bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcellular Localization Directs Signaling Specificity of the
Cryptococcus neoformans
Ras1 Protein
Authors: Nichols Connie B. , Ferreyra Jessica , Ballou Elizabeth R. , Alspaugh J. Andrew 
Published: December 2008

ABSTRACT

In the human fungal pathogen
Cryptococcus neoformans
, Ras signaling mediates sexual differentiation, morphogenesis, and pathogenesis. By studying Ras prenylation and palmitoylation in this organism, we have found that the subcellular localization of this protein dictates its downstream signaling specificity. Inhibiting
C. neoformans
Ras1 prenylation results in the defective general membrane targeting of this protein and the loss of all Ras function. In contrast, palmitoylation mediates localization of Ras1 to the plasma membrane and is required for normal morphogenesis and survival at high temperatures. However, palmitoylation and plasma membrane localization are not required for Ras-dependent sexual differentiation. Likely as a result of its effect on thermotolerance, Ras1 palmitoylation is also required for the pathogenesis of
C. neoformans
. These data support an emerging paradigm of compartmentalized Ras signaling. However, our studies also demonstrate fundamental differences between the Ras pathways in different organisms that emphasize the functional flexibility of conserved signaling cascades.
Late-onset retinal macular degeneration: clinical insights into an inherited retinal degeneration
Authors: Borooah S , Collins C , Wright A , Dhillon B 
Published: December 2008

Abstract

Aim
This study describes, in detail, the phenotype of late-onset retinal macular degeneration (L-ORMD) an inherited condition affecting both the retina and anterior segment. A staging based on clinical characteristics is proposed, and the relevance of this condition to current understanding of age-related macular degeneration is discussed.

Methods
A systematic review of the literature regarding this condition supports a detailed description of the natural history. Clinical experiences in identifying, monitoring and managing patients are also presented.

Results
L-ORMD is a rare fully penetrant autosomal dominant condition resulting from a mutation in the C1QTNF5 gene on chromosome 11. Affected individuals develop bilateral loss of vision, dark-adaptation abnormalities, fundus drusen-like yellow spots, midperipheral pigmentation, choroidal neovascularisation, chorioretinal atrophy and long anteriorly inserted lens zonules. Patients may benefit from treatment with high-dose vitamin A.

Conclusions
Raised awareness of L-ORMD should lead to earlier diagnosis and improved care for patients. New antivascular endothelial growth factor treatment may provide a new possibility for management. A deeper insight into molecular and genetic mechanisms of L-ORMD may suggest avenues to explore new treatments of this disorder.
Thyrotropin-secreting pituitary tumours: significance of “atypical adenomas” in a series of 10 patients and association with Hashimoto thyroiditis as a cause of delay in diagnosis
Authors: Marucci G , Faustini-Fustini M , Righi A , Pasquini E , Frank G , Agati R , Foschini M P 
Published: December 2008

Background:Thyrotropin-secreting adenomas (TSH-As) are rare and, according to the World Health Organization criteria (WHO 2004), a significant proportion of them present features of atypical adenomas at the time of diagnosis.Aims:To determine the frequency of “atypical adenomas” and the significance of this definition as regards follow-up. To investigate their possible association with Hashimoto thyroiditis, leading to a delay in diagnosis.Methods:Case notes for patients who underwent trans-sphenoidal surgery between 1992 and 2006 were retrieved. Follow-up ranged from 6 to 180 months.Results:Ten cases of TSH-As out of 908 pituitary adenomas were selected. Before surgery, eight patients had hyperthyroidism, one was euthyroid and another one showed hypothyroidism associated with Hashimoto thyroiditis. All cases were macroadenomas; six of them were invasive. Three cases met the criteria for classification as atypical. In none of the cases, including the three “atypical adenomas”, were clinical or radiological signs of recurrence observed.Conclusions:The three cases with features of atypical adenoma did not recur or metastasise, suggesting that, at least in the present series, a strict relationship between the morphological criteria for diagnosing atypical adenomas and biological behaviour may be sometimes lacking. Furthermore, the casual association of TSH-As with Hashimoto thyroiditis may led to an adjunctive delay in diagnosis, because of low thyroid hormone levels.
Purpura hyperglobulinaemia in association with rheumatoid arthritis and ulcerative colitis
Authors: Wardle E N 
Published: December 2008

