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Biomedical subjects

M Kaku

Publications and source records attributed to M Kaku.

At least 217 records · Page 12Linked to original sources

Immune reactivity to Thomsen-Friedenreich antigen in patients with lung cancer detected by superoxide assay-leukocyte adherence inhibition test.

The immune reactivity to partially purified Thomsen-Friedenreich antigen was investigated in patients with lung cancer. The modified method of original leukocyte adherence inhibition test, termed superoxide assay-leukocyte adherence inhibition test, was used to detect the reactivity. The coded peripheral mononuclear cells from 34 of 50 (68%) patients with lung cancer showed a positive response to the antigen whereas in only 3 of 19 (16%) patients with benign pulmonary disease was there a reaction to the antigen. The same experiments were performed using the 3 m KCl extract of lung tumors as an antigen. In this case in 39 of 50 (78%) patients with lung cancer but in only 4 of 24 (17%) with benign pulmonary disease and in none of the breast cancer patients (0 of 17) was there a reaction to the antigen. These results strongly suggest that patients with lung cancer are sensitized to both Thomsen-Friedenreich antigen and tumor-associated antigens expressed in cancer cells of lung tissue origin.

Adult↗

Infants in Juba, southern Sudan: the first twelve months of life.

A prospective survey of child health in Juba has been continued till the infants were 12 months old. They were visited monthly or more often if unwell. During the second 6 months of life 6 died; these deaths added to the 9 which occurred in the first 6 months produced an infant mortality rate of 11.8%. Diarrhoea was the whole or a partial cause of 11 of the 15 deaths in the first year. Growth in length by 12 months was satisfactory but the mean weight of the study infants was then at the third centile for healthy girls. Head circumference at 12 months was below normal and poor development was associated with the smaller head circumferences. Supplementary feeding had been started for all babies by the 12th month but only 4 of 127 had been weaned. 30 documented attacks of diarrhoea took place before supplementary feeding was started, suggesting that water given to infants is often contaminated.

Birth Weight↗

Hydroxylation of prostaglandin A1 by the microsomes of rabbit intestinal mucosa.

Microsomes from rabbit small intestine mucosa were found to catalyze the hydroxylation of PGA1 in the presence of NADPH. The major product was identified as 20-hydroxy PGA1 by using high performance liquid chromatography and gas chromatography-mass spectrometry, and the minor product was assumed to be 19-hydroxy PGA1. The ratio of the former product to the latter was about 24.1. The specific PGA1 omega-hydroxylase activity of small intestine microsomes was comparable to that of liver microsomes, and was significantly higher than those of microsomes from other tissues such as kidney cortex and lung. Microsomes from rabbit colon mucosa also catalyzed the hydroxylation of PGA1 in the presence of NADPH, with the ratio of omega- to (omega-1)-hydroxy PGA1 formed being 33.0. The PGA1 hydroxylase activities of the microsomes from both small intestine and colon were inhibited markedly by carbon monoxide, indicating the participation of cytochrome P-450. A cytochrome P-450 was solubilized from small intestine microsomes, and purified to a specific content of 10.5 nmol of cytochrome P-450/mg of protein. This cytochrome hydroxylated PGA1 at the omega-position with a turnover rate of 38.2 nmol/min/nmol of cytochrome P-450 in the reconstituted system containing cytochrome P-450, NADPH-cytochrome P-450 reductase, cytochrome b5 and phosphatidylcholine. It is suggested that this cytochrome P-450 is specialized for the omega-hydroxylation of PGA1 in small intestine microsomes.

Animals↗

Isolation of cytochrome P-450 highly active in prostaglandin omega-hydroxylation from lung microsomes of rabbits treated with progesterone.

