Adverse reactions and effects on renal function of COVID-19 vaccines in patients with IgA nephropathy.

BACKGROUND: Although vaccination has been reported to reduce the morbidity and severity of COVID-19 infection in patients with kidney disease, gross hematuria is frequently reported following vaccination in patients with IgA nephropathy. We investigated the frequency of gross hematuria following COVID-19 vaccination and its effect on renal function in IgA nephropathy patients. METHODS: Adverse reactions after two or more COVID-19 vaccine doses were investigated in 295 IgA nephropathy patients attending Osaka Cty general hospital from September 2021 to November 2022. We compared differences in background characteristics and other adverse reactions between groups with and without gross hematuria after vaccination, and examined changes in renal function and proteinuria. RESULTS: Twenty-eight patients (9.5%) had gross hematuria. The median age of patients with and without gross hematuria was 44 (29-48) and 49 (42-61) years, respectively, indicating a significant difference. The percentage of patients with microscopic hematuria before vaccination differed significantly between those with (65.2%) and without (32%) gross hematuria. Adverse reactions, such as fever, chills, headache and arthralgia, were more frequent in patients with gross hematuria. There was no difference in renal functional decline after approximately 1 year between patients with and without gross hematuria. We also found no significant changes in estimated glomerular filtration rate or proteinuria before and after vaccination in the gross hematuria group. However, some patients clearly had worsening of renal function. CONCLUSIONS: While COVID-19 vaccination is beneficial, care is required since it might adversely affect renal function in some patients.

Genomic analysis of the appearance of ovarian mast cells in neonatal MRL/MpJ mice.

In MRL/MpJ mice, ovarian mast cells (OMCs) are more abundant than in other mouse strains, and tend to distribute beneath the ovarian surface epithelium at birth. This study investigated the factors regulating the appearance of neonatal OMCs in progeny of the cross between MRL/MpJ and C57BL/6N strains. F1 neonates had less than half the number of OMCs than MRL/MpJ. Interestingly, MRLB6F1 had more neonatal OMCs than B6MRLF1, although they were distributed over comparable areas. Furthermore, in MRL/MpJ fetuses for which parturition was delayed until embryonic day 21.5, the number of OMCs was significantly higher than in age-matched controls at postnatal day 2. These results suggest that the number of OMCs was influenced by the environmental factors during pregnancy. Quantitative trait locus analysis using N2 backcross progeny revealed two significant loci on chromosome 8: D8Mit343-D8Mit312 for the number of OMCs and D8Mit86-D8Mit89 for their distribution, designated as mast cell in the ovary of MRL/MpJ 1 (mcom1) and mcom2, respectively. Among MC migration-associated genes, ovarian expression of chemokine (C-C motif) ligand 17 at mcom1 locus was significantly higher in MRL/MpJ than in C57BL/6N, and positively correlated with the expression of OMC marker genes. These results indicate that the appearance of neonatal OMCs in MRL/MpJ is controlled by environmental factors and filial genetic factors, and that the abundance and distribution of OMCs are regulated by independent filial genetic elements.

Relationship between numerous mast cells and early follicular development in neonatal MRL/MpJ mouse ovaries.

In the neonatal mouse ovary, clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. During this period, we found numerous mast cells in the ovary of MRL/MpJ mice and investigated their appearance and morphology with follicular development. The ovarian mast cells, which were already present at postnatal day 0, tended to localize adjacent to the surface epithelium. Among 11 different mouse strains, MRL/MpJ mice possessed the greatest number of ovarian mast cells. Ovarian mast cells were also found in DBA/1, BALB/c, NZW, and DBA/2 mice but rarely in C57BL/6, NZB, AKR, C3H/He, CBA, and ICR mice. The ovarian mast cells expressed connective tissue mast cell markers, although mast cells around the surface epithelium also expressed a mucosal mast cell marker in MRL/MpJ mice. Some ovarian mast cells migrated into the oocyte nests and directly contacted the compressed and degenerated oocytes. In MRL/MpJ mice, the number of oocytes in the nest was significantly lower than in the other strains, and the number of oocytes showed a positive correlation with the number of ovarian mast cells. The gene expression of a mast cell marker also correlated with the expression of an oocyte nest marker, suggesting a link between the appearance of ovarian ? 4mast cells and early follicular development. Furthermore, the expression of follicle developmental markers was significantly higher in MRL/MpJ mice than in C57BL/6 mice. These results indicate that the appearance of ovarian mast cells is a unique phenotype of neonatal MRL/MpJ mice, and that ovarian mast cells participate in early follicular development, especially nest breakdown.