Summary
Five patients with purpura hyperglobulinaemia are reviewed. One patient developed ulcerative colitis; female members of this patient’s family suffered from rheumatoid arthritis. The family showed immunoglobulin abnormalities.
Although the clinical picture of purpura hyperglobulinaemia and Henoch-Schönlein purpura can show some common features, the former may well be separated as a ‘disturbed-tolerance’ disease with a different prognosis.
Virological aspects of neurological disease
Authors: Waterson A P , Almeida June D 
Published: December 2008

Summary
Viruses are now known to consist of only two major components; the nucleic acid which is essential for infectivity and an external covering to protect this. Visualization of this external shell by electron microscopy has revealed that viruses display distinctive arrangements of sub-units by which they can be both recognized and characterized. This has made it possible to classify viruses according to their structural and chemical features and such a classification has superseded earlier and essentially biological classifications without contradicting them.
The action of a virus upon a cell may take one of three forms. The virus in the process of replication may destroy the cell which it has infected (lytic action). A second possibility is that it may transform the cell to malignancy (oncogenic action). A third possibility is that the virus may remain latent within the cell for long periods with no obvious manifestations of its presence (symbiotic relationship). It is this last type of interaction between a virus and the host cell which appears to be of particular interest in the context of the nervous system.
Six generations of ill-used children in a Huntington’s pedigree
Authors: Oliver J E , Dewhurst K E 
Published: December 2008

Summary
This Huntington’s pedigree of six generations illustrates the interaction of environmental and genetic factors causing prolonged suffering to children reared in such families.
This pedigree is representative of many others studied in depth involving at least 425 families. In general, children reared in these families later manifest subtle anti-social tendencies. Even when these children do not carry the specific gene themselves, the consequences of their upbringing results in psychiatric and anti-social sequelae in their adult lives. These are most serious where both parents are psychotic. In such cases the third generation is almost invariably crippled by alcoholism, chronic neurosis or psychopathy, initiating ‘problem families’ in subsequent generations.
Attention is drawn to recent legislation concerning family planning and therapeutic abortion which are still, unfortunately, the only means of preventing the devastating hereditary consequences of this disease.
Clinical features and detection of osteomalacia in the elderly
Authors: Rosin Arnold J 
Published: December 2008

Summary
Fifteen elderly patients with osteomalacia were investigated in 2½ years in a geriatric unit. Although they all had bone pain the diagnosis in some cases was overshadowed by other common diseases with which they were referred to hospital, such as impaired balance or mental confusion. The bone pain had been present for weeks or months and was often attributed to arthritis. Biochemical investigations showed a low serum calcium and low or low-normal serum phosphate levels and a moderate to large increase in alkaline phosphatase above 15 KA units/100 ml. Only six patients had radiological signs of osteomalacia but all had histological evidence on bone biopsy.
Five subjects died within 3 weeks of admission from pneumonia or myocardial infarction. In the other ten, relief of pain occurred within 2-4 weeks of starting vitamin D, and bone tenderness disappeared after 2-3 months. The earliest biochemical sign of recovery was the rise in serum phosphate. Calciferol 1·25 mg daily (50,000 units of vitamin D) was given for 2-4 weeks or until there was a rise in the serum phosphate or calcium. One woman of 74 showed resistance to vitamin D associated with renal insufficiency.
Dietary history in seven patients revealed daily vitamin D intakes below 100 units. Four of the fifteen patients had a previous history of partial gastrectomy.
In addition to routine biochemical and X-ray investigations in elderly patients with generalized bone pain, trephine biopsy of the bone is a useful procedure for the diagnosis of osteomalacia.
Correlation of clinical, biochemical and functional parameters with histological lesions in secondary renal amyloidosis
Authors: Gulati P D , Mathur G P , Aurora A L , Vaishnava H 
Published: December 2008

