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Biomedical subjects

S Chin

Publications and source records attributed to S Chin.

At least 55 records · Page 3Linked to original sources

Virucidal short wavelength ultraviolet light treatment of plasma and factor VIII concentrate: protection of proteins by antioxidants.

The use of solvent/detergent mixtures and various forms of heat treatment to inactivate viruses has become widespread in the preparation of blood derivatives. Because viruses that lack lipid envelopes and/or are heat resistant, eg, hepatitis A virus (HAV) or parvovirus B19 may be present, the use of two methods of virus elimination that operate by different mechanisms has been advocated. We now report on short wavelength ultraviolet light (UVC) irradiation for virus inactivation and enhancement of its compatibility with proteins by quenchers of reactive oxygen species (ROS). Treatment of an antihemophilic factor (AHF) concentrate or whole plasma with 0.1 J/cm2 inactivated 10(5) to > or = 10(6) infectious doses (ID) of encephalomyocarditis virus (EMCV), HAV, bacteriophage M13, vesicular stomatitis virus (VSV), and porcine parvovirus. However, the recovery of factor VIII was 30% or lower on treatment of an AHF concentrate and 60% on treatment of plasma. Factor VIII recovery could be increased with little or no effect on virus kill by addition of rutin, a flavonoid known to quench both type I and type II ROS. On treatment of plasma in the presence of rutin, the recovery of several other coagulation factors was also enhanced by rutin addition and typically exceeded 75%. Electrophoretic analysis of treated AHF concentrate confirmed the advantage of rutin presence; UVC irradiation of plasma did not cause discernible changes in electrophoretic banding patterns, even in the absence of rutin. We conclude that addition of UVC treatment to existing processes used in the manufacture of blood derivatives will provide an added margin of safety, especially for nonenveloped or heat-stable viruses.

Animals↗

A positron emission tomography [18F]deoxyglucose study of developmental stuttering.

Positron emission tomography using [18F]deoxyglucose (FDG) as a marker of regional brain metabolism was used to investigate the neural substrate of stuttering. Four patients with severe developmental stuttering were studied while reading aloud to another person (stuttering condition) and while reading aloud in unison with someone else (non-stuttering condition). The patients were also compared with four normal controls reading aloud by themselves. In the stuttering condition, significant decreases in regional glucose metabolism in Broca's area, Wernicke's area and frontal pole were seen compared with themselves while not stuttering. These differences were also seen in stuttering condition compared with normal controls. Significantly lower left caudate metabolism was seen in patients during both stuttering and non-stuttering conditions compared with normal controls. A circuit for stuttering is proposed based on these findings.

Adult↗

Arachidonoyl ethanolamide-[1,2-14C] as a substrate for anandamide amidase.

Arachidonoyl ethanolamide-[1,2-14C] was prepared and evaluated as a substrate for anandamide amidase in a radioenzymatic assay that does not require a thin layer chromatography separation step. Using this substrate the release of ethanolamine-[1,2-14C] is linear for approximately thirty minutes. Anandamide amidase exhibits maximal activity between pH 8 and pH 9 with a steep decline in activity at pH values below 6 and above 10. Arachidonoyl ethanolamide-[1,2-14C] was used for the assay of anandamide amidase from 10 micrograms to 100 micrograms protein, from cow brain homogenate, in a 0.2 ml incubation mixture. When plotted as a rectangular hyperbola of the steady-state Michaelis-Menten equation, an approximate Km of 30 +/- 7 microM and a Vmax of 198 +/- 13 nmoles ethanolamine formed per hour per mg protein homogenate was obtained.

Amidohydrolases↗

Elimination of potential mutagenicity in platelet concentrates that are virally inactivated with psoralens and ultraviolet A light.

