Cellulose acetate, a new candidate feed supplement for ruminant animals: In vitro evaluations.

Cellulose acetate (CA), a derivative of cellulose in which some hydroxyl groups are substituted with acetyl groups, was evaluated as a new cellulosic feed source for ruminants. In the present work, a series of in vitro studies was carried out to determine how CA supplementation affects rumen fermentation and microbiota. Batch culture studies were conducted to select the type of CA suitable for feed use and to define the optimal supplementation level. Rumen fluid from 2 Holstein cows was mixed with McDougall's buffer in test tubes into which grass hay and concentrate containing a fiber source [cellulose (control), water-soluble CA (WSCA), or insoluble CA] had been placed. Each fiber source was supplemented at 10% of total substrate. Tubes were incubated for 24 h to determine fermentation and microbial parameters. Then, the dose response of these parameters to different supplementation levels of WSCA (0, 7.5, 15, 22.5, and 30%) was tested in the same manner. We also operated a continuous culture system with WSCA supplementation and evaluated the effects on digestibility, fermentation, and microbial parameters. The supplementation level of WSCA was set at 15% of total feed. In batch culture studies, WSCA, but not insoluble CA, yielded dose-dependent increases in ruminal acetate levels. In the continuous culture system study, WSCA yielded increases in ruminal acetate levels and in the abundance of bacteria of the genus Prevotella, including Prevotella ruminicola. Dry matter digestibility and total gas production were not affected. These results suggest that WSCA supplementation at 15% of total feed yielded increased acetate levels without negatively affecting feed digestion; these effects may reflect activation of Prevotella species. As ruminal acetate is involved in milk fat synthesis, WSCA can be considered as a candidate feed additive suitable for dairy cattle.

ACTN4 copy number increase as a predictive biomarker for chemoradiotherapy of locally advanced pancreatic cancer.

BACKGROUND: Several clinical trials have compared chemotherapy alone and chemoradiotherapy (CRT) for locally advanced pancreatic cancer (LAPC) treatment. However, predictive biomarkers for optimal therapy of LAPC remain to be identified.We retrospectively estimated amplification of the ACTN4 gene to determine its usefulness as a predictive biomarker for LAPC. METHODS: The copy number of ACTN4 in 91 biopsy specimens of LAPC before treatment was evaluated using fluorescence in situ hybridisation (FISH). RESULTS: There were no statistically significant differences in overall survival (OS) or progression-free survival (PFS) of LAPC between patients treated with chemotherapy alone or with CRT. In a subgroup analysis of patients treated with CRT, patients with a copy number increase (CNI) of ACTN4 had a worse prognosis of OS than those with a normal copy number (NCN) of ACTN4 (P=0.0005, log-rank test). However, OS in the subgroup treated with chemotherapy alone was not significantly different between patients with a CNI and a NCN of ACTN4. In the patients with a NCN of ACTN4, the median survival time of PFS in CRT-treated patients was longer than that of patients treated with chemotherapy alone (P=0.049). CONCLUSIONS: The copy number of ACTN4 is a predictive biomarker for CRT of LAPC.

A preoperative prognostic nutritional index is a prognostic indicator in oral squamous cell carcinoma patients undergoing radical surgery.

The purpose of this study was to investigate the prognostic value of prognostic nutritional index (PNI) in oral squamous cell carcinoma (OSCC) patients and to undertake a comparative evaluation of the prognostic value of comparing PNI, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in terms of prognostic utility. A retrospective study was conducted involving 203 consecutive patients with OSCC who were treated with radical surgery with curative intent. The PNI and systemic inflammatory response were developed, and their prognostic utility was evaluated. Kaplan-Meier curve analysis and log-rank testing showed that PNI (P< 0.001), NLR (P=0.011), PLR (P=0.013), and LMR (P=0.014) were significantly associated with overall survival. Multivariate analysis identified PNI as an independent prognostic factor for OSCC patients (P=0.029). In time-dependent receiver operating characteristic curve analysis, PNI was continuously superior to that of NLR, PLR, and LMR. In conclusion, this study suggested that PNI offered an independent prognostic biomarker in OSCC patients undergoing radical surgery. However, this study was small and retrospective, thus further investigations are needed to clarify the utility of PNI for tailor-made treatments in clinical settings.

