Successful treatment of monomorphic primary central nervous system post-transplantation lymphoproliferative disorder 5 years after kidney transplantation.

A 31-year-old man underwent living-related kidney transplantation in 2004 as a consequence of primary focal segmental glomerulosclerosis (FSGS). Four years after the transplantation, we confirmed nephrotic syndrome caused by recurrent FSGS. We performed plasmapheresis and low-density lipoprotein adsorption. We also combined steroid therapy with a reduction in the dose of tacrolimus and an increased dose of mycophenolate mofetil. The nephrotic syndrome improved dramatically with this combined therapeutic approach. However, 10 months after these treatments, he revisited our hospital because of altered consciousness. We detected multiple tumor masses in his brain that were ring enhanced on contrast magnetic resonance imaging. Consequently, we suspected primary central nervous system post-transplantation lymphoproliferative disorder (CNS-PTLD). We performed a craniotomy to biopsy the brain tumors. The biopsy specimen showed Epstein-Barr virus-associated diffuse large B-cell lymphoma. There is no definitive treatment for CNS-PTLD. Therefore, we treated the primary CNS-PTLD successfully with whole-brain radiation and discontinuation of immunosuppression therapy.

Difference in coronary artery intima and media calcification in autopsied patients with chronic kidney disease.

BACKGROUND: In patients with chronic kidney disease (CKD), coronary artery calcification occurs at two distinct sites in the vessel wall: the intima and the media. Arterial media calcification (AMC), a nonocclusive condition, affects hemodynamics differently compared to arterial intima calcification (AIC), which occurs in atherosclerotic plaques. Arterial calcification is considered a cell-regulated process resembling intramembranous bone formation. The purpose of this retrospective observational study was to clarify the morphological differences between AIC and AMC and to evaluate the role of vascular smooth muscle cells (VSMCs) and macrophages in AIC and AMC formation. METHODS: We histologically analyzed 14 tissue specimens from 14 autopsies of patients with CKD Stage 5D who underwent hemodialysis and 5 specimens from 5 patients with CKD Stage 2 - 3 (90 ml/min/1.73 m2 > estimated GFR >= 30 ml/min/1.73 m2). We performed immunohistochemical staining of osteopontin (OPN) as a marker for bone matrix protein, alpha-smooth muscle actin (alphaSMA) for VSMCs, Cbfa1/Runx2 as a marker for osteoblastic differentiation of VSMCs, and CD68 for macrophages. RESULTS: In the CKD 2/3 group, we also found AIC and AMC. OPN and CD68 expression in the CKD 2/3 group was similar to that in the CKD 5D group. Although we did not find Cbfa1/Runx2 positive cell expression in the CKD 2/3 group, we did find it in the CKD 5D group. We found CD68-positive cells predominantly in AIC and absent in AMC in both groups. CONCLUSIONS: These findings suggest that the influence of Cbfa1/Runx2 pathway in coronary artery calcification depends on the CKD Stage. Expression of CD68-positive cells depends on the location of the coronary artery calcification.

Vestigial and scalloped in the ladybird beetle: a conserved function in wing development and a novel function in pupal ecdysis.

In Drosophila melanogaster, Vestigial (Vg) and Scalloped (Sd) form a transcription factor complex and play a crucial role in wing development. To extend our knowledge of insect wing formation, we isolated vg and sd homologues from two ladybird beetle species, Henosepilachna vigintioctopunctata and Harmonia axyridis. Although the ladybird beetle vg homologues had only low homology with D. melanogaster vg, ectopic expression of H. vigintioctopunctata vg induced wing-like tissues in antennae and legs of D. melanogaster. Subsequent larval RNA interference (RNAi) analysis in H. vigintioctopunctata demonstrated conserved functions of vg and sd in wing development, and an unexpected novel function of sd in pupal ecdysis. Furthermore, our results can be applied to the production of a flightless ladybird beetle for biological control purposes using larval RNAi.

Molecular cloning and characterization of cDNAs encoding dopamine receptor-1 and -2 from brain-suboesophageal ganglion of the silkworm, Bombyx mori.

