Intravascular ultrasound detects coarctation of the renal artery in a patient with Moyamoya disease.

A 19-year-old man with moyamoya disease was diagnosed as having renovascular hypertension, based on stenosis of the proximal portion of the right renal artery with elevated plasma renin activity. Intravascular ultrasound (IVUS) imaging at the renal artery lesion revealed focal narrowing of the renal artery without vascular wall thickening (i.e., coarctation). The coarctation of the renal artery was adequately dilated by stent implantation after suboptimal balloon angioplasty. After the procedure, the patient's hypertension improved. The findings of the present case suggest that IVUS-guided renal angioplasty is an effective therapeutic procedure for correcting coarctation of the renal artery in patients with moyamoya disease.

DNA mapping of gastric cancers using flow cytometric analysis.

Although numerous studies of gastric cancers on DNA ploidy have been reported, differences in the degree of aneuploidy (DNA index, DI) during progression have not been identified. We attempted to chart the differences in DIs during progression to clarify the role of aneuploidy in gastric cancers. We classified the gastric cancers examined into intestinal (n = 88) and diffuse (n = 48) types, and then analyzed 136 gastric cancers (intramucosal cancer, 42; submucosal cancer, 39; advanced cancer, 55) by flow cytometry using multiple sampling. In addition, we examined the DNA ploidy pattern of mucosal and submucosal lesions using the same submucosal cancers to study the tumor progression in individual cancers. Intratumoral DNA differences in DNA ploidy were observed in both types of gastric cancers. In intestinal-type cancers, multiple subclones indicated by a different DI occurred during the early stage of gastric cancers, whereas in diffuse-type cancers, multiple subclones were found primarily in advanced cancers. Although the DI varied widely in early intestinal-type cancers between 1.0 and 2.0, in early diffuse-type cancers, the DI tended to be less than 1.2. However, in advanced stage gastric cancers, the DI distribution was similar for both histological types. In intestinal-type cancers, high DI (>1.3) aneuploidy was frequently found in mucosal lesions. In contrast, only low DI (<1.2) aneuploid clones were observed in mucosal lesions of diffuse-type cancers. The present results suggest that high DI aneuploid tumor clones in intramucosal cancers acquire invasive ability when they progress to submucosal cancers, whereas DNA aneuploidy itself plays an important role in submucosal invasion of diffuse-type cancers.

Brunner's gland adenoma with a focus of p53-positive atypical glands.

A submucosal tumor was resected endoscopically from the duodenal bulb in a 43-year-old man complaining of epigastric discomfort. The tumor, measuring 22 x 20 x 19mm, consisted mainly of Brunner's glands with no atypia. However, close histologic examination disclosed a focus of glands with cellular and structural atypia. The atypical glands showed staining by periodic acid-Schiff, alcian blue, and high iron-diamine methods. Mucin histochemistry was examined, and the atypical glands resembled the excretory ducts rather than the acinar cells of the tumor. Immunohistochemically, positivity for MIB-1 was high (38.0%), and p53-positive cells were detected sporadically in the atypical glands. These results indicated that the atypical glands probably represented a neoplastic lesion. Brunner's gland adenomas associated with foci of true neoplasm are very rare; only two cases, including one patient with microcarcinoid tumors, have been reported.

Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin.

