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Biomedical subjects

J Sugimoto

Publications and source records attributed to J Sugimoto.

At least 37 records · Page 2Linked to original sources

Assignment of the human poly(A) polymerase (PAP) gene to chromosome 14q32.1-q32.2 and isolation of a polymorphic CA repeat sequence.

We report the chromosomal localization of the gene for human poly(A) polymerase (PAP) and the characterization of a newly isolated CA repeat near the PAP locus. By fluorescence in situ hybridization and polymerase chain reaction (PCR)-based analysis with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel, this gene was mapped on the q32.1-q32.2 region of chromosome 14. From a genomic clone containing the human PAP locus, we have isolated a polymorphic dinucleotide (CA) sequence. High heterozygosity (0.81) makes this polymorphism a useful marker in the genetic study of disorders localized at the 14q32 region, such as autosomal recessive congenital microphthalmia (CMIC).

Chromosome Mapping↗

REM sleep components predict the response to initial treatment of infantile spasms.

PURPOSE: The phasic inhibition index (PII) is the rate of the simultaneous occurrence of rapid eye movement bursts (RBs) and phasic chin muscle activity (PCMA) during rapid eye movement sleep (REMS). PII is low insofar as physiologically occurring REM-related phasic inhibition acts on chin muscles. Previously we found that PII was significantly higher in patients with infantile spasms (ISs) who had a recurrence of convulsions than in patients with ISs who exhibited no recurrence. We aimed to predict the response of patients with ISs to conventional anticonvulsants (AEDs) by means of REMS components including PII, expecting to facilitate avoidance of potentially hazardous hormonal therapy. METHODS: REMS, recorded before the beginning of any medication, was retrospectively examined in 15 patients with ISs. The patients were classified into two groups according to the response to initial treatment with conventional AEDs. Conventional AEDs were enough to control the spasms in six good responders (GRs), whereas further hormonal therapy was required in nine poor responders (PRs) to control the spasms. RESULTS: The amount of REMS was significantly lower in patients with ISs than in controls. GRs had less REMS than did PRs, although no significant difference was observed. Although the frequencies of RB and PCMA showed no significant differences among GRs, PRs, and controls, the average PII value in PRs (12.6+/-3.4; mean+/-SD) was significantly (p < 0.001) higher than that in GRs (6.1+/-1.7). CONCLUSIONS: PII is a useful parameter for differentiating GRs from PRs.

Anticonvulsants↗

[Auditory brainstem responses in group A xeroderma pigmentosum].

Xeroderma pigmentosum has been known to result from disturbance in the repair of injured DNA caused by the ultra violet light. According to cell fusion studies, this disease is classified into 8 groups. Among these groups, group A (A-XP) shows the most severe type of neurological disturbance. Slowly progressive diffuse impairment both in the central and the peripheral nervous systems has been reported. Although hearing loss occurs in all the patients, few papers have described the chronological changes of this disability. This study aimed to clarify the development of audiological abnormalities in A-XP patients. We recorded auditory brainstem evoked responses (ABRs) in 20 Japanese children with A-XP. All patients had homozygous intron 3 splicing mutations of xeroderma pigmentosum group A complementing gene, the most common type mutations in Japan. ABR threshold, peak latency of 5th wave and the peak interval latency between the 1st and 5th waves (I-V interpeak latency) were measured, and were compared with those obtained from age-matched controls. ABRs were well detected in all patients examined under 4 years old. The I-V interpeak latencies became shorter with age as in the controls. In 3 ears, the 5th wave was recorded without 1st wave. In 4 ears which no ABRs were detected with 90 dBHL stimulation, the only 5th wave was detected. No waves were obtained from the patients aged over 10 years. The current study revealed that ABR disturbance in A-XP patients became obvious after 4 years of age. In addition, no ABR was found to be identified after 10 years of age. During 4 to 10 years of age, some patients showed the elevation of the threshold of the 5th wave. In A-XP patients, the peripheral nerve was hypothesized to be affected earlier than the central pathway involved in ABR.

