 0 and stage 1, major pathological changes in the gray matter and the degree of compression on the spinal cord were well correlated to deformity of the anterior horn. In stage 2 and stage 3, neurons were almost completely obliterated and necrosis with cavitation were frequently observed. Destruction of the spinal cord in stage 2 and stage 3 is considered to be irreversible; therefore, surgical treatment is recommended at stage 0 or stage 1.

Significance of egg-jelly substances in the internal fertilization of the newt, Cynops pyrrhogaster.

Japanese newt, Cynops pyrrhogaster, undergoes internal fertilization as do most urodeles. In this study, we focused on the roles of egg-jelly in fertilization of C. pyrrhogaster and characterized the substances associated with those roles. When dry sperm were directly inseminated onto the egg, normal fertilization occurred without the presence of water. Egg-jelly extract (JE) prepared with Steinberg's salt solution contained the activity for the initiation of sperm motility. A substance of about 50 kDa in JE was significant for this activity; an inactive form of the substance probably exists in JE. Strong activity to induce acrosome reaction was detected in JE. It was inhibited by the treatment of JE with WGA, suggesting that carbohydrate in JE may be important for the induction of the acrosome reaction. This study suggests that two significant processes of fertilization are regulated by substances in the egg-jelly of the newt, C. pyrrhogaster.

Primary amyloidoma of the thoracic spine presenting with acute paraplegia.

BACKGROUND: Primary solitary amyloidoma of the spine is a rare disease characterized by localized deposition of amyloid. To the best of our knowledge, there have been only 14 cases previously reported in the literature. Patients with focal spinal amyloidoma usually have relatively long symptomatic periods preoperatively, ranging from 3 weeks to 6 years (mean: 12 months). Only two reported patients had acute paraplegia. We add a third case of a thoracic spine amyloidoma presenting with acute paraplegia. CASE DESCRIPTION: A 65-year-old man presented with a three-day history of progressive paraplegia and urinary retention. He was found to have severe cord compression at T2 on magnetic resonance imaging. He underwent emergent decompressive laminectomy with instrumentation for spinal stabilization. Histopathology revealed abundant amyloid deposits. A systemic work-up was negative for amyloidosis. The patient showed marked neurological improvement with residual mild spastic gait after 1 year. CONCLUSIONS: Primary spinal amyloidoma with acute paraplegia is rare. One-stage surgery combining prompt decompression and stabilization of the spinal column is mandatory in cases of spinal amyloidoma with acute myelopathy, because primary solitary amyloidoma carries a good prognosis.

Lumbar herniated disc presenting with cauda equina syndrome. Long-term follow-up of four cases.

BACKGROUND: Cauda equina syndrome is a relatively rare presenting symptom of lumbar herniated discs. Early operative decompression is advocated, but it may not always restore the bladder function. In such cases, knowing the long-term outcome of bladder or sphincter disturbances is quite useful in planning the management of these patients. METHODS: Hospital records of patients operated on for lumbar herniated discs were reviewed. Charts and imaging studies of those patients who presented with classic cauda equina syndrome were analyzed. RESULTS: There were 4 patients (2.8%) of 144 consecutive surgical series of lumbar disc herniation, whose presenting symptom was classic cauda equina syndrome. Postoperatively, the patients had been followed at the clinic for a mean period of 6.4 years. Certain characteristic findings were noted on patients' neurological and radiological examinations. Although the recovery process of bladder function was very slow, taking months to years, all four patients achieved almost normal voiding with no major impairment of daily activities. CONCLUSIONS: Even if short-term recovery of bladder function is poor after lumbar disc surgery for cauda equina syndrome, the long-term outcome is not necessarily so. We should follow up on these patients with such measures as intermittent self-catheterization and drug therapy, expecting slow but steady recovery of bladder and sphincter function.

Hybrid logistic characterization of isometric twitch force curve of isolated ferret right ventricular papillary muscle.

