AN AUTOPSY CASE OF IDIOPATHIC ENLARGEMENT OF THE RIGHT ATRIUM, AND A REVIEW OF THE LITERATURE

A 69-year-old man in whom idiopathic enlargement of the right atrium was revealed at autopsy is described. The patient had had cardiomegaly of at least 19 years'duration prior to his death, even though cardiac symptoms were absent. Cause of death was pancreatic carcinoma. Postmortem examination revealed marked and diffuse dilatation of the right atrium and moderate dilatation of the left atrium. Measurement of the cardiac chambers showed that the right and left atria were 7.6 and 4.7 times as large as those of normal hearts, respectively. The volume of either ventricle was about twice the normal value. Histologically, widespread cardiac muscular degeneration and necrosis, diffuse fibrosis, and focal lymphocytic infiltration were found in the right atrium and also, to a lesser degree, in the left atrium. Such pathologic changes were not found in either of the ventricles. The etiology of these muscular changes, which might have been related to atrial enlargement, was unclear. The present case was thought to be consistent with idiopathic enlargement of the right atrium, and a brief review of the literature is given.     

Co-occurrence of mucoepidermoid carcinoma and squamous cell carcinoma of the esophagus: Report of a case

A case of co-occurrence of a mucoepidermoid carcinoma (MEC) and a squamous cell carcinoma (SCC) in the esophagus is described. The present patient was a 61-year-old man who underwent a curative esophagectomy with a regional lymph node dissection for a MEC in the lower esophagus and a SCC near the esophagogastric junction. The two lesions were endoscopically and histologically divided by a normal esophageal mucosa. The MEC of the esophagus consisted of SCC cells and signet-ring cells, and a mucin product and carcinoembryonic antigen, which were found at high levels in the blood serum before surgery, were detected histochemically in the signet-ring cells. The follow-up survey of the patients with esophageal MEC previously reported in Japan showed that most of the patients died of either local recurrence or widespread metastasis after treatment; the overall 5-year survival rate was 24.4% in the total 25 cases, and 27.7% in the 22 resected cases. However, 6 patients who died of therapeutic complications were included among these patients; furthermore, the 5-year survival rate after surgery was 29.2% in the patients treated over the last decade (1989–1998). We expect that the clinical outcome of patients treated for esophageal MEC will therefore improve in the future. Received: July 30, 1999 / Accepted: January 7, 2000     

Combined therapy with a new bisphosphonate, minodronate (YM529), and chemotherapy for multiple organ metastases of small cell lung cancer cells in severe combined immunodeficient mice.

PURPOSE: Lung cancer in the advanced stage frequently metastasizes to multiple organs, including the liver, lungs, lymph nodes, and bone. Bisphosphonates have been widely used to treat osteolytic bone metastasis in the past years; however, many studies have implicated that a single use of bisphosphonates could not prolong the survival of patients. In the present study, using a multiple-organ metastasis model of human lung cancer cells, we examined the effect of combined therapy with a new bisphosphonate (YM529) and etoposide (VP-16). EXPERIMENTAL DESIGN: Human small cell lung cancer (SBC-5) cells i.v. inoculated into natural killer cell-depleted severe combined immunodeficient mice metastasized to multiple organs, including the lungs, liver, kidneys, lymph nodes, and bone. SBC-5-bearing mice were treated with YM529 and/or VP-16 and sacrificed 5 weeks after tumor cell inoculation. Bone metastasis was assessed by X-ray photographs, and visceral metastasis was evaluated macroscopically. The number of osteoclasts in the bone lesions was examined by tartrate-resistant acid phosphatase staining. RESULTS: Monotherapy with YM529 suppressed the production of bone metastases, but not visceral metastasis. Histological analyses revealed that the number of osteoclasts in bone lesions was lower in YM526-treated mice, compared with control mice. VP-16 inhibited both bone metastasis and visceral (lung and liver) metastasis. However, neither YM529 alone nor VP-16 alone significantly prolonged the survival of SBC-5-bearing mice. Combined use of YM529 and VP-16 further inhibited the production of bone metastasis and significantly prolonged survival. CONCLUSIONS: Combined therapy with bisphosphonate and chemotherapy may be useful for small cell lung cancer patients with multiple organ metastases including bone metastasis.     