Two forms of cytochrome P-450, designated as cytochrome P-450p-1 and cytochrome P-450p-2, were separated and purified to specific contents of 8.2 and 8.9 nmol/mg of protein, respectively, from lung microsomes of rabbits treated with progesterone. Cytochrome P-450p-1 and cytochrome P-450p-2 migrated as single polypeptide bands with molecular weights of 49,000 and 52,000, respectively, on SDS-polyacrylamide gel. Their CO-reduced difference spectral peaks were at 451.5 and 450 nm, respectively. Cytochrome P-450p-1 catalyzed the N-demethylation of benzphetamine, O-demethylation of p-nitroanisole, and O-deethylation of 7-ethoxycoumarin, whereas no activity was observed with cytochrome P-450p-2. On the other hand, cytochrome P-450p-2 catalyzed the omega-hydroxylation of prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), and prostaglandin A1 (PGA1) with turnover rates of 9.0, 7.5, and 5.0 nmol of product/min/nmol of cytochrome P-450, respectively, as well as the omega- and (omega-1)-hydroxylation of palmitate and myristate with turnover rates of 27.7 and 16.4 nmol products/min/nmol of cytochrome P-450, respectively. This cytochrome showed a greater affinity for prostaglandins (PGs) than for fatty acids. These reactions were absolutely dependent on cytochrome P-450p-2 and NADPH-cytochrome P-450 reductase, and stimulated by addition of phosphatidylcholine and cytochrome b5. Cytochrome P-450p-2 is thought to be a new form of cytochrome P-450 induced by progesterone treatment in rabbit lung microsomes.

Animals↗

Purification and characterization of cytochrome P-450 specific for prostaglandin and fatty acid hydroxylase activities from the microsomes of rabbit small intestinal mucosa.

Earlier studies (Kusunose, E., Kaku, M., Ichihara, K., Yamamoto, S., Yano, I., & Kusunose, M. (1984) J. Biochem. 95, 1733-1739) showed that a form of cytochrome P-450 isolated from microsomes of rabbit small intestinal mucosa had the highest prostaglandin A1 (PGA1) hydroxylase activity so far reported among cytochrome P-450s. The present paper describes the procedure for the purification and further characterization of this cytochrome (designated as cytochrome P-450ia). Cytochrome P-450ia had a monomeric molecular weight of 53,000. The CO-difference spectra of its reduced form showed a maximal absorption at 451 nm, and the absolute spectra of its oxidized form indicated that cytochrome P-450ia was present largely in the low-spin state, and partially in the high-spin state. The cytochrome efficiently catalyzed the hydroxylation of fatty acids as well as prostaglandins in a reconstituted system containing cytochrome P-450, NADPH-cytochrome P-450 reductase, phospholipid, and cytochrome b5. PGA1 was the most efficient substrate, followed by myristate, laurate, palmitate, caprate, and PGE1 or PGE2. Among phospholipids, didecanoyl- and dilauroylphosphatidylcholines had the most stimulatory effect for both activities. 20-Hydroxy PGA1 was identified as the hydroxylation product of PGA1 by gas chromatography-mass spectrometry and mass fragmentography; the possibility of 19-hydroxy PGA1 being the product was excluded. In contrast, both omega- and (omega-1)-hydroxy fatty acids were identified as hydroxylation products of fatty acids. Cytochrome P-450ia had no detectable activity toward aminopyrine, benzphetamine, p-nitroanisole, 7-ethoxycoumarin, benzo(a)pyrene, or hexadecane.

Animals↗

Biphasic effects of muramyl dipeptide or lipopolysaccharide on superoxide anion-generating activities of macrophages.

The superoxide anion (O2-)-generating activity of guinea pig macrophages stimulated by wheat germ agglutinin (WGA), immune complexes, or phorbol myristate acetate (PMA) was studied after short- and long-term exposures of the cells to muramyl dipeptide (MDP) or lipopolysaccharide (LPS). Neither MDP nor LPS alone induced O2- release in macrophages. Short-term (30 min) exposure to these agents caused the enhanced release of O2- in response to WGA or immune complexes, though the PMA-induced O2- generation was not affected. On the other hand, long-term exposure (more than 24 h) to MDP or LPS progressively enhanced O2- generation of the cells induced by WGA, immune complexes, or even PMA. These results suggest that the mechanism for O2- generation of macrophages stimulated by WGA or immune complexes differs from that stimulated by PMA and that the differences also exist between short- and long-term exposure to MDP or LPS.

