A case of diaphragmatic hernia incarceration after a heart transplant operation

We report a case of a diaphragmatic hernia after a heart transplant operation. A 43-year-old woman, who underwent orthotropic heart transplantation for hypertrophic cadiomyopathy two year earlier, presented with vomiting and epigastric pain. A computed tomography scan showed that the stomach and transverse colon were dislocated in the left thoracic cavity. We diagnosed left diaphragmatic hernia incarceration and performed laparoscopic repair of the diaphragmatic hernia. A 12 × 8 cm diaphragmatic defect was found intraoperatively on the ventrolateral aspect of the left diaphragm, and the stomach with volvulus had herniated into the thorax through the defect. The hernia was considered to be iatrogenic. The diaphragmatic defect was large, and the diaphragm was thinning. We closed the defect by mesh repair. Laparoscopic mesh repair of the diaphragmatic hernia could be performed safely and with minimal invasiveness.     

Gene polymorphism of myospryn (cardiomyopathy-associated 5) is associated with left ventricular wall thickness in patients with hypertension.

We examined a gene polymorphism of a novel Z-disc-related protein, myospryn (cardiomyopathy-associated 5). We focused on one haplotype block associated with a tag single nucleotide polymorphism (SNP) that covered 16 of 27 coding SNPs with linkage disequilibrium (minor allele frequency 0.413). Screening a myospryn polymorphism (K2906N) in a general health check-up of a rural Japanese population revealed an association with cardiac diseases (p=0.0082). In further analysis of the interaction between K2906N and cardiac function in patients, K2906N was associated with the anteroseptal wall thickness of the left ventricle in a recessive model (p=0.0324) and with the ratio of the peak velocity of the early diastolic filling wave to the peak velocity of atrial filling (A/E) (p=0.0278). In an association study based on left ventricular wall thickness, we found a significant difference in the K2906N genotype between controls and patients with cardiac hypertrophy. These results suggest that the K2906N polymorphism could be clinically associated with left ventricular hypertrophy and diastolic dysfunction independent of known parameters. Although the precise mechanism underlying this association remains to be elucidated, treatment with angiotensin II induced an increase in heart myospryn mRNA level in vitro and in vivo. Our results suggest that the polymorphism of myospryn is associated with left ventricular hypertrophy, and an association between a Z-disc protein and cardiac adaptation in response to pressure overload.     

A case of acute hepatitis E associated with multidrug hypersensitivity and cytomegalovirus reactivation

A 65-year-old Japanese man was hospitalized because of acute hepatitis and severe cholestasis due to hepatitis E virus (HEV) infection combined with a drug reaction to a cold preparation. He died of disseminated intravascular coagulation and severe intestinal bleeding due to systemic cytomegalovirus reactivation following the development of severe eruptions with marked eosinophilia due to drug hypersensitivity to taurine and ursodeoxycholate preparations. The close interaction between viral infection or reactivation and drug hypersensitivity was considered as a pathophysiology in this case, which emphasizes the need for further study of the immunological mechanism of the interaction.     

A case of primary ureteral carcinoma in the duplicated renal pelvis and ureter diagnosed by transurethral uretero-renoscopy

We present a case of primary ureteral carcinoma in the duplicated renal pelvis and ureter diagnosed by transurethral uretero-renoscopy. The case was of a 78-year-old man with the complaint of sudden asymptomatic macrohematuria. An excretory urogram strongly suggested the presence of duplication of the right collecting system, and cystoscopy revealed a gross hematuria from the right ureteral orifice. A retrograde ureteropyelogram revealed incomplete duplication of the right renal pelvis and ureter fused at about the ureter crossing over the iliac vessels, and a polyp-like filling defect in the lower segment of duplicated ureter at about 4 cm from the fusion of the ureters. Transurethral uretero-renoscopy was employed to investigate the filling defect, and a papillary tumor extended into the lower segment of duplicated ureter was revealed. Tumor was resected by a rigid operating instrument under transurethral uretero-renoscopy. The pathological diagnosis was grade I-transitional cell carcinoma of the ureter, so that right total nephroureterectomy with partial cystectomy was carried out subsequently. Surgical specimen after right total nephroureterectomy with partial cystectomy showed no other tumor in the pelvis or ureter macroscopically, and histopathological studies of surgical specimens were no evidence of malignancy. We believe that transurethral uretero-renoscopy significantly increases the diagnostic accuracy in determining the nature of upper urinary tract lesions, and this procedure is indispensable in the diagnosis of ureteral tumors. The present case was the 7th case of primary ureteral carcinoma in the duplicated renal pelvis and ureter in the Japanese literature.     

Role of macrophage and smooth muscle cell apoptosis in association with oxidized low-density lipoprotein in the atherosclerotic development.

To examine the role of the apoptosis of macrophages and smooth muscle cells in the development of atherosclerosis, human aortic tissues with intimal lesions were immunostained with antibodies against terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL), single-stranded DNA (clone F7-26), and active caspase-3. Apoptotic cells were detected in the intima using both TUNEL and single-stranded DNA, however, the latter method was the more sensitive one for detecting apoptotic cells in the early stages of atherosclerosis. The number of apoptotic cells increased as the disease progressed. It implies that the apoptosis of intimal cells is involved in the formation of atherosclerotic lesions. In addition, quantitative analyses of the cell types undergoing apoptosis using double-immunostaining revealed that the susceptibility of macrophages and smooth muscle cells to apoptosis was greater specifically in atheroma than in the other atherosclerotic lesions, and macrophages were more susceptible to apoptosis than smooth muscle cells. The frequency and spatial distribution of oxidized low-density lipoprotein (oxLDL) (FOH1a/DLH3)-positive cells were examined by immunohistochemistry, and the results resembled those of apoptotic cells. The number of oxLDL-positive cells in the intima significantly correlated with the susceptibility of smooth muscle cells, but not with that of macrophages, to apoptosis. These results suggest that oxLDL affects the apoptosis of smooth muscle cells during the atherosclerotic development.     