We investigated the effects of recombinant human BMP-2 (rhBMP-2) on differentiation of cells isolated from human bone, muscle, and skin. Cells isolated from bones of six patients (HBM-1 to HBM-6), muscle from five patients (HM-1 to HM-5), and skin from three patients (HF-1 to HF-3) were used. rhBMP-2 had no effects on proliferation of two HBM cells, but had a stimulatory effect on three HM cell samples. rhBMP-2 stimulated both alkaline phosphatase (ALP) activity in all HBM cells and parathyroid hormone (PTH)-dependent cAMP production in three of the four HBM cell samples, although the magnitudes of these stimulatory effects differed among the cells tested. Although none of the HBM cells examined produced detectable amounts of osteocalcin in the absence of 1,25-(OH)2vitamin D3, they synthesized measurable amounts of osteocalcin in its presence. rhBMP-2 inhibited 1,25-(OH)2vitamin D3-dependent osteocalcin production in all of the HBM cell samples. Transplantation of HBM-6 cells with rhBMP-2 using diffusion chambers into the peritoneal cavity of athymic mice induced formation of cartilage and bone in the diffusion chambers, but neither cartilage nor bone was formed in chambers transplanted without rhBMP-2. rhBMP-2 also stimulated ALP activity in all of the HM and HF cell samples examined and PTH-dependent cAMP production in three of four HM cell samples. rhBMP-2 induced no osteocalcin production in any of the HM or HF cells in the presence of 1,25-(OH)2vitamin D3. rhBMP-2 markedly inhibited myotube formation by all of the HM cell samples. Transplantation of HM-4 cells with rhBMP-2, using diffusion chambers, into athymic mice induced ALP-positive cells in the chambers, but neither cartilage nor bone was observed. These results suggest that rhBMP-2 is a potent stimulator of osteoblast differentiation and bone formation in human cells.

Immunohistochemical study of extracellular matrices and elastic fibers in a human sternoclavicular joint.

In this study, we clarified the distribution of elastic and oxytalan fibers in a human sternoclavicular joint (SCJ) using a color image system and in extracellular matrices using immunoperoxidase staining. Fine elastic fibers (EFs) were scattered in the fibrous layer of the sternoclavicular disk. This articular disk was composed of a collagenous bundle on the sternum side of the articular disk in the SCJ and cellular components including connective tissue on the clavicular side of the articular disk. The thickness of the disk gradually increased from the inferior to superior portion. Collagen fibers type I, III and V and other extracellular matrices (ECMs) were detected in the hypertrophic zone in the clavicular and sternum side of the SCJ and in the connective tissue of the articulatio condylar. On the cervical surface of the articular disk, cellular activity was higher than on the sternum surface.

The effect of the platelet derived wound healing formula and the nerve growth factor on the experimentally injured spinal cord.

The main purpose of this study is to investigate the effect of platelet derived wound healing formula (PDWHF) and nerve growth factor (NGF) in the treatment of experimental spinal cord injury. PDWHF is a conglomerate of growth factors which include platelet derived growth factor (PDGF), platelet derived angiogenesis factor (PDAF), transforming growth factor-beta (TGF beta) and platelet factor IV (PF4). Complete spinal cord transection was performed at T12 in rats and the treatment of the spinal cord injury was achieved by filling the dead space with type 1 collagen gel impregnated with PDWHF, or with 2.5S-NGF. Controls were treated with only type 1 collagen gel. Animals were sacrificed at 1, 2 or 3 months. Histopathologically, tissue autolysis and cavity formation by phagocytosis expanded 1-3 mm into the cord stumps and the volume of cavitation was less in the two treated groups. In the NGF group, a greater number of surviving nerve cells were observed in this region. Most of the control animals formed only thin, short axonal bundles, however, increased axonal regrowth was noted in animals treated with trophic factors, especially in the NGF group. The NGF group formed thick axonal bundles and abundant neuroma. Increased angiogenesis was observed in the collagen gel matrix and the injured spinal cord parenchyma, in the PDWHF group. Recent studies have shown that mammalian adult CNS possesses the ability for structural and/or functional plasticity following injury under appropriate circumstances. In this in vivo study, exogenous NGF appeared to induce axomal outgrowth and nerve cell survival. PDWHF produced notable angiogenesis which seemed to improve the extracellular microenvironment. This may be important for the delivery of exogenous trophic factors, nutrients and for the changes of extracellular matrices to support nerve cells and axons.

DNA ploidy heterogeneity in early and advanced gastric cancers.