Acetylmuramyl-Alanyl-Isoglutamine↗

Phorbol myristate acetate-induced modulation of antibody-dependent cellular cytotoxicity by human polymorphonuclear leukocytes.

The effect of phorbol myristate acetate (PMA) on the antibody-dependent cellular cytotoxicity (ADCC) of human polymorphonuclear leukocytes (PMNs) against human erythroleukemic K562 cells was studied by the use of a 3-h 51Cr-release assay. Pretreatment of PMNs with PMA (10 ng/ml) for 60 min resulted in inhibition of subsequent ADCC. This inhibition was dependent on doses of PMA. The effect of pretreatment of PMNs with PMA on O2- generation of the cells was also studied. The ability of the cells to generate O2- was not suppressed, and the expression of Fc receptors on the cell membrane was well preserved. In contrast, the addition of PMA to the ongoing ADCC (5 to 30 min after the start of the ADCC assay) enhanced the activity of the cells for ADCC. This augmentation was abolished by catalase, whereas ADCC itself was not affected by the agent. These results imply divalent effects of PMA on the ADCC of PMNs. The suppression of ADCC activity of PMNs by pretreatment with PMA is not due to inhibition of the reactive oxygen burst of the cells. The augmentation of ongoing ADCC by the addition of PMA is due to secretion of hydrogen peroxide from the cells induced by PMA, and this augmentation occurs only when the interaction between effector and target cells exists through Fc receptor.

Antibody-Dependent Cell Cytotoxicity↗

Synthesis of adult-type hemoglobin in human erythremia cell line.

KMOE -2/05 cells, derived from a patient with acute erythremia, became benzidine-positive after the addition of cytosine arabinoside (CA). Radioimmunoassays using antihuman hemoglobin antibodies revealed an elevated amount of hemoglobin in the CA-exposed cells over that in the control cells (without CA). Isoelectric focusing of the CA-exposed cell lysate formed benzidine-positive foci in the positions of human adult Hb (HbA) and human fetal Hb (HbF). To determine the types of globin synthesized in the CA-exposed cells, globin chains internally labeled with [3H] leucine were purified by carboxy-methyl (CM)-Sephadex column chromatography, immunoadsorption by Sepharose-coupled antihuman Hb antibodies and Sephadex G-100. The labeled globin chains were finally separated by CM-cellulose chromatography in urea. Two distinct peaks of radioactivity were shown in exactly the same fractions as carrier human globin alpha- and beta-chains. These observations indicate that these KMOE -2/05 cells synthesize HbA.

Cell Line↗

[A clinico-physiological study on the generators of short latency somatosensory evoked potential].

The purpose of this paper is to locate the generators of each wave component in the short latency somatosensory evoked potential (SSEP), by means of cumulative analysis of the SSEP obtained from various localized lesions in the upper cervical cord through brain stem and cerebral subcortical structures. Since there are considerable inconsistency of naming each component in the literature, SSEP to median nerve stimulation of 10 normal subjects were examined by two different recordings, i.e. recording from an electrode at the parietal scalp with a reference electrode on Erb's point (Par.-Erb), and the other at the frontal scalp with a reference electrode on Cv 7 (Fro.-Cv 7), and the SSEP was carefully studied. In normal subjects, the SSEP by Par.-Erb lead yielded 5 negative components (N 7, N 11, N 16, N 18 & N 26) and 4 positive components (P 9, P 13, P 22 & P 42), while by Fro.-Cv 7 5 negative components (N 7, N 10, N 12, N 16 & N 28) and 5 positive components (P 9, P 11, P 13, P 20 & P 44). Thirty three patients were subjected to analyse the influence of localized lesions to each component of the SSEP and the recording was evaluated in regard to (a) identification of each component, (b) latency of each component and inter-peak latency difference exceeding 2 SD, and (c) over 50% asymmetry and laterality of the amplitude. Cervical spondylotic myelopathy, high cervical cord tumor, tonsillar herniation, pontine infarct and hemorrhage, circumscribed thalamic lesion, and vascular lesion of centrum semiovale were carefully examined with CT scan and the findings were compared with neurological findings periodically. SSEP was taken repeatedly, especially before and after operative intervention, and alteration of the component was referred to the clinical progress of the lesion. In conclusion, results obtained from our present observation indicated that P 9 was the extramedullary projection, P 11 was intramedullary origin of the lower cervical cord, P 13 was medulla oblongata origin and P 13-N 16 was projection from medulla oblongata to thalamus. N 16-N 18 and N 26 were considered projection from thalamus to hand area of the parietal lobe with some association area and N 28 had the generator widely based on frontal projection system. These findings appeared to be quite useful for topographic diagnosis and functional evaluation of the lesions in central nervous system.