We previously found that the isovolumic pressure curve of the left ventricle and the isometric twitch force curve of the right ventricular in situ papillary muscle, both of the blood-perfused canine heart, were precisely fitted by our newly proposed hybrid logistic function. This function describes the difference between the two S-shaped logistic functions for the rising and falling components: A/[1+exp{-(4B/A)(t-C)}]-D/[1+exp{-(4E/D)(t-F)}]+G. This function characterizes comprehensively both ventricular and in situ papillary muscle contraction and relaxation. In the present study, we hypothesized that this function could also characterize the force curve of the most popular, standard-type, isolated and Tyrode-superfused papillary muscle preparation. To test this hypothesis, we investigated how precisely the hybrid logistic function could fit 112 isometric twitch force curves observed in eight isolated and Tyrode-superfused ferret right ventricular papillary muscles at different muscle lengths and extracellular Ca2+ concentrations. We always obtained a precise curve fitting with a correlation coefficient above 0.9987. This fitting was much more precise than sinusoidal and polynomial exponential function curve fittings. These results supported the present hypothesis. We conclude that our hybrid logistic function reasonably characterizes the force curve of the isolated myocardial preparation. This result broadens the generality of the hybrid logistic characterization of ventricular isovolumic pressure and myocardial isometric twitch force generation. The hybrid logistic characterization seems to be an integrative expression of contractile processes in myocardial twitch contraction.

Frank-Starling mechanism retains recirculation fraction of myocardial Ca(2+) in the beating heart.

Myocardial Ca(2+) handling in excitation-contraction coupling is the second primary determinant of energy or O(2) demand in a working heart. The intracellular and extracellular routes remove myocardial Ca(2+) that was released into the sarcoplasma with different Ca(2+): ATP stoichiometries. The intracellular route is twice as economical as the extracellular route. Therefore the fraction of total Ca(2+) removed via the sarcoplasmic reticulum, i.e., the recirculation fraction of intracellular Ca(2+) (RF), determines the economy of myocardial Ca(2+) handling. RF has conventionally been estimated as the exponential decay rate of postextrasystolic potentiation (PESP). However, we have found that PESP usually decays in alternans, but not exponentially in the canine left ventricle beating above 100 beats/min. We have succeeded in estimating RF from the exponential decay component of an alternans PESP. We previously found that the Frank-Starling mechanism or varied ventricular preload did not affect the economy of myocardial Ca(2+) handling. Then, to account for this important finding, we hypothesized that the Frank-Starling mechanism would not affect RF at a constant heart rate. We tested this hypothesis and found its supportive evidence in 11 canine left ventricles. We conclude that RF at a constant heart rate would remain constant, independent of the Frank-Starling mechanism.

Logistic time constant of isometric relaxation force curve of ferret ventricular papillary muscle: reliable index of lusitropism.

We have found that a logistic function fits the left ventricular isovolumic relaxation pressure curve in the canine excised, cross-circulated heart more precisely than a monoexponential function. On this basis, we have proposed a logistic time constant (tau(L)) as a better index of ventricular isovolumic lusitropism than the conventional monoexponential time constant (tau(E)). We hypothesize in the present study that this tau(L) would also be a better index of myocardial isometric lusitropism than the conventional tau(E). We tested this hypothesis by analyzing the isometric relaxation force curve of 114 twitches of eight ferret isolated right ventricular papillary muscles. The muscle length was changed between 82 and 100% L(max) and extracellular Ca(2+) concentrations ([Ca(2+)](o)) between 0.2 and 8 mmol/l. We found that the logistic function always fitted the isometric relaxation force curve much more precisely than the monoexponential function at any muscle length and [Ca(2+)](o) level. We also found that tau(L) was independent of the choice of the end of isometric relaxation but tau(E) was considerably dependent on it as in ventricular relaxation. These results validated our present hypothesis. We conclude that tau(L) is a more reliable, though still empirical, index of lusitropism than conventional tau(E) in the myocardium as in the ventricle.

Effects of Ca2+ and epinephrine on Ca2+ recirculation fraction and total Ca2+ handling in canine left ventricles.

