Biomedical subjects
Publications and source records attributed to K H Yoo.
The synthesis and biological activity of the novel series of 1 beta-methylcarbapenems, 1 and 2 were described. Most compounds displayed high potent antibacterial activity. The best compound in this series, 2a (IH201; R2 = NH2) showed an excellent and a broad spectrum as well as high renal DHP-I stability. It also possessed good in vivo efficacy and high safety.
The synthesis of new 1 beta-methylcarbapenems (1a-l) having a proline reverse amide moiety at the C-2 position and their in vitro antibacterial activities are described. The compounds were evaluated by the Mueller-Hinton agar dilution method and compared with meropenem as control. Aliphatic amides (1a-h) are found to show greater antibacterial activity than aromatic amides (1i-l). Moreover, C-2 free amino compound (1m) reveals greater activity than any other amide compounds (1a-l).
Angiotensin II (ANG II) has been implicated in the hypertrophic and fibrotic responses of the heart and kidney to systemic hypertension. To determine whether these actions of ANG II are related to tissue-specific stimulation of growth factors, we infused adult Sprague-Dawley rats with ANG II at 50 ng/min (low dose), 100 ng/min (high dose), or vehicle for 1 week. Rats receiving vehicle or low-dose ANG II were normotensive with normal plasma aldosterone concentration, whereas rats receiving high-dose ANG II were hypertensive with increased plasma aldosterone. Tissue fibrosis was quantified morphometrically, and messenger RNA (mRNA) for transforming growth factor-beta1 (TGF-beta1) and prepro-epidermal growth factor (EGF) was measured in liver, heart, and renal glomeruli and tubules. In addition, mRNA was determined for clusterin, a glycoprotein expressed in response to tissue injury. Compared to vehicle, low-dose ANG II increased TGF-beta1 expression in glomeruli, tubules, and heart, but not in liver, and increased EGF expression in renal tubules only. High-dose ANG II decreased clusterin expression in liver only. Fibrosis was induced by low- and high-dose ANG II in kidney and heart, but not in liver. We conclude that ANG II selectively stimulates TGF-beta1 mRNA in the heart and kidney, which may contribute to cardiac and renal interstitial fibrosis resulting from activation of the renin-angiotensin system independent of hypertension. By stimulating cellular proliferation, selective stimulation by ANG II of EGF in renal tubules may amplify the effects of TGF-beta1. Suppression of clusterin expression in the liver of hypertensive rats may represent a specific response to high levels of circulating ANG II or a response to hypertensive injury.
Chronic unilateral ureteral obstruction (UUO) in early development activates the intrarenal renin-angiotensin system and leads to profound renal vasoconstriction, renal growth arrest, and interstitial fibrosis. To investigate the response of the AT1 and AT2 subtypes of the angiotensin II (ANG II) receptors to UUO, Sprague-Dawley rats underwent UUO or control sham operation in the first 48 h of life and were studied 1-28 days later. Renal mRNA for renin, AT1 and AT2 receptor, and receptor binding and distribution were determined. In contrast to controls, renin mRNA increased from 14 to 28 days in the obstructed kidney. After ipsilateral UUO, AT1 mRNA was suppressed at 1 day, but had increased compared with controls at 28 days. AT2 receptor mRNA fell rapidly in all kidneys from 1 to 3 days of age, after which it remained undetectable. Compared with the intact opposite kidney, AT2 mRNA was suppressed in the obstructed kidney 1 day after UUO. Compared with controls, AT1 and AT2 receptor binding was decreased by ipsilateral UUO at 1 day, whereas AT1 binding was increased at 28 days. Renal ANG II content was increased in the obstructed compared with the intact opposite kidney 28 days after UUO. In view of the increase in renal renin and angiotensin II production resulting from UUO, increased renal AT1 mRNA and receptor binding are likely to contribute to the vasoconstriction and interstitial fibrosis of the neonatal kidney after prolonged UUO.
The renin-angiotensin system plays an important role in renal growth and development: exposure of the fetus or neonate to angiotensin-converting enzyme (ACE) inhibitors increases mortality and results in growth retardation and abnormal renal development. This study was designed to investigate the effects of ACE inhibition in the neonatal rat on the expression of genes known to modulate renal cellular proliferation, cell interactions, and extracellular matrix. Newborn rat pups were treated with enalapril (30 mg/kg/d) or vehicle for 14 d, and kidneys were removed for Northern analysis of mRNA for transforming growth factor-beta1 (TGF-beta1), prepro epidermal growth factor (EGF), clusterin, and renin. Distribution of TGF-beta1, EGF, and clusterin was also determined by immunohistochemistry. Enalapril treatment resulted in 40% mortality by d 14, reduced body and kidney weight, decreased glomerular area, and caused tubular dilatation (p < 0.05 versus vehicle group). Enalapril decreased renal TGF-beta1 and EGF mRNA expression, and increased renal clusterin and renin expression (p < 0.05). Renal tubular immunoreactive EGF was decreased, and clusterin was increased by enalapril treatment. These results indicate that ACE inhibition in the developing kidney reduces the renal expression of critical growth factors, which may account for renal growth impairment. Clusterin expression may increase either due to blockade of tonic angiotensin-mediated inhibition, or as an adaptive response to renal ischemia.
