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Biomedical subjects

H Okabe

Publications and source records attributed to H Okabe.

At least 145 records · Page 8Linked to original sources

Bronchial hyperreactivity in patients with familial amyloidotic polyneuropathy and autonomic neuropathy.

To investigate the role of autonomic regulation on airway reactivity, we performed bronchial inhalation tests of methacholine (MCh) and histamine (Hist) in Japanese patients with familial amyloidotic polyneuropathy (FAP) and autonomic neuropathy. First we examined the FEV1 and Raw in seven patients with FAP and in six normal subjects, then we administered aerosols of increasing concentrations of MCh (0.075 to 25 mg/ml) at about 5-min intervals via a nebulizer controlled by a dosimeter. We measured the FEV1 until either the concentration of MCh producing a 20% reduction from the basal value (PD20) or the maximal concentration was reached. Five of the seven patients with FAP showed bronchial hyperreactivity to MCh, and PD20 to MCh was significantly lower than that of the normal subjects (p < 0.01). Furthermore the PD20 tended to correlate inversely with the severity of autonomic neuropathy (p = 0.052). The bronchial hyperreactivity to MCh was completely blocked by pretreatment inhalation of ipratropium bromide, suggesting the muscarinic receptor-mediated mechanism. Of these five patients with hyperreactivity to MCh, three with low PD20 to MCh (< 50 units) did not respond to Hist, but two with high PD20 (> 50 units) to MCh did, suggesting different mechanisms of hyperreactivity to MCh and Hist in FAP. The PD20 to Hist significantly correlated inversely to the PD20 to MCh (p < 0.05). Histochemical examination revealed marked amyloid deposition in the vagus nerves and tracheal wall in an autopsied patient with FAP and severe autonomic symptoms. These data suggest that patients with FAP and advanced autonomic neuropathy have bronchial hyperreactivity to MCh and/or Hist, probably because of denervation supersensitivity resulting from amyloid deposition in the peripheral autonomic nerves of the airways.

Adult↗

Structures and antiproliferative activity of saponins from Sechium pittieri and S. talamancense.

Six bisdesmosidic bayogenin saponins, named tacacosides A1, A2, B1, B2, B3 and C, were isolated from the fruit and aerial parts of Sechium pittieri (COGN.) C. Jeffrey and S. talamancense (WUNDERLIN) C. Jeffrey, Costa Rican cucurbitaceae plants. Their structures were elucidated on spectral and chemical evidence as follows. Tacacoside A1: 3-O[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl]bayogenin 28-O-(alpha-L-rhamnopyranosyl- (1-->3)-beta-D-xylopyranosyl-(1-->4)-beta-D-apiofuranosyl-(1-->3)] - alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl) ester, tacacoside A2: 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl]bayogenin 28-O-(alpha-L-rhamnopyranosyl- (1-->3)-beta-D-xylopyranosyl-(1-->4)-[beta-D-xylopyranosyl-(1-->3)]-a lph a-L- rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl) ester, tacacoside B1: 3-O-[beta-D-glucopyranosyl]bayogenin 28-O-(alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl- (1-->4)-[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1- ->2)-alpha- arabinopyranosyl) ester, tacacoside B2: 3-O-[beta-D-glucopyranosyl]bayogenin 28-O-(alpha-L-rhamnopyranosyl-(1-->3)- beta-D-xylpyranosyl-(1-->4)-[beta-D-xylopyranosyl- (1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl) ester, tacacoside B3: 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] bayogenin 28-O-[alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl- (1-->4)-alpha-L-rhamnopyranosyl- (1-->2)-alpha-L-arabinopyranosyl] ester, and tacacoside C: 3-O-[beta-D-glucopyranosyl]bayogenin 28-O-[alpha-L-rhamnopyranosyl- (1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)- alpha-L-arabinopyranosyl] ester. These saponins showed moderate antiproliferative activity (ED50:10-74 micrograms/ml) against MK-1, HeLa and B16F10 cells.

