Joseph M. Guileyardo

Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression.

The synthesis of dihydrotestosterone is catalyzed by steroid 5 alpha-reductase isozymes, designated types 1 and 2. Mutation of type 2 results in male pseudohermaphroditism, in which the external genitalia are phenotypically female at birth. Two striking and unexplained features of this disorder are that external genitalia of affected males undergo virilization during puberty and that these individuals have less temporal hair regression. The tissue-specific and developmental expression patterns of the 5 alpha-reductase isozymes were investigated by immunoblotting. The type 1 isozyme is not detectable in the fetus, is transiently expressed in newborn skin and scalp, and permanently expressed in skin from the time of puberty. There was no qualitative difference in 5 alpha-reductase type 1 expression between adult balding vs. nonbalding scalp. The type 2 isozyme is transiently expressed in skin and scalp of newborns. Type 2 is the predominant isozyme detectable in fetal genital skin, male accessory sex glands, and in the prostate, including benign prostatic hyperplasia and prostate adenocarcinoma tissues. Both isozymes are expressed in the liver, but only after birth. These results are consistent with 5 alpha-reductase type 1 being responsible for virilization in type 2-deficient subjects during puberty, and suggest that the type 2 isozyme may be an initiating factor in development of male pattern baldness.

Cell type specific expression of steroid 5α-reductase 2

AbstractIsozymes of steroid 5α-reductase (5α-reductase) have crucial roles in androgen physiology by synthesizing the potent hormone dihydrotestosterone. The expression pattern of the 5α-reductase type 2 isozyme was determined in genital and extragenital tissues by developing an immunohistochemical assay using formalin-fixed tissue and affinity purified polyclonal antibodies that specifically recognize this isozyme. Expression was detected in basal epithelial and stromal cells of the normal prostate but not in luminal epithelial cells. Stromal cells of the seminal vesicle also expressed the type 2 isozyme. In contrast, staining was detected in epithelial cells of the epididymis but not in the surrounding stroma. Myofibroblasts in foreskin samples of normal and hypospadiac individuals expressed antigen and were distributed in bands throughout the prepuce, suggesting a clonal origin. In most cells the type 2 isozyme exhibited a perinuclear subcellular distribution. However, in liver hepatocytes the protein ...

Increased expression of early growth response-1 messenger ribonucleic acid in prostatic adenocarcinoma.

PURPOSE We isolated genes whose expression differs between normal and malignant prostate. MATERIALS AND METHODS Differential display polymerase chain reactions revealed a messenger ribonucleic acid (mRNA) with higher expression in prostatic adenocarcinoma versus age matched normal tissue. Deoxyribonucleic acid sequencing identified this mRNA as the product of the early growth response-1 gene. RESULTS Early growth response-1 mRNA levels were elevated in 12 of 12 intraprostatic adenocarcinomas but not in breast or ovarian cancers, or in rapidly dividing rat ventral prostate cells. Early growth response-1 mRNA was detected in epithelial and stromal cells at tumor margins but not in lymph node metastases. CONCLUSIONS Early growth response-1, a nuclear transcription factor, is implicated in the growth and invasion of intraprostatic cancers.

Familial filicide and filicide classification.

Filicide is the killing of a child by his or her parent. Despite the disturbing nature of these crimes, a study of filicide classification can provide insight into their causes. Furthermore, a study of filicide classification provides information essential to accurate death certification. We report a rare case of familial filicide in which twin sisters both attempted to kill their respective children. We then suggest a detailed classification of filicide subtypes that provides a framework of motives and precipitating factors leading to filicide. We identify 16 subtypes of filicide, each of which is sufficiently characteristic to warrant a separate category. We describe in some detail the characteristic features of these subtypes. A knowledge of filicide subtypes contributes to interpretation of difficult cases. Furthermore, to protect potential child homicide victims, it is necessary to know how and why they are killed. Epidemiologic studies using filicide subtypes as their basis could provide information leading to strategies for prevention.

