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Biomedical subjects

N Sakamoto

Publications and source records attributed to N Sakamoto.

At least 145 records · Page 8Linked to original sources

Strong control on the transit time in metabolic channelling.

A suite of different characteristic times is used to describe the temporal behavior of a metabolic pathway. Here we focus on the 'transit' time, that is the average time it takes for a molecule, entering the steady-state pathway as a substrate, to exit the pathway as a product. We show that metabolic channelling results in dramatic changes in control exerted by pathway enzymes on the transit time. In an 'ideal' pathway a doubling of the enzyme concentrations halves the transit time. In a dynamic channel such an increase can reduce the transit time by a factor of four or more.

Enzymes↗

Effects of long-term enalapril treatment on persistent microalbuminuria in normotensive type 2 diabetic patients: results of a 4-year, prospective, randomized study.

The beneficial effect of long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor on urinary microalbumin excretion (UAE) and renal function was investigated in a 4 year, randomized prospective study in normotensive patients with non-insulin-dependent (Type 2) diabetes mellitus. Sixty-two normotensive patients with Type 2 diabetes mellitus and microalbuminuria but normal renal function were randomized to receive either enalapril 5 mg day-1 or no treatment. In the enalapril-treated patients, UAE was reduced from 115.4 +/- 80.1 to 95.6 +/- 61.7 mg 24 h-1 after 12 months (p < 0.05) and to 75.3 +/- 44.8 mg 24 h-1 after 48 months (p < 0.001). In the untreated group, UAE increased slowly from 93.9 +/- 69.9 to 150.0 +/- 144.5 mg 24 h-1 after 48 months. No changes in creatinine clearance, blood pressure or HbA1C were seen in either group during the 4-year period. In normotensive Type 2 diabetic patients with early stage of diabetic microalbuminuria. This effect is long-lasting and probably independent of the antihypertensive action of the drug.

Aged↗

Relationship of ultrasonic and histologic findings in benign prostatic hyperplasia.

We compared the ultrasonic and histologic findings in 25 patients with benign prostatic hyperplasia (BPH) who underwent retropubic subcapsular prostatectomy. Preoperative ultrasonograms showed a fine echogenic pattern in one case, a rough echopenic pattern in four cases, and a combination of these patterns in 20 cases. In cases exhibiting a mixed pattern, we analyzed each region individually. Ultrasonic and histologic findings were compared in a total of 45 regions. In the 21 regions with a fine echogenic pattern, 14 regions corresponded to those with complicated hyperplastic glands, one region with small cystic atrophic glands, and six regions with a mixture of the two types on histology in observation. In the 24 regions with a rough echopenic pattern, 20 regions corresponded to those with large cystic atrophic glands and an equal volume of large and small cystic atrophic glands were found in the other four. Thus, the echogenic structures observed in patients with BPH were determined by the presence of complicated hyperplastic glands and small cystic atrophic glands.

Aged↗

Effects of released products from platelets on neutrophilic adhesion to endothelial cells and nylon fibers.

In this study, the effects of platelet release products (PRPr), ATP, and ADP on the adhesion of human neutrophils to human umbilical vein endothelial cells (HUVEC) and nylon fibers (NF) are described and the implications of various adhesion molecules are considered. Adhesion of neutrophils to HUVEC and NF was increased by PRPr, ATP, and ADP, while their adhesion-increasing actions were cancelled or considerably repressed by apyrase treatment. When anti-CD11a or anti-CD11b was added to neutrophils with PRPr, ATP, or ADP, the adhesion-increasing action was cancelled or considerably repressed. On the other hand, anti-ICAM-1 and anti-CD35 had no significant effects on this action. The above results indicated that platelets, through ATP and ADP in PRPr, increased the adhesion of neutrophils to endothelial cells and foreign bodies. Although it was suggested that the adhesion-increasing action was at least partially based on CD11a and CD11b, ICAM-1 and CD35 had no part in the enhancement of the adhesion.

Adenosine Diphosphate↗

Proliferation of osteoclast-like giant cells in a metastatic bone tumor from stomach cancer: report of a case and analysis of the autopsy findings.