Carbohydrate Sequence↗

beta-Sitosterolemia with generalized eruptive xanthomatosis.

The clinical features of the first case of a patient with sitosterolemia and generalized eruptive xanthomatosis are described. A six-year-old girl with generalized eruption was referred to the lipid clinic because of the high plasma cholesterol levels determined by the enzymatic method. Neither clinical signs nor results of laboratory examinations appeared to be abnormal, except for the eruption and the increase in the plasma cholesterol concentration. A family survey revealed high plasma cholesterol concentrations in the mother and one of two other siblings. Histological examination showed the eruption to be a xanthoma. Plasma sterol analysis by high-performance liquid chromatography revealed a noticeable increase in plasma plant sterol as well as cholestanol concentrations in the proband and the hypercholesterolemic sibling. The other family members had slightly high plasma sterol concentrations. This is the first case of a sitosterolemic patient with eruptive xanthomatosis. The case indicates that the clinical features of the xanthoma in sitosterolemia are not only tuberous or tendon but also eruptive, and also suggests that sitosterolemia should be considered in the differential diagnosis of hypercholesterolemia in almost every case with tuberous or eruptive xanthoma. The diagnosis is clinically important, since the disease can be treated successfully by diet therapy and bile acid binding resins.

Child↗

Separation method of IgG fragments using protein L.

Protein L (IgG kappa-chain-binding bacterial protein) showed a precipitate line(pseudo-immuno-reaction) with IgG and F(ab')2 fragment, but did not show any line with the Fab fragment, the Fc fragment and free kappa-chains in the micro-Ouchterlony method. The IgG and Fab fraction obtained from pa-pain-digested IgG (from the sera of patients with chronic thyroiditis), followed by Protein A-Sepharose, were separated by Protein L-Sepharose affinity chromatography. The unbound fraction (UF) consisted of IgG(lambda) or Fab(lambda) and the bound fraction (BF) consisted of IgG(kappa) or Fab(kappa) were obtained. Anti-thyroglobulin and anti-thyroid peroxidase antibody activities were found equally in both the UF and the BF. When Fab(kappa) was reduced with dithiothreitol (DTT), the Fd fragment in the UF could be separated from the free kappa-chain and the unreduced Fab(kappa) in the BF with a Protein L-Sepharose column. A separation method of human IgG fragments such as free kappa-chain, combined forms of kappa-chain [Fab or F(ab')2], and the Fd region, using Protein L, is described.

Bacterial Proteins↗

Reduction of spinal cord injury by administration of iloprost, a stable prostacyclin analog.

To investigate whether iloprost, a stable analog of prostacyclin, is useful for the prevention of posttraumatic spinal cord injury, we examined its effects on compression trauma-induced spinal cord injury in rats. Spinal cord injury was induced by applying a 20-g weight for 20 minutes to the spinal cord at the level of T-12, resulting in motor disturbances in the hindlimbs. These motor disturbances, evaluated using Tarlov's index, were markedly attenuated in rats with nitrogen mustard-induced leukocytopenia. Administration of iloprost also attenuated the motor deficits. Histological examination revealed that intramedullary hemorrhages observed 24 hours after trauma were significantly attenuated in leukocytopenic animals and in animals that received iloprost. The accumulation of leukocytes at the site of trauma, evaluated by measuring tissue myeloperoxidase activity, significantly increased with time following the trauma, peaking at 3 hours postinjury. Spinal cord myeloperoxidase activity in sham-operated animals did not increase postoperatively. Leukocyte depletion and administration of iloprost reduced the accumulation of leukocytes in the damaged spinal cord segment 3 hours posttrauma. These findings indicate that iloprost attenuates motor disturbances induced by spinal cord trauma and that its therapeutic efficacy can be partly explained by its inhibition of leukocyte accumulation at the traumatized site.