Prognostic significance of gene amplification of ACTN4 in stage I and II oral tongue cancer.

Despite complete resection of the early stage of oral tongue cancer by partial glossectomy, late cervical lymph node metastasis is frequently observed. Gene amplification of ACTN4 (protein name: actinin-4) is closely associated with the metastatic potential of various cancers. This retrospective study was performed to demonstrate the potential usefulness of ACTN4 gene amplification as a prognostic biomarker in patients with stage I/II oral tongue cancer. Fifty-four patients with stage I/II oral tongue cancer were enrolled retrospectively, in accordance with the reporting recommendations for tumour marker prognostic studies (REMARK) guidelines. The copy number of ACTN4 and the protein expression of actinin-4 were evaluated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. The overall survival time of patients with gene amplification of ACTN4 was significantly shorter than that of patients without gene amplification (P=0.0010, log-rank test). Gene amplification of ACTN4 was a significant independent risk factor for death in patients with stage I/II oral tongue cancer (hazard ratio 6.08, 95% confidence interval 1.66-22.27). Gene amplification of ACTN4 is a potential prognostic biomarker for overall survival in oral tongue cancer.

Anti-anhedonic effect of selective serotonin reuptake inhibitors with affinity for sigma-1 receptors in picrotoxin-treated mice.

BACKGROUND AND PURPOSE: Prefrontal dopamine release by the combined activation of 5-HT1A and sigma-1 (σ1 ) receptors is enhanced by the GABAA receptor antagonist picrotoxin in mice. Here, we examined whether this neurochemical event was accompanied by behavioural changes. EXPERIMENTAL APPROACH: Male mice were treated with picrotoxin to decrease GABAA receptor function. Their anhedonic behaviour was measured using the female encounter test. The expression of c-Fos was determined immunohistochemically. KEY RESULTS: Picrotoxin caused an anxiogenic effect on three behavioural tests, but it did not affect the immobility time in the forced swim test. Picrotoxin decreased female preference in the female encounter test and attenuated the female encounter-induced increase in c-Fos expression in the nucleus accumbens. Picrotoxin-induced anhedonia was ameliorated by fluvoxamine and S-(+)-fluoxetine, selective serotonin reuptake inhibitors with high affinity for the σ1 receptor. The effect of fluvoxamine was blocked by a 5-HT1A or a σ1 receptor antagonist, and co-administration of the σ1 receptor agonist (+)-SKF-10047 and the 5-HT1A receptor agonist osemozotan mimicked the effect of fluvoxamine. By contrast, desipramine, duloxetine and paroxetine, which have little affinity for the σ1 receptor, did not affect picrotoxin-induced anhedonia. The effect of fluvoxamine was blocked by a dopamine D2/3 receptor antagonist. Methylphenidate, an activator of the prefrontal dopamine system, ameliorated picrotoxin-induced anhedonia. CONCLUSION AND IMPLICATIONS: Picrotoxin-treated mice show anhedonic behaviour that is ameliorated by simultaneous activation of 5-HT1A and σ1 receptors. These findings suggest that the increased prefrontal dopamine release is associated with the anti-anhedonic effect observed in picrotoxin-treated mice.

Androgen receptor gene mutations in human prostate cancer.

To investigate the structural abnormality of the androgen receptor (AR) in human prostate cancers, exons B-H encoding DNA- and hormone-binding domains were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products using originally designed oligoprimers. Tissues from 7 cases of untreated stage B prostate cancer surgically removed and from 8 cases of endocrine therapy-resistant cancers obtained at autopsy were used in the study. Two different mutations were identified in exons D and H in the different cancer foci of the same cancer death patient. One mutation in exon D (at codon 701, Leu to His) was detected in the prostate, and the other in exon H (at codon 877, Thr to Ala) was found in metastatic tissues. In untreated cancer tissues and the other autopsy samples, no mutations were detected. The mutation in exon H was identical to that reported in LNCaP cells. These results indicate that AR gene mutations occur in relation to endocrine therapy-resistance, although the mutation was found in 1 out of 8 resistant cases (12.5%) at autopsy.

Loss of androgen dependency with preservation of functional androgen receptors in androgen-dependent mouse tumor (Shionogi Carcinoma 115).

