[Clinicopathological features of BAP1 mutated clear cell renal cell carcinoma].

Objective: To investigate the clinicopathological characteristics, immunophenotypes, molecular features, and differential diagnosis of BAP1 mutated clear cell renal cell carcinoma (CCRCC) for better understanding this entity. Methods: Clinical data, histological morphology, immunophenotypes and molecular characteristics of 18 BAP1 mutated CCRCC cases diagnosed at the Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China from January 2020 to December 2022 were analyzed. The patients were followed up. Results: There were 17 males and 1 female patients, aged from 39 to 72 years, with an average age of 56.3 years. Sixteen patients with primary CCRCC were followed up for an average of 24 months, 7 patients had metastases occurred from 4 to 22 months postoperatively. Thirteen of the 16 patients were alive at the time of the last follow-up while 3 patients died 12, 15, and 20 months after the surgery, respectively. One patient underwent retroperitoneal mass resection, but had lung metastasis 32 months after surgery. One case received cervical tumor resection and died at 22 months after the surgery. Characteristic CCRCC regions were identified in 11 of the 18 cases. The tumor cells were arranged in papillary, alveolar, and large nest patterns. Abundant lymphoid tissue, necrosis, and psammoma bodies were seen. Tumor cells showed abundant eosinophilic cytoplasm, and sometimes exhibited rhabdoid differentiation. Round eosinophilic globules were located in the cytoplasm and extracellular matrix. There were 9 cases with WHO/International Society of Urological Pathology grade 3, and 9 cases with grade 4. PAX8 (18/18), carbonic anhydrase 9 (CA9, 16/18), CD10 (18/18), and vimentin (18/18) were positive in the vast majority of tumors.TFE3 was expressed in 5 cases, with strong expression in only 1 case. Eighteen cases were all positive for P504s. Twelve cases harbored a BAP1 mutation combined with von Hippel-Lindau (VHL) mutation, and 2 cases had mutations in BAP1, VHL and PBRM1 simultaneously. SETD2 mutation was not found in any of the cases. Conclusions: BAP1 mutated CCRCC contained papillary, alveolar, and large nest patterns, eosinophilic cytoplasm, high-grade nucleoli, and collagen globules, with P504s positivity. In practical work, when encountering CCRCC containing these features, pathologists should consider the possibility of BAP1 mutations and conduct related molecular tests.

[Precise immunological classification guidance for early initiation of antiviral therapy in patients with chronic HBV infection].

Chronic hepatitis B virus (HBV) infection is a major problem affecting global public health. Appropriate antiviral therapy use can prevent or delay the occurrence of liver cirrhosis and liver cancer. Precise immunological classification can be helpful to formulate personalized therapy and management plans for HBV-infected patients. Antiviral therapy should be started early in those who meet antiviral indications, and nucleos(t)ide analogue therapeutic regimens alone or in combination with pegylated interferon alpha should be optimized according to antiviral therapy response, in order to maximize the realization of virological and serological response, improve clinical cure rate, and enhance long-term prognosis.

[Real-world study on the efficacy and safety of first-line antiviral therapy for chronic hepatitis B].

Objective: To clarify the clinical efficacy of first-line oral antiviral drugs tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) in the treatment of chronic hepatitis B (CHB) and their safety profiles with lipid, bone, and kidney metabolism. Methods: 458 CHB cases diagnosed and treated at the Department of Hepatology of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University from February 2010 to November 2022 were selected. TAF (175 cases), TDF (124 cases), and ETV (159 cases) were used as therapies. At 24 and 48 weeks, the virology, biochemical response, changes in liver stiffness measurement (LSM), and bone, kidney, and blood lipid metabolism safety profiles were compared and analyzed. Results: After 24 and 48 weeks of TAF, TDF, and ETV therapy, HBV DNA load decreased by 3.28, 2.69, and 3.14 log10 IU/ml and 3.28, 2.83, and 3.65 log10 IU/ml, respectively, compared with the baseline, and the differences between the three groups were statistically significant, P < 0.001. The complete virological response rates were 73.95%, 66.09%, 67.19%, and 82.22%, 72.48%, and 70.49%, respectively. The incidence rates of low-level viremia were 16.67%, 21.70%, and 23.08%, while poor response rates were 1.11%, 3.67%, and 4.10%. ALT normalization rates were 64.00%, 63.89%, 67.96%, and 85.33%, 80.56%, 78.64%, respectively, and there was no statistically significant difference among the groups. LSM was significantly improved in patients treated with TAF for 48 weeks, P = 0.022. Serum phosphorus level gradually decreased with the prolongation of TDF treatment. The TAF treatment group had a good safety profile for kidney, bone, and phosphorus metabolism, with no dyslipidemia or related occurrences of risk. Conclusion: There are some differences in the therapeutic effects of first-line anti-HBV drugs. TAF has the lowest incidence of low-level viremia after 48 weeks of treatment and has a good safety profile in kidney, bone, and blood lipid metabolism.

