On-line identification of fermentation processes for ethanol production.

A strategy for monitoring fermentation processes, specifically, simultaneous saccharification and fermentation (SSF) of corn mash, was developed. The strategy covered the development and use of first principles, semimechanistic and unstructured process model based on major kinetic phenomena, along with mass and energy balances. The model was then used as a reference model within an identification procedure capable of running on-line. The on-line identification procedure consists on updating the reference model through the estimation of corrective parameters for certain reaction rates using the most recent process measurements. The strategy makes use of standard laboratory measurements for sugars quantification and in situ temperature and liquid level data. The model, along with the on-line identification procedure, has been tested against real industrial data and have been able to accurately predict the main variables of operational interest, i.e., state variables and its dynamics, and key process indicators. The results demonstrate that the strategy is capable of monitoring, in real time, this complex industrial biomass fermentation. This new tool provides a great support for decision-making and opens a new range of opportunities for industrial optimization.

[Management of quadruple valves for severe infective endocarditis; report of a case].

A 74-year-old man had pustulant bilateral arthritis complicated with sepsis and disseminated intravascular coagulation (DIC). Microbiologic study of blood sample showed Streptococcus and methicillin resistant Staphylococcus aureus (MRSA). He was complicated with postulant diskitis since then. Medical treatment for DIC and administration of antibiotics were performed. Preoperative echocardiography revealed massive aortic regurgitation and vegetation of aortic valve, moderate pulmonary regurgitation and vegetation of pulmonary valve, massive mitral regurgitation, massive tricuspid regurgitation. He was diagnosed as infective quadruple valve endocarditis. He received aortic valve replacement, pulmonary valve replacement, mitral valve repair and tricuspid valve repair. Postoperative echocardiography showed satisfactory function of bioprosthesis. Postoperative course was uneventful.

[Patient-prosthesis mismatch after aortic valve replacement; tolerable lower limit of indexed effective orifice area].

This study was aimed at determining the tolerable lower limit of the indexed effective orifice area (EOAI) to prevent patient-prosthesis mismatch (PPM). Echocardiography was performed in 87 consecutive patients who underwent aortic valve replacement (AVR). EOAI was estimated for each type and size of prosthesis and used to define PPM as moderate if >0.65 cm2/ m2 and < or = 0.85 cm2/m2, and severe if < or = 0.65 cm/m2. Aortic valve pressure gradients, left ventricular dimensions, and outcome (in-hospital and 1-year) were analyzed in the presence or absence of abnormal gradients (> or = 40 mmHg) to assess the influence of a small valve (19 mm or less labeled size). Severe PPM was found in 23% of all patients, and 50% of the severe PPM patients had an abnormal gradient. There was 1 death and 1 brain damage from ventricular fibrillation because of severe PPM in the abnormal gradient group with a small valve. In PPM patients with a small valve, EOAI (0.61 +/- 0.04 vs 0.69 +/- 0.07) and preoperative interventricular septal thickness (IVST : 16.4 +/- 2.6 mm vs 13.5 +/- 1.5 mm) were significantly different between abnormal and normal gradient groups. An EOAI > or = 0.69 appeared to be tolerable in patients with a lower level of hypertrophy (IVST < 16 mm).

A rare case of shunt malfunction attributable to a broken Codman-Hakim programmable shunt valve after a blow to the head.

We report a rare case of shunt malfunction resulting from breakage of the Codman-Hakim programmable shunt valve system following a blow to the head. Originally, the patient had suffered intraventricular hemorrhage a month after birth; ventriculoperitoneal shunt was performed at 7 months. After that, the shunt valve functioned well for 7 years. The patient presented with headaches after receiving a blow behind the right ear. The headache became exacerbated with activity and improved with rest. Damage to the shunt valve was identified during surgery, with a crack at the top of the valve housing. Symptoms resolved following a change of the complete shunt system. The possibility of damage to the shunt valve following a blow should be considered in shunt patients presenting with headaches.

[Secondary abnormal development of the bronchial artery: report of a case].