Shionogi Carcinoma 115 (SC 115) is an androgen-dependent mouse tumor. Chiba Subline 2 (CS 2) is an androgen-independent subline derived from SC 115. CS 2 contains androgen receptors (AR), but is refractory to androgen and does not exhibit androgen-related responses which are observed in SC 115. In the present study the structure and function of AR in SC 115 and CS 2 are examined using cloned cells. There were no gross rearrangements or deletions in the AR genes of these cell lines when compared by Southern blot analysis with the AR gene in the mouse seminal vesicle. SC 115 and CS 2 expressed AR mRNA of normal size. When the cDNA containing DNA- and androgen-binding domains of the AR genes of both cell lines were amplified by polymerase chain reaction, no mutations were found in these regions. SC 115 and CS 2 were transfected with a plasmid containing a long terminal repeat of mouse mammary tumor virus linked to the chloramphenicol acetyltransferase (CAT) gene. Androgen stimulation of these transfectants resulted in equal elevation of CAT activity. These results indicated that the androgen-independent CS 2 contained functionally normal AR which were identical to those in the androgen-dependent parent tumor.

Proliferative activity of the parathyroid cells in rats with secondary hyperparathyroidism.

Proliferative kinetics of parathyroid cells in secondary hyperparathyroidism (HPT) are still unknown. We examined the histopathological changes and proliferative activity of parathyroid cells in spontaneously hypercholesterolemic (SHC) rats that exhibit secondary HPT and in normal Sprague Dawley (SD) rats from 3 weeks to 32 weeks of age. Proliferative activity [proliferating cell nuclear antigen(PCNA) labeling index], evaluated by means of immunohistochemical examination of PCNA, declined in SD rats with age from 10.8% at 3 weeks of age to 0.15% at 32 weeks of age. In SHC rats, a PCNA labeling index of 11.6% declined to 3.12% at 14 weeks of age and rebounded to 6.15% at 26 weeks of age. Parathyroid glands increased in size as determined by the maximum cross-sectional area, but in SHC rats, the increase was significantly greater, paralleling the progression of renal dysfunction, and at 32 weeks they were almost three times larger than in SD rats. Parathyroid hormone (PTH) levels in SHC rats also rose sharply after 20 weeks and reached 611 pg/ml at 32 weeks, while PTH in SD rats remained unchanged at approximately 110 pg/ml. This study showed that in the course of developing HPT in SHC rats, there is a large increase in the size of the parathyroid gland, a concomitant increase in PTH levels, and a PCNA labeling index that is higher than in normal SD rats.

MR and CT of tuberous sclerosis: linear abnormalities in the cerebral white matter.

A review of MR and CT images in five patients, 8 months to 22 years old, diagnosed as having tuberous sclerosis, revealed linear abnormalities in the cerebral white matter. A linear abnormality connecting a subependymal nodule to a subcortical lesion was shown in two patients as an area of hypointensity on T1-weighted MR images and as an area of hyperintensity on T2-weighted images. These appeared as faintly high-density areas on CT images. Seventeen linear abnormalities extending from the ventricle to the cortex with a subependymal nodule or subcortical lesion on each end were visible in all five patients as areas of hyperintensity on the T2-weighted images. On the T1-weighted images, only nine hypointense lines were noted. CT scans did not show these latter lines. Linear abnormalities in cerebral white matter are suggestive of lesions of demyelination, dysmyelination, hypomyelination, or lines of migration disorder. MR imaging, especially T2-weighted, is particularly sensitive in detecting these abnormalities.

The action of a novel vitamin D3 analogue, OCT, on immunomodulatory function of keratinocytes and lymphocytes.

Topical vitamin D3 has relatively recently been introduced for the treatment of psoriasis. Synthetic vitamin D3 analogues with a high potential for inducing differentiation of cells, but with a low hypercalcemic effect have recently been developed. One such synthetic analogue of 1,25-dihydroxyvitamin D3 (calcitriol), 22-oxacalcitriol (OCT), is a novel agent for the topical treatment of psoriasis. The activity of OCT in vitro was investigated and compared with that of a series of vitamin D3 analogues as to their ability to inhibit murine T lymphocyte proliferation stimulated by con-A, to suppress IL-6 and IL-8 production by keratinocytes stimulated with IL-1alpha and TNFalpha, and to inhibit AP-1- and NFkappaB-dependent reporter gene expression. OCT inhibited the proliferation of lymphocytes and suppressed IL-8 and IL-6 production by keratinocytes to the same extent as the other vitamin D3 analogues. It also inhibited AP-1- and NFkappaB-controlled luciferase activity to the same extent as the other vitamin D3 analogues, which demonstrates its mechanism of action in the suppression of inflammatory processes.