[Clinical value of plasma scaffold protein SEC16A in evaluating hepatitis B-related liver cirrhosis and hepatocellular carcinoma].

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.

[CK7+/CD117- low grade oncocytic tumor of the kidney: a clinicopathological analysis].

Objective: To investigate the clinicopathological, immunohistochemical and molecular characteristics of low grade oncocytic tumors (LOT) of the kidney with CK7+/CD117- staining pattern for enhancing the understanding of renal LOT. Methods: The clinical data, histological morphology and immunophenotypes of seven renal LOT cases diagnosed at the Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine from January 2017 to April 2021 were analyzed. The patients were followed up. Among the seven patients, five underwent high-throughput DNA targeted sequencing, and their molecular characteristics were analyzed. Results: The patients' age ranged 59-82 years, with an average of 70 years. There were 2 males and 5 females. The boundary of the tumor was clear. The tumor cells had homogeneous eosinophilic cytoplasm and round or oval nuclei, with a perinuclear halo. Small basophilic nucleoli were conspicuous (WHO/International Society of Urological Pathology grade 2). In the hypercellular areas, the tumor cells were mainly arranged in dense solid or nest. In the stroma, there were dilated veins, thick-walled arterioles and thick collagen fiber bundles that divided the cells into pseudonodules. In the sparsely cellular area, the tumor cells were arranged in the so-called "tissue culture" fashion. In addition, the stroma contained fresh hemorrhagic foci and lymphoid aggregates. High-throughput sequencing of 5 cases revealed that one case harbored mTOR gene missense mutation and another case harbored TSC1 frameshift mutation. Conclusions: LOT of the kidney is an indolent tumor with an overall good prognosis. Pathologists should not misdiagnose it as renal oncocytoma and chromophobe renal cell carcinoma.

Transcriptional and posttranscriptional regulation of the proliferating cell nuclear antigen gene.

The steady-state mRNA levels of the proliferating cell nuclear antigen (PCNA) gene are growth regulated. In a previous paper (L. Ottavio, C.-D. Chang, M. G. Rizzo, S. Travali, C. Casadevall, and R. Baserga, Mol. Cell. Biol. 10:303-309, 1990), we reported that introns (especially intron 4) participate in growth regulation of the PCNA gene. We have now investigated the role of the 5'-flanking sequence of the human PCNA gene stably transfected into BALB/c 3T3 cells. Promoters of different lengths (from -2856 to -45 upstream of the cap site) were tested. All promoters except the AatII promoter (-45), including a short HpaII promoter (-210), were sufficient for a response to serum, platelet-derived growth factor, and to a lesser extent epidermal growth factor. No construct responded to insulin or platelet-poor plasma. The AatII promoter had little detectable activity. Transcriptional activity was also determined in BALB/c 3T3 cells carrying various constructs of the human PCNA gene by two methods: run-on transcription and reverse transcription-polymerase chain reaction (the latter measuring the heterogeneous nuclear RNA [hnRNA] steady-state levels). There was very little difference in the rate of transcription of the PCNA gene between G0 cells and serum-stimulated cells, although the levels of hnRNA were much higher after stimulation. In G0 cells carrying a human PCNA gene without introns 4 and 5, both transcription rate and hnRNA levels were high. Together with data on the mRNA half-life, these results suggest a posttranscriptional component in the regulation of PCNA mRNA levels after serum stimulation but a transcriptional regulation by intron 4.

Importance of introns in the growth regulation of mRNA levels of the proliferating cell nuclear antigen gene.

