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Hereditary alpha 1-antitrypsin deficiency may be very rarely associated with chronic panniculitis and is therefore often diagnosed only with delay.The typical clinical features of the disease are described in a 37-year-old woman. This case underlines the importance of determining alpha 1-antitrypsin levels in patients with chronic relapsing panniculitis. Therapeutic approaches are discussed.

A review of the properties of purified and tissue bound phosphate activated glutaminase (PAG) in brain and kidney (pig and rat) is presented, based on kinetic, electron microscopic and immunocytochemical studies. PAG is a mitochondrial enzyme and two pools can be separated, a soluble and membrane associated one. Intact mitochondria appear to express PAG accessible only to the outer phase of the inner mitochondrial membrane. This PAG has properties similar to that of the membrane fraction and polymeric form of purified enzyme. PAG in the soluble fraction has properties similar to that of the monomeric form of purified enzyme and is assumed to be dormant due to the high matrix concentration of the inhibitor glutamate. A hypothetical model for the localization of PAG in the mitochondria is presented. The activity of PAG in vivo is assumed to be regulated by cytosolic glutamate and other compounds, that affect the activation by phosphate. Glutamine is transported into brain and kidney mitochondria by a protein catalyzed energy requiring process, which may be mediated by more than one protein. There is no correlation between glutamine hydrolysis and transport.

Glutamate has been implicated in signal transmission between sensory hair cells and afferent fibers in the inner ear. However, the mechanisms responsible for glutamate replenishment in these cells are not known. Here we provide evidence that phosphate activated glutaminase, which is thought to be the predominant glutamate-synthesizing enzyme in the brain, is concentrated in all types of hair cell in the organ of Corti and vestibular epithelium. By use of two different antibodies (directed to the N and C terminus, respectively) it was shown that glutaminase is largely restricted to mitochondria and that part of the enzyme pool is associated with the inner membrane of this organelle. Quantitative analysis of immunogold labelled Lowicryl sections revealed that the level of glutaminase immunoreactivity in mitochondria of supporting cells is less than 15% of that in hair cell mitochondria. Using triple labelling for glutaminase, glutamate, and glutamine, evidence was provided of a positive correlation between the glutamate/glutamine ratio and the level of glutaminase immunoreactivity, suggesting that the glutaminase antibodies identify a functional enzyme pool. Our results strengthen the idea that glutamate is a hair cell transmitter and indicate that the sensory epithelia in the inner ear show a metabolic compartmentation analogous to that in the brain.

Glutamine transport into rat brain synaptic and non-synaptic mitochondria has been monitored by the uptake of [3H]glutamine and by mitochondrial swelling. The concentration of glutamate in brain mitochondria is calculated to be high, 5-10 mM, indicating that phosphate activated glutaminase localized inside the mitochondria is likely to be dormant and the glutamine taken up not hydrolyzed. The uptake of [3H]glutamine is largely stereospecific. It is inhibited by glutamate, asparagine, aspartate, 2-oxoglutarate and succinate. Glutamate inhibits this uptake into synaptic and non-synaptic mitochondria by 95 and 85%, respectively. The inhibition by glutamate, asparagine, aspartate and succinate can be explained by binding to an inhibitory site whereas the inhibition by 2-oxoglutarate is counteracted by aminooxyacetic acid, which indicates that it is dependent on transamination. The glutamine-induced swelling, a measure of a very low affinity uptake, is inhibited by glutamate at a glutamine concentration of 100 mM, but this inhibition is abolished when the glutamine concentration is raised to 200 mM. This suggests that the very low affinity glutamine uptake is competitively inhibited by glutamate. Furthermore, glutamine-induced swelling is inhibited by 2-oxoglutarate, succinate and malate, similarly to that of the [3H]glutamine uptake. The properties of the mitochondrial glutamine transport are not identical with those of a recently purified renal glutamine carrier.