To evaluate the clinical utility of flow cytometric DNA analysis in gastric cancers, four or more fresh tissue specimens were systematically taken from gastric cancers in 127 consecutive patients including 68 early cancers. DNA ploidy and its variation in individual tumors were determined, and the data were related to clinicopathologic findings. DNA aneuploidy was detected frequently (84.3%) irrespective of tumor progression and correlated significantly with histologic grade (G1-2 [89.6%] vs. G3-4 [76.0%], P < 0.05). DNA ploidy heterogeneity was found in 67.7% of tumors and correlated with invasion depth (mucosa [40.5%] vs. submucosa-serosa [81.2%], P < 0.001), regional lymph node metastases (negative [58.4%] vs. positive [82.0%], P < 0.01), and stage grouping (I [58.8%] vs. II-IV [86.0%], P < 0.01). The maximum DNA index of a tumor correlated significantly with invasion depth (mucosa [1.16, median] vs. submucosa [1.82], P < 0.01) and lymph node metastases (negative [1.22] vs. positive [1.86], P < 0.001). The DNA index of the subpopulation that was the most widely distributed within the tumor was significantly associated with lymph node metastases (negative [1.14, median] vs. positive [1.44], P < 0.001) and histologic grade (G1-2 [1.37] vs. G3-4 [1.12], P < 0.001). More than 80% of the diploid and/or single aneuploid stemline tumors were stage I, whereas more than half of diploid and multiple aneuploid stemline tumors were stage IV. Variation in DNA ploidy rather than presence of DNA aneuploidy correlates best with progression of gastric cancer.

The sign of Leser-Trelat associated with esophageal carcinoma.

A 79-year-old woman was admitted to our hospital with complaints of dysphagia and multiple verrucous papules that had developed over the previous year. The diagnosis of esophageal carcinoma was based on upper gastrointestinal radiography and endoscopic examination with biopsy. The clinical syndrome was consistent with the sign of Leser-Trelat associated with esophageal carcinoma. Although radiation therapy and chemotherapy were undertaken, the patient died 8 months later because of the sign of Leser-Trelat in association with squamous cell esophageal carcinoma.

Application of polyvinyl alcohol hydrogel membrane as anti-adhesive interposition after spinal surgery.

STUDY DESIGN: Three inflammatory and adhesive changes inside the spinal canal were analyzed histopathologically in cats. OBJECTIVE: To investigate the usefulness of a polyvinyl alcohol hydrogel sheet as an interposition over the dura to prevent inflammatory and adhesive reaction after laminectomy. SUMMARY OF BACKGROUND DATA: A major concern after laminectomy is scar tissue formation that may result in extradural compression or make subsequent surgery to the same area difficult and hazardous. METHODS: Wide laminectomy was performed at L5 in 30 adult cats. The dura was covered with a polyvinyl alcohol hydrogel sheet, free fat graft, or without interposition as a control. Animals were killed at 3 or 12 weeks. RESULTS: In the control group, adhesion of the exposed dura was apparent. Thick, fibrous connective tissue was observed between the dura and the paravertebral muscles. In the fat graft group, the dura was separated from the scar tissue by living grafted fat. However, the dura was adherent to the grafted fat and fibroblasts migrated into the interstitial space. In the polyvinyl alcohol hydrogel group, only a thin synovium-like layer was formed around the polyvinyl alcohol hydrogel sheet. CONCLUSIONS: Polyvinyl alcohol hydrogel is made of water and alcohol, and has been shown to be nontoxic to tissues. This is permeable to low molecular weight, but impermeable to large cells such as fibroblasts. Thus, the polyvinyl alcohol hydrogel sheet prevents migration of inflammatory cells and subsequently reduces intraspinal canal scar tissue formation and adhesive reaction. Other beneficial properties are extreme elasticity and low friction, which eliminate mechanical reaction to the spinal cord. The polyvinyl alcohol hydrogel sheet is believed to be useful in eliminating scar tissue formation and does not interfere with the dynamic gliding movement of the spinal cord and nerve roots.