BACKGROUND: For virus sterilization of platelet concentrates (PCs), treatment with aminomethyltrimethyl psoralen (AMT) and long-wavelength ultraviolet A light (UVA) has shown efficacy. It has been found that treatment with 50 micrograms per mL of AMT and 38 J per cm2 of UVA in the presence of 0.35-mM rutin efficiently kills viruses while maintaining platelet integrity. There is, however, concern about the mutagenic potential of psoralens and UVA (PUVA)-treated PCs. STUDY DESIGN AND METHODS: Adsorption of PUVA-treated PCs with a hydrophobic resin containing C18 as the ligand was used for AMT removal, which was quantitated by the use of radioactive AMT. PUVA-treated PCs, with and without C18 treatment, were examined for solution pH and platelet aggregation response to agonists. In addition, residual AMT activity was determined by AMT's virucidal activity or incorporation into cellular DNA upon a second UVA irradiation and by its mutagenic potential in the Ames test. RESULTS: After PUVA treatment of PCs, residual AMT retained virucidal and adduct-forming ability upon re-exposure to UVA, but activities were less than those observed originally. As has been found previously, AMT had mutagenic potential following incubation in the dark with rat liver S9 microsomal enzymes. The PUVA treatment reduced this potential by 90 percent. C18 adsorption following PUVA treatment had no negative effect on platelet integrity and eliminated 50 percent of the added radioactive AMT. In addition, all detectable virucidal, nucleic acid-modifying, and mutagenic activities of AMT-treated PCs were removed by C18. CONCLUSION: These results suggest that hydrophobic resin adsorption of PUVA-treated PCs will conveniently remove functional psoralens and eliminates their mutagenic potential.

Adsorption↗

Biodistribution and virus inactivation efficacy of a silicon phthalocyanine in red blood cell concentrates as a function of delivery vehicle.

The silicon phthalocyanine, HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc 4), is a new photosensitizer that can inactivate lipid-enveloped viruses in red blood cell concentrates (RBCC) upon exposure to red light. Because Pc 4 is insoluble in water, it was delivered either as an emulsion in saline and cremophor EL (CRM) or as a solution in dimethyl sulfoxide (DMSO). In RBCC, Pc 4 added in either vehicle distributed between the plasma and red blood cells (RBC) in a ratio of 4:6, similar to the ratio of these components in RBCC 3:7 (i.e. a hematocrit of 70%). Light exposure did not affect this distribution and caused only marginal degradation of Pc 4 at a light dose that inactivates > 5 log10 vesicular stomatitis virus (VSV). Among human plasma proteins, Pc 4 bound mainly (about 70%) to lipoproteins and to a lesser extent to albumin and lower molecular weight proteins when delivered in DMSO. When delivered in CRM, distribution between lipoproteins and albumin became more even. Among the lipoproteins Pc 4 bound almost exclusively to very low-density lipoproteins (VLDL) when delivered in DMSO and to both VLDL and low-density lipoproteins when added in CRM. The rate of VSV inactivation was independent of the delivery vehicle but there was less RBC damage, as measured by hemolysis during storage, when Pc 4 was added in CRM. These results indicate that using CRM as emulsifier can enhance the specificity of Pc 4-induced photochemical decontamination of RBCC for transfusion.

Animals↗

Blunting of the immediate-early gene and mitogenic response in hepatectomized type 1 diabetic animals.

Studies suggest that liver regeneration is delayed in insulin-deficient animals, but defining a role of insulin as a growth factor in hepatic regeneration has remained elusive. By examining gene expression of hepatectomized liver in type 1 diabetic BB rats, we have identified dramatic changes in the expression of primary or immediate-early growth response genes compared with normal animals. These include altered expression of insulin-regulated genes such as glucose-6-phosphatase (G-6-Pase), phosphoenolpyruvate carboxykinase (PEPCK), and beta-actin, and genes such as CL-6 and map kinase phosphatase-1 (MKP-1) that were previously unlinked to insulin action in animals. Abnormal elevation of mRNAs encoding G-6-Pase, MKP-1, and PEPCK in the time 0 diabetic liver results in decreased induction after partial hepatectomy. Other genes, such as CL-6 and beta-actin, are induced at a lower level in the hepatectomized diabetic animals. The net effect is a blunting of the immediate-early gene response after partial hepatectomy in diabetic animals. As determined by DNA synthesis assays, the regenerative capacity of insulin-deficient BB diabetic livers is reduced, and this defect is corrected at least in part by insulin therapy. These findings suggest that because of insulin deficiency, common intracellular signaling pathways that are required for both metabolism and mitogenesis are aberrant in the type 1 diabetic liver and, as a result, the regenerative response is deficient.