Summary
The records of fifty-five patients with secondary renal amyloidosis have been scrutinized in order to evaluate statistically the correlation of the various clinical features and biochemical alterations with the severity of histological lesions in this disease. An ‘amyloid factor’, calculated on the basis of the extent of glomerular amyloid deposition, was utilized for the grading of the latter.
A significant correlation of the histological grading was observed with the duration of predisposing illness (P &lt;0·02), alteration of total serum protein (P &lt;0·001) and functional impairment as determined by the creatinine clearance test (P &lt;0·002). There was, however, no significant correlation between the extent of glomerular lesions and clinical severity, the duration of oedema, the degree of proteinuria and the levels of blood urea, serum albumin and serum cholesterol.
Medical library and information services
Authors: Tabor R B 
Published: December 2008

Summary
The medical libraries in the Postgraduate Medical Education Centres which are now being built in many regions are generally of a simple pattern based on traditional library practices.
In view of the recent advances in information science it is suggested that a more radical approach should be made to the design of medical library and information centres.
The basic requirements for medical information in relation to education and medical practice are discussed together with recommendations for a regional and national network for the co-ordination of information-handling in the field of the health sciences.
Diseases of Jews
Authors: Krikler Dennis M 
Published: December 2008

SummaryThe relative social and genetic isolation of Jews from other communities, which was much more marked in the past than now, has led to the belief that they are unusually prone to a variety of illnesses. Until the last few decades assessments of the incidence of various diseases among them were usually based on impressions rather than planned surveys or careful analyses, and many misconceptions still persist. It is proposed to consider the present state of knowledge as well as to indicate the historical and social basis for any tendencies for Jews to suffer from, or perhaps to resist, some diseases. No attempt has been made to analyse every single report in which Jewish pre-disposition to various diseases is mentioned; attention will be focused on those conditions that have received greater attention or from which it is possible to draw meaningful conclusions.
The accessory artery in essential hypertension
Authors: Ooi Boon Seng , Yu Sheng Fong , Chen Beatrice T M , Khoo Oon Teik 
Published: December 2008

Summary
Ninety hypertensive patients were investigated by intravenous pyelography, abdominal aortography, and renal biopsy. Accessory arteries were present in four of thirty-nine patients with secondary hypertension, whereas sixteen of fifty-one patients with primary hypertension exhibited this anomaly.
These differences in distribution are statistically significant, and the relationship between accessory arteries and primary hypertension is discussed.
Epidemiological features of ruptured dissecting and saccular aortic aneurysms
Authors: Talbot S , Langman M J S 
Published: December 2008

Summary
An analysis based upon necropsy figures has been made of the frequency of deaths with dissecting aneurysms and ruptured fusiform or saccular aortic aneurysms. More deaths from these conditions were found at necropsies conducted on people dying suddenly in the community than in those dying in hospital.
Dissecting aneurysms were nearly all found to involve the thoracic segment of the aorta and were equally common in men and women whereas ruptured saccular and fusiform aneurysms were usually sited in the abdominal aorta and mainly occurred in men.
There was also a clear seasonal variation in death rates with ruptured and dissecting aneurysms. Death more commonly occurred with both types in the winter months.
Facial myokymia: a clue to the diagnosis of multiple sclerosis
Authors: de Silva K L , Pearce John 
Published: December 2008

Summary
Three patients with multiple sclerosis in whom facial myokymia occurred are described. The clinical and electromyographic features of this phenomenon are reviewed. The phenomenon is most frequently associated with multiple sclerosis, and when it is transient and unassociated with progressive facial paresis and other signs of a pontine tumour, is a strong indication of this condition.
Use of recombination in the production of influenza vaccine strains
Authors: McCahon D , Beare A S , Schild G C , Hall T S 
Published: December 2008

