Comparisons of several dosages of a GnRH analog with the standard dose of hCG in the treatment of follicular cysts in dairy cows.

Two experiments were carried out to examine therapeutic effect of a gonadotropin-releasing hormone analog, buserelin, on ovarian follicular cysts in dairy cows. Follicular cysts were diagnosed by palpation per rectum as well as by milk progesterone assay. Luteinization of the follicular cysts following treatment was judged by an increase in milk progesterone. In Experiment 1, 35 cows were diagnosed to have follicular cysts on the basis of palpations and low milk progesterone concentrations 1 week before treatment. Another 19 cows which were clinically diagnosed with follicular cysts but showed high milk progesterone levels before treatment were excluded. Sixty-two percent (11/18) of cows with follicular cysts treated with 20 microg of buserelin and 82% (14/17) of cows treated with 10,000 IU of human chorionic gonadotropin (hCG) showed luteinization of follicular cysts within 4 to 5 days after the treatments. The percentage of cows conceiving within 100 days after treatment and the average interval in days between treatment and conception were 44% and 42+/-18 (SD) days for the buserelin-treated cows and 47% and 42+/-18 days for the hCG-treated cows. In Experiment 2, the effects of treatment doses (6, 10, 20 and 30 microg of buserelin and 10,000 IU of hCG) on follicular cysts were compared using 103 cows. An additional 23 cows which were clinically diagnosed as having follicular cysts and which were given treatment showed a high milk progesterone concentration on the day of treatment and were therefore excluded. Fifty to 64% of the cows responded with luteinization of follicular cysts after treatment. There was no significant difference in response among cows given either the different dosages of buserelin or the hCG. However, the percentage of the total number of cows that conceived after a single or a repeated treatment with 6 microg buserelin was lower than that of cows after a single or a repeated treatment with 10 microg buserelin (P<0.05). An increase in the dose of buserelin from 10 to 30 microg did not improve the therapeutic effect of the drug. Thus, it is concluded that a single intramuscular injection of buserelin at a dose of 10 microg or higher is as effective as 10,000 IU hCG, and is, therefore, recommended for the treatment of ovarian follicular cysts in cows.

Spatial distribution of nociceptive neuropeptide and nerve growth factor depletion in experimental diabetic peripheral nervous system.

This study investigated the time-course of the nociceptive neuropeptide substance P and nerve growth factor (NGF), which facilitates substance P production, in lumbar and cervical dorsal root ganglia (DRG) of streptozotocin-induced diabetic rats. Levels of substance P and NGF were measured by radioimmunoassay and sandwich enzyme-linked immunosorbent assay, respectively, 2 months, 4 months and 8 months after induction of diabetes, and compared with age-matched non-diabetic control rats. At 2 months and 4 months, substance P and NGF levels were lower in the lumbar DRG of the diabetic rats than in controls. At 8 months, substance P and NGF were lower in both the lumbar and cervical DRG of the diabetic rats than in controls. These data demonstrate that a decrease in substance P levels in primary sensory neurons with NGF depletion occurs in an axonal length-dependent manner in diabetic rats, and that this decrease may be correlated with the duration of diabetes.

[A study of differential expression of HLA class II antigens in human lymphocytes].

Flow cytometric data of human lymphocyte subset in routine samples of patients have often shown differential expression of HLA Class II (Class II) antigens on T and B lymphocytes in our laboratory. I2 and I3 (both Coulter) were used as monoclonal antibodies for detection of Class II antigens. I2 was able to recognize HLA-DR except for haplotype of HLA-DR7, whose frequency was 1.8% in Japanese. Differential expression of Class II antigens of B lymphocytes in the present study was noticed in approximately 10% of our samples in frequency. In all of the 7 follow-up cases with renal transplantation, decrease of I2 expression on B lymphocytes was consistently noticed. On the other hand, increase of Class II expression on T lymphocytes was often recognized in autoimmune diseases, compared with those of diseases. Two of seven cases of hematologic neoplastic disorders were B cell type of malignant lymphoma and failed to express I2 despite the presence of I3 in terms of differential expression of Class II. In conclusion, the present study indicates that acquired decrease of HLA-DR expression on B lymphocytes was recognized in all of the studied patients with renal transplantation and that lack or decrease of HLA-DR expression on neoplastic B lymphocytes might be one of the characteristics of monoclonal growth.

