Synthesis and permeation behavior of membranes from segmented multiblock copolymers containing poly(ethylene oxide) and poly(β-benzyl L-aspartate) blocks

Novel segmented multiblock copolymers ( 7 ) were synthesized by linking poly(ethylene oxide) (PEO) blocks with poly(β-benzyl L -aspartate)(PBLA) blocks via urethane and urea bonds, which were formed by the reaction of 4,4′-methylenediphenyl isocyanate ( 5 ) with the terminal hydroxyl groups of α-hydro-ω-hydroxypoly(oxyethylene) ( 4 ) and the terminal amino groups of poly(β-benzyl L -aspartate)-block-iminohexamethyleneimino-block-poly(β-benzyl L -aspartate) ( 3 ) [prepared from 1,6-hexanediamine ( 1 ) and β-benzyl L -aspartate N-carboxy anhydride ( 2 )], respectively. Membranes with various water contents were obtained from these copolymers by changing the lengths of the PEO and PBLA segments. The study of the permeation of 1-phenyl-1,2-ethanediol, vitamin B₁₂ and myoglobin through the membranes showed a high dependency of the permeability on the molecular weight of the solutes.     

Expression profiles and functional implications of p53-like transcription factors in thymic epithelial cell subtypes

In this study, we investigated the localization and functional significance of p53 tumor suppressor-like molecules, p63 and p73, in human thymic epithelial cells (TECs). Immunohistochemical studies showed particular distribution profiles of p63 and p73 in thymic epithelium, in which cortical TECs preferentially expressed p63 in their nuclei whereas subcapsular and medullary TECs expressed both p63 and p73 in their nuclei. The wide distribution of p63 in TECs was further suggested by studies using TECs of primary culture. In vitro studies using two human TEC lines demonstrated that p63 was capable of up-regulating intercellular adhesion molecule-1 (ICAM-1) and enhancing the production of IL-6 and IL-8. Moreover, in vitro studies also indicated that p73, but not p63, had the capacity to induce granulocyte macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) in the TEC lines. These findings suggest that p63 would regulate the cell adhesive property through ICAM-1/LFA-1 interaction and the production of IL-6 and IL-8, probably in all TEC subtypes. p73 in subcapslar and medullary TECs was suggested to play a role in the regulation of the production of GM-CSF and G-CSF, which might stimulate other stromal cells such as dendritic cells, macrophages and endothelial cells around these regions.     

Chronic myelogenous leukemia with a complex Ph1 translocation in an XYY male

We encountered a 38-year-old Japanese male patient with chronic myelogenous leukemia (CML), whose bone marrow and peripheral blood cells during the chronic and blastic phases contained a complex Ph¹ translocation and an extra Y chromosome [i.e., 47,XYY,t(9;22;13)(q34;q11;q14)]. A karyotypic analysis of PHA-stimulated lymphocytes showed the constitutional karyotype to be 47,XYY. Thus, it was considered that CML with a complex Ph¹ translocation developed in an XYY male; such a case has not been reported, so far. A B-lymphocyte cell line with the complex Ph¹ translocation was established by the procedure of Epstein-Barr virus transformation. The presence of the complex Ph¹ translocation in the B-lymphocyte cell line suggests that some of the B lymphocytes in this patient originated from the CML clone.     

Carpal Tunnel Syndrome Due to Iatrogenic Amyloidosis After Domino Liver Transplantation From Hereditary Transthyretin Amyloidosis: A Case Report

BackgroundCarpal tunnel syndrome is the most common compression syndrome of the peripheral nerve. Transthyretin amyloidosis and dialysis-related β2-microglobulin amyloidosis are known causes of carpal tunnel syndrome.Case ReportA Japanese woman showed carpal tunnel syndrome 16 years after a domino liver transplantation (DLT) from the donor with hereditary transthyretin amyloidosis. DLT indication was congenital extrahepatic portosystemic shunt, and the patient had been put on maintenance hemodialysis because of chronic kidney disease 6 years before DLT. Moreover, the amyloid precursor protein of the patient was histologically confirmed not to be β2-microglobulin, but transthyretin.ConclusionsThe existence of amyloid was speculated when the patient who underwent DLT from hereditary transthyretin amyloidosis showed carpal tunnel syndrome. Additionally, elucidating the amyloid precursor protein when the patient has another cause of amyloidosis is necessary.     

