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Biomedical subjects

G J Davis

Publications and source records attributed to G J Davis.

At least 19 recordsLinked to original sources
PubMed1996

Survival of rabbit limbal stem cell allografts.

Failure of a specialized population of corneal epithelial stem cells found in the peripheral cornea and limbus results in ocular surface disease, which may be amenable to treatment by transplantation of limbal tissue. This study was designed to investigate donor limbal stem cell allograft survival in rabbits with ocular surface disease. Rabbits underwent corneal epithelial debridement and limbal ablation to induce ocular surface disease and were then treated by limbal stem cell allotransplantation, by allotransplantation plus topical steroid, or by topical steroid only (n = 7 for each group). Donors and recipients were sex mismatched. Recipients were followed for up to 5 months. Outcome was assessed by daily slit-lamp examination, weekly impression cytology and photographic record, end-point sex chromatin and fluorescent cell tracer analyses, histology, and immunohistochemistry. In no case was a completely normal ocular surface regained, but some animals that received grafts plus corticosteroids fared best by all criteria used. In the absence of immunosuppression, graft hemorrhagia (believed to be a manifestation of graft rejection) occurred within the first month, the cornea became resurfaced with conjunctiva-derived cells, and no donor cells survived centrally in the long term. Topical corticosteroids reduced the number and severity of these episodes significantly, and were associated with survival of some donor-derived cells in the central cornea of some grafted animals. Thus, rabbit limbal stem cell allografts appeared to undergo rejection, which could be modified by immunosuppression, but useful regeneration of the ocular surface occurred only where rejection was circumvented.

Animals↗
PubMed1996

X-ray structure of human beta3beta3 alcohol dehydrogenase. The contribution of ionic interactions to coenzyme binding.

The three-dimensional structure of the human beta3beta3 dimeric alcohol dehydrogenase (beta3) was determined to 2.4-A resolution. beta3 was crystallized as a ternary complex with the coenzyme NAD+ and the competitive inhibitor 4-iodopyrazole. beta3 is a polymorphic variant at ADH2 that differs from beta1 by a single amino acid substitution of Arg-369 --> Cys. The available x-ray structures of mammalian alcohol dehydrogenases show that the side chain of Arg-369 forms an ion pair with the NAD(H) pyrophosphate to stabilize the E.NAD(H) complex. The Cys-369 side chain of beta3 cannot form this interaction. The three-dimensional structures of beta3 and beta1 are virtually identical, with the exception that Cys-369 and two water molecules in beta3 occupy the position of Arg-369 in beta1. The two waters occupy the same positions as two guanidino nitrogens of Arg-369. Hence, the number of hydrogen bonding interactions between the enzyme and NAD(H) are the same for both isoenzymes. However, beta3 differs from beta1 by the loss of the electrostatic interaction between the NAD(H) pyrophosphate and the Arg-369 side chain. The equilibrium dissociation constants of beta3 for NAD+ and NADH are 350-fold and 4000-fold higher, respectively, than those for beta1. These changes correspond to binding free energy differences of 3.5 kcal/mol for NAD+ and 4.9 kcal/mol for NADH. Thus, the Arg-369 --> Cys substitution of beta3 isoenzyme destabilizes the interaction between coenzyme and beta3 alcohol dehydrogenase.

Alcohol Dehydrogenase↗
PubMed1996

Dilemmas and solutions for the pathologist and clinician encountering religious views of the autopsy.

Religious objections to the autopsy are as old as autopsies themselves. The development of anatomic studies was hindered in ancient eras, as well as in more recent times, by spiritual views occasionally hostile to the opening of bodies. This review addresses historical and recent attitudes of the three major monotheistic faiths--Judaism, Christianity, and Islam--toward postmortem examinations. Two case examples will illustrate that in many clinical scenarios in which an autopsy is desired or warranted but met with initial resistance by loved ones, a combination of patience and learned communication can pave the way to a family's understanding and acceptance of the procedure.

Adult↗
PubMed1996

A whiff of death: fatal volatile solvent inhalation abuse.

Inhalation abuse of volatile solvents, previously known generically as "glue sniffing," is typically pursued by adolescents. A wide range of legal, easily obtained products containing volatile substances are available for abuse. We report two illustrative cases of fatal volatile substance abuse: gasoline sniffing in a 20-year-old man and aerosol propellant gas inhalation (aerosol air freshener) in a 16-year-old girl with underlying reactive airway disease. Although the ratio of deaths to nonfatal inhalation escapades is extremely low, volatile solvent abuse carries the risk of sudden death due to cardiac arrest after a dysrhythmia or vasovagal event, central nervous system respiratory depression, hypoxia and hypercapnia due to the techniques of inhalation, and other mechanisms. Investigation of the patient's substance abuse history, examination of the scene of death, and special toxicologic analyses are critical to identifying volatile substance inhalation abuse as the cause of death because anatomic autopsy findings will typically be nonspecific. Above all, physicians must suspect the diagnosis of volatile substance inhalation abuse, especially in any case of sudden death involving an otherwise healthy young person.