In order to better understand the relationship between dopamine and the release of diapause hormone into the blood, we cloned and characterized cDNAs encoding Bombyx mori dopamine receptor-1 and -2 (BmDopR1 and 2) from the pupal brain-suboesophageal ganglion. BmDopR1 and 2 had high similarities to group 1 (Drosophila melanogaster DOP1 and Apis mellifera DOP1) and group 2 (D. melanogaster DopR99B, A. mellifera DOP2 and Papilio xuthus DOP1), respectively. When BmDopR1 and 2 were expressed in human embryonic kidney (HEK) cells, they responded to dopamine by increasing intracellular cAMP levels, thus indicating the presence of D1-like receptors. There were no clear differences in BmDopR1 and 2 mRNA levels between brain-suboesophageal ganglion complexes of diapause and nondiapause egg producers during pupal-adult development. BmDopR1 and 2 mRNAs were concentrated in the mushroom body calyx rather than in the suboesophageal ganglion. Taking into account the results of earlier experiments on excised regions corresponding to mushroom bodies, BmDopR1 and 2 in the mushroom body apparently play a role in the release of diapause hormone.

Wave reflections and the arterial pulse.

Studies of aortic dynamics have provided new information about the peripheral pulse. This brief review provides a summary of these findings and relates them to a number of clinical conditions.

Effect of glyceryl trinitrate on peripheral arteries alters left ventricular hydraulic load in man.

Effects of sublingual glyceryl trinitrate (GTN) were studied in ten patients without heart failure during diagnostic cardiac catheterisation following angiography. GTN caused substantial reduction in peak left ventricular and aortic pressure (19 mmHg) with lesser reduction in mean aortic pressure (9 mmHg) and no change in diastolic aortic pressure. Reduction in stroke volume (by 15%), associated with fall in left ventricular end diastolic pressure (by 4 mmHg) was insufficient to explain the marked (17 mmHg - 34%) reduction in pulse pressure. Decrease in pulse pressure was associated with loss of the late systolic peak on both the aortic and left ventricular pressure wave. This peak is caused by pulse wave reflection. GTN caused no change in peripheral resistance or in indices of aortic compliance (characteristic impedance, total arterial compliance) but was associated with reduction in fluctuations of both modulus and phase of aortic impedance. All these changes in pressure waves and in impedance spectra are explicable on the basis of decreased peripheral wave reflection. This can be attributed to the known vasodilatory effect of GTN on the peripheral arteries. Simulation of arterial vasodilatation in a multi-branched model of the systemic arterial system confirmed this interpretation. Dilatation of peripheral arteries explains in part the beneficial effects of GTN in adult man.

Reduced calcium sensitivity of dihydropyridine binding to calcium channels in spontaneously hypertensive rats.

To explore the role of calcium channels in hypertension, dihydropyridine ([3H]PN200-110) binding to heart, brain, and skeletal muscle microsomes of 4-, 8- and 15-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was measured. At a constant Ca2+ ion concentration (pCa 3.0), maximal binding (Bmax) of dihydropyridine binding to heart and brain microsomes was significantly enhanced in 8- and 15-week-old SHR compared with WKY rats (p less than 0.01), whereas this phenomenon was not observed in 4-week-old SHR and WKY rats. Bmax and dissociation constant (Kd) values for skeletal muscle microsomes from SHR showed no difference compared with WKY rats irrespective of age. Dihydropyridine binding to heart microsomes, brain microsomes, and solubilized skeletal muscle microsomes exhibited strong calcium dependence. The Ca2(+)-dependent dihydropyridine binding curves for heart showed a Hill slope, and pK 0.5 values for 15-week-old SHR and WKY rats were 0.70 +/- 0.12 and 4.66 +/- 0.12 versus 0.72 +/- 0.12 and 5.66 +/- 0.08 (n = 4, mean +/- SD), respectively, indicating that 15-week-old SHR require 10-fold higher calcium concentration than WKY rats to promote dihydropyridine binding. The pK 0.5 values of calcium for brain and solubilized skeletal muscle calcium channels in 15-week-old SHR were also significantly lower than in WKY rats. This difference first became apparent in SHR and WKY rats as early as 4 and 8 weeks after birth. These results suggest that enhancement of calcium channel density might occur in the heart and brain of SHR in response to elevated blood pressure and that reduced calcium sensitivity of dihydropyridine binding to calcium channels might be a primary characteristic of this rat strain.

The profiles of mRNA levels for BHR39, a Bombyx homolog of Drosophila hormone receptor 39, and Bombyx FTZ-F1 in the course of embryonic development and diapause.