Animals↗

Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid. 1st communication: absorption, distribution, metabolism and excretion after topical application and subcutaneous administration in rats.

4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have a potent topical antipsoriatic activity. The pharmacokinetic profiles of Am-80 were studied in rats after topical application and subcutaneous administration of 14C-labeled Am-80. After topical application at a dose of 1 g ointment (0.1%)/kg to normal skin rats by the occlusive dressing technique, radioactivity was scarcely detected in the blood or plasma. In the stripped skin rats, plasma radioactivity reached the peak at 2 h and decreased with a half-life of 5.5 h. The recovery of radioactivity in the excreta and carcass amounted to 54.7% of the dose, indicating about six times higher absorption than that in the normal skin rats. After subcutaneous administration at a dose of 1 mg/kg, the maximum concentration of blood radioactivity was attained at 1-2 h and declined with a half-life of 4-5 h until 24 h. Biliary excretion was about 80% of the dose, and enterohepatic circulation was estimated to be 36.5%. Radioactivity was distributed systemically, particularly in abundance in the liver followed by adrenal gland and kidney. Elimination of radioactivity in most tissues was extremely slow and the radioactivity was detected even at 240 h after dosing. There was no gender-related difference in the profile of distribution and elimination of 14C-Am-80 in the rats. Two major metabolic pathways in rats have been postulated for Am-80; one involves the 6- or 7-hydroxylation to yield related hydroxy-Am-80 that lead to the formation of oxo-Am-80, and another involves the hydrolysis of the carboxamide bond to yield tetrahydro-tetramethyl-naphthalenylamine and terephthalic acid. Furthermore, Am-80 itself an 6- or 7-hydroxy-Am-80 were susceptible to the formation of taurine conjugates. In the plasma, unchanged Am-80 was present in a high proportion to total radioactivity, while in the urine and bile the proportion of unchanged Am-80 was low.

Administration, Topical↗

Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid. 2nd communication: absorption, distribution and excretion after single and consecutive subcutaneous administration in rats.

4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl]benzoic acid (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have a potent topical antisporiatic activity. The accumulation characteristics of Am-80 were examined in rats after a single and consecutive subcutaneous administration of 14C-labeled Am-80 once a day for 24 days, at a daily dose of 0.2 mg/kg. As compared with the single administration, Tmax (1-2 h) and Cmax (about 50 ng eq./ml) of the blood radioactivity were not altered markedly after the consecutive administration. During the daily subcutaneous dosing, the blood level of radioactivity at 24 h after each dosing was also very low. These findings suggested that accumulation in the blood was low after long term consecutive administration of Am-80. The plasma levels of total radioactivity and the proportion of unchanged Am-80 to the total plasma radioactivity, being about 80% at 2 h after administration, and plasma elimination half-life of Am-80, being approximately 3 h, appeared to be hardly affected by the consecutive administration. The cumulative excretion of radioactivity at 168 h after the final dosing was 6.7% and 89.1% in the urine and feces, respectively. The radioactivity remaining in the carcass at this time was about 3% of the total dose. The excretion profile was not altered by the consecutive administration. In most tissues, the concentration of radioactivity at 24 h after each dose reached a steady-state within 24 doses. At 2 h after the consecutive administration for 24 days, the highest concentration of radioactivity was found in the liver followed by the adrenal gland. Accumulation and delayed elimination of radioactivity in most tissues, especially in the adrenal gland, fat, skin and epididymis, were evidently observed as predicted from the previous study where 14C-Am-80 was administered at a dose of 1 mg/kg. The profile of accumulation and retention of radioactivity after the consecutive administration may be considered as a common characteristic of retinoids, such as etretinate.

Animals↗

Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl]benzoic acid. 3rd communication: placental transfer and excretion into milk in rats.