Adolescent↗
PubMed1995

Cimetidine inhibition of human gastric and liver alcohol dehydrogenase isoenzymes: identification of inhibitor complexes by kinetics and molecular modeling.

Cimetidine, an H2-receptor antagonist, is one of the most commonly prescribed drugs in the world. It has been reported to increase blood alcohol concentrations in drinking individuals. To determine if this increase could be due to inhibition of alcohol dehydrogenase activity, the effect of the drug on ethanol oxidation by gastric sigma sigma alcohol dehydrogenase and liver beta 2 beta 2, pi pi, and chi chi alcohol dehydrogenase isoenzymes was observed. Cimetidine inhibited all isoenzymes studied except chi chi; the chi chi isoenzyme showed no inhibition up to 5 mM cimetidine. Inhibition of the alcohol dehydrogenase isoenzymes by the H2-receptor antagonists nizatidine, ranitidine, and famotidine was negligible. Docking simulations with the beta 2.NAD+.4-iodopyrazole X-ray structure indicated that cimetidine fit well into the substrate binding site. The substitution on the thiazole ring of nizatidine, however, prevented docking into the binding site. Cimetidine inhibition of ethanol oxidation by sigma sigma and beta 2 beta 2 was competitive with varied ethanol, exhibiting Ki values of 2.8 +/- 0.4 mM and 0.77 +/- 0.07 mM, respectively. Cimetidine inhibition of ethanol oxidation by pi pi was noncompetitive with varied ethanol (Ki = 0.50 +/- 0.03 mM). Inhibition of ethanol oxidation by sigma sigma and beta 2 beta 2 with varied NAD+ was competitive. These results, together with the cimetidine inhibition kinetics of acetaldehyde reduction by sigma sigma and beta 2 beta 2, with either varied NADH or varied acetaldehyde, are consistent with cimetidine binding to two enzyme species. These species are free enzyme and the productive enzyme.NAD+ complex.

Alcohol Dehydrogenase↗
PubMed1995

Death by bull-edger. An unusual homicide using a woodworking implement.

Impulsive killers often use whatever instrument is close at hand in the perpetration of their deed. We describe a homicidal death, first thought to be accidental, in a rural sawmill where the assailant manipulated a large board of wood into a machine known as a bull-edger (which cuts logs into rough boards) in such a fashion as to cause the death of his work partner. The physics of the events at the scene as well as the subsequent investigation are discussed.

Accidents, Occupational↗
PubMed1995

Angiotropic large cell lymphoma.

Lymphomas are malignant neoplasms of cells native to lymphoid tissue that can arise anywhere in the body. Angiotropic large cell lymphoma (ALCL) is characterized by a proliferation of neoplastic mononuclear cells within the lumina of small blood vessels. The clinical manifestations are usually neurologic, including progressive dementia and nonlocalizing deficits, cutaneous infiltration, adrenal masses, or fever of unknown origin. The diagnosis is made at autopsy or on skin biopsy, brain biopsy, or other surgical resection. Differential diagnoses include metastatic malignant neoplasms and vascular tumors. We report the case of a 63-year-old white man who had neurologic signs and symptoms as well as dyspnea. Autopsy revealed ALCL involving multiple organ systems, including the central nervous system. Diagnostic techniques currently used to confirm the nature of this malignant neoplasm include immunohistochemistry, ultrastructural analysis, cytogenetics, and molecular biologic studies.

Brain↗
PubMed1994

Comparative roles of histidine 51 in human beta 1 beta 1 and threonine 51 in pi pi alcohol dehydrogenases.

Histidine at position 51 of the class I beta 1 alcohol dehydrogenase (ADH) functions as a general base by indirectly abstracting a proton from the alcohol substrate through a hydrogen-bonded proton relay system. The human class II pi-ADH was reported to be polymorphic, having either Ser or Thr, but not His at position 51. It is unknown whether Ser or Thr51 have a catalytic role in ethanol oxidation with pi-ADH. Accordingly, we expressed and purified recombinant mutants of pi-ADH with Thr, Ser, and His at position 51. At pH 6.5, values for Vmax/Km for ethanol were 0.30, 0.10, and 0.09 min-1 mM-1 for pi 51Thr, pi 51Ser, and pi 51His ADH, respectively. Hence the effects of the substitutions were much less than the 11-fold decrease in Vmax/Km observed for beta 1-ADH when a neutral amino acid (Gln) was substituted for His51. Addition of a buffer base (400 mM glycylglycine) had little effect on Vmax/Km of recombinant pi 51Thr or pi 51Ser ADH, while it increased Vmax/Km for ethanol 7-fold for the beta (1)51 Gln ADH. We conclude that there is no evidence for Thr51 of pi-ADH participating in a proton relay similar to that seen in beta 1-ADH and that a base at position 51 may not be a universal requirement for a functional alcohol dehydrogenase with a moderate efficiency for ethanol oxidation at a physiological pH.

Alcohol Dehydrogenase↗
PubMed1994

An unusual case of maternal-fetal death due to vaginal insufflation of cocaine.

