Biomedical subjects
Publications and source records attributed to T Sugimoto.
In a 19-year-old patient with status epilepticus arising in the right parietal neocortex, unenhanced ictal MRI showed abnormalities mainly in the right cerebral cortex, contralateral cerebellum, and ipsilateral thalamus. The thalamus is considered a key site of functional abnormality in this patient.
Membrane conductance of cultured rabbit articular chondrocytes was characterized by means of the patch-clamp technique. The resting membrane potential of the articular chondrocytes was about -42 mV. The membrane potential shifted in accordance with the prediction by the Nernst equation for Cl- when intracellular and extracellular concentrations of Cl- were changed. On the other hand, change in extracellular concentration of K+ produced no shift in the membrane potential of chondrocytes. The Cl- channel blocker 4-acetamido-4'-isothiocyanatostilbene-2'2-disulfonic acid (SITS) depolarized the membrane potential. These findings suggest that the membrane potential of the chondrocytes is determined mainly by Cl- conductance. Using the cell-attached patch-clamp method, a large unitary conductance of 217 pS was observed in the articular chondrocytes. The unitary current was reversibly blocked by SITS. Therefore, the unitary current was carried by Cl-. The Cl- channel showed voltage-dependent activation and the channels exhibited long-lasting openings. Therefore, the membrane potential of rabbit cultured articular chondrocytes was mainly determined by the activities of the large-conductance and voltage-dependent Cl- channels.
The co-expression of vanilloid receptor 1-like receptor (VRL-1), a newly cloned capsaicin-receptor homologue, with calbindin D-28k was examined in the rat sensory ganglia. The co-expression was rare in the dorsal root, trigeminal and jugular ganglia and abundant in the petrosal and nodose ganglia. In the dorsal root ganglion, none of VRL-1-immunoreactive (ir) neuron co-expressed calbindin D-28k-immunoreactivity (ir). Of the VRL-1-ir neurons, 9 and 5% showed calbindin D-28k ir in the trigeminal and jugular ganglia, respectively. On the other hand, 35 and 63% of VRL-1-ir neurons in the petrosal and nodose ganglia, respectively, co-expressed these substances. The retrograde tracing method indicated that petrosal neurons which co-expressed VRL-1-and calbindin D-28k-ir innervated taste buds in the circumvallate papilla. The present findings may suggest that VRL-1 is associated with chemosensory functions in visceral sensory neurons.
We examined the relationship between the presence of esophageal hiatal hernia (HH) assessed by endoscopy and the presence of vertebral fractures (VFs) in 87 Japanese postmenopausal women (age range 52-87 years). We found that 29 (63%) of 46 patients with HH (71.2+/-6.1 years, mean +/- SD) had one or more VFs, compared with 14 (34%) of 41 patients without HH (70.8+/-6.8 years), which was a significant difference in the frequency of VFs (c2 = 7.242; p = 0.0071). The average number of VFs per patient was significantly higher for the patients with HH than for those without HH (1.67+/-1.75 vs 0.68+/-1.21, p = 0.0032). There were no significant differences in absolute or age-matched bone mineral density (BMD) values at the lumbar spine (0.656+/-0.131 vs 0.662+/-0.148 g/cm2; Z-score, -0.35+/-1.17 vs -0.26+/-1.00) and there were no significant differences in biochemical parameters, age, years since menopause or body mass index (BMI) between the two groups. When patients were divided into those with reflux esophagitis (RE) (n = 30, 70.2+/-7.3 years) and those without RE (n = 57, 71.4+/-5.9 years), no significant differences were detected in any of the above parameters including the presence or number of VFs. The patients were further subdivided into four groups: those with 'HH only' (n = 23, 72.3+/-4.6 years), with 'RE only' (n = 7, 70.9+/-7.7 years), with 'both' (n = 23, 70.0+/-7.3 years) and with 'neither' (n = 34, 70.8+/-6.7 years). One or more VFs were found in 12 (52%), 1 (14%), 17 (74%), and 13 (38%) patients in each group, respectively, and the difference in frequency was significant (c2 = 10.748; p = 0.0132). The average number of VFs per patient in each group was 1.57+/-2.06, 0.14+/-0.38, 1.78+/-1.41 and 0.79+/-1.30, respectively, and there were significant differences between the 'both' and 'neither' groups, and between the 'both' and 'RE only' groups (p<0.05). When univariate logistic regression analysis was performed with the presence of HH as a dependent variable and each of the presence of VFs, the number of VFs per patient, absolute or age-matched BMD values at the lumbar spine, BMI and plasma albumin as independent variables, the presence of VFs and the number of VFs per patient were selected as indices affecting the presence of HH (odds ratio: 3.29 and 1.59, 95% confidence interval: 1.36-7.94 and 1.14-2.23; p=0.0080 and 0.0064, respectively). These results show that the presence and severity of VFs are associated with the presence of HH but not of RE in Japanese postmenopausal women, and suggest that kyphosis induced by multiple VFs might predispose elderly women to a complication with HH.
