Congenital Orotic Aciduria: Demonstration of an Enzyme Defect in Leukocytes and Comparison with Drug-induced Orotic Aciduria

1. Leukocytes from presumed heterozygotes of congenital orotic aciduriahave been found to exhibit a partial defect in the metabolism of orotic acid.In disrupted cell preparations, orotidylic decarboxylase activity was reduced.Assay of orotidylic pyrophosphorylase activity proved to be unsatisfactory inleukocyte preparations.

2. Orotic aciduria and orotidinuria were produced by the administrationof 6-azauridine to patients with chronic myelocytic leukemia. This drug-induced impairment of pyrimidine nucleotide biosynthesis has been comparedto the genetically determined disorder.

3. A summary of enzymatic defects previously demonstrated in hemic cellsin human genetic disorders has been presented.

Submitted on June 11, 1962 Accepted on July 12, 1962     

BULK FLOW IN THE CEREBROSPINAL FLUID SYSTEM OF THE DOG

Ventriculo-cisternal, intracranial subarachnoid-to-subarachnoid space and spinal subarachnoid space perfusions were carried out on dogs. The perfusate contained inulin as a tracer and the design of these experiments was based upon the concept that inulin leaves cerebro-spinal fluid (CSF) compartments only by means of bulk absorption, and that actual diffusion and active transport of inulin is negligibly small. Inulin was removed from different CSF spaces by bulk absorption at rates which varied linearly with hydrostatic pressure. The rate of formation of CSF is equal to inulin clearance plus the difference between outflow and inflow rates. The total CSF formation in dogs weighing 12 to 17 kg was measured as 0.065 ml/min, and 58.5 per cent of this amount was found to come from extraventricular CSF space. The rates are independent of hydrostatic pressure in the range studied.     

CHILD HEALTH PROBLEMS AND PROGRAMMES IN TWO UNDERDEVELOPED AREAS OE THE USA

There are areas in the USA where the health problems of children a similar to those of children in some developing countries. Traditional US health programmes have contributed to an improvement in the health status of many of these children but there remains much more to be done.     

Immunological reactivity in dermatophytosis

Patients with Trichophyton mentagrophytes and T. rubrum infections were compared in terms of cutaneous responses and in vitro lymphocyte reactivity to trichophytin and other antigens. Twelve out of fourteen T. mentagrophytes patients exhibited delayed cutaneous hypersensitivity to trichophytin. Most T. rubrum patients (thirty-seven out of forty-nine) lacked delayed reactions to trichophytin specifically, but these patients frequently manifested immediate weal reactions to this antigen. Positive lymphocyte responses correlated with the presence of delayed but not immediate cutaneous reactions. Serum from chronic T. rubrum patients failed to inhibit lymphocyte responses. Possible mechanisms for selective anergy in chronic T. rubrum patients are discussed.     

Subchronic Inhalation Toxicity of Methyl Isoamyl Ketone in Rats

Subchronic Inhalation Toxicity of Methyl Isoamyl Ketone in Rats.KATZ, G. V., RENNER, E. R., JR., AND TERHAAR, C. J. (1986).Fundam. Appl. Toxicol. 6, 498–505. Rats were exposed byinhalation, 6 hr/day, 5 days/week, to target vapor concentrationsof 2000, 1000, or 0 ppm of methyl isoamyl ketone (MIAK) for12 exposures spanning 16 days, and 2000, 1000, 200, or 0 ppmfor 69 exposures spanning 96 days. Body weights, hematology,and serum clinical chemistry determinations were comparableto controls in both inhalation studies. Clinical signs of toxicitywere lethargy and decreased aural response (2000 ppm, 2-weekstudy; 2000 and 1000 ppm, 90-day study) and nasal and eye irritation(2000 and 1000 ppm, 90-day study). In addition, the excretionof gel-like casts in seminal fluid was seen in males exposedto 2000 and 1000 ppm in both studies. increases in absoluteand relative liver and kidney weights were observed in bothsexes following exposure to 2000 and 1000 ppm in the 2-weekand 90-day studies. Liver weight increases were exposure dependentand in the 90-day study reflected hepatocyte hypertrophy observedon microscopic examination. Microscopic kidney changes werehyalin degeneration or hyalin droplet formation in males inthe 2-week (2000 and 1000 ppm) and 90-day (2000 ppm) studies;and minor to moderate regeneration of tubular epithelium (2000and 1000 ppm) in both studies. Minor tubular epithelium regenerationwas seen in females exposed to 2000 ppm for 90 days. The toxicityof MIAK following inhalation exposure was not as extensive orsevere as that resulting from a prior study in which male ratswere dosed orally with 2000 mg/kg/day (a dose comparable to2000 ppm) for 13 weeks. The 90-day inhalation exposure no-observed-effectlevel for toxicity was 200 ppm MIAK.     

