Partial reversion in yeast: genetic evidence for a new type of bifunctional protein.

Two kinds of phenotypic expression in purine biosynthesis result from recessive mutation to adel2 in baker's yeast. The mutants are adenine-specific, blocked in the conversion of inosine 5'-phosphate to adenylosuccinic acid; their response to inhibition of pathway activity by adenine is considerably reduced. Allelic partial reversions can restore prototrophy without correcting the regulatory defect imparted by the primary mutation. The separation of the two properties of the locus by allelic mutation supports the hypothesis that the locus specifies a protein of two independent functions, enzymatic and regulatory.

Local chemotherapy in the rat brainstem with multiple catheters: a feasibility study.

OBJECTS: Technical aspects of local chemotherapy in inoperable brainstem gliomas by convection-enhanced delivery (CED) are still under experimental considerations. In this study, we characterize the feasibility of multiple cannula placements in the rat brainstem. MATERIALS AND METHODS: In 38 male Fisher rats, up to three guided screws were positioned in burr holes paramedian at 2.5 mm anterior and posterior to as well as at the lambdoid suture. Using Alzettrade mark pumps (1 microl/h flow rate over 7 days) either vehicle (5% dextrose) or 0.1 mg carboplatin was delivered via one, two, or three cannulas, respectively. During cannula insertion, electrocardiogram and respiratory rate was monitored. All rats were subsequently evaluated neurologically for 8 days. For drug distribution in coronal sections, the brain tissue concentration of platinum was measured. HE staining was used to evaluate the local site of drug delivery. Heart and respiratory rate remained within normal range during surgical procedure. Neurological scoring showed only mild neurological impairment in the groups receiving two or three cannulas, which resolved after vehicle delivery. However, after carboplatin delivery, this deficit remained unchanged. Drug distribution was more homogeneous in the three cannula group. Histological slices visualized edematous changes at the sight of cannula placement. CONCLUSION: The unilateral application of up to three cannulas in the brainstem of rats for local drug delivery studies is feasible. The remaining neurological deficit in carboplatin-treated animals underlines the need of low toxicity drugs for CED in the brainstem.

Neurological grading, survival, MR imaging, and histological evaluation in the rat brainstem glioma model.

OBJECTIVE: Convection-enhanced delivery using carboplatin in brainstem glioma models was reported to prolong survival. Functional impairment is of additional importance to evaluate the value of local chemotherapy. We established a neurological scoring system for the rat brainstem glioma model. MATERIAL AND METHODS: In 46 male Fisher rats stereotactically 10(5) F-98 cells were implanted at 1.4-mm lateral to midline and at the lambdoid suture using guided screws. Following 4 days local delivery was performed using Alzet pumps (1 microl/h over 7 days) with either vehicle (5% dextrose) or carboplatin via one or two cannulas, respectively. All rats were subsequently tested neurologically using a specified neurological score. In 38 animals survival time was recorded. Representative MR imaging were acquired in eight rats, respectively, at day 12 after implantation. HE staining was used to evaluate tumor extension. RESULTS: Neurological scoring showed significantly higher impairment in the high dose carboplatin group during the treatment period. Survival was significantly prolonged compared to control animals in the high dose carboplatin-one cannula group as well as in both low dose carboplatin groups (18.6 +/- 3 versus 26.3 +/- 9, 22.8 +/- 2, 23.6 +/- 2 days; p < 0.05). Overall neurological grading correlated with survival time. MR imaging showed a focal contrast enhancing mass in the pontine brainstem, which was less exaggerated after local chemotherapy. Histological slices visualized decreased cellular density in treatment animals versus controls. CONCLUSION: Local chemotherapy in the brainstem glioma model showed significant efficacy for histological changes and survival. Our neurological grading enables quantification of drug and tumor-related morbidity as an important factor for functional performance during therapy.

Petroclival tumors: a synthesis.

This article focuses on petroclival tumors, which are rare lesions of the posterior fossa-an area that is difficult to access. Because of their location, rarity, insidious growth, and relentless natural progression toward a fatal outcome, petroclival tumors pose major management problems. With improved microsurgical techniques, however, these tumors can be approached and removed with preservation of vital neural and vascular structures.