In the silkworm, Bombyx mori, the 5'-upstream region of the sorbitol dehydrogenase (SDH) gene contains nucleotide sequences that might be recognized and bound by steroid hormone receptors such as Drosophila hormone receptor 39 (DHR39) and Fushi tarazu transcription factor 1 (FTZ-F1). As a first trial to find out regulator(s) involved in gene expression for SDH in Bombyx eggs, we have cloned a cDNA encoding a Bombyx homolog (BHR39) of DHR39, and examined levels of mRNA expressions for BHR39 and Bombyx FTZ-F1 (BmFTZ-F1) during the entire embryonic development and diapause. During embryonic development of non-diapause eggs, mRNA expression for BmFTZ-F1, but not for BHR39, was shown to occur in parallel with that for SDH, although such a parallelism was not found at the termination of diapause, when SDH mRNA was expressed.

Mitogenic action of interleukin-1 alpha on vascular smooth muscle cells mediated by PDGF.

We have investigated the effect of interleukin-1 (IL-1) on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortae. Murine recombinant IL-1 alpha increased tritiated leucine incorporation into VSMC. IL-1 also stimulated tritiated thymidine uptake by VSMC in a dose-dependent manner. On the other hand, Ca2(+)-channel blocker, verapamil, inhibited the IL-1-induced thymidine uptake by VSMC with an IC50 of 10(-8) M. Antibody specific for platelet-derived growth factor (PDGF) also totally inhibited the IL-1-induced thymidine uptake. IL-1 showed no effects on the intracellular Ca2+ level in VSMC. Above results support the premise that IL-1 promotes the growth of VSMC via induction of endogenous PDGF production and might thus participate in the abnormal proliferation of VSMC that occurs early in atherogenesis.

Vascular smooth muscle cells from genetically hyperlipidemic rabbit (WHHL rabbit) exhibit decreased growth response.

The Watanabe Heritable Hyperlipidemic (WHHL) rabbit is a widely studied animal model for the human genetic disorder familial hypercholesterolemia, and spontaneously develops atherosclerotic disease. We studied the growth characteristics of cultured vascular smooth muscle cells (VSMC) from WHHL rabbits compared with VSMC from Japanese white rabbits. We measured cell proliferation, DNA synthesis, and c-myc proto-oncogene expression, in response to growth stimuli such as fetal bovine serum (FBS) and platelet-derived growth factor (PDGF). VSMC from Japanese white rabbits exhibited a 4-fold increase in cell numbers during a 5-day incubation period compared with those from WHHL rabbits. FBS and PDGF stimulated DNA synthesis, as measured by thymidine incorporation into VSMC, in both Japanese white rabbits and WHHL rabbits, however the response was significantly higher in the former strain. The intracellular pH value of VSMC determined using the pH-sensitive fluorescence dye 2',7'-bis-carboxyethyl-carboxyfluorescein was significantly higher in WHHL rabbits than in Japanese white rabbits. Proto-oncogene c-myc was induced by exposure of VSMC to FBS, however there was no significant difference in c-myc mRNA levels between the two strains. These results suggest that VSMC from WHHL rabbits are not genetically growth accelerated, but show decreased growth response to growth stimuli.

Ventricular cells in culture from adult spontaneously hypertensive rats exhibit decreased growth.

We have investigated the growth characteristics of adult rat ventricular cells (ARVC) in culture from 8-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Protein synthesis in ARVC estimated from tritiated leucine uptake was augmented in both strains after exposure of cells to either norepinephrine or fetal bovine serum (FBS), but the response was significantly smaller in SHR than in WKY. A relative increase in the protein content of ARVC incubated with norepinephrine or FBS was also smaller in SHR than in WKY. These results demonstrate that SHR cardiac myocytes are not genetically growth-accelerated and show a decreased growth response to growth stimuli such as norepinephrine and serum during the adult period.

Further ST elevation at reperfusion by direct percutaneous transluminal coronary angioplasty predicts poor recovery of left ventricular systolic function in anterior wall AMI.