Animals↗

High levels of glucose-6-phosphatase gene and protein expression reflect an adaptive response in proliferating liver and diabetes.

The regenerating liver after partial hepatectomy is one of the few physiologic models of cellular proliferation in the adult animal. During hepatic regeneration, the animal is able to maintain metabolic homeostasis despite the acute loss of two thirds of hepatic tissue. In examining the molecular mechanisms regulating hepatic regeneration, we isolated novel immediate-early genes that are rapidly induced as the remnant liver undergoes the transition from its normal quiescent state into the G1 phase of the cell cycle. One of the most rapidly and highly induced genes which we initially termed RL-1, encodes rat glucose-6-phosphatase (rG6Pase). G6Pase mRNA peaks at 30 min and 36-48 h after hepatectomy correlating with the first and second rounds of cell division. This finding is compatible with studies that showed that G6Pase enzyme activity increases during liver regeneration. However, the increase in G6Pase mRNA is much more dramatic, indicating that it is a more sensitive indicator of this regulation. G6Pase gene expression peaks in the perinatal time period in the liver and remains elevated during the first month of life. The expression of the G6Pase gene is also dramatically elevated in BB diabetic rats, again higher than the enzyme elevation, and its relative induction after partial hepatectomy is blunted in these animals. Insulin treatment of partially hepatectomized diabetic animals downregulates the expression of G6Pase mRNA. Using specific antibodies against G6Pase, we detect a 36-kD G6Pase protein, and its level is elevated in regenerating and diabetic livers. The pattern of G6Pase mRNA expression appears to reflect similar changes in insulin and glucagon levels which accompany diabetes and hepatic proliferation. The elevation of G6Pase expression in these conditions is indicative of its importance as a regulator of glucose homeostasis in normal and abnormal physiologic states.

3T3 Cells↗

[Two cases of inferior branch palsy of the oculomotor nerve in children].

Two cases of inferior branch palsy of the oculomoter nerve in children are reported. A Six-year-old and a 14-year-old child had diplopia. Adduction and depression were restricted and mydriasis of the affected eye were observed. There were no restrictions on elevation. Ptosis was absent. They were diagnosed as having inferior branch palsy of the oculomotor nerve. Neurological examinations and diagnostic imagings showed no other abnormalities. Herpes simplex and influenza antibody titer were high in both cases. Oral steroid treatment was given. The eye position and movement recovered within 3 months in both cases. But the light reflexes of the affected eye remained diminished and light-near dissociation were observed. These findings have not changed for two years.

Adolescent↗

[Long-term prolongation of direct pupillary light reflex latency and P100 latency of pattern visual evoked potential in unilateral optic neuritis].

We evaluated the visual functions of visual acuity, color sense, direct pupillary light reflex and pattern visual evoked potentials (P100) in five patients with unilateral optic neuritis whose visual acuity improved to 1.0 or better in order to assess the recovery of the impaired optic nerve fibers from the inflammatory process. During follow-up periods the direct light pupillary reflex was electropupillographically recorded and the P100 latency of visual evoked potentials was examined in both eyes. The temporal course of their differences showed a biphasic curve: the acute stage showed a rapid decrease of the differences and the chronic stage showed a flat line analysis of Pearson's correlation coefficient revealed that latency differences were mutually altered although there was a tendency for differences of direct pupillary reflex latency to decrease more rapidly at the acute stage than those of P100 latency. The present study demonstrated that the two different classes of the optic nerve fibers originating from the retinal ganglion cells, pupillary reflex-related fibers and form vision-related fibers, were damaged to the same degree by the inflammation, in spite of their morphological differences.

Adult↗

Visual function in patients with optic neuritis associated with acute transverse myelopathy in multiple sclerosis.