The steady-state mRNA levels of the proliferating cell nuclear antigen (PCNA) gene are growth regulated. We have begun to identify the elements in the human PCNA gene that participate in its growth regulation by transfecting appropriate constructs in BALB/c3T3 cells. The results can be summarized as follows. (i) The 400 base pairs of the 5'-flanking sequence of the human PCNA gene upstream of the preferred cap site are sufficient for directing expression of a heterologous cDNA (S. Travali, D.-H. Ku, M. G. Rizzo, L. Ottavio, R. Baserga, and B. Calabretta, J. Biol. Chem. 264:7466-7472, 1989). (ii) Intron 4 is necessary for the proper regulation of PCNA mRNA levels in G0 cells. Removal of intron 4 leads to abnormally high levels of PCNA mRNA in serum-deprived cells, although the shortened PCNA gene with its own promoter is still responsive to serum stimulation. (iii) The presence of introns also increases the steady-state levels of PCNA mRNA in proliferating cells. These results are especially interesting for two reasons: (i) because of the extensive sequence similarities among introns and between introns and exons of the human PCNA gene, and (ii) because, usually, the presence of introns leads to increased expression, whereas in this case, removal of intron 4 caused an increase in mRNA levels, and this occurred only in quiescent cells.

Pharmacokinetic Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Distinguishing Hepatocellular Carcinoma From Cholangiocarcinoma in Pre-Liver Transplantation Evaluation.

OBJECTIVE: Liver transplantation for intrahepatic cholangiocarcinoma is notorious for rapid recurrence with poor survival rate postoperatively and has therefore been discontinued in most centers. The purpose of this study is to distinguish hepatocellular carcinoma (HCC) from cholangiocarcinoma in pretransplantation imaging evaluation by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: From January 2014 to September 2015, 19 patients were included in the study, with a mean age of 62.8 years. All subjects underwent pretransplantation DCE-MRI and surgical excision or core biopsy. The DCE-MRI parameters were measured using the Tofts model 1999. Statistical analysis included nonparametric tests and area under the curve for the receiver operating characteristic. RESULTS: Fourteen HCCs and 5 cholangiocarcinomas were diagnosed by surgical pathology. The mean size of tumor was 6.4 cm (range, 1.5 cm to 13.7 cm). All DCE-MRI parameters were calculated as the ratio between the tumor and normal liver parenchyma and K(trans) (1/min) was used as a distinguishing parameter between the two tumors. K(trans) was higher in the cholangiocarcinoma group (1.89 ± 1.13) than in the HCC group (0.46 ± 0.35). Univariate analysis revealed that K(trans) has a high significant difference (P = .001). The optimal K(trans) value cutoffs were 1 or more (area under the curve = 0.971) for detection of HCCs or cholangiocarcinomas. CONCLUSION: The analysis of DCE-MRI with the kinetic model (Tofts, 1999) presents a new and practical approach indiscrimination of HCC from cholangiocarcinoma for pretransplantation imaging evaluation.

cDNA cloning of an alternatively spliced isoform of the regulatory subunit of Ca2+/calmodulin-dependent protein phosphatase (calcineurin B alpha 2).

A cDNA encoding the regulatory subunit of Ca2+/calmodulin-dependent protein phosphatase, calcineurin B (CNB), was isolated from a rat testis cDNA library. It differs from the cDNA obtained from a rat brain cDNA library by an addition of 138 base pairs in the coding region. The codon of the clone from a testis library corresponding to the initiation codon of the clone from a brain library is not ATG but AAG, 5'-noncoding regions of these cDNAs are also different. The addition in the coding region results in the gain of 46 amino acids at the N-terminus. These findings suggest that two distinct isoforms of CNB alpha are derived from the same gene through a process involving alternative utilization of two promoters. We designate the brain type isoform as CNB alpha 1 and the longer isoform as CNB alpha 2. Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot analysis suggest that CNB alpha 2 is specifically expressed in the testis, and its expression is developmentally regulated.

Isolation and characterization of CAJ1, a novel yeast homolog of dnaJ.

A novel member of the Escherichia coli dnaJ family, designated CAJ1, was isolated from a yeast expression library using antiserum against a yeast calmodulin-binding fraction. Although CAJ1 contains neither a Gly-rich region nor a Cys-rich repeat, as are found in other DnaJ relatives, it contains a leucine zipper-like motif.

Analogues of S-adenosylhomocysteine as potential inhibitors of biological transmethylation. Synthesis of analogues with modifications at the 5'-thioether linkage.

The synthesis of S-adenosylhomocysteine analogues, in which the 5'-thioether linkage is replaced by an oxygen or nitrogen isostere, has been investigated. These compounds were disigned to be resistant to enzyme-catalyzed hydrolytic cleavage of the 5'-substituent. The amine analogue Id and two amide analogues 20 were prepared via alkylation or acylation of appropriately blocked adenosine derivatives. These new analogues were evaluated as inhibitors of catechol O-methyltransferase and tRNA methylases and found to have poor inhibitory activity.

