Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 649 records · Page 36Linked to original sources

PubMed1993

Role of iron and superoxide in mediating hydrogen peroxide injury to cultured rat gastric cells.

BACKGROUND: Gastric epithelium is exposed to toxic, reactive oxygen species generated within the lumen. The present study examined the role of cellular iron and superoxide (O2-) in mediating hydrogen peroxide (H2O2)-induced damage to cultured gastric mucosal cells. METHODS: H2O2 was generated by glucose oxidase acting on b-D(+)glucose. Cytotoxicity was assessed by 51Cr release from prelabeled cells. RESULTS: Deferoxamine (a chelator of Fe3+) prevented injury induced by H2O2, whether present before or during H2O2 production. In contrast, whereas the presence of phenanthroline (a chelator of Fe2+) during the cytotoxicity assay prevented damage, prior treatment with the agent did not; this suggested that cellular Fe3+ reduced to Fe2+ upon exposure to H2O2 is responsible for damage. Neither extracellular superoxide dismutase nor inhibitors of xanthine oxidase (a possible source of cellular O2- production) protected against H2O2. Further, protection by iron chelators was not associated with modulation of endogenous antioxidants. CONCLUSIONS: Deferoxamine and phenanthroline protect cells from H2O2 by chelating stored iron (Fe3+) or reduced iron (Fe2+), respectively. Reduction of cellular Fe3+ appears to be a prerequisite for mediation of damage, but this reduction is independent of extracellular O2- or cellular xanthine oxidase-derived O2-.

Allopurinol↗

PubMed1993

Direct vasopressor effects of erythropoietin in genetically hypertensive rats.

The purpose of this study is to compare the direct vasopressor effects of erythropoietin between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The aortic rings from SHR or WKY were suspended in tissue baths coupled with tension-recording devices. High concentrations of recombinant human erythropoietin (more than 20 U/ml) induced vasoconstriction in the aortic ring of genetically hypertensive SHR. Furthermore, only in SHR, 10 U/ml erythropoietin enhanced contraction induced by 10(-7) M norepinephrine (+145% vs +121%, p < 0.04) and reduced relaxation by 10(-7) M acetylcholine (-69% vs -96%, p < 0.05). On the other hand, erythropoietin did not influence the contractility of aortic ring in normotensive WKY. These results suggest that erythropoietin exhibits its direct vasopressor effect preferentially in the blood vessels of genetically hypertensive animals.

Acetylcholine↗

PubMed1993

Relationships among residual beta cells, exocrine pancreas, and islet cell antibodies in insulin-dependent diabetes mellitus.

Quantitative analysis was performed using computerized morphometry on the relationships between residual beta cells, pancreatic exocrine glands, and islet cell antibodies (ICA) in 14 pancreata of insulin-dependent diabetic (IDDM) patients. Both pancreatic exocrine glands and beta cells were markedly reduced in weight in IDDM patients compared with non-insulin-dependent diabetic (NIDDM) patients or nondiabetic controls. beta cells were preserved in six cases and were completely abolished in eight cases. In nine IDDM pancreata weighed at autopsy, the weights of pancreatic exocrine glands in six patients with either no or virtually no residual beta cells (32.3 +/- 1.6 g) were greater than those in three patients with residual beta cells (23.1 +/- 2.5 g, P < .05). Infiltration of lymphocytes positive for leukocyte common antigen (LCA) around the islet was observed in only one case with ICA and residual beta cells. Infiltration of LCA-positive lymphocytes around pancreatic acinar cells was observed in 50% (six of 12) of patients examined. The weight of pancreatic exocrine glands in patients with LCA-positive lymphocyte infiltration (26.2 +/- 2.3 g) was lower than that in patients without this condition (33.2 +/- 2.4 g, P < .05). Pancreatic cytokeratin autoantibodies (PKA) were detected in four of 10 patients examined. In addition, all four ICA-positive patients had residual beta cells, while only one of seven ICA-negative patients had residual beta cells (P = .03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Serum lipoprotein(a) levels differ in different phenotypes of primary hyperlipoproteinemia.