Adolescent↗

Comparative toxic effects of iobitridol and iohexol on the kidney.

RATIONALE AND OBJECTIVES: The authors compare the toxic effects of iobitridol and iohexol, which are nonionic contrast media with equivalent osmolalities and viscosities on the kidney. METHODS: In a rat acute renal failure (ARF) model, iobitridol or iohexol (both at the dose of 2.87 g I/kg) were injected to rats after pretreatment with indomethacin and N omega-nitro-L-arginin methyl ester. The effects on histopathology, creatinine clearance, and urinary N-acethyl-beta-D-glucosaminidase (NAG) activity were assessed. In a rat renal slice system, the slices were exposed to iobitridol or iohexol (both at the concentration range of 17.5-70 mg iodine/mL) for 60 min. The accumulation of para-aminohippuric acid (PAH), an organic anion, and the intracellular potassium content as the indicators of renal tubular injury were measured to assess the direct effects of iobitridol and iohexol on renal tubules. RESULTS: In the ARF model, no significant difference was detected between the effects of iobitridol and those of iohexol on the creatinine clearance and urinary NAG activity 24 hours after the injection. However, iobitridol produced a lower degree and incidence of renal tubular injury of renal proximal tubules (P < 0.001) and distal tubules (P < 0.05) compared with iohexol. In the rat renal slice system, the iobitridol treatment had significantly less effect on the PAH accumulation compared with iohexol (P < 0.001). There were no changes in the intracellular potassium content. CONCLUSIONS: These findings suggest that iobitridol has significantly less toxic effects on the kidney compared with iohexol under the condition of our experiment.

Analysis of Variance↗

Video analysis of gross body movements during sleep.

Gross body movements (GM) during sleep, classified into four GM types by the involved parts of body, were evaluated using two-dimensional video analysis in five normal children aged 4-12 years. The rate of occurrence of all GM types showed apparent sleep stage dependency. Among four GM types, GM-1 (GM with axial rotation) was the most frequent. Averaged duration of GM-1 was the longest. A total of 77.2% of GM-1 started with the contraction of chin muscle and 35% of total sleep changes (tSC) were related to GM. A total of 5.6% of tSC following GM shifted to the deeper stage. Further evaluation is necessary in order to understand the physiological mechanism of GM.

Child↗

Alteration of anionic sites in renal glomerular basement membrane of pigs.

Ultrastructural alteration of anionic sites (ASs) in the glomerular basement membrane (GBM) was studied in 10 cases of swine mesangial proliferative glomerulonephritis using a cationic ultrastructural tracer, 0.5% polyethyleneimine (M.W. = 1,800). Glomerular ASs were seen as discrete electron-dense particles in the GBM, mesangial matrix and epithelial cell surfaces by electron microscopy. In the lamina rara externa (LRE) of the normal GBM, ASs were distributed regularly in a single layer. In those areas of the LRE that contained electron dense deposits or clusters of spherical microparticles (SMPs), however, a distinct reduction or loss of ASs was observed in all the pigs. Quantitative assessment of ASs in the LRE over 1,000 nm of the GBM revealed a significant reduction in ASs in one case with diffuse global thickening of the GBM as compared with the remaining nine pigs without GBM thickening (P < 0.001, Mann-Whitney's U-test). There were no ASs in the lamina densa (LD) of the normal GBM, but an irregular distribution of ASs was seen within the LD of the pig showing diffuse global thickening of the GBM. These results suggest that a disturbance of the charge-selective barrier in the GBM may be induced by electron-dense deposits or SMPs, in the LRE as well as thickening of the GBM in swine glomerulonephritis.

Animals↗

Effects of a thrombin inhibitor, argatroban, on ischemic brain damage in the rat distal middle cerebral artery occlusion model.