Glutamine transport into rat brain mitochondria (synaptic and non-synaptic) was monitored by the uptake of [3H]glutamine as well as by mitochondrial swelling. The uptake is inversely correlated to medium osmolarity, temperature-dependent, saturable and inhibited by mersalyl, and glutamine is upconcentrated in the mitochondria. These results indicate that glutamine is transported into an osmotically active space by a protein catalyzed mechanism. The uptake is slightly higher in synaptic mitochondria than in non-synaptic ones. It is inhibited both by rotenone and the protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone, the latter at pH 6.5, showing that the transport is activated by an electrochemical proton gradient. The K+/H+ ionophore nigericin also inhibits the uptake at pH 6.5 in the presence of external K+, which indicates that glutamine, at least in part, is taken up by a proton symport transporter. In addition, glutamine uptake as measured by the swelling technique revealed an additional glutamine transport activity with at least 10 times higher Km value. This uptake is inhibited by valinomycin in the presence of K+ and is thus also activated by the membrane potential. Otherwise, the two methods show similar results. These data indicate that glutamine transport in brain mitochondria cannot be described by merely a simple electroneutral uniport mechanism, but are consistent with the uptake of both the anionic and the zwitterionic glutamine.

6082 Background: The present study was undertaken to evaluate the possibility of using the expression of a panel of proteins involved in apoptosis and/or growth control as predictive markers for radiotherapy response. Methods: Nine head and neck squamous cell carcinoma (HNSCC) cell lines were selected to represent different parts of the spectrum of in vitro radiosensitivity. These cell lines have an intrinsic radiosensitivity (IR) between 1.4 and 2.6 measured with a 96 well plate clonogenic assay. Results: Fourteen proteins e.g. Bcl-2, Bcl-XL, Bax, Bad, Bak, Puma, survivin, COX-2, Hsp70, MDM2, p53, EGFR, cyklin D1 and SMAD4 were investigated in above mentioned cell lines and in normal oral keratinocytes (NOK). Each protein was quantified using Western blot analyse and the relative densiometric value from each blot was adjusted for actin and standardized to NOK. The correlation between each protein and IR was analyzed but none significant correlation was found. When combine different proteins, EGFR, Survivin, Bcl-2, Bak, Hsp70 and Smad4 together show the highest significant correlation to the IR. As Western blot is a semi quantitative method we decided that a division into groups depending on the level of protein expression would give a more realistic description of the prognostic value of the detected changes The protein expression was classified into four groups (0–4 point; no, small, middle or large changes compared to NOK) and each p53 mutation got one point. We named this grouping Number of Negative Points (NNP). The NNP for all 15 factors together show a significant correlations to IR, R=0.826 and P= 0.006. A multivariate statistical calculation was carried out to select the combination of factors that had the strongest correlation to IR and the best combination was EGFR, survivin and p53 mutations, R=0.935 and P No significant financial relationships to disclose.

Heparinization, started one hour following coronary ligation, was maintained for twenty-four hours. One week after recovery the hearts were perfused in vivo with india ink. After clearing, the proportion of ventricular mass infarcted was determined. No appreciable difference from the control series was found.

The Harvard Medical School set up a teaching service at Boston City Hospital in 1914; in 1923, the school added a specially endowed research facility, the Thorndike Memorial Laboratory. The combination, known as the Harvard Medical Unit at Boston City Hospital, endured for 52 years. Its history, by Finland and Castle, 1 is monumental in scope, but personal recollections will, perhaps, render vivid the medical experiences of an intern with the unit during the 1930s. The unit then comprised two general medical services and the Thorndike, as it was called. The Thorndike had separate wards for clinical investigation and for research laboratories, where the internists, the attending men, pursued their special interests. The emphasis on the wards was bedside teaching. The dean, David Edsall, had increased tenfold the funds for bedside teaching and had tripled those for research. As interns, we were told that there would be no time for

These volumes contain more than "Cutaneous Changes in Internal Diseases," more than the authors' aim "to encompass almost the total pathology of human illness in its dermatological aspects." They include also cyanoses; localized and generalized edema (200 correlations); reflex hyperesthesia and reflex oculocutaneous changes in visceral disease; Sudeck atrophy; subcutaneous emphysema; tumors and atrophy; venous thromboses; venous patterns and varices; gangrenes; vasculitis; abnormal obesities; genetic defects; pallor and flushing (carcinoid); the facies dolorosa of many diseases; and descriptions or lists of all interrelated internal and cutaneous disorders. An introductory chapter describes the causes of common disorders of the skin, nails, and hair; then follows 27 chapters of the dermatological components or concomitants of all organ systems; of metabolic, hematopoeic, lymphatic, infectious, and parasitic diseases; deficiency states; collagenoses and lipidoses; and sections on puberty, menarche, pregnancy, menopause, and gynecological disease. Two final chapters cover skin diseases related to diseases of the