Hypoxia-ischemic insult in neonatal rats induced slowly progressive brain damage related to memory impairment

The present study was designed to determine potential associations between the brain damage induced by hypoxic-ischemic (HI) insult and spatial learning impairment in an eight-arm radial maze task. We first determined the pathological outcomes after 2, 5, 9, and 17 weeks of recovery following the HI insult. The results show that the brain damage progressed from 2 up to 17 weeks of recovery. To clarify the time course of the brain damage changes, we investigated the histological changes of the same individual with magnetic resonance imaging (MRI) after 5, 9, and 57 weeks of recovery following the HI insult. The MRI changes were similar to the histological changes, and the brain damages were exacerbated in the contralateral hemisphere after 57 weeks of recovery following the HI insult. To investigate whether alteration in brain function was correlated with MRI and histological changes, the rats were made to find their way through an eight-arm radial maze was performed at either 7th or 16th weeks of recovery. According to the results, the spatial learning impairments of rats in the maze starting at 16 weeks of recovery were more severe than those at 7 weeks of recovery, indicating that the impairments were progressive and depended on the degree of brain damage. The results of the present study are the first demonstration that the evolutional and specific brain damage following the HI insult is slowly and progressively exacerbated to the contralateral hemisphere and rats who experience the HI are at risk for showing a late impairment of brain function.     

Does the washout phenomenon of Tc-99m HM-PAO correlate to the “Filling-in” phenomenon of I-123 IMP with brain SPECT?

Summary Using SPECT, the time course of brain uptake was compared between N-isopropyl-p-[I-123]-iodoamphetamine (I-123 IMP) and Tc-99m d,l hexamethyl-propyleneamine oxime (Tc-99m HM-PAO). Of 14 patients with cerebrovascular disease showing areas of the filling-in phenomenon (i.e. delayed uptake) with I-123 IMP brain SPECT, 7 exhibited persistent defects with Tc-99m HM-PAO (Group I), and 7 showed early washout after the initial uptake (Group II). The filling-in of I-123 IMP did not always correlate to the washout region of Tc-99m HM-PAO. The temporal changes were also confirmed by semiquantitative analysis. While the filling-in of I-123 IMP was affected by many factors, the washout of Tc-99m HM-PAO was attributed to significant reduction of Tc-99m HM-PAO in the plasma. Delayed imaging of the brain with Tc-99m HM-PAO using SPECT may give a more accurate estimate of regional cerebral blood flow in cerebrovascular disease, because it should be lees effected by cerebral blood volume.     

Mutagenicity of the bile of dogs with an experimental model of an anomalous arrangement of the pancreaticobiliary duct