4-[5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl]benzoic acid (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have a potent topical antipsoriatic activity. Placental transfer and excretion into milk after administration of 14C-Am-80 to pregnant or nursing rats were investigated in view of reproductive and developmental toxicity studies. When 14C-Am-80 was administered topically at a dose of 10 mg/kg to normal-skin pregnant rats on the 12th day of pregnancy, plasma radioactivity in the dam and fetus was detected only at low levels. However, at a dose of 1 mg/kg to the stripped-skin pregnant rats, radioactivity levels peaked at 6 h in the maternal plasma (188.7 ng eq./g) and fetus (64.6 ng eq./g) and at a dose of 10 mg/kg, the peak maternal plasma level of radioactivity and the concentration of radioactivity in the fetus up to 24 h after dosing rose about 10-fold in proportion to the increased dose. At both doses, the radioactivity level in the fetus at the peak corresponded to approximately one-third of the maternal plasma level. When 14C-Am-80 was administered subcutaneously at a dose of 1 mg/kg to pregnant rats on the 12th day of pregnancy, radioactivity in the fetus peaked at 4 h after dosing, being about one-fourth of the maternal plasma level at the same time point. Radioactivity in the fetus after subcutaneous administration of 14C-Am-80 at a dose of 1 mg/kg to pregnant rats on the 19th day of pregnancy peaked (156.4 ng eq./g) at 4 h after dosing, corresponding to approximately one-half the maternal plasma level at the same time point, and then decreased gradually. Among the fetal tissues, relatively high radioactivity was found in the liver. Whole-body autoradiography showed that in most tissues in the dam, the distribution pattern of radioactivity was similar to that in the non-pregnant rat. The concentration of radioactivity in the milk after subcutaneous administration of 14C-Am-80 at a dose of 1 mg/kg to lactating rats on the 9th day after delivery peaked at 8 h after dosing, being 94 times greater than that in the plasma. Unchanged Am-80 in the milk was largely recovered after hydrolysis of hexane extracts of the intact milk with lipase, suggesting extensive incorporation of Am-80 into the triglyceride in the milk because of its benzoic acid structure and high lipophilicity. As for radioactive metabolites which have hitherto been identified in rats, only M-6 (taurine conjugate of Am-80) and tetrahydro-tetra-methyl-naphthylamine (TTNA) were detectable in small amounts in the milk.

Administration, Topical↗

Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid. 4th communication: absorption, metabolism, excretion and plasma protein binding in various animals and man.

4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl]benzoic acid (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have a potent topical antipsoriatic activity. Pharmaco-kinetic profiles of Am-80 were studied in dogs, mice and rabbits after percutaneous or subcutaneous administration of 14C-Am-80. Plasma protein binding of 14C-Am-80 was also studied in rats, dogs and humans. After topical application of 14C-labeled Am-80 by occlusive dressing technique at a dose of 1 mg 14C-Am-80/1,000 mg ointment/kg, the blood and plasma levels of radioactivity were below the detection limit in normal-skin dogs. In normal skin mice and rabbits, the plasma radioactivity peaked at 8 h (40.8 ng eq./ml) and at 12 h (34.0 ng eq./ml) after application, respectively. Percutaneous absorption of 14C-Am-80 was less than 2% of the dose for dogs, 34% for mice and 23% for rabbits. After subcutaneous administration at a dose of 1 mg/kg to mice, dogs and rabbits, plasma levels of radioactivity peaked at 1, 4 and 4 h after dosing with a concentration of 614.0, 902.9 and 757.7 ng eq./ml and then it declined with half-lives of 2.4, 7.2 and 4.1 h, respectively. Urinary and fecal excretion of radioactivity after subcutaneous administration at a dose of 1 mg/kg was 3.5 and 94.7% of the dose in dogs, 27.0 and 73.2% in mice and 43.5 and 45.6% in rabbits. A possible gastrointestinal secretion, which might lead to excretion into feces, was suggested from the results with bile-duct-cannulated dogs. Unchanged Am-80 was present in high amounts in the plasma and bile or feces of all animal species tested except in rat bile, in which Am-80 was predominantly detected in the form of its taurine conjugate (M-6). Hydroxylation of Am-80 to yield 7-hydroxy-Am-80 (M-4) and 6-hydroxy-Am-80 (M-3), which lead to the formation of 6-oxo-Am-80 (M-5), were commonly observed in all animal species. Taurine conjugation reaction of unchanged Am-80 and hydroxy-Am-80 (to form M-6 and both M-1 and M-2, respectively) was distinct in rats and dogs, but, hardly detected in mice and rabbits. The presence of tetrahydro-tetramethyl-naphtylamine (TTNA) was most marked in mice, followed by rabbits and rats, but it was almost absent in dogs. HPLC-RIA analysis of human samples obtained from the phase II and phase III clinical trials of Am-80 ointment suggested that fecal excretion was the major elimination route, and that hydroxylation and taurine conjugation reaction of unchanged and hydroxy-Am-80 also occurred. Unchanged Am-80 was predominant in human plasma as compared with metabolites M-1 to M-6. In vitro binding of 14C-Am-80 to the plasma protein was found to be more than 99% in rats, dogs and humans. In vivo plasma protein binding of 14C-Am-80 and/or its radioactive metabolites was also found to be more than 98% in rats and dogs after subcutaneous administration of 14C-Am-80. In both dogs and humans, in vitro. 14C-Am-80 appeared to be bound predominantly to serum albumin. The binding of 14C-Am-80 to human serum albumin was scarcely affected in the presence of diazepam, digitoxin or warfarin, indicating that there are no specific binding sites for Am-80 on serum albumin.

