Unlike other tissues, bone marrow (BM) seldom displays fibrosis after injury, suggesting a possible suppressive mechanism against secondary myelofibrosis in BM tissues. We investigated if fibrosis-related factors, such as matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP), were expressed in BM tissues in vivo. We attempted immunohistochemical studies on specimens of 16 BM aspiration materials with normal hematological findings and 21 BM tissues from autopsy cases who had succumbed to acute heart failure or cerebrovascular diseases without any BM injuries. Identification of immunohistochemically reactive MMP-2, MMP-9 and TIMP-2 in BM tissue samples revealed for the first time that MMP-2 was localized in the myeloid cells, erythroblasts and megakaryocytes, MMP-9 in the myeloid cells and megakaryocytes. In addition, expression of TIMP-2 in the megakaryocytes as well as in the histiocytes within the stroma was verified. In the non-pathological condition, MMP/TIMP expressions were not encountered in BM stromal cells, such as fibroblasts, vascular endothelial cells, reticulum cells on adipocytes, except for TIMP-2 identification in stromal histiocytes. It is highly possible that these MMP and TIMP expressions in the BM hematopoietic cells and stromal histiocytes are significantly associated with suppression or induction of myelofibrosis.

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In some cases of early colorectal carcinoma, radical surgical resection might be required because of vessel invasion, distant metastasis, or inadequate surgical margin. To characterize submucosal invasive colorectal carcinoma, we investigated expression of PCNA and p53 protein. Sixty-seven patients who underwent curative resection of submucosal invasive colorectal carcinoma participated in this study. The PCNA labeling index (PCNA-LI) is determined at the deepest lesion of carcinoma. The expression of PCNA and p53 protein were analyzed according to clinicopathological factors. 1) The PCNA-LI was correlated to histological grade, depth of invasion or vessel invasion in polypoid type. 2) The flat type had significantly higher PCNA-LI (65.1± 8.2%) and p53 protein expression (69.6%) than the polypoid type. 3) The PCNA-LI was higher in cases with lymph node metastasis than in these without lymph node metastasis. 4) Overexpression of the p53 protein was detected in all cases with liver metastasis. Our results suggest that in order to determine the treatment for the patients with submucosal invasive colorectal carcinoma, the expression of PCNA and p53 protein may be a useful biologic marker.

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We examined Helicobacter pylori (H. p. ) infection and changes in biopsied gastric mucosa as observed in biopsy specimens (inflammatory changes and atrophic changes) -with reference to their pathophysiological significance. We examined 68 patients with peptic ulcers and 19 patients with atrophic gastritis as controls. We confirmed H. p. infection of the gastric mucosa in biopsies from two points by tissue culture, microscopy and urease testing. We examined gastric mucosal flakes under microscopy, scoring the inflammatory changes and atrophic changes, from biopsies at Sano's 4 points. We compared the gastric mucosal condition of the H. p. (+) group and that of the H. p. (-) group histopathologically. The mucosal condition of the success fully treated H. p. infection group and that of the failure group were also investigated in the same way, as were the conditions before and after treatment.
Results: 1) The gastric mucosal inflammatory changes in the H. p. (+) group were more severe than those in the H. p. (-) group at all 4 biopsy points. 2) The gastric mucosal atrophy of the H. p. (+) group was more severe than that of the H. p. (-) group at all 4 biopsy points. 3) The gastric mucosal inflammatory changes in the treatment failure group were more severe than those in the Successful treatment group at all 4 biopsy points. 4) The gastric mucosal atrophy of the treatment failure group was more severe than that of the successful, treatment group at the anterior wall and the posterior wall of the body of the stomach. 5) The gastric mucosal inflammatory changes before treatment were more severe than those after treatment at all 4 biopsy points. 6) The gastric mucosal atrophy before treatment was more severe than that after treatment at the antrum and the angle of the stomach.
Discussion: H. p. infection seemed to cause changes in mucosal condition, severity of gastric mucosal inflammation and gastric mucosal atrophy at all 4 of Sano's points.