[Clinical significance of DNA ploidy heterogeneity in early gastric cancers].

To evaluate the clinical significance of DNA ploidy heterogeneity (DH), four or more fresh tissue specimens were obtained from a tumor in 68 resected early gastric cancers. DNA content was measured by flow cytometry and the presence of DH was prospectively investigated. The incidence of DH correlated to invasion depth (m < sm), lymph vessel invasion (negative < positive) and tumor size (10 mm or less in diameter < more than 10). When the criteria of indication for minimum surgery were determined as the intramucosal cancer without n, ly and v factor, 85% of contraindication cases demonstrated DH. These results indicate that DH is a useful marker of tumor progression in early gastric cancer and will be an aid for determining indications for minimum resection.

[Flow cytometric analysis of DNA ploidy in intramucosal gastric carcinoma].

In order to investigate whether or not DNA ploidy was altered in intramucosal gastric carcinomas, nuclear DNA content of biopsy specimen was measured using flow cytometry in 38 intramucosal carcinomas. DNA aneuploidy was detected in 27 of 38 lesions (71.1%), and noted more frequently in differentiated carcinomas than in undifferentiated ones (83.0% vs. 20.0%, p < 0.01). There was no significant relationship between the frequency of DNA aneuploidy and macroscopical type or tumor size. DNA aneuploidy was even found in two of three minute carcinomas (5 mm or less in diameter). DNA indices showed 1.2 or lower values in 40% of the lesions with DNA aneuploidy. The average value of DNA index was significantly larger in depressed type than in elevated type (p < 0.01). In conclusion, DNA ploidy is altered in most differentiated intramucosal carcinomas. A high resolution method is essential for accurate determination of DNA ploidy in intramucosal carcinomas, especially elevated ones.

[Flow cytometric DNA analysis of colorectal carcinoma in adenoma].

We evaluated the DNA ploidy in 23 lesions of colorectal carcinoma in adenoma (CIA) and 90 adenomas without carcinomas by flow cytometry using fresh samples. DNA ploidy of carcinoma and adenoma components were assessed, respectively, with 17 paraffin-embedded samples of CIAs. The incidence of DNA aneuploidy (AP) was significantly higher in CIAs than in adenomas (47.8% vs. 12.2%, p < 0.01). Even in adenoma components of CIAs, AP tended to be found more frequent than in adenomas (41.2% vs. 12.2%). The incidence of AP in adenoma components was similar to that in carcinoma components (35.3%) in CIAs. In conclusion, DNA aneuploidy in adenomas may be a marker of malignant potential.

Electrophysiologic evaluation of intermittent sacral nerve dysfunction in lumbar spinal canal stenosis.

Intermittent sacral nerve dysfunction, induced by walking in lumbar spinal canal stenosis, may cause symptoms including hyperesthesia and pain in perineum, urinary bladder incontinence, and penile erection. However, it is difficult to objectively document these symptoms. Evoked external urethral sphincter potentials by conus medullaris stimulation were measured both before walking and after walking in five patients who complained of sexual organ or urinary dysfunction during walking, and were compared with simultaneously induced sacral nerve symptoms. These potentials were also measured during surgery. Sacral nerve symptoms were reproduced by walking 80-350 meters (average 177.5 m). These potentials disappeared in one patient and were decreased in four patients at the time when the claudicant symptoms disabled the patient during walking. The amplitude subsequently recovered in keeping with relief of those symptoms during rest. Monitoring of these potentials during surgery showed an increase of amplitude shortly after the decompression procedure of the cauda equina. In conclusion, this measuring method was valuable as an objective evaluation of intermittent sacral nerve dysfunction in lumbar spinal canal stenosis.

[Flow cytometric analysis of DNA ploidy in colorectal adenoma].