To elucidate the role of thrombin in brain damage during focal cerebral ischemia, we investigated the effects of a selective thrombin inhibitor, argatroban, on microthrombi formation, regional cerebral blood flow (rCBF), infarct areas and neurological deficits using a rat thrombotic distal middle cerebral artery (dMCA) occlusion model. The rat dMCA was occluded by a platelet-rich thrombus formed after photochemical reaction between rose bengal and green light. One day after dMCA occlusion, the number of microthrombi were counted. In the separate animals, rCBF was measured by using the iodoantipyrine method 1 day after dMCA occlusion. Three days after dMCA occlusion, behavioral tests were performed and the size of the cerebral infarction was determined. In the present study, argatroban was administered i.p. by continuous infusion after dMCA occlusion. Argatroban (0.3 mg/h/rat) significantly (P < .05) decreased the number of microthrombi 1 day after dMCA occlusion. Argatroban (0.1 and 0.3 mg/h/rat) significantly (P < .01) reversed a decrease in rCBF 1 day after dMCA occlusion. Argatroban (0.3 mg/h/rat) also significantly (P < .01) reduced the size of the cerebral infarction. Administration of argatroban (0.1 and 0.3 mg/h/rat) resulted in a significant improvement in neurological deficits 3 days after dMCA occlusion (P < .01 and P < .05, respectively). Argatroban decreased the size of the cerebral infarction and improved neurological deficits in the rat thrombotic dMCA occlusion model. These effects were thought to be due to the improvement of rCBF and to the reduction in secondary thrombus formation after dMCA occlusion.

Animals↗

Effective production of the hepatitis C virus core antigen having high purity in Escherichia coli.

The amino-terminal half of putative nucleocapsid (core) protein (amino acids 1-115) of hepatitis C virus (HCV) was directly overproduced in Escherichia coli under the control of the tac promoter. Overproduction of core antigen was achieved by inserting several target genes and by optimizing the culture conditions, whereas a large amount of directly expressed and purified core antigen has not yet been reported. Although the level of expression was comparable to that of the conventional E. coli fused expression system, our recombinant proteins contain only HCV amino acid sequence. Using recombinant E. coli, overproduced large-scale culture system was achieved in jar-fermenter. A highly purified sample of the expressed protein was obtained by ion-exchange and gel permeation column chromatography in the presence of 8 M urea. From a 3.5 l culture, approximately 440 mg of recombinant core protein was obtained after a two-step purification procedure. An enzyme-linked immunosorbent assay developed using the highly purified antigen satisfactorily diagnosed hepatitis C.

Base Sequence↗

Motor disturbance during REM sleep in group A xeroderma pigmentosum.

We investigated motor phenomena during rapid eye movement (REM) sleep in 13 patients with group A xeroderma pigmentosum aged from 11 to 39 months, and compared them with those obtained from 12 age-matched controls. At the time of sleep study, they had no abnormality on routine electrophysiological examinations. The amount of REM sleep and the incidence of motor phenomena during REM sleep in patients were similar to those in age-matched controls. However using the newly designated indices, we demonstrated disturbance on both the tonic motor inhibition occurring during the whole REM sleep period and the phasic one acting simultaneously with horizontal rapid eye movements in these patients. Since the motor inhibition during REM sleep is mediated by the subcortical structures, our study indicate that these structures are functionally impaired in group A xeroderma pigmentosum even during the early stage of the illness.

Brain Stem↗

Lipoatrophic diabetes.

A female patient with acanthosis nigricans, insulin resistant diabetes, and generalized lipoatrophy is reported. The patient developed skin pigmentation and acanthosis nigricans around the age of 34. Arthralgia, muscle weakness, and peripheral neuropathy were also present when she first visited us at 36 years of age. Dermatomyositis, systemic sclerosis, and internal malignancy were ruled out, and the diagnosis of acanthosis nigricans and insulin resistant diabetes was made. Her diabetes gradually worsened and, since the age of 39, she has been treated with an oral anti-diabetic drug. Around the age of 47, generalized lipoatrophy became prominent. Insulin receptor studies ruled out insulin resistant diabetes type A and B. At this point, we diagnosed this patient as having lipoatrophic diabetes, which is a syndrome characterized by insulin resistant diabetes, acanthosis nigricans, generalized lipoatrophy, and other metabolic disturbances. The control of her diabetes has been poor, and diabetic neuropathy and lipoatrophy-induced painful skin lesions such as clavus and tylosis have been persistent. The present case indicates the importance of careful skin examinations in the diagnosis of this syndrome.