[Effective methyl prednisolone pulse therapy for a patient with retinoic acid syndrome in acute promyelocytic leukemia].

A 46-year-old woman with acute promyelocytic leukemia (APL) was treated with all-trans retinoic acid (ATRA) and chemotherapy according to the AML-92, M3 regimen of the Japan Adult Leukemia Study Group (JALSG). Between days 7 and 18 of therapy, she suffered chest discomfort, fever, cough, dyspnea and general fatigue. A chest roentogenogram showed bilateral interstitial infiltrates. Her leukocyte count began to increase rapidly to 6,400/microliters on day 14. Marked hypoxia (PO2 35.9 mmHg) suggested occurrence of retinoic acid (RA) syndrome. She underwent endotracheal intubation and mechanical ventilation with administration of methyl-prednisolone (m-PSL) pulse therapy. Her symptoms promptly abated. Therapy with ATRA was continued and her leukocyte count reached 44,800/microliters on day 19 of therapy. She achieved complete remission on day 48.

[Successful cholecystectomy in a patient with paroxysmal nocturnal hemoglobinuria].

We report a case of paroxysmal nocturnal hemoglobinuria (PNH) and review the literature regarding transfusion of red blood cells in PNH patients. A 42-year-old woman with myelodysplastic syndrome (MDS) complaining of right hypochondralgia and high fever was admitted to the hospital for acute cholecystitis with gall stone. Blood examination revealed bicytopenia (leukocytes, 1,700/microliters and hemoglobin, 8.5 g/dl) and bone marrow examination showed normocellular but hypererythroid bone marrow and dyshematopoiesis, which suggested MDS. Laboratory data revealed obstructive jaundice and hemolytic anemia. Positive sucrose and Ham tests, which were compatible with the diagnosis of PNH. Cholecystectomy was successful, and the patient showed no postoperative complications of increased hemolysis or thrombosis. As hemoglobin level gradually decreased for the first two postoperative weeks, filtrated white cell-depleted red blood cells (total, 1,000 ml) were transfused instead of washed red blood cells. No side effects of the transfusion were noted. On the basis of findings in this case and those reported in the literature, it is concluded that in some case of PNH, the use of washed red blood cells is unnecessary, and that the use of white cell-depleted red blood cells is indicated.

[Polyclonal B-cell lymphocytosis with clinical and hematological features resembling hairy cell leukemia].

A 49-year-old man was admitted to our hospital for investigation of splenomegaly and lymphocytosis. He had no significant past history and was not a smoker. Physical examination revealed massive splenomegaly and no palpable superficial lymph nodes. Hematological examination showed a hemoglobin concentration of 10.5g/dl, a platelet count of 9.8 x 10(4)/microliter, and a leukocyte count of 21.2 x 10(3)/microliter with 70% abnormal lymphocytes. In May-Giemsa stained blood films, the abnormal lymphocytes had round nuclei, abundant, pale cytoplasm, and slightly serrated edges. Phase-contrast microscopic and scanning electron microscopic examinations revealed many long surface villi. Tartrate-resistant acid phosphatase activity in these cells was negative. The abnormal lymphocytes had a CD5-, CD10-, CD11a+, CD11c+, CD19+, CD20+, CD22+ phenotype. These features were similar to those described for a variant form of hairy cell leukemia (HCL-Japanese variant). However, studies of Ig gene rearrangement and expression of sIg revealed a polyclonal proliferation of B cells. On the basis of these findings, this case was diagnosed as hairy B-cell lymphoproliferative disorder, a recently described condition characterized by polyclonal B-cell lymphocytosis and features resembling HCL-Japanese variant. Serological assays for antibodies against Epstein-Barr virus suggested a past infection. Splenectomy alleviated the anemia and thrombocytopenia, but not the lymphocytosis.

The gene transfer of soluble VEGF type I receptor (Flt-1) attenuates peritoneal fibrosis formation in mice but not soluble TGF-beta type II receptor gene transfer.