A 65-year-old man was admitted to our hospital because of massive hemoptysis. The patient had suffered from pneumonia since 1999, but he had refused to undertake further examinations. In 2002, the patient was transferred to our emergency room because of massive hemoptysis. Following endotracheal intubation, the patient underwent bronchial artery embolization. The X-ray and computed tomography (CT) films on admission revealed localized bronchiectasis in the left upper lung. Bronchoscopic findings revealed massive bleeding from the left upper bronchus. Bronchial arteriography of the left bronchial artery showed peripherally hypervascular finding in the left upper lobe. A segmentectomy of the left upper division was performed as a radical therapy for localized lesions with massive hemoptysis. The pathological diagnosis was secondary abnormal development of the bronchial artery. We speculated that massive hemoptysis had occurred probably due to infection in the focus.

Unique Colony Housing the Coexisting Escherichia coli and Dictyostelium discoideum.

Two well-characterized and phylogenetically diverse species, Escherichiacoli and Dictyostelium discoideum, were used as the modelorganisms. When the two species were mixed and allowed to grow onminimal agar plates at 22 (°)C, instead of the predator Dictyostelium exterminating E.coli, the two species remarkablyachieved a state of stable coexistence in about two weeks. In addition, theemerged colonies housing the coexisting species have a mucoidal naturethat is distinctive from its origin. The simplicity of the system and the shorttime span for the two species to develop the coexistence state, that isproven stable and reproducible on laboratory conditions, hence, providesa new model system for the study of symbiosis, particularly with referenceto the initial stages.

Fourteen year experience with the omnicarbon prosthetic heart valve.

The Omnicarbon prosthetic valve was implanted in 168 patients (mean age, 53 years); 84 had aortic valve replacement (AVR), 57 had mitral valve replacement (MVR), and 27 had both aortic and mitral valve replacement (DVR). The mean follow-up period was 6.8 years, with a maximum of 13.7 years. Three patients (1.8%) were lost to follow-up. There were 4 (2.4%) early deaths and 26 late deaths. Survival at 10 years was 76% in the AVR and MVR groups, and 85% in the DVR group. Freedom from thromboembolism at 10 years was 94% in the AVR group, 80% in the MVR group, and 92% in the DVR group. Freedom from hemorrhagic complications at 10 years was 86% in the AVR group and 92% in the MVR group. At 10 years, 97% in the AVR group and 96% in the MVR group were free from endocarditis. One patient in the DVR group suffered a paravalvular leak. At 10 years, 97% in the AVR group and 95% in the MVR group had not needed reoperation. Elevation of the postoperative serum lactate dehydrogenase levels were acceptable in the three groups. In conclusion, the Omnicarbon prosthetic valve has shown excellent long-term clinical results.

An unusual complication associated with the Carpentier-Edwards porcine bioprosthesis.

Primary tissue failure of bioprosthetic heart valves refers primarily to calcification of the leaflets of the bioprosthesis. A 75 year old patient underwent reoperation 15 years after mitral valve replacement with a Carpentier-Edwards porcine bioprosthesis. The extracted bioprosthetic valve was found to have one prolapsed leaflet and a small amount of calcification on all three leaflets without tear or perforation. The two commissures suspending the prolapsed leaflet were detached, causing mitral valve regurgitation.

[A case of free-floating ball thrombus in left atrium with mitral stenosis].

We report a rare case of free-floating ball thrombus in the left atrium with mitral stenosis. The patient was 71-year-old woman who admitted to the local hospital for transient ischemic attack. Electrocardiography showed atrial fibrillation and an echocardiogram examination revealed free-floating ball thrombus in the left atrium with mitral stenosis. She was transferred to our hospital for emergency open heart operation. After removal of the ball thrombus, mitral valve replacement and modified MAZE procedure were successfully performed. The size of the ball thrombus was 40 x 30 x 33 mm and weighed 20 g. Postoperative course was uneventful.

Age changes of neuromuscular junctions in the extensor digitorum longus muscle of spontaneous thymoma BUF/Mna rats. A scanning and transmission electron microscopic study.