A 70-year-old man who had undergone esophagectomy with reconstructive surgery using a portion of the stomach 5 years earlier for esophageal cancer was admitted to our hospital after a routine endoscopy and histological examination of a biopsy specimen revealed poorly differentiated adenocarcinoma in the stomach. A gastrectomy and intrathoracic esophagojejunostomy was performed on January 20, 1993; however, the patient suffered a cerebral infarction and died of septic shock on April 9, 1993. At autopsy, metastatic tumors were macroscopically observed in various organs, including a bone tumor measuring 1.0 cm in diameter in the L4 vertebra. To clarify the origin of the bone tumor, we conducted histological and immunohistochemical examinations. Histological examination revealed a mixture of osteoclast-like giant cells (OGCs) and poorly differentiated adenocarcinoma cells, although no histologic features of OGCs were observed either in a primary site or in any of the multiple metastatic lesions. On immunohistochemistry, adenocarcinoma cells in the bone stained positively for the carcinoembryonic antigen (CEA), whereas no staining for CEA was observed in the OGCs which demonstrated negative staining for all the antigens of epithelial markers. These findings led us to conclude that this bone tumor had metastasized from the stomach cancer and that the OGCs may have originated from mesenchymal cells reacting to the adenocarcinoma cells.

Adenocarcinoma↗

Effects of propionyl-L-carnitine and insulin on the electroretinogram, nerve conduction and nerve blood flow in rats with streptozotocin-induced diabetes.

The effect of an analogue of L-carnitine, propionyl-L-carnitine, on the electroretinogram, motor nerve conduction velocity and nerve blood flow was determined in rats with streptozotocin-induced diabetes, and was compared with the effects of insulin alone or combined therapy. Oral administration of propionyl-L-carnitine (3 g/kg daily for 4 weeks) significantly increased caudal nerve motor conduction velocity and sciatic nerve blood flow in diabetic rats. There were no differences in the effects of insulin (8-10 U daily for 4 weeks), propionyl-L-carnitine and combined therapy. Although propionyl-L-carnitine significantly shortened the peak latency of the electroretinogram b-wave in diabetic rats, its effect was far weaker than that of insulin or combined therapy, with combined therapy producing the greatest improvement. These effects of propionyl-L-carnitine were accompanied by a decrease of serum lipid levels, an increase of the sciatic nerve carnitine content, and no changes of the tissue (nerve and retinal) sorbitol and myo-inositol concentrations. In contrast, insulin significantly reduced the tissue sorbitol content and markedly increased myo-inositol. These findings suggest that propionyl-L-carnitine may improve diabetic neuropathy and retinopathy without influencing the polyol pathway, and that this beneficial effect may be mediated through the amelioration of microcirculation and tissue carnitine content, thus probably increasing fatty acid oxidation.

Animals↗

Object-oriented development of a concept learning system for time-centered clinical data.

A concept learning system is expected to be a powerful tool for filtering and analyzing a large amount of data in a variety of scientific fields. A simple application of it to clinical data, however, fails to mine medical information and knowledge. One of the major obstacles in mining a clinical database is time, which is a very important concept in clinical medicine. To be successful in data mining in clinical medicine, an efficient model of clinical data with time and a flexible concept learning system augmented to handle the model are both necessary. Herein we modeled clinical data to easily express and manipulate time and extended a concept learning system to utilize a time-centered clinical data model. The modified concept learning system is based on the message-value method rather than the traditional attribute-value method. The object-oriented technology was of great help in modeling time-centered clinical data and in developing a modified concept learning system.

Algorithms↗

Dopamine-beta-hydroxylase and tyrosine hydroxylase immunoreactive neurons in the human brainstem.

