Birefringence and optical activity of the incommensurate phase of
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Biomedical subjects
Publications and source records attributed to J Kobayashi.
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To elucidate the reversibility of right ventricular (RV) myocardial hypertrophy in tetralogy of Fallot (TF), 30 patients underwent RV endomyocardial biopsies 1 to 25 years (mean 9.7 +/- 6.6) after corrective surgery. Myocardial cell diameter was evaluated by comparing histopathologic data with preoperative patients with TF and normal subjects. As a whole, postoperative cell diameter was smaller than that of age-matched preoperative patients with TF, and larger than that of age-matched normal subjects. In 7 patients without significant residual pulmonary stenosis whose preoperative data were also available, cell diameter significantly decreased after surgery (17.1 +/- 2.1 to 14.0 +/- 2.1 microns, p < 0.01). There was a positive correlation between postoperative cell diameter and age at study (p < 0.01). To negate the influence of age, cell diameter was expressed in terms of a percentage of age-matched normal values (percent cell diameter). There was no significant correlation between percent cell diameter and age at surgery, age at study or the follow-up periods. There were positive correlations between percent cell diameter and the following parameters: RV systolic pressure (p < 0.05), percent normal RV end-diastolic (p < 0.05) and end-systolic (p < 0.01) volumes. These results demonstrate that RV myocardial hypertrophy in TF can regress to some extent after corrective surgery if significant residual pulmonary stenosis is avoided.
3H-Labeled 9-methyl-7-bromoeudistomin D ([3H] MBED), the most powerful inducer of Ca2+ release from sarcoplasmic reticulum (SR), was successfully prepared with a high specific activity of 10.2 Ci/mmol. [3H]MBED bound to terminal cisternae (TC) of skeletal muscle SR in a replacable and saturable manner, indicating the existence of its specific binding site. Caffeine inhibited the [3H]MBED binding to the TC-SR membranes from skeletal muscle with an IC50 value of 0.8 mM, in close agreement with a concentration that causes Ca2+ release from SR. Scatchard analysis gave values of KD = 40 nM and Bmax = 10 pmol/mg protein. The KD value was increased by caffeine, while that of Bmax was not changed, indicating a competitive mode of inhibition. Adenosine 5'-(beta, gamma-methylene)triphosphate enhanced [3H]MBED binding, but ryanodine and Ca2+ did not affect it. [3H]MBED binding to TC-SR membranes was inhibited by procaine, a representative blocker of Ca(2+)-induced Ca2+ release channels, whereas that was not changed by Mg2+, suggesting that procaine but not Mg2+ may exert its inhibitory effect on Ca(2+)-induced Ca2+ release by affecting the caffeine-binding sites. These results suggest that MBED shares the same binding site as that of caffeine in TC-SR. The [3H]MBED is the first radiolabeled ligand for caffeine-binding sites in Ca2+ release channels and thus may provide an essential biochemical tool for elucidating this site.
To clarify the role of defective lipoprotein lipase (LPL) in hypertriglyceridemia, the LPL masses and LPL activities in post-heparin plasma (PHP) were studied in severe hypertriglyceridemias. The developed sandwich enzyme immunoassay for the LPL was sensitive from 0.5 to 20 ng/ml of LPL in human PHP. The plasma LPL mass increased by heparin injection (30 USP units/kg) and was found to positively correlate with LPL activity. The mean LPL activity from PHP of normal controls was 2,960 +/- 1,057 nmol/ml/h. The mean LPL masses from human pre- and 15-min post-heparin plasma from normal subjects were 25 +/- 5 ng/ml and 224 +/- 60 ng/ml, respectively. Thus the specific activity of LPL from PHP of normal controls was calculated to be 13.3 mumol FFA released/h/microgram LPL. Among hypertriglyceridemic patients with over 1,000 mg/dl of serum triglyceride, the incidence of patients with LPL masses less than -2 standard deviations (S.D.) of those of average normal control subjects was found to be 27%. Seventy percent of patients showed specific activities within + 2 S.D. of those of average control LPL, and 30% showed significantly low specific activities less than -2 S.D. despite the fact that LPL masses were not less than -2 S.D. of the average normal controls. These results suggest that the evaluation of LPL masses in PHP would be useful for finding functionally defective LPL in patients with hypertriglyceridemia, and that up to 30% severe hypertriglyceridemias may have functionally defective LPL.
We studied the molecular basis of a case of apolipoprotein CII (apo CII) deficiency with a history of familial consanguinity. DNA sequence analysis of the apo CII gene from the patient revealed a homozygous nucleotide change: a T-->C transition for codon 26 (TGG) at nucleotide 2967 of the third exon resulting in a Trp26-->Arg substitution. His mother was heterozygous of the same mutation and showed half the value of normal apo CII/apo CIII. Analysis of his brother who showed the normal apo CII concentration revealed no mutation at the same place. These results suggested that this missense mutation could be the cause of apo CII deficiency in this kindred.