[Anesthetic management of a patient with transfusion-related acute lung injury (TRALI)].

Transfusion-related acute lung injury (TRALI) is characterized by pulmonary edema and hypoxemia within 6 hours of transfusion in the absence of other causes of acute lung injury or circulatory overload and is now considered the leading cause of transfusion-related death. We report a female patient who showed hypoxemia after transfusion without any other causes of acute lung injury. The patient is a 43-year-old woman, who received emergency transurethral hemostasis for bladder hemorrhage with hematuria and low hemoglobin concentration (3.2 g x dl(-1)). General anesthesia was maintained with sevoflurane, remifentanil, and vecuronium. Two units of RBC were transfused during operation. Since she showed high blood pressure, tachycardia, and a painful expression after operation, we extubated her. Although we gave her O2 6 l x min(-1) after extubation, she showed low oxygen saturation (90%), thus we started bag-mask ventilation. However, she complained of dyspnea and the chest X-ray revealed bilateral diffuse pulmonary edema following hypoxemia (80%). Thus we inserted endotracheal tube and started positive pressure assist ventilation. The next day, hypoxemia was improved under PEEP therapy. The anti-HLA antibody in the transfused plasma was positive. We conclude that the early recognition and management of TRALI is essential during and after operation.

Synthesis and glycosidase inhibitory activity of some N-substituted 5a-carba-beta-fuco- and beta-galactopyranosylamines, and selected derivatives.

In the course of chemical modification of alpha-fucosidase inhibitors of 5a-carba-fucopyranosylamine type, an N-dodecyl derivative of the enantiomer 6-deoxy-5a-carba-beta-D-galactopyranosylamine demonstrated very strong inhibition of beta-galactosidase and beta-glucosidase. This finding led us to synthesize corresponding 6-hydroxy compounds, in order to elucidate structure-activity relationships for inhibitors of this type. Among four N-alkyl-5a-carba-beta-D-galactopyranosylamines prepared, the N-octyl derivative could be demonstrated to possess moderate activity toward alpha- and beta-galactosidases, and beta-glucosidase.

[The effect of radiotherapy on patients with prostate specific antigen failure after radical prostatectomy].

We studied the effect of radiotherapy on patients with re-elevation of prostate specific antigen (PSA) after radical prostatectomy. Radiotherapy was performed on 8 patients with re-elevated PSA after radical prostatectomy without any previous treatment. Pathological stages were B in 2 patients, and C in 6 patients. Patients received three-dimensional dynamic conformal radiotherapy, and irradiation doses ranged from 44 to 70 Gy (median 60). The target area of irradiation included prostatic bed and seminal vesicles. PSA levels before radiotherapy were 0.31-1.9 ng/ml (median 0.40). In 7 patients, PSA levels decreased and no increase has been observed thereafter. In one patient, PSA level increased during radiotherapy; therefore, the treatment was discontinued at 44 Gy. Two patients suffered grade 1 to 2 acute toxicities, and no late toxicity has been observed so far. Radiotherapy is considered one of the effective treatments for re-elevation of PSA after radical prostatectomy.

Renal lymphoma associated with Castleman's disease.

We report the second case in the literature of a renal lymphoma associated with multicentric Castleman's disease.

Convenient synthesis and evaluation of glycosidase inhibitory activity of alpha- and beta-galactose-type valienamines, and some N-alkyl derivatives.

Valienamine analogues having alpha- and beta-galactose-type structures were synthesized by racemic modification from (1SR,2RS,3SR)-6-methylenecyclohex-4-ene-1,2,3-triol. Four N-alkyl derivatives of the beta-anomer were readily prepared selectively by treatment of key intermediate 2,6-di-O-acetyl-3,4-O-isopropylidene-5a-carba-alpha- and beta-l-arabino-hex-5(5a)-enopyranosyl bromides with alkyl amines. All compounds were assayed for inhibitory activity against six glycosidases, and the N-dodecyl derivative was shown to be a very strong inhibitor of beta-galactosidase (IC(50) 0.01 microM, bovine liver).

