26 September, 2008

Streptococcal throat in child

Photo. 1) reddishness of the palate, petechial rash(not well seen) and
tonsil (not seen) in streptococcal infection.
Photo 2) Skin rash. Unclear reddish eruption with itching appear
in trunk, arm and leg. If not treated, spread all over the
body and more red, which been called as " Scarlet fever".

Photo 3) Rapid test for group A, β streptococci
Photo 4) Rapid test for group A, β streptococci.
Photo. 5) tiny colonies of streptococcus pyogenes on blood agar plate.

Photo. 6) A hallow around colonies are seen, indicating β hemolysis.
(Mr. Mizuno, Department of Clinical Laboratory, Yamaguchi
University School of Medicine)


❑Etiology: Streptococcus pyogenes
( group A, β hemolytic streptococci)
❑Route of transmission: close contact with child
or asymptomatic carriers.
❑Incubation period: 2-5 days
❑Symptoms: 1) high fever and sore throat without cough and
nasal discharge.
2) skin rash: 1/20-50 cases developed red skin
rash( if severe, called as "scarlet fever")
❑Diagnosis: Rapid strep test, take just 15 minutes, about 98%
accurate, which means that it will miss about 2%
of strep throat.
1) acute glomeruronephritis( around 3-6 weeks later)
rare in developed countries.
2) rheumatic fever( rare in developed countries)
very rare
❏Therapy: 1) oral antibiotics( penicillin still effective) for 10 days.
2) throat gargle

Any questions, write to Keiji Hagiwara, M.D.
E-mail: keijihagiwara@gmail.com

The Nobel prize in Physiology or Medicine 1945

        → http://nobelprize.org/nobel_prizes/medicine/laureates/1945/index.html

The British media incorrectly reported the story of penicillin, 
in which Fleming is the developer of penicillin therapy for 
bacterial infections in human. 

But the Nobel committee made fair judge. In 1945, Alexander 
the Nobel prize in Physiology or Medicine.
Without Dr. Chain's new knowledge of biochemistry,The work
did not succeed. Without Dr. Florey's leadership, penicillin 
project did not succeed. Without Heatley's technical assistance, 
did not succeed.

I think that Dr. Fleming have been overestimated by mass
media,as in the case of Dr. Hideo Noguchi, in the History 
of Medicine.

As a researcher of Bacteriology, Fleming was a genius. 
but he was a lonely, egoistic man. On the other, Dr.Florey 
did not find any something new in field of Pathology or 
Medicine. He followed up the previous findings or discoveries, 
and deduced the final conclusion on the subject. He was 
pragmatist and organizer.

Heatley contributed the technical device and idea for the 
assay or extraction, isolation of penicillin. 

In 1990, Norman George Heatley was awarded the unusual 
distinction of an honorary Doctorate of Medicine from Oxford 
University, the first given to a non-medic in Oxford's 800-year 

1) Abraham EP, Chain E, Fletcher CM, Florey HW,Gardner AD, 
     Heatley NG, Jennings MA,: Further observations on Penicillin.
    The Lancet 238:177-188, August 16, 1941. 
    The article described the first human trials of penicillin for 
    bacterial infection. 
    Nobel Lecture, March 20, 1946 
3) Gwyn Macfarlane: Howard Florey; The making of a great scientist.
    Oxford University Press, 1980. 
  The biography, written by Oxford Medical doctor. Based on his research    
 experience in Hematology, Dr. Macfarlane described the Florey's medical   
 research in detail, and not forcas in human story.
4) Gwyn Macfarlane: Alexander Fleming: The Man and the Myth. 
     Oxford University Press, 1985.
  So many books of Fleming's biography have been published. 
  However, Almost all biographer have been writers without medical 
  training or knowledges. This biography was written by medical 
  doctor of Oxford. Dr.Macfarlane accessed to unpublished material
  about Fleming. and described the true fact of his penicillin 

Any questions: write to Keiji Hagiwara, M.D. 
                            E-mail: keijihagiwara@gmail.com

25 September, 2008

Penicillin producing mold

Photo:  The mold culture of penicillium notatum
             which produce penicillins.
          Microbe Library; American Society for Microbiology

In 1928, Dr Alexander Fleming accidentally discovered that  around green
mold, the staphylococcal colonies are dissolved. He named unidentified 
substance , which killed staphylococcus, as penicillin.  But Dr. Fleming did 
not continued the study of penicillin.

Ten years later Dr. Chain and Professor Florey at Oxford University,
picked up the penicillin and to extract, purified of it.   In 1940, they 
succeeded the cure of infected mouse by penicillin. and next year, 
done the first clinical trials of penicillin in human infection.

The mold which produce penicillins belong to penicillium notatum.  
The extraction of penicillins were difficult works, because the 
productivity of penicillins by mold were vary in culture media and 
conditions and very unstable small molecules(its molecular weights
is from 310 to 350).

Any questions ?     write to Keiji Hagiwara, MD
                                                 Kami-Ube Pediatric Clinic

Bacteriostatic effects of natural penicillin

  Photo: Professor Gardner

Bacteriostatic  effects of natural penicillin
1)  inhibitory effect against;  (sensitivity order) 
  N. gonorrhae 
  B. anthracis 



Pneumococcus: differ from types

3)poor effect;
V. cholerae 
  Bact. coli 

Ref) Abraham EP, Chain E, Fletcher CM, Florey HW,Gardner AD, 
        Heatley NG, Jennings MA,: Further observations on Penicillin. 
        The Lancet 238:177-188,August 16, 1941 。

08 September, 2008

Dr. Margaret Jennings

                                 Photo: Dr. Margaret Jennings

She look like a woman with strong will, look like a woman 
who appear on Ken Follett's Nobel "The eye of the Needle
------  when a German spy trying to communicate by wireless, 
She insert her hand to the socket for short-circuit the electricity 
for blocking ------
Dr. Jennings worked with Professor Florey for studying the 
biological properties of penicillin. After Florey wife(Ether)
died, Jennings married Florey in June 1967.   

But their happiness was to be sadly brief.   Florey died suddenly 
from a heart attack on 21 February 1968. He was 69 years of age.   
The funeral was in the small parish church almost exactly opposite 
his house at Marston, England.

 Ref:  Gwyn Macfarlane: Howard Florey; The making of a great scientist.
 Oxford University Press, 1980.

British penicillin vs. American penicillin

1) Dr. Chain said:

I had come across this paper early in 1938 and reading it
I immediately became interested. The reason was that,
according to Fleming's description, the mould had strong
bacteriolytic properties against the Staphylococcus
------ when I saw Fleming's paper for the first time
I thought Fleming had discovered a sort of mould lysozyme,
which, in contrast to egg white lysozyme, acted on a wide
range of gram-positive pathogenic bacteria.
I further thought that in all probability the cell wall of all
these pathogenic bacteria whose growth was inhibited by
penicillin contained a common substrate on which the
supposed enzyme acted, and that it would be worth trying
to isolate and characterise the hypothetical common substrate.
For this purpose it would, of course, be necessary to purify
the supposed enzyme, but I did not foresee any undue difficulties
with this task for which I was well prepared from my previous

Shortly after the chemical work had been started at Oxford,
a number of other British research centres( the Imperial College
of Science, Burroughs Wellcome Ltd., Imperial Chemical Industries,
Glaxo), began similar studies.

Simultaneously with the work in England, American chemists began
an intensive study of the structure of penicillin with the aim of quickly
achieving a synthesis. This work was carried out on a very large scale,
with something like 200 academic and industrial research chemists
taking part in the project.

Until May 1944 this work was entirely independent of the British effort,
and we in Britain had no information about the state of the American
investigations, except for a few fragmentary rumours.

In 1943, the British and U.S. Government imposed a ban the publication
of all chemical work on penicillin and simultaneously negotiations were
begun between the two governments for the purpose of finding a suitable
method for a complete exchange of information between the various
groups of workers on both sides of the Atlantic.

These negotiations were protracted, and while they were in progress we
at Oxford got on with our studies and were able to propose the first
complete structural formulae for penicillin in October, 1943.


During the purification studies it became clear that there existed several
penicillins which had very similar biological and chemical properties,
but which differed in their chemical composition. Later work showed that
all penicilins contained common nucleus, but differ in the structure of
their side chains.

So far four different penicillins have been obtained in the form of their
crystalline sodium salts. They are designated in England as penicillins
I,II,III,IV, according to the sequence of their historical discovery;
in America they are termed, F,G,Xand K.


Elementary analysis of the crystalline sodium salts has shown that the
penciliins have the following composition:

Penicillin I (F) C14H20O4N2S
Penicillin II (G) C16H18O4N2S
Penicillin III(X) C16H18O5N2S
Penicillin IV(K) C16H26O4N2S


The final solution of the problem of the structure of penicillin
came from crystallographic X-ray studies. This work, in which
Mrs.D.Crowfoot and her colleague Mrs. Barbara Roger-Low
have played a predominant role, has led to the difinite exclusion
of the thiozolidine-oxazolone structure and to the conclusive
proof of the beta-lactam structure.


Any questions: write to Keiji Hagiwara, MD