We investigated the effects of intracoronary Ca2+ and epinephrine on the intracellular Ca2+ recirculation fraction (RF) and total Ca2+ handling in the left ventricle (LV) of the excised cross-circulated canine heart preparation. We analyzed LV postextrasystolic potentiation (PESP) following a spontaneous extrasystole that occurred sporadically under constant atrial pacing. All PESPs decayed in alternans and none decayed monotonically. We extracted an exponential decay component from the alternans PESP, determined its beat constant (taue), and calculated RF = exp(-1/taue). Increased intracoronary Ca2+ slightly increased taue and RF, but epinephrine did not change them, although both agents enhanced LV contractility 2-3 times. Neither Ca2+ nor epinephrine affected the sinusoidal decay of the alternans PESP. These results indicate that RF via the sarcoplasmic reticulum was slightly augmented by Ca2+, but not by epinephrine. We combined these RF data with LV Ca2+ handling O2 consumption data and obtained 40-110 micromol/kg as the total amount of Ca2+ handled in one cardiac cycle in the control and enhanced contractile states. These results indicate that this new LV-level approach seems to better the understanding of the Ca2+ mass dynamics responsible for the mechanoenergetics enhanced by inotropic interventions.

Load independence of temperature-dependent Ca2+ recirculation fraction in canine heart.

Intramyocardial Ca(2+) recirculation fraction (RF) critically determines the economy of excitation-contraction coupling. RF is obtainable from the exponential decay of the postextrasystolic potentiation of left ventricular (LV) contractility. We have shown that RF remains unchanged despite increasing LV volume (LVV) at normothermia, but decreases with increasing temperature at a constant LVV. However, it remains unknown whether the temperature-dependent RF was not due to the simultaneously changed peak LV pressure (LVP) at a constant LVV. We hypothesized that this temperature-dependent RF would be independent of the simultaneous change in LVP. We used nine excised, cross-circulated canine hearts and allowed their LVs to contract isovolumically. During stable regular beats at 500 msec intervals, we inserted an extrasystolic beat at 360 msec interval followed by the postextrasystolic beats (PESs) at 500 msec intervals. We equalized the temperature-dependent peak LVPs of the regular beats at 36 degrees C and 38 degrees C to the peak LVP level of the stable regular beat at 33 degrees C by adjusting LVV. We fitted the same equation: nEmax = a.exp[-(i - 1)/tau(e)] + b.exp[-(i - 1)/tau(s)]cos[pi(i - 1)] + 1, used before to the normalized Emax (maximum elastance) values of PESi (i = 1-6) relative to the regular beat Emax. RF given by exp(-1/tau(e)) decreased by 19% to 38 degrees C from 33 degrees C. The temperature coefficient (Q(10)) of 1/RF was significantly greater than 1.3. The present results indicated a similar temperature dependence of RF and its Q(10) to those we observed previously without equalizing peak LVP. Thus, the temperature-dependent RF is independent of ventricular loading conditions.

Outcome analysis of anterior decompressive surgery and fusion for cervical ossification of the posterior longitudinal ligament: report of 107 cases and review of the literature.

OBJECT: This study was designed to determine the surgical technique and surgery-related outcome, fusion rate, and complication of anterior decompression and fusion (with various graft materials) performed in patients with ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. METHODS: Between 1980 and 1998, 107 patients with radiologically proven OPLL underwent surgery via the anterior approach for direct removal of the ossified mass. Graft materials included iliac crest in 45 cases, vertebral body (VB) in 37 cases; and interbody fusion cages in 25 cases. In four patients with three-level VB grafts and one with a two-level VB graft, anterior plates were placed. Surgery-related outcome was excellent or good in 89% and fair in 11%. This clinical improvement correlated well with the severity of preoperative myelopathy. Only one patient with severe myelopathy due to extensive mixed-type OPLL developed a segmental weakness of the bilateral upper extremities. The overall fusion rate was 97%. Three patients with obvious spinal instability due to pseudarthrosis required reoperation. Of the graft materials used in this series, VB grafts were the most fragile. CONCLUSIONS: The anterior approach is an effective route for decompressing the cervical cord with OPLL. Slight asymptomatic kyphotic deformity may be encountered. Of the graft materials used in our series, VB graft was considered most fragile, and thus least optimal.