Racial and ethnic patterns in firearms deaths

In the United States, there is currently an epidemic of firearms violence. Among victims of this violence, there are striking racial and ethnic patterns in the manners and circumstances of death. This study was conducted to explore and quantitate some of these differences. Autopsy and investigation reports of 554 consecutive firearms deaths in Dallas County, Texas, from March 1992 to February 1993 were reviewed. Overall suicide rates by race for 1970 and 1990 were calculated. Suicide rates for blacks have increased while overall rates (all races) have decreased slightly. Large racial and ethnic differences in the homicide-suicide ratio (H:S) were found (0.42 in non-Hispanic whites; 7.44 in others) (p < 0.001). Non-Hispanic whites who committed suicide with a firearm were less likely than other groups to do so with another person present (12% non-Hispanic whites; 49% others) (p < 0.001). Blacks and Asians who committed suicide with a firearm killed another person in 67% of witnessed cases (those with another person present during the incident). Whites (Hispanics and non-Hispanics) killed another person in only 12% of witnessed firearm suicides. The data suggest that the subtypes, psychodynamics, and causes of suicide may currently differ among racial and ethnic groups. These differences should be considered in order to formulate adequate prevention strategies and to assess the suicide and homicide risk in depressed individuals. The difficulty of accurate death certification in some cases is also discussed.

Renovasculopathies of hypertension in Hispanic residents of Dallas, Texas.

BACKGROUND Mean blood pressure levels (MBP) appear to rise with age slowly in the population of Mexico City and more swiftly in the U.S. in the black and white population, judging from published survey data. Some evidence suggests that MBP rises at intermediate rates in Hispanics in the U.S. METHOD This question is explored here in two ways, by review of published survey data and by a novel approach that uses renal tissues obtained from forensic autopsies to estimate MBP. Past studies have revealed good agreement between the two methods of estimating MBP. RESULTS Good agreement is again observed from the results of this study. Results from both methods agree that MBP is much lower at all ages in Mexican men and women than in blacks and whites in the U.S. Both methods also agree that Hispanics in the U.S. demonstrate an intermediate rise in MBP. A speculative first look at a small sample of U.S. Hispanics suggest that MBP rates of recent immigrants tend to resemble those of Mexico, while MBP levels of migrants of long-term residence resemble the native-born U.S. populations. CONCLUSIONS The findings underscore the need for definitive testing to confirm if Mexicans who relocate to the U.S. may acquire an acceleration of the renovasculopathies, and of the lifelong progression toward hypertension that this implies.

Automatic implantable cardioverter defibrillator rhythm strip data as used in interpretation of a motor vehicle accident.

The automatic implantable cardioverter defibrillator (AICD) is an electronic device that monitors the rhythm of the heart and, upon detecting a life-threatening arrhythmia, shocks the heart in an attempt to restore a normal rhythm. The AICD will electronically store the information of the event. Later, the AICD can be “interrogated” and the information electronically retrieved, with a printout of the rhythm strip obtained. The interrogation is fairly simple and involves a magnetic device placed over the AICD, which in turn is connected to a portable computer, which, with specialized software, can deliver the information in a usable form. Not only can information about the most recent shock be obtained, but also information about previous shocks can be retrieved. This case presentation highlights how such preterminal information retrieved from an AICD helped to interpret the circumstances leading to a death—in this case, a fatal motor vehicle accident. Additionally, driving restrictions that may be placed on individuals with AICDs are discussed.

Renal artery bullet embolism.

Bullet embolism is a well-recognized phenomenon. While bullet embolism is not common, renal artery bullet embolism appears to be very rare. We report three cases of bullet embolism to a renal artery. Autopsy findings and bullet types are presented. Such cases are of particular interest to both the medical examiner and the clinician. Failure to consider this phenomenon clinically could lead to infarction of a kidney. A consideration of this phenomenon at autopsy could shorten the dissection time required to retrieve the bullet

Immersion Technique for Brain Removal in Perinatal Autopsies

Perinatal autopsies present forensic patholgists with a variety of challenges, not the least of which involves the removal and examination of very small and sometimes fragile organs. Removal of the immature brain can be particularly troublesome. Even if great care is taken during brain removal, one is often left with no more than a semifluid amorphous mass of softened tissue by the time the brain is ready to be fixed in formalin. We describe a method of perinatal brain removal which helps to preserve brain shape and integrity. By removing the brain while the head (and body) is totally immersed in water, we find that the brain is easier to remove and less apt to destruction. Subsequent fixation in formalin results in well-preserved, intact specimens, allowing for optimal examination and sectioning.

Pressure sores in a Christian Science sanatorium.

We reviewed the Dallas County Medical Examiners Office records of all individuals who had died in a local Christian Science Sanatorium during a 51/2-year period. Of 116 such patients, only 13 (11%) had pressure sores (decubitus ulcers). In 10 of these patients, the sores were described as small, superficial, and/or healing, while the other three patients had more serious ulcers. In contrast, for patients dying in nursing homes or hospitals, the incidence of pressure sores may be as high as 54–57%. It is our opinion that the difference in incidence is due to the personal and conscientious nursing care provided by Christian Science institutions.