Administration, Topical↗

Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl]benzoic acid. 5th communication: factors affecting percutaneous absorption in rats.

4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have a potent topical antipsoriatic activity. Factors affecting the percutaneous absorption of Am-80 were studied with the intention of obtaining information for toxicity and clinical investigations. The percutaneous absorption of radioactivity was compared after topical application of 0.1% 14C-Am-80 ointment to female rats by simple application (SA), occlusive dressing technique (ODT), and application using lint (AUL). After single topical application to normal skin female rats, the percutaneous absorption of radioactivity was very low with no significant differences in the extent of absorption among the three application methods. In the stripped skin female rats, a distinct increase of the percutaneous absorption was observed indicating that it was markedly affected by the lack of the stratum corneum. Compared with the single dosing, a considerable increase of percutaneous absorption was observed following repetitive topical application once daily for 4 or 7 days to the normal skin female rats. The extent of increase was highest in ODT rats followed by SA rats, but was relatively low in AUL rats. The effects of concentration, dose and application area of 14C-Am-80 ointment on the percutaneous absorption of radioactivity were studied following topical application of 0.002%-0.008% 14C-Am-80 ointment to normal skin male rats by ODT to areas of 72 cm2/kg-360 cm2/kg (5%-25% of the body surface area) at ointment doses of 2g/kg-8 g/kg. When the application area and the amount of ointment applied were fixed at 144 cm2/kg (10% of the body surface area) and 2 g/kg, respectively, the amount of radioactivity absorbed increased in proportion to the 14C-Am-80 concentration in the ointment, whereas the rate of percutaneous absorption, expressed as the percent of dose, was nearly constant. When the 14C-Am-80 concentration in the ointment and the amount of ointment applied were fixed at 0.08% and 2 g/kg, respectively, both the amount of radioactivity absorbed and the rate of percutaneous absorption markedly increased with an increase in the application area. When the concentration of 14C-Am-80 in the ointment was set at 0.008% and the application area at 72 cm2/kg, 144 cm2/kg or 288 cm2/kg (5%, 10% or 20% of the body surface area), the amount of radioactivity absorbed increased as the amount of ointment applied increased for areas of the same, though the rate of percutaneous absorption remained almost constant. When the 14C-Am-80 concentration in the ointment was fixed at 0.008%, the amount of radioactivity absorbed increased markedly about 20-fold with 4-fold simultaneous increases in both the application area (from 72 cm2/kg to 288 cm2/kg) and the amount of ointment applied (from 2 g/kg to 8 g/kg).