Immunohistochemistry for parvalbumin, calbindin D-28k, calretinin and calcitonin gene-related peptide (CGRP) was performed on the trigeminal ganglion and oro-facial tissues in Brn-3a wildtype and knockout mice at embryonic day 18.5 and postnatal day 0. In wildtype mice, the trigeminal ganglion contained abundant parvalbumin-, calbindin D-28k- and CGRP-immunoreactive neurons while the ganglion was almost devoid of calretinin-immunoreactive neurons. In Brn-3a knockout mice, a 63% decrease of parvalbumin-immunoreactive neurons was detected. In contrast, the absence of Brn-3a dramatically increased the number of calbindin D-28k-immunoreactive (3.5-fold increase) and calretinin-immunoreactive neurons (91-fold increase). The number of CGRP-immunoreactive neurons, however, was not altered by the Brn-3a deficiency. Cell size analysis indicated that loss of Brn-3a increased the proportions of small (<100 microm (2)) parvalbumin-, calbindin D-28k- and CGRP-immunoreactive neurons while it decreased those of large (>200 microm(2)) immunoreactive cells. Calretinin-immunoreactive neurons were either small or medium (100-200 microm (2)) in mutant mice. The oro-facial tissues contained parvalbumin-, calbindin D-28k- and CGRP-immunoreactive fibers, but not calretinin-immunoreactive ones in wildtype mice. In Brn-3a knockout mice, the number of parvalbumin-immunoreactive fibers markedly decreased in the infraorbital nerve and parvalbumin-immunoreactive endings disappeared in the vibrissa. In contrast, the number of calbindin D-28k-immunoreactive fibers increased significantly in the infraorbital and mental nerves. In addition, calbindin D-28k-immunoreactive endings appeared in the vibrissa. As well, some fibers showed calretinin-immunoreactivity in the infraorbital nerve of the mutant. However, no obvious change of CGRP-immunoreactive fibers was observed in the oro-facial region of knockout mice. Taken together, our data suggest that Brn-3a deficiency has effects on the expression of neurochemical substances in the trigeminal ganglion.
Infant acute lymphoblastic leukemia (ALL) is characterized by the presence of the proB phenotype (CD10(-)/CD19(+)), poor prognosis and frequent rearrangement of the mixed lineage leukemia (MLL) gene. The most frequent rearrangement is t(4;11)(q21;q23), the role of whose product, the MLL-AF4 fusion transcript, has been extensively studied in leukemogenesis. In a cell line of infant leukemia with MLL rearrangement denoted KP-L-RY, panhandle PCR amplification of cDNA revealed the presence of a fusion transcript, MLL-AF5q31, indicating that AF5q31 is also a partner gene of MLL. In this fusion transcript the MLL exon 6 is fused in frame to the 5' side of the putative transactivation domain of AF5q31. The AF5q31 protein is a member of the AF4/LAF4/FMR2-related family of proteins, which have been suggested to play a role in hematopoietic cell growth and differentiation. The MLL-AF5q31 fusion transcript, although probably rare, appears to be associated with the pathogenesis of infant ALL like MLL-AF4. Co-expression of HoxA9 and Meis1 genes in the KP-L-RY cell line indicated possible functional similarity between MLL-AF4 and MLL-AF5q31. Further understanding of the function of AF5q31 as well as the specific leukemogenic mechanism of MLL-AF5q31 awaits future studies.