Previous studies have indicated that serum lipoprotein(a) [Lp(a)] levels are mostly under genetic control. We have attempted to determine whether serum Lp(a) levels differ in different phenotypes of primary hyperlipoproteinemia (HL). A total of 129 subjects with HL (three with type I, 43 with familial hypercholesterolemia [FH], 17 with type IIa [non-FH], 11 with type IIb, six with type III [E2/2], 44 with type IV, and five with type V) and 18 normolipidemic controls were included in the study. Thirty-two FH subjects were being treated with hypolipidemic agents, but none of the other subjects were receiving any medication. Fasting blood samples were collected for determination of both serum lipid and Lp(a) levels. Lp(a) level was measured by enzyme-linked immunosorbent assay. The 18 controls had serum Lp(a) concentrations of 18.0 +/- 14.5 mg/dL (mean +/- SD), and four of them had high serum Lp(a) levels (> or = 25 mg/dL). Serum Lp(a) concentrations in FH subjects tended to be higher than in the controls (30.5 +/- 25.0 mg/dL), and the incidence of high Lp(a) levels in FH subjects was significantly higher than in the controls (51% v 22%, P < .01). There was no difference between serum Lp(a) levels of FH subjects depending on whether they were receiving medication. In contrast, most of the subjects with selective hypertriglyceridemia had very low serum Lp(a) levels (1.5 +/- 0.7, 8.1 +/- 8.3, and 3.5 +/- 5.3 mg/dL in type I, IV, and V, respectively; P < .01 v controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Congenital sarcoma in the terminal ileum histologically resembling clear cell sarcoma of the kidney: a case report with an immunohistochemical study.

We report a case of a newborn female with a rare tumor, a congenital sarcoma, presenting as an abdominal mass. Laparotomy demonstrated the tumor arising from the wall of the terminal ileum. Histologically, the tumor tissue was indistinguishable from clear cell sarcoma of the kidney and was composed of proliferating cells with poorly stained cytoplasm divided into nests or cords by arborizing vasculature. Immunohistochemical staining revealed that the neoplastic cells had a phenotype similar to metanephric blastemal cells of fetal kidney, ie, positive for vimentin and CD24 but negative for cytokeratin and CD9. The results suggest that this congenital tumor may originate from primitive mesenchymal cells phenotypically related to cells present in the fetal kidney.

Diagnosis, Differential↗

PubMed1993

Primary colonic epithelial cell culture of the rabbit producing prostaglandins.

We have established primary colonic epithelial cell culture from adult rabbits and examined effects of anti-inflammatory drugs on prostaglandin (PG) E2 production. Colonic epithelium of adult rabbits was scraped and minced into small pieces. They were incubated for isolation in Hanks' balanced salt solution with 0.35% collagenase and Earle's solution with 1 mM EDTA. Isolated cells were cultured in Coon's modified Ham's F-12 medium with 10% fetal bovine serum and antibiotics on collagen coated cell wells. The medium was refed twice a week. The production of PGs was assessed by high pressure liquid chromatography (HPLC). PGE2 and PGF2 alpha were measured by radioimmunoassay. Within 24 hours after inoculation, the cell clumps attached to the surface of the wells and cells began to spread out and grow. Monolayer cultures became confluent in 4 days. Phase contrast microscopy showed that these cells consisted of a homogeneous population of epithelial cells with large oval nuclei, polyhedral shape, and organized sheet-like growth pattern. HPLC profile showed synthesis of 6-keto-PGF1 alpha, thromboxane B2, PGF2 alpha, PGE2, and PGD2 by cultured cells. Quantitatively, 117 +/- 7 ng/mg-protein/hour PGE2 and 7.4 +/- 0.7 ng/mg-protein/hour PGF2 alpha were produced. While hydrocortisone (10(-4) - 10(-2) M) did not show a significant effect on PGE2 production, indomethacin (10(-8) - 10(-6) M), and 5-aminosalicylic acid (2X10(-4)-5X10(-3) M) inhibited PGE2 production. We have established relatively convenient procedure for primary culture of colonic epithelial cells from adult rabbits. Different actions of anti-inflammatory drugs on PGE2 synthesis suggest that these cultured cells might be a good tool for the various cellular functional studies of normal colonic epithelial cells.