Haemorrhagic fever with renal syndrome (HFRS) is an acute disease caused by Hantavirus and clinically characterised by abrupt onset of fever, various haemorrhagic manifestations and transient renal and hepatic dysfunction. We retrospectively reviewed 63 cases of HFRS in children from 13 different hospitals in Korea who presented over a 15-year period. The age of the patients ranged from 7 to 15 years, with a male to female ratio of 8 to 1. Fifty-four (86%) patients were 10 years or older. On admission, 24 (38%) were in the febrile phase and 35 (56%) were in the oliguric phase. Fever (100%) abdominal pain (91%), headache (76%) and vomiting (73%) were the most common symptoms. Backache, subconjunctival haemorrhage and hypertension were also noted in about one-third of patients. Hypotension was documented in only 7 (11%) patients. Leucocytosis (> 10,000/mm3) and thrombocytopenia (< 150,000/mm3) were noted in more than two-thirds of patients. Elevated blood urea nitrogen and serum creatinine was observed in 94% by the 7th (median) day of illness. Elevated aspartate aminotransferase and/or alanine aminotransferase were found in more than two-thirds of patients. Renal biopsy was performed in 12 patients and revealed various stages of acute tubular necrosis with occasional interstitial cell infiltration and oedema. Only 2 showed evidence of interstitial haemorrhage. Eleven patients required 1-3 days of dialysis and the remaining patients required only conservative management. Three (5%) patients died of shock, respiratory failure and pulmonary haemorrhage. All other patients recovered without sequelae. Although childhood cases were much less common than adults, clinical and laboratory findings were in general similar between children and adults.
Primary hyperparathyroidism is a rare disease in children and is characterized by conspicuous skeletal and renal changes. A 12 year old male patient presented with symptoms of polydipsia, polyuria, general weakness, nausea, and vomiting which had begun 3 months earlier, and showed typical laboratory findings of primary hyperparathyroidism. Confirmatory diagnosis was made by elevated parathyroid hormone concentration in serum, technetium-thallium subtraction scan imaging method and histopathologic finding of chief cell hyperplasia. The laboratory findings revealed elevated levels of BUN, creatinine and decreased GFR. Kidney biopsy showed typical calcium deposits in tubules with marked tubulointerstitial infiltration. After subtotal parathyroidectomy, clinical findings improved remarkably.
A structured questionnaire was used to investigate the relationship between expectation and evaluation of occupational health nursing services as perceived by providers (nurses) and receivers (employers and employees) in the United Kingdom. The response rate was 66.55% (254) from nurses, 51.32% (194) from employees and 44.97% (170) from employers. Data from 144 triads of nurse, employer and employee were used to test 13 null hypotheses, which were all rejected. The strong positive correlation between nurses', employers' and employees' expectations and evaluations indicates that, on the whole, their expectations were met. However, there were differences in the extent to which this was so and the level of expectation varied between groups. Nurses perceived themselves as not meeting their high expectations as well in non-traditional (care-supportive) as in traditional (care-orientated) services. On the whole, employers had significantly lower expectations than nurses, except in the area of care and treatment. Employees had high expectations of preventive services, but their lower evaluations indicate that these were not met. Discussion of these and other findings suggests that employers need education on the value and scope of occupational health nursing, and a model may assist nurses' conceptual understanding of it.
There is no know scientifically accurate method of determining the correct vertical dimension. By the vertical dimension we mean the distance between the subnasale & the bottom of chin when patients were radiograped in the physiologic rest positions with & without prostheses. The author measured seven selected points in a midsagittal profile plane of 50 patients (26 complete upper & lower denture, 24 complete upper & removable lower partial denture) by the cephalometric methods. The following conclusions were obtained from this study. 1. Vertical dimension was measured 70.03 mm during removal of upper & lower dentures in mouth, 70.18 mm during insertion of upper denture only, 70.83 mm during insertion of lower denture only & 70.88 mm during insertion of upper & lower dentures, therefore mandibular denture alone in mouth has a slightly significant effects. 2. Vertical dimension between male & female from partially/fully edentulous patients was proved 72.15 mm in male & 68.81 mm in female. 3. Anterior-posterior displacement is largely associated with upper lip movement & superior-inferior displacement is generally associated with a function of lower lip & mandibular structure movements. 4. The magnitude of horizontal displacement for all points ranged from 0 to 8.4 mm & vertical displacement for all points ranged from 0 to 12 mm displacement. The maximum horizontal displacement in point II & maximum vertical displacement in point III was measured. 5. Increase in height may be associated with contraction of dental arches; or conversely, reduction of vertical height may be associated with expansion of the dental arches due to muscle tonicity & lip contours.
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