Total excision of a thalamic arteriovenous malformation using an orbito-fronto-malar approach: case report.

A 37-year-old woman was admitted to Osaka Neurological Institute after the sudden onset of left hemiplegia, hemihypesthesia, and ipsilateral hemianopia on February 4, 1992. Computed tomography (CT) disclosed the presence of hemorrhage in the right thalamus extending to the ipsilateral internal capsule. Cerebral angiography after CT scanning disclosed the presence of a cerebral arteriovenous malformation (AVM) fed by copsulothalamic and lateral geniculate body arteries originating from the right anterior choroidal artery. She was operated on with removal of the AVM using a right orbito-fronto-malar approach (OFM approach), which did not require transection of the cerebral parenchyma. The anterior choroidal artery could be followed distally from its origin and small feeding branches originating from the parent artery were easily identified, and the cerebral base could be examined in greater detail than with the conventional frontotemporal approach. The nidus could be excised in its entirety without difficulty. Postoperative angiography confirmed total excision of the AVM. She was transferred to another hospital for rehabilitation on April 13, 1992. Motor strength on the left side had improved to 3/5 by that time. The OFM approach appears to be potentially useful for the resection of inferolateral thalamic AVMs, because it does not require corticotomy and feeding branches can be identified and dealt with prior to other surgical manipulations.

Secretory meningioma with elevated serum carcinoembryonic antigen level.

We recently encountered a 68-year-old woman with right sphenoid wing meningioma of the secretory type accompanied by an elevated serum carcinoembryonic antigen level. This case was neuroradiologically characterized by marked brain edema. Histologically, the lesion was rated as having meningothelial components and was rich in blood vessels and pseudopsammoma bodies. Carcinoembryonic antigen, epithelial membrane antigen, keratin, and cytokeratin were immunohistochemically detected in the pseudopsammoma bodies and the cells producing these bodies.

Multiple intramedullary spinal sarcoidosis: case report.

BACKGROUND: According to past reported cases, spinal intramedullary sarcoidosis has the radiologic characteristics of a single enhanced lesion with cord swelling. However, it is difficult to make a diagnosis using only radiologic examinations. Including our case, 20 cases have been reported of intramedullary spinal sarcoidosis. Only six cases were diagnosed as primary spinal sarcoidosis. We present a rare case of multiple spinal intramedullary sarcoidosis without cord swelling. CASE DESCRIPTION: This 63 year-old man was afflicted with progressive paraparesis and numbness of the lower extremities. Magnetic resonance imaging showed intramedullary lesions without cord swelling. The patient underwent biopsy for diagnosis and the specimen showed a noncaseating granuloma mainly composed of epitheloid cells. Postoperative corticosteroid therapy was effective and the lesion disappeared 1 month after the operation. CONCLUSIONS: Biopsy is a less invasive method and is useful for early diagnosis. Early diagnosis is important for spinal sarcoidosis so that high-dose corticosteroid therapy can be commenced while the lesion still has a good chance of being successfully treated.

Spinal intramedullary ependymal cyst: a case report.

BACKGROUND: Spinal intramedullary ependymal cysts are extremely rare. Only seven pathologically proven cases have been reported in the literature. METHOD: We present an 18-month-old female with thoracic spinal intramedullary ependymal cyst that was diagnosed pathologically. RESULTS: Histological diagnosis was made by light microscopy after immunostaining. After partially removing the cyst wall and establishing communication between the cyst and the subarachnoid space, the patient improved neurologically. CONCLUSIONS: For spinal intramedullary ependymal cyst we recommend diagnosis by MR imaging without myelography, then enucleation of the cyst, if possible. Otherwise, we remove the cyst wall as much as possible and create adequate communication between the cyst and the subarachnoid space.

Anastomosis of occipital artery to anterior inferior cerebellar artery with interposition of superficial temporal artery. Case report.