Peritoneal fibrosis formation is a consequence of inflammation/injury and a significant medical problem to be solved. The effects of soluble VEGF receptor type I (sFlt-1) gene transfer on experimental peritoneal fibrosis were examined and compared with soluble transforming growth factor-beta (TGF-beta) receptor type II (sTGF beta RII) gene transfer. Male C57BL/6 mice were injected with 1.5 x 10(8) plaque-forming unit of adenovirus encoding active TGF-beta (AdTGF beta) intraperitoneally. Some mice had been treated with sTGF betaRII or sFlt-1 plasmid injection into skeletal muscle with electroporation 4 days before virus administration. Mice were euthanized at day 14 after virus administration. AdTGF beta induced significant elevation of serum active TGF-beta, caused significant inflammatory response [weight loss, elevation of serum amyloid-P (SAP) and IL-12, increased expression of monocyte chemoattractant protein-1 (MCP-1) mRNA], and induced marked thickening of the peritoneum and collagen deposition. Gene transfer of sFlt-1 reduced the collagen deposition approximately 81% in mesenteric tissue. Treatment with sFlt-1 decreased ICAM-1 and MCP-1 mRNA expression significantly. Significant negative correlation between serum sFlt-1 and placental growth factor level was observed, whereas there was no significant negative correlation between sFlt-1 and VEGF. On the other hand, sTGF beta RII treatment enhanced the AdTGF beta-induced inflammation (significant elevation of SAP, TNF-alpha, and IL-12 levels and upregulation of ICAM-1 and MCP-1 mRNA expressions) and failed to prevent collagen deposition. These observations indicate that sFlt-1 gene transfer might be of therapeutic benefit in peritoneal fibrosis.

Disruption of CD40-CD40 ligand pathway inhibits the development of intestinal muscle hypercontractility and protective immunity in nematode infection.

In our previous studies, we demonstrated that during Trichinella spiralis infection, T helper (Th) 2 cells contribute to the development of intestinal muscle hypercontractility and worm expulsion from the gut via STAT6. In addition, we have linked the altered muscle contractility to the eviction of the parasite and thereby to the host defense. However, the initial events linking infection to the development of muscle hypercontractility are poorly understood. In this study, we examined the contribution of CD40-CD40 ligand (CD40L) interaction in the development of intestinal muscle hypercontractility, in monocyte chemoattractant protein-1 (MCP-1) production, and in the Th2 response in CD40 ligand-deficient (CD40L -/-) mice infected with T. spiralis. Expulsion of intestinal worms was substantially delayed in CD40L -/- mice compared with the wild-type mice after T. spiralis infection. Consistent with delayed worm expulsion, there was a significant attenuation of intestinal muscle contractility in CD40L -/- mice. Infected CD40L -/- mice also exhibited marked impairment in the production of MCP-1, IL-4, IL-13, IgG1, IgE, and mouse mucosal MCP 1 (MMCP-1), and in goblet cell response. These results demonstrate that CD40-CD40 ligand interaction plays an important role in MCP-1 production, Th2 response, intestinal muscle hypercontractility, and worm expulsion in nematode infection. The present data suggest that the early events leading to the generation of Th2 response include CD40-CD40 ligand interaction, which subsequently influences the production of Th2 cytokines, most likely via upregulation of MCP-1.

Etiology of IgA nephropathy syndrome.

Since Berger's original paper on mesangial IgA-IgG deposition with hematuria, there have been a number of clinical and pathological studies regarding IgA immune complexes, the mechanisms of glomerular IgA deposition leading to glomerular injury and animal models of IgA nephropathy. During the last quarter of this century, glomerular changes such as IgA nephropathy have also been observed in cases associated with other diseases, such as systemic lupus erythematosus, Schoenlein-Henoch purpura, liver cirrhosis and chronic inflammatory diseases of the lung. This evidence supports the idea of an IgA nephropathy syndrome. On the other hand, IgA is thought to be an important humoral factor at the mucosal immune system and appears to have an antibody function against various etiologic candidates of extrinsic or intrinsic substances at the mucosal and systemic immune system. Glomerular IgA deposition in IgA nephropathy syndrome is thought to result from elevated levels of circulating immune complexes or aggregated IgA due to an overproduction of polymeric IgA as antibodies in the serum and due to the clearance impairment of IgA immune complexes in the hepatic and splenic phagocytic system. The glomerular IgA subclass is not one-sided, but should be evaluated in comparison with the age of patients at renal biopsy; this indicates the approximate age of onset. Cirrhotic IgA glomerulonephritis is not related to Hepatitis B or C virus infection, but to the pathophysiologic condition of liver cirrhosis. Various etiologic candidates such as viral, microbial, dietary antigens or auto-antigens have been listed and experimental models of IgA nephropathy syndrome have provided some clues in understanding the etiology of primary IgA nephropathy. However much still remains to be clarified and some specific epitopes common among these etiologic candidates will have to be identified.