BUF/Mna rats spontaneously develop thymomas and cause muscle weakness of hind legs at an advanced age. This rat strain has been recognized as a suitable animal model for human myasthenia gravis or related myopathies. To characterize the structural changes of neuromuscular junctions (NMJs) in BUF/Mna rats, subneural apparatuses (SNAs) of extensor digitorum longus muscles of young-adult (4-month-old) and aged (22- to 25-month-old) male rats were examined using scanning and transmission electron microscopy. The SNAs of NMJs in young rats consist of complex labyrinthine gutters with numerous slit-like junctional folds. SNAs in aged BUF/Mna rats, however, are characterized by: (1) a group of cup-like depressions with very wide slit-like junctional folds in relatively large muscle fibers (the major type), (2) the presence of slit-like folds on the flat sarcoplasm outside the cup-like depressions or on the protruded sarcoplasm, and (3) winding gutters or a small number of round depressions with poorly developed synaptic folds in small and medium-sized muscle fibers (the minor type). Since similar structural changes have been reported in dystrophic mice or normally aged rats, it is suggested that both the slowly progressing muscle atrophy and age-dependent turnover of muscle fibers may occur in the aged BUF/Mna rats.

[Malignant peripheral nerve sheath tumor with divergent cartilage differentiation from the acoustic nerve: case report].

Malignant peripheral nerve sheath tumors(MPNSTs) of the acoustic nerve are very rare. Only seven cases of MPNST arising from the acoustic nerve have been reported. The authors present a case of MPNST with divergent cartilage and melanotic differentiation of the acoustic nerve. The patient was a 69 year old man admitted to our neurosurgical service in January 1999 complaining of left facial nerve palsy and hearing difficulty of his left ear. The initial CT showed a tumor at the left cerebellopontine angle region. On MRI the tumor was depicted as low intensity on T 1-weighted image and high intensity on T 2-weighted image, the mass was heterogeneously enhanced after administration of Gd-DTPA. The partial removal of the tumor was performed in January 1999. He was discharged February 1999. But he was admitted again because of progressive cerebellar ataxia. MRI showed the rapid regrowth of the residual tumor. In March 1999, complete removal of the tumor was performed. Histopathological analysis revealed a malignant spindle cell neoplasm with divergent cartilage and melanotic differentiation. We review the relevant literature concerning MPNST of the acoustic nerve and discuss the clinical features of malignant eighth cranial nerve tumor.

[Clinical evaluation of granisetron hydrochloride for nausea and vomiting induced by oral anticancer drugs].

We investigated the antiemetic effect, safety and usefulness of granisetron hydrochloride tablets on nausea and vomiting induced by oral anticancer drugs used in chemotherapy for gastric cancer and colorectal cancer. In the present trial, oral administration of granisetron hydrochloride was performed during 5 days after nausea or vomiting. 1) Clinically, the effective rate of granisetron hydrochloride (the percentage of cases in which the drug was assessed as "Remarkably effective" or "Effective") was more than 75% on each day of administration. There were no adverse events or abnormal laboratory tests. 2) In terms of usefulness, granisetron hydrochloride was rated "Extremely useful" or "Useful" in 17 out of 23 cases (78.2%). The above results have shown that granisetron hydrochloride tablets, administrated orally once daily at a dose of 2 mg, have an excellent antiemetic effect, and that this is a safe and useful drug.

Morphological changes of capillaries in the rat soleus muscle following experimental tenotomy.

We examined the structural changes of capillaries in the rat soleus muscle 4, 7, 14, and 35 days after experimental limb tenotomy. In the soleus muscles after tenotomy, muscle fibres degenerated and some of them were destroyed; the muscle did not seem to recover until the 35th day. On the 14th day, some small muscle fibres, probably regenerating muscle fibres, started forming within the basal-lamina tube and remained after necrosis of a pre-existing muscle fibre. Most capillaries at each stage were of the continuous type. However, about 10% of the capillaries around degenerated muscle fibres at days 4, 7 and 14 consisted of endothelial cells with a small number of fenestrae bridged by a single-layered diaphragm. On the 14th day, capillaries around small regenerating muscle fibres also often had a small number of fenestrations. Even on the 35th day, capillaries occasionally had fenestrations. Additionally, some of the fenestrated capillaries formed small pores at the fenestrated portion of the endothelial cells. The untreated muscles contained only continuous capillaries. These findings suggest that fenestrations in the endothelial cells may occur in intramuscular capillaries not only around degenerated muscle fibres but also around regenerating muscle fibres after tenotomy.