GUIDELINES FOR AUTOPSY IN HIV POSITIVE CASES

Autopsy on a patient who had died as a consequence of acquired immune deficiency syndrome (AIDS) can be of great value in understanding the disease process. A potential risk to the prosector for acquiring the HIV exists, but if adequate preventive measures are undertaken, the risk is negligible. Indeed there is no documented evidence of a pathologist or an autopsy room attendant acquiring HIV infection while performing autopsy on a patient with AIDS. The procedures to be followed in the autopsy of the patient with AIDS are discussed.KEY WORDS: Acquired immune deficiency syndrome (AIDS), Autopsy in HIV Positive, Autopsy, Hospital acquired infections     

ANEURYSMAL BONE CYST IN THE MANDIBLE (A Case Report)

Aneurysmal bone cyst is commonly seen in the long bones and vertebrae and is rare in the jaws. Its association with other lesions of the bone has been stressed by many workers. Because of its variable radiological appearance, diagnosis of the lesion is established by histopathological examination. A case of aneurysmal bone cyst occurring in the mandible is reported.KEY WORDS: Aneurysmal bone cyst, Mandible     

LEUKAEMIC INVOLVEMENT OF CENTRAL NERVOUS SYSTEM

Eighty two patients of leukaemia consisting of 25 cases of acute lymphocytic leukaemia, 38 cases of acute myeloid leukaemia, 14 cases of chronic myeloid leukaemia and 5 cases of chronic lymphocytic leukaemia were evaluated for central nervous system (CNS) involvement. Speech disorders, cranial nerve palsies, encephalopathy, ataxia, intracranial haemorrhage, peripheral neuropathy and spinal cord involvement were the main neurological findings detected in 23 (28.1%) cases. All except one were subjected to autopsy after death. Leukaemic infiltrations (36.6%) and intracranial haemorrhage (26.8%) were the prominent CNS autopsy findings. In addition, demyelination with astrocytosis (9.7%) and gliosis (2.4%) were seen. In all, 45 (54.9%) of the patients showed CNS involvement at autopsy. Thus a large number of CNS lesions were missed clinically and detected only on autopsy.KEY WORDS: Intracranial haemorrhage, Leukemia, Metastasis     

PRELIMINARY STUDY OF HOW ALCOHOL CONSUMPTION DURING PREGNANCY AFFECTS IMMUNE COMPONENTS IN BREAST MILK AND BLOOD OF POSTPARTUM WOMEN

Human milk has been shown to contain numerous immune componentsthat can potentially protect the infant during the period beforeits own immune system is completely developed. Alcohol consumptionin both experimental animals and humans has been associatedwith alterations to a number of immune parameters. We have investigatedthe possibility that alcohol consumption during pregnancy alterscertain immune components in day 3 postpartum breast milk andperipheral blood of women. Our study group consisted of 10 alcoholicbeverage drinkers (moderate to heavy, most of whom smoked a1/2-1 pack of cigarettes per day), 15 non-drinking/non-smokingcontrols, and 10 non-drinking/smokers (1/2-1 pack per day) controls.The immune parameters measured in these otherwise healthy womenwere: (1) percentage and absolute number of the various subsetsof leukocytes; (2) percentage of T cells, B cells, T helperand cytotoxic/suppressors subsets, and natural killer cells;(3) levels of the cytokines IL-6, IL-8 and TNF-; (4) levelsof IgA in milk and IgG in serum. Milk from the alcohol groupcontained an elevated amount of IL-8 as compared with milk fromnon-smoker controls; however, it did not differ statisticallyfrom that of the smoker controls. Blood from the alcohol groupshowed an increased level of IL-8 when compared with that fromboth smoker and non-smoker controls. The total number of leukocytesin milk was elevated in milk from the alcohol group as comparedto both the smoker and non-smoker control groups. In the leukocytecomponent of milk, neutrophils predominate and are responsiblefor the elevation in total number of cells, as both lymphocyteand macrophage populations did not differ from those of thecontrols. For lymphocytes, B cells were also increased in bloodof the smokers as compared with the alcohol and non-smoker controls.There were no statistical differences in any of the other immuneparameters tested among the three groups. The present studyfound that alcohol consumption during pregnancy could modulatethe production of IL-8 and infiltration of certain leukocytesin milk and blood of postpartum women. Some of these alterationswere also evident in the smoker controls and thus could notbe attributed to alcohol consumption alone.     

Mathematical and Biostatistical Methods for Designing and Analyzing Complex Interactions

Mathematical and Biostatistical Methods for Designing and AnalyzingComplex Chemical Interactions. CARTER, W.H., Jr., AND CARCHMAN,R.A. (1988). Fundam Appl. Toxicol 10, 590–595. In thispresentation, statistical methods for designing and analyzingexperiments evaluating a mixture of drugs/chemicals are discussed.These methods are promising in that they are not limited bythe number of interacting agents in the combination. Severalexamples are given and a discussion of the results follows.