A 56-year-old man with vertebrobasilar insufficiency and associated findings including quadriparesis, dysarthria, cerebellar ataxia, nystagmus, and somnolence underwent left occipital artery (OA) to anterior inferior cerebellar artery (AICA) anastomosis with interposition of a superficial temporal artery (STA) graft. This procedure was chosen because cerebral angiograms demonstrated occlusion of the right vertebral artery (V3) and severe stenosis of the V4 segment of the left vertebral artery, with perfusion of the territory of the left posterior inferior cerebellar artery via the ipsilateral AICA, and because dissection of the OA is a relatively difficult and time-consuming procedure. Dissection of the STA, on the other hand, is much easier. Preoperative measurements of local cerebral blood flow in the vertebrobasilar circulation before and after intravenous administration of acetazolamide (500 mg) were obtained, and demonstrated low flow and hemodynamic compromise in the posterior circulation. The patient's hemodynamic and neurological status improved following surgery. In this report, we present a new and simplified method of OA-AICA anastomosis with interposition of STA graft.

Intradural spinal hibernoma: case report.

BACKGROUND: Hibernoma is a rare, benign tumor arising from vestigial remnants of brown adipose tissue. It usually affects muscle and subcutaneous tissue and is asymptomatic and slow growing. METHODS: A review of the worldwide literature contains about 110 cases of hibernomas. However, only two cases (including our case) of hibernoma located in the intradural spine have been reported. We present an extremely rare case of intradural extramedullary spinal hibernoma and summarize the magnetic resonance imaging (MRI) findings of the lesion. CASE DESCRIPTION: A 35-year-old woman suffered from motor weakness and numbness of the left upper extremity. Cervical spinal MRI revealed an intradural extramedullary mass at C7. She underwent surgery via the posterior approach and the lesion was completely removed. Histopathologic examination showed multivacuolated cells with centrally placed nuclei, and the diagnosis of hibernoma was made. CONCLUSIONS: Because the CT and MRI findings of hibernoma are almost same as those of other lipomatous tumors, a surgical specimen of this tumor is necessary to establish the correct diagnosis. Early diagnosis and total resection are necessary as some cases showed malignant features or rapid growth. Etiologically, the tumor may have developed by the ectopic growth or migration of adipose tissue.

Improvement of T2-weighted images of central nervous system by motion artifact suppression technique (MAST).

Standard spin echo sequences of MRI with and without motion artifact suppression technique (MAST) were compared in 45 paired images of brain and 21 paired images of spine. The images were obtained on a Picker 1.5 T system with TR = 2 sec and TE = 100 or 120 msec. MAST is a method of refocusing transverse magnetization at echo time by modification of the gradient waveforms. Transverse, coronal, and sagittal planes of brain were compared in 10 paired images obtained from adults and five paired images from children. The spine was studied in sagittal images, 11 cervical images of adults, five lumbar images of adults, and five lumbar images of children. MAST was proven to be valuable not only for the detection of lesions but also for picturing anatomical details as in MR-cisternography and MR-myelography and the effects of iron ions. MAST improves significantly the quality of T2-weighted images, especially in children.

Lateral approach for anterior thoracic spinal lesions.

A lateral approach, consisting of a modified transversectomy, hemilaminectomy, and adequate transversectomy with costectomy of 7-8 cm, was used to treat four cases of anterior or anterolateral thoracic lesions, including two cases of thoracic disc herniations, one of thoracic meningioma, and one of hypertrophic pachymeningitis. All patients presented with gait disturbance, but recovered well postoperatively except for one who needed rehabilitation of the lower extremities. This approach provides a greater access to the anterior thoracic canal, and can achieve effective anterior decompression, and a good outcome for thoracic spinal disease if recognized early.

Cervical ventral epithelial cyst treated by anterior corpectomy--case report.

A 15-year-old boy presented with a cervical ventral epithelial cyst manifesting as intractable cervical pain. Neurological examination revealed weakness of his left grasp and increased deep tendon reflexes. The anterior approach was selected because the lesion was located directly ventral to the spinal cord. He underwent C4-5 anterior corpectomy and subtotal resection of the cyst wall. He made a good recovery without additional deficits. Most previously reported cases have been treated using the posterior approach despite the ventral location of the lesion. The anterior approach offers a safer and more effective means of treating such lesions because it allows direct access to the lesion without manipulation of the spinal cord.