Immunohistochemistry of dopamine-beta-hydroxylase in the human hind brain indicates that neuronal cell bodies containing the antigen form prominent populations in the nucleus tractus solitarius and nearby medial and dorsal edge of the medial vestibular nucleus. They are frequent in and around the periphery of the dorsal motor nucleus of the vagus and in an oblique band extending from that region to the ventrolateral aspect of the reticular formation, where they are most numerous at the mid medullary levels. Dopamine-beta-hydroxylase immunoreactive neurons are also closely packed in the nuclei coeruleus and subcoeruleus. Concomitant immunohistochemistry for tyrosine hydroxylase demonstrates small numbers of neuronal cell bodies that are reactive only for this antigen, and which do not contain detectable dopamine-beta-hydroxylase. Such neurons are present in the nucleus tractus solitarius, the pontine lateral parabrachial nucleus and within the core of the rostral pontine reticular formation. Some medullary and pontine axon bundles similarly stain for tyrosine hydroxylase but not for dopamine-beta-hydroxylase. These differential staining patterns suggest, among other possibilities, that in humans some neurons of the caudal brainstem are dopamine (if they contain the second step catecholamine synthesizing enzyme, aromatic L-aminoacid decarboxylase) rather than noradrenaline or adrenaline containing catecholamine neurotransmitters.

Aged↗

Recovery of macromolecular activators of phagocytosis from platelets (MAPP) producing and releasing function in stored human platelets.

Macromolecular activators of phagocytosis from platelets (MAPP) were not released from platelets prepared from platelet concentrates (PC) obtained after anticoagulation with CPD solution and stored for more than 48 h. The MAPP activity which had escaped into the plasma disappeared after 72 h of storage. After incubation in dialyzed and Ca(2+)-supplemented plasma prepared from the same PC or from fresh peripheral blood, the platelets obtained after storage for 72 h released both MAPP (l-MAPP and s-MAPP) upon thrombin stimulation. Gel filtration studies of the plasma revealed that l-MAPP and s-MAPP were produced from the platelets incubated in plasma fractions corresponding to l-MAPP and s-MAPP, respectively. These observations suggest that platelets accumulate precursors of MAPP, pre-MAPP comprising pre-l-MAPP and pre-s-MAPP, in the presence of Ca2+, and produce and release MAPP when stimulated with thrombin.

Biological Factors↗

The occurrence of macrophage-like cholera toxin uptake cells in the intestinal villi of suckling rats.

An oral administration of cholera toxin (CT. 10m g) caused diarrhea in infant rats ranging in age from 1 to 14 days. After administration of the toxin a time sequence study was carried out using highly sensitive immunohistochemical procedures. CT was exclusively incorporated into a type of macrophage-like (ML) phagocytic cell. These cells were identified within the intestinal epithelium of rats suffering choleraic diarrhea. After 2 hrs cells taking up the toxin markedly increased in number and were found in both the mucosa and the lamina propria mucosae. After 4 hrs a small number of ML cells containing CT were still present in the mucosal epithelium, but were no longer observed in the lamina propria. Two kinds of monoclonal antibodies against rat macrophages were used to gain a clue as to the cytological characteristics of ML cells. ED1- or ED2-positive macrophages were demonstrable in the lamina propria and submucosa of the small intestines from control rats. In CT-treated rats a considerable number of cells positive for CT and ED1, or CT and ED2 antisera, were found within the epithelial cell layer and the lamina propria of intestinal villi. It is suggested that many ML cells responsive to CT, if not all, are ED1 and ED2 macrophages and are resident in the villous lamina propria where they can migrate to uptake CT in the intestinal lumen. CT B-subunit and heat-labile toxin (LT) B'-subunit from a mutant strain Escherichia coli were given to the rats in order to know the onset mechanism of toxin uptake. It seems likely that the toxin receptor, GM1 ganglioside, participates in the initiation of CT-uptake mechanism. A possible role of the intestinal ML cells was discussed.

Animals↗

LIF and CNTF, which share the gp130 transduction system, stimulate hepatic lipid metabolism in rats.