Summary
Recombination between influenza A viruses as a method of producing strains suitable for use in vaccines is discussed with particular reference to a recombination system involving an attentuated laboratory strain A/PR8/34 (HoN1) and a recent isolate of the epidemic strain A/Hong Kong/68 (H3N2). A variety of properties of the viruses were shown to be segregated independently of one another during recombination. These properties included the envelope antigens (haemagglutinin and neuraminidase), growth capacity in the fertile egg and attenuation for man. Some of the recombinants were considered suitable for use in vaccines either inactivated (whole virus particles or subunits) or live. The application of this technique to future requirements for vaccine strains are discussed with particular reference to the safety aspect of using recombinants in live vaccines.
The effect of a low-calorie diet with and without fenfluramine, and fenfluramine alone on the glucose tolerance and insulin secretion of overweight non-diabetics
Authors: Dykes J Ranald W 
Published: December 2008

Summary
Glucose tolerance and insulin secretion have been measured in six overweight non-diabetic subjects on first presentation and after 5 weeks of fenfluramine treatment without dietary restriction. There was a significant improvement in glucose tolerance and a marginally significant decrease in insulin secretion.
In another six overweight non-diabetic subjects, insulin secretion and glucose tolerance were measured on first presentation, after 10 weeks of low-calorie diet, and then after a further 10 weeks of the same low-calorie diet with the addition of fenfluramine. Diet alone did not produce any significant effect on glucose tolerance, but did bring about a significant decrease in insulin secretion. The addition of fenfluramine to the dietary therapy was associated with a marginally significant improvement in the glucose tolerance and a highly significant decrease in insulin secretion. This further decrease in insulin secretion was significantly greater than the decrease produced by diet alone in these six subjects.
Meningitis as the presenting symptom of pituitary adenomata
Authors: Lascelles R G , Bhalla K K , Tuck S J , Graves Paul S 
Published: December 2008

Summary
We have recently seen two patients, both men in their forties, who presented with a clinical picture of meningitis which was later found to be secondary to infarction of an underlying chromophobe adenoma of the pituitary.
Aspects of human brucellosis
Authors: Mann P G , Richens Elizabeth R 
Published: December 2008

Summary
Human brucellosis still presents difficulties in diagnosis and prevention. Townspeople may be infected by drinking raw milk while on holiday. Laboratory tests are still unsatisfactory as indicators of clinically active disease. High titre antibodies may be found without overt symptoms, particularly in persons occupationally exposed to repeated infection. In contrast, cases have been recorded in which no antibody appeared despite a positive blood culture. A preliminary study of leukocyte migration inhibition suggests that this may prove useful in detecting disease associated with low or absent antibodies, but is not likely to provide an infallible guide to clinical activity.
A double-blind clinical trial of griseofulvin in patients with Raynaud's phenomenon
Authors: Sabri S , Roberts V C , Higgins R F , Cotton L T , Williams D I , Wilson L C 
Published: December 2008

Summary
Twenty-four patients with Raynaud's phenomenon were treated with griseofulvin and a placebo in a double-blind cross-over clinical trial. The results were assessed subjectively and plotted sequentially. The number of patients able to distinguish the active from the placebo treatment was statistically significant (P=0·05). There were indications that the response was dose dependent. Further studies are needed to establish whether griseofulvin offers useful clinical improvement in this condition.
Pathophysiology of achalasia of the cardia
Authors: Misiewicz J J 
Published: December 2008

Summary
The symptoms and signs of achalasia are due to the loss of ganglion cells in the body of the oesophagus, leading to dilatation and loss of peristaltic activity. The data pertaining to the lower oesophageal sphincter are still somewhat conflicting. The ganglion cells may be absent, but pharmacological evidence suggests denervation to be pre-ganglionic. The classical view of a normotensive, non-relaxing achalasic sphincter has been challenged by recent observations which suggest the presence of a hypertensive, partially relaxing sphincter, which is supersensitive to gastrin and acetylcholine.
Carcinoma of the oesophagus and cardia—endoscopy
Authors: Roesch W 
Published: December 2008

Summary
Oesophagoscopy will establish a definite preoperative diagnosis of a radiologically suspected malignancy by guided biopsy and/or brush cytology. The rigid instruments should only be used for photodocumentation since the hazards are considerably greater compared with the fibre-endoscopes. In obstructing lesions of the lower third of the oesophagus where a primary gastric cancer is suspected a passage of the instrument into the stomach should be attempted since a positive biopsy is easier obtained after a U-turn manoeuvre.
Radiotherapy
Authors: Jelliffe A M 
Published: December 2008

