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Biomedical subjects

H Baba

Publications and source records attributed to H Baba.

At least 397 records · Page 22Linked to original sources

Increase of aqueous humor proteins with aging.

Quantitative analyses by crossed immunoelectrophoresis were carried out on 31 eyes of 26 cataract patients, age 4-80 years, to detect age changes in the human aqueous humor especially in the following aqueous humor proteins: prealbumin, albumin, alpha 1-acid glycoprotein and transferrin. There was a significant correlation between age and concentration of each of the 4 proteins. The results reported in this paper may be due to senile alteration of the pathway that serum proteins follow from the leaky vessels of the ciliary body to the anterior chamber and/or to a decrease of the aqueous flow rate with advancing age. The relationship between the ages and the aqueous humor protein levels established in this study can be utilized as controls in studying the aqueous humor proteins in uveitis and other ocular diseases.

Adult↗

[Experimental study on the pathophysiology of endotoxin shock as analysed by alterations in thromboxane B2 and 6-keto-PGF1 alpha levels].

To evaluate the pathophysiological role of thromboxane A2 (TXA2) in endotoxin shock, plasma concentrations of TXA2 and PGI2 following E. coli endotoxin (ET) administration were measured in dogs and rats by radioimmunoassay of their stable metabolites TXB2 and 6-keto-PGF1 alpha, respectively. Also, the effects of TXA2 synthetase inhibitor (OKY046) on eicosanoid levels, haemodynamics and survival were assessed. The following results were obtained: 1) Survival rates of the rats given 50 mg/kg of ET were 31% at 12 hrs and 17% at 24 hrs. Pretreatment with OKY046 markedly improved the survival rates. 2) Plasma concentrations of TXB2 were rapidly elevated in untreated control dogs and rats following ET administration, whereas plasma 6-keto-PGF1 alpha levels were gradually elevated. TXB2/6-keto-PGF1 alpha ratio showed an early elevation at 15 minutes after ET administration. The ratio became lower than base line, thereafter. 3) In contrast to the controls, animals pretreated with OKY046 did not exhibit significant elevations in plasma TXB2 levels. On the other hand, plasma levels of 6-keto-PGF1 alpha were not altered by OKY046 treatment. 4) In the control dogs given ET, the early elevations in pulmonary artery pressure (PAP) and reduction in lung compliance correlated with the early elevation in plasma TXB2/6-keto-PGF1 alpha ratio. 5) In OKY046-treated dogs, the early elevation in TXB2/6-keto-PGF1 alpha ratio was not seen and PAP increase and lung compliance reduction were prevented. The results suggest that TXA2 plays an important pathophysiological role in the development of endotoxin shock.

6-Ketoprostaglandin F1 alpha↗

A role of the striatum in premotor cortical seizure development.

Striatal function in partial seizure development induced by low frequency cortical stimulation of the ipsilateral premotor cortex was investigated by either electrolytic lesion placement or microinjection of putative neurotransmitter-related drugs into the ipsilateral striatum. Unilateral striatal lesioning and intrastriatal injection of muscimol, a GABA-agonist, and glutamic acid diethylester, a presumed antagonist for glutamatergic neurotransmission, were effective in suppressing seizure development, whereas intrastriatal injection of a subconvulsive dose of carbamylcholine chloride (carbachol), a cholinergic agonist, decreased the seizure threshold. In contrast to the ipsilaterally dominant metabolic activation in the intact animal, an inverse asymmetry due to a considerable reduction of deoxyglucose uptake in the ipsilateral thalamus, entopeduncular nucleus, substantia nigra, striatum and surrounding cortex of the focus was found in those brains with striatal lesion. Altogether, the findings suggest that experimental reduction of the inhibitory striatal outputs to both the entopeduncular nucleus and the substantia nigra enhances tonic activities of the projection GABAergic neurons in those nuclei, thereby inhibiting seizure development.

Animals↗

Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors.