Chronic phosphorus supplementation decreases the expression of renal PTH/PTHrP receptor mRNA in rats

Dietary intake of high levels of phosphorus is known to increase serum levels of parathyroid hormone (PTH); however, how this increased serum PTH affects the action of PTH in major target tissues, particularly by kidney, remains unknown. In the present study, we therefore undertook to clarify this point in intact animals fed a high-P diet by examining various parameters of PTH action. Twelve weanling Wistar male rats were assigned randomly to two groups: a control group with dietary Ca:P = 1:1 and a high-P group (Ca:P = 1:3) fed the standard AIN-76 diet supplemented with P (0.5 and 1.5 g/100 g of diet). After 3 weeks of feeding, in the high-P diet group, we observed that serum Ca was lowered, without a difference in serum P, when compared to the control group. Excretion of urinary cAMP, an index of renal PTH action, was also decreased, with higher excretion of urinary P in those rats fed the high-P diet. In agreement with the decreased cAMP excretion, a clear reduction in PTH/PTH-related protein (PTHrP) receptor gene expression as estimated by Northern blotting was observed in the kidney, despite increased levels of serum PTH. Thus, the present study indicated that a high-P diet reduces PTH action in the kidney, though the serum PTH is increased.     

A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion

Periventricular leukomalacia is an important cause of cerebral palsy and characterized by cysts and coagulation necrosis in the periventricular white matter. Since no model of periventricular leukomalacia has been established in small animals, it is expected to establish a new model of white matter injury in immature rodents. Bilateral carotid arteries were occluded in neonatal rats at 5 days of age, and the brain neuropathologically examined at 7 days of age. Among 22 brains histologically examined, 20 (90.9%) had white matter changes including coagulation necrosis and cystic lesions in and around the internal capsule, while only two had small cerebral infarction and five showed some ischemic neurons in the cerebral cortex. Cerebral blood flow (CBF) decreased to about 25% of controls in the subcortical white matter in the animals with bilateral carotid artery occlusion (BCAO). Amyloid precursor protein (APP) immunohistochemistry demonstrated various APP-immunoreactive axonal profiles in the internal capsule and the subcortical white matter, and stronger expression of APP in pyramidal neurons in the cerebral cortex of BCAO brains. These results indicated that the white matter is more vulnerable than the cerebral cortex in 5-day-old rats when CBF decreases to about 25% and suggested that this model is useful for investigating the white matter changes induced by cerebral hypoperfusion in the neonatal brain, since previous models of hypoxic-ischemic brain injury in neonatal mice and rats revealed preferential susceptibility of the gray matter. It was also indicated that APP is a sensitive marker for mild axonal disruption in the white matter of the immature brain.     

Designing highly emissive over-1000 nm near-infrared fluorescent dye-loaded polystyrene-based nanoparticles for in vivo deep imaging

Polystyrene-based nanoparticles (PSt NPs) prepared by emulsion polymerization are promising organic matrices for encapsulating over-thousand-nanometer near-infrared (OTN-NIR) fluorescent dyes, such as thiopyrilium IR-1061, for OTN-NIR dynamic live imaging. Herein, we propose an effective approach to obtain highly emissive OTN-NIR fluorescent PSt NPs (OTN-PSt NPs) in which the polarity of the PSt NPs was adjusted by changing the monomer ratio (styrene to acrylic acid) in the PSt NPs and the dimethyl sulfoxide concentration in the IR-1061 loading process. Moreover, OTN-PSt NPs covalently modified with poly(ethylene glycol) (PEG) (OTN-PSt-PEG NPs) showed high dispersion stability under physiological conditions and minimal cytotoxicity. Notably, the optimized OTN-PSt-PEG NPs were effective in the dynamic live imaging of mice. This methodology is expected to facilitate the design of certain polar thiopyrilium dye-loaded OTN-NIR fluorescent imaging probes with high emissivity.

By changing the ratio of acrylic acid to styrene, the loading amount of fluorescent dye can be increased and the optical properties of the resulting bioimaging probe can be improved.     

Point mutations in the steroid-binding domain of the androgen receptor gene of five Japanese patients with androgen insensitivity syndrome.

We analyzed the androgen receptor (AR) gene in five Japanese patients diagnosed with androgen insensitivity syndrome (AIS). All AR genes from the five patients had single-nucleotide substitutions, which introduced a premature termination codon in three patients (Gln640, Arg752, and Gln640 and Trp751), and a single amino acid substitution in two patients (Arg831 to Gln, and Leu812 to Phe). All the mutations occurred in the steroid-binding domain, comprising exons D through G. The three patients with the premature termination codon(s) and the one patient with Arg831Gln were clinically diagnosed as having complete AIS, while the patient with Leu812Phe had a partial form of AIS. Pubic skin fibroblasts from four of the five patients did not show detectable androgen binding. These data on mutations that have not been reported previously, provide valuable information for the further characterization of structural and functional relationships in the steroid-binding domain of the AR protein.