Stat6 activation and Th2 cell differentiation [correction of proliferation] driven by CD28 [correction of CD28 signals].

CD28 engagement by specific monoclonal antibody (mAb) or binding of the natural ligands, CD80 and CD86, induces tyrosine phosphorylation of CD28, which in turn recruits and activates the signal transducer and activator of transcription 6 (Stat6). The Stat6 association with CD28 is specifically induced by CD80 or CD86 ligand binding and is not dependent upon the secretion of IL-4 or IL-13. Activated Stat6 translocates to the nucleus and binds to a Stat6-responsive element on the human IL-4 promoter. CD28 ligation induces Stat6-dependent transcriptional activation of a reporter gene under the control of a multimerized Stat6-responsive element fused to an essential part of the IL-4 promoter. Primary stimulation of naive CD4(+) T cells with anti-CD28 mAb in the presence of IL-2, but in the absence of anti-CD3 mAb induces preferential production of IL-4 and expression of CCR4 mRNA after secondary stimulation with anti-CD3, indicating the preferential differentiation of Th2 cells. These findings suggest that initial IL-4 production required for commitment of naive T cells toward Th2 cells may be provided in response to signals delivered via CD28 by antigen-presenting cells.

[Myelopathy caused by tentorial dural arteriovenous fistula: a rare case report].

A 51-year-old man with myelopathy due to intracranial dural arteriovenous fistula (dural AVF) is reported. At age 46, the patient experienced subarachnoid hemorrhage caused by rupture of the dural AVF and underwent embolization of the lesion at another hospital. At this time, the patient complained of numbness in his legs and showed paraplegic gait disturbance. MRI scan revealed swelling of the cervical spinal cord. Cerebral angiograms demonstrated the recurrence of tentorial dural AVF fed by bilateral meningohypopheseal trunks and the right posterior inferior cerebellar artery. Arteriovenous shunt (AV shunt) flow was drained into the anterior spinal vein. It seemed that the swelling of the spinal cord and myelopathy was caused by venous hypertension of spinal veins. After surgical interruption of the right petrosal vein which connected dAVF with cerebellar veins, AV shunt was obliterated successfully. Postoperative cerebral angiograms showed disappearance of dural AVF. The patient became ambulant and his cervical spinal cord appeared normal on the postoperative MRI scan. Surgical interruption of the draining vein was simple, effective and essential treatment.

Postoperative brain complications following retrograde cerebral perfusion.

This study was undertaken to investigate the neurological risk factors associated with the retrograde cerebral perfusion (RCP) technique, by examining the relationship between intraoperative parameters and post-operative brain complications. A total of 12 patients who underwent surgery for thoracic aortic aneurysms using the RCP technique were included in this study. Profound hypothermia was induced through cardiopulmonary bypass which was established with a femoral arterial cannula and bicaval return. During RCP, a venous drainage cannula from the superior vena cava (SVC) was switched over to the arterial return circuit, and oxygenated blood was retrogradely infused through the SVC. The perfusion flow rate was maintained at 273 +/- 113 ml/min and the SVC pressure was maintained at 15 +/- 6 mmHg. The RCP time was 68 +/- 27 min with a range of 27-130 min, and the lowest rectal temperature was 16 +/- 1 degrees C. The total elapsed time until emergence from anesthesia after the operation was 12 +/- 6 h. The operation time correlated with the awakening time (r = 0.729, P = 0.0088). Longer RCP times of up to 101 and 130 min tended to result in post-operative brain damage. The lowest rectal temperature also correlated with the awakening time (r = 0.697, P = 0.0149), and an inverse correlation between the SVC pressure and the awakening time was observed (r = -0. 727, P = 0.0091). These findings demonstrate the importance of reducing both the RCP and operation times to decrease the incidence of brain damage. If carried out under optimal conditions, including perfusion pressure and brain temperature, RCP could be marginally prolonged safely without causing major neurological complications.

[Efficacy of adjuvant hepatic arterial infusion chemotherapy following resection of colorectal liver metastases].