Coexistence of renal replacement lipomatosis with xanthogranulomatous pyelonephritis.

We report on a case of coexistence of replacement lipomatosis with xanthogranulomatous pyelonephritis (XGP) in the same kidney associated with staghorn calculi. A 63-year-old man was admitted to hospital complaining of a right abdominal mass. Computed tomography (CT) showed renal parenchymal atrophy with extremely increased perirenal fat. Right nephrectomy was performed. Postoperative diagnosis was renal replacement lipomatosis with XGP. Renal replacement lipomatosis and XGP have several similarities in terms of clinical background and CT findings. Sometimes it is difficult to differentiate them from malignant diseases. It is extremely rare that both conditions coexist in the same kidney. To our knowledge, only one such case has been reported.

Chemical chaperone therapy for brain pathology in G(M1)-gangliosidosis.

We synthesized a galactose derivative, N-octyl-4-epi-beta-valienamine (NOEV), for a molecular therapy (chemical chaperone therapy) of a human neurogenetic disease, beta-galactosidosis (GM1-gangliosidosis and Morquio B disease). It is a potent inhibitor of lysosomal beta-galactosidase in vitro. Addition of NOEV in the culture medium restored mutant enzyme activity in cultured human or murine fibroblasts at low intracellular concentrations, resulting in a marked decrease of intracellular substrate storage. Short-term oral administration of NOEV to a model mouse of juvenile GM1-gangliosidosis, expressing a mutant enzyme protein R201C, resulted in significant enhancement of the enzyme activity in the brain and other tissues. Immunohistochemical stain revealed a decrease in the amount of GM1 and GA1 in neuronal cells in the fronto-temporal cerebral cortex and brainstem. However, mass biochemical analysis did not show the substrate reduction observed histochemically in these limited areas in the brain probably because of the brief duration of this investigation. Chemical chaperone therapy may be useful for certain patients with beta-galactosidosis and potentially other lysosomal storage diseases with central nervous system involvement.

[Laparoscopic cholecystectomy under general anesthesia for a woman in the 28th week of gestation].

Anesthesia for laparoscopic cholecystectomy under hypobaric pneumoperitoneum was given to a pregnant woman in 28th week of gestation. Anesthesia was induced by administering thiopental(5 mg.kg-1) and vecuronium (0.1 mg.kg-1). The lungs were artificially ventilated with oxygen, nitrous oxide, and low concentrations of sevoflurane to maintain the end-expiratory CO2 pressure at 30 to 35 mmHg. Before inducing anesthesia, a thoracic epidural catheter was inserted, and 2% mepivacaine was administered through the catheter. During the operative period, the operating field was secured by the pneumoperitoneum pressure at 8 mmHg and Fowler's and left down position. Mother's blood gases and the fetal heart beat monitored with the abdominal supersonic wave stayed steady through the perioperative periods. The pneumoperitoneum time was 34 minutes and the operation time was 40 minutes without any troubles. But we should pay much attention to anesthesia and operation in any pregnant patient.

[Treatment results of radical prostatectomy in clinical stage B and C prostate cancer: comparison of the neoadjuvant therapy group versus the surgery group; retrospective analysis of 80 cases].