Air embolism secondary to vaginal insufflation has been documented as a cause of death in pregnant women. Under pressure, the air enters the uterus, causing air emboli within the uterine venous drainage and subsequently the systemic circulation. Death is usually sudden as the air obstructs the normal flow of circulation. Acute cocaine toxicity is also a well-known cause of sudden death. Cocaine use is prevalent in our society, even among pregnant women. We report the sudden death of a 31-year-old gravid female and 39-week gestational age male fetus. The cause of death was air embolism secondary to oral-vaginal insufflation of cocaine smoke.

Administration, Intravaginal↗
PubMed1994

Death due to cocaine intoxication initially thought to be a homicide.

We present a case of accidental death due to cocaine ingestion in which the victim's bizarre behavioral manifestations initially led law enforcement officials to consider the death a homicide. By virtue of the medical examiner's thorough investigation, the true accidental nature of the death was brought to light.

Adult↗
PubMed1994

Peripapillary disciform lesions in the elderly.

We present seven consecutive cases of peripapillary disciform lesions (PPDL) managed over a period of four and a half years. All patients were elderly, with a median age of 74 years. A protocol was used for the management of these patients. Four underwent ablative laser treatment when the lesion demonstrated growth and was sight threatening. The final visual acuity in this treated group improved by one line in one patient, was reduced by one line in two and was unchanged in the other. No recurrent lesions were seen beyond three months after treatment. The lesions in the remaining three patients were non-progressive and required no treatment. Of these, the final visual acuity remained unchanged in two patients and was reduced by one line in the other.

Aged↗
PubMed1994

Catalytic efficiency of human alcohol dehydrogenases for retinol oxidation and retinal reduction.

Mammalian alcohol dehydrogenase (ADH) is thought to be involved in the reversible oxidation of vitamin A or retinol to retinal for retinoic acid synthesis. Retinoic acid is a potent transcriptional regulator and a morphogen. It was proposed that the competition of consumed ethanol with retinol oxidation by ADH might explain developmental disorders seen with fetal alcohol syndrome. We report herein the relative efficiency (V/Km) of eight human ADH isoenzymes for oxidation of all-trans-retinol and reduction of three retinal isomers (all-trans, 9-cis, and 13-cis-retinal). Class IV sigma sigma and class II pi pi isoenzymes are the most efficient forms, with V/Km values approximately 100 and 30 times greater, respectively, than class I beta 1 beta 1 or gamma 1 gamma 1, sigma sigma exhibits the highest V/Km (1-2 microns-1min-1), followed by pi pi, with V/Km of 0.5-0.6 microns-1min-1 for all-trans-retinol, all-trans-retinal, and 9-cis-retinal. pi pi also has the lowest Km (11-14 microns) for all-trans-retinol and three retinal isomers. alpha alpha shows an intermediate efficiency, with V/Km of 0.09-0.2 microns-1min-1 and a relatively low Km of 16-24 microns for all four substrates. alpha alpha has the highest efficiency of all tested isoenzymes for 13-cis-retinal. Class III chi chi is inactive with all the tested retinoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase↗
PubMed1994

Intrasplenic transplantation of isolated periportal and perivenous hepatocytes as a long-term system for study of liver-specific gene expression.

Many hepatocyte-specific genes are expressed heterogeneously in the liver lobule depending on the location of the hepatocytes in relation to the inflow or outflow of portal blood (i.e., periportal or perivenous). For example, albumin is expressed in all hepatocytes but more so in the periportal zone, cytochrome P-450IIE1 is exclusively expressed in the perivenous zone and glutamine synthetase is limited to one or two cell layers next to the terminal hepatic venule. Additionally, hepatic damage caused by several xenobiotics, including carbon tetrachloride, is more severe in the perivenous zone. We have isolated highly enriched perivenous and periportal hepatocytes by means of a digitonin-collagenase perfusion method and transplanted them separately into the spleens of syngeneic rats. After transplantation, hepatocyte-specific gene expression in the transplanted perivenous and periportal cells was monitored for up to 13 mo with in situ hybridization to detect the specific gene transcripts (mRNAs). We also studied the effects of carbon tetrachloride administration on transplanted periportal cells by comparing them with intrasplenic transplanted periportal hepatocytes without carbon tetrachloride treatment. Our results showed that: (a) both transplanted perivenous and periportal hepatocytes could survive and proliferate in the splenic microenvironment for a prolonged period; (b) long-term-transplanted periportal hepatocytes in spleen could eventually express a high level of cytochrome P-450IIE1 mRNA in all transplanted hepatocytes and could express glutamine synthetase mRNA in only about 5% to 10% of them, specifically those hepatocytes located adjacent to splenic blood vessels. It is noteworthy that periportal hepatocytes in situ normally do not express the glutamine synthetase gene and express only a low level of cytochrome P-450IIE1 mRNA; and (c) carbon tetrachloride yielded different toxic effects on transplanted periportal hepatocytes at day 3 and mo 8. Necrosis was seen only when transplanted periportal hepatocytes expressed a high level of cytochrome P-450IIE1 mRNA by mo 8.

Albumins↗