Acanthosis Nigricans↗

Aortic root replacement for complicated bacterial endocarditis in an infant.

We report the case of a 10-week-old girl with streptococcal aortic valve endocarditis that was resistant to medical management and complicated by aortic insufficiency, congestive heart failure, annular abscess, and a large periaortic pseudoaneurysm. She underwent successful aortic valve and root replacement (with coronary artery reimplantation) utilizing an aortic valve homograft (allograft). The patient recovered completely and was discharged 3 weeks postoperatively. To our knowledge, this is the youngest patient to receive an aortic homograft for bacterial endocarditis and annular abscess.

Aorta↗

Mobilization of intracellular calcium as a mechanism for the positive inotropic effect by prostaglandin F2 alpha in isolated guinea pig atria.

The mechanism of the positive inotropic effect of prostaglandin F2 alpha (PGF2 alpha) was investigated using spontaneously beating isolated guinea pig atria. PGF2 alpha increased the contractile force in a concentration dependent fashion in a range between 10(-7)M to 10(-5)M. The maximal response to PGF2 alpha was obtained within 5 min and continued for at least 20 min. This positive inotropic effect of PGF2 alpha was not affected by verapamil, but was inhibited by procaine or TMB-8, potent inhibitors of Ca2+ release from intracellular Ca2+ compartments. Increase in extracellular Ca2+ concentration failed to provoke a significant positive inotropic effect by PGF2 alpha, suggesting that this response is relatively independent of extracellular Ca2+. These results suggest that the PGF2 alpha-mediated positive inotropic effect is produced by a mobilization of intracellular Ca2+.

Animals↗

Increase in Ca2+ (Mg2+)-ATPase activity induced by a molsidomine derivative (SIN-1 A) and nitroglycerin in microsomal fraction of guinea-pig thoracic aorta.

The amount of phosphoric acid liberated from ATP by Ca2+ (Mg2+)-ATPase in microsomal fraction of guinea-pig thoracic aorta decreased with decreasing concentrations of calcium ions from 20.0 to 2.5 mM in the mixture of the enzyme and substrate. When CaCl2 (2.5 mM) and MgCl2 (5.0 mM) were present in the substrate, both nitroglycerin (0.1 to 1.0 mM) and SIN-1 A (a molsidomine derivative, 0.05 to 1.0 mM) increased the liberated phosphoric acid in a concentration-dependent manner. The contractile tension of smooth muscle prepared from guinea-pig thoracic aorta, which was previously increased by the pretreatment with prostaglandin F2 alpha (5.0 microM), was relaxed by both nitroglycerin and SIN-1 A (0.01 to 100 microM each) in a concentration-dependent manner. From the results, it is assumed that the stimulation of Ca2+ (Mg2+)-ATPase [Ca2+-pump ATPase] activity induced by nitroglycerin and SIN-1 A in the microsome of thoracic aorta takes part in the relaxation of contractile tension in the tissue.

Animals↗

Rectal carcinoid tumors--treatment and prognosis.

Because of their location, rectal carcinoid tumors present a special therapeutic challenge for the surgeon. Only about 15% of these tumors manifest metastases and the others can be cured by complete local excision; hence performing a low anterior resection or an abdominoperineal resection for all patients would result in excessive rates of morbidity and death. Present-day treatment programs call for radical cancer resections only for lesions 2 cm in diameter or larger and local resection for all others. However, in a review of 595 patients, including 29 from the University of Chicago Hospitals, it was determined that this practice results in undertreatment of 24% (19/78) of all rectal carcinoid tumors that were associated with metastases, for 5% of all lesions smaller than 2 cm also had metastases. Invasion of the muscularis propria, we found, was an excellent additional prognostic sign for tumor progression. If the criteria for radical cancer resection included both size (all tumors 2 cm or larger and invasion of the muscularis propria in all smaller lesions, only 6% (5/78) of all aggressive tumors would have been missed and only 1.2% of all individuals with rectal carcinoid tumors would have received too limited an operation. It is hoped that the use of these new criteria will improve present-day survival statistics for patients with rectal carcinoid tumors.