BACKGROUND: Liver resection of segments VII and/or VIII sometimes requires segmental resection of the right hepatic vein in patients with liver tumours invading or located close to the hepatic vein. In this situation, hepatic vein reconstruction is thought to have an important role in the postoperative function of segment VI. This study investigated whether preoperative embolization of the major hepatic vein could obviate the need for hepatic vein reconstruction after cranial partial resection of the liver including the major hepatic vein trunk in a preclinical model. METHODS: Sixteen beagles were divided into two groups of eight: control group (hepatectomy alone) and hepatic venous embolization (HVE) group (hepatectomy after HVE). HVE was performed 2 weeks before hepatectomy. All dogs underwent resection of the cranial third of the left lateral liver lobe together with the major trunk of the left hepatic vein. Following hepatectomy, survival, histological features, portal venous pressure and serum aspartate aminotransferase (AST) levels were determined. RESULTS: Six control animals and seven in the HVE group were alive 1 week after hepatectomy. Immediately after hepatectomy, portal venous pressure was significantly higher in the control group compared with the HVE group (mean(s.d.) 14.0(1.1) versus 8.1(1.0) mmHg; P < 0.01). Histological examination of the remnant left lateral lobe demonstrated patchy parenchymal haemorrhage in the control group and normal parenchymal architecture in the HVE group. Peak AST levels were observed on day 1 in both groups and were significantly higher in the control group (mean(s.d.) 182(42) versus 67(40) units/l; P < 0.01). CONCLUSION: In this model, preoperative HVE facilitated interlobar venous collateral formation and minimized the untoward effects of segmental hepatic vein resection. This procedure may obviate the need for hepatic vein reconstruction after cranial partial liver resection including the major hepatic vein.
Plasma macrophage colony-stimulating factor (M-CSF) levels were measured in 13 haematologic patients treated with autologous peripheral blood stem cell transplantation (PBSCT). Six of the patients showed an increase in M-CSF peak levels (>3000 pg/ml) during the conditioning and stem cell infusion period. The peak levels of M-CSF in this phase correlated with thrombomodulin levels, indicating the endothelial origin of plasma M-CSF. However, the M-CSF levels were not influenced by TNFalpha. More patients with high M-CSF levels (>5000 pg/ml) suffered from organ failure than those with lower M-CSF levels. These results suggest that high M-CSF levels may correlate with cellular or organ damage in patients treated with PBSCT.
We previously reported an automatic method for quantitative analysis of schistocytes or fragmented red cells using an automatic hematology analyzer, XE-2100. In the study reported here, we evaluated the accuracy of this detection method in patients with thrombotic microangiopathy (TMA). A follow-up study was performed on 14 patients with two types of TMA, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. Schistocyte percent was evaluated both with an automatic counter and by means of microscopic observation. Total activity and isoenzyme pattern of lactate dehydrogenase (LD) were also determined. In these patients, schistocyte percent determined by automatic counting correlated highly with that determined by manual counting under microscopic observation (r = 0.852, P < 0.0001). Schistocyte percent was shown to correlate significantly with isoenzyme fractions 1 and 2 of LD (r = 0.732, P < 0.02), reflecting hemolysis. Nine of 11 patients tested had high concentrations of LD isoenzyme five without distinct liver damage, and schistocyte percent did not relate to fraction 5 of LD. Automatic detection of schistocyte percent using a hematology analyzer was useful for an accurate diagnosis and follow-up of thrombotic microangiopathy. The origin of LD fraction 5 remains to be determined.