Animals↗

[The correlation between thymidylate synthase expression and cytotoxicity of 5-fluorouracil in human cancer cell lines: study using polyclonal antibody against recombinant human thymidylate synthase].

To estimate the relationship between the expression of thymidylate synthase (TS) in tumors and clinical response and prognosis in cancer patients treated with 5-fluorouracil (5-FU), the anti-TS polyclonal antibody against recombinant human TS (rhTS) was prepared and purified. At the initial stage, we attempted to clarify the relationships between the expression of TS protein and the cytotoxicity of 5-FU in established human cancer cells in vitro. Our purified anti-TS antibody was demonstrated to react specifically with intracellular TS as revealed by western blot analysis and immunohistochemistry. Furthermore, it was revealed that the expression of TS proteins correlated with cytotoxicity (IC50 value) of 5-FU against human colorectal tumor cells, both sensitive and those with acquired resistance to 5-fluoropyrimidines, and other cancer cell lines as well. These results suggest that our anti-TS polyclonal antibody (IgG) is suitable for clinical prospective and retrospective studies on TS expression in various cancers as a prognostic factor and 5-FU response-predicting parameter.

Antibodies↗

[Acute retrograde dissection of the aorta is a formidable complication in retrograde perfusion through the femoral artery].

To avoid this complication, we applied a Nelaton catheter (Imamura, Tokyo, Japan: standard type) as a guide to insert an arterial perfusion cannula (Bardic) into the femoral artery. Initially, the Nelaton catheter is accurately placed into the femoral artery through a purse string suture without applying vascular clamps on the artery or its branches. Then the perfusion cannula is advanced using the Nelaton catheter as a guide. We believe this procedure will avoid acute retrograde dissection of the aorta since it protects the femoral artery from injuries caused by the vascular clamps or the tip of the perfusion cannula.

Aortic Dissection↗

[Problems of the immunohistochemical differential diagnosis of neuroendocrine carcinoma and neuroblastomas].

Neurons arising from neural tube or neural crest do not express epithelial markers from the beginning of their differentiation and neuroblastomas arising from these anlages also do not express epithelial markers. On the other hand, neuroendocrine carcinomas, such as small cell carcinomas of the respiratory tract, express epithelial markers in addition to neuronal or neuroendocrine markers and demonstration of epithelial marker has been regarded as subtle evidence to rule out neuroblastomas. However, this general rule can not be applied to olfactory neuroblastomas. Unlike neurons derives from neural tube or neural crest, developing neurons arising from the anlage of olfactory nerve, i.e., olfactory placode, have keratin during the embryonic stage. Accordingly, it is unnatural for neoplastic neuroblasts of olfactory placodal origin to have keratin as the embryonic phenotype. In addition, neurons arising from this anlage have an epithelial antigen (EA) detected by Ber-EP4 from the beginning of their differentiation, and this antigen is preserved in the olfactory sensory nerve even in the postnatal stage, though it is lost from the neurons migrating from olfactory placode to brain, i.e., luteinizing hormone-releasing hormone producing neurons (LHRH neurons) during post embryonic stage. Therefore, demonstration of this epithelial antigen in the tumor with neurite formation can be regarded as a satisfactory diagnostic evidence of true olfactory neuroblastoma. LHRH also seems to be a useful marker to determine true olfactory placodal origin of the neuroblastoma. Finally, it is concluded that demonstration of epithelial markers could not be regarded as evidence to rule out neuroblastoma developed in the olfactory nerve region.

Antigens↗

[Tumor marker--present and future].