The patient is a 34-year-old female. Her fasting plasma triglyceride and cholesterol levels were 7523 mg/dl and 818 mg/dl, respectively, at 35 weeks' gestation. The lipoprotein lipase (LPL) activity and mass from postheparin plasma of the proband were 0.02 (normal range: 5.51 +/- 1.12 mu mol/ml/h) and 168 ng/ml (normal range: 220 +/- 42 ng/ml), respectively, indicating that the LPL of the patient would be functionally defective LPL. DNA sequence analysis of the LPL gene from the patient revealed a homozygous nucleotide change: a G--> A transition at nucleotide position of 1255 resulting in an amino acid substitution of Thr for Ala 334. This is the first natural missense mutation identified in exon 7 of the LPL gene.
The hydration of cis-epoxyeicosatrienoic acids to the corresponding vic-dihydroxyeicosatrienoic acids by cytosolic epoxide hydrolase demonstrates moderate regioselectivity with rates of hydration highest for the 14,15-epoxide and lower for the 11,12- and 8,9-epoxide (4.5, 1.6, and 1.5 mumol of product/mg of protein/min, respectively). Incubations of the 8,9- and 14,15-epoxides with cytosolic epoxide hydrolase show stereoselective formation of diols (7:3 and 4:1 ratio of antipodes, respectively) and concomitant chiral enrichment of the remaining unmetabolized substrate. In contrast, hydration of the 11,12-epoxide is nonenantioselective. The Km value of the enzyme for the 14(R),15(S)-epoxide is 3 microM. Incubations of the enantiomerically pure 8,9- and 14,15-epoxides with lung or liver cytosol, followed by chiral analysis of the resulting diols demonstrate selective cleavage of the oxirane ring at C9 and C15, respectively. On the other hand, cleavage of the 11,12- oxirane ring was less selective. The stereochemical preference of the cytosolic epoxide hydrolase, together with the known chiral composition of the endogenous arachidonate epoxide pools, suggests a functional role for this enzyme in the metabolism of these important compounds.
We conducted clinical research using transbronchial lung biopsy in 60 patients with suspected ocular sarcoidosis who showed no bilateral hilar lymphadenopathy and sparse contributory evidence for sarcoidosis. The patients had a combination of granulomatous iritis with mutton-fat keratic precipitates or iris nodules, trabecular nodules, tent-like peripheral anterior synechiae, snowball or string-of-pearls vitreous opacities, retinal perivasculitis, and spotty retinochoroidal exudates. The transbronchial lung biopsy specimen showed noncaseating epithelioid granuloma in 37 patients (61.7%); these patients were diagnosed as having sarcoidosis. Bronchoalveolar lavage showed a high percentage of patients with an increased lymphocyte fraction among those with positive transbronchial lung biopsy results. The present results may serve as a basis for a clinical diagnosis of sarcoidosis in patients with suspected sarcoidosis without apparent extraocular manifestations.
To evaluate the mechanism of increased serum concentrations of the N-terminal propeptide of type III procollagen and the 7S fragment of type IV collagen in acute liver injury, we serially measured serum levels of these substances after transcatheter arterial embolization in patients with hepatocellular carcinoma. The results demonstrated marked increases in serum levels of the 7S fragment of type IV collagen in accordance with increased serum levels of transaminase after transcatheter arterial embolization. In contrast, a transient decrease in serum levels of the N-terminal propeptide of type III procollagen was found after transcatheter arterial embolization and transcatheter arterial infusion, although no significant changes in serum levels of the N-terminal propeptide and 7S fragment were seen after hepatic arteriography alone. The absolute change in serum levels of the 7S fragment after treatment showed positive correlation with serum transaminase levels and negative correlation with the decrease in serum levels of alpha-fetoprotein, although serum levels of N-terminal peptide did not demonstrate such a correlation. The results suggest that in acute liver injury induced by transcatheter arterial embolization, at least in part, increased in serum levels of the 7S fragment of type IV collagen reflect accelerated liberation of type IV collagen from the destroyed surrounding nontumorous tissues and that decreased serum N-terminal propeptide of type III procollagen reflects diminished synthesis of type III collagen caused by anticancer drugs.
Between 1989 and 1991, 17 children underwent 18 right ventricle-to-pulmonary artery conduit placement operations using a composite of an aortic or pulmonary valved homograft and a Hemashield extension to the ventricle. Hemashield is a collagen-coated knitted Dacron graft with excellent compliance and hemostatic properties. Diagnoses included tetralogy of Fallot with pulmonary atresia (7), truncus arteriosus (6), and complex transposition of the great arteries (4). Mean age at conduit placement was 4.9 +/- 4.2 years, and all patients survived. At a mean follow-up of 14 +/- 4 months, postoperative Doppler echocardiographic gradients between the ventricle and pulmonary artery ranged from less than 20 to 60 mm Hg. At cardiac catheterization 13 +/- 3 months postoperatively (6 patients), the systolic pressure gradient across the conduits ranged from 14 to 90 mm Hg (mean gradient, 59 +/- 29 mm Hg). Conduit obstruction, when present, was demonstrated angiographically to be in the Hemashield portion and led to early conduit replacement six times in 5 patients (33% of operations) within 10 to 18 months (mean time, 14 months) after insertion of the original conduit. Pathologic examination of the explanted conduits revealed the obstruction to be a thick neointimal peel that was impossible to separate from the Hemashield graft. Failure of the Hemashield as an extension for ventricle-to-pulmonary artery conduits secondary to accelerated neointimal formation has led us to abandon its use in clinical practice.