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A 19-year-old female with aplastic anemia who developed subglottal aspergillosis is reported. She presented with fever, cough and stridor. Inspiratory dyspnea progressed rapidly and emergent tracheostomy was performed, which confirmed the diagnosis. In spite of intensive anti-fungal treatment combined with adoptive immunotherapy, Aspergillus infection expanded and she died of pulmonary aspergillosis. Autopsy revealed the fungal mass obstructing the trachea and disseminated pulmonary aspergillosis. Difficulties in diagnosis and management of subglottal Aspergillus infection are discussed.
A 53 year old woman presented with a lump in the inner lower quadrant of the left breast. Histological examination of the breast tumour confirmed that the lesion was a mammary hamartoma. Carcinoma with foci of microinvasion was observed in the lobules of the hamartoma concomitant with the intraductal spread of lobular carcinoma. Immunohistochemically, the cancer cells were negative for beta-catenin, which generally stained normal breast ducts and ductal carcinomas. This is only the sixth case of breast carcinoma arising in a mammary hamartoma to be reported and, moreover, the fourth case of lobular carcinoma occurring within a hamartoma. Despite the apparent rarity of this case, pathologists should be aware of the possibility of carcinomas arising within mammary hamartomas.
In recent years the number of the patients with occlusive disease of the peripheral arteries is increasing also in Japan. For such patients there are many methods to make final diagnosis. Among a lot of methods we have chosen color duplex sonography for functional diagnosis in the patients with occlusive disease of the peripheral artery. During 2 years we have investigated color duplex sonography in addition to digital subtraction arteriography for 40 patients (68 limbs) with occlusive disease of the peripheral artery. First of all waveform of blood flow and the systolic velocities of the dorsal- and the posterior tibial arteries as well as the brachial artery were observed and measured. The blood flow volume and the ratio of systolic velocities and flow volume of lower to upper extremity (AVI, AFI) were measured and their values were also analysed in each patient. These data were compared with Fontaine's classification as a clinical symptom. For the patients with Fontaine class I, or II conservative treatments were carried out, and operative interventions such as bypass graft, or endovascular operation were carefully performed for the patients with Fontaine's class III or IV. Consequently, clinical symptoms and waveforms of systolic flow, and its velocity were remarkably improved by surgical interventions. Thus, color duplex sonography was a useful procedure to make diagnosis and to decide operative indication in the patients with occlusive disease of the peripheral artery.
[reaction: see text] An efficient synthesis of the C10-C31 (BCDEF ring) portion of pinnatoxin A has been achieved. The key step is a highly stereoselective construction of the dispiroketal (BCD ring) system employing an intramolecular hetero-Michael reaction of a reversibly formed hemiketal alkoxide through the use of LiOMe.
Osteopontin-immunoreactivity (OPN-ir) was examined in the oro-facial tissues and trigeminal sensory nuclei (principal sensory nucleus and spinal trigeminal nucleus) to ascertain the peripheral ending and central projection of OPN-containing primary sensory neurons in the trigeminal ganglion (TG). No staining was observed using mouse monoclonal anti-OPN antibody preabsorbed with recombinant mature OPN. OPN-immunoreactive (ir) peripheral endings were classified into two types: encapsulated and unencapsulated types. Unencapsulated endings were subdivided into two types: simple and complex types. Simple endings were characterized by the thin neurite that was usually devoid of ramification. These endings were seen in the hard plate and gingiva. The complex type was characterized by the thick ramified neurite, and observed in the vibrissa, hard palate, and molar periodontal ligament. Encapsulated endings were found only in the hard palate. The trigeminal sensory nuclei contained OPN-ir cell bodies and neuropil. The neuropil was devoid of ir in laminae I and II of the medullary dorsal horn (MDH), and had various staining intensities in other regions of the trigeminal sensory nuclei. Transection of the infraorbital and inferior alveolar nerves caused an increase of OPN-ir intensity in ipsilateral TG neurons. The staining intensity of the neuropil also increased in the trigeminal sensory nuclei ipsilateral to the neurotomy excepting laminae I and II of the MDH. The present study indicates that OPN-ir primary sensory neurons in the TG innervate encapsulated and unencapsulated corpuscular endings. Such neurons probably project their central terminals to the trigeminal sensory nuclei except for the superficial laminae of the MDH.