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Tooth pulp primary neurons: cell size analysis, central connection, and carbonic anhydrase activity.

Cell bodies and central terminals of trigeminal primary afferent neurons innervating the mandibular molar and incisor tooth pulps were labeled by injecting various neuroanatomical tracers into these tooth pulps. The cell bodies of major constituents of primary neurons innervating the tooth pulp, cornea, and cutaneous branch of the mylohyoid nerve were large (> or = 500 microns2, 65%), medium (300-400 microns2, 35%), and small (100-200 microns2, 34%), respectively. Those innervating the tooth pulp (tooth pulp cells) had the Nissl pattern characteristic of large light cells of the A type, while those innervating the cornea were small dark cells of the B type. Thirty percent of the tooth pulp cells exhibited histochemically demonstrable carbonic anhydrase activity. The transganglionic transport of HRP-WGA indicated marked concentration of central terminals of the tooth pulp primaries in the rostral subdivisions of the brain stem sensory trigeminal nuclear complex. In contrast, central terminals of the corneal primaries were concentrated in the medullary dorsal horn.

Animals↗

PubMed1993

New subtype of apical hypertrophic cardiomyopathy identified with nuclear magnetic resonance imaging as an underlying cause of markedly inverted T waves.

OBJECTIVES: The aim of this study was to elucidate the clinical importance of a new subtype of apical hypertrophic cardiomyopathy that could not be diagnosed with the classical diagnostic criteria. BACKGROUND: Apical hypertrophic cardiomyopathy is recognized by a characteristic spade-shaped intraventricular cavity on the end-diastolic left ventriculogram in the right anterior oblique projection, often associated with giant negative T waves [negativity > or = 1.0 mV (10 mm)]. As an underlying cause of giant negative T waves, an additional new subtype of apical hypertrophic cardiomyopathy has been identified. METHODS: In 40 patients with inverted T waves (negativity > or = 0.5 mV), including 26 patients with giant negative T waves, nuclear magnetic resonance (NMR) long-axis images corresponding to the left ventriculogram in the right anterior oblique projection and short-axis images at various levels, including the apical level, were obtained to define the site of hypertrophied myocardium. RESULTS: Long-axis images indicated a spadelike configuration in 17 patients, whereas this diagnostic configuration was not present in the other 23 patients. Nine of these 23 patients had significantly hypertrophied myocardium at the basal level. In the 14 remaining patients, short-axis images indicated no hypertrophy at the basal level and proved that the area of hypertrophied myocardium was confined to a narrow region of the septum or the anterior or lateral wall at the apical level (nonspade apical hypertrophic cardiomyopathy). The hypertrophied myocardium of the nonspade type was so narrowly confined that the mass did not form a spadelike configuration or could not be detected on the long-axis image. CONCLUSIONS: Nonspade apical hypertrophic cardiomyopathy was newly identified on NMR short-axis images, and this could be an additional, important underlying cause of moderately to severely inverted T waves.

Aged↗

PubMed1993

Relationship between distribution of hypertrophy and electrocardiographic changes in hypertrophic cardiomyopathy.