Some patients with acute myocardial infarction (AMI) develop further ST elevation at reperfusion by percutaneous transluminal coronary angioplasty (PTCA). This study reports the ST deviation at reperfusion by direct PTCA in relation to the clinical factors and the recovery of left ventricular (LV) systolic function. Fifty-two patients with anterior wall AMI were treated with direct PTCA. They were classified into the following 3 groups according to the change in ST elevation at reperfusion: increase of > or = 20% (ST reelevation); reduction of > or = 20% (ST resolution); and the other (ST no change). Angina pectoris preceding AMI occurred less often in the ST reelevation group (ST reelevation group, 38%; ST no change group, 81%; ST resolution group, 70%; p < 0.05). Recovery of LV ejection fraction during the first month after direct PTCA was significantly poor in the ST reelevation group in contrast to the ST resolution group (ST reelevation group, -6.3 +/- 13%; ST no change group, 18 +/- 20%; ST resolution group, 45 +/- 29%; p < 0.0001). The change in ST elevation at reperfusion was an index predicting the recovery of LV systolic function in the reperfusion by direct PTCA.

Effects of age on ventricular-vascular coupling.

The effects of age on the interrelation between the physical properties of the arterial tree (aortic input impedance) and left ventricular performance (cardiac output) were studied in 45 subjects, aged 19 to 62 years, without apparent cardiovascular disease. Ascending aortic pulsatile pressure and blood flow velocity were measured with a multisensor catheter and cardiac output by green dye or the Fick method. Heart rate and end-diastolic aortic pressure remained unchanged with age, whereas aortic systolic, mean and pulse pressures and aortic radius increased. In subjects younger than 30 years, early systolic pressure usually exceeded late systolic pressure (type C beat); in subjects older than 50 years, late systolic pressure usually exceeded early systolic pressure (type A beat). In 55% of subjects aged 30 to 50 years, early and late systolic pressures were essentially equal (type B beat). The impedance spectra from all subjects showed fluctuations about the characteristic impedance (index of elastance) that were greater in the older subjects. Peripheral resistance increased 37% (r = 0.47, p less than 0.001) over the age range of 20 to 60 years, whereas characteristic impedance increased 137% (r = 0.66, p less than 0.001). The fundamental impedance modulus increased, and the impedance modulus minimum shifted to a higher frequency. These changes in the impedance spectral pattern indicate that the ascending aorta becomes stiffer and the cross section of the peripheral vascular bed decreases with age, causing increased pulse wave velocity and wave reflection.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural analysis of gene encoding cuticle protein BMCP18, and characterization of its putative transcription factor in the silkworm, Bombyx mori.

BMCP18(2) is one of the major cuticle proteins identified in the larval cuticle of the silkworm, Bombyx mori. A genomic clone coding for BMCP18 was isolated from a B. mori genomic library, and its structure was analyzed. The BMCP18 gene consists of three exons interspersed by two introns. Bm1 element-like sequences were identified around this gene, suggesting possible involvement of this retroposon in the duplication of B. mori cuticle protein genes during evolution. A structural comparison of the BMCP18 gene and related cuticle protein genes of other lepidopteran species (MSCP14.6 and HCCP12) showed that the 5' upstream region of the BMCP18, MSCP14.6, and HCCP12 genes has a 12-bp identical sequence matching the recognition sequence for transcription factors COUP-TF and HNF-4. This implies that molecular mechanisms regulating expression of these cuticle protein genes are also conserved. mRNAs coding for Bmsvp, the B. mori homolog of Drosophila Seven-up, which is known as a homolog of vertebrate COUP-TF, and BmHNF-4, a homolog of vertebrate HNF-4, were detected in the larval epidermis. Bmsvp bound to the 12-bp sequence in vitro, suggesting that Bmsvp regulates the BMCP18 gene expression.

Progress and therapy of stress amenorrhea.

Thirty-two patients with stress amenorrhea of less than 1 years duration were found to have withdrawal bleeding after progestin administration, normal serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and good responsiveness to LH-releasing hormone (LH-RH); ovulation was induced following the admininstration of clomiphene citrate. On the other hand, in 11 of 14 patients with stress amenorrhea of longer than 1 years duration, no bleeding followed the administration of progestin, and there were noted high serum FSH and LH levels, exaggerated release responsiveness to LH-RH, and atrophic vaginal smears and endometrium. In addition, it was difficult to induce ovulation by various treatments. The findings suggest that dysfunction in the hypothalamic cyclic (not tonic) center regulating ovulation was the originating factor in the amenorrhea in question and that ovulation should be induced at least once yearly to prevent ovarian function from declining in this type of anovulatory state existing for more than 1 year.

