Effect of Perioperative Blood Transfusions in Renal Transplant Patients.

BACKGROUND: In patients eligible for organ transplantation, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines specifically recommend avoiding red blood cell transfusions (RBCT) when possible to minimize the risk of allosensitization. OBJECTIVE: To assess the effect of perioperative RBCT on outcomes in living-related kidney transplantation (LRKT) recipients. METHODS: We retrospectively assessed 97 patients who underwent LRKT and whose data were evaluable at our institution between March 2009 and May 2016. We measured serum creatinine levels and calculated the estimated glomerular filtration rate (eGFR) at 3 months, 6 months, and 1 year after kidney transplantation (KTx). We evaluated the rejection rate within a year after KTx. We compared the renal function and rejection rate between those who received blood transfusions (n = 21) and those who did not (n = 76) during the perioperative period. RESULTS: Among patient characteristics, the rate of ABO-incompatible KTx and the mean hemoglobin levels before KTx differed significantly between the groups. The serum creatinine levels and eGFR within 1 year after KTx did not differ significantly between the two groups. The rejection rate in those who received blood transfusions and those who did not was 28.6% (6/21 patients) and 25.0% (19/76 patients) (P = .741), respectively. CONCLUSIONS: We found that the rejection rate was slightly higher in patients who received perioperative RBCT than in those who did not, but the difference was not significant within a year after KTx. Perioperative RBCT may not affect renal function within a year after KTx.

Effect of Influenza Vaccine in Patients With Kidney Transplant.

BACKGROUND: Among infectious diseases, influenza is the most common cause of infection in Japan and worldwide. We aimed to evaluate the effect of influenza vaccination in kidney transplantation (KTx) recipients. METHODS: We retrospectively evaluated the records of 98 participants who underwent KTx at our institution between March 2009 and May 2016. All patients received tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone for maintenance immunosuppression after KTx. In accordance with the criteria of our institution, everolimus was administered for the maintenance of immunosuppression after KTx. We compared the rate of influenza infection during the 2016-2017 season (8 months, from October 2016-May 2017) between KTx patients treated with 1 or 2 doses of influenza vaccine (treatment group, n = 71) and KTx patients who did not receive a vaccine (nontreatment group, n = 27). RESULTS: Among patient characteristics, only the prevalence of diabetes mellitus differed significantly between the groups (treatment group: 9.9%, 7 of 71 patients; nontreatment group: 29.6%, 8 of 21 patients; P = .02). Influenza infection occurred at similar rates in the 2 groups (treatment group, 5.63% 4 of 71 patients; nontreatment group: 3.70%, 1 of 27 patients; P = .70). CONCLUSIONS: Among KTx patients managed in our institution, treatment with 1 or 2 doses of influenza vaccine did not reduce the rate of influenza infection in the 2016-2017 season, suggesting that influenza vaccination may currently be ineffective in KTx patients.

Morules and morule-like features associated with carcinomas in various organs: report with immunohistochemical and molecular studies.

BACKGROUND: Morules have been reported in pulmonary blastoma (PB), well differentiated fetal adenocarcinoma of the lung (WDFA), and uterine endometrioid carcinoma (EC), and rarely in other carcinomas. beta Catenin gene mutation has been associated with morule formation. AIMS: To compare and clarify the cellular characteristics of morules in carcinomas in various organs and show that morules are distinct from epithelial cellular nodules. METHODS: Twenty tumours were studied: two PBs, three WDFAs, three papillary lung adenocarcinomas, 11 ECs, and one papillary thyroid carcinoma. Numerous epithelial cell, oncofetal, and neuropeptide antibodies were used for immunohistochemistry. beta Catenin gene mutation was investigated. RESULTS: Morules in PBs and ECs were uniform cell clusters distinct from squamous differentiation. All were immunonegative for epithelial cell and oncofetal antigens, but those in ECs were positive for neurone specific enolase gamma (NSEgamma). Synaptophysin, encephalin, and somatostatin were sporadically immunopositive in PB morules. Morules were not seen in the other carcinomas and WDFAs, although morule-like features closely resembling morules histopathologically were seen. These were positive for epithelial cell and oncofetal antigens, and showed squamous differentiation. Their nuclei were more atypical and slightly larger than those in morules. Morule-like features were seen in WDFAs. beta Catenin gene mutation was demonstrated in one EC and PB, and in two WDFAs. CONCLUSION: Morules were non-epithelial cell clusters showing neuronal differentiation. There were two types: endometrioid type, expressing NSEgamma, and blastoma type, expressing neuropeptides. In contrast, similar morule-like features were epithelial nodules. Although the number of cases was small, the presence of morules showed no clear prognostic correlations.