To assess the relationship between the distribution of hypertrophy and electrocardiographic changes in patients with hypertrophic cardiomyopathy, magnetic resonance imaging and ECG findings were correlated in 25 patients with apical hypertrophy (group I), 15 patients with both apical and basal hypertrophy (group II), and 11 patients with hypertrophy localized to the basal left ventricle (group III). The number of precordial leads with negative T waves (-0.5 mV or more) was greater in group I than in groups II and III (I = 3.0 +/- 1.5, II = 1.7 +/- 1.5, III = 0.3 +/- 0.6; p < 0.01). Giant negative T waves (-1.0 mV or more) in precordial leads were found in 13 patients (52%) in group I and five patients (33%) in group II but were not found in group III. In contrast, tall positive T waves (> or = 1.0 mV) in precordial leads were found in two patients (13%) in group II and five (45%) in group III but were not found in group I. These results suggest that the distribution of hypertrophy in patients with hypertrophic cardiomyopathy produces a particular T wave polarity in precordial leads.

Adult↗

PubMed1993

Recovery from postoperative hypothermia predicts survival in extensively burned patients.

To clarify the cause of postoperative hypothermia in extensively burned patients, factors affecting postoperative hypothermia were studied in 16 extensively burned adult patients (8 survivors and 8 nonsurvivors) with a burn index greater than 35. Body temperature was monitored continuously in either the urinary bladder or rectum. Hypothermia of less than 35 degrees C occurred in 89% (66 of 74) of the total operations performed in these 16 patients. The rate of temperature rise (RTR) was significantly lower in nonsurvivors (0.4 +/- 0.2 degrees C/h) than in survivors (1.7 +/- 0.9 degrees C/h; p < 0.001). Continuous indirect calorimetry performed in seven patients (four survivors and three nonsurvivors) demonstrated that RTR was determined primarily by heat production. The measured energy expenditure reached only 1.7 +/- 0.2 times the basal energy expenditure during rewarming in nonsurvivors, whereas it was 2.7 +/- 0.9 times the basal energy expenditure in survivors (p < 0.01). Surprisingly, in nonsurvivors, the RTR was significantly decreased even during the first 2 weeks. These findings suggest that those who cannot generate heat well in postoperative hypothermia are unable to produce the additional energy required to overcome sepsis.

Adult↗

PubMed1993

Corneal endothelial cell loss induced by air bags.

BACKGROUND: Although the automobile air bag is a safety device used to protect drivers from death and moderate-to-severe injury, recently it also has been reported to be associated with some ophthalmic injuries. The authors have encountered a case in which a normal air bag may have caused a driver's corneal endothelial cell loss. In this study, the authors evaluate corneal endothelial cell loss caused by several types of air bags in the hope that air bag technology may be improved. METHODS: The authors performed impact tests with whole pig eyes fixed in a crash test dummy, using five different types of air bags. The area of damaged corneal endothelial cell was analyzed quantitatively. RESULTS: The authors found that corneal endothelial cell loss was correlated with the inflator power of the air bag but not with its weight. CONCLUSION: Although greater inflator power is needed for rapid air bag expansion, the effect on the eye should be considered in further refining this device. There may be greater latitude in the selection of air bag material. The authors believe their technique is applicable to the assessment of many air bag or passenger variables.

Accidents, Traffic↗

PubMed1993

Malignant oncocytoma of the parotid gland: a case report with an immunohistochemical and ultrastructural study.

A rare case of a 71-year-old man with malignant oncocytoma is presented. The tumour was found in the left parotid region with enlarged lymph nodes in the neck. The resected parotid mass consisted of three discrete nodules, each histologically characterized by a uniform proliferation of oncocytic tumour cells. The patient underwent repeated operations for recurrences and metastases, and eventually died of acute pneumonia 18 months after the first admission. Metastases to the lymph nodes, ribs, spine and liver had been clinically pointed out. Immunohistochemically, the tumour cells were positive for alpha-1-antitrypsin, alpha-1-antichymotrypsin, lactoferrin, secretory component and carcinoembryonic antigen (CEA), while they were negative for S-100 protein and HHF35 (muscle specific actin). Ultrastructural pictures disclosed numerous mitochondria in the cytoplasm of the tumour cells, revealing neither myofibrils nor secretory granules. These findings therefore support the concept that this tumour is of a glandular epithelial origin.