Use of adenine nucleotide derivatives to assess the potential of exo-active-site-directed reagents as species- or isozyme-specific enzyme inactivators. 3. Synthesis of adenosine 5'-triphosphate derivatives with N6- or 8-substituents bearing iodoacetyl groups.

Several series of N6- or 8-substituted derivatives of adenosine 5'-triphosphate (ATP) were synthesized. N6-(omega-Aminoalkyl) derivatives of adenosine 5'-monophosphate (AMP) were converted into their omega-N-carbobenzyloxy derivatives, and these were converted, via the 2',3'-O-carbonyl derivatives of their 5'-phosphorimidazolidates, into the corresponding ATP derivatives. Hydrogenolytic removal of the carbobenzyloxy groups, followed by iodoacetylation of the omega-amino groups with N-(iodoacetoxy)succinimide, gave N6-R-ATP, where R = (CH2)nNHCOCH2I (n = 2--8) or (CH2)nCON)CH3)(CH2)mN(CH3)CO(CH2)nNHCOCH2I (n = m = 3; n = 3, m = 4; n = 4, m = 3; n = m = 4). Condensation of N6-(omega-aminoalkyl) derivatives of AMP with N-hydroxysuccinimide esters of omega-[N-(carbobenzyloxy)amino] carboxylic acids gave N6-(CH2)nNHCO(CH2)mNH-Cbz derivatives of AMP which, upon conversion to the corresponding derivatives of ATP, followed by removal of the carbobenzyloxy group and iodoacetylation, as described above, gave N6-(CH2)nNHCO(CH2)mNHCOCH2I-ATP derivatives (n = 3, m = 5 or 6; n = 4, m = 5; n = 6, m = 1--6). The same sequence of reactions starting with N6-[omega-(methylamino)alkyl] derivatives of N6-CH3-AMP gave N6-CH3, N6-(CH2)nH(CH3)CO(CH2)mNHCOCH2I derivatives of ATP (n = 4, m = 3, 5 or 6; n = 6, m = 5 or 6). Reaction of alpha, omega-diaminoalkanes with 8-Br-ATP gave 8-NH(CH2)nNH2 derivatives of ATP, which upon iodoacetylation gave 8-NH(CH2)nNHCOCH2I derivatives of ATP (n = 2, 4, 6, or 8). Substrate and inhibitor properties indicated that the ATP derivatives are potential exco-ATP-site-directed inactivators of hexokinases, adenylate kinases, and pyruvate kinases.

FKBP12-FK506 complex inhibits phosphatase activity of two mammalian isoforms of calcineurin irrespective of their substrates or activation mechanisms.

The interaction of calcineurin (Ca2+/calmodulin-dependent protein phosphatase) with the potent immunosuppressive agent FK506 and its 12 kDa isoform binding protein (FKBP12) was investigated. The FKBP12-FK506 complex inhibited the Ca2+/calmodulin-stimulated phosphatase activity of each of two calcineurin isoforms, which contain either the catalytic subunit A alpha or A beta (calcineurin A alpha or A beta) of bovine calcineurin. Calcineurin phosphatase activity was inhibited by the FKBP12-FK506 complex irrespective of the substrate or the enzyme activation mechanism. FK506 and FKBP-12 inhibited calcineurin in a concentration-dependent manner, and complete inhibition of the phosphatase activity appeared to require a molar excess of FKBP12-FK506 complex. Immunochemical measurements revealed tissue differences in the concentration of calcineurin, which may be of importance to the selectivity for immunosuppression of all of the biological effects. Direct binding studies with [3H]dihydro-FK506 suggest that the ratio of FKBP12-FK506 complex to calcineurin in vivo when IL2 production is inhibited is well correlated with the ratio when calcineurin phosphatase activity is inhibited in vitro. These results suggest that calcineurin is a relevant cellular target of FK506 when bound to FKBP-12.

Comparison of two molecular techniques for the detection of avian reoviruses in formalin-fixed, paraffin-embedded chicken tissues.

Reverse transcription (RT) in situ polymerase chain reaction (PCR) and in situ hybridization (ISH) techniques were used to detect the sigma c-encoded gene of avian reovirus (ARV) in chicken tissue sections. The advantage of using in situ methods is to make more rapid and accurate diagnosis of ARV infections. The sensitivity of these two techniques were compared. Of the two techniques, the RT in situ PCR test was found to be more sensitive than ISH and provided the rapid, sensitive, and specific detection of ARV infections.

Cationic lipid structure and formulation considerations for optimal gene transfection of the lung.