A case of apolipoprotein C-II deficiency with coronary artery disease.

A 56-year-old male with apolipoprotein C-II deficiency experienced a myocardial infarction without pancreatitis. A coronary angiogram showed complete occlusions of both the right and circumflex coronary arteries. His serum lipid levels were as follows: fasting total cholesterol 3.15 mmol/l; postprandial total cholesterol 3.62 mmol/l; fasting triglycerides 1.46 mmol/A; postprandial triglycerides 6.14 mmol/l; fasting high-density lipoprotein-cholesterol 0.47 mmol/l; and postprandial high-density lipoprotein cholesterol 0.36 mmol/l. His fasting level of plasma apolipoprotein C-II was 0.005 g/l, but his plasma levels of other apolipoproteins were within normal ranges. A DNA sequence analysis of the apolipoprotein C-II gene showed no mutations in exon 1, 2, 3, or 4, where most gene mutations related to apolipoprotein C-II deficiency occur. We report this patient's very rare heterozygous apolipoprotein C-II deficiency with coronary artery disease. Although this patient had some risk factors for coronary artery disease, coronary atherosclerosis in this patient might have occurred as a result of lipoprotein abnormalities caused by at least one mutation in the apolipoprotein C-II gene.

Hyponatremia and hyperreninemic hypoaldosteronism in a critically ill patient: combination of insensitivity to angiotensin II and tubular unresponsiveness to mineralocorticoid.

A 62-year-old man with pneumonia and left flank pain had a clinical syndrome of hyponatremia, hypotension, dehydration, and high urinary sodium excretion in the presence of a normal glomerular filtration rate. The plasma level of antidiuretic hormone was relatively high despite decreased serum osmolality. Thyroid function and excretion of glucocorticoid and sex steroids were normal. The serum aldosterone level was very low despite elevated plasma renin activity. Angiotensin II failed to stimulate any secretion of aldosterone, despite the occurrence of a progressive rise in blood pressure. On the other hand, rapid ACTH administration increased both serum aldosterone and cortisol. The patient showed no effective response to increased salt intake, but large doses of mineralocorticoid resulted in a normal serum sodium level without dehydration. Subsequently, he suffered cardiac arrest secondary to ventricular tachycardia. Postmortem examination showed well differentiated adenocarcinoma in the left pleura and an intact, histologically normal adrenal zona glomerulosa and kidney. This is the first reported case of a critically ill patient with hyponatremia caused by hyperreninemic hypoaldosteronism possibly due to angiotensin II insensitivity and tubular unresponsiveness to mineralocorticoid.

Case report: new sonographic finding in renal infarction.

We observed a unique sonographic finding in a patient with right global renal infarction associated with an abdominal aortic dissection. Sonography in the acute phase revealed a highly echogenic and thickened perirenal fascia without demonstrable abnormality of the renal parenchyma. This finding may be helpful in the early diagnosis of renal infarction by routine sonography.

Effect of social factors on metabolic improvement in type II diabetic patients.

Psychological and social factors can profoundly influence a patient's success in adhering to a prescribed self-care regimen. A total of 34 inpatients with type II diabetes who attended the diabetes education program at a single clinic were studied as a retrospective cohort, beginning between 6 and 12 months after discharge. At the start of the study, the patients were classified into two groups, those with good control and those with poor control of diabetes, based on the rate of change of the glycosylated hemoglobin (HbAlc) value relative to the value at admission. Data for each patient were collected retrospectively from their medical records. Patients' family function was assessed by the adaptability, partnership, growth, affection, and resolve (APGAR) scoring system. Multiple regression analysis was used to determine the effect of demographic, medical, and social factors on metabolic improvement. The family APGAR score was higher in the good control group than in the group with poor control.

Postcholecystectomy syndrome mimicking angina pectoris detected by the morphine provocation test.

A 66-year old woman had had intermittent anterior chest pain and upper abdominal pain for 15 years. Angina pectoris was diagnosed at the age of 51 years, as she had typical anginal pain that was relieved by nitroglycerine, although coronary arteriography was normal and the ergonovine provocative test was negative. She had undergone cholecystectomy at the age of 38 years. Her bile duct pressure increased markedly after morphine injection and severe pain with the aforementioned distribution was produced. Postcholecystectomy syndrome due to sphincter of Oddi spasm was diagnosed and her pain was relieved by endoscopic sphincterotomy.