Isolation of zooxanthellatoxins, novel vasoconstrictive substances from the zooxanthella Symbiodinium sp. Toxicon 31, 371-376, 1993. New polyhydroxypolyenes with potent vasoconstrictive activity, zooxanthellatoxin-A and -B, were isolated from a symbiotic marine alga Symbiodinium sp. These compounds caused sustained contractions of isolated rabbit aorta at concentrations above 7 x 10(-7) M; this effect was abolished in Ca(2+)-free solution or in the presence of verapamil. Both compounds were relatively large molecules (mol. wt about 2900), containing a large number of oxygen atoms and olefinic carbons, thus differing from two other vasoconstrictive marine toxins, palytoxin and maitotoxin, in containing more olefins than palytoxin, and fewer ethereal rings than maitotoxin.
OBJECTIVE: To determine the incidence of hospital-acquired (nosocomial) infection in pediatric long-term care facilities. DESIGN: Prospective cohort. SETTING: An 87-bed pediatric long-term care facility. PATIENTS: All patients receiving long-term care at Bloorview Children's Hospital during the study period. RESULTS: Infection developed in 40.1% of patients (n = 456). The nosocomial infection rate per 1000 patient days (mean, 7.84) varied substantially, from 1.66 in May 1988 to 16.37 day in April, 1989. The proportional frequencies of infections were as follows: respiratory, 41.6% (37.0% upper, 4.6% lower); urinary tract, 31.0%; skin, 15.6% (gastric tube site 5.0%, other 10.6%), eyes, 6.4%; gastrointestinal, 3.5%; and other, 1.5%. Of those infections for which an organism was recovered (48.5%), pathogens included Escherichia coli (22.5%), Enterococcus (14.8%), Staphylococcus (14.8%), Streptococcus (11.2%), Klebsiella (10.5%), Pseudomonas (10.1%), Proteus (4.3%), yeast (4.3%), Salmonella (0.7%), Clostridium difficile (0.4%), and other (6.2%). CONCLUSIONS: The incidence and nature of infections in pediatric long-term care facilities differs from those in acute care facilities. Physicians should become familiar with the infection rates in the populations whom they treat. Control requires compliance with currently recognized effective strategies as well as innovative practical approaches to respiratory disease. Behavioral problems related to frequent clean, intermittent catheterization in young adults need to be addressed.
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Biemnasterol [2], a new sterol with a 22,25-diene side chain possessing cytotoxic activity, has been isolated from the Okinawan marine sponge Biemna sp. and the structure elucidated on the basis of spectroscopic data and chemical means.
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Fellutamide A, a tripeptide derivative from Penicillium fellutanum was found to be a potent enhancer of nerve growth factor (NGF) synthesis and secretion in vitro. This compound enhanced production of NGF in L-M cells, rat brain cells, and rat glial cells. The mode of action of this compound was suggested to be different from that of a known NGF inducer, epinephrine, as inducing activities of fellutamide A and epinephrine were additive when they were admixed at the concentration which gave saturation in its respective activity. Furthermore, fellutamide A but not epinephrine induced production of NGF in the rat brain cells. NGF-inducing activity of several tripeptides and other compounds related to fellutamide A was examined.
BACKGROUND: Transplant coronary artery disease (CAD) is characterized by severe myointimal proliferation causing vascular stenosis. Nontransplant vascular injury models have shown that angiotensin converting enzyme (ACE) inhibitors reduce myointimal proliferation and preserve lumen integrity. We examined the effect of the ACE inhibitor captopril on graft CAD in a Lewis to F344 rat heterotopic cardiac transplantation model. METHODS AND RESULTS: Twenty-five control rats (group 1) were observed without captopril administration after heterotopic cardiac transplantation, and the other 19 rats (group 2) were administered captopril (50 mg/kg per day in drinking water) after heart transplantation. Graft survival 3 months after transplantation was significantly (P < .02) higher in group 2 (18 of 19, 95%) than that in group 1 (16 of 25, 64%). Cellular rejection grades of the heart allografts were significantly higher in group 1 than those in group 2 both at 3 months (grades, 2.5 +/- 0.4 vs 1.3 +/- 0.7; P < .01) and 6 months (grades, 2.4 +/- 0.9 vs 0.8 +/- 0.5; P < .05) after transplantation. The grades of graft CAD (vascular rejection) were also significantly higher in group 1 than those in group 2 both at 3 months (grades, 2.3 +/- 0.7 vs 0.9 +/- 0.9; P < .05) and 6 months (grades, 3.0 +/- 0.9 vs 0.9 +/- 0.3; P < .01) after transplantation. The cardiac allographs in group 2 showed minimal intimal proliferation, intact elastic laminae, and reduced smooth muscle cell proliferation. CONCLUSIONS: These results suggest that the ACE inhibitor captopril may be effective in prevention of accelerated graft CAD.