Adenoma↗

PubMed1993

Clinicopathology of kidneys from brain-dead patients treated with vasopressin and epinephrine.

Studies were made on the biochemical and pathological conditions of kidneys of 20 brain-dead patients who were maintained for 0 to 48 days after brain death by administration of vasopressin and epinephrine. Twenty specimens were obtained by percutaneous biopsy or at autopsy. The biochemical and pathological degrees were compared with those on the day of brain death (day 0). Biochemical tests on day 0 indicated that they showed the diuretic phase of prerenal failure, and then glomerular hyperemia was extensive. Renal function recovered on day 1 and remained almost normal during the 14 day period. Their urine retained high levels of sodium and osmolarity for days 0 to 14, with mild hyponatremia and hypo-osmolarity of the plasma. Tubulointerstitial nephritis gradually became extensive. There was no significant change in the degrees of mesangial widening, mesangial cell proliferation or hyalinosis. Arterial intimal proliferation was gradually extensive after day 3 and glomerular endothelial proliferation was gradually extensive after a week. Brain-dead patients have been mostly reported to develop diabetes insipidus, but our brain-dead patients did not show any manifestation of this disease. We suggest that constant natriuresis and continuing high level of urine osmolarity might have been caused by prerenal renal failure, brain death followed by neurogenic impairment, high level of serum vasopressin, or interstitial nephritis.

Adult↗

PubMed1993

Role of dual signal transduction systems in the stimulation of bone resorption by parathyroid hormone-related peptide. The direct involvement of cAMP-dependent protein kinase.

The present study was performed to compare the effect of parathyroid hormone-related peptide (PTHrP) on bone resorption with that of parathyroid hormone (PTH) and clarify the participation of PTHrP-responsive dual signal transduction systems involving cAMP-dependent protein kinase (PKA) and calcium/protein kinase C (Ca/PKC) in the stimulation of bone resorption by PTHrP. Bone resorbing activity was estimated as the number of pits formed on the dentine slice and total area of pits per slice in bone cells derived from 2 week-old mice. Human (h)PTHrP-(1-34) (10(7) M) stimulated bone resorption as potent as hPTH-(1-34) (10(7) M) did. The stimulation of bone resorption by hPTHrP-(1-34) and hPTH-(1-34) was equally blocked by either simultaneous treatment with 10(-8) M Elcatonin (eel calcitonin derivative; from Asahi Chemical Industry, Tokyo, Japan) [corrected] or pretreatment with 10(-7) M [Nle8,18Tyr34]hPTH-(3-34)amide. Rp-cAMPs, an antagonist in the activation of PKA, equally attenuated bone resorption stimulated by PTHrP as well as by PTH. A23187 (10(-7) M) caused a significant stimulation of bone resorption. These findings indicate the direct involvement of PKA activation and a contributory role of an increase in cytosolic calcium in the stimulation of bone resorption by PTHrP and suggest that PTHrP stimulates bone resorption presumably through the same mechanism as PTH does.

Animals↗

PubMed1993

Role of calcium/protein kinase C in the regulation of DNA synthesis by parathyroid hormone-related peptide in osteoblastic osteosarcoma cells.