These eight essays from Cambridge University describe clearly, without oversimplification, the fundamental factors governing food production and population growth. They emphasize that increasing cost, rather than productive capacity or distribution, limits food production throughout the world. Arable land can not be increased appreciably because the irrigation of deserts and the conversion of rain forests to rice paddies is very expensive. Increased food supplies depend, therefore, primarily upon the increased productivity of land now under cultivation, and this requires costly machines and fertilizers. Thus, food becomes progressively more expensive. Only through industrial growth, increased wealth per capita, and a sound economy can poorer countries produce, or buy, more food. The rich countries can assist, but not support, the poor ones. The United States, short of water and doubling its population within 50 years, is no longer a world granary. Increased food production, made possible by comparably increased industrial wealth, could supply

This symposium, sponsored by the National Institutes of Health, contains 12 brief, excellent essays by students and educators of diverse nationality, background, and opinion. The subjects include medical educational reform in France, Japan, and Latin America; new medical schools in Germany and New Zealand; the views of medical students of different countries concerning medical reform and their participation in curricular revision; and the relationships of welfare systems and of biomedical research groups to the reorganization of medical schools. The book includes discussions as well as formal papers, and the sharp debates and critical analyses are of particular value. The historical influences upon medical education and practice, often neglected in the United States, are well presented. The problems of Latin America are predominantly those of a feudalistic social and university organization, while the rigid academic and administrative hierarchies of France have Renaissance and Napoleonic origin. Belgium is trapped in the nationalistic

Should diagnostic and therapeutic procedures, performed without informed consent, be classified any longer, legally, with the attack of a common cutthroat? Should one patient, who can prove negligent treatment, receive compensation, while another patient, who lacks proof, receives none? Can jurists evaluate the adequacy of informed consent? Should heads of departments be responsible for the professional errors of their resident physicians? Do communications remain confidential when known to many doctors, nurses, students, and social security personnel? If, in a socialist state, the interests of individual and society coincide, is there any need to preserve the concept of confidential communication? Doctors and jurists discussed these and related questions in a symposium in Germany. Socialist East Germany, revising its constitution and civil and criminal codes, plans two innovations: a legal code governing medical practice (Arztliches Berufsrecht); and disciplinary commissions of physicians, each including a jurist, which will consider the medical technicalities and

Three interesting and important types of headache are those of histaminic cephalgia, of expanding intracranial aneurysm and of classic migraine, the last mentioned being associated occasionally with ophthalmoplegia. Histaminic cephalgia, clearly defined as a disease syndrome by Horton, 1 has these salient features: It is a brief, recurrent, violent, unilateral headache involving the temple, the eye and the neck. Usually nocturnal in onset, it is associated with congestion of the nostril and eye on the affected side, and there is profuse watering of the eye. Pressure over the swollen temporal arteries or over the common carotid artery will give transient relief. The syndrome may be precipitated by alcohol or by histamine, may be relieved in the individual attack by epinephrine, and may be permanently relieved by desensitization with histamine. The second type of headache, brought about by expanding intracranial aneurysm, may give rise to varied headaches. However, Dandy 2 has

By 1450 Gutenberg, in Mainz, had invented the essential of modern typography: the mechanical reduplication of movable metal type. There is general agreement about the dates when printing began in various cities: 1454 in Mainz, 1458 in Bamberg and Strassburg, 1465 in Subiaco, 1467 in Rome, 1469 in Venice and Paris, 1470 in Utrecht, and 1477 in Westminster. It seems natural that so important an invention should have spread rapidly but, when we look at the data, several questions arise. Why did so valuable a trade secret leave Mainz so early? Why in 1464 did three printers from Mainz— Konrad Schweinheim, Arnold Pannartz, and Ulrigh Hahn—cart their heavy printing presses over the Alps and the Apennines all the way to Rome? Why, once in Rome, did they then bring their presses (probably by ox cart) over mountainous roads to remote Subiaco, and there print the first books which were printed

To the Editor.— Dr. Egan's EDITORIAL (219:1471, 1972) deplored the passage by the House of Representatives of a bill establishing medical schools under the US Department of Defense, and recommended the alternative— scholarships in our present civilian schools for students interested in careers in the medical departments of the armed services. The advantages of such scholarships over the establishment of military medical academies should appeal to the Department of Defense and to the Congress, as well as to those physicians familiar with both medical education and military medicine. The scholarships would be economical of teachers and of money; the medical schools would need only to develop teaching in the area of military medicine; and the Department of Defense would be spared a further responsibility. The government can offer the same contracts and inducements to the holders of military scholarships in civilian schools, as it would to students entering military academies.