Between 1994 and 2001, 80 patients underwent radical prostatectomy without adjuvant therapy for clinical stage B and C prostate cancer. The patients were not treated with adjuvant therapy before biochemical prostate specific antigen (PSA) failure. Of all 80 patients, 35 patients (43.8%) received neoadjuvant hormonal therapy prior to radical prostatectomy (the neoadjuvant therapy group), 45 patients (56.2%) underwent prostatectomy alone (the surgery alone group). Retrospective analysis to evaluate the effects of neoadjuvant therapy was performed from clinicopathological findings and the biochemical PSA failure-free rate. Of all patients, 58 (72.5%) were in clinical stage B and 22 (27.5%) were in clinical stage C. Of 58 patients in clinical stage B, 19 (32.8%) underwent prostatectomy combined with neoadjuvant therapy. Of the 22 patients in clinical stage C, 17 (77.3%) underwent prostatectomy combined with neoadjuvant therapy. Pathologically, 37 (46.3%) were in stage B, 38 (47.5%) in stage C and 2 (2.5%) in stage D1. Three patients in the neoadjuvant therapy group had no malignant findings in specimens of prostatectomy. In comparison with the clinical stage, pathologically 8 (22.9%) showed overstaging, 4 (5.0%) understaging and 23 (28.8%) accurate staging in the neoadjuvant therapy group, respectively, 0 (0.0%), 20 (44.4%), and 25 (55.6%) in the surgery alone group. In clinical stage B and C, there was no significant difference in the biochemical PSA failure-free rate between the neoadjuvant therapy group and the surgery alone group. On the other hand, in pathological stages B, the 5-year PSA failure-free rate was 63.2% in the neoadjuvant therapy group, but 100% in the surgery alone group. Although neoadjuvant therapy may have some effect on downstaging, our retrospective analysis suggests that it has no significant effect on PSA failure-free rate.

[Successful treatment for renal cell carcinoma with lung metastases by interleukin-2 and interferon-alfa: a case report].

We report a case in which a regimen of interleukin-2 (IL-2) and interferon alfa (IFN-alpha) was effective against renal cell carcinoma with lung metastases. A 69-year-old man diagnosed with right renal tumor had not received treatment for 28 months. He was admitted to our hospital for treatment. Computed tomographic (CT) findings showed a right renal tumor 11.5 cm in diameter and multiple lung metastases. Right nephrectomy was performed, and pathological examination was renal cell carcinoma (clear cell carcinoma, G2, pT3a). A regimen of IL-2 and IFN-alpha was selected as an adjuvant therapy. He received 70 x 10(4) JRU/day of IL-2 (div) 5 times a week, and 600 x 10(4) IU/day of IFN-alpha intramuscularly 3 times a week for 8 weeks. Thereafter, both treatments were continued 3 times a week. CT scan showed a complete response on lung metastases 12 months and no recurrence has been observed on CT scan for 16 months after operation.

Synthesis and glycosidase inhibitory activity of some N-substituted 6-deoxy-5a-carba-beta-DL- and L-galactopyranosylamines.

Chemical modification of 5a-carba-beta-DL-fucopyranosylamine (3) generated six N-substituted derivatives 9a-f, among which N-octyl 9b, decyl 9c, and phenylbutyl ones 9f were found to be very strong beta-galactosidase as well as beta-glucosidase inhibitors. The inhibitory activity appeared attributable to D-enantiomers from biological assays of prepared L-enantiomers. Therefore, 6-deoxy-5a-carba-beta-D-galactopyranosylamine (D-3) might be a promising lead compound for further design of new carba sugar-type beta-galactosidase inhibitors.

Pheochromocytoma of the urinary bladder without typical symptoms.

Pheochromocytoma of the urinary bladder is an unusual tumor that typically presents with hypertensive crises related to micturition. We report, herein, the case of a 62-year-old woman with bladder pheochromocytoma. The patient presented with a bladder tumor that was incidentally found by computed tomography (CT) without the triad of sustained hypertension, hematuria and postmicturitional syncope. Cystoscopy revealed a yellowish submucosal tumor in the right lateral wall of the bladder. Treatment consisted of transurethral resection in the initial diagnosis of bladder tumor. A definitive diagnosis was made postoperatively upon pathological examination. The patient has been followed up for 12 months and has shown no recurrence.

Convenient synthesis and evaluation of enzyme inhibitory activity of several N-alkyl-, N-phenylalkyl, and cyclic isourea derivatives of 5a-carba-alpha-DL-fucopyranosylamine.

Convenient synthesis and chemical modification of the potent alpha-L-fucosidase inhibitor, 5a-carba-alpha-DL-fucopyranosylamine (1), are described. Among seven N-substituted and three cyclic isourea derivatives newly prepared, the N-octyl derivative was found to be the strongest inhibitor of alpha-L-fucosidase (bovine kidney) more potent (K(i)=0.016 microM) than deoxyfuconojirimycin (K(i)=0.031 microM) with p-nitrophenyl-alpha-L-fucopyranoside as the substrate.