The search for new water-soluble analogues of camptothecin (CPT) with higher activity and less toxicity has led to the development of a novel compound, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11), which showed significant antitumor activity against a broad spectrum of experimental tumor models by i.p., i.v., or oral administration. When its activity against L1210 was compared with that of CPT and known derivatives, CPT-11 was most effective, giving the highest maximum increase in life span (ILS) and showing good activity over a wide dose range. The antitumor activity of CPT-11 was shown against tumors not only in the ascites form but also in the solid form. Included among the more susceptible murine tumors are S180, Meth A fibrosarcoma, Lewis lung carcinoma, Ehrlich carcinoma, MH134 hepatoma, mammary carcinoma of C3H/HeN mice, L1210, and P388 leukemia. Probable cures of these tumors were induced frequently by CPT-11. The antitumor activity of CPT-11 against i.p.-implanted L1210 was superior to that of Adriamycin in maximum ILS, the number of cured mice, and the therapeutic ratio. CPT-11 at a dose of 100 mg/kg produced an ILS in excess of 300% with five of six mice surviving tumor free, and effected 100% tumor regression at 200 mg/kg, whereas the optimum dose of Adriamycin, 12.5-25 mg/kg, brought about 114-129% ILS with one of six mice surviving. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration. CPT-11 is expected to be clinically useful.

Animals↗

Murine monoclonal antibodies to the myelin-associated glycoprotein (MAG) recognize Leu-7-reactive molecules on human mononuclear cells.

It is known that the antibody to human myelin-associated glycoprotein (MAG) reacts with a subset of human mononuclear cells (MNC) mediating a natural killer (NK) activity. The properties of the target molecule of the anti-MAG antibody, however, have not yet been elucidated. Three (GC-J4, MC-P2, and MC-P4) of five murine monoclonal antibodies (mAb) to MAG bound to human MNC. Moreover, MC-P2 and MC-P4 inhibited the binding of 125I-labeled anti-Leu-7 to MNC in a dose-dependent fashion. Conversely, anti-Leu-7 inhibited the binding of MC-P2 and MC-P4 to MNC, but did not inhibit the binding of GC-J4. Therefore, it is possible that MC-P2 and MC-P4 bind directly to or close to the Leu-7 epitope, and that GC-J4 binds to the epitope which is distinct from the Leu-7 epitope. The electrophoretic patterns of immunoprecipitates with GC-J4, MC-P2 and anti-Leu-7 from detergent lysates of surface-labeled human MNC were very similar. The target molecules of anti-Leu-7 and anti-MAG mAb have apparent m.w. of 205, 170, 150, 135, 110, 85, 65, and 55 kDa. All of the molecules precipitated by these mAb are monomeric or noncovalently associated proteins, because the electrophoretic mobilities of the proteins remained unchanged whether the samples were reduced or not. MC-P4 may have a higher affinity for the 65 kDa molecule than the other mAb, and precipitates the 58 kDa molecule as well. Therefore, the fine antigenic specificity of MC-P4 is slightly different from those of anti-Leu-7 or MC-P2. The implication of these results is that mAb, whose specificity is directed to the carbohydrate part of human MAG, reacts with the Leu-7 reactive molecules on human MNC, and that at least two epitopes detected by anti-MAG mAb coexist on the surface molecules with various apparent m.w.

Animals↗

Possible involvement of protein kinase C in parathyroid hormone degradation by osteoblast-like rat osteosarcoma cell line UMR106.

The effects of 12-O-tetraadecanoyl phorbol-13-acetate (TPA), 1-oleoyl-2-acetyl-glycerol (OAG), and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) on the parathyroid hormone (PTH) degrading activity in a PTH-responsive osteoblast-like rat osteosarcoma cell line UMR106 were investigated to assess the role of Ca2+-activated. Phospholipid dependent protein kinase (protein kinase C) on the degradation of hormones. TPA and OAG, activators of protein kinase C, enhanced the PTH degrading activity dose-dependently, whereas H-7, an inhibitor of protein kinase C, exhibited a dose-dependent inhibition on this activity. These data suggest that protein kinase C activation may enhance PTH degrading activity by UMR106 cells as a possible regulator of PTH degradation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Developmental changes of myelin-associated glycoprotein in rat brain: study on experimental hyperphenylalaninemia.

We examined developmental changes of myelin-associated glycoprotein (MAG), basic protein (BP), and proteolipid protein (PLP) in central nervous system myelin isolated from experimental hyperphenylalaninemic rats (PKU rats) and controls. Higher amounts of MAG, including high-molecular-weight MAG in myelin, were found in 12- to 21-day-old control rats than in adult rats. MAG in developing myelin was at a maximum in 18-day-old rats and began to decrease in 21-day-old rats, while PLP and BP in developing myelin increased at these developmental stages. The level of high-molecular-weight MAG decreased in myelin prepared from 21-day-old rats. These results suggest that the decreasing high-molecular-weight MAG is important for compaction of myelin in the early stage of myelination. In myelin from 12- to 18-day-old PKU rats, the ratio of each protein such as MAG, PLP, or BP to that of control was about 0.5 at 12 days, and increased to almost 1.0 at 18 days. The myelination seems to be initially delayed but to be close to that of controls in PKU rats about 18 days old.