Morules in endometrial carcinoma and benign endometrial lesions differ from squamous differentiation tissue and are not infected with human papillomavirus.

BACKGROUND: Squamous differentiation/squamous metaplasia is often associated with endometrial adenocarcinoma and benign lesions, such as endometrial hyperplasia and chronic endometritis. Morules have distinct histological characteristics, and are referred to as squamous metaplasia or squamoid metaplasia. AIM: To focus on the histological characteristics of morules and clarify the difference between morules and squamous differentiation. MATERIALS/METHODS: Twenty endometrioid carcinomas with morules or squamous differentiation, five adenosquamous carcinomas, and eight non-carcinomatous endometrial lesions with morules were investigated. Numerous antibodies for epithelial membrane antigen (EMA), involucrin, cytokeratins, neuropeptides, and oncofetal antigens were used for immunohistochemistry. In situ hybridisation and polymerase chain reaction were used to detect human papillomavirus (HPV). RESULTS: The morules observed were uniform cell clusters, with no squamous differentiation. They were immunonegative for epithelial antigens including involucrin, EMA, and cytokeratins, but were positive for neurone specific enolase. A few morules were immunopositive for acetylcholine esterase, and one case was positive for somatostatin; neither oncofetal nor proliferative cell markers, including blood group A, B, and AB, or other neuropeptides were demonstrated in the morules. HPV DNA was not found in either the morules in the carcinomas or in the benign lesions. However, true squamous differentiation tissue in four endometrioid carcinomas and two adenosquamous carcinomas was HPV positive using in situ hybridisation. CONCLUSION: Morules are histologically distinct from squamous metaplasia/squamous differentiation tissue. Morules are thought to be neuroectodermal-like cell clusters, and are not infected with HPV. In contrast, some of the true squamous differentiation tissue was associated with HPV infection.

Human herpesvirus 8 (HHV8) sequence variations in HHV8 related tumours in Okinawa, a subtropical island in southern Japan.

BACKGROUND: Although rare in mainland Japan, classic Kaposi's sarcoma (KS) is frequently reported in Okinawa, a subtropical island in southern Japan. Human herpesvirus 8 (HHV8) has been identified in the tumours and geographical differences occur. AIM: To sequence HHV8 in classic and AIDS associated KS in Okinawa. MATERIALS/METHODS: Eight classic KS cases, one AIDS associated KS, five granuloma pyogenicum cases, two inflammatory pseudotumours, two Castleman's disease cases, one angiosarcoma, and one primary effusion lymphoma (PEL) were studied. As a control, HHV8 positive cultured PEL cells (TY-1) were used. The presence of HHV8 sequences was evaluated by PCR and in situ hybridisation. PCR products were sequenced. RESULTS: There were no histological differences among KS resulting from the different virus genotypes. HHV8 was detected in all cases of KS, in one PEL, and one granuloma pyogenicum. Eight classic KS cases and one granuloma pyogenicum were infected with HHV8 genotype II/C (K1 region) or subtype C (ORF26 region), which had a five amino acid deletion at K1 VR2 region. An AIDS associated KS and a PEL were infected with type I/A virus. CONCLUSION: In Okinawa, classic KS cases and one granuloma pyogenicum case were infected with HHV8 genotype II/C, also classified as subtype C. AIDS associated KS and PEL were infected with a different HHV8 (genotype I/A), similar to that found in the USA. In Okinawa, HHV8 infection is more than four times higher than in mainland Japan, resulting in many cases of KS because of HHV8 genotype II/C infection.

Squamous metaplasia induced by transfection of human papillomavirus DNA into cultured adenocarcinoma cells.