Adult↗

Postoperative hypocalcemia - its relation to operative techniques.

The relationship between the type of operation for primary hyperparathyroidism and the incidence of postoperative hypocalcemia has not been completely elucidated. The pre- and postoperative serum calcium concentrations in 107 patients with this disease who were operated upon for the first time utilizing several different procedures were evaluated. Group 1. Prior to 1978, our aim was the excision of an adenoma, if present, and any other questionably enlarged parathyroid glands. All other appearing glands that could be found were biopsied. If parathyroid normal hyperplasia was present clinically, three and one-half glands were removed. Group 2. (1980 through 1981). A bilateral neck exploration was performed. If an adenoma was present, this was removed. However, only one or two other parathyroid glands were biopsied. The last normal appearing gland was intentionally left undisturbed. If hyperplasia was present, 2 glands were resected and remnants of two other glands were left in situ. Following their initial neck exploration, 52 of 57 (91%) Group 1 patients were cured. During the first 4 postoperative days, 48% had one or more serum calcium values of 7.9 mg/dl or lower (our criterion for significant postoperative hypocalcemia). None had permanent hypoparathyroidism, however. Their serum calcium concentrations fell to the same level whether one, two or three glands were excised. All 50 patients in Group 2 were cured by their initial neck exploration. Only 26% developed serum calcium values of 7.9 mg/dl or lower (p less than 0.05. when compared to Group 1). However, one patient who had the removal of a large substernal goiter and a parathyroid adenoma has manifested prolonged hypocalcemia. Our data demonstrate that by performing a more conservative operation, transient postoperative hypocalcemia can be lessened. Furthermore, it is quite suggestive that excessive parathyroid biopsy may be deleterious and should be avoided.

Adenoma↗

Serum calcium, parathyroid hormone, and urinary cyclic adenosine monophosphate after parathyroidectomy.

In specific cases of primary hyperparathyroidism (HPT), an intraoperative measure of parathyroid function might aid the surgeon. Ideally this would permit the surgeons to recognize that sufficient parathyroid tissue had been removed to cure the patient, but that viable glandular tissue remains. This study was designed to evaluate the efficacy of urinary cyclic adenosine monophosphate (cAMP) concentrations as such a determinant. We studied serum calcium and parathyroid hormone concentrations and urinary cAMP levels in 11 control patients undergoing thyroid and non-neck operations and in 22 persons undergoing parathyroidectomy for primary HPT. The serum calcium and parathyroid hormone concentrations were normal in control patients and elevated in each person with primary HPT. Changes of these parameters after successful parathyroidectomy took too long either to occur or to be measured to be clinically useful intraoperatively. Basal urinary cAMP concentrations were normal in 10 of 11 control patients and remained so during their operations. Elevations of basal urinary cAMP levels were found in 78% of those with primary HPT. At 30 minutes after removal of all abnormal parathyroid tissue, urinary cAMP levels remained high in 41% of those in whom it as elevated in the basal state. However, by 60 minutes all urinary cAMP values were normal or low. Plasma cAMP values were normal in three of four patients with primary HPT and did not change within 90 minutes after operation despite the performance of a successful parathyroidectomy. As expected, urinary cAMP levels returned to normal in each of these individuals. Intraoperative changes of urinary cAMP levels do reflect changes in parathyroid status. However, because of the delay of 40 to 60 minutes before urinary cAMP normalizes after parathyroidectomy and because of the sophisticated technology necessary for rapid determination of this cyclic nucleotide, its present clinical applicability is limited.

Calcium↗