Psoriasiform eruption induced by captopril and chlorthalidone.

We present findings from two patients who experienced a psoriasiform eruption apparently due to captopril and chlorthalidone. These drugs should be added to the growing list of drugs that may produce a psoriasiform eruption. Drugs other than beta-adrenergic blocking agents should be considered in the differential diagnosis of a psoriasiform drug eruption.

An unusual pattern of arthritis dermatitis syndrome.

A 27-year-old woman presented with skin lesions and arthritis of the right knee of two days' duration. Her medical history was noncontributory and synovial fluid aspirated from the affected knee and a biopsy of a skin lesion were negative for gonococci. However, after methylene blue staining of cervical and urethral smears, intracellular and extracellular diplococci were demonstrated. Immunofluorescence showed deposits of immunoglobulin complexes of the skin section within the wall of blood vessels and dermal-epidermal junction. Treatment with ampicillin, 4 gm a day, resulted in resolution of the lesions and arthritis in two days. The need for cervical and urethral smears and for better, as yet unavailable tools for the diagnosis of the arthritis dermatitis syndrome, is emphasized.

[Guidelines for the treatment of aneurysmal subarachnoid hemorrhage. A consensus conference]. / Recomendaciones para el tratamiento médico de la hemorragia subaracnoidea de causa aneurismática. Conferencia de consenso.

The subarachnoid hemorrhage (SAH) by aneurysmatic rupture is responsible for 6% of the cerebral vascular accidents. The cerebral aneurysms are present in 0.2-9.9% of the population and the bleeding rate is of 10 out of 100,000 inhabitants per year. The consensus conference analyzed the different schemes of treatment and made therapeutic recommendations according to the criteria of medicine based on evidence. Levels of evidence were determined from I to V. The recommendation degrees were classified in: A, determined by evidence level I, B by evidence level II, and C suggested by evidence levels III, IV and V. These recommendations should be adapted to each patient. However, grade A recommendations are treatment standards. Seriousness of patients was evaluated on the basis of Hunt and Hess scale upon admission. Successive analyses covered: general medical treatment measures, cerebral vasospasm, diagnostic procedures and treatment of the hyponatremia and convulsion prevention.

[Liver allografts from donors older than 60: benefits and risks].

With limited organ resources and an increasing number of candidates for liver transplantation, the world-wide trend is towards using liver allografts from donors older than 60 years. This strategy, however, may be hazardous because of the known correlation between advanced donor age and graft dysfunction. Since January 1996, each of 5 patients received a liver allograft from a donor older than 60 years. Preservation time in these cases was shortened as much as possible and liver allografts were used only if there were no other potential risk factors for primary nonfunction. Mean cold ischemic time was significantly shorter in this donor group (7.8 hrs) than for livers from 28 younger donors (10.2 hour; p < 0.01). 3 of the 5 grafts from older donors had normal function immediately. The other 2 initially had biochemical features of preservation injury, but graft function returned to normal within the first week after transplantation. All 5 patients currently have normal graft function, with follow-up ranging from 3-8 months. There was no difference between the 5 recipients of grafts from older donors and 28 adult recipients of grafts from younger donors in extent of preservation injury and in immediate graft function. We conclude that in countries with limited organ resources, such as Israel, liver allografts from older donors can be used within defined limits and minimal preservation time.

Allelic variability in comparative complementation confirming that the ade12-specified protein of yeast is bifunctional.

Mutants at the adel2 locus of Saccharomyces cerevisiae are deficient in adenylosuccinate synthetase and are also responsible for constitutive purine biosynthetic activity. Ninety-six alleles were tested for restoration of each of these functions by allelic complementation and the results from the two types of test of every allele pair in the two matrices were compared with each other. Either the reactions were consistent, both complementing or noncomplementing, or inconsistent, with either enzymatic or regulatory function restored. The frequency and distribution of inconsistent behavior accords with the expectation that the adel2 locus specifies a bifunctional protein serving independent roles in enzymatic activity and in regulation of pathway activity. In a parallel experiment and analysis the addition of 1.0 m KCl increases the overall frequency of positive complementation, but skews the distribution of inconsistency sharply toward restoration of the regulatory function.