Enhanced gene transduction to the lung using cationic lipids could be attained through optimization of the structure of the lipids and the formulation of the cationic lipid:plasmid DNA (pDNA) complexes. We have expanded on our earlier observation of the importance of the structural orientation of the cationic lipid headgroup. Through the synthesis of a number of matched pairs of cationic lipids differing only in the configuration of their headgroup, we confirmed that those harboring a T-shape headgroup are more active than their linear counterparts, at least when tested in the lungs of BALB/c mice. Additionally, we demonstrated that not only are the structural considerations of these cationic lipids important, but also their protonation state, the free base being invariably more active than its salt counterpart. The salt forms of cationic lipids bound pDNA with greater avidity, which may have affected their subsequent intracellular dissolution and transit of the pDNA to the nucleus. Inclusion of a number of frequently used solutes in the vehicle severely inhibited the gene transfection activity of the cationic lipids. The selection of neutral co-lipids was also an important factor for overall transfection activity of the formulation, with significant gains in transfection activity realized when diphytanoylphosphatidylethanolamine or dilinoleoylphosphatidylethanolamine were used in lieu of dioleoylphosphatidylethanolamine. Finally, we showed that a transacylation reaction could occur between the cationic lipid and neutral co-lipid which reduced the transfection activity of the complexes. It is the hope that as our understanding of the many factors that influence the activity of these cationic lipid:pDNA complexes improves, formulations with much greater potency can be realized for use in the treatment of pulmonary diseases.

2-Octyl cyanoacrylate medical adhesive in treatment of a corneal perforation.

PURPOSE: To describe a case of successful treatment of a corneal perforation with 2-octyl cyanoacrylate. METHODS: 2-Octyl cyanoacrylate was applied at the slit lamp with topical proparacaine anesthesia to a cornea with an inferior perforation with iris plugging the defect. RESULTS: After application of 2-octyl cyanoacrylate, the anterior chamber was noted to deepen, and visual acuity improved to 20/200. The glue remained intact for more than 6 weeks and eventually fell out. The underlying cornea healed without scarring, vascularization, or thinning. CONCLUSION: We have described a case in which 2-octyl cyanoacrylate was used to treat a corneal perforation with excellent results. Further study of this adhesive will be useful in comparing the effectiveness and safety of 2-octyl cyanoacrylate with that of previously studied adhesives.

Beta-cyclodextrin chiral stationary phases for liquid chromatography. Effect of the spacer arm on chiral recognition.

Cyclodextrins (CDs) can be bound on silica to prepare chiral stationary phases (CSPs) for liquid chromatography. The cyclodextrin ring is connected to a spacer previously bonded on the silica surface. Three different CD-CSPs were prepared with three different spacers. (i) A dimethylethoxysilane with a linear 6 carbon chain produced a monomeric layer. The bonded CD units can move and rotate freely. (ii) The corresponding trimethoxysilane produced a polymeric layer. The bonded CD units were not located at the same distance of the silica surface, but they could still move and rotate freely. (iii) The third spacer contained a cyclohexyl ring that may introduce some conformational rigidity in the CD connection to silica. The three CSPs prepared contained a CD surface coverage of about 0.3 micromol/m(2) which is approximately half of the maximum theoretical CD coverage. The first spacer was the most efficient to bond CDs with an average value of 1.7 spacers per CD ring, whereas 5.5 spacers per CD ring were needed with the two other spacers. The chiral recognition capabilities of the three phases were compared using 14 racemic compounds. No pronounced differences were noted, but the CSP prepared with the dimethylethoxysilane monomeric spacer seems to be the most efficient for chiral recognition.

Postmortem diagnosis of hemoglobin SC disease complicated by fat embolism.

A case is reported of a previously healthy 52-year-old African American male who presented with acute onset of abdominal pain. Progressive increase in his abdominal symptoms led to an exploratory laparotomy; however, no pathology was discovered. Postoperatively, the patient became hypoxemic which progressed to diffuse infiltrates on chest x-ray, suggestive of adult respiratory distress syndrome. He had a rapidly fatal course. Autopsy showed bone marrow infarction, fat embolism, splenomegaly, and widespread congestion with sickle erythrocytes. Hemoglobin electrophoresis done postmortem showed hemoglobin (Hb) SC disease that was undiagnosed antemortem. To the best of our knowledge, it is unusual for Hb SC to be diagnosed postmortem in adults. This case suggests that sickle cell disorders should be ruled out in patients at risk for hemoglobinopathy in the presence of signs and symptoms compatible with the disease, irrespective of age.