Animals↗

Ultrastructural cytochemistry of oxytalan fibres in monkey periodontal ligaments with the high iron diamine method.

Monkey periodontal ligaments have been examined at the ultrastructural level to demonstrate the nature of reactive sites in oxytalan fibres. The high iron diamine (HID) and HID-thiocarbohydrazide-silver proteinate methods specific for sulphate groups, with and without prior oxidation with monopersulphate, were used. Oxytalan fibres were composed of bundles of microfibrils with a diameter of 11.5 +/- 1.7 nm (mean +/- S.D., n = 50). In cross section the microfibrils were found to have a denser periphery, giving them a 'tubular' appearance. The oxytalan microfibrils of non-oxidized specimens showed little reactivity with either HID method, except that the extracellular matrix material in close association with collagen fibrils stained weakly; in oxidized specimens, both HID methods strongly stained oxytalan microfibrils and weakly stained the extracellular matrix material. Such reactivity of oxytalan microfibrils was not altered by digestion with testicular hyaluronidase or chondroitinase ABC, performed prior to or after persulphate oxidation. Further, the sequential thiosulphation and HID method for the demonstration of disulphide and sulphhydryl groups stained oxytalan fibres moderately. These results indicate that the oxidative generation of sulphate groups in oxytalan fibres may occur from either disulphide or sulphhydryl groups, or both, rather than the result of unmasking of sulphated glycosaminoglycans.

Animals↗

Transcallosal response (TCR) in the chronic photosensitive baboon preparation, Papio papio. I. Premotor cortical stimulation, recovery cycle and neurotropic drug effect.

Transcallosal response (TCR) and its recovery cycle were studied in the chronic photosensitive baboon, Papio papio. Bipolar premotor intracortical stimulation evoked early positive (P1) and negative (N1) sequences followed by late small positivity (P2) and large negativity (N2) in the contralateral homotopic site. The sequential pattern of P1 and N1 was similar to that previously described in acute preparations. The recovery cycle as measured by means of paired stimuli with varying inter-stimulus intervals (ISI) showed a marked supernormality of P1 and N1 at an ISI of 15-200 msec with maximal facilitation up to 250-300% of the conditioning response at an ISI of 30-50 msec. Pentobarbital (10 mg/kg) suppressed this supernormality without causing a constant TCR amplitude change. In contrast, a significant increase in both the TCR amplitude and the supernormality of the recovery cycle was observed with a subconvulsive dose (3 mg/kg) of Megimide, a presumed antagonist of pentobarbital. Our results suggest that (a) the recovery cycle is a more sensitive measure than amplitude for assessing the effect of neurotropic drugs on TCR, and (b) the P1, N1 amplitudes and the supernormality may represent different neuronal processes involved in the TCR.

Animals↗

Transcallosal response (TCR) in the chronic photosensitive baboon preparation, Papio papio. II. Effect of premotor cortical kindling.

The chronological pattern of transcallosal response (TCR) and its recovery cycle were studied by single or paired stimulation of the homotopic primary and the secondary (contralateral) cortical site before, during and after primary site premotor cortical kindling in Papio papio. Prior to kindling, the sequential pattern of TCR was early positive (P1), negative (N1), late small positive (P2) and large negative (N2) components. The recovery cycle of both P1 and N1 showed a marked supernormal phase at an inter-stimulus interval of 15-200 msec with a peak at about 30 msec, showing maximal facilitation up to 300%. Kindling, with or without prior low frequency cortical stimulation, resulted in a long-lasting amplitude potentiation of both P1 and N1 and a significant modification of the late components. However, a transient amplitude reduction was noted immediately following completion of stage 5 kindling, presumably due to repeated generalized convulsions. These changes occurred only during primary (kindling), but not secondary, homotopic site stimulation. These findings suggest that a persistently increased callosal transmission is probably due to primary site kindling-induced functional alteration of the synaptic site at the homotopic secondary site cortex. In contrast, the supernormal phase of the TCR recovery cycle was suppressed significantly at the secondary site cortex. Since a similar suppressive effect was observed with a small dose of pentobarbital in naive baboons, kindling is considered to produce enhancement of the inhibitory mechanism. However, a diminished suppressive effect on the supernormality 20 days after the termination of kindling suggests that this suppressive effect is transient. It is probably related to the repeated kindled convulsive seizures rather than to the kindling process itself.