Nociceptin peptide-receptor system is known to be essential for the regulation of hearing ability. The mRNA for nociceptin precursor protein is highly expressed in the brainstem. We explored a detailed hybridohistochemical expression pattern of the nociceptin precursor mRNA in the mouse brainstem, and identified positive cells in several auditory brainstem nuclei. Positive cells were seen in the dorsal and ventral nuclei of the lateral lemniscus, the rostral periolivary region, the lateroventral and medioventral periolivary nuclei, the dorsal periolivary region, the superior paraolivary nucleus, and the external cortex and dorsal cortex of the inferior colliculus. Of these, the medioventral and lateroventral periolivary nuclei, the major sites of origin of olivocochlear bundle, were most populated by positive cells.
Spontaneous transient outward currents have been found in peripheral neurons and smooth muscle cells, but rarely in central neurons. Using a nystatin-perforated patch clamp technique, we succeeded in recording spontaneous transient outward currents in mouse dentate gyrus granule cells. Nociceptin/orphanin FQ increased the amplitude and frequency of transient outward currents. We consider modulation of spontaneous transient outward currents to be a new means to regulate cell activity in central neurons, and studied their characteristics and mechanism of augmentation. The whole-cell current-voltage relationship showed outward rectification and the reversal potential was close to the equilibrium potential for K+. The frequency of spontaneous transient outward currents increased at depolarized potentials. Tetraethylammonium, iberiotoxin and a Ca2+ chelator BAPTA-AM inhibited spontaneous transient outward currents. These results suggest the involvement of large-conductance Ca2+-activated K+ channels. Single-channel recordings in the inside-out configuration revealed Ca2+-activated K+ channels with a conductance ranging from 82 to 352 pS. The augmenting effect of nociceptin/orphanin FQ was cancelled by [Phe1psi(CH2-NH)Gly2]Nociceptin(1-13)NH2. Cd2+ did not affect the transient outward currents or augmentation by nociceptin/orphanin FQ. Whereas nociceptin/orphanin FQ, theophylline and cyclic ADP ribose induced transient outward currents with short duration observed under control conditions, inositol 1,4,5-trisphosphate induced transient outward currents with long duration, in addition to those with short duration. Ryanodine inhibited nociceptin/orphanin FQ from augmenting spontaneous transient outward currents. Our data suggest that Ca2+ sparks transiently activate large-conductance Ca2+-activated K+ channels to induce transient outward currents. Nociceptin/orphanin FQ probably sensitizes ryanodine receptors and increases transient outward currents to reduce cell excitability.
T-cell prolymphocytic leukemia (T-PLL) is a postthymic T-cell neoplasm with a characteristic morphology and heterogeneous immunophenotype. Most cases of T-PLL express membrane T-cell receptors (TCRs) of the alphabeta phenotype. We experienced a 30-year-old man suffering from TCRgammadelta T-cell leukemia with morphology compatible to T-PLL with a postthymic phenotype. He was admitted with skin eruption and pancytopenia. Peripheral blood and bone marrow were occupied with medium-sized lymphocytes, which had moderately condensed chromatin with a single nucleolus and sparse, nongranular basophilic cytoplasm. The immunophenotype was CD1a-, CD2-, CD3+, CD4-, CD5+, CD7+, CD8-, and terminal deoxynucleotidyl transferase negative. Hepatosplenomegaly was absent. He was diagnosed as having T-PLL and was treated with combination chemotherapy. Six months later the leukemic cell became chemoresistant. Although the patient showed transient improvement in response to pentostatin, he died 13 months after the diagnosis. To our knowledge, this is the first case of T-PLL with a TCRgammadelta phenotype.