BACKGROUND/AIM: It has been reported previously in cases of adenosquamous carcinoma of the lung in Okinawa, a subtropical island 2000 km south of mainland Japan, that the squamous cell carcinoma components were positive for human papillomavirus (HPV) by non-isotopic in situ hybridisation (NISH). The adenocarcinoma cells adjacent to the squamous cell carcinoma components were enlarged and also positive for HPV. This is thought to indicate that after adenocarcinoma cells are infected with HPV, they undergo morphological changes, and that "squamous metaplasia" follows. In this present study, the effects of HPV transfection into adenocarcinoma cells were examined. The relation between the region expressing the HPV gene and squamous metaplasia was also studied. METHODS: Plasmid pBR322 containing HPV type 16 (HPV-16) was transfected into cultured colonic adenocarcinoma (DLD-1) and lung adenocarcinoma (PC-14) cells using the calcium phosphate method. Neomycin was used as a selection marker. The presence of HPV E1, E2, E4, E5, E6, E7, L1, and L2 mRNAs and also transglutaminase 1, involucrin, cyclin dependent kinases (CDKs), cyclins, caspases, apoptosis inducing factor, DNase gamma, Fas, and Fas ligand mRNAs in HPV transfected cells was investigated by means of reverse transcription polymerase chain reaction (RT-PCR). The G0-G1 cell population was analysed by flow cytometry. Morphological examination under light and electron microscopes was also carried out. RESULTS: The virus transfected cells showed squamous metaplasia when they were injected into severe combined immunodeficient mice, expressing the high molecular weight keratin (Moll's number 1 keratin) and involucrin molecules immunohistochemically, and involucrin and transglutaminase I mRNAs by RT-PCR. The squamous metaplasia was most conspicuous in the HPV transfected DLD-1 cell when compared with HPV transfected PC-14 cells. Squamous metaplasia was most clearly demonstrated in one HPV transfected DLD-1 cell clone, which expressed not only E2 but also E6-E7 fusion gene mRNA. Viral L1 mRNA expression was absent in HPV transfected cell clones, and was not related to squamous metaplasia. The growth rate of HPV transfected cells was reduced. Transfection of the virus into the cultured adenocarcinoma cells increased the G0-G1 cell population greatly, as assessed by flow cytometer analysis. Furthermore, in the virus transfected cells, apoptosis was also observed by means of the terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labelling method. CONCLUSION: HPV transfection into adenocarcinoma cells induced clear squamous metaplasia. One of the HPV transfected cell clones that expressed E2 and E6-E7 fusion gene mRNA showed the squamous metaplasia particularly clearly, and apoptosis was also demonstrated.

[Spinal myoclonus possibly caused by epidural anesthesia].

We report a patient who developed a rare neurological complication of spinal myoclonus possibly caused by an epidural catheter. A 24-yr-old female received laparoscopy and intrauterine curettage under general combined with epidural anesthesia. Spinal myoclonus started about 4 hours after the last epidural drug injection and disappeared 2 hours following removal of the epidural catheter. The patient was discharged without any untoward neurological sequelae.

[Pathological examination of the lung in leprosy patients].

To study pulmonary lesions in leprosy, five autopsy cases were histopathologically examined. Case 1 (BL type) died of renal failure, case 2 (LL type) of myocardial infarction, case 3 (TT type) and 4 (BL type) of cerebral hemorrhage and case 5 (BL type) of pancreas cancer. The mean age was 78 years old. Uremic lung (case 1), old tuberculous lesion (case 3) and metastatic adenocarcinoma (case 5) were demonstrated. Pulmonary congestion and mild emphysema were seen in all cases. Aspiration pneumonia was found in all but case 4. Small foci of adenomatous hyperplasia were found in cases 1 and 5. In addition, pulmonary findings of 13 outpatients with leprosy were roentgenologically examined. No patient except one with mild emphysema showed any abnormality in the lung. In our cases, no characteristic pulmonary lesion to leprosy was found.

Isolation and mapping of a human gene (SEC14L), partially homologous to yeast SEC14, that contains a variable number of tandem repeats (VNTR) site in its 3' untranslated region.

We have isolated a novel human gene, designated SEC14L, that contains tandemly-repeated sequences in the 3' untranslated region. This gene includes an open reading frame of 2,145 bp encoding a 715-amino-acid protein. Partial homologies to yeast SEC14 and to retinal-binding protein (RALBP) of the Japanese flying squid suggest a possible role of the gene product in an intracellular transport system. As the predicted protein is also highly homologous to hypothetical proteins of C. elegans, evolutionary conservation is indicated. SEC14L, which was expressed in all human tissues examined, was localized to chromosome bands 17q25.1 --> q25.2 by fluorescence in situ hybridization.

Isolation of 45 exon-like fragments from 8p22-->p21.3, a region that is commonly deleted in hepatocellular, colorectal, and non-small cell lung carcinomas.

The loss of heterozygosity that is frequently observed at chromosome 8p22-->p21.3 in hepatocellular carcinomas (HCC), colorectal cancers (CRC), prostate cancers (PRC). and non-small cell lung cancers (NSCLC), suggests the presence there of one or more tumor suppressor genes associated with development and/or progression of these types of carcinomas. We have constructed a cosmid contig map of the target region by means of Southern hybridization and have isolated 45 exon-like fragments by exon amplification, using cosmid clones derived from three yeast artificial chromosomes (YACs). The map and the exon-like fragments reported here will be useful resources for isolation of the putative tumor suppressor gene(s) as well as other novel genes located in the 8p22-->p21.3 region.