Flow cytometric measurement of nuclear DNA content in 159 colorectal adenomas was carried out to investigate the relationship between DNA ploidy and the histological findings. DNA aneuploidy was detected in 18 lesions (12.8%). The incidence of DNA aneuploidy was significantly higher in tubulovillous adenomas than in tubular adenomas (30.4% vs. 8.1%; p < 0.01). DNA aneuploidy was not found in any adenoma with mild dysplasia, but was noted in 19.1% of those with moderate dysplasia and in 33.3% of those with severe dysplasia. The mean size of the lesions was significantly larger in adenomas with aneuploidy than in those without aneuploidy (14.0 mm vs. 7.7 mm; p < 0.01). The DNA index values of 18 adenomas with aneuploidy were divided into two groups: one ranged from 1.07 to 1.23 and the other from 1.66 to 1.85. DNA index values correlated with the size of the lesions (p < 0.05), but not with the histologic type and degree of dysplasia.

[Diagnostic value of DNA ploidy in epithelial elevated lesions of the stomach].

Using flow cytometry, we evaluated the diagnostic usefulness of DNA aneuploidy in epithelial elevated lesions of the stomach. Four biopsy specimens were obtained from each lesion in 14 elevated early cancers, 21 adenomas, 37 hyperplastic polyps and 11 cases of chronic gastritis with intestinal metaplasia. All samples obtained from benign lesions indicated diploidy. DNA aneuploidy was detected in 12 lesions (85.7%) of early cancers. DNA indices ranged from 1.10 to 1.19 in six of 10 intramucosal cancers with DNA aneuploidy. Meanwhile, a total of two submucosally invasive cancers had stemlines with a DNA index of more than 2.00. Four early cancers, including two submucosally invasive ones, had multiple aneuploid stemlines. DNA aneuploidy is a useful marker of malignancy in epithelial elevated lesions of the stomach. A higher DNA index and multiple aneuploid stemlines may be possible markers of submucosal invasion in early cancer.

Long-term morphology of spastic or flaccid muscles in spinal cord-transected rabbits.

Despite difficulty in long-term maintenance of spinalized rabbits, muscular pathologic changes in chronic spinalized rabbits could be observed for a period of four weeks. Rabbits were prepared by spinal cord transection at T10 (spastic paralysis) or by spinal cord removal below L7 (flaccid paralysis). Spastic preparations showed hind-limb spasticity and reflex incontinence one to two days after operation. Hypertrophic fibers began to appear in spastic muscles after two weeks. This hypertrophy, thought to be caused by phasic repetitive contraction, was verified by electron microscopy to be different from normal exercise hypertrophy. Flaccid preparations maintained hind-limb flaccidity and overflow incontinence. In flaccid muscle, marked muscle fiber necrosis indicated rapid atrophy. Spinal deformity and joint contracture inactivate spinalized rabbits, and cause pressure sores. However, feeding assistance and avoidance of complications make long-term maintenance possible.

Long term observation of micturition by spinal cord transected rabbits.

Neurogenic bladder was observed in chronic spinalized animals. Since these animals are difficult to maintain for long periods, there are few reports of systemic study of these preparations. We have recently observed micturition by spinalized rabbits over a period of 4 weeks. In thoracic or lumbar spinalized rabbits, urinary bladder contraction and external urethral sphincter activity were initially recorded from 1-2 days postoperative. Contraction coincided with appearance of hind-limb spasticity. This micturition was the so-called detrusor-external urethral sphincter dyssynergy with residual urine. In sacral spinalized rabbits, no micturition reflex, external urethral sphincter activity, or hind-limb spasticity were observed and the flaccid state continued for 4 weeks. It is suggested that a segmental micturition reflex pathway exists initially in the rabbit sacral cord, because reappearance of the micturition reflex was extremely quick (1-2 days) compared to that of cats (2-3 weeks). Animal hypnosis enabled immobilization during measurement without anesthetic or decerebration. Chronic spinalized rabbits, which are very intolerant to spinal damage, can be maintained alive by intensive care at and post operation and are useful for systemic study of spinal cord injury.