We determined the effects of leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) on lipid metabolism in intact rats. Administration of LIF and CNTF increased serum triglycerides in a dose-dependent manner with peak values at 2 h. The effects of LIF and CNTF on serum cholesterol were very small, and serum glucose was unaffected. Both LIF and CNTF stimulated hepatic triglyceride secretion, hepatic de novo fatty acid synthesis, and lipolysis. Pretreatment with phenylisopropyl adenosine, which inhibits lipolysis, partially inhibited LIF- and CNTF-induced hypertriglyceridemia. Interleukin-4, which inhibits cytokine-induced hepatic fatty acid synthesis, also partially inhibited LIF- and CNTF-induced hypertriglyceridemia. These results indicate that both lipolysis and de novo fatty acid synthesis play a role in providing fatty acids for the increase in hepatic triglyceride secretion. Neither indomethacin nor adrenergic receptor antagonists affected the hypertriglyceridemia. The combination of LIF plus CNTF showed no additive effects consistent with the action of both cytokines through the gp130 transduction system. Thus LIF and CNTF have similar effects on lipid metabolism; they join a growing list of cytokines that stimulate hepatic triglyceride secretion and may mediate the changes in lipid metabolism that accompany the acute phase response.

Animals↗

A triplex DNA structure of the polypyrimidine: polypurine stretch in the 5' flanking region of the sea urchin arylsulfatase gene.

Previously we reported that a long (522 bp) polypyrimidine: polypurine stretch in the 5' flanking region of the arylsulfatase gene of the sea urchin, Hemicentrotus pulcherrimus, took an unusual, perhaps triplex, DNA structure, when subjected to an acidic pH (pH 5) (Yamamoto et al., 1994). In the present study we have isolated a polypyrimidine: polypurine containing fragment from the arylsulfatase gene and surveyed the sensitivities of the polypyrimidine: polypurine stretch to base modification by diethylpyrocarbonate and osmium tetroxide under various levels of negative supercoiling. Based on the sensitivity of highly negatively supercoiled DNA to these base-modifying reagents, we conclude that, when highly negatively supercoiled, the polypyrimidine: polypurine stretch can take a triplex DNA structure even at a neutral pH and under physiological ionic strength in the presence of Mg2+.

Amino Acid Sequence↗

Effects of beraprost sodium and insulin on the electroretinogram, nerve conduction, and nerve blood flow in rats with streptozotocin-induced diabetes.

The effect of a prostacyclin analog, beraprost sodium, on the electroretinogram, motor nerve conduction velocity, and nerve blood flow was determined in rats with streptozotocin-induced diabetes and was compared with the effect of insulin. Beraprost sodium (0.01 mg x kg-1 x day-1 for 8 weeks) significantly shortened the peak latency of the electroretinogram b-wave, increased tail nerve conduction velocity, and increased sciatic nerve blood flow in diabetic rats (P < 0.0003, 0.0001, and 0.0001 vs. untreated diabetic rats, respectively). This was accompanied by a significant increase in the 6-keto-prostaglandin F1alpha content of the thoracic aorta and a marked increase in the cAMP content of the sciatic nerve. Beraprost sodium had no effect on the sorbitol and fructose contents of the sciatic nerve and retina, but insulin (8-10 U/day) significantly reduced both parameters. These findings suggest that beraprost sodium may be useful for prevention of vascular and neural dysfunction in the retina and peripheral nerve.

6-Ketoprostaglandin F1 alpha↗

Effect of propionyl-L-carnitine on motor nerve conduction, autonomic cardiac function, and nerve blood flow in rats with streptozotocin-induced diabetes: comparison with an aldose reductase inhibitor.

The effects of propionyl-L-carnitine (PCAL) on caudal motor nerve conduction velocity, the coefficient of variation of the R-R interval on the electrocardiogram, and sciatic nerve blood flow were compared with those of [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate, an aldose reductase inhibitor, in rats with streptozotocin-induced diabetes. Diabetic control rats showed significantly delayed nerve conduction (P < .05), decreased R-R variability (P < .05) and reduced sciatic nerve blood flow (P < .05). Oral administration of PCAL (0.5 g/kg/day) and [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (0.05% in the diet: 60 mg/kg/day) for 8 weeks significantly improved both nerve conduction (P < .05) and R-R variability (P < .05) in diabetic rats, along with the normalization of sciatic nerve blood flow. PCAL treatment increased the nerve tissue levels of carnitine and myo-inositol and reduced the serum triglyceride level in diabetic rats. Our results suggests that PCAL could have therapeutic potential for the treatment of diabetic neuropathy.

Aldehyde Reductase↗