Experimental immunoglobulin A nephropathy induced by gram-negative bacteria.

A study was conducted to determine whether intraperitoneal and oral administration of formalin-fixed gram-negative bacteria induced immunohistologically and ultrastructurally evident glomerular deposition of IgA and C3 in C3H/HeN mice. Separate treatments with strains of Pseudomonas aeruginosa, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, and two kinds of lipopolysaccharide (LPS) were used. Two mice in each treatment group were sacrificed at 10, 20 and 30 weeks of age to examine sequential glomerular changes. In addition to the intraperitoneal administration (IP) groups receiving whole formalin-fixed bacterial cells, cell precipitate and supernatant fractions of each bacterial strain after sonication were injected intraperitoneally once a week, and the mice were sacrificed at 30 weeks of age. Sequential quantitation or IgG, IgA or IgM in serum and the isotypes specific for each of the bacterial strains or LPS administered was performed by ELISA. The incidence of immunofluorescence positivity for glomerular IgA and C3 was 37-71 and 37-66.7%, respectively, in the IP groups that had received bacterial cells of each strain, which was significantly higher than that in the IP groups given LPS or in the controls. These results suggest that cell wall components common among gram-negative bacteria, other than LPS, play a major role in the glomerular deposition of IgA and C3. This is the first use of gram-negative bacteria to establish an active model of IgA nephropathy.

[An autopsy case of Paget's disease of the scrotum with general metastasis].

An autopsy case of genital Paget's disease with a widespread metastases is reported. A 69-year-old man with redness, itching and swelling of the scrotum obtained dermatological consultation and underwent tumor resection for Paget's disease. At 8 months after discharge, he suffered from a costal fracture because of carcinomatosis of the bone marrow. In laboratory data the serum level of alkaline phosphatase and carcinoembryonic antigen was shown to be high. Four months later, he died of severe congestive edema of the lung with diffuse micrometastases. An autopsy revealed a widespread metastases in various organs and lymph nodes. The Paget cells were positive in carcinoembryonic antigen.

Renal lesion of type Ia glycogen storage disease: the glomerular size and renal localization of apolipoprotein.

In order to investigate the glomerular size and renal localization of apolipoprotein in type Ia glycogen storage disease, a renal biopsy was performed in two proteinuric patients. Histopathological examination of the biopsy specimens revealed focal sclerotic glomerular sclerosis in both patients. The mean glomerular area was 21.6 +/- 11.6 x 10(3) microns 2, indicating enlargement of the glomeruli. Immunohistochemical staining of the specimens for apolipoprotein showed localization of apolipoprotein AI on the inner side of the glomerular capillary wall, and in proximal tubular epithelial cells. In one patient with a history of several episodes of hypoglycemia, treatment with corn starch improved the carbohydrate and lipid metabolic profile and reduced the daily urinary protein excretion from 2.23 to 0.5 g. These results suggest that focal sclerotic glomerular lesions associated with type Ia glycogen storage disease may be related to disorders of carbohydrate and lipid metabolism.

[A case report of pleural involvement in primary macroglobulinemia].

A case of primary macroglobulinemia with pleural and gastric involvement was presented. A 48-year-old female was admitted with productive cough. On physical examination neither lymphoadenopathy nor hepatosplenomegaly were found. In addition, no bleeding tendency nor disturbance of the visual acuity were detected. Her chest roentgenogram showed a moderate amount of pleural effusion in the left pleural cavity without infiltration in the lung fields and no evidence of swollen hilar or mediastinal lymphnodes. A monoclonal M-band of to IgM-kappa type was observed in her serum and the pleural effusion. The diffuse ulcerative lesion in the gastric mucosa was detected by gastrofiberscopy. The lymphoid cells taken from the pleural effusion and the gastric mucosa stained positively with fluorescein-conjugated antiserum to u or the kappa chain. Pleural effusion and gastric infiltration of lymphoid cells improved remarkably following ACOP therapy.