It is known that the serum in cancer patients has the characteristics of the heat-stability. The factor produce the heat-stability is known to be due to tumor marker(TM) such as CEA, CA125(glycoprotein), CA19-9, CA15-3, SLX, CA50, CA72-4, DU-PAN-2, ST-439, SPAN-1(mucin) and alpha 1-acid glycoprotein, IAP(acute reactants). CEA belongs to IgG supergene family protein and is not oncofetal protein. CA19-9 is synthesis in subjects with Le(a) or Le(b) type, but negative in Le(a- b-) type. Thus, CA19-9 is not available as TM in Le(a- b-) type. Many TMs can be classified in 3 types because cancer cell has the character of immature cells which composed of immature proteins or glycoproteins. (1) Oncofetal protein: AFP(fetal albumin), PTHrP(fetal PTH) (2) The immature isozyme type: increase of amylase(salivary type), CPK(brain type) and aldolase (muscle and brain type) (3) The immature protein in biosynthesis process: increase of precursor protein(prepro type or pro type) such as PIVKA-II(preprothrombin), ProGRP, TPA or CYFRA 21-1(pro-keratin?) and hormone precursor in hormone producing tumor.

Biomarkers, Tumor↗

Effects of plasma kallikrein specific inhibitor and active-site blocked factor VIIa on the pulmonary vascular injury induced by endotoxin in rats.

The acute respiratory distress syndrome (ARDS) is a serious complication of sepsis. To evaluate the role of the coagulation system in the pathogenesis of ARDS in sepsis, we examined the effects of the administration of a synthetic plasma kallikrein specific inhibitor (PKSI) and of active-site blocked factor VIIa (DEGR-VIIa) on the pulmonary vascular injury induced by E. coli endotoxin (ET) in rats. Administration of PKSI prevented the pulmonary vascular injury induced by ET as well as pulmonary histological changes in animals administered ET, but it did not affect the intravascular coagulation. The opposite effect was seen with DEGR-VIIa, which prevented the intravascular coagulation but not the pulmonary vascular injury. PKSI did not inhibit the activation of the complement system induced by ET leading to the activation of neutrophils. Findings suggest that PKSI may prevent the pulmonary vascular injury induced by ET by inhibiting kallikrein, which activates the neutrophils. The intrinsic pathway of coagulation may be more important than the extrinsic pathway in the pulmonary vascular injury produced by ET.

Amino Acid Chloromethyl Ketones↗

[A prospective study on the timing of discontinuation of aspirin before coronary artery bypass grafting].

The effects of the timing of discontinuation of aspirin before coronary artery bypass grafting (CABG) on postoperative blood loss and blood requirements were examined in 22 patients undergoing elective CABG, who were randomly assigned into two groups. In Group I (11 patients), aspirin was discontinued two days before the operation and in Group II (11 patients), aspirin was continued up to the operation. The other 40 patients, who did not take aspirin for at least seven days before the operation, served as a control Group. There were no differences in preoperative data including the platelet count and the hemoglobin concentration, nor in operative variables such as operation time, cardiopulmonary bypass duration and aortic crossclamp time among the groups. Although postoperative blood loss (six hours' loss; Group I 218 ml, Group II 183 ml and control Group 172 ml) and red blood cells transfusion requirements were not different among the groups, platelet concentrates transfusion was more frequently required in Group II (54.5%) as compared with control Group (7.5%) and Group I (9.1%). The difference between Group II and the control Group reached statistical significance (p < 0.01), but there was no significant difference between Group I and control Group. This fact suggests that preoperative two days' discontinuation of aspirin works as effectively as seven days' discontinuation.

Aged↗

Glycogen-rich Clear Cell Carcinoma of the Breast: A Case Report and Review of the Literature.

A case of glycogen-rich clear cell carcinoma (GRCC) which arose in the right breast of a 35-year-old Japanese woman is reported. Light microscopic examination of the tumor revealed solid alveolar proliferation of clear cells containing abundant glycogen. Electron microscopy identified aggregates of glycogen particles and numerous empty glycogen lakes. This case is reported with a discussion on the other 42 GRCC cases reported in the international literature.

Journal Article↗