This remarkable little book, absorbing for the physician and sufficiently explicit for the layman, uses an infrequent disease, dystonia musculorum, to show the complementary natures of the science and the art of medicine in the care of all patients. It tells the story of the surgical treatment of involuntary movements, the accidental discovery of the effectiveness of thalamic ablation, and the history, clinical course, and treatment of dystonia musculorum, as well as the ethical aspects of subjecting patients to untried procedures. We are in the homes, hospital, and operating room with three patients and their families: girls of 11 and 14 years, undiagnosed for five and eight years, and a man of 24 undiagnosed for 17 years. We hear how these patients, brushed off by family physicians and specialists who found "nothing wrong physically," were subjected to years of inappropriate and traumatic psychotherapy; how a harmonious family was almost destroyed

Systems of education reflect the sociopolitical histories of their countries, and the German and American educational systems have been as different as their historical heritages. For six centuries the character of a German university was a contract between an absolute ruler, who needed educated men for his kingdom, and the faculties, which tried to insure their academic freedom against royal intrusion. Now, since 1949, the universities are the responsibility of the 11 states of the West German Republic, but the fundamental organization has not changed. Because all German universities are state institutions, there are no private medical schools. An appointed state minister of education is responsible for education, and he selects the new head of a department from a list of three candidates submitted by the faculty. There is no board of trustees which represents the public interest. The internal organization of the faculty is democratic but ineffectual. Although the

This excellent volume explains the changing concept of medical care, the systems of care in 23 countries, and the medical and administrative problems encountered by all nations. The contributors include both physicians and administrators; they recognize the obligation to make medical care available to all people; and all make critical and realistic judgments born of experience and free of polemic, utopianism, and political oversimplification. Fry describes the inevitable involvement of the state in medical care: medical care must be coordinated with all other aspects of the nation's welfare, aside from the problem of financing. He and Robinson describe how progress increases demand, how resources will remain inadequate to meet the public's "insatiable wants and total needs," and how, with growing governmental involvement, the relationship between the medical profession and government inevitably becomes strained. Cohen explains the problems of insurance (no panacea) and, with others, emphasizes the need for professional participation

Written for intelligent laymen, this book presents a balanced discussion of demographic principles and applies them dispassionately to the population problems of the United States and other countries. Interesting is the historical analysis of the factors influencing the numbers and composition of the immigrants who populated the United States, and the correlation of these immigrational patterns with population movements within the United States: legislative restrictions upon immigration from Europe, for example, accelerated the Negro migration to the northern states. The author emphasizes that underpopulation and overpopulation are relative to the balance between numbers, resources, and technology, and that America is becoming overpopulated: we produce relatively less food, must import more iron and oil, and suffer a lack of water, recreational areas, roads, schools, and hospitals. He develops the thesis that the increased population of the United States has led already to restrictions of the individual's freedom to motor, fish, hunt

Deans and professors from 18 countries of Africa, the Americas, Asia, Europe, and India describe the evolution of their medical schools, and the current changes in curricula, postgraduate education, and internal governance. The "world trends" refer to the growing social-utilitaristic role of the medical school in serving the needs of the countries for medical services, and the increasing influences of governments, health ministries, and insurance systems upon education and training. The curricular changes, admission policies, programs of postgraduate education, and changes in governance of the medical schools reflect these social and political pressures. The historical sections, especially those on the newer nations, illustrate the transition from colonial to national medical schools, the desire of these countries to adapt training to their desperate needs for medical care, and the efforts to be scientifically independent and respected. In all countries, rich or poor, money limits medical services and, as the medical school

This book offers an intimate account of Dr. Bean's interest in patients with unusual diseases. It is a vivid and interesting survey of rare diseases, some no longer rare, and others unusual only because they cut across conventional classifications and ontological concepts. Students, residents, and practitioners will find brief and illuminating descriptions and wise advice, which will enlarge their knowledge and lead them to observe patients better and with greater interest. The sections on bleeding from the gut, angiomatosis, the lung, and miscellaneous diseases are especially good. The preface comments upon, but does not explain, Hippocratic, Platonic and ontological thought. The epilogue is a potpourri: "A pigeon breast may contain a cooing dove murmur, though the two are not usually related" and "The body as a volume container may be disgraced by obscene obesity or violated as an empty shrine of neglect in anorexia nervosa." The reader encounters a distinct