Animals↗

Antibody to sialosyllactosaminylparagloboside in a patient with IgM paraproteinemia and polyradiculoneuropathy.

Serum from a patient with IgM paraproteinemia and polyradiculoneuropathy, diagnosed as malignant lymphoma, reacted specifically with a ganglioside, sialosyllactosaminylparagloboside (SLPG), in human peripheral nerve but not with myelin-associated glycoprotein (MAG). This finding demonstrates the existence of anti-SLPG antibody in the patient's serum, suggesting that this antibody may play a role in the pathogenesis of neuropathy.

Aged↗

Shared carbohydrate antigenic determinant between the myelin-associated glycoprotein (MAG) and lung cancers. An immunohistochemical study by an anti-MAG IgM monoclonal antibody.

An immunochemical study has shown that monoclonal anti-myelin-associated glycoprotein (MAG) antibodies identify some membrane glycoproteins from cell lines of small cell lung cancer. We investigated immunohistochemically 85 specimens of lung cancer from resection and autopsy using one of the monoclonal antibodies against MAG. One adenocarcinoma was highly reactive with the anti-MAG antibody, and in three small cell carcinomas immunostained tumor cells were distributed either singly or in occasional small clusters. These results show that a shared antigenic determinant with MAG appears on the tumor cells. MAG is believed to play the role of antigen in the development of carcinomatous polyneuropathy, and contributes to cancer development by its reduction of natural killer (NK) cell activity.

Antibodies, Monoclonal↗

Construction of an excretion vector and extracellular production of human growth hormone from Escherichia coli.

A new excretion vector, pEAP8, was constructed to develop an excretion system for Escherichia coli. This plasmid, derived from pEAP37, carried the weakly activated kil gene of plasmid pMB9 [Kobayashi et al., J. Bacteriol. 166 (1986) 728-732] and the penicillinase promoter and signal region of an alkalophilic Bacillus sp. to excrete foreign gene products. A gene for human growth hormone (hGH) was joined to this signal sequence through the HindIII site. The recombinant plasmid p8hGH1 thus constructed, was introduced into E. coli. The hybrid protein which was produced in E. coli carrying p8hGH1 was processed during transport through the inner membrane, with the mature hGH being excreted into the medium through the outer membrane which was made permeable by the action of the kil gene. The N-terminal amino acid sequence and the biological activity of the extracellular hGH were consistent with those of the authentic hGH.

Animals↗

Neutral protease in cerebrospinal fluid from patients with multiple sclerosis and other neurological diseases.

Neutral protease activity was significantly elevated in the cerebro-spinal fluid of patients with multiple sclerosis (MS) in exacerbation and in the acute phase of acute viral meningoencephalitis (AME) compared with that of MS in remission, amyotrophic lateral sclerosis or psychosomatic disease. Since in each relapse of MS, protease activity was higher in exacerbation than in remission, this activity may be one good marker of disease activity in MS. One hundred micro molar of FOY305, synthetic protease inhibitor, inhibited in vitro increased neutral protease activity in MS in exacerbation, which suggests the possibility of a clinical application of this protease inhibitor for MS.

Amyotrophic Lateral Sclerosis↗

Antitumor activity of a new camptothecin derivative, SN-22, against various murine tumors.

The antitumor activity of a new camptothecin derivative, SN-22, was evaluated by using various murine tumors. SN-22 showed strong activity against the ascites tumors Ehrlich carcinoma, MM46, CCM, L1210, L5178Y, P388, Meth A, and B16 melanoma. In particular, the maximum increase in life span values for Ehrlich, MM46 and CCM were as high as 253-606% and many mice were cured of these tumors. The effect of SN-22 against solid tumors was also determined. The inhibition ratios were higher than 70% for MM46 and L5178Y. The LD50 of SN-22 in ICR mice was about 1.5 times that of the parent camptothecin.

Animals↗