[Glycogenosis type II; acid alpha-glucosidase deficiency].

Knowledge of the general enzymology of lysosomal acid alpha-glucosidase (acid maltase) including that of the intracellular processing mechanism and of the cDNA sequence has advanced recently. Genetic heterogeneity of the mRNA of acid alpha-glucosidase deficient patients has also been reported. Referring to these recent advances, and based on our previously reported results, the pathologic aspects of the disease are reviewed. Heterogeneity of the enzyme molecules themselves and their characteristics in various tissues are also demonstrated.

Isolation and mapping of the human beta-signal sequence receptor gene (SSR2).

We have isolated a human cDNA clone homologous to the canine beta-signal sequence receptor gene, which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane. Northern blot analysis revealed its ubiquitous expression in all organs examined. We also localized the human beta-signal sequence receptor gene (SSR2) to chromosome bands 1q21-->q23 by fluorescence in situ hybridization.

2058 expressed sequence tags (ESTs) from a human fetal lung cDNA library.

ESTs (expressed sequence tags) provide complementary resources for structural and functional analyses of the human genome. We have performed single-pass sequencing of 2058 randomly selected, directionally cloned cDNAs isolated from a fetal-lung cDNA library constructed with oligo(dT) primers. Computer analyses of the 5'-end sequences revealed that 60.4% of the clones were considered to be identical to previously reported human genes or ESTs; 9.0% of them showed significant homology to known genes in human, other mammals, or lower organisms; 30.6% showed no homology to any genes or DNA sequences in the public database. These data and reagents will be useful for future investigations of gene expression during prenatal development of human lung.

[Pompe's disease--acid alpha-glucosidase deficiency--a review].

The importance of the role of acid alpha-glucosidase in the lysosomal degradation of glycogen has been emphasized because the deficiency of this enzyme in glycogenosis type II causes glycogen accumulation in lysosomes. Three clinical variants are distinguished. The infantile type has its onset shortly after birth and is known as generalized glycogen storage disease. The adult variant manifests itself mostly after the second decade of life and is characterized by progressive skeletal muscle weakness. The other is childhood type which is usually fatal by the second decade of life. Many biochemical reports of acid alpha-glucosidase have been published. Martiniuk et al reported the cDNA and amino acid sequence of human acid alpha-glucosidase. In prior studies, they reported that the lysosomal acid alpha-glucosidase was polymorphic with three alleles. The rarer allele GAA2 allozyme had a lower affinity for glycogen and starch. We also reported the enzyme heterogeneity in its affinity to Sephacryl S-200 gel. Whereby the enzyme separated into two fractions, S1 and S2. Each fraction contained 76 kDa and 67 kDa components on SDS/PAGE. The spleen enzyme consisted mainly of S1 fraction, containing only a 76 kDa component. In previous extensive studies, different mutations of Pompe's disease have been inferred from alterations in biochemical parameters. More recently Martiniuk et al, Hoefsloot et al and Van der Ploeg et al reported the analysis of cDNA and mRNA. These studies have revealed an absence or abnormal size of mRNA in large numbers of patients and altered restriction endonuclease fragments in a few patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of a subdural motor blockade.

We report an unusual development of motor blockade following the subdural injection of local anaesthetic during attempted continuous lumbar epidural anaesthesia. Four characteristic features of subdural block, extensive spread, segmental distribution, delayed onset, and short duration of motor blockade were all features of the case. The patient had gradual development of complete motor blockade in the left upper extremity, incomplete in the right upper extremity, but absence of motor blockade in the lower extremities. The duration of complete motor blockade was 10 min in the hand and 35 min in the arm. The spread of contrast medium in the subdural space revealed the extent and degree of motor blockade.

Peroxidized lipids isolated by HPLC from atherosclerotic aorta.

Conjugated dienes of fatty acids were detected in cholesterol esters in lipid droplets prepared from atherosclerotic aorta of WHHL rabbits. Two peroxidized fatty acids were recovered by reverse phase HPLC. These peroxidized fatty acids showed maximum absorption at 233 nm, suggesting that they were peroxidized lipids containing cis-trans conjugated diene, and one of them was shown to be 13-hydroxy octadecadienoic acid.