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Twenty-three patients with HBe antigen-positive chronic hepatitis B were treated with capitalite first letters Maruyama (SSM). HBe antigen turned negative in 15 patients. The levels of various cytokines in pre- and post-treatment frozen serum samples from six patients whose HBe antigen turned negative and from five whose HBe antigen did not were examined. Reduction of serum interleukin (IL) -10 level to below 20 pg/ml was observed after SSM treatment in four of the six patients whose HBe antigen turned negative. SSM was found to stimulate the production of interferon (IFN) -γin peripheral blood cells from two healthy volunteers. This stimulatory effect was confirmed in 12 out of 24 healthy volunteers. SSM augmented the production of IFN-γin eight out of 10 patients with chronic hepatitis B and nine of 10 with hepatitis C. These results demonstrate for the first time that SSM stimulates the production of IFN-γin human peripheral blood cells and also suggest that treatment of HBe antigen-positive chronic hepatitis B patients with SSM leads to the clearance of HBe antigen and normalization of serum aspartate aminotransferase levels through inhibition of IL-10 and stimulation of IFN-γ(J Nippon Med Sch 2000; 67: 261-266)

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Aside from vertebral compression fractures, the most common site of insufficiency fractures is the pelvis and lower extremities. In the pelvis, the fractures usually occur in the ilium, the pubis and the ischium, but rarely in the fossa acetabuli. We report a severe insufficiency fracture of the fossa acetabuli in a 78-year-old woman with rheumatoid arthritis (RA). She had associated insufficiency fractures of the rib, the thoracic spine and the sacrum. In our case, senile osteoporosis was present before the onset of the fracture was recognized on radiographs, and RA and corticosteroid therapy might have further aggravated the porosis, resulting in the destruction of the fossa acetabuli. Regarding treatment for the fracture, a cemented total hip replacement without bone graft was attempted for several reasons such as the patient's activities, postoperative rehabilitaion and the bone mass of the acetabulum. The postoperative course was satisfactory during study period. However, further follow-up is needed to monitor carefully how the patient will be in the future.

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We report an 11-year-old female patient with multiple fish vertebra deformity, which occurred in the course of treatment with corticosteroids for systemic lupus erythematosus (SLE). She was treated for SLE with predonisolone (30 mg per day) from April 2, 1996, and presented at our outpatient clinic for an osteoporosis check-up on April 27. She was 132 cm tall with-1.7 standard deviation of the average height, and X-ray examination revealed no evidence of osteoporosis in the spine. Bone mineral density (BMD) was 74.7% of the average BMD. Subsequently, she grew to 136 cm in September. However she began to have low back pain (LBP) from November, and received alfacalcidol. LBP deteriorated after pulse therapy with methylpredonisolone. In June 1997, X-ray examination revealed multiple fish vertebra deformity with 58.3% of the average BMD. Moreover her height had decreased to 131cm. She underwent combination therapy with elcatonin and alfacalcidol. In September 1999, she had no LBP nor progression of fish vertebra deformity. However she had no growth in height. Corticoseroids and SLE have multiple effects on bone metabolism, making the treatment of porosis complicated and difficult.

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Aldosteronism is a rare complication of pregnancy. We report a case of a 26-year-old woman who became pregnant soon after a diagnosis of primary aldosteronism due to left adrenal adenoma was made. Only oral potassium supplementation was required in addition to routine prenatal care until 36 weeks' gestation. Subsequently, antihypertensive medication was needed to control elevated blood pressure. A healthy male infant was delivered by cesarean section because of abruptio placentae. The postoperative course was uneventful. Left adrenalectomy was conducted eight months after delivery under laparoscopic visualization. In this case report, we discuss management of aldosteronism in pregnancy and review the literature.

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To identify apoptosis of nonparenchymal cells in fibrotic livers, we established a triple staining method which combined immunohistochemistry for cell markers and Masson staining for collagen as well as terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL). Five μm formalin fixed, paraffin-embedded liver sections were prepared for staining. Firstly, TUNEL staining was carried out to detect apoptosis of liver cells. Then, the sections were subjected to immunohistochemistry for a-smooth muscle actin (α-SMA) or KP-1 to identify hepatic stellate cells or Kupffer cells. Finally, Masson staining was performed to show the relationship between apoptosis and collagens. In addition, we optimized different conditions of fixation, digestion and color development which may affect the results.

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