PURPOSE: The aim of this study is to evaluate the effect of adjuvant hepatic arterial infusion chemotherapy (HAIC) following liver resection on the frequency of residual liver recurrence and overall survival. PATIENTS AND METHODS: During 1992 to 1997, 84 patients with liver metastasis from colorectal cancer resected curatively had undergone adjuvant HAIC. The regimen of the HAIC is 1,500 mg of 5-FU by 24-hr continuous infusion once a week for eight weeks. 37 cases in the HAIC group, including patients given more than 7 g of 5-FU, were compared with the control group. RESULT: The cumulative 5-year liver recurrence-free ratios were 72.6% in the HAIC group and 29.8% in the control group (p = 0.0005). The cumulative 5-year survival ratios were 61.4% in the HAIC group and 28.0% in the control group (p = 0.0069). Multivariate analysis revealed that more than 5 mm of surgical margin and adjuvant HAIC significantly decreased the risk of recurrences in residual liver. CONCLUSION: Adjuvant HAIC is an effective procedure to prevent recurrence in residual liver and improve the prognosis of patients with liver metastasis from colorectal cancer.

Augmentation of CTLA-4 expression by wortmannin: involvement of lysosomal sorting properties of CTLA-4.

CTLA-4 (CD152) is transiently induced on the cell surface of activated T cells and expression is limited at a low level. In this study, we investigated the possibility that phosphatidylinositol 3 kinase (PI 3-K) and other related PI kinases associated with the cytoplasmic domain of CTLA-4 are involved in intracellular trafficking and sorting of CTLA-4 protein. Treatment with micromolar concentrations of wortmannin (WN) for >4 h enhanced both cell-surface and intracellular CTLA-4 without affecting its transcriptional activities in a murine mastocytoma cell line transfected with the human CTLA-4 gene and normal activated CD4(+) T cells. However, a more specific PI 3-K inhibitor, LY294002, failed to affect CTLA-4 expression, indicating that the action of WN is independent of conventional PI 3-K activities. WN down-regulated specific association of CTLA-4 with adaptor proteins and its endocytosis. The fact that lysosomotropic agents, ammonium chloride and monensin, enhanced CTLA-4 expression suggests that WN may also block lysosomal sorting and consequent degradation of CTLA-4. Co-localization of CTLA-4 and lysosome-associated membrane protein-1 detected by immunofluorescence microscopy indicates the actual lysosomal sorting of CTLA-4. Our data suggest the existence of WN-sensitive enzymes, which promote lysosomal sorting of CTLA-4. In addition to rapid endocytosis by clathrin-associated adaptor complex, a prompt sorting of CTLA-4 to lysosomes may be one of the regulatory mechanisms for managing CTLA-4 signals in intracellular trafficking pathways.

High incidence of meningioma among Hiroshima atomic bomb survivors.

Since the atomic bomb explosions in Hiroshima and Nagasaki, high incidences of leukemia, thyroid cancer and other tumors have been reported as atomic bomb-induced tumors. We investigated the incidence of meningioma among Hiroshima atomic bomb survivors. Sixty-eight patients surgically treated for meningioma who had been within 2.0 km of the hypocenter of the explosion were identified. Six hundred and seven non-exposed patients with meningioma were also studied. Treatment dates were from 1975 to 1992. The incidences of meningioma among 68 subjects within 2.0 km and 607 non-exposed patients were 8.7 and 3.0 cases per 10(5) persons per year, respectively. The incidences of meningioma among the survivors of Hiroshima in 5-year intervals since 1975 were 5.3, 7.4, 10.1, and 14.9, respectively. The incidences of meningioma classified by distances from the hypocenter of 1.5-2.0 km, 1.0-1.5 km and less than 1.0 km were 6.3, 7.6 and 20.0, respectively. The incidences of meningioma classified by doses to the brain of 0-0.099 Sv, 0.1-0.99 Sv and more than 1.0 Sv were 7.7, 9.2 and 18.2, respectively. The incidence of meningioma among Hiroshima atomic bomb survivors has increased since 1975. There was a significant correlation between the incidence and the dose of radiation to the brain. The present findings strongly suggest that meningioma is one of the tumors induced by atomic bombing in Hiroshima.