Quinidine-induced lichenoid and eczematous photodermatitis.

We report 6 cases of photodistributed rashes due to oral administration of quinidine: 4 cases with a lichen-planus-like eruption and 2 with an eczematous dermatitis. The casual relationship between the drug and the eruption was established mainly by means of circumstantial evidence. It was further strengthened by an in vitro challenge test in 4 cases and by a rechallenge in 2 patients. The in vitro challenge test used was the macrophage migration inhibition test, which can be of diagnostic aid whenever a rechallenge of the patient is contraindicated. Quinidine-induced lichenoid eruption in a photodistribution seems to be more common than previously reported. Physicians should be aware of this type of drug eruption.

Familial pemphigus vulgaris.

A case of familial pemphigus vulgaris is described in an uncle and his niece who developed the disease 18 years apart. The man died from pemphigus in 1964. The diagnosis was confirmed histopathologically in both cases, but immunofluorescent microscopic studies were performed only in the woman because the technique was not available in 1964. HLA typing in the woman and her daughter and sister showed A 26, BW 38 and DRW 4 in all of them. Clinical disease did not develop in the other family members.

Extracellular protein release and its response to pH level in Saccharomyces cerevisiae.

Saccharomyces cerevisiae grown in batch culture at pH 5.5 releases 0.1 to 0.2 pg protein per cell to the external medium over a period of four to five days, final concentration 20-40 micrograms/ml. Cells grown at pH 3.0 release 10-fold this quantity (1-2 pg/cell, final concentration 100-200 micrograms/ml). A kinetic model based on published behavior of periplasmic protein gave a good fit to the observed kinetics of exoprotein yield. The electrophoretic pattern of exoprotein differed from that of cell lysate protein, and exoprotein synthesis was apparently limited to early stages of the life cycle. These results are consistent with the identification of exoprotein as periplasmic protein released to the external medium through the cell wall. Analysis of the observed kinetics of exoprotein yield, utilizing the kinetic model suggests that the greater exoprotein production of cells grown at pH 3.0 was due entirely to greater synthesis of periplasmic proteins while the fraction of periplasmic protein released per unit time was greater for cells grown at pH 5.5. The latter conclusion is supported by thicker cell walls of cells grown at pH 3.0 as observed by electron microscopy. At an applied level the apparent limitation of exoprotein synthesis to the first few hours of cell life, the slow leakage of exoprotein through the cell wall, and the dilute nature of a yeast suspension do not favor the utilization of yeast cells for direct conversion of substrate into protein released to the external medium.

Increased intestinal permeability: implications for thoracoabdominal aneurysm repair.

Coagulopathy and massive bleeding plays a major role in the mortality of thoraco-abdominal aneurysm repair. Increasing supraceliac aortic cross-clamp time from 0 to 90 minutes increases the degree of disseminated intravascular coagulation, which occurs as a result of occlusion and reperfusion of the superior mesenteric artery. The purpose of this study was to investigate the mechanism of the superior mesenteric artery reperfusion disseminated intravascular coagulation. Twenty dogs were divided into four groups: cross-clamp time of 30 minutes; cross-clamp time of 60 minutes; cross-clamp time of 90 minutes; and control. Permeability was determined by lactulose/mannitol absorption. The venous effluent was sampled for endotoxin, potassium, bacteria, and pH every hour and urine was collected for six hours. Lactulose absorption was significantly higher in all of the experimental groups. There was increased permeability in the 60 and 90 minute groups which correlated significantly with time. Venous endotoxin, potassium, and blood cultures for bacteria did not change significantly. The pH was significantly lower every hour for six hours in the 90 minute group. These data suggest that intestinal permeability is increased with supraceliac aortic clamping and can be kept to a minimum for clamp times of under one hour.