Our recent study demonstrated the direct involvement of cAMP-dependent protein kinase (PKA) in the regulation of DNA synthesis by PTH-related peptide (PTHrP) in osteoblastic osteosarcoma cells, UMR-106. Since PTHrP has been reported to possess dual signal transduction systems [PKA and calcium/protein kinase C (Ca/PKC]), present study was performed to characterize the involvement of Ca/PKC signal transduction system in the regulation of DNA synthesis by PTHrP in these cells. Human PTHrP-(1-34) (10(-7) M) caused a rapid increase in intracellular Ca ([Ca2+]i), followed by return to the basal level within 1 min. Pretreatment with 10(-4) M TMB-8 or 10(-5) M dantrolene, inhibitors of calcium release from intracellular calcium store, significantly blocked the PTHrP-induced increase in [Ca2+]i, but did not affect the PTHrP-induced inhibition of DNA synthesis. Pretreatment with 50 uM H-7 or 1 nM staurosporine, inhibitors of PKC, significantly blocked the PTHrP (10(-9) to 10(-7) M)-induced inhibition of DNA synthesis. Pretreatment with 10(-6) M phorbol 12-myristate 13-acetate, which downregulated PKC, significantly blocked the inhibition of DNA synthesis by PTHrP. Present study indicates that in addition to PKA activation, PKC activation is coupled to the regulation of DNA synthesis by PTHrP in osteoblasts.

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

PubMed1993

MRI of the head in the evaluation of microcephaly.

Fifty-five patients with microcephaly (head circumference < -2SD) were identified. The 55 patients were divided into two groups, consisting of group 1 (34 cases) in which genetic causes were considered primary, and group 2 (21 cases) in which intrauterine and/or postnatal acquired factors were thought to be responsible. MRI abnormalities were present in 80% of the total series: 68 and 100% in groups 1 and 2, respectively. In group 1, migration abnormalities were the most prominent and mental retardation was the major neurological handicap, while in group 2, hydranencephaly and infarction secondary to brain circulatory derangements were the most frequently observed abnormalities, with severe multiple handicaps such as cerebral palsy, epilepsy and mental retardation seen. Head MRI was considered indispensable in the investigation of the causes of microcephaly and in determining the neurological prognosis of affected patients.

Agenesis of Corpus Callosum↗

PubMed1993

Possible radical scavenging properties of cicletanine and renal protection in Dahl salt sensitive rats.

Much interest in cicletanine, a novel antihypertensive drug, has grown because it uniquely stimulates prostacyclin (PGI2) production and may, thereby, provide further cardiovascular protection. We postulated that cicletanine may be an antioxidant, and assessed its ability to protect the kidney in Dahl salt-sensitive (Dahl S) rats on a high salt diet. Cicletanine eradicated in vitro a stable radical, DPPH, and decreased the lipid peroxidation both in rat brain homogenate and in a xanthine-xanthine oxidase (X-XOD) superoxide generating system. Furthermore, cicletanine attenuated the inhibition of PGI2 synthase activity by 15HPETE. However, cicletanine did not exhibit superoxide dismutase-like activity in X-XOD system, suggesting that it behaves primarily as a hydroxy radical scavenger. A 6 week cicletanine treatment reduced blood pressure in Dahl S rats fed a high salt diet, and ameliorated functional and morphological injury to the kidney. This attenuation of glomerular sclerosis correlated with the attenuation of lipid peroxidation in the kidney homogenate. These data indicate that cicletanine is an antioxidant that protects the kidney from salt-induced hypertension in Dahl salt-sensitive strain rats.

Animals↗

PubMed1993

Elevated levels of oncopterin, N2-(3-aminopropyl)biopterin, a new pterin compound, in urine from patients with solid and blood cancers.

The concentrations of oncopterin, N2-(3-aminopropyl)biopterin, a new pterin compound, were determined in urine from various cancer patients by HPLC on a reverse-phase or ion-exchange column. The concentration of oncopterin increased after acid hydrolysis, indicating that it exists as an amide in urine. The oncopterin concentrations were very low in the urine of healthy controls. Among the urine samples examined, those from cases of solid cancers, e.g., hepatomas, prostatic cancer and bladder cancer, exhibited very high levels; and those from cases of blood cancers, e.g., myelomas, acute myelocytic leukemia, and lymphomas, showed moderate increases. Oncopterin may thus be a new biochemical marker of some types of cancer.

Adult↗