Summary
The author examines the place of radiotherapy in the management of oesophageal cancer. Many of these tumours are locally curable with radiotherapy. This is so particularly with the proliferative, poorly differentiated tumour. The upper and middle thirds of the oesophagus are the most suitable sites for attempted cure by radiotherapy; surgery is always the better method in the lower third.
Before adopting a definitive treatment policy it is important to eliminate metastatic spread as far as is possible. The overall prognosis is poor: long unnecessary courses of treatment or extensive operations should be avoided unless there is a reasonable chance of long-term cure.
Lead poisoning with low blood lead levels
Authors: Torkington P , Bhalla K K 
Published: December 2008

Summary
Two cases are reported in which symptomatic lead poisoning coincided with normal haemoglobin concentrations and blood lead levels below 80 μg/100 ml. Urinary coproporphyrins and amino laevulinic acid concentrations were elevated. These latter tests are useful for confirmation of clinical diagnoses and for the screening of industrial lead workers.
Spontaneous cholecystectomy
Authors: McGregor J C , Sammon D J 
Published: December 2008

Summary
A young female, who presented with acute appendicitis and peritonitis, is described. Following laparotomy she developed a series of intraperitoneal abscesses. After drainage of a subphrenic abscess a necrosed gallbladder was discharged several days later through the drainage wound in the abdominal wall.
Antepartum diagnosis of vasa praevia—report of a case causing sudden foetal death
Authors: Pallewela C S 
Published: December 2008

Summary
A case of sudden foetal death due to vasa praevia is reported. The main problem is early ante-partum diagnosis. Three methods are discussed.
(1) Tests to recognize foetal blood as a routine in ante-partum haemorrhage;
(2) amnioscopy before amniotomy; in foetal irregularity or bradycardia; in ante-partum haemorrhage;
(3) tests for foetal bradycardia in early labour as a part of the routine abdominal examination.
The treatment of priapism by corpus-saphenous by-pass
Authors: Foley R J E , De Jode L R 
Published: December 2008

Summary
Two cases of priapism treated by corpus-saphenous by-pass are presented. Priapism responded to treatment successfully in both cases. Satisfactory erection and sexual intercourse followed 6 weeks after operation in one case. The second patient failed to have further erections. It was thought that this was due to the length of time (6 weeks) between onset of priapism and operation.
Problems in the management of mediastinal tumours
Authors: Lallemand R C , Keates J R W 
Published: December 2008

Summary
Five cases of anterior mediastinal tumour are presented. Two cases were asymptomatic, being discovered by routine chest radiography. The remainder presented with dyspnoea, dysphagia and a sinus over the manubrium.
Each case provided a lesson in the management of the mediastinal mass. Pathologies included haemangioma, teratoma, secondary carcinoma from the kidney and a malignant thymoma which caused cardiac tamponade.
Features of interest in the presentation, treatment and pathology are discussed.
It is concluded that a full investigation of mediastinal swellings is needed before mediastinoscopy is performed; that incision of swellings in the base of the neck should be avoided; and it is suggested that the management of asymptomatic mediastinal haemangioma in adults may be expectant.
Prognostic factors in the rehabilitation of patients with spinal problems
Authors: Richardson Alan E , Tupper Annemarie D 
Published: December 2008

Summary
One hundred patients undergoing intensive rehabilitation for painful spinal lesions were studied. They were divided into three groups in relation to result, these being ‘good’, ‘moderate’ or ‘poor’. Seventy-eight per cent were regarded as ‘good’ or ‘moderate’. The ‘poor’ group showed significantly raised neuroticism scores measured by the Middlesex Hospital Questionnaire, particularly sub-scores for ‘depression’ and ‘somatic concomitants of anxiety’ in women and ‘free floating anxiety’, ‘depression’ and ‘obsessionality’ in men. Other factors associated with poor outcome were long history, multiple operations and a nonspecific diagnosis of ‘low back pain’. It is suggested that this group can be identified early and might benefit from a combined physical rehabilitation and psychotherapy programme. A controlled study to test this is planned.