Relationship of histamine expression with chemokine balance in the tumor microenvironment of squamous cell carcinoma of the tongue.

BACKGROUND: Tumor-associated macrophages in the tumor microenvironment (TME), as a factor affecting lymphocytes, have received much attention. Both lymphocytes and macrophages can switch the expression of histamine receptors. In this study, we investigated the role of histamine in the TME of tongue squamous cell carcinoma (SCC). METHODS: Sixty-seven patients with stage I tongue SCC were studied. Histamine was evaluated by the expression of L-histidine decarboxylase (HDC). Macrophages, T lymphocytes, and lymph vessel density, as well as the Ki-67 labeling index (LI) and depth of invasion (DOI), were compared with HDC expression. RESULTS: HDC expression was significantly affected by the TME. The DOI, worst pattern of invasion, and Ki-67 LI were associated with histamine expression. C-C motif chemokine ligand (CCL) 2 and CCL22 were co-expressed with histamine H1 and H2 receptors. Histamine expression was most affected by the DOI. CONCLUSIONS: Tongue SCC expressing histamine affected the TME via histamine receptors and chemokines.

A case of sudden cardiac death due to mitochondrial disease.

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.

Assessment of Triage DOA®, Status DS10, and DRIVEN-FLOW® M8-Z on-site drug screening kits for postmortem urine.

Based on the screening results of mass analyses using gas chromatography- mass spectrometry (GC-MS) and liquid chromatograph-tandem mass spectrometry (LC-MS/MS), we assessed the performance of Status DS10 (Status) and DRIVEN-FLOW® M8-Z (DF8), and compared the results with those of Triage DOA® (Triage) using 356 autopsy urine samples within one month of death. The sensitivity to benzodiazepines was 0.52 in Triage, 0.59 in Status, and 0.58 in DF8 with few false-positive cases. Triage detected triazolo-derivatives more easily than DF8. DF8 detected diazepam and nitro-benzodiazepines more easily than Status and Triage, with Status performing better than Triage. However, lorazepam detection with Status was difficult. There were 11 false-positive cases for amphetamines in Triage and 12 for Status-AMP at more than one week after death, but there were no false-positive in Status-MET and DF8. Tricyclic antidepressant (TCA) was detected in five cases by mass analysis, while there were 6 false-positive cases in Triage and 10 in both Status and DF8. In the TCA false-positive cases, tricyclic psychotics such as quetiapine, chlorpromazine, and carbamazepine existed. There were 23 true-positive and 6 false-positive cases for zolpidem in DF8 without false-negative cases. The accuracy of Status and DF8 for barbiturates or opiates was almost 1, but Triage was 0.98. There were no samples containing cocaine, THC, phencyclidine, or methadone. Based on the above, we conclude that Status and DF8 are comparable or slightly better than Triage, with fewer false-positive and fewer false-negative cases, except for TCA.

The Role of Brain Methamidophos in Acephate Poisoning in Mice.

We gave mice a 540 mg/kg dose of LD50 acephate, followed by an assessment of acephate, methamidophos (MP), and choline esterase (ChE) activity for up to 4 hours (hr) in order to investigate the time course of acephate intoxication. At 1 hr, the blood acephate and MP levels were 428 ± 90 µg/ml (mean ± SEM) and 4.2 ± 0.4 µg/ ml, respectively. The liver acephate levels were similar to those in the blood, but the liver MP levels were approximately 3.5 times that of the blood at 1 hr. The brain MP level tended to be higher than the blood MP at 1 hr. These levels decreased gradually over 4 hr, but the brain acephate and MP levels surpassed the blood levels significantly at 4 hr, and after 2 hr, respectively. Serum, liver, cerebrum, cerebellum, and brainstem cholinesterase activity (ChE) were inhibited at 1 hr, and remained inhibited in all but the cerebellum until the end of the experiment. The obtained data were applied to previously reported autopsy cases of acephate intake. Experimental data suggest that brain MP is involved in acute acephate-induced poisoning, even after a reduction in blood acephate. In autopsy cases with suspected acephate poisoning, the MP level in the brain should be considered in addition to the ChE activity to diagnose the cause of death.

Autopsy case of fatal hypoglycemia following ingestion of a therapeutic dose of tramadol.

An 86-year-old female was found unconscious the day after taking a prescribed tablet containing a combination of tramadol and acetaminophen. At admission to the hospital, marked hypoglycemia (blood glucose: 4 mg/dL) was confirmed, but serum insulin and C-peptide were within the normal range, which suggested that neither endogenous hyperinsulinemia nor exogenous insulin administration was responsible for the hypoglycemia. Despite resuscitation efforts, the woman subsequently died. At autopsy, there was renal disorder, but any pathological abnormalities that could have caused hypoglycemia were not observed. Blood tramadol and acetaminophen were in the therapeutic range. We speculate that the cause of fatal hypoglycemia was tramadol intake at the therapeutic dose. Older age and renal insufficiency are factors that could have potentially caused the fatal hypoglycemia in this case despite tramadol having been taken at a therapeutic dose. This is the first case report of fatal hypoglycemia following ingestion of a therapeutic dose of tramadol.

Butane detection after long-term treatment of burns in two autopsy cases.

A man and a woman were rescued from a room that had exploded. Many empty cassette gas cylinders were found in the room. The man and woman were hospitalized immediately for the treatment of burns. The woman died 6 days later, and the man died 31 days later without regaining consciousness. Carbonization and hardening of the frontal facial skin and parts of the left and right fingers were observed on the man's body. In both cases, systemic burns had led to progressive systemic edema and markedly suppressed circulation. Analytical samples for butanes obtained from their bodies at autopsy were stored at -20 °C for 14 and 25 days, respectively, before analysis. Normal butane and isobutane were quantified in the brain and subcutaneous adipose tissue of the woman. Only the isobutane was quantified in the adipose tissue of the man. The evidence suggests that the man lit a cigarette while breathing gas and the entire room exploded. Our results also suggest that butane can be detected in the adipose tissue of autopsy cases long after inhalation even under the present storage conditions, and isobutane may remain in adipose tissue longer than n-butane.

Efficacy of DRIVEN-FLOW® M7-II, a new on-site drug screening kit in postmortem urine compared with Triage DOA®.

The efficacy of DRIVEN-FLOW® M7-II(DFM7II) for seven drug groups was compared with Triage DOA® (Triage) using 340 autopsy urine samples taken from bodies within 1 month of death based on mass screening analysis of GC/MS and LC-MS/MS. The sensitivity to benzodiazepines was 0.56 in Triage and 0.53 in DFM7II with few false positives, and their accuracy was 0.88. Triage detected triazolo diazepine derivatives more easily than DFM7II. DFM7II detected diazepam and nitro benzodiazepines more easily than Triage. There were nine amphetamine false-positive cases of more than 10 days after death in Triage, but these were absent in DFM7II during this period. The accuracy of amphetamines for Triage was 0.96 and for DFM7II was 1. Tricyclic antidepressant (TCA) was detected in five cases by mass analysis, while there were four false-positive cases using Triage and eight cases using DFM7II. In the TCA false-positive cases of both kits, tricyclic psychotics such as chlorpromazine, carbamazepine, and quetiapine were included as well as the drug poisoning cases. There were no samples containing cocaine or THC. The accuracy of DFM7II for opiate and barbiturates was 1, but those of Triage was less than 1. Based on the above, DFM7II is a more accurate kit with fewer false-positives for target drug groups, other than TCA, than Triage.