The authors reviewed the records of 20 patients with optic neuritis, all of whom were diagnosed as having clinically definite multiple sclerosis (MS). They were classified into two subgroups: Group A, consisting of 9 patients who had shown acute transverse myelopathy (ATM); and Group B, 11 patients without ATM. Four patients (44%) in Group A had complete visual loss, but none in Group B. Six patients (67%) in Group A had less than 0.1 visual acuity in the affected eye, but only 2 patients (18%) in Group B. Four patients in Group A showed evidence of anticardiolipin antibodies. While both groups were diagnosed as having clinically definite MS, there were differences between them in the clinical features. We assume that the patients with ATM may constitute a different subgroup among MS patients.

Acute Disease↗

A case of neuroretinitis associated with long-standing polyarteritis nodosa.

We reported a 45-year-old man suffering from neuroretinitis with long-standing polyarteritis nodosa and anterior uveitis. Fluorescein angiography, made at the stage when optic disk swelling developed, demonstrated a hypofluorescent area at the temporal part of the optic disc presenting exudates in its prelaminar region. When the swelling of the optic disc had resolved as verified ophthalmoscopically, and the hypofluorescence was angiographically undetectable, a macular star was observed, showing a configuration corresponding to Henle's layer.

Humans↗

[Visual function in patients with optic neuritis associated with acute transverse myelopathy in multiple sclerosis].

We reviewed the records of 20 patients with optic neuritis who were diagnosed to have clinically definite multiple sclerosis (MS). We classified them into 2 subgroups: group A, consisting of 9 patients who had acute transverse myelopathy (ATM); and group B, 11 patients without ATM. 4 patients (44%) in group A had complete visual loss, but none in group B. 6 patients (67%) in group A had less than 0.1 visual acuity in the affected eye, but only 2 patients (18%) in group B. 4 patients in group A had evidence of anticardiolipin antibodies. While both groups were diagnosed as having clinically definite MS, there were differences in the clinical features between them. We assume that the patients with ATM constitute a different subgroup among MS patients.

Acute Disease↗

[Electronmicroscopic study on the vitreous membrane of the Stickler syndrome].

The vitreous membrane obtained from a patient with Stickler syndrome, an 8 year-old female, was investigated electronmicroscopically. The cells found in the membrane had cilia, microvilli and cytoplasmic filaments. Gap junctions and basement membrane-like structures were also found. Several of the cells had phagosomes containing crystalline materials. Thus, these cells seemed to be glial cells.

Abnormalities, Multiple↗

Lymphangioma of the jejunal mesentery in an adult: a case report and a review of the Japanese literature.

A rare case of lymphangioma of the jejunal mesentery in a 34-year-old woman is presented. She was diagnosed as having an ovarian cyst preoperatively, but laparotomy revealed a cystic tumor of the mesentery that was histologically diagnosed as lymphangioma. Thus far, 44 cases of adult mesenteric lymphangioma have been reported in Japan. In nine cases, accurate diagnosis of mesenteric cysts was obtained preoperatively. In 31 cases, complete excision with or without bowel resection was done, whereas two cases were partially resected and one case was drained.

Adult↗

Osmolality electrolyte and carbohydrate type and oral rehydration solutions: a controlled study to compare the efficacy of two commercially available solutions (osmolalities 240 mmol/L and 340 mmol/L).

An open-label, inpatient study was undertaken to compare the efficacy of two oral rehydration solutions (ORS) given randomly to children aged 1-10 years who had acute gastroenteritis with mild or moderate dehydration (n = 45). One solution contained 60 mmol/l sodium and 1.8% glucose, total osmolality 240 mosm/l (Gastrolyte, Rhone-poulenc, Rorer) and the other contained 26 mmol/l sodium, 2.7% glucose and 3.6% sucrose, total osmolality 340 mOsm/l (Glucolyte, Gilseal). Analysis of data indicated that Gastrolyte therapy resulted in significantly fewer episodes and volume of vomiting over all time periods in comparison to Glucolyte and significantly less stool volume during the first 8 h and in the 0-24 h period. The differences between treatments in degree of dehydration at each follow-up period, duration of diarrhoea, and duration of hospital stay were not significant. No adverse drug reactions occurred. Six patients received intravenous rehydration treatment and were considered treatment failures. We conclude that oral rehydration therapy is safe and efficacious in the management of dehydration in acute diarrhoea and that the lower osmolar rehydration solution has clinically marginal advantages.

Acute Disease↗