Adolescent↗

Infants in Juba, Southern Sudan: the first six months of life.

A longitudinal survey of child health in Juba was done to secure data on which preventive schemes could be based. 223 pregnant women were identified in a systematic search of a district. 5 infants were stillborn and 10 were born prematurely. The mothers of 5 of the 10 premature infants had had acute malaria at or immediately preceding delivery. 2 of these premature babies later died from causes attributable to prematurity and therefore indirectly to the preventable maternal malaria. The causes of neonatal mortality included tetanus caused by cutting the cord with a blade of grass. Between the 1st and 6th month, 5 infants died of infective enteritis, 1 of bronchopneumonia, and 1 of pyrexia of undetermined origin associated with convulsions. Growth was much impaired by diarrhoea, which caused 85 attacks among 63 babies, and by lower respiratory infections, of which there were 119 among 74 of the babies. Skin and eye infections were also common. Removal of the unerupted canine teeth, believed to cure or prevent illness, caused much distress and some aspiration bronchopneumonia. Health education and improved hygiene and water supplies would greatly reduce the extent of morbidity and mortality.

Birth Weight↗

Enhanced superoxide anion release from phagocytes by muramyl dipeptide or lipopolysaccharide.

Muramyl dipeptide (MDP) and lipopolysaccharide (LPS) from Escherichia coli were tested for the ability to influence superoxide anion (O2-) release from guinea pig phagocytes. Both MDP and LPS alone did not, by themselves, stimulate O2- release by macrophages and polymorphonuclear leukocytes. However, the preincubation of macrophages with MDP or LPS primed the macrophages to release an enhanced amount of O2- when stimulated by cytochalasin E and wheat germ agglutinin. When polymorphonuclear leukocytes were treated in the same way, only LPS showed an enhancing effect. MDP enhanced NADPH oxidase activity of macrophages, which is probably the reason for enhanced O2- release by MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗

Characteristics of specific binding of epidermal growth factor (EGF) on human tumor cell lines.

Using seventeen human tumor cell lines derived from a variety of tissues, specific binding sites for epidermal growth factor (EGF), a mouse submandibular gland-derived growth factor, has been characterized. A significant amount of membrane-bound EGF receptors, although considerably varied, was demonstrated in all the tumor cell lines studied. Epidermoid carcinoma appeared to have more EGF receptors than adenocarcinoma. One small cell carcinoma of the lung, one choriocarcinoma of the stomach and three bone tumors also possessed EGF receptors comparable to those of epidermoid carcinoma, while one adenoacanthoma of the stomach had less EGF receptors comparable to adenocarcinoma. Among a variety of phorbol esters tested, tetradecanoyl phorbol acetate, a potent tumor promotor, was shown to be the most effective compound in inhibiting 125I-labeled EGF binding to its receptors. Our results indicate that human tumor cells contain varying amounts of membrane-bound receptors for EGF and that phorbol esters interact with these EGF receptor sites. However, the relationship between EGF receptor sites on tumor cells and cellular proliferation and/or differentiation awaits further study.

Cell Line↗