Activated caspase expression and apoptosis increase in keloids: cytochrome c release and caspase-9 activation during the apoptosis of keloid fibroblast lines

To characterize apoptosis in keloids and the mechanisms responsible for this process, the expression of activated caspase-9 and -3 in fibroblasts obtained from keloids was analyzed. Immunohistochemistry revealed that the number of fibroblasts positive for terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) or activated caspase-9 or -3 was low but was significantly higher in keloid tissues than in normal scar tissues. Significant relationships between the number of caspase-positive fibroblasts and TUNEL-positive fibroblasts suggested that the activation of caspase-9 and -3 induces apoptosis in a subpopulation of keloid fibroblasts. All keloid fibroblast cell lines established in this study showed activation of caspase-9 and -3 after serum deprivation for 3 or 4 hours, as shown using Western blotting. Furthermore, serum deprivation-induced apoptosis in a keloid fibroblast line was blocked by a caspase-9 inhibitor (acetyl-Leu-Glu-His-Asp-al), indicating that activation of caspase-9 was necessary for the process of apoptosis in keloid fibroblasts. Although serum deprivation did not significantly change the level of apoptosis protease activating factor-1 in any of the lines, cytochrome c release was detected in cytosolic fractions of the lines after serum deprivation for 3 or 4 hours. These results strongly suggest that keloid fibroblasts are predisposed to apoptosis and cytochrome c release and that caspase-9 activation may underlie regulation of apoptosis in keloid fibroblasts in vivo.     

A double blind study of the effectiveness of ketotifen in preventing the development of asthma in atopic dermatitis patients

Many asthmatic children have experienced atopic dermatitis in their younger days. As it is very difficult to cure childhood asthma we attempted to determine the anti-allergic drug effects in preventing the development of asthma by using ketotifen on atopic dermatitis patients. The study was designed as a placebo controlled double blind trial of 128 atopic dermatitis patients aged from 2-34 months. 91 patients were given complete analysis in the study, 33 patients were given only a safety rate and 4 patients were dropped. The 91 patients were followed for 52 weeks. Our primary finding was that the development of bronchial asthma was inhibited in the ketotifen group compared to the placebo controlled group with a statistically significant degree (p less than 0.001). We also found that clinical symptoms of atopic dermatitis were significantly improved in the ketotifen group (p less than 0.001). Only 5 patients complained of mild side effects.     

Effects of continuous distraction on cartilage in a moving joint: An investigation on adult rabbits

An animal model, using distraction force on adult rabbits, was developed to study the effects of nonweight-bearing on articular cartilage in a moving joint. Histologic evaluation was used to compare the morphology of chondrocytes, safranin O intensity, cartilage thickness, and structural changes between the test and contralateral joints. At 3 and 6 weeks, the chondrocytes in superficial and intermediate zones were round, with an increase in cellular volume density and mean cell volume and with less metachromasia; the safranin O intensity and cartilage thickness were the same as in the controls. In cartilage of the 9-week group, mean cell volume decreased with cell cloning in the superficial zone, while numerical density increased and mean matrix volume per cell decreased in the superficial and intermediate zones. The cartilage, with a 34% reduction in thickness and a 53–72% decrease in safranin O intensity from the superficial to the deep zone, had superficial fibrotic proliferation, suface erosion or depression, ard tidemark irregularity. Continuous distraction in a moving joint caused morphological changes in chondrocytes prior to degeneration of cartilage. These results support the hypothesis that the forces perceived by cells may dictate their shape and then stimulate alterations in cellular biochemistry and matrix metabolism.     

A new method of perfusion fixation for the rabbit femur

We report a new method of perfusion fixation for the proximal one-third of the femur of the Japanese white rabbit. Fluids to flush the blood and fix the marrow were injected into the abdominal aorta and drained from the stump of the femur. The oozing of the fluids from the stumps guaranteed complete flushing and fixation. The new method facilitated fixation and decreased the volume of necessary fluids. Scanning electron microscopy (SEM) images of bone marrow fixed using the new method and using the conventional method did not differ. Large fat globules were not observed in the SEM specimens produced using either the new or the conventional method.     

TCR repertoire in early fetal mouse thymus

We investigated the rearrangement and expression of TCR genesin mouse fetal thymus organ culture, a system that avoids subsequententry of hematopoietic precursor cells. The first observablerearranged TCR gene was homogeneous V2-J2, detectable as earlyas fetal day 11 (d11) in the thymic primordla. The productiveTCR was homogeneous V5-J1, first detectable in d13 thymocytes,followed by adult-type TCR (V4 and V7). Sequence analysis ofTCR revealed five types of V-J junctional sequences. In thevery early stage, a homogeneous V-J junction is generated viaa short homology sequence in the coding region (Type I), whilea short homology sequence in the P-nucleotlde rather than thecoding region is used in the following stage (Type II). In thelater embryonic stages, diverse V-J junctions are generatedby well-known mechanisms, such as P-nucleotide (Type III), N-regioninsertion (Type IV) or trimming of the coding ends (Type V).These findings suggest that the generation of homogeneous TCR (V2 and V5) in the early fetal stages is due to the intrinsicrearrangement mechanisms and is in stage specific manner.