To learn the reasons for the high incidence of biliary carcinomain patients with anomalous arrangement of the pancreaticobiliaryduct (APBD) mutagenicity of the bile of APBD-modeled dogs thathad received a dorsal pancreatico-cholecystostomy was assayedby the Ames Salmonella mutation test. The bile from two outof 18 APBD dogs was mutagenic for Salmonella typhimurium strainTA98 under the condition of metabolic activation by rat liverS9 fraction, while the bile from 17 normal dogs was not mutagenic.Furthermore, the bile from five APBD dogs i.p. administered1-nitropyrene (1-NP), which is a typical environmental mutagen,was more mutagenic for strain TA98 than that from 1-NP-treatednormal dogs. The bile from the APBD dogs had very high amylaseactivity, indicating that the bile contained pancreatic juiceas a result of the pancreatico-cholecystostomy. When pancreaticjuice from a normal dog was added to the bile from 1-NP-treatednormal dogs, mutagenicity of the bile increased 1.6- to 2.0-fold.Furthermore, sulfatase increased the mutagenic activity of thebile in the presence of the pancreatic juice. HPLC revealedthat the bile from a 1-NP-treated APBD dog contained mutagenic1-nitro-6/8-hydroxypyrene and 1-nitro-3-hydroxypyrene, whilebile from a 1-NP-treated normal dog did not contain these deconjugatedproducts. The pancreatic juice from a normal dog had very high-glutamyltransferase (GGT) and aminopeptidase activities andlow sulfatase activity, but it had no ß-glucuronidaseactivity. In addition, the bacteria that easily infect the biliaryduct of APBD dogs, Escherichia coli, Klebsiella, Enterobacterand Proteus, had high ß-glucuronidase activity. Inparticular, Klebsiella showed a very high sulfatase activity.These results suggest that pancreatic juice enzymes and bacteriainfecting the biliary duct deconjugate the detoxified mutagensin the bile and induce mutagenicity of the bile from APBD dogsor APBD patients.     

Nutrient-induced thermogenesis (NIT) following amino acid infusion

Nutrient-induced thermogenesis (NIT) induced by parenteral infusion of amino acid (AA) mixtures of different composition and of the same AA mixtures given via different routes (parenteral or intraportal infusion) were investigated in rats using a small animal indirect calorimeter. When 8 different AA solutions of differing composition but with the same total concentration were infused parenterally, both standard NIT (each AA is assumed to generate 3.28 kcal/g) and specific NIT (heat energy of each AA is calculated assuming that it is oxidized to carbon dioxide and water, and metabolised to urea and sulphuric acid) values of the leucine (Leu)-rich and the glycine (Gly)-rich solutions were significantly greater than those of the control solution. Removal of Leu or Gly from the respective AA solutions reversed the increase of both NIT values down to control levels. When the parenteral and portal infusion routes were used in one rat, both NIT values for parenteral infusion of the Leu-rich solution were again significantly greater than those of the control. Likewise, both NIT values for intrportal infusion of the Leu-rich solution were also significantly greater than those of the control. However, no difference in NIT values was found between parenteral and portal infusion of either solution. The result of this study indicated that Leu and Gly may be thermogenic AAs, and the thermogenic effect of Leu is not dependent upon the route of infusion.     

Influence of denervation on neurogenic inhibitory response of corpus cavernosum and nitric oxide synthase histochemistry

Aims of this study were to functionally and histologically determine the localization of ganglia that distribute inhibitory nerves to the penile corpus cavernosum in dogs. In isolated corpus cavernosa from seven control dogs contracted with endothelin-1, transmural electrical stimulation (5 Hz for 40 s) elicited contractions which were reversed to relaxations by prazosin. The relaxation was abolished by NG-nitro-l-arginine (l-NNA), a nitric oxide (NO) synthase inhibitor, and restored by l-arginine. Parts of bilateral pelvic nerve plexuses running to the penis were surgically denervated in anesthetized three dogs, or the bilateral neuronal tissues close to the corpus cavernosum were removed for denervation in seven dogs. One week after the operation, the dogs were sacrificed. Denervation of pelvic plexus did not attenuate neurogenic relaxations, whereas denervation of the distal portion abolished the responses. In the tissues close to the corpus cavernosum excised for denervation, ganglia containing abundant nerve cells and fibers stained by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase method were histochemically detected. One week after the denervation, there were no NADPH diaphorase-positive nerve fibers in the trabecula of corpus cavernosum. It is concluded that neurogenic relaxations of canine corpus cavernosum are mediated by NO synthesized from l-arginine in nerve terminals, and this nerve is originated from ganglia